Express Pharma May 16-31, 2013

VOL .8 NO.14 PAGES 86

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Market Trial(s) by fire Management Clinical research: Building trust Pharma Technology Review 'Not having a big data strategy can hurt your business big time' 16-31 MAY, 2013, `40

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V O L 8 . N O . 1 4 M AY 1 6 - 3 1 , 2 0 1 3

CONTENTS

Chairman of the Board Viveck Goenka

MANAGEMENT

Editor Viveka Roychowdhury*

Clinical research: Building trust

BUREAUS

PAGE 31

India has a moral obligation to participate in

Mumbai Sachin Jagdale, Usha Sharma, Raelene Kambli, Lakshmipriya Nair, Sanjiv Das

clinical trials

PAGE 35

Without ethics, there is no credibility for the

Bangalore Neelam M Kachhap

clinical trials

PAGE 36

Delhi Shalini Gupta

Clinical trials: Safety of research participant

MARKETING

is the ethical mandate!

Deputy General Manager Harit Mohanty

Need to take a pragmatic view of clinical trials

Senior Manager Rajesh Bhatkal

PAGE 37

PAGE 40

PRODUCTION

RESEARCH

General Manager B R Tipnis

From trash to treasure

PAGE 42

In situ gelling polymeric drug

Production Manager Bhadresh Valia

delivery system

Asst. Manager - Scheduling & Coordination Arvind Mane

PAGE 44

Asst. Art Director Surajit Patro

PHARMA TECHNOLOGY REVIEW

Chief Designer Pravin Temble

Leveraging data science to accelerate clinical

Senior Graphic Designer Rushikesh Konka

trial results

Photo Editor Sandeep Patil

digital patient

C I R C U L AT I O N

May 16-31, 2013

PAGE 53

PHARMA LIFE

Circulation Team Mohan Varadkar

Copyright @ 2011 The Indian Express Ltd. All rights reserved throughout the world. Reproduction in any manner, electronic or otherwise, in whole or in part, without prior written permission is prohibited.

PAGE 52

Harnessing the power of the

Layout Rakesh Sharma

Express Pharma Reg. No.MH/MR/SOUTH-77/2013-15 RNI Regn. No.MAHENG/2005/21398 Printed for the proprietors,The Indian Express Limited by Ms.Vaidehi Thakar at The Indian Express Press, Plot No. EL-208,TTC Industrial Area, Mahape, Navi Mumbai - 400710 and Published from Express Towers, 2nd Floor, Nariman Point, Mumbai - 400021.

(Editorial & Administra-tive Offices: Express Towers, 1st Floor, Nariman Point, Mumbai - 400021) *Responsible for selection of news under the PRB Act.

PAGE 50

The design of safe chemical processes

‘What motivates us is trying to find something better for our patients’ PAGE 80 ‘Patient is doing us a favour by enrolling in a trial’

PAGE 81

MARKET Venus signs marketing agreement with Korean Goodwills

PAGE 20

Pharmac India 2013 to focus on pharma machinery, packaging and bulk drugs

PAGE 23

iPHEX 2013 exhibition records over `1000 crore profit PAGE 26 6th international conference of SAC ACCP seeks active research to provide better healthcare delivery

PAGE 27

SPDS organises 1st international convention on dissolution in Mumbai

www.expresspharmaonline.com

PAGE 28

EXPRESS PHARMA

13

EDITOR’S NOTE Needed: A renaissance in clinical research

IF THE EARLIER DECADES WERE ABOUT A BREAKNECK GROWTH IN THE NUMBER OF CLINICAL TRIALS IN INDIA, I HOPE THAT IN THIS DECADE, WE FOCUS ON QUALITY RATHER THAN QUANTITY

Clinical research in India seems destined to be in the

Express

limelight for the wrong reasons. The regulators seem

experiences and hopes of patients and their relatives

to be making up for lost time, going into overdrive

participating in clinical trials.

Pharma

will

soon

also

reflect

the

after a PIL was filed in the Supreme Court in

Clinical research in India has many centres of

January. Since then, new guidances and advisory

excellence but it also has a dark side. Like the

boards have been announced and debated with

parallel existence of illegal buildings in India's

typical kneejerk reactions from all sides. The

metros,

industry thus feels hounded on all fronts: media,

builders out to make a quick buck. With no regard

patient groups, parliamentarians.

for any civic laws, these structures were built with

hastily

constructed

by

unscrupulous

The common refrain from corporate stakeholders

substandard materials literally sprouting overnight.

seems to be that more regulations and a review of

It is no wonder that many of these sandcastles are

the existing process are welcome but should not

collapsing today, like the unethical practices coming

slow down approvals. Many appeals have been

to light in clinical research as well.

made to media and NGOs to be ‘more rational, less

If the earlier decades were about a breakneck

emotional’ and not behave like ambulance-chasers,

growth in the number of clinical trials in India, I

a reference to lawyers who hound patients and their

hope that in this decade, we focus on quality rather

relatives to sue just about anybody.

than quantity. I hope we will see a more measured

I hope the Express Pharma May 16-31 Special on

consolidation, tempered by introspection.

International Clinical Trials (ICT) Day has achieved

We at Express Pharma hope to be part of this

a fair balance between the many interested parties.

process, as the industry re-builds the foundations of

We have tried to feature all stakeholders: sponsors,

clinical research in India, in line with a reinforced

CROs, thought leaders from the legal and ethics

regulatory blueprint, with each stakeholder being

fields as well as doctors who serve as principal

part of the process.

investigators on trials.

And as we move towards the formalisation of

The only voice we do not have in enough detail,

medical research protocols, lets hope that next

except for one very short comment, is the patient’s

year’s ICT Day Special will reflect a true renaissance.

voice. I admit to not pushing too hard, because I felt it was an intrusion on the doctor-patient bond and the patient's privacy. But I remain optimistic that

14 EXPRESS PHARMA

www.expresspharmaonline.com

Viveka Roychowdhury viveka.r@expressindia.com

May 16-31, 2013

MARKET

W H AT ’ S INSIDE

THE BUSINESS OF PHARMACEUTICALS

Venus signs marketing agreement with Korean Goodwills PG 20 Pharmac India 2013 to focus on pharma machinery, packaging and bulk drugs PG 23 iPHEX 2013 exhibition records over ` 1000 crore profit PG 26 6th international conference of SAC ACCP seeks active research to provide better healthcare delivery PG 27 SPDS organises 1st international convention on dissolution in Mumbai PG 28

MANAGEMENT 31 RESEARCH 42 PHARMA TECHNOLOGY REVIEW 49 PHARMA LIFE 80 May 16-31, 2013

www.expresspharmaonline.com

EXPRESS PHARMA

17

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C

Circa 2010: As per a study published in the Indian Journal of Medical Ethics, the number of trials conducted in India grew at a whopping rate of 36 per cent annually from 2006-07 to 2010-11. Even these figures, it claimed were an under representation since registration as a part of the clinical trial registry was made mandatory only in 2009. Availability of a diverse gene pool, cost effectiveness (conducting trials in India is upto 50 per cent cheaper than in tightly regulated markets such as the US and Canada) and a faster patient recruitment fuelled the country's rise on the world map. Data reveals that as much as 250 new trials were conducted by MNCs every year from 2007 -2010.

Riding on the trend above, there were predictions that the industry would continue its upward swing and gain a market share of 15 per cent by 2011. However, the same year saw the number of trials steeply decline as opposed to the early years. Lack of certified trial sites was further accentuated by DCGI's stringent guidelines on clinical trial inspection programme in late 2010. This along with recession, concerns on data protection, skill sets, infrastructure and delay in approvals were

DR DEVEN PARMAR some of the reasons analysts gave for the slowdown. The situation worsened further after a PIL was filed in the Supreme Court in January this year on alleged illegal trials on untested drugs that further exacerbated the issue putting companies in the line of fire.

The Drugs Controller General of India (DCGI) and health ministry have sprung into action putting forth guidelines making it mandatory to register clinical trials and form ethics committees to monitor the same.

Pause for a cause?

The current market for clinical trials is estimated to be between $200 million to $600 million as against $1 billion dollar projection by Frost and Sullivan in a report last year.

However, Utkarsh Palnitkar, Partner, National Head, Life Sciences Practice, HeadTransactions and Restructuring, KPMG India pegs it to $620 million in 2012.

It is difficult to project a CAGR, although it should be significantly lower than that forecasted some years ago, he adds. The numbers translate to a share of two per cent or even less in the global pie.

Defending India's position, Dr Sauren Das from Excel Life Sciences, a Clinical Trial Management Organisation based in the US says, “India only joined the WTO in 2005 and subsequently started conducting more global clinical trials. Any significant drop off has really only occurred during the last six to eight months - during which time there was a lull in the review of new applications, while the agency revamped regulatory process.”

China, on the other hand has cornered over nine per cent share of the global clinical tri-

Chief Scientific Officer, Karmic Life Sciences

DR ANAND ESWARAIAH MD, Head, Clinical Development & Regulatory Affairs, Clinigene

In such a scenario, de-risking by conducting trials in countries with a more robust regulatory framework is a better strategy.

Karmic Life Sciences has just completed its first study in South Africa

A spate of negative media coverage has projected clinical research in a poor light and NGOs petitioning the courts have made matters worse resulting in a moratorium on clinical trials with the government having decided to penalise everybody for the non-compliance of a few

als market.

Even as the noose on erring companies is tightened and regulations get tougher, the brunt is borne by everyone. Indefinite timelines and delays in approval can cost much to a company on the brink of discovering novel compounds. “Once you have filed an application with the drug regulator, you have no idea how long it may take to get approval for trials here. In early trials, time is money since many other companies across the globe are doing similar drug research,” adds Dr Deven Parmar, Medical Director, Americas, Karmic Life Sciences. He cites a lack of technical competence, improper confidential data

management, misplacing of files and absence of a delegation system when an officer in charge goes on a leave, further leading to inordinate delays.

The industry also strongly feels that while adhering to ethics and compliance issues is understandable, the current scenario puts all and sundry under the scanner, putting processes to a halt for even those going by the book.

“A spate of negative media coverage has projected clinical research in a poor light and NGOs petitioning the courts have made matters worse resulting in a moratorium on clinical trials with the government having decided to penalise everybody for the non-compliance of a few. Only

Opportunities in adversity: Dr Sauren Das O

n the regulatory front, we see a plenty of opportunities for even further improvement. For example, New drugs Advisory committee (NDAC) members need to be exposed to the complexities of drug development in a well thought out and user friendly manner. It is crucial they appreciate nuances of clinical research and consider modalities of increasing the physician base in India.

18

EXPRESS PHARMA

One safe and effective manner could be to direct applicants to conduct post approval studies with as much rigour and respect to ICH GCP guidelines as pre approval studies. This will not only increase the number of physicians to gain valuable experience in the conduct of clinical research, but also help the DCGI take informed decisions related to safety of a drug based on well conducted clinical trials.

In the light of the government and DCGI approving IP protected products made by Indian companies, there is an excellent opportunity for the DCGI to ask the Indian applicants to provide efficacy and safety data of such products through well-conducted clinical trials conforming to world class standards and discourage these companies from relying on clinical data generated by the innovator.

www.expresspharmaonline.com

May 16-31, 2013

M|A|R|K|E|T

six studies have been cleared in 2013 by the DCGI,” Dr Anand Eswaraiah, MD, Head, Clinical Development & Regulatory Affairs, Clinigene, makes a point. And, there are a number of applications still pending. Clarity on insurance cover and compensation norms has also hampered growth.

Even though the US continues to be the largest market for clinical trial services and along with Western Europe dominated the market, accounting for more than three quarters of global revenues in 2011, emerging countries will continue to hold interest and its not hard to understand why. The market share for the BRIC nations (Brazil, Russia, India and China) will triple during the period 2011-2023, reveals a report by ASD Reports. But until then, companies are trying to figure a way out of the chaos and gather some momentum.

This too shall pass “In such a scenario, derisking by conducting trials in

May 16-31, 2013

countries with a more robust regulatory framework is a better strategy. Karmic Life Sciences has just completed its first study in South Africa,” informs Dr Parmar. While South East Asian countries like Malaysia, Singapore are well known clinical trial hubs, companies are exploring conducting trials in places like South Africa, Eastern Europe etc, he adds. These destinations might be in addition to and also at times as an alternative to India, chips in Palnitkar. Some of the bigger CRO’s have increased their footprint in countries such as Philippines, Malaysia, South Korea, and are also considering Vietnam, Cambodia etc, he opines.

Industry is hopeful that even as their business has been hit hard, regulators certainly seem to have taken on board the pertinent issues and are working on setting them right. Says Das in retrospect, “With a robust and growing industry, there are bound to be issues and rogue players. The industry’s problems were magnified due to the rapid

www.expresspharmaonline.com

expansion of studies during a relatively short time period. A slower start followed by regulated acceleration could possibly have been better.” He thinks that amendments are in order, as reflected by some of the recent regulatory changes, that will help us bounce back again.

He argues that most companies are doing good ethical research and in compliance with ICH-GCP guidelines. A look at the FDA inspection data reveals that Indian sites are passing muster with one of the world’s most stringent regulatory agencies. Over a seven-year period between 2005 and 2011 and more than 30 site inspections, they have not received a single, OAI – Official Action Initiated, the most significant and negative of findings the agency can levy following an inspection. A site-centric operating model as followed by ELS focused on support of the investigator on a 1:1 basis could also be where the answer lies considering that less 15 per cent research sites in India have a full time clinical research coor-

dinator (CRC) and even those are spread out across multiple trials. “We believe that India is still in its infancy in terms of the conduct of global clinical trials. Such support is critical to ensuring high quality of work that benefits both the patient and the sponsor respectively,” he adds.

Looking ahead, as the global market continues to grow at a high single digit CAGR and is projected to be worth $30 billion in 2015 largely driven by the demand for late phase trial services, India surely has a part to play as soon as it gets its act together. “Instead of blindly putting clinical trial approvals on hold, the government needs to efficiently monitor ongoing trials for regulatory compliance and penalise non-compliant companies. We believe we need to address the issue of clinical trials not with blind emotion but with a rational understanding of the benefits and with greater compassion for those suffering for want of effective medicine,” sums up Eswaraiah. shalini.g@expressindia.com

EXPRESS PHARMA

19

M|A|R|K|E|T

COMPANY WATCH Venus signs marketing agreement with Korean Goodwills Elores to fight `superbugs’ wins patent from South Korea

enus Remedies announced the signing of a deal with Korean pharma giant Goodwills for the exclusive marketing rights of Elores, a novel antibiotic adjuvant entity. Venus has inked this deal after the grant of a patent by the Companies and Intellectual Property Registration Office (CIPRO) of the Republic of South Korea.

The South Korean major is planning to launch this product in mid 2014 post regulatory approval from Korean FDA for which the dossier is already under evaluation.

Bridging clinical trials on the Korean population are being conducted in six leading hospitals of Seoul, the capital city of South Korea.

Pawan Chaudhary, CMD Venus Remedies said, “Patent grant from CIPRO is testimo-

V

ny to the merits of Elores and we are confident that our partnership with Goodwills Korea shall take our research product to its meaningful stage in South Korea.

Goodwills will have exclusive marketing rights of the product till validity of its patent in year 2025.”

After Adcock Ingram, a manufacturer and distributor of healthcare product from South Africa, this is Venus Remedies' second deal this year for out licensing its research products.

Elores is an antibiotic product meant for multidrug resistant infections in ICU, specially in hospital acquired infections where the rise in resistance is reported to the extent of >70 per cent in Asia Pacific region. This product is also reportedly unique in its

mode of action in that it not only kills resistant pathogens (bacteria) but also prevents the spread of resistance.

As per Dr Manu Chaudhary, DirectorResearch - VMRC, JMD Venus Remedies said, “Elores is addressing a huge unmet medical need and in South Korean market at such point of time, it can prove to be all the more significant for society at large”.

South Korea has very high rates of extended-spectrum ßlactamase (ESBL) producing gram negative infections, as high as 40 per cent. Almost 52 per cent of K pneumonia isolates from South Korea are multi drug resistant and producing common ESBL’s to which Elores exhibits excellent efficacy.

The increasing prevalence

National Forum on Tuberculosis launched Will help to raise awareness of TB in India

he National Forum on Tuberculosis (TB) was launched in New Delhi.

Convened by Dalbir Singh, Head of Dept, All India Congress Committee, the forum was launched in the presence of Shiela Dikshit, Chief Minister, Delhi; AH

T

(L-R) Dalbir Singh and Sheila Dikshit

20

EXPRESS PHARMA

Khan Choudhury, Health and Family Welfare Minister of State and Deepa Dasmunsi, Urban Development Minister. The launch was supported by Global Health Strategies (GHS) a health organisation which works on TB, cervical cancer and childhood diseases.

The forum launch brought together parliamentarians, policy makers and civil society representatives to discuss the challenges for TB prevention and control.

The event also saw the release of a handbook on TB in India. This hand book provides a comprehensive overview of the challenges around TB control in India and the role of policy makers and parliamentarians in this regard.

Dalbir Singh, Convener of the Forum commented, “The National Forum on TB will serve as a platform to bring together various stakeholders to highlight and address the complex challenges facing TB in India, a disease that is easily preventable and treatable.”

TB kills one Indian every two minutes. India bears the highest burden of TB in the www.expresspharmaonline.com

world, two million annually.

This accounts for one-fifth of the global disease burden.

TB is the cause of extensive economic losses leading to individual, family and community suffering. TB is also associated with a deep-seated stigma that often leads to discrimination within the workplace and the community.

The National Forum on TB will work to raise awareness on the need for improved TB control. The members of the Forum will meet several times in a year to discuss critical challenges in TB control. Based on these discussions, the members will formulate key recommendations to address these challenges which will then be presented to the Ministry of Health and Family Welfare (MoHFW) for further action.

As representatives of the world’s largest democracy, policy makers, parliamentarians and the civil society play a pivotal role in influencing policy decisions. The Forum will aim to leverage this power to make an impact on the TB landscape in India.

EP News Bureau – Mumbai

of resistance among other gram negative pathogens to commonly used antibiotics is a major concern for the entire Asia Pacific region. According to a recent surveillance study in South Korea increasing prevalence to last resort drugs such as Meropenem and Colistin is drastic and has increased by more than 18 fold in the last three years.

Venus will supply Elores out of its state-of-art manufacturing facility at Baddi accredited with GMP from EU, PIC, TGA and many more. The company has recently launched Elores in India and received an encouraging response. The company is also in talks with international pharma companies in regulated markets for strategic tie-ups for Elores.

EP News Bureau – Mumbai

Aurobindo gets US FDA nod urobindo Pharma has received final approvals from the US Food and Drug Administration (US FDA) to manufacture and market tamsulosin hydrochloride capsules USP 0.4mg (ANDA 202433) and clindamycin palmitate hydrochloride for oral solution USP (Paediatric), 75mg (base)/5mL (ANDA 202409).

The products will be launched soon. Tamsulosin hydrochloride capsules USP 0.4mg is the generic equivalent of Boehringer Ingelheim Pharmaceuticals’ Flomax capsules, 0.4mg and is indicated for the treatment of symptoms of an enlarged prostate (Benign Prostatic Hyperplasia - BPH) in men.

The market size of the product is estimated to be $244 million. Clindamycin palmitate hydrochloride for Oral Solution USP(Paediatric), 75mg (base)/5ml is the generic equivalent of Pharmacia and Upjohn’s Cleocin Paediatric for oral solution, 75mg (base)/5mL and is indicated for the treatment of serious infections caused by susceptible anaerobic bacteria in infants.

EP News Bureau – Mumbai

A

May 16-31, 2013

M|A|R|K|E|T

SeQuent obtains US FDA approval for API facility at Mangalore The facility is ISO 9001 certified for Quality Management systems and ISO 14000 certified for Environment Management systems eQuent Scientific (SeQuent) has received an US FDA approval for its API drug manufacturing facility at Mangalore, Karnataka (SeQuent Mangalore). The SeQuent Mangalore facility is ISO 9001 certified for Quality Management systems and ISO 14000 certified for Environment Management systems. This state-of-the-art facility is engaged in the development and manufacture of APIs and API Intermediaries.

The facility has earlier received quality approval from TGA, Australia and certified by World Health Organisation, Geneva under its Prequalification’s of

S

May 16-31, 2013

Medicines Programme.

Dr Gautam Kumar Das, Executive Director, said, “The US FD A approval endorses our commitment to ensure strong regulatory compliance as well as our dedication to offer quality products through research. Being the

first ever for the company, this approval will further rejuvenate us in establishing SeQuent among the finest global API Manufacturers.”

SeQuent Mangalore specialises in niche and difficult to manufacture APIs and has five of its APIs pre-qualified

by WHO Prequalification of Medicines programme. It has filed more than 30 drug master files covering US FDA, Europe, WHO, Australia, Canada with several more niche APIs in the pipeline for future filings.

EP News Bureau – Mumbai

Quintiles announces pricing of IPO Stock begins trading on NYSE uintiles announced the pricing of its initial public offering of 23,684,210 shares of its common stock at a price to the public of $40.00 per share. The shares of Quintiles common stock are expected to begin trading on the New York Stock Exchange under the single-letter symbol 'Q'.

Quintiles is offering 13,125,000 shares of common stock, and selling shareholders are offering 10,559,210 shares of common stock.

In addition, the selling shareholders have granted the underwriters a 30-day option to purchase up to an additional 3,552,631 shares

Q

www.expresspharmaonline.com

of common stock. The offering is expected to close on May 14, 2013.

Morgan Stanley, Barclays and JP Morgan are serving as joint lead book-running managers for the offering. Citigroup, Goldman, Sachs & Co, Wells Fargo Securities, BofA Merrill Lynch and Deutsche Bank Securities are serving as book-running managers for the offering. Baird, William Blair and Jefferies are serving as lead co-managers, and Guggenheim Securities, Piper Jaffray, Raymond James, RBC Capital Markets and UBS Investment Bank are serving as co-managers for the offering.

EP News Bureau – Mumbai

EXPRESS PHARMA

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M|A|R|K|E|T DEAL TRACKER

M&A activity focuses on broadening product pipelines in selected specialty markets The Indian pharma sector witnessed no deals during April 2013 M&A (including private equity) trend analysis

Source:

Top M&A deals (Apr 2013) Target

Acquirer

&A activity in the pharmaceutical sector was focused on broadening product pipelines in selected specialty markets.

In line with the above trend, Auxilium Pharmaceuticals acquired Actient Holdings, a US-based urology specialty therapeutics company, for approximately $635 million. This transaction will expand Auxilium's specialty therapeutic offering, thereby helping to enhance its growth trajectory.

With this acquisition, Auxilium will gain access to TESTOPEL and Striant, for testosterone replacement therapy and Edex, and Osbon ErecAid, for erectile dysfunction therapy.

In another key deal, US-based OPKO Health agreed to acquire PROLOR Biotech, an Israel-based biopharmaceutical company for approximately $480 million. This transaction is consistent with OPKO's objective of broadening its portfolio, of markettransforming therapies, in selected specialty markets.

With this transaction, OPKO will have four significant products in phase III clinical development and a robust pipeline of important therapeutic and unique diagnostic products in various stages of development.

M&A activity in the pharma sector decreased in both volume and value terms, when compared to the average of previous six months (Oct 2012 – Mar 2013).

According to Datamonitor's Medtrack database, the pharma sector recorded 24 M&A transactions in April 2013, against the previous six months’ average of 36 transactions. In value terms, the sector recorded deals worth $1.7 billion against the previous six months’ average of $2.7 billion.

The Indian pharma sector witnessed no deals during April 2013, against the average of 1.1 deals over the previous six months.

M

Rank

Date

1

04/29/13 Actient Pharmaceuticals LLC (US) Auxilium Pharmaceuticals, Inc. (US)

Deal value ($m) 635

2

04/24/13 PROLOR Biotech, Inc. (IL)

OPKO Health, Inc. (US)

480

3

04/02/13 KYORIN Co., Ltd. (JP)

Teijin Ltd (JP)

197.37

4

04/29/13 Ingenuity Systems (US)

QIAGEN N.V. (NL)

105

5

04/29/13 Opsona Therapeutics, Ltd. (IE)

BB Biotech Ventures; Novartis Venture Funds; Sunstone Capital A/S; Baxter Ventures; Amgen Ventures; EMBL Ventures GmbH; Fountain Healthcare Partners; Roche Venture Fund; Seroba Kernel Life Sciences Ltd

43.02

6

04/25/13 Radius Health, Inc. (US)

F2 Biosciences III, L.P; Biotech Growth NV; MPM Capital; Brookside Capital; MPM Bio IV NVS Strategic Fund LP; BB Biotech Ventures

43

7

04/25/13 Esperion Therapeutics, Inc. (US)

Longitude Capital Management Co., LLC; Aisling Capital; Alta Partners; Domain 33 Associates, L.L.C.; Arboretum Ventures; Asset Management Finance, LLC

8

04/01/13 Pfanstiehl, Inc. (US)

Med Opportunity Partners, LLC (US)

29.9

9

04/02/13 Revance Therapeutics, Inc. (US)

Essex Woodlands Health Ventures; NovaQuest Pharma Opportunities Fund; Delphi Ventures; Vivo Ventures; Technology Partners; Shepherd Ventures; Bio*One Capital Pte, Ltd.; PAC-LINK BioVentures; Palo Alto Investors; Undisclosed Investors

28

10

04/24/13 Genticel S.A. (FR)

Wellington Partners Venture Capital GmbH; IdInvest Partners; Edmond de Rothschild Investment Partners; InnoBio; IRDI; Amundi Pvt Equity Funds

23.7

Venture funding Companies in the pharma sector raised $213.2 million during April 2013, against the previous six months’ average of $299 million. In terms of volume, the sector recorded 15 venture funded deals, when compared to the previous six months’ average of 25 transactions.

Source:

Venture financing trend analysis

Notes and definitions

Source:

Top venture financing deals (Apr 2013) Rank

Date

Target

Investors

Deal value ($m)

1

04/16/13

Auris Medical AG (CH)

Sofinnova Ventures, Inc. ; Sofinnova Partners

50.67

2

04/08/13

GenSight Biologics SA (FR)

The Novartis Venture Fund; Abingworth Management Ltd; Versant Venture Management LLC; Index Ventures LLP

41.59

3

04/11/13

Syros Pharmaceuticals (US)

ARCH Venture Partners; Flagship Ventures; WuXi PharmaTech Corporate Venture Fund; Undisclosed Investors

30

4

04/25/13

Acumen Pharmaceuticals, Inc. (US)

BVF Partners, LP; NeuroVentures Fund LP; Glynn Ventures; Undisclosed Investors; Praxis Technologies

20

5

04/11/13

Novaliq GmbH (DE)

dievini Hopp BioTech holding GmbH & Co. KG

18.18

Source:

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EXPRESS PHARMA

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Medtrack is a comprehensive, fully integrated, global biomedical database providing information on companies, products, patents, deals, venture financing, and epidemiology. It is a live database, constantly updated with news, milestones, trial information, etc.

Medtrack’s unmatched coverage is supported by a userfriendly, highly dynamic set of decision support tools and analytics. In-house analysts and researchers add key insights and conclusions to provide you with the primary and secondary information you need. Key uses of the database include competitive intelligence, target identification, screen potential licensing and investment opportunities, patent assessments, product due diligence, royalty valuations, and developmental benchmarking.

For more information, visit at www.medtrack.com

Definitions 1. Deal value trend is based on transactions where associate values have been disclosed.

2. Trend analysis excludes rumored and terminated deals.

3. Value and volume analysis excludes private equity exits.

May 16-31, 2013

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PRE EVENT Pharmac India 2013 to focus on pharma machinery, packaging and bulk drugs Event to be held in Hyderabad from September 5-7 harmac India 2013, the 4th international pharma machinery, equipment, bulk drugs, API and material exhibition will be held in Hyderabad from September 5-7, 2013. The event will be jointly organised by Orbitz Exhibitions and IDMA (GSB) and actively supported by BDMA and CIPI. Around 300 plus exhibitors from the pharmaceutical industry in India and overseas will participate.

Special focus will be on pharma machinery, packaging and bulk drugs. The event will also see new products being launched.

Visitor's profile includes pharmaceutical companies

P

AROUND 300 PLUS EXHIBITORS FROM THE PHARMACEUTICAL INDUSTRY IN INDIA AND OVERSEAS WILL PARTICIPATE marketing/purchase/export professionals across India and abroad; merchant exporters; contract manufacturers; pharma distributors/ C&F/manufacturers; generic and OTC manufacturers and wholesalers and government suppliers/liaison agents.

Exhibitor's profile includes pharma bulk drugs producer, veterinary drugs, additives, intermediates; pharmaceutical machinery; pharmaceutical formulation; pharmaceutical printing, packaging, lab, material and machinery; pharma ancillary and utility services and maintenance.

The media partner for the event is Express Pharma.

EP News Bureau- Mumbai May 16-31, 2013

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EVENT BRIEF RDD Europe 2013 Date: May 21-24, 2013 Venue: Intercontinental Hotel, Berlin, Germany Summary: The Respiratory Drug Delivery (RDD) Europe 2013 scientific conference will welcome pulmonary and nasal drug delivery experts from all over the world to Berlin, May 21-24, 2013. The three-day interactive symposium of the highest level will begin with a plenary lecture titled “Biomarkers and Targeted Treatments for Small Airways Diseases – The Past, Present and Future”.

The symposium will also focus on drug development – new drugs, targets and formulations, weighing the evidence in support of bioequivalence, orphan drugs – opportunities, regulatory and clinical challenges, harmonising the clinical requirements for lab/ ICS combinations in the US and Europe, designing devices for the marketplace, optimising formulation and device partnerships. RDD Europe conferences highlight innovative research contributions through podium and scientific poster sessions. These are enhanced by 12 technical interactive workshops from vendors and service providers in the industry. In all sessions, the latest technological advances related to nasal and pulmonary drug development will be presented.

Contact details: Marion Baschet Vernet London, Great Britain Tel: +44 (0)797 609 41 00 Email: mbvernet@gmail.com

Drug Delivery & Complex Generics Conference Date: May 28-30, 2013 Venue: Mumbai Summary: With the patent cliff reaching its peak, complex generics and innovations in drug delivery present huge opportunities for the pharmaceutical industry to gain the

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first mover advantage.

Visitors will be able to delve deeper into innovative formulation and manufacturing techniques and latest drug delivery systems orals, injectibles, nasal, transdermal and opthalmics by attending the conference. Latest case studies on controlled release formulations, HME and spray drying techniques, depot injections, nanoparticle technology will be discussed. A workshop will be held on how to ensure smooth scale-up of complex generics that will address all critical scale-up issues - from concept to commercialisation.

Technologies – with moving times; and Bridging the Generation Gap: Present and Past in pharmacy.

Apart from honouring the retired professionals and faculty members of the college, the two-day celebrations will have group discussions led by the distinguished alumni of the college. It will also involve talks about how professional pharmacists can serve the patients and consumers better.

Contact details: Email: goldengcp@gmail.com

Contact details: Tel: (022) 61727001 Email: Conferencesindia@ubm.com Website url: http://www.drugdelivery-complexgenerics.com?utm_campaign=MEDIAPARTNER&ut m_medium=EVENTLISTING&utm_source=EXPRESS PHARMA

Govt. College of Pharmacy, Bangalore (Golden Jubilee Celebrations) Date: June 1-2, 2013 Venue: Government College of Pharmacy (GCP), Bangalore Summary: The Government College of Pharmacy (GCP), Bangalore will celebrate the 50 years of beginning of pharmacy education in the state of Karnataka.A local organising committee has been formed with Professor S Shashidhara, Principal of the college, Shiva Hiremath, President of the Alumni association, GCP, and KP Ravindra, President of American Association of GCP Alumnae, US. Dr S Ramachandra Shetty, Professor in the college is the organising secretary. Sessions will be held on – Remembering 50 Golden Years (Reminiscence); Pharmacists: Professional Challenges for better service to patients; Challenging

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Pharma Quality by Design Date: June 12-14, 2013 Venue: Mumbai Summary: The 2nd Annual Pharm QbD Forum will have case study sessions on various dosage forms (pulsatile drugs, solid oral dosage, lyophilised products), on API synthesis and scale up, on various analytical sciences and development. Workshop on DOE covering all the basic statistical approach all supported with different case studies will be held. Speakers who have been implementing and working on the QbD principles for their respective organisations like Dr Reddys Laboratory, Emcure, Lupin, Jubilant Life science, Teva Pharmaceuticals, Bristol-Myers Squibb, Orchid Pharmaceuticals will attend the event.

Summary: InnoPack India 2013 focuses on innovation in pharma packaging for compliance and safety. A contentbased conference with high level keynotes, exciting learning formats and unparalleled networking sessions covering a host of topics like, innovations in patient compliance packaging, packaging materials and drug delivery devices, effective anti-counterfeiting measures and packaging regulatory compliance, will be held.

InnoPack India 2013 will gather a host of packaging experts including Laura Bix, Associate Professor, School of Packaging - Michigan State University, Robert Winter, Director Materials Management, Pfizer, Gautama Buddha, Senior Director Packaging Development, Dr Reddy's Laboratories, Santanu Chowdhury, Associate Director Packaging Development, Ranbaxy, Prashant Kane, Senior General Manager Packaging Development, Sun Pharma Advanced Research Centre and others who all are at the centre stage of developing innovative packaging for pharma globally.

Contact details: Tel: (022) 61727001 Email: Conferencesindia@ubm.com Website url: http://www.innopackindia.com/?utm_campaign=M EDIAPARTNER&utm_medium=EVENTLISTING&utm_so urce=EXPRESSPHARMA

Contact details: Tel: (022) 61727001 Email: Conferencesindia@ubm.com Website url: http://pharmaqbd.com/?utm_campaign= MEDIAPARTNER&utm_medi um=EVENTLISTING&utm_so urce=EXPRESSPHARMA

Innopack Pharma Conference Date: June 27-28, 2013 Venue: Mumbai, India

4th Annual Pharma Supply Chain Summit Date: July 11-12, 2013 Venue: Mumbai Summary: Now in its 4th year, CPhI’s Annual Pharma Supply Chain Summit would be focusing on practical case studies and open discussions on important topics like Government Policies - GST Act, extensive use of IT for visibility and automation of supply chain, optimising international logistics and the critical debate on 3PL for

May 16-31, 2013

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effective outsourcing of supply chain. The topics will be discussed in innovative networking formats like speed geeking, i3 centre, clash of the titans and the end of the conference by a relaxing cocktail reception.

Contact details:

tries on the Indian sub-continent, CPhI India and related pharma services events saw an increase in visitors and exhibitors. CPhI India will bring pharma professionals from all over the world to Mumbai and facilitates initiating and closing business deals. Take this opportunity to showcase your products and

services while enhancing your brand at South Asia's leading pharma industry event.

Contact details:

Marol Andheri (East) Mumbai - 400 059 T +91 22 61727162 F +91 22 61727273 E chaitali.patil@ubm.com

Chaitali Patil UBM India Times Square Unit No 1 and 2, B Wing, 5th Floor, Andheri Kurla Road,

Tel: (022) 61727001 Email: Conferencesindia@ubm.com Website url: http://www.pharmasupplychainindia.com?utm _campaign=MEDIAPARTNER&utm_medium=EVENTL ISTING&utm_source=EXPRE SSPHARMA

An Investment in Drug Protection

Pharmac India 2013 Date: September 5-7, 2013 Venue: Hitex, Hyderabad Summary: Pharmac India 2013 is 4th International pharma machinery, equipment, bulk drugs, API and material exhibition going to be held in Hyderabad, Hitex.

It has successfully brought together manufacturers and buyers on a common platform and contributed substantially towards the growth of the industry. Pharmac India 2013 is jointly organised by Orbit Exhibitions and IDMA (GSB) and actively supported by BDMA and CIPI. Contact details: Varsha Surve Manager - Exhibitions Orbitz Exhibitions 101, Navyug Industrial Estate TJ Road, Siwree (W) Mumbai - 400015 Mob: 9322037955 Email: info@pharmacindia.com

CPhI India Date: December 3-5, 2013

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Venue: Bombay Exhibition Centre, Mumbai Summary: Reflecting the continued growth in the API, generics, fine chemicals and bio-pharmaceuticals indus-

May 16-31, 2013

#6682

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FluroTec® technology is licensed from Daikyo Seiko, Ltd. Copyright ©2011 West Pharmaceutical Services, Inc.

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POST EVENT iPHEX 2013 pharma exhibition records over `1000 crore profit Over 5,000 trade visitors including overseas buyers, delegates from highly regulated markets like US, Europe, Australia and New Zealand took part he Pharmaceuticals Export Promotion Council of India (Pharmexcil) recently hosted iPHEX 2013, under the support of Ministry of Commerce and Industry, Department of Commerce, and Government of India. The three-day exhibition was inaugurated by Prithviraj Chavan, Chief Minister, Maharashtra and Rajeev Kher, Additional Secretary — Ministry of Commerce and Industry in the presence of Dr GN Singh, Drug Controller General of India (DCGI) and Mahesh Zagade, FDA Commissioner, Maharashtra. The exhibition witnessed a business turn over of ` 1000 crores for the exhibitors. iPHEX 2013 witnessed the presence of 250 stalls where pharmaceutical companies like Ranbaxy, Lupin, Glenmark, Mylan, MSN Labs, Ipca, Ind-Swift, Strides, Aurobindo, Mankind exhibited their products. Over 5,000 trade visitors including overseas buyer, delegates from highly regulated market like the US, Europe, Australia, New Zealand and 3,000 Pharmexcil registered members took part in the exhibition. Apart form this, over 500 overseas buyers were invited with the support of Ministry of Commerce and Industry Government of India.

Around 40 senior regulatory professionals from 20 countries like Ghana, Tanzania, Senegal, Taiwan, Vietnam,

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THE PRESENCE OF A LARGE NUMBER OF DRUG REGULATORS FROM THE OVERSEAS MARKET IMMENSELY HELPED PHARMEXCIL AND ITS MEMBERS TO PROMOTE THE QUALITY AND AFFORDABILITY ASPECTS 26

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Philippine, Benin, Botswana, Burkina Faso, Egypt, Ghana, Niger, Nigeria, Seychelles, Uganda, Belaru, Haiti, Cuba, Dominic Republic, Mongolia, Sri Lanka, Zimbabwe and Health Ministry officials and drug regulator chiefs from Maharashtra, Andhra Pradesh, Gujarat, Karnataka were present for iPHEX-2013.

The presence of a large number of drug regulators from the overseas market immensely helped Pharmexcil and its members to promote the quality and affordability aspect as envisaged in Brand India Pharma Campaign. The campaign was initiated by Ministry of Commerce and executed by Pharmexcil in association with IBEF. Dr PV Appaji, Director General, Pharmexcil said, “We have observed over 19,500 footfalls in the past three days.

We were honoured to interact with the Indian and international regulators. The panel discussion supported the exhibitors as it discussed various issues faced by each other.

Indian regulators assured that all the medicines to be exported from India will be better in terms of quality.”Bhavin Mehta Committee Chief, iPHEX and CoA member, Pharmexcil said, “The exhibition gave high opportunities and supported to explore new avenues. The international exhibitors were happy with the hospitality given by Pharmexcil and assured that there will be quantum leads of business for pharma industry in India.”

Besides iPHEX, PHARMA Pro and Pack Expo 2013 also saw a beeline of visitors. This expo provided an opportunity to join the industry majors from India and across the world at the technology show. It also proved to be a single point of contact to meet potential clients. PHARMA Pro and Pack Expo 2013 emerged as a very successful event providing excellent opportunity for technology exchange and marketing tie-ups.

EP News Bureau-Mumbai www.expresspharmaonline.com

May 16-31, 2013

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th

6 international conference of SAC ACCP seeks active research to provide better healthcare delivery Conducts workshops on outcomes research, pharmacovigilance PKPD, antibiotics stewardship and statistics he 6th international conference of the South Asian Chapter (SAC) of the American College of Clinical Pharmacology (ACCP) and the pre conference workshop on WHO ATC DDD methodology and drug utilisation research was recently held in Mumbai. The event was held in collaboration with the NIRRH ICMR Mumbai, WHO Oslo, GS Medical College, KEM Hospital and MUHS Nashik.

The conference was culmination of the ICMR, ACCP, WHO and Academic Institutions coming together.

In 2012-2013 ICMR conducted five workshops on outcomes research, pharmacovigilance PKPD, antibiotics stewardship and statistics.

The proceedings of the Outcomes research workshop were released by Dr VM Katoch, Secretary DHR, DG ICMR, who promoted the development of clinical pharmacology in India.

Katoch said, “Outcomes research workshop, training participants from all over the country is important from the perspective of healthcare providers and regulators specially in the changing patients demography, disease patterns, drug development and access.�

Katoch in his inaugural speech emphasised the need for younger generation to do active research and translate it into better healthcare delivery to the poorest man in the country. He lauded the efforts of the National Chair in Clinical Pharmacology and the hard work done by the coordinators, mentors and participants of the ICMR workshops and appreciated specially in the multi-centre research projects done by them. He recog-

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Continued on Pg 29 May 16-31, 2013

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st

SPDS organises 1 international convention on dissolution in Mumbai Disso India 2013 was attended by more than 300 delegates

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ociety for Pharmaceutical Dissolution Science (SPDS) has recently organised its first annual international convention, Disso India 2013. The event held at The Lalit, Mumbai focussed on introduction of new technology, innovation and various issues faced related to dissolution. Disso India was attended by the professionals from R&D, QA and QC, as well as the academia. Around 250-300 delegates have registered and had participated in this event.

Disso India 2013 was organised under the Chairmanship of Dr Vinay G Nayak, the PresidentTechnical of Alembic Pharmaceuticals.

Dr L Ramaswamy, Managing Director, Sotax India was the organising secretary of the event and the General

S

Secretary of SPDS. The scientific sessions were programmed and executed under the chairmanship of Dr Mangal Nagarsenker, HOD and Professor of Pharmaceutics, Bombay College of Pharmacy, Mumbai.

Eminent professionals from the pharmaceutical industry took part in the event. Global speakers such as Dr Diane J Burgess, Professor of Pharmaceutics, University of Connecticut, USA discussed on 'In vitro release testing for particulate systems'; Dr Umesh Banakar, Professor and President, Banakar Consulting Services, US, discussed on 'In vitro in vivo co relation : What makes them Challenging?'; Dr Vinod Shah, Ex US FDA, Pharmaceutical Consultant, US, spoke on 'Role of Dissolution and In vitro

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release in regulating pharmaceuticals'; Vijay Kshirsagar, Executive Vice PresidentCorporate QA and Regulatory Affairs, Unichem Lab, Mumbai gave an insight on the topic 'Dealing with out of specification results in dissolution results'; Dr Jean Michelle Cardot, Professor and Head of the Department of Biopharmaceutics and Pharmaceutical Technology from the Universite d’Auvergne, France spoke on 'Statistics and modeling in in vitro release studies'; Samir Haddouchi, Managing Director, SPS Pharma Services, France gave an insight on 'Automation in dissolution testing and validation'; Vatsala Nageshwaran MS, Associate Director, Scientific Operations, Absorption Systems, US spoke on 'Permeability classification

of highly variable drugs using the In vitro Caco-2 Assay; Kailas Thakker, Cofounder and President, Tergus Pharma, discussed on 'Drug release testing of topical dosage forms using diffusion cells; Dr Vinay Nayak, P r e s i d e n t - Te c h n i c a l Operations, Alembic Pharmaceuticals, Vadodara spoke on the topic 'Harmonasation of pharmacopoeal dissolution testing'; Dr Sandip Tiwari, Technical Director: South Asia, Colorcon Asia, Verna, Goa spoke on 'Effect of exciepients on dissolution: Case studies with bio relevant/hydro alchoholic media and Dr Mukesh C Gohel-Course Coordinator, Ahmedabad University, Gujarat spoke on 'Gaining indepth insights on QbD in dissolution testing.'

EP News Bureau-Mumbai

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6th international conference...

Continued from Pg 27 nised the need for developing a network of researchers so that data from India representing all sectors can be obtained to take policy decisions.

Lectures were delivered by experts like Dr Ashok Vaidya, Dr Arun Bhatt, Dr YK Gupta, Dr NA Kshirsagar and Dr Nithya Gogtay. Besides lectures, demonstrations and group work, the participants who represented various states from the far-flung North East to down south, worked on multi-centric projects of great importance such as malaria, tuberculosis, anti platelet drugs and diabetes, They worked under difficult circumstances without funding, The interim analysis of their studies was presented at the conference.

The hard copy of the ICMR book on regulatory requirements for drug development and clinical research was released by Dr VG Somani, Deputy Drug Controller, CDSCO. This multi-authored book consisting of 27 chapter divided into three sections, was conceived and edited by

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SAC-ACCP 2013 Conference organising committee with guest faculty academicians, researchers and industry experts with unique perspective and experience in regulatory requirements.

WHO workshop on ATC DDD methodology and drug utilisation research was conducted by Hanne Strom, Solveig Sakshaug, Christian Berg of the WHO Drug Statistics Methodology Center in Oslo Norway. The need for ATC/DDD methodology and drug utilisation research to evaluate prescription, product safety and efficiency and healthcare delivery was high-

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lighted. Dr NA Kshirsagar, (ICMR) National Chair Clinical Pharmacology and Swati Chaudhary, IMS heath discussed opportunities in India, which was attended by 75 participants selected out of many applicants.

The conference was organised under the aegis of SACACCP by organising committee where Sagar Bachhav was the organising secretary and Vishal Shinde was the treasurer. The conference allowed over 130 free paper presentations. The souvenir and CD of the confer-

ence was released by Dr GD Yadav, Vice Chancellor of Institute of Chemical Technology. International guest speakers Robin Ferner from the UK, Hartmund Derendorf and Guenther Haucchaus from the US, Priya Bari from European Medical Agency (EMA) highlighted various aspects of drug development, communicating and avoiding adverse reaction to drugs and Dr VP Kamboj and Dr OP Agarwal guided the participants with their expert comments.

EP News Bureau- Mumbai

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POST EVENT NIRRH ICMR workshop enhances capacity for pharmacovigilance study Programme consists of two contact sessions and one project work ith an aim to enhance the capacity for pharmacovigilance studies, a workshop for pharmacovigilance was conducted by National Institute for Research in Reproductive Health (NIRRH) ICMR, Mumbai. It was coordinated

by Dr Acchelal Pasi and Sagar S Bachhav with the help of Manish Mahajan and under the guidance of Dr SD Kholkute, Director, NIRRH and Dr NA Kshirsagar, National Chair (Clinical Pharmacology), ICMR. The programme consisted of two contact sessions and one project work. Out of 44 applicants, 20 were selected on the basis of their prior experience and need for capacity building in their region.

The first contact session was inaugurated by Dr VM Katoch, Secretary DHR and DG ICMR. Lectures and hands on work were delivered. Dr Shanthi Pal (WHO,

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Geneva) delivered lectures on basics, as well as advanced topics including international issues. Participants practiced assessment of adverse reactions, using vigiflow which was provided online courtesy WHO, Uppsala monitoring centres WHO. The participants presented their research project to experts Dr YK Gupta, Dr RD Lele and others and refined the protocol based on valuable suggestions from the experts. All participants were asked to work in group to develop multi-centric projects.

Participants worked on projects to evaluate knowledge, attitude and practices of physicians and paediatrician to report ADRS and AEFIs respectively, metabolic risks associated with antipsychotic drugs: A cross sectional study, adverse drug reaction profile of anti snake venom in a rural tertiary care teaching hospital and comparison of Indian and non Indian published literature reporting adverse drug reac-

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ALL PARTICIPANTS WERE ASKED TO WORK IN GROUP TO DEVELOP MULTICENTRIC PROJECTS. PARTICIPANTS WORKED ON PROJECTS TO EVALUATE KNOWLEDGE, ATTITUDE AND PRACTICES OF PHYSICIANS AND PAEDIATRICIAN TO REPORT ADRS AND AEFIS RESPECTIVELY tion of new drugs marketed in India and under safety scrutiny by US FDA and EMA. The second contact session had lectures on data management and statistical analysis, qualitative research, manuscript development, good clinical practices, ethics in descriptive and observational studies and pharmacovigilance programme in India. Lectures were delivered by Dr Nandini Kumar, Dr RR Shinde, Dr YK Gupta, Dr Nithya Gogtay, Dr Shahina Begum. Participants presented interim analysis

data of above mentioned ongoing projects. All the presentations were refined in the light of guidance and comments received from Dr Ashok Vaidya and Dr Robin Ferner, Consultant physician and clinical pharmacologist, Birmingham (UK). It is expected that the training and research project will help develop pharmacovigilance capacity in various parts of the country, enhance safety of medicines and contribute to regulatory decision.

EP News Bureau- Mumbai

May 16-31, 2013

MANAGEMENT INSIGHT FOR MANAGING PHARMA

W H AT ’ S INSIDE

India has a moral obligation to participate in clinical trials PG 35 Without ethics, there is no credibility for clinical trials PG 36 Clinical trials: Safety of research participant is the ethical mandate! PG 37 Need to take a pragmatic view of clinical trials PG 40 Celebrating the new era of clinical research in India on International Clinical Trials day PG 41

RESEARCH 42 PHARMA TECHNOLOGY REVIEW 49 PHARMA LIFE 80

May 16-31, 2013

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Come what may, you have to pay." The compensation guidelines recently put in place by the regulators for study related injuries seems to have only this message for the clinical research industry, says Dr Arun Bhatt, President Clininvent Research But Bhatt is not against regulation per se. He is all for a "transparent and fair regulatory process", with a "reasonable timeframe: three months". Considering that the current timeline is around nine months, Bhatt's concern is understandable.

And the flight of trials from India to other geographies is apparently already happening (See Market cover: Trial(s) by fire: page 17). As Dr Shubhangi Desai, Head Clinical Operations- Asia Pacific, SIRO Clinpharm confirms, in the last three years, pharmaceutical companies don’t mind spending the extra buck to conduct trials in other South East Asian countries, in order to get approvals in the given timeline.

Giving their views in their individual capacity, Dr Viraj

DR ARUN BHATT President Clininvent Research

The problem is that all these actions have come in a span of few months creating a sense of panic amongst all stakeholders

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Suvarna and Dr Partha Gokhale make the point that clinical trials generally ensure better patient care than normal clinical practice and it is unfortunate that Indians are losing out on the good quality care accorded by clinical studies/trials.

SUNEELA THATTE

APURVA SHAH

President, Indian Society for Clinical Research (ISCR)

Chairman, Association of Contract Research Organisations (ACRO)

We have been concerned about over the last year on the uncertainty and unpredictability of the regulatory environment

We can’t want clinical trials for our benefit but ignore the way the industry works

regulators need to look at before finalising these laws so that they don’t create a system that doesn’t work and the local industry just can’t function. Of course, that has nothing to do with the safety or quality, he avers.

Thatte too says that they have been concerned about over the last year on the "uncertainty and unpredictability of the regulatory environment and more recently, the compensation guidelines which have acted as a disincentive to do clinical research in the country."

She says most organisations and institutions are adopting a wait and watch approach at the moment and while they may not see an immediate impact of the compensation guidelines, in the long run it could impact business if the regulatory authorities do not address the concerns of stakeholders on priority. Taking a broader view, she says their greater concern is about the impact on patients. A slow down in clinical research will impact patients and the future availability of effective and affordable medicines in our country, she opines.

What seems to have spooked the industry is the timing and frequency of the recent changes after years of relative inaction. As Bhatt says, the problem is that all these actions have come in a span of few months as a result of a Supreme Court order, creating a sense of panic amongst all stake holders - ethics committee (ECs), investigators, and sponsors.

In spite of their concerns over the implementation of regulatory guidance, industry

would like more rather than less regulatory oversight, a fact borne out when ISCR's Thatte mentions that they have also drawn the Ministry’s attention to four more areas which are equally important components of research governance: investigator site registration and accreditation, CRO registration and accreditation, regulatory capacity building, and credibility of the informed consent process.

Regulations ok, delays not Industry associations have welcomed the efforts by regulators to frame new policy guidelines and refine those already in existence and have in fact been a key part of the drafting process.

Stating ISCR's position, President Suneela Thatte, says they believe there is need for better governance of clinical trials in the country and have welcomed the intent of the Ministry of Health & Family Welfare and the Central Drugs Standard Control Organisation (CDSCO) to create a more robust framework for the conduct of clinical research in the country. "Any steps, therefore, to ensure the practice of the highest standards of ethics and quality and the protection of patient rights and safety is welcomed by us."

Apurva Shah, Chairman, Association of Contract Research Organisations (ACRO) feels that these recent changes are a welcome step and will go a long way in plugging the holes in the system and give a feeling of comfort to the patients/volunteers that the system is in place to ensure their safety and well being.

However Shah cautions that there are a lot of finer points in the process that the

DR SHUBHANGI DESAI Head Clinical OperationsAsia Pacific, SIRO Clinpharm

Some of the points (in the compensation guidelines) will in fact induce the patient to participate in the clinical trial www.expresspharmaonline.com

Sounding the alarm Shah emphasises that the majority of industry players who do a good quality job are in favour of high quality checks so that the weaker players who don’t take ethics and quality seriously are weeded out. Right now due to the wrong doings of a few, the whole industry gets a bad name but what worries him is that the regulators and lawmakers seem to lack an “understanding of how the global industry works and the demands of the market.

We can’t want clinical trials for our benefit but ignore the way the industry works,” he says. Spelling out the issues involved, he says, “India has proven its quality to a large extent but its been failing miserably on time predictability. Regulatory delays are due to lack of manpower, training and understanding of the functioning of the industry.”

He charges that most times, delays and uncertainty due to timing is due to external issues like politics and media heat. Thus it is seen that most times, it is these issues that control the drug development process in India May 16-31, 2013

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rather than it being driven and controlled by scientific issues and concerns. Shah cautions that other smaller countries like South Korea who have a planned approach are beating India on every front.

Sounding a warning, he says,“The net result is that our local capability of developing new drugs is diminishing fast and it will become a distant dream. That’s a pity because clinical research could have been a huge socio-economic opportunity for India and would have helped solve some of our country’s problems such as lowering the cost of healthcare, improving the delivery of medical care, offering employment and foreign exchange earnings.”

Suvarna and Gokhale bring forth another related reason for the decrease in clinical trials coming to India: the unreasonable demands of the National Drug Advisory Committee (NDAC) with respect to protocol amendments, site selection etc. which add to the delays.

per the new amendment, PIs need to report serious adverse events (SAEs) to licensing authority, EC and the sponsor/ its representatives within 24 hours of occurrence.

They contend that this is unreasonable and unrealistic, as investigators will be able to report a SAE only once they become aware about it

through the patient or the relative of patient, as the case may be, making this regulation impossible to follow.

Desai of Siro Clinpharm too highlights the cumbersome nature of this request, and cites one rule which requires different colour envelopes for different types of SAEs, which only stretches timelines further.

This will be an additional workload for the PI predicts Bhatt and in addition, they also have to consider issues related to compensation guidelines when they carry out their own clinical research. Additionally, there is apprehension about surprise regulatory inspections.

Most investigators might become reluctant to take part

in trials because of these issues, feels Bhatt.

An IT raid or site visit?

Suvarna and Gokhale also point out that PIs are concerned regarding the lack of training and background (i.e. expertise/profession etc.) of drug inspectors who come to inspect their clinical trial sites.

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Impacting innovation Bridging the sponsor/CRO and the patient, lies the investigator community, comprising doctors and other clinical staff who actually conduct the clinical research study and are therefore possibly the most vital link in a clinical trial. On the shoulders of the principal investigator (PI) lies the responsibility of doing right by the patients he recruits to trials as well as to corporates who sponsor the trial. (See testimonials from PIs on pages 80-81) But not all trials are initiated by corporates. As Thatte of ISCR points out, “There is a lot of institution-initiated and investigator-initiated research being done in India and they are perhaps the most impacted in particular by the new compensation guidelines. We believe that these guidelines could negatively impact the spirit of innovation and research that exists in many of our best medical institutions.”

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From the idea to turnkey production in the pharmaceutical and biotech industries

Headquarters: Glatt Ingenieurtechnik GmbH Nordstrasse 12, 99427 Weimar / Germany phone: +49 -3643 -47-0 fax: +49 -3643 -47-1271 eMail: info@glatt-weimar.de Indian Office: Glatt (India) Pharma Engineering Pvt. Ltd. 13 Ground Floor Palam Marg, Vasant Vihar New Delhi - 110057 / India phone: +91 -11 - 460 529 60 / 61 / 62 fax: +91 -11 - 460 529 64 eMail: info@glatt-india.com

Investigator issues Going into more detail, Suvarna and Gokhale say that PIs are worried because of the unreasonable regulations put forth by the current amendment to the Schedule Y of Drugs and Cosmetics Act, 1940. For example, as May 16-31, 2013

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Sharing their experiences, the duo point out that the observations shared by global regulatory staff like the US FDA inspectors, are to generally develop the quality of research at the site. At the end of the inspection, an inspection site report is shared which not only points out the deficiencies but also the good practices followed by the site. The report encourages the site to correct the deficiencies and improve the quality of research for future trials, they explain.

On the other hand, they allege that the attitude of Indian drug inspectors is like conducting a sting operation or an Income Tax raid.

Further, many of the inspectors are not from the field of clinical trials/ studies and have a background of conducting good manufacturing practice (GMP) inspections and the duo allege that they use the same yardstick for good clinical research practice (GCP) inspections.

If the industry is unhappy with the quality of regulation and the regulators, is self regulation the answer? To some extent, internal checks already exists. As Desai points out, all ethical companies already have best practices on maintaining quality and compliance in GCP guidelines through periodic audits to demonstrate compliance to the framework.

But self regulation is not the full answer. Thatte believes that "self-regulation cannot and should not replace regulations and policies. Rather it will add an extra layer of governance for the industry and an extra layer of protection for patients, and should co-exist with government regulation.

The role of robust governance mechanisms by the regulator cannot be over-emphasised," is her reasoning.

Industry believes that they are unnecessarily maligned and the perception that they are trying to escape the regulator's net is baseless.

For instance, Suvarna and Gokhale make the point that the DCGI and Indian media also need to realise that global multinationals who conduct clinical trials in India are not only governed by Schedule Y of Drugs and Cosmetics Act, 1940 and Indian Good Clinical Practices but also by international guidelines like

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US-FDA, EMEA, Health Canada etc which have much more stringent regulations.

They state that there have been a number of international site inspections conducted by global regulators like US-FDA, EMEA, Japan, UK-MHRA till date and no major concerns have been seen in any of their Indian sites. The point seems to be that with so much at stake, playing by the rules is in the interest of industry.

Besides the regulators, the industry directs equal censure on the media for its reportage on the sector. As Thatte comments, the contin-

'happily ever after'; of course after some ‘prescribed’ medicine.

Thatte expresses ISCR's appreciation of the various efforts taken by CDSCO but also highlights how more needs to be done on each front. For instance, while the CSDCO's intention was to bring clarity and robustness in the clinical trial approval process with the setting up of the Apex Committee, Technical Committee and Expert Committees, ISCR has requested for complete clarity on the functioning of these committees, perhaps alluding to a lack of transparency.

“While these committees re- evaluate the current

VIRAJ SUVARNA

PARTHA GOKHALE

Media’s role?

The attitude of the Indian drug inspectors is like conducting a sting operation or an Income Tax raid. Further, they have a background of conducting GMP inspections and use the same yardstick for GCP inspections uous negative reporting of clinical research and, at times misrepresentation of information, has done little to encourage investigators to pursue clinical research. She adds that this does not mean misconduct should not be reported ... but the value and role of clinical research and positive benefits it has brought to hundreds and thousands of patients in our country needs to be and should be highlighted.”

Bhatt says that it is likely that due to recent media stories focusing on deaths in clinical trials, patients would be afraid of taking part in clinical trials.

So what approach would industry like media to take?

Thatte believes media can and should play an important role in educating patients about their rights and responsibilities in a clinical trial so that they can make a more discerning choice.

Learning to co-exist Inspite of the 'gloom and doom' scenario painted above, each stakeholder still seems to be hoping for a www.expresspharmaonline.com

approval processes, the routine functioning of the CDSCO should not be compromised, thereby leading to unpredictability in the review and approval process of clinical trials,” highlights Thatte.

The common refrain seems to be that more regulations and a review of the existing process are welcome but this should not slow down the routine process. So what measures need to be taken to end the impasse?

Thatte's suggestions as the ISCR spokesperson range from the need for more consistency and stability in the regulatory office; openness and transparency; to continued industry dialogue; quicker responsiveness and action on issues addressed.

She also asks for a policy framework that provides clarity of the Ministry’s intent and larger vision. “We also believe that those found guilty of violating existing rules and guidelines should be brought to task and blacklisted. We do not condone violation of any guidelines,” asserts Thatte.

Desai too advocates

measures like a system of deaccreditation or penalising companies, sites, CROs, investigators, for non-compliance, just like US FDA. She suggests that industry must also consider leveraging IT to better the process (for instance, its easy to envisage that improved IT processes could ease and speed up the safety reporting process). Her other suggestions include regular periodic inspections of sites, CROs and ECs to ensure compliance and requiring training certifications for participation of a principal investigator in a clinical trial.

Suvarna and Gokhale believe that the answer lies is more empowerment of the DCGI (Drugs Controller General of India) who should be brought to a level of a joint secretary in the health ministry. Only once the DCGI is empowered will it have the authority to answer parliamentary queries.

Manpower is the next target, with the duo calling for a ramp up of the department with input of people who understand and/or have necessary professional background of medicine and pharma science. They point out that only medical and scientific people could answer some of the “out of context questions” raised by our parliamentarians. Haring back to Desai's point about leveraging IT, they opine that the records management of the (DCGI's) office needs a complete overhaul with computerisation in key areas.

Shah signs off expressing the hope that if we can plug these regulatory holes in India, we soon have a chance to compete and secure a place in the industry as a preferred destination.

The last word belongs to Bhatt, as he probably speaks for all stakeholders when he calls for a regulatory system with a balance of safeguarding clinical trial subjects and supporting innovation, with the the inspection process being used to improve the quality of clinical trials and train various stakeholders.

As the industry comes together on International Clinical Trials Day on May 20, let’s hope the occasion spurs more solutions and productive debate rather than a rehash of previous issues. viveka.r@expressindia.com (With inputs from Usha Sharma) May 16-31, 2013

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OPINION India has a moral obligation to participate in clinical trials Milind Rege, Clinical Team Leader – Clinical Monitoring, SIRO Clinpharm and Dr Shubhangi Desai, Head Clinical Operations - Asia Pacific, SIRO Clinpharm make the moral case for participation in clinical trials

Milind Rege

the same cannot be said about their contribution to the lifesciences. Due to better opportunities in other established fields such as IT, these gradu-

ates could not contribute to life sciences. However, clinical research is an area where Continued on Pg 39

Dr Shubhangi Desai

he global pharmaceutical business, like any other industry, sustains itself on innovation.

Stakeholders in this process, patients, doctors (principal investigators), pharma / biotech companies (sponsors), clinical research organisations (outsourcing partners) and millions of healthcare professionals form the path of innovation. A major part of the process is testing the drug for its safety and efficacy and over the years the drug development industry has evolved to meet the global healthcare needs.

According to various industry estimates, it takes approximately 10-12 years for a new drug to enter the market with more than $1 billion investment. Each drug moving through the drug development pipeline is rigorously scrutinised for its safety and efficacy. Industry estimates suggest that amongst the various costs associated with drug development, the share of the conducting clinical trials is the highest. Be it a commonly used drug like paracetamol or an advanced cancer drug like Trastuzumab, they have all gone through rigorously monitored phases of drug testing.

So, why is this industry, which seems to be a very important part of our lives, not known to us? How many people really understand the process? Where is India on the global clinical research map?

Do we have a moral obligation to be a part of it?

Throughout history India has made notable contribution to the fields of science and technology. Every year hundreds of thousands of new science graduates enter into the workforce and their contribution in the fields of engineering and computer sciences is well documented. However,

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INSIGHT Without ethics, there is no credibility for clinical trials Amar Jesani, Editor, Indian Journal of Medical Ethics, says ethical considerations are absolutely essential for upholding the science of clinical trials, and more importantly, their credibility cience is a new religion of society. The globalisation of clinical trials (CTs) by pharmaceutical companies with the expansion of activities of the contract research organisation (CROs) to whom the former outsource CTs, have sought to convert many doctors who were hitherto involved in only clinical practice into 'scientists'. The doctor-clinical investigators as new converts, along with the clinical investigators in the industry, are dismayed by the recent political developments demanding more stringent regulations on the CTs. The extreme positivist members of the scientist community is therefore struggling to uphold its unfettered or 'self-regulated' right to research people, including experimenting on them in the same way that natural scientists would like to do, or are doing, on the inert material available in nature.

Science without ethics is like economic growth without concern for the good of masses labouring for it and the inclusive redistribution of the surplus created by the growth.

The science of CTs demands experimentation on the living human beings. A large number of them come from the excluded strata of the society.

In the ethics discourse they are termed as vulnerable participants in research. They suffer medical and social handicap – inadequate access to health care in their diseased state, low education, poverty, low social status, discrimination and so on.

The ethics of science would demand that the CTs are conducted primarily for their good, their autonomy respected and are not tricked into participation, they are not harmed, are compensated when harm occurs, they are provided medical and other benefits for volunteering to be a part of the experiments,

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and they and the other similar members are not left high and dry from post-research benefits after experiments are concluded.

The social value of the CTs must be evaluated in terms of its benefits to them, and not merely in terms of new knowledge created, the experience gained by clinical researchers and above all, the business such research brings.

Thus, ethics while taking care of science of the CTs (unscientific research is unethical per se) and its relevance to people, also demand high ethical standards in the very performance of scientific activities. These ethical considerations are absolutely essential for upholding science of CTs, and more importantly, their credibility.

The regulations coming from the state are therefore only a response to increasing erosion of this credibility brought about by last eight years of failure of the 'self-regulations' by the clinical researchers. While they may taste as bitter pills today, if the regulations take the basic logic of transparency, accountability, respect for rights of participants and independent oversight of the CTs to logical conclusion, they may do good to the clinical research in the long run in the country.

Vulnerability v/s 'cheap' and 'quick' research The international selling pitch of CROs in India to get more business of the CTs in last eight years has been the idea of 'cheap' and 'quick' research — both general for resources needed and early conclusion of CTs as well as in terms of recruitment of participants and absence of accountability for provision of trial and post-trial benefits.

This marketing mindset is contrary to the fundamental principle of research ethics when vulnerable people with reduced autonomy, comprehension and power to exercise their rights are used in experiments. That is, vulnerable people need more protection, www.expresspharmaonline.com

more benefits, longer and aided process of comprehension and specialised assistance to exercise their rights.

This can neither be cheap, nor quick.

The earlier such a mindset is changed, the better it would be for the science of CTs. The investigators and clinical researchers, as professionals, should have been the first to raise objection to such marketing gimmicks. Not they, but the people in civil society and enlightened media professionals seem to be doing their job at present. That does not do any good for the credibility of the science of CTs and professionals involved in it.

Ethical obligation to participants As a member of ethics committees of several biomedical institutions in last over a decade I observed that doctor-investigators in India suffer as much from the therapeutic misconception (conviction that the new drug being tested is better) as the patients they recruit for the CTs. This situation introduces bias, which they help transmit to the participants in the recruitment process. It also signifies that these investigators have not imbibed the scientific temper, a hallmark of good researcher.

There is some strong clamour against the new regulation providing right to compensation for serious adverse outcomes of the CTs and not merely due to the adverse effect of the experimental drug.

This opposition is based on the faulty ethical understanding that only those who receive the experimental drug are being experimented upon, and others are not. In clinical practice, a doctor designs therapeutic measures solely based on the best interests of the patients. In the process, those measures are modified from time to time keeping in mind the needs of the patients and progress of disease.

This flexibility of clinical practice is seriously curtailed in CTs, as experiments neces-

sarily demand standardised constant protocols. There is space to manage adverse events of experimental as well as standard drugs, but there is hardly any space to prevent them by making timely adjustments as on blinded trials it is not known who is receiving what. This creates an ethical obligation to provide full free medical management for all adverse events in all participants, and compensation for all those who suffer injuries or deaths.

There is no doubt that the credibility of clinical research has been seriously dented in last eight years of liberalisation of CTs in India. The data coming in the public domain on the number of serious adverse outcome and deaths reported show the lack of transparency on how they are related to the CTs and very few provided compensation of measly amounts. Added to that are recurrent reports of violation of other ethical standards. They make the situation only worse.

It is no use blaming others – the civil society, media or politicians. They are doing their jobs. The credibility of clinical research will not be re-established by playing the blame game, but by strictly ensuring that high ethical standards are observed in the CTs. Not just that, like it is said in reference to dispensation of justice, they must also be seen to be observed.

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LEGAL EAGLE Clinical trials: Safety of research participant is the ethical mandate!

Dr SV Joga Rao, Advocate, Solicitor & Healthcare Consultant, Legalexcel, Bengaluru, shares his experiences about the role, responsibility, accountability and functioning of institutional ethics committees in the context of regulating clinical trials he Supreme Court of India in its recent order directed the Government of India to furnish details as to regulatory controls governing clinical trials in India. This is in response to a writ petition filed by a group of public spirited citizens seeking judicial intervention pertaining to certain clinical trials conducted on women undergoing psychiatric treatment in one of the cities in India.

Initial media reports claimed that these trials were conducted over a period of two years flagrantly violating the applicable regulatory guidelines and mostly without getting mandated approvals from institutional ethics committees (IEC).

This particular incident is not an isolated one. Of late, there were reports indicating such conduct of trials involving women and children in other states as well.

Speaking for Indian context, the clinical trial industry which is barely a decade old has recently been projected by an influential industry association to grab business value to the tune of $1 billion by 2012-13.

Naturally this kind of projections made the sub-continent as one of the world's most preferred destinations for clinical trials. According to some quarters by this year-end, India will be conducting more than 15 per cent of total global clinical trials.

The conducive environment has succeeded in drawing drug companies to India to undertake diverse clinical trials for multiple reasons like, technically competent workforce, low cost, adequate infrastructure, and friendly drug control system and more importantly availability of patients and

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healthy volunteers.

Booming clinical trial industry has raised very serious issues pertaining to conduct of trials and human safety. The regulatory framework governing clinical trials in India takes within its fold, The Drugs and Cosmetics Act and allied rules, Schedule Y and most significantly Ethical Guidelines for Bio-Medical Research on Human Participants generated by Indian Council of Medical Research.

Apparently, owing to the pressure mounted by Supreme Court, recently two Gazette Notifications have been issued dealing with Registration of IEC and related formalities and compensation in case of injury or death during clinical trial.

In the entire ambit of regulatory control governing clinical trials, ethical review

by IEC plays a crucial and pivotal role. In fact the role of IEC informs us that the gamut of clinical trial is not merely a matter of business proposition but an area of humanitarian concern.

As a teacher of healthcare ethics and law for more than two decades and as a chairperson of select institutional ethics committees for almost a decade, I write to share my experiences about the role, responsibility,

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accountability and functioning of IEC in the context of regulatory framework and particularly the landscape of challenges that are encountered.

As a chairperson, by and large I was a mute spectator during first few meetings.

Literally, I could not decipher anything that was deliberated. Presentations by PIs and ensued interactions were too technical, fully loaded with medical jargon.

Apart, I could not comprehend what has been stated in protocols and large volumes of related documents. I used to wonder, why participation of a person from legal background was mandated by the guidelines.

At that time, fortunately, I came across Dr Vasantha Muthuswamy and Dr Nandini Kumar (then with ICMR, New Delhi) in a National Conference held in New Delhi. From then onwards, on several occasions, I used to interact with them about IECs and its role in clinical trials. Till their superannuation and even thereafter they have played a singular role in generating public awareness and facilitating evolution of pertinent guidelines.

I have had the opportunity of receiving tremendous insight about clinical trials and the need for sensitive policy and law sensitive to human concerns.

These experiences enabled me to realise the role of a legal professional (either as a chairperson or member of IEC). While taking other members into confidence, I took several initiatives of bringing awareness among IEC members about the legal and regulatory framework governing clinical trials, and more particularly, the role and responsibility of IEC in the backdrop of ICMR and related international guidelines. Similarly, members have been consistently informed about legally binding contractual relationships between and among key stakeholders like sponsor, CRO, SMO, hospital and principal investigators.

By and large, none of the PIs were aware about any of the clauses envisaged in Clinical Trial Agreement (CTA) and significantly clauses like Indemnification and Limitation or Exclusion of Liability were absolutely incomprehensible. I used to discuss threadbare about the

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meaning and implications of this type of clauses in the Scheduled IEC meetings. In addition, the role and responsibility of IEC in according approvals to trials and particularly the basis on which the approval requires to be premised was repeatedly and consistently emphasized.

During that period ICMR had invited me to participate in several workshops organised exclusively for IEC members (nationwide) focusing on capacity building pertaining to legal and regulatory framework governing clinical trials.

Singularly, I would want to mention about our struggle relating to incorporation of certain clauses in Informed Consent Form (ICF) and Patient Information Sheet.

When it comes to participation in a clinical trial (either as a patient or healthy volunteer) informed consent plays a crucial role.

From ethics point of view, this is a very significant nonnegotiable compliance factor. Rigorous and close scrutiny of all the clauses envisaged in ICF is very crucial for IEC for the purposes of deciding whether a particular proposal deserves to be approved or not.

Quite often, we used to encounter serious dilemmas relating to envisaged risks and complications. Either the words used to convey risks or complications are very vague or contradictory in nature at times.

Particularly, with regard to ‘medical care’ to be provided to a research subject in the event of any kind of adverse event, we used to get a stock response from almost all trial sponsors i.e., clinical trial insurance takes care about the same.

On the basis of detailed perusal of relevant terms and conditions of clinical trial insurance, I used to vehemently contest this claim on the ground that the insurance policy provides compensation (provided if such adverse event encountered by the research subject doesn’t fall under the ambit of exclusion clauses stated in the policy) only but not medical care. Even assuming for the sake, when will such compensation be paid to the research participant and till that point of time who will be responsible for the care and well being of the research participant? www.expresspharmaonline.com

Literally, these concerns were never given credence, during the initial years.

On several occasions, approvals have been withheld seeking amendments and incorporation of specific clauses to this effect. Very rarely, we used to get positive response from sponsors, in this specific regard.

On a couple of occasions, our decisions were contested by arguing that IECs at other centres have already approved and more particularly, the trial being a multisite centric, amendments cannot be accepted heeding a site specific decision. In addition, they used to justify their claim on the ground that there is not statutory mandate towards this end.

In majority cases, our concern about ‘medical care’ to be rendered to a research participant in the event of any injury or adverse consequence has not been positively addressed.

From then onwards, we have collectively taken a decision to insist on such a clause as a matter of institutional policy. To that effect, we have substantially succeeded in seeking compliance from several sponsors.

Recently issued gazette notification quite explicitly puts at rest the so called ‘contest’ as projected by select sponsors. Now it is amply clear that warranted ‘medical care’ must be rendered to needy research participants as a matter of statutory mandate. Hereinafter, sponsors can not take the shelter under convenient contractual terms and conditions to support their claim in not rendering medical care.

In a way recently issued gazette notification mandating registration of IEC is the warranted step in the right direction. This is something that is long overdue at a fundamental level.

However, the responsibilities of IEC envisaged under the notification relating to compensation to injury or death warrant a thorough reexamination. For instance, as per the notification, IEC is expected to file a report before Drugs Controller General of India (DCGI) as and when asked detailing with clear reasoning as to whether the adverse consequence (injury or death) experienced by the research participant is attributable to clinical trial or not. And if so, what is the recommended

amount payable by sponsor as compensation. The ultimate decision will be made by the licensing authority.

The crucial issue in this regard is, on what basis IEC can come to appropriate conclusions. No doubt, the input rendered by PI is a matter of great relevance.

Particularly, in cases where, the research participant is a patient, it would almost be impossible for IEC to reach an objectively verifiable finding. On many occasions, the cause of adverse consequence may not be ascertainable without postmortem. Speaking for our context, getting nod of postmortem is a very difficult task. Unless such death is construed as medico-legal case, postmortem as such cannot be mandated. Even assuming that, there is a consensus as to postmortem, nevertheless, facility to conduct or organise postmortem as such may not be feasible.

In the absence of convincing and reliable input and information, IEC may find it very difficult to either decide about the cause of adverse consequence or recommend quantification of compensation. No doubt, there are guidelines pertaining to quantification are made available. However, there is mounting criticism against these guidelines questioning the rationale and basis. Similarly, some of the clauses require substantial changes. In this regard, the clause dealing with deemed clinical trial injury or death warrant need a re-look.

While positively appreciating the evolving and emerging nature of regulatory framework governing clinical trials in India, the need for a more meaningful consultation particularly with IEC members cannot be undermined. Undoubtedly, issuance of recent Notifications indicates a knee-jerk reaction and apparent response to Supreme Court’s ongoing interventionist role.

While considering safety of research participants as the most fundamental ethical mandate, it is our bounden duty to ensure that the applicable policy, law and regulatory framework are sensitive to this concern.

Towards this end, purposeful contribution from everyone concerned is the need of the hour.

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India has a moral...

Continued from Pg 35 these graduates can make a positive contribution. Just as IT industry boosted economic growth in the nineties, the clinical trial industry has the potential to create thousands of jobs and contribute to economic growth. Globally, about 20,000 trials are registered in a year. About 90 per cent of these trials happen in the developed countries of North America and Western Europe.

Additionally, there is a well developed regulatory framework for conducting clinical trials which highlights responsibilities of sponsors, investigators and patients.

This framework provides strong regulatory oversight and risk mitigation measures to ensure patient protection and scientific and ethical validity of the study. Less than two per cent of the global clinical trials happen in India.

Low R&D spend, uncertain IP protection and regulatory uncertainty has contributed to the slow pace of growth of clinical trials in India.

In contrast, the disease burden in India is growing at an alarming rate. As per the latest prevalence data, cumulatively 150 million patients in India are suffering from diabetes, cardiovascular or respiratory diseases. Additionally, another two million patients are reported to have been diagnosed with cancer. The incidence rate of these diseases is also increasing much faster than developed countries due to changes in lifestyle and risk factors such as tobacco use, obesity and stress.

The healthcare facilities in India are woefully inadequate to effectively tackle the growing disease burden. Also, the quality of care offered in most hospitals is sub-par and not necessarily in accordance to international standards. Such a scenario is more likely in Tier II & III cities of India.

Also, there is a need to develop medicines specific to the needs of the population of India.

However, since pharma R&D is highly risky, indigenous companies tend to shy away from the massive investments required. This is evident from the fact that filings in the pharma sector annually in US is more than 20 times than that of India despite having a comparable disease burden. We therefore, need to rely on western medications to May 16-31, 2013

tackle our healthcare needs. In many instances this is detrimental as the innovator company may launch the drug in India anywhere between two to 14 years after other markets, thereby denying best-inclass treatments to patients.

Therefore, it can be argued that India has a moral obligation to participate in clinical research. By actively participating in clinical research India can make a positive contribution in the furtherance of the pharma sciences.

Additionally, during the course of a clinical trial the subjects not only get access to cutting edge medications but also to advanced healthcare modalities which they would not have otherwise got access to.

Conducting trials in India meant better patient reach for global trials and access to cutting-edge life saving drugs for patients in India. Increased patient population for a trial results in quicker enrolment and eventually leads to the drug coming to the drug much earlier. The trials were extended to Asia in order to increase the gene pool and bring data from different parts of the world, thus presenting better results of drug efficacy.

The growth in this industry, like any other commercial sectors, has also created its share of criticism. Clinical trials being an essential step in drug development, regulatory bodies in the US, Europe and Japan have established documented procedures for overseeing and regulating clinical trials. India too is taking steps to ensure that a strong regulatory framework is established to support the growing trends in outsourcing of trials by multinational sponsors to optimise the costs for drug development. With the right regulation India can leverage its deep genetic pool and its ability to provide high quality clinical data by being an active participant in pivotal trials.

Many rare diseases or cancers require treatments that are well beyond the reach of the general public even in western countries. The only point of access for such medications is clinical trials since many of them are awaiting marketing approval pending submission of data.

Finally, we must also ask ourselves the question whether we are willing to consume drugs that have never been tested or inadequately tested on Indian population. www.expresspharmaonline.com

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INDUSTRY SPEAK Need to take a pragmatic view of clinical trials Kiran Mazumdar-Shaw, Chairman and Managing Director, Biocon says that without trials there is no way pharmaceutical research can advance to improve disease management and the very quality of life

KIRAN MAZUMDAR SHAW CMD, Biocon

he drugs we use to treat any condition – from an innocuous cough to a life-threatening cancer – are the outcome of painstaking human clinical trials. These trials are the only way to credibly determine the safety and efficacy of drugs. Without trials there is no way pharmaceutical research can advance to improve disease management and the very quality of life.

Drugs go through several stages of development prior to human trials. The trials themselves are approved and regulated by government agencies and undertaken only after animal experiments prove their safety beyond any evidentiary doubt. Even then, the safety and efficacy of a drug on humans needs to be proven before it can go to market.

Unpredictable outcomes are but natural in this process – no wonder then that they are known as ‘trials’! The successful outcomes are of vital significance – for they not only help the patients involved in the trial but also transform the lives of hundreds of thousands who benefit from the commercial launch of such experimental drugs. Take some recent life-changing cancer drugs which have helped overcome what was thought to be an incurable condition – two such that readily come to mind are Herceptin for the treatment of breast cancer and Gleevec for the treatment of leukaemia.

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I believe we need to address the issue of clinical trials not with blind emotion but with a rational understanding of the benefits and with greater compassion for those suffering for want of effective medicine

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The recent controversy over human clinical trials in India is worrisome as it has had a chilling effect on the clinical trial approvals in the country. Only six studies have been cleared by DCGI in 2013 so far, last year over 260 studies were approved. A series of articles in newspapers apparently aimed at tarnishing the entire clinical trials sector and some NGOs going to court with public interest litigations seem to be fuelling it. These individuals and entities are whipping up emotions by portraying only the darker side – showing how some terminally ill patients didn't survive in a clinical trial. As the Indian Society for Clinical Research (ISCR) has said, those partici-

pating in trials are already afflicted. Their death, therefore, was not due to the drug.

If they were terminally ill, the drug perhaps was not as effective as was anticipated.

It is important to note that many trials in India are phase III trials which are global trials with a stringent common protocol for already well-tested drugs. Hence, the risks to patients are minimal. In any case, without a trial it is impossible to determine if and how a drug works. Factors such as racial characteristics, genetic make-up, and individual biochemistry also have a bearing on the outcome of a trial. Using Herceptin as a case in point, without a clinical trial it would have been impossible to learn that the drug is only useful for patients who have tumours that are HER2 positive.

In this entire discourse, what is really frightening is that we are succumbing to a herd mentality. Instead of addressing specific issues that need fixing in some clinical trials, the effort seems to be to paint all clinical trials with the same brush.

The result is that the government is now penalising everybody for the non-compliance of a few instead of weeding out the bad elements.

The Government’s move is destroying the innovation culture in India and hindering access to affordable treatment options for patients in India.

Such knee-jerk reactions will only make much-needed new drugs inaccessible to more Indians. Beyond the horror fiction, let us examine the reality of clinical trials in India.

Trials in India All drugs need to be tested on ethnic populations to ensure their efficacy; so Indian patients must have representation in trials. Genetic variations can result in different levels of drug efficacy and hence the need for local clinical trials. For example, the cancer drug Iressa worked well in Japanese populations but not so in Caucasians which led to the identification of a gene mutation that determined response. Moreover, some diseases are more prevalent in India. These range from malaria and chikunguniya to www.expresspharmaonline.com

tuberculosis, kala azar and head and neck cancer. Drugs for such diseases can be best tested in India.

For innovative drugs like Itolizumab, which Biocon has developed for the treatment of psoriasis, or the oral insulin drug that is under development, clinical trials in India are very critical to bring novel treatments for patients in India. If we do not have a conducive environment for clinical trials in India, companies like Biocon and others will be forced to conduct these studies in other parts of the world, which will be a huge setback not just to the Indian patients but also to Indian companies engaged in innovation.

The answer, therefore, is not in shackling clinical trials – it will only result in denying better and cheaper drugs to millions of Indian patients.

We must remember that trials are conducted with the highest degree of transparency and with the complete consent of patients and families, disclosing not just potential benefits but also risks involved.

As in any industry, there may be some black sheep – and they must be dealt with utmost severity. But that does not mean that the entire industry is suspect. Industry is conducting ethical clinical research, and the term 'guinea pigs' being used for participating patients is a serious insult.

India advantage blunted India was well placed to be the largest clinical research hub of Asia but due to shackling of clinical trials the CRO sector, is under huge pressure.

The genetic diversity of the Indian population makes India an attractive destination for companies to carry out tests.

But currently just about two per cent of global trials take place in India. China, a rela-

tively late starter, has over nine per cent share of the global clinical trials. Clearly, India is losing out this battle as well.

Pragmatic view paramount The fact is that our current legal framework is strong enough to ensure transparency and ethical practices during the conduct of clinical trials.

However, India has not been able to capitalise on its potential in clinical trials owing chiefly to a lack of effective implementation of regulation.

Additionally, the illinformed and unfounded media reports are hindering the clinical progress in India.

One writer in a recent newspaper article suggested that poor patients should be given a higher compensation. Does the writer realise that this is tantamount to inducement?

All human life is equally precious, so how does one price it? Instead of dismissing clinical trials, we need to adopt a rational perspective of clinical trials – understand how they are run, realise their criticality to patients, and address issues objectively.

Putting clinical trial approvals on hold is not the solution, instead the government needs to efficiently monitor ongoing trials for regulatory compliance and penalise non-compliant companies, investigators and CROs. Existing laws need to be implemented stringently to ensure that trials are conducted ethically with utmost diligence and transparency.

Compensation in case of adverse events should not just be fair but also equitable without discriminating between patients. A better way of compensation would be to provide patients who participated in a successful trial with free or subsidised drug.

If we curtail clinical trials and global pharma companies move to China, South Korea and other East and South Asian countries – as they are doing – we will only end up hurting Indian patients. We believe we need to address the issue of clinical trials not with blind emotion but with a rational understanding of the benefits and with greater compassion for those suffering for want of effective medicine.

May 16-31, 2013

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OPINION Celebrating the new era of clinical research in India on International Clinical Trials day Paula Brown Stafford, Global Head, Clinical Development, Quintiles, gives an insight about the challenges of clinical research and how it can be addressed ay 20 may be an unexceptional date to most, but to those of us within the clinical research community, it marks International Clinical Trials Day – a commemoration of the day that James Lind began his famous clinical trials into the causes of scurvy in 1747. More importantly, it provides a focal point to raise awareness of the significance of research to healthcare, which contributes to a better understanding of patient needs around the word.

International Clinical Trials Day seems like an appropriate time to consider just how far we have come in regard to clinical research.

Lind's experiments in 1747 consisted of just 12 men, grouped into pairs and given a variety of dietary supplements from cider to oranges and lemons. The trial only lasted six days before Lind saw notable improvement in the fruit-eating group, providing him evidence of a clear link between citrus fruits and scurvy.

These days, I am happy to say that we bring much more sophistication to clinical trials, thanks to the innovation of our forbearers.

Edward Jenner’s development of the first ever vaccine for smallpox in 1796 repre-

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sented a huge breakthrough, but it wasn’t until 1946 that British epidemiologist Sir Austin Bradford Hill pioneered the randomised clinical trial, eliminating bias and introducing us to the power of statistical reasoning in clinical research.

And now, we are at the precipice of the next big leap forward — the era of datadriven, intelligent drug development.

Innovative processes, like risk-based monitoring, and the powerful data analytics of today’s technology, are currently converging to transform the clinical trial on an unprecedented scale. Today’s Clinical Trialists have the unique opportunity to become information managers, combining their skills with data to create insights that can improve drug development globally.

We are truly on the threshold, about to step into a new, knowledge-driven world.

The positive impact of this transformation will benefit clinical research worldwide, including in India, which represents a key component of our global solution at Quintiles. We invested in this region early on back in 1997, and our collaborations there have now successfully evolved, first from local trials to global trials, and then from functional resourcing to full-service. From a clinical research standpoint, the region remains particularly attractive due to the availability of large pools of potential patients and moti-

COST AND SPEED TO MARKET ARE ESSENTIAL ELEMENTS OF EFFECTIVE CLINICAL RESEARCH, BUT ENSURING IMPECCABLE CONDUCT AND QUALITY ARE ALWAYS AT THE HEART OF OUR WORK; IN THESE AREAS,WE WILL NOT COMPROMISE.THE GOOD NEWS IS THAT WE NOW HAVE MORE TOOLS TO ADDRESS EACH OF THESE CHALLENGES THAN EVER BEFORE May 16-31, 2013

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vated investigators for clinical trials.

India is integral to our global workforce with greater than 2,500 Quintiles resources based locally there today. This heavy resource investment reflects not only our confidence that the region will flourish as an essential hub for clinical trials, but also the fact that the therapeutic spread in India mirrors many other countries, which helps us serve patients on both a global and local scale. For example, diabetes is one of the most common lifestyle diseases in India, and it also leads the US in cost of care; therefore, by leveraging our local expertise in conjunction with our global footprint, Quintiles is uniquely positioned to make a significant impact in this disease area in the coming years — but only if we are able to research biopharma products related to diabetes within and outside of India.

India has been a significant contributor to clinical research and the development of new medicines for patients worldwide. In recent months, however, the current regulatory climate in India has been challenging and could prove to be a barrier to including patients from this country in global research efforts. Although we have performed several pivotal regulatory trials with large international companies in India, the regulatory milieu could preclude a lot of the region’s potential growth.

Whereas in other Asia Pacific countries the time to obtain protocol approval is generally decreasing, in India it appears to be on the rise. In addition, some of the rules in the country’s new compensation guidelines go against the basic principles of research.

If we cannot resolve these challenges quickly, it will be very difficult for India to compete with other Asia Pacific countries as we enter this new era of clinical research.

In James Lind’s day, the conduct of clinical trials was much simpler. Now, the cur-

rent drug development landscape is a complex balancing act of several key factors. Of course, cost and speed to market are essential elements of effective clinical research, but ensuring impeccable conduct and quality are always at the heart of our work; in these areas, we will not compromise. The good news is that we now have more tools to address each of these challenges than ever before.

Intelligent trial design and novel data integration technology are allowing us to coordinate our research on a global scale with unprecedented efficiency, quality and transparency. With gene sequencing and new biomarkers, we are transforming clinical research into a more targeted effort via personalised medicine. India has an important part to play in this new era if we can use these tools to address its current challenges.

As we celebrate International Clinical Trials Day, let us remember why India and the rest of the world should all be proud to be part of clinical drug research. The clinical trial has contributed to nearly all of the life-saving medicines that we know today. It has led to drugs that make organ transplants possible, make diabetes a manageable condition, and added nearly 20 years of life expectancy to AIDS patients. Clinical trials are a necessity to the advancement and launch of new products to treat the diseases that plague our young and old in both India and the rest of the world.

India holds 16 per cent of the world’s population and the highest disease burden in the world, creating a compelling case for clinical research in this country. We have come a long way, and I have no doubt if India can work together with the global clinical community to address its current regulatory challenges, this region will continue to play a pivotal role in the great medical invention knoswn as clinical research.

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W H AT ’ S INSIDE

RESEARCH EXPERTISE FOR DRUG DEVELOPMENT

In situ gelling polymeric drug delivery system PG 44 Regulatory impact on clinical trial insurance PG 47 FDA warns on use of certain migraine drugs during pregnancy PG 48

PHARMA TECHNOLOGY REVIEW 49 PHARMA LIFE 80 42

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R|E|S|E|A|R|C|H anipal Institute of Regenerative Medicine (MIRM) has been the frontier institution in India for the past seven years, fostering and advancing stem cell research and training aspiring stem cell researchers. Regenerative medicine is the rapidly developing science. In the quest to further develop on Manipal University’s leadership in medical education and research, the institute was established in 2007.

“From its inception at 2007 to present, MIRM has achieved enviable goals in cutting edge research, patent and publications in stem cells. It has also managed to get vast public and private funding both nationally and internationally and has nurtured a body of talent in regenerative medicine through its Master’s (M.Sc), M. Phil and PhD programmes,” informs, Dr Ramesh Bhonde, Professor and Dean, MIRM. The curriculum of MIRM is recognised internationally by reputed universities across Europe, Australia and the US. The limited number of batches create a highly cooperative environment between faculty and students. MIRM provides a ecosystem of teaching and research excellence for making it a universally accepted destination by students.

MIRM has further attracted sponsorship in industrial ventures and is well equipped for conducting comprehensive research in any branch of stem cell development with industry tie-ups. This has been possible partly due to its accessibility to the Manipal Hospital and patients and also due to its location in the 'Silicon Valley' and the biotech hub of India, Bangalore. This has

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Dr Ramesh Bhonde Professor and Dean MIRM

May 16-31, 2013

set the stage for collaborations with scientists, clinical researchers, biomedical engineers, business leaders, and venture capitalists Bhonde says, “In a nutshell, research at MIRM encompasses both understanding of fundamental mechanisms in stem cell biology and regenerative medicine and also to ask key translational questions which would help to bridge the gap between basic research and clinical application.”

Research activities Investigators at MIRM study all forms of stem cells including embryonic, newborn (umbilical cord and placenta), adult and patient-specific stem cells and their collective applications in the generation of new cells and tissues for treatment of many of the most devastating diseases. The research includes the basic understanding of molecular mechanisms underlying self-renewal, as well as directed differentiation of stem cells to form heart, hepatic, pancreas, neuronal cells and repair and regeneration of immune, respiratory, liver, spinal and neural tissues. Research focus also include using the natural anti-inflammatory and repair-inducing properties of adult mesenchymal cells in the repair of chronic injury and also on cancer stem cells.

“The ultimate goal of MIRM is to translate this knowledge into dramatic new medical therapies for some of the world’s most serious and intractable afflictions. In future, MIRM is optimistic to be able to offer an excellent in vitro platform for screening of novel pharmacological drugs and toxicity testing including providing impor-

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tant insights into their mechanism of action,” says Bhonde.

Rewards for regeneration Stem cells and the future of regenerative medicine summarise the replacement or regeneration of human tissue and organs, to counter chronic diseases that debilitate organs. While speaking about the advantages that are associated with the institute, Bhonde opines, “MIRM standout from other institutes by its infrastructure and the advanced curriculum set for the students. Each MIRM faculties has expertise in their particular field of stem cell biology and have carved their niche by displaying some of their best ground breaking work in basic stem cell biology. This has been reflected in the number of publications in peer reviewed international journals, which accounts to be approximately 50 in number within a meagre seven years of MIRM’s inception.”

An interaction with the scientists at MIRM highlighted the fact that an amalgamation of basic researchers and pharma industry is very essential to achieve a better human beneficial therapeutic product. Even MIRM has always been in forefront in collaborating with pharma industry and has always kept the door open for such initiatives.

Global demand Manipal University recently signed a MoU with University of Colombo. This is an academic support programme to undertake under graduate and post graduate courses in regenerative medicines. Initially, this MoU will be valid for two years. To understand the course in regenerative medicines, two faculty members and two stu-

dents from Department of Medicines, Colombo University, visited Manipal Institute of Regenerative Medicines (MIRM).

PG course in regenerative medicines will be initiated at Colombo University from August 1 2013. To take this association further, faculty members from MIRM will also visit Sri Lanka depending on the need to conduct specific aspects of theory and practicals. As this association is new, at this point of time, it is only restricted to academic support in teaching and training and there would not be participation from any other pharma companies.

While speaking about the future activities of this partnership, Bhonde says, “We plan to conduct 'Indo-Sri Lanka' joint workshop on stem cell culture. Research projects will be jointly submitted to funding agencies for financial support.”

Future plans MIRM wants to maintain its uniqueness in the future.

Institute would be investing in novel way of using facilities and extending the collaborative projects. “A focus on the big science questions, with an emphasis on applying the stem cell product to help people, coupled with an innovative structure, will be our prime goal. Specifically, MIRM will build on the platform by investing in the areas like obtaining self-sufficient grants from granting agencies, an approach to combine faculty across labs and institutions with a bias towards combating diseases with stem cell products, establishing stem cell banking facilities for research purpose and making MIRM as a centre of excellence in stem cell field,” Bhonde concludes.

Sachin.jagdale@expressindia.com

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INSIGHT In situ gelling polymeric drug delivery system Dr Pradnya Palekar Shanbhag, Associate Professor in Pharmaceutics, Department of Pharmaceutics and Prajal P. Pandhare, Vivekanand Education Society’s College of Pharmacy talk about in situ gel forming systems and how these are used in various biomedical applications including drug delivery n the past few years, increasing number of in situ gel forming systems have been investigated and many patents for their use in various biomedical applications including drug delivery have been reported. This interest has been sparked by the advantages shown by in situ forming polymeric delivery systems such as ease of administration and reduced frequency of administration, improved patient compliance and comfort, also capable of releasing the drug in a sustained manner maintaining relatively constant plasma profile. These systems are liquid at room temperature but undergo gelation once administered. These have a characteristic property of temperature dependence, pH dependence and cation induced gelation. In situ gels are administered by oral, ocular, rectal,

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vaginal, injectable and intraperitoneal routes. Both natural and synthetic polymers can be used for the production of in situ gels. Recent advances in in situ gels have made it possible to exploit the changes in physiological uniqueness in different regions of the GI tract for the improved drug absorption as well as patient’s convenience and compliance.

Approaches for in situ gelling polymeric drug delivery system 1) Physiological stimuli approach a) Temperature induced in situ gel system: The use of biomaterial whose transitions from sol-gel is triggered by increase in temperature is an attractive way to approach in situ formation. The ideal critical temperature range for such system is ambient and physiologic temperature. In this system, gelling of the solution is triggered by change in temperature, thus sustaining the drug release.

These hydrogels are liquid at room temperature (20 –25°C) and undergo gelation when in contact with body fluids (35 – 37°C), due to an increase in

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Dr Pradnya Palekar Shanbhag, Associate Professor in Pharmaceutics, Department of Pharmaceutic

Prajal P. Pandhare, Vivekanand Education Society’s College of Pharmacy

temperature. b) pH induced in situ gel systems: Another formation of in situ gel based on physiologic stimuli is formation of gel is induced by pH changes.

All the pH-sensitive polymers contain acidic or basic groups that either accept or release protons in response to changes in environmental pH. Swelling of polymer increases as the external pH increases in the case of weakly acidic (anionic) groups also known as polyacids, but decreases if polymer contains weakly basic (cationic) groups termed as polybases.

2) Physical change in biomaterial approach a) Swelling mechanism: In situ formation may also occur when material absorbs water from surrounding environment and expand to occur desired space. One such substance is myverol 18-99 (glycerol mono-oleate), which is polar lipid that swells in water to form lyotropic liquid crystalline phase structures. b) Diffusion mechanism: This method involves the diffusion of solvent from polymer solution into surrounding tissue and results in precipitation or solidification of polymer matrix. N- methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), tertahydrofuran, 2-pyrrolidone and triacetin has been shown to be useful solvents for such system.

3) Chemical reaction approach a) Ionic crosslinking: Certain ion sensitive polysaccharides such as carrageenan, gellan gum (Gelrite), pectin, sodium alginate undergo

phase transition in presence of various ions such as K+, Ca2+, Mg2+, Na+. These polysaccharides fall into the class of ion-sensitive ones. b) Photo-polymerisation: A solution of monomers or reactive macromer and initiator can be injected into a tissues site and application of electromagnetic radiation used to form gel. Acrylate or similar polymerizable functional groups are typically used as the polymerizable groups on the individual monomers and macromers because they rapidly undergo photopolymerisation in the presence of suitable photo initiator. Photopolymerizable systems when introduced to the desired site via injection get photocured in situ with the help of fibre optic cables and then release the drug for prolonged period of time. c) Enzymatic cross-linking: In situ formation catalysed by natural enzymes has not been investigated widely but seems to have some advantages over chemical and photochemical approaches. For example, an enzymatic process operates efficiently under physiologic conditions without need for potentially harmful chemicals such as monomers and initiators.

Intelligent stimuli-responsive delivery systems using hydrogels that can release insulin have been investigated.

Polymers for In Situ gelling polymeric drug delivery system ●

Thermosensitive polymers: Cellulose derivatives, Poloxamer, May 16-31, 2013

R|E|S|E|A|R|C|H

●

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Marketed product

Active ingredient

Use

Atridox

8.5% doxycycline

Periodontal treatment with subgingival delivery

Atrisorb D

4% doxycycline

Periodontal tissue regeneration

Eligard

Leuprolide acetate

Treatment of Prostate cancer

Sandostatin

Octreotide

Treatment of Acromegaly

Poly(ethylene oxide) / Poly(D, L-lactic acid coglycolic acid) pH sensitive polymers: Carbopol, Cellulose acetophalate latex Ionic crosslinking polymers: Pectin, Alginic acid, Gellan gum

●

not require removal.

Economic factors: Operating expenses for the production of in situ forming applications are marginal, thus lowering investment and manufacturing costs.

Atrigel system Applications 1) In situ forming drug delivery system for parenteral administration Controlled parenteral systems used in drug delivery are implants, microspheres and liposomes. These suffer from limitations such as implants need surgical implantation, microspheres for parenteral delivery have complex manufacturing process and on other hand liposomes have high production cost and drug leakage is a problem.

Injectable in situ gel forming drug delivery system represents an attractive alternative to microspheres and implants as parenteral depot systems and has following advantages over conventional parenteral system: ● Less invasive technique: The application is less invasive and less painful compared to implants. ● Direct delivery to a target area: This helps in achieving higher drug concentration at the desired site of action to minimise systemic side effects. ● Biodegradable and biocompatible: Injectable in situ system is made of biodegradable polymers and biocompatible solvents and therefore do

The formulation of these systems includes dissolution of water insoluble biodegradable polymer into a biocompatible solvent. The drug is then added to the solution where it dissolves or forms a suspension. This drug and polymer mixture is then easily and conveniently injected into the body where it forms a solid implant inside the tissue.

Most commonly used polymers are poly (dl-lactide), lactide/glycolide copolymers and lactide / caprolactone copolymers because of their degradation characteristics. The solvents employed in the Atrigel system includes dimethyl sulfoxide, N-methyl-2-pyrrolidone (NMP), tetraglycol and glycolfurol to more hydrophobic solvents such as propylene carbonate, triacetin, ethyl acetate. When this formulation is injected into the body the water miscible organic solvent dissipates and water penetrates into the organic phase. This leads to phase separation and precipitation of the polymer forming a depot at the site of injection.

2) In situ forming drug delivery system for ocular administration Conventional ocular drug delivery systems used are eye drops, eye gels, eye ointments suffer from poor bioavailabil-

AN INCREASED BIOAVAILABILITY WITH SUSTAINED DRUG RELEASE PROFILE OF THEOPHYLLINE IN RATS AND RABBITS WAS OBSERVED FROM GELLAN FORMULATIONS AS COMPARED TO THE COMMERCIAL SUSTAINED RELEASE LIQUID DOSAGE FORM May 16-31, 2013

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ity due to tear production, transient residence time, impermeability of corneal epithelium, binding to the lachrymal proteins and problem like blurring of vision.

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid precorneal elimination of the drug may be overcome by the use of a gel system instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac. For in situ gel based ocular delivery, natural polymers such as gellan gum, alginic acid and xyloglucan are most commonly used polymers. Local ophthalmic drug delivery has been used for various compounds such as antimicrobial agents, antiinflammatory agents and autonomic drugs used to relieve intraocular tension in glaucoma.

Case studies 1) In situ forming drug delivery system for oral administration Pectin, xyloglucan and gellan gum are the natural polymers used for in situ forming oral drug delivery systems. The potential of an orally administered in situ gelling pectin formulation for the sustained delivery of paracetamol has been reported. The main advantage of using pectin for these formulations is that it is water soluble, so organic solvents are not necessary in the formulation. In situ gelling gellan formulation as vehicle for oral delivery of theophylline is reported. The formulation consisted of gellan solution with calcium chloride and sodium citrate complex.

When administered orally, the calcium ions are released in acidic environment of stomach leading to gelation of gellan thus forming a gel in situ. An increased bioavailability with sustained drug release profile of theophylline in rats and rabbits was observed from gellan formulations as compared to the commercial sustained release

liquid dosage form.

2) In situ forming drug delivery system for nasal administration An in situ gel system for nasal delivery of mometasone furoate was developed and evaluated for its efficacy for the treatment of allergic rhinitis. Gellan gum and xanthan gum were used as in situ gel forming polymers. Animal studies were conducted using an allergic rhinitis model and the effect of in situ gel on antigen induced nasal symptoms in sensitised rats was observed. In situ gel was found to inhibit the increase in nasal symptoms as compared to marketed formulation nasonex (mometasonefuroate suspension 0.05 per cent). Intact ciliated respiratory epithelium and normal goblet cell appearance indicated from histopathology of rat nasal cavity proved that these formulations were safe for nasal administration.

Thermoreversible gel formulations of flunarizine hydrochloride for improved drug residence time in the nasal cavity have been investigated. The formulations so prepared were in the liquid state at 4°C but turned into a gel at the temperature of the nasal cavity. Poloxamer 407 was used as the polymer which exhibited the phase transition behaviour.

Inclusion complexes using ßcyclodextrin were prepared for increasing the solubility of flunarizine in nasal secretion.

The prepared formulations were characterised for drug loading, content uniformity, in vitro drug diffusion, bioadhesion strength, gel strength, viscosity and gelation point.

The formulations exhibited drastic increase in the viscosity at the temperature of 37°C indicating their possible use as in situ gelling systems. Out of all the formulations studied, the ß-cyclodextrin formulations shows the fastest release, possibly due to increase in the solubility and dissolution rate of flunarizine hydrochloride.

3) In situ forming drug delivery system for rectal EXPRESS PHARMA

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R|E|S|E|A|R|C|H and vaginal administration In situ gels also possess a potential application for drug delivery by rectal and vaginal route. Miyazaki et al. investigated the use of xyloglucan based thermoreversible gels for rectal drug delivery of indomethacin. Administration of indomethacin loaded xyloglucan based systems to rabbits indicated broad drug absorption peak and a longer drug residence time as compared to that resulting after the administration of commercial suppository. For a better therapeutic efficacy and patient compliance, mucoadhesive, thermosensitive, prolonged release vaginal gel incorporating clotrimazole-ßcyclodextrin complex was formulated for the treatment of vaginitis. In addition, a significant reduction of drug Cmax was observed after administration of in situ polymeric system thus indicating the avoidance of adverse effects of indomethacin on nervous system.

Marketed products of Ocular In Situ gelling system ●

Timoptic-XE: Timolol maleate ophthalmic gel formulation of Merck and Co Inc, supplied as a sterile, isotonic, buffered, aqueous gel forming solution of timolol maleate.

●

AzaSite: Marketed product of InSite Vision.

AzaSite is a topical ophthalmic solution of azithromycin formulated in DuraSite (polycarbophil, edetate disodium, sodium chloride).

Akten: HPMC based gel of lidocaine hydrochloride for ocular surface anesthesia. Akten also contains hypromellose, sodium chloride, and purified water as inactive ingredients.

●

Conclusion With the advent of novel delivery systems, various drug molecules have been revived of their therapeutic and commercial benefits. The introduction of in situ gelling systems has further strengthened the link between therapeutic need and drug delivery. The primary requirement of a successful controlled release product focuses on increasing patient compliance which the in situ gels offer.

Sustained and prolonged release of the drug, good stability and biocompatibility characteristics make the in situ gel dosage forms very reliable. Use of biodegradable and water soluble polymers for the in situ gel formulations can make them more acceptable and excellent drug delivery systems. Moreover in

situ gels have ease of commercialisation which is added advantage from industrial point of view.

References 1. Nirmal H.B, Bakliwal S.R, Pawar S.P; In Situ gel: New Trend in Controlled and Sustained Drug Delivery System, International Journal of Pharm Tech Research AprilJune 2010 Vol. 2 Pg. 13981408.

2. Vyas Jigar et al; A Review On In Situ Polymeric Drug Delivery System, International Journal Of Pharmaceutical Research And Development (IJPRD), July 2011 Vol. 3(5) pg.53-59.

3. Madan, et al In Situ Forming Polymeric Drug Delivery Systems; Indian Journal of Pharmaceutical Sciences May-June 2009 pg.

242-251.

4. Aman Kant et al, In situ Gelling system-An Overview, Pharmacology online 2011 pg.

28-44.

5. Kulkarni S.S, Aloorkar N.H; Smart polymers in drug delivery: An overview, Journal of Pharmacy Research Vol. 3 January 2010 pg 100-108.

6. M. R. Aguilar et al, Smart Polymers and Their Applications as Biomaterials, Topics in Tissue Engineering Vol. 3, 2007, pg 1- 22.

7. Shaikh R G et al; A Review on Polymers Used in In

Situ Drug Delivery Systems, International Journal for Pharmaceutical Research Scholars, Vol.1 2012 Pg.17-31.

8. Eve Ruel-Gariepy, JeanChristophe Leroux; In Situ forming hydrogels-review of temperature sensitive systems, European Journal of Pharmaceutics and Biopharmaceutics, 2004 pg.

409-426.

9. C.B. Packhaeuseret al; In Situ forming parenteral drug delivery system: An overview, European Journal of Pharmaceutics and Biopharmaceutics, 2004 pg 445-455.

10. Kullwany Singh, S.L Harikumar; Injectable In situ gelling controlled release drug delivery system, International Journal of Drug Delivery And Research Vol. 4 April-June 2012 pg 56-69.

11. N G N Swamy, Zaheer Abbas; Mucoadhesive In Situ gel as nasal drug delivery system: an overview, Asian Journal of Pharmaceutical Sciences 2012(3) pg 168-180.

12. K S Rathore; In Situ Gelling Ophthalmic Drug Delivery system: An Overview, International Journal of Pharmacy and Pharmaceutical Sciences Vol. 2, 2010, pg 30-34.

13. Madhugiri P et al; In situ Gels Based Drug Delivery, Current drug Therapy 2011 Vol. 6 (3) pg 213-222.

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Regulatory impact on clinical trial insurance Deepali A Rao, Head, Specialty Lines, India Insure Risk Management & Insurance Broking Services, talks about the benefits of insurance cover while conducting clinical trials t has been close to a decade since India has been seeing the clinical trial industry grow. Global companies have been coming to India to conduct trials for their research drugs on a regular basis. India has been a preferred option for multiple reasons, population, cost effective and good quality resource availability, technologically on par with the global world and also the fact that we are a largely english speaking population. The industry has been growing steadily and is now getting closer to being a billion dollar industry in India alone. Like any other industry, this also has significant risks associated with it, especially considering that we are talking about experiments being done on human lives.

The growth in the industry has led to an increasing awareness amongst stakeholders about the severity of the risks associated and its possible financial impact on the organisations. This has led to the logical search for the right insurance cover which could protect their balance sheet. Initially clinical trial insurance was purchased by the local CROs only on the insistence of the international sponsor. Today, all key stakeholders in the chain are aware that conducting a clinical trial without an insurance cover in place would not be a wise and prudent business decision.

A quick overview of the value of insurance purchased by companies give an indication of the levels of compensation companies were offering or intending to offer to the volunteers. While internationally the indemnity limits are usually in the range of $2 million to $5 million, in India it was rare for companies to be looking at indemnity limits beyond ` 10 to 15 crores. It would be a rare case of a large company doing a very prominent trial where the indemnity limits would be much higher. Insurance companies have not seen too many claims on these policies and the ones see are not very large in no; thus indicating that the levels

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of compensation offered may not be a substantial amount.

As a result the insurance industry has had a fairly profitable book of business from the clinical trial insurance covers; albeit a small book contributing to not more than one per cent of their total premium volumes.

A look at the insurance covers offered to the industry will reveal that the insurance products are definitely in line with what the international markets offer. The policies include coverage for not only the sponsor but all the stakeholders in the chain including the CRO, the ethics committee and the investigators as well.

Policies tend to cover the 'No Fault Compensation', as well as the legal liability cover under the programme. The compensation conditions are typically defined within the policy and the amount of compensation is to be decided by an independent lawyer who would investigate the serious adverse event (SAE) and hear both parties, sponsors and the volunteers before arriving at the amount. So far sponsors and CROs have been satisfied with the insurance covers available.

Like any industry does, the clinical trials industry in India is also going through the regulatory evolution phase.

From a time where there was little or no regulation about the compensations to be paid to volunteers in these trials, to a time today where the regulation is becoming so stringent that global players are wanting to think twice before continuing their association in the country. The compensation guidelines which have come out earlier this year have the following critical aspects: ● The escalation matrix to be followed in case of an SAE ● The entitlements to a volunteer in case of a clinical trial related injury ● The methodology of arriving at the compensation payable ● The definition of a clinical trial related injury/death The compensation mechanism does appear to be very comprehensive and is very strongly in favour of the Research Subject (RS)/Volunteer who participate in the trials. The regulations insist on medical manwww.expresspharmaonline.com

agement to be provided to the RS for as long as required and also indicate that financial compensation should be paid to the RS or their nominee. If the sponsor were to trigger their insurance policy for both these aspects, they would need to first ensure that the value of insurance purchased is significantly higher than the current trends in the country.

The insurance companies, however, would offer higher limits but would also insist on much higher deductible levels (self-insured portion of the risk) in order to avoid attritional losses. Many of the international underwriters who have been offering support to Indian companies on the clinical trial insurance policies have expressed their concern on these regulations and have indicated that they would not be very interested in continuing to offer support on these programmes.

The regulations also define cases which would be termed as clinical trials related injury/death. Product inefficacy has been termed as a clinical trial injury which is again raising a lot of eyebrows. The whole purpose of a clinical trial is to test the efficacy of a product.

Insurance companies offer clinical trials insurance coverage on a ‘No Fault Basis’, however, it is a pre-requisite that there has to be an adverse event to the subject which could either be a drastic decline in the subject’s condition which would not have been the case if regular medication had continued or a side effect leading to a completely new complication in the health of the subject. The

insurance cover offered consequently is only to compensate a volunteer in case of any additional complications that may arise due to participation in a trial. All insurance policies very clearly exclude coverage for claims where the test drug/product fail to perform its intended purpose.

This has been a practice not only in India but also internationally. Insurance companies are not contemplating deletion of this exclusion in light of the regulatory changes.

This would have a direct impact on the sponsors/CROs and they would incur a higher financial burden. This could also lead to international sponsors not showing any more interest in the Indian Territory to conduct their clinical trials.

It is imperative to ensure the welfare of a volunteer; however, there is also an urgent need to safeguard the industry from collapsing all of a sudden. Keeping the regulations in line with international standards/jurisdictions would be prudent to make it a win-win situation to all.

Without this, it is quite possible that the clinical trial industry in India would not grow at the pace it is growing, it may actually see a degrowth which would definitely not be healthy for the country itself.

Disclaimer: The views expressed are that of the author and does not reflect the views of the companies.

Insurance coverage mentioned above is only an interpretation and the actual coverage and exclusions would be as per the policies issued by various insurance companies.

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UPDATE FDA warns on use of certain migraine drugs during pregnancy Drugs containing valproate already carry a boxed warning for birth defects he U S Food and Drug Administration (FDA) warned on the use of migraine drug valproate sodium in pregnant women as it could result in lower IQ scores in the baby. The FDA said the results of a recent study showed that children exposed to valproate products in the womb had lower IQ at the age of six than children who were exposed to other antiepileptics.

Drugs containing valproate are used to prevent migraine headaches, treat epileptic seizures and manic

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episodes associated with bipolar disorder.

Abbott Laboratories' Depacon, Depakote, Depakote CP, Depakote ER and Depakene, and Noven Therapeutics LLC's Stavzor and their generics contain valproate. (r.reuters.com/nej87t) Drugs containing valproate already carry a boxed warning for birth defects.

"Valproate medications should never be used in pregnant women for the prevention of migraine headaches because we have even more data now that shows the risks to the children outweigh any treatment benefits for this use," FDA's Director of the Division of Neurology Products, Russell

Katz said. This is the second time the FDA has warned on drugs containing valproate. In a June 2011 press release, the regulator had issued interim

Drugs from Amgen, others assessed

by FDA as radiation treatments Treatment with Amgen's Neupogen and Neulasta, Teva's Tbo-filgrastim and Sanofi's Leukine, may decrease death rates from radiation exposure

rugs from Amgen, Teva Pharmaceutical Industries and Sanofi that boost white blood cells are being evaluated

by US regulators as treatments for radiation exposure caused by a nuclear attack or accident. The drugs, known as leukocyte growth factors, will be the subject of a meeting of an advisory committee to the US Food and Drug Administration.

Treatment with Amgen's Neupogen and Neulasta, Teva's Tbo-filgrastim and Sanofi's Leukine, may decrease death rates from radiation exposure, according to

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FDA staff documents released ahead of the meeting.

Neupogen, which like the other drugs in the class is given by injection, has been tested in monkeys exposed to radiation by researchers at the National Institutes of Health and the University of Maryland.

Meeting's hearing was prompted by data from the trial showing that the drug reduced mortality following lethal irradiation of the animals. Amgen spokeswoman Ashleigh Koss said the company provided additional

nonclinical data from studies using the drugs in radiationexposed animals, and an overview of literature case studies of their use in victims of radiological accidents. She declined to comment on whether Amgen planned to participate in any future trials of Neupogen or Neulasta as treatments for radiation exposure. The Amgen drugs, currently used to reduce the risk of infection for cancer patients undergoing chemotherapy, had 2012 sales of $5.4 billion.

Reuters

FDA approves Merck combination cholesterol lowering pill The new combination drug will be sold under the brand name Liptruzet

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he US Food and Drug Administration approved a Merck & Co cholesterol lowering pill that combines a generic version of Pfizer's Lipitor with its own Zetia, Merck said. The new combination drug will be sold under the brand name Liptruzet and will begin shipping to wholesalers next week, the company said.

Merck already sells a twodrug cholesterol fighter called Vytorin that combines Zetia,

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known chemically as ezetimibe, with Merck's older LDL lowering medicine Zocor.

Lipitor, known chemically as atorvastatin, is considered to a more powerful statin than Zocor. Vytorin, which had sales of $1.75 billion in 2012, is currently undergoing a long-term trial to prove that it can reduce heart attacks and strokes better than Zocor (simvastatin) alone. While results of that study should definitively determine the www.expresspharmaonline.com

value of Zetia to patients, the drug on its own rang up sales of $2.67 billion in 2012.

"No incremental benefit of Liptruzet on cardiovascular morbidity and mortality over and above that demonstrated for atorvastatin has been established," Merck said. The new drug will be available in four doses, combining 10 milligrams of Zetia with either 10, 20, 40 or 80mg of atorvastatin.

Reuters

results of a study showing reduced cognitive functions in three-year-old children exposed to valproate.

Reuters

FDA approves J&J sedation drug device The system reduces the risks of oversedation when compared to other traditional methods S regulators have approved Johnson & Johnson's Sedasys system to sedate patients during colonoscopies without the need for a physician to monitor delivery of the injectable sedating agent, the company said. The device injects the patients who have different types of colonoscopy procedures with propofol, a minimal-to-moderate sedation agent widely used in colonoscopy procedures.

The system reduces the risks of oversedation when compared to other traditional methods, Johnson & Johnson said in a release, with 99 per cent of patients recovering from the effects within 10 minutes after administration of the drug. J&J said the system is expected to be introduced on a limited basis beginning in 2014. The company estimates that 15 million patients in the US are candidates for these procedures.

Reuters

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PHARMA TECHNOLOGY REVIEW 'Not having a big data strategy can hurt your business big time' In an exclusive interaction with Express Pharma, Simon Ulrich, Head of Business Intelligence (BI) and Master Data Management (MDM), Hoffmann-La Roche, discusses the importance of these strategies for the pharmaceutical industry What is the business case for a pharmaceutical company to invest in a BI and MDM strategy? What are the primary challenges you see in pharma industry which can be solved using BI and analytics?

A challenging question!

The primary challenges we face in pharma industries are at one front very similar to other industries such as to optimise our supply chain, generate accurate financial reports, etc. but on the other hand, pharma faces few unique challenges on its own such as, understanding the influence network around a decision if an innovative drug will be made available for treating a patient.

This includes physicians, healthcare providers but also payers (e.g. insurances) and patients themselves. As we sell and distribute drugs mostly to an apothecary or wholesalers and not directly to healthcare providers, physicians or patients, the challenge is to understand whether influencers are aware of our latest drugs and are using it for optimal treatment. Analytics play a very important role here to help us understand the influence networks at least on a macro level and identifying places where we need to raise awareness as well as guiding us to use marketing effectively.

If you observe how the healthcare market is changing, there are two new nonprescribe influencers added in today’s era. On one hand, the payer or insurance carrier plays an important role in deciding which drugs should be prescribed by providers from a cost effectiveness point of view. And on the other hand, individual patients who are tech savvy May 16-31, 2013

and participate in review forums, micro blogging etc. are becoming more popular influencers. Knowing these details and a 360 degree view of patients is becoming extremely important to understand and big data and analytics play another important role here. While part of this information comes from internal sources, to acquire this picture we have to work with (often multiple) external data providers. This generates a significant integration challenge and business teams are right to demand state-of-the-art BI applications and services to help them tackle them. While I am happy to see new opportunities arising from health IT, this of course generates significant challenges from an informatics perspective to make sure they can be converted into reality. Analytics play a key role here.

Why is data analytics becoming so crucial in the pharma industry?

I would argue that it has been crucial for the industry since quite a while, for reasons discussed in the previous question. We also have to keep in mind that the market is actually getting significantly tougher.

Government increases regulations to comply with. It gets more difficult to develop new blockbuster products keeping in mind that one needs to invest more and more in research to get there. Further genericisation is making it harder to achieve ROI with your products. Analytics of course can’t solve that problem of the industry. I see it rather as a tool that is being applied intelligently which helps to address upcoming challenges more effectively.

How do companies like Roche determine ROI on such spends?

It is another difficult question to answer.

Naturally it is hard to proof the exact financial value of the often quoted "better decision making." Honestly, we do have analytics projects where we can’t calculate ROI. We know we need them either to gain insights (faster) that will generate value or they are mandatory to track success of business processes and changes. In those cases we normally assume that part of the generated value is to be attributed to the analytics implementation/service that was part of enabling it. There are also the more easy cases (which are getting less and less though) where analytics replace manual work processes either in business or IT so ROI can be calculated based on savings generated by that.

What in your opinion should be the road map to a company devising and then implementing such a strategy?

You should be closely engaging with your business.

You should ask questions like, what questions do they need to get insights on? How should information be accessible within your company (get some external input as well). Define your vision as where you need to be in next two-three years. Assess your gaps versus this vision from a technology and organisational readiness standpoint.

Devise your hedgehog principle, what your teams really have the potential to be best at, for your organisation and be clear on how you would like to structure yourself.

Decide which companies you www.expresspharmaonline.com

W H AT ’ S INSIDE

INTERVIEW

Leveraging data science to accelerate clinical trial results PG 50 The design of safe chemical processes PG 52 Harnessing the power of the digital patient PG 53 Avacta Analytical's instrument saves time.... PG 55 like to partner with to cover the areas where your internal team cannot be best at.

While I tried different strategies in the past I have found that it is of higher value for a non IT technology company to attract talent focusing on business understanding, project/process management and doing the triage between business output and it service. Pure play technical skills are easy to buy from the IT services market compared to those skills.

Last but not the least, do the back planning to establish what your teams should focus on today, Should such a strategy include external BI vendors and if so, given the knowledge driven nature of the industry and the attendant security concerns, how would you determine the reliability of such a partner?

Yes, I think that is mandatory. Especially, as in BI the demand for solutions is highly fluctuating.

Without strong external

Waters introduces Fit-for-Purpose LC Purification PG 56 Industrial EquipWash launches mixing battery PG 56

PHARMA LIFE 80

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INSIGHT Leveraging data science to accelerate clinical trial results Sagar Anisingaraju, Chief Strategy Officer, Saama Technologies and Scott Clarke,Vice President, Life Sciences and Healthcare, Saama Technologies give an insight on data science techniques and methods used to improve the success for clinical trials ecruiting patients has been a challenge for pharmaceutical companies. 90 per cent of trials are delayed with patient enrollment as a primary cause. It makes sense to look at newer methods of recruitment. Timely enrollment of qualified patients needs to be substantially improved for clinical trials to complete on time. Each day of delay in a phase III trial costs pharma companies anywhere from $600,000 to $8,000,000 in opportunity costs.

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Adding data science modeling to trials data Data science techniques dealing with large volumes of structured and unstructured data (collectively known as ‘Big Data’) offer prescriptive clues to solve recruitment and retention

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issues. A data science approach generates insights by harvesting the data with sophisticated algorithms.

With this approach, we can better understand why timely enrollment isn’t happening, and ultimately what needs to happen to improve success for clinical trials.

Building key attribute data models Effective target segmentation for enrollment is a key to success. Traditional methods of enrollment rely upon campaign and segmentation based on disease lines across wider populations. Using data science, we can look at the past data to identify proper signals and help planners with more precise and predictive segmentation.

Data scientists will look at the key attributes that matter for a given patient to successfully get enrolled. For each disease type, there may be several attributes that matter. For example, a clinical trial that is focused on a new diabetes medication targets populations’ A1C levels, age group, demographics,

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Sagar Anisingaraju, Chief Strategy Officer, Saama Technologies

Scott Clarke, Vice President, Life Sciences and Healthcare, Saama Technologies

outreach methods, and site performance. Data science looks at the above attribute values for the target users past enrollment data and then builds ‘patient enrollment propensity’ and ‘dropout propensity’ models.

These models can generate multi variant probabilities for predicting future success.

modeling, we can identify the target segment’s social media footprint for valuable clues. We can see which outreach methods are working, and which social media channels the ‘generation Googlers’ are using. This can be tracked on a continuous basis from the unstructured data of social media.

Natural language processing (NLP) techniques to understand the target population’s sentiment on clinical trial sites, physicians, and facilities can be generated and coded into a machine understandable form. Influencer segments can be generated from this user base to finely tune campaign methods for improving effectiveness.

Combining structured prediction models such as patient enrollment propensity described above and the social media data gives us valuable signals that were previously not available to clinical trial planners.

Moore’s law for clinical trials namely, ‘doubling enrollments at half the costs’ may still be far away, but leveraging big data is certainly a step in that direction.

This data science approach has been successfully leveraged by retail, telco, and media companies to gain critical insights. The pharma industry has recognised the opportunity of big data and needs a strategic plan to answer key business questions that will drive and quantify improvement. A data science-driven clinical trials management approach is an advanced strategic process to get trials back on schedule.

Social media provides previously unavailable insights In addition to the above

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'Not having a big data strategy...

Continued from Pg 49 partners you kill your organisation by constant hiring and firing. I strongly believe every manager should focus his team on what potential they have to do best for the company. If that is not enough to provide the needed results then you should partner with those organisations that have this ability/potential to provide.

Now assuming the "basics" are there, the company I would like to partner with should have the ability to pass security audits. Their rates should be in a range to be cost effective. I determine reliability to be of prime importance by the performance delivered by every individual my team is working with. I know that with that I am going against the trend of managed services but I believe that all services are in the end provided by people. So having the best people is the building block to have the best service delivered. Secondly, seeing that our partners are taking accountability for issues and helping us to develop new business opportunities is critical to establish a long

term trust based relationship. Having said that , I would never rely on a single supplier only. The risk of that would just be too high.

Is MDM a must or optional for mid-sized and/or niche pharma industry going forwards?

I have to say that I worked all my life for big pharma companies so I would like to put a caveat before giving an answer.

MDM is becoming mandatory irrespective of company sizes there are many legal regulatory requirements that a company needs to fulfill .

In addition, sooner or later a small company needs to partner with a big company for growth and having a clean MDM is a very essential component on establishing reliable partner.

The pharma industry generates a lot of data. What in your opinion can be the potential effective business cases for big data?

I see multiple business cases here. Research is already working with technology that got wrapped under the term "Big Data". If you just think of the volume

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May 16-31, 2013

aspect out of the 3V (Volume, Velocity and Variety) and think about a genome sequencer which with one trial run can easily generate 6 PB of data. So if you need to analyse that then you need to find the best cost effective ways to store those data and run statistical models to get the best meaningful analytics done on it. Another example would be to capture machine generated data on manufacturing units for batch specific data and predicting batch failure before it occurs to control cost more effectively. Also the classics of sentiment analysis can be an interesting business case as for most of other industries as well.

Another case for the pharma industry can be identifying adverse events from patient sentiments. Getting even more input to be considered for improving drug quality. Big data plays a quite important role to get that to us. As mentioned before, health IT and the challenge to get a 360 degree view of your customers is another important business case of big data. Strong statistical analysis can help you to better manage your trials and

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proof superior value of your products. Lastly I think expert systems will become more important in the healthcare industry as a whole in the future. Ultimately they (can) rely on several sources of "Big Data."

What are the few things the CIO of a pharma / life sciences company should look out for while implementing BI and MDM strategies?

Not that I have been a CIO before but from a BI technology prospective, I would recommend CIOs to look for, Mobile BI solutions – To generate device independence data.

Contextual/operational BI – detaching BI from data warehousing system but. integrating them with transactional systems to make operational decisions in real time.

In-memory DBs - to meet the ever growing demand for speed and faster decision making Big data – A pharma company can’t ignore big data in their strategies. It is a must-have business tool and if ignored, you can hurt your business big time.

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The design of safe chemical processes typical example would be: ● Failure of cooling water ● Agitation failure ● Operator error (for example, too much catalyst) Ideally, these questions need to be asked at the same time as the process is being developed, but this is not always possible.

A systematic approach is required for the design of safe chemical processes; this not only ensures a safe plant but can also speed up process development, especially in the pilot stages.

Dr Jasbir Singh, Founder and Managing Director, HEL, gives an outlook typical process in the pharmaceutical and related industries consists of a number of sequential steps where a range of carefully selected compounds are allowed to react in order to produce the required product or intermediate. In many cases, the reactions involved are exothermic, and therefore require cooling and careful process control in order to ensure safe operation. In addition, some of the raw materials or products may be unstable and have a tendency to thermally explode under certain operating conditions.

Experienced chemists will often be aware of some potential problems based purely on a knowledge of the chemical species involved, but this is frequently insufficient to ensure safe operation. It is now widely accepted that the chemist’s experience must be supplemented by bench scale testing using suitable test procedures. The objective of this article is to make process chemists aware of the presently accepted techniques for

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Figure 1: Thermal screening unit (TSU) for screening thermally unstable chemicals

Thermal screening

hazard evaluation, and how these can affect both development and scale-up of chemical reactions.

A step-wise approach In order to ensure that all potential hazards are properly understood, the following step-wise approach is suggested: (i) Screen potential hazards: this will involve suitable consideration of all feeds, products and intermediates, as well as the main reactions using up to a few grams of sample. The methods used for screening must by necessity be inexpensive and fast, but the key is also the reliability of the data as a false negative reading is potentially disastrous. (ii) Evaluate main reactions: if the screening work permits, the evaluation can be increased to, say, the one litre scale and can concentrate on the main reactions, looking both at the safety and operability aspects. Here reaction calorimetry is the main method of study. (iii) Evaluate `what if’ scenarios: when the intended process has been suitably demonstrated, it is necessary also to consider deviations from the desired conditions. A

This is a vital step in getting a safe process, and the test is historically performed in standard differential scanning calorimetry (DSC) equipment using only a few milligrams of sample. However, this is widely recognised as being inadequate and sometimes even unsafe, and it is far better to use a larger sample size and – importantly – to measure pressure generation.

An example of a system suited to screening in this way is the thermal screening unit (TSU) shown in Figure 1, and sample data is shown in Figure 2. This shows the pressure generated by the sample as the temperature is raised by heating an ‘oven.’ Even a cursory look at the data in Figure 2 shows that the test sample begins to seriously decompose at below 140ºC, and will generate around 50 bar pressure rather quickly. A more detailed review of the data can give a more precise figure for the ‘onset’ of the runaway; the energy release and kinetics can also be quantified.

The test can be performed in a couple of hours, requires a sample of only around one gram and generates data that is easy to interpret.

Detailed evaluation If the materials being handled, including the product, have been screened in terms

of stability, attention can next shift to an understanding of the chemistry, ensuring that it does not deviate from the prescribed route after scale up to the plant. In order to do this, the key objective is to evaluate the instantaneous heat output rate as the chemistry proceeds. For example, if the feed rate is too high, it may become impossible to remove the heat generated and hence keep the reaction under control, leading to the possibility of an uncontrolled explosion.

Therefore, this is a very important step for successful scale up. The best method for evaluating a semi-batch reaction is reaction calorimetry.

Reaction calorimeters in principle are designed to allow the normal process chemistry to be exactly replicated at the laboratory scale, while measuring the heat release rate. The heat data can be used to understand the broad kinetics, which then helps to develop the process; also, in the context of a safe plant, this information is invaluable. An example of a reaction calorimeter (the SIMULAR) is shown in Figure 3.

The results of an evaluation in the SIMULAR reaction calorimeter are shown in Figure 4. This shows the heat output rate (in watts) and reagent dosed into a reactor containing typically one other reactant in solution. The numerical value of the heat output and even the shape of the curve provide useful insight into the chemistry.

The heat output rate can be scaled directly to a large scale plant; this will specify the cooling duty needed.

The total heat that can potentially be released can Continued on Pg 54

Figure 2: Typical thermal screening data

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Harnessing the power of the digital patient David Coman, Senior Vice President of Communications and Patient Recruitment, Quintiles, explains on how by properly engaging with digital patients, more effective healthcare products can be developed at significantly less cost and time compared to what the industry has spent in years past oday’s patients have a growing intellectual curiosity about their own health and a desire to gain the knowledge needed to empower them to advocate on their own behalf. Increasingly, patients are searching for health information online via a growing cadre of digital tools that enable self-education and greater personal control, even before consulting their physicians. As a result, patients enter the conversation about their healthcare needs far more informed than at any other time in history.

While dramatic advancements in communications have empowered the digital patient, eroding patient access to physicians has accelerated their plight. According to a 2012 survey by The Physicians Foundation, physicians are now seeing nearly 17 per cent fewer patients per day than they did in 2008. Among other reasons, these dynamics are fuelling the patient empowerment movement.

Patients, in fact, may be the most underutilised

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resource in the healthcare system, because many of the traditional approaches for interacting with patients were born in an unwired century.

Understanding the digital patient and enabling them to become actively and appropriately involved in achieving better healthcare outcomes must become a new priority for the healthcare industry.

The key to success in the age of the digital patient is to think about the patient as being at the centre of the healthcare and communication network and establish relationships to make it easier for them to participate in their own healthcare. By properly engaging with digital patients, more effective healthcare products can be developed at significantly less cost and time compared to what the industry has spent in years past.

Engaged patient relationships can also be leveraged to study product value and safety, and also to help biopharma companies maximise the return on their development investment through realisation of time and cost efficiencies in product development and patient retention during product commercialisation.

The age of the digital patient We have now entered an era in which the digital world will dramatically shape

healthcare, much as it has done to other industries.

Today is the age of the digital patient — with the patient at the centre of the networked environment — and patients are actively seeking information about their health without the constraint of geographical boundaries or physician intermediaries.

The Pew Research Center reports that the search for healthcare information is the third most common activity taking place online, and that nearly six in 10 patients turn to the Internet first when researching a health concern — before talking to their friends, parents, spouse, or even their doctor. To be successful in the age of the digital patient, biopharma companies will need to be expert in their ability to interact with patients who are equipped with information and empowered to approach their health care providers based on this information obtained on the Internet.

Harnessing the power of the digital patient At the heart of engaging the digital patient is a relationship built on trust. As with any relationship, it starts with an introduction (awareness), which can happen at any number of digital destinations.

By continuously providing content that has clear utility to that individual, the relationship can progress to familiarity and favourability. Providing content to patients on demand (as requested) begins to build a two-way dialogue through which a trusting relationship can be forged.

Engaging the digital patient in this manner makes it simple for the patient to participate, and far more cost effective and expeditious for the biopharma company.

Furthermore, harnessing the power of the digital patient will have a profound effect on streamlining product development, accelerating product adoption and adherence, and demonstrating product value and safety.

Streamlining product development The ability to conduct clinical research efficiently is dependent upon enrollment into clinical research studies.

Yet, a study published in Annals of Internal Medicine by Luce, et al, reported more than 90 per cent of industry-sponsored clinical trials experience May 16-31, 2013

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delayed enrollment, and a Tufts Center for the Study of Drug Development report found that 37 per cent of investigative sites fail to enroll a single patient. A lack of study participants creates delays in new drugs entering the market, which not only prolongs the time it takes to get new therapies to patients, but also adds to the overall development cost to the biopharma company. In addition, failure to enroll the necessary number of patients at each investigator site in a timely manner can compromise a trial’s statistical power and scientific validity. The use of digital tools and online communities offers a host of opportunities to improve upon the clinical research process from beginning to end.

Accelerating product adoption and adherence The opportunity to engage patients in their own healthcare does not stop at regulatory approval. Upon product launch, the objective is clear for biopharma and patients alike: to enable as many patients to benefit from the product as possible. This takes on two forms: product adoption and product adherence.

Driving both ensures the greatest marginal return along the product lifecycle for biopharma companies and the best patient outcomes for the greatest number of people.

With an embedded universe of engaged patients made possible by the clinical trial alumni community, there is ample opportunity to help accelerate the product adoption process. Typically, there are hundreds of clinical trial alumni, and, as a result of product approval, most of them have already experienced the benefits of the product. The engaged patient relationship enables the biopharma company to immediately contact these patients and EXPRESS PHARMA

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notify them that the product is commercially available.

In addition, data from these patients on their patientreported outcomes quality of life, work productivity, etc. can be extremely helpful in supporting market access by integrating this data into formulary dossiers and budget impact and other health economic models. Finally, the information from these patients can be a supplement to the observational and market research being conducted to better understand patient attitudes, behaviors, and treatment patterns as they change over time with introduction of other new products and services.

Demonstrating product value and safety Increasingly, healthcare payers and provider organisations are looking for proof of economic value when making decisions about which therapies they will and won’t reimburse. At the same time, regulators are increasingly insistent upon measuring ongoing product safety.

Biopharmaceutical companies face the pressure of doing both and typically use a combination of physician-constructed patient registries and long-term investigator follow-

up.

Both of these tried and true methods are important, and can be enhanced or in some cases offset by direct-topatient methodologies.

Executing direct-to-patient engagement strategies requires a unique combination of patient engagement and analysis made possible by collecting patient reported outcomes (PRO), medical records and in many cases lab data.

By working directly through the patient, we can now conduct some types of observational research by obtaining consent for medical record access, generating a laboratory prescription for sample collection, and/or delivering a DNA collection kit directly to the patient’s home.

Similarly, we can collect data from a growing universe of biosensor devices.

In addition to validating patient condition, this linkage between PRO, electronic medical records (EMR), laboratory information (Labs), and device data (Device) begins to closely approximate the type of information that can be generated through longitudinal, physician-based, observational registries (i.e., PRO+EMR+Labs+Device).

Further, directly engaging with patients in this manner

enables remote follow-up of clinical trial participants.

Instead of asking a patient to return to their physician for assessment, outcomes data can be gleaned from the patient him or herself, thereby reducing study attrition as well the considerable time and cost of traditional physicianbased follow-up.

The digital patient’s impact on future research The digital patient is pushing the biopharmaceutical industry to make fundamental changes, many of which present solutions to a number of the industry’s biggest challenges. Harnessing the digital universe can not only help to save money from the health

care system, but also improve patient outcomes. Online patient communities represent new opportunities for the industry, and help to raise patient awareness about clinical research, how to manage and cope with illnesses and available treatments.

Investing in patient-driven services and online communities that help to build a networked model of communication among patients, their health care providers and other stakeholders will be critical for the biopharmaceutical industry going forward.

Companies that embrace the idea of digital patients and learn to successfully engage with them will distinguish themselves.

The design of safe...

Continued from Pg 52

Establish `worst credible case’

be translated into an equivalent temperature rise if, for some reason, cooling is lost.

Since the data in Figure 4 is generated by performing the reaction in the same way as a full-scale process would be run, it will provide valuable insight into any potential control problems.

It may also point to any byproduct gas that may be generated.

The next stage of the evaluation is to consider what happens if things go wrong and, in particular, the worst possible but still credible scenario. In order to do this, a hazard and operability study (HAZOP) is frequently carried out. This involves consideration of each operating step and each process line individually, and postulating devia-

Figure 3: Example of reaction calorimeter (SIMULAR)

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tions from the normal.

Where the deviations (for example, loss of cooling) are credible (for example, cooling pump failure) then the consequences are considered in more detail. An assessment of this type may be carried out at several stages during the development of a process and would involve chemists, chemical engineers, instrument engineers and possibly other specialists.

Conclusion The design of safe processes requires a systematic approach during development, and this includes using certain types of calorimetry tools. It is widely recognised that this not only produces a safe plant, but also speeds up the development, especially in the pilot stages. Thus, the payback is considerable and is often understated.

Figure 4: Typical heat flow data from reaction calorimeter

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VENDOR NEWS Avacta Analytical's instrument saves time on formulation studies at biotech company in Korea Optim 1000 microvolume protein analysis and characterisation instrument completes formulation and stability studies in a fraction of time cientists at the specialised biotech company PharmAbcine are completing formulation and stability studies in a fraction of the time thanks to an Optim 1000 microvolume protein analysis and characterisation instrument from Avacta Analytical.

PharmAbcine was established in the Republic of Korea in 2008 specifically for the

S

development of human monoclonal antibodies into drugs for the treatment of human diseases, including cancer and inflammatory diseases.

Dr Weon Sup Lee, Head of the R&D Centre, PharmAbcine explained, “With one product already undergoing clinical trials for blocking angiogenesis in glioblastomas, and a second monoclonal in development stages, the company is keen to use high throughput technologies where possible.”

Lee continued, “High throughput is very important

in the development of drug formulations, especially for a small company like PharmAbcine. With the Optim 1000 we can simultaneously check conformational change and the aggregation status of our molecule.

We now use it routinely for looking at formulation and stability, and for developing purification processes taking many different combinations of factors – pH, buffers, adjuvants – into account. The Optim 1000 is easy to use and requires small sample volumes, which is a real advan-

tage. Unlike techniques such as dynamic light scattering, the samples do not need any pre treatment in order to get good results, so we save time and costs there too.”

He concluded, “For our first product we used spectrophotometers and HPLC for the preformulation studies and it took several months. In contrast, the same process for our second molecule was completed within a week using the Optim 1000 with DOE (Design of Experiment).”

EP News Bureau- Mumbai

PRODUCTS Phenomenex combines core-shell media and Axia packing technology for high-performance lab-scale purification P henomenex has announced the availability of Kinetex Core-Shell media packed in Axia hardware for preparative HPLC and SFC in lab-scale purification. Kinetex 5-micron particles in four phases – C18, XB-C18, Phenyl-Hexyl and PFP – are now offered in 21.2 mm ID Axia packing. This marks the first time that core-shell media has been offered in the Phenomenex Axia preparative format, which delivers longer column lifetime, higher efficiencies, improved performance and high reproducibility, compared to conventionally packed columns for lab-scale prep chromatography.

Kinetex 5-micron coreshell media, introduced just a few months ago, is the largest particle in the family and delivers better performance than 5-micron fully porous offerings, with no increase in backpressure. In fact, the new 5-micron media provides 60 to 90 per cent higher average efficiencies compared to the same size fully porous columns with little to no method development.

The Phenomenex patented Axia packing and hardware technology, introduced in 2005, eliminates the draw-

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backs of traditional slurry packing, delivering uniform bed density and dramatic performance advances.

Kinetex Core-Shell Technology in the Axia preparative format delivers a performance advantage to customers in pharmaceutical and natural products development, who can now use scalable core-shell solutions from analytical stage UHPLC or HPLC methods to purification.

Phenomenex is a global technology leader committed to developing novel analytical chemistry solutions that solve the separation and purification challenges of researchers in industrial, clinical research, government, and academic laboratories. From drug discovery and pharmaceutical development to food safety and environmental analysis, Phenomenex chromatography solutions accelerate science and help researchers improve global health and well-being.

Contact details: JT Presley Phenomenex, Inc. Phone: (310) 212-0555 Ext. 2261 e-mail: jpresley@phenomenex.com EXPRESS PHARMA

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Waters introduces Fit-for-Purpose LC Purification System for medicinal chemistry and natural product extraction aters Corporation has introduced Waters Prep 150 LC System, a new fit-for-purpose preparative chromatography system designed to isolate target compounds from crude mixtures synthesised in the laboratory or extracted from natural sources during initial purification processes.

Based on innovative high performance liquid chromatography (HPLC) hardware and software, the Waters Prep 150 LC System features ChromScope software intended for scientists and technicians of all skill levels - from novice to expert - with minimal training. This dedicated HPLC system enables chemists to purify and capture quantities of specific molecular entities as part of their research into new drugs, natural products, and speciality chemicals.

The Waters Prep 150 LC System operates at flow rate ranges of up to 150 mL/min. and features options for detection, sample injection, and solvent delivery systems in order to better suit specific application needs. The Prep 150 LC is supported with a full complement of scalable Waters OBD prepar-

W

ative 10 – 50 mm (i.d) columns featuring 5 – 10 micron chemistries.

Contact details:

Dayamani SantoshAdministrative OfficerWaters India Pvt Ltd.36A, II Phase, Peenya Indl.

AreaBangalore - 560058,

IndiaWebsite: www.waters.comEmail: dayamani_santosh @waters.com

Industrial EquipWash launches mixing battery ndustrial EquipWash's mixing battery is designed to provide instantaneous hot water economically by mixing steam and cold water to the required temperature through the simple turn of the knob.

The mixing battery is supplied with isolation valves, check valves, union joints, strainers and temperature indicating gauge to know the temperature of the emerging hot water.

Mixing battery provides industry with cheap hot water wherever steam is available along with the water. It incorporates hydraulic fail safe device so that when correctly installed and maintained, no steam regardless of its pressure can enter the mixing chamber until the water flows to raise the steam valve of its seat. When turned off at the outlet, there is immediate and positive shut-off.

The unit can be provided

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with self rewinding hose reel.

Using heavy duty internal spring the reel quickly and easily rewinds the hose. The ratchet assembly locks the reel when the desired length of the hose is pulled out. All hose reel are preset with enough force to fully retract the hose.

The hose reel is fabricated from SS-304 / SS -306 for heavy duty use.

Contact details: Industrial Equipwash 8/B, Surat Singh Indl. Estate, Behind Agrawal Indl. Estate, SV Road, Jogeshwari (West), Mumbai - 400 102 Tel: +91-22-2679 7941 / 2679 8066 Fax : +91-22-2679 2936 / 2679 8066 Mob: 9869231815 e-mail : iewi@vsnl.net

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Product Range Horizontal Plate Filter Press Plate & Frame Filter Press Bag Filter Cartridge Filter Single Plate Filter Holder Basket Filter Rotary Spray Ball Recess Plate Filter Press

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Express Pharma Business Avenues CLEANING, SANITISING EQUIPMENTS CLEAN ROOM ACCESSORIES ASEPTIC PIPING , PW / WFI DISTRIBUTION LOOPS

Floor Drain Traps

Hand Sanitiser

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Shoe Cover Dispenser

Foot Sanitiser

Split Butterfly Valve

Pendents(Service Shafts) CIP/ SIP MODULE We also design & manufacture # IBC Washing/ Drying Modules # Containers/ Glass Ware Wash Modules # FBD Bag Washing/ Drying Modules # Cannisters Washing Modules # Drums Washing Modules

Wash Down Hose Station

SIP MODULE

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Top Tank / Reactor Sampler

Flush Bottom valve

BRK Instruments India LLP

CT3 Texture Analyzer

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compression and tension testing for rapid QC analysis An extensive history and customer input have contributed to the development of the most powerful, low cost, stand-alone Texture Analyzer ever produced. With six test modes (plus calibration check) and a wide choice of accessories, no other texture analyzer has ever done so much without requiring a computer and software!

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GEL STRENGTH /BLOOM TEST SPREADABILITY OF CREAMS,GELS,LOTION,SHAMPOO ETC. EXTRUSION TESTS All CT3 Model Specifications TABLET BILAYER SHEAR TEST Speed: TABLET COATING TABLET SWELLING CHARACTERIZATION Range 0.01 - 0.1mm/s (increments 0.01mm/s) MUCO ADHESION OF BUCCAL TABLETS / FILMS / GELS 0.1 - 10mm/s (increments 0.1mm/s) EMPTY CAPSULE LOOP TENSILE TEST Accuracy ±0.1% of set speed TENSILE TEST OF POLYMER, GELATIN FILMS BLISTER PACKAGING INTEGRITY TEST Position: TRANSDERMAL PATCH CONSISTENCY TEST IN NDDS Range 0 - 101.6mm ALGINATE RAFT STRENGTH Resolution 0.1mm* RESILIENCE OF FILMS ADHESIVENESS OF FILMS, PATCHES, CREAMS Accuracy 0.1mm

CT3 with Muco-Adhesion Accessory

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Full ISO-grade barcode verifiers Globally acclaimed systems for ISO/ANSI/CEN verification Features to meet 21 CFR Part 11 GS1 reporting template as applicable 12000 range meets ISO 15415, ISO 15426-2, ISO 16022 Single model to handle both LINEAR as well as 2D barcode symbols A XICON verifiers operating at leading Pharma Companies, performing barcode verification according to global standards, aid improving quality, and generate verification REPORTS!

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Identification and quantification of Organic process impurities by LC-MS/MS – GCMS/MS. Inorganic impurities by ICP-MS and A.A.S with Graphite furnace, IC Solvent impurities by GC-MS/MS and GC head space with MS.

Genotoxic impurity quantification Genotoxic Studies.

1. Sub chronic oral Toxicity 2. Bacterial Mutation Assay.

3. Micro Nucleus test 4. Bone marrow chromosome aberration test.

Qualification of Impurities.

Degradation products Method Validations as per ICH Guidelines Extractable and Leachable studies INVITRO safety STUDIES Polymorphic studies by XRPD. Protein impurities by capillary Electrophoresis.

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‘What motivates us is trying to find something better for our patients’ Dr C S Pramesh, Professor, Thoracic Surgery, Department of Surgical Oncology, Tata Memorial Centre has been an investigator on clinical trials for the past 11 years. He is also Convener, Thoracic Oncology Disease Management group and tells Viveka Roychowdhury about his main motivation for being an investigator, his frustration at the negative publicity and what he would like to change Dr Pramesh, you have been an investigator on clinical trials in India for 11 years. What keeps you motivated?

Clinicians who stick on at academic institutions like Tata Memorial Centre, or KEM or CMC Vellore choose to stay on because we want to do more than just patient care.

I can speak for cancer but I am sure it’s true for most other diseases as well that the kind of cure rates we are able to offer patients, as a result of clinical research, are far better (than in normal practice). And I guess that is what motivates us: trying to find something better for our patients.

Especially in diseases like cancer, there is always scope for improvement. And numerous clinical trials have given us better treatment options than we’ve ever had before.

Having said that, in clinical research there is always the possibility of the experimental treatment being only as good as the current treatment (that’s the reason it’s called research!) but the only way we can look for something better is to try it in a trial. So we won’t know unless we test the new treatment in a rigorously conducted clinical trial.

In fact cancer is one area where personalised treatment really works because we have to try to fit the treatment to the patient rather than giving

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a standardised drug to all patients.

What are the vulnerabilities that you face as an investigator and how do you handle them; both your own as well as that of patients?

There is always the possibility that a drug might not work and that is something that both the investigator and patient have in mind. So what we typically do is see what other preliminary research has been done on this treatment; has it shown some success in preclinical animal studies, does it have a sound biological rationale, has it shown some promise in earlier phase human studies, etc. So you are looking for some kind of signal that it might actually work. So if you see some kind of signal of such success, then we are more comfortable trying it out in a larger trial.

Secondly, what happens in a trial is that there are so many safety mechanisms built into the process that we would not miss out on a drug that is not working for too long. Nor would we miss out on important side effects for too long. And typically in a cancer trial, new treatment is usually tried as an add-on to the current treatment or in a situation where the patient has already exhausted all available options.

What changes would you like to see?

There are a few things that I

would like to see changed. One, I’d like biomedical researchers to introspect - I think the medical profession needs to change a lot as far as research goes. Some doctors get into clinical research for the wrong reasons. They are not adequately trained for clinical research. Unfortunately, even today there is no formal training in medical research at either the under graduate (UG) or post graduate (PG) level. This is a shame because a lot of them do end up doing research and they are not very well trained to do it. Training in research methodology should be a mandatory part of UG and PG training.

Another thing that I think needs to change is the level of public awareness about medical research. And by public, I don’t just mean patients on clinical trials but the general public.

The most aggravating thing about this situation is that in the developed countries like the US and the UK, medical research is being driven by the lay public. They are demanding that their governments spend more on medical research. In fact, the “war against cancer” in the US came into being because of public pressure on the Federal government to increase funding for cancer research. In many cases, public charity groups are actually funding trials. That is the way it should be.

On the other hand, here in India, you have the press as well as the general public up in arms. So forget about being a positive push, these activities are becoming a deterrent to medical research. I strongly feel that the general public has to be more proactive when it comes to clinical trials. We all want better medical treatment for ourselves. How can better treatment be ever discovered if we don’t participate in medical research?

I feel it is a moral imperative for all of us to participate in medical research.

Every pill that we pop today for a headache, for high blood pressure, for cancer, is available to us only because someone, somewhere has participated in a clinical trial to prove that the pill works. How are we justified in expecting better treatment if we don’t participate in research ourselves?

Lay public in India are guided by what the media portrays and unfortunately the negative publicity in the recent past leads them to equate medical research with experimenting on guinea pigs. This is unfair because you have bad apples in all professions. Just like you have bad engi-

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INTERVIEW neers, bad lawyers and bad accountants, you have bad medical researchers. Unfortunately the problem created by the small proportion of bad researchers is amplified and projected onto the whole profession.

This is not fair because there are so many checks and balances that for instance, in most academic institutions, a maverick researcher going wayward would be found out in just a few days. The data and safety monitoring committees and ethics committees are so stringent that they would be picked out in days. So it’s very unusual that bad research and a bad researcher go unnoticed for too long. The public needs to get this message. It is actually in the interest of pharmaceutical companies (the sponsors) and lead investigators to choose good researchers on their trials because all you need is just one bad researcher to spoil the reputation of the trial. Pharma companies and CROs are always extra careful when they are selecting sites because it is in their own interest to select good researchers.

How has your role as an investigator helped you over the years?

One major thought is that you are actually contributing to medical research and this is very gratifying.

Especially in a disease like cancer where disease outcomes are not very encouraging, even a small improvement in clinical outcomes is very welcome. For example, lets take advanced lung cancer. 1995 was the first time we got proof that chemotherapy gave better outcomes in advanced lung cancer over the standard of care. If you did not give May 16-31, 2013

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‘Patient is doing us a favour by enrolling in a trial’ Dr VK Chopra , Director Heart Failure Programme, Medanta Heart Institute, Gurgaon takes Shalini Gupta through his experiences on the ELIXA trial, highlighting how transparency is built into the system with trust as the bedrock The drug: India is the diabetes capital of the world and the search is always on to find newer methods of treatment.

Majority of deaths in diabetic patients occur because of heart diseases. A new set of injectable medicines not only control blood sugar but also reduce the incidence of heart disease in patients. An inbuilt safety mechanism ensures that although blood sugar comes down to normal, it does not cause hypoglycemia, including other complications of present day medicines including loss of consciousness, sweating etc.

Approved for use in Europe, it is still under consideration in the US. The trial: Called the ELIXA trial, the aim is to validate reduction in cardiovascular events in diabetics, who have had a recent acute coronary syndrome Extending over a period of 3.5 years, the multinational trial is being conducted in 35 centres in India. Longterm trials such as this one, give meaningful results, they are harder to do, but

chemotherapy, the average lifespan was six months but with it, it was eight months.

Even though the improvement in clinical outcomes was only two months, it was then considered an important improvement in survival rates. Today, there are some targeted treatments for advanced lung cancer which can improve survival to 24 months. Two years may not seem a big deal but for a cancer patient and his family, it is an improvement in survival by 400 per cent when you consider the baseline survival of six months. So that’s how much medical treatment has progressed thanks to cutting edge clinical research.

If we had stopped trials of May 16-31, 2013

the information is much more useful.

Selection of patients: Out of the hundreds of patients that we see over the course of 10-11 months, we have been able to recruit 17 patients for the study. This is itself indicative of the transparency of the process.

We have several patients undergoing angioplasty or those admitted with a heart disease. Ideally we take the permission of the physician under whom they are undergoing treatment to enroll them for the study. Usually patients who live nearby are preferred since they need to make frequent visits to the hospital. Our selection criteria are strict. We explain the study details to the patient, address their queries and apprehensions and if they are willing, give them an informed consent form in the language they understand. We need to judge whether the person is likely to continue during the course of the trial, or might drop out midway. More people dropping out takes away from the value of the trial.

Transparency is important: If you keep the process very transparent, only a small number agree, but that is how to do things. Out of 50 people, four or five may agree. Adverse publicity has instilled fear in people and

that has to change. The blame also lies on us, because there are people who have done things they should not have done. It has to be an ethical transparent process. Above all, we need to remember that the patient is doing us a favour by enrolling in a trial.

Caring for the patient: Trust works both ways, When a patient trusts you, you also feel more responsible. Also such patients would follow instructions much more carefully. We meet them personally on every visit. They are given a diary to keep track and blood sugar checked on a daily basis, which is stored in the glucometer. This data is logged in once the patient visits us, more frequent intially and less later as we adjust the dose. At the end of the study, we’ll call them after a month to see that there are no long-term adverse events.

Safety is paramount: The patient may either be on placebo or may be taking the drug. It is an end point driven study, blind data is analysed at the end of the study. Only the Data Safety Monitoring Agency has access to unblinded data. If they find that in one arm there are more adverse events, they can stop the study, or if they see the drug

that ‘experimental’ treatment in 1995, we would still have a survival of just six months.

This is just one example – there are numerous others in practically all branches of medicine.

understand everything about the trial and then make and then take a decision whether to participate or not in the trial. The third group of patients are those in the middle, who seem to understand the study when you are explaining it to them and may sign up to the study but may not actually understand all the details of the study.

This could be a dangerous situation.

The first group should never be part of a trial because they do not understand anything of it. It would not be a truly informed consent. So I would be extremely wary about taking them on a trial. The second category I respect completely because theirs is an informed deci-

How do you counsel a patient that he needs to be on a clinical trial?

We do not try excessively hard to convince a patient to join a trial. We have three types of patients.

One group, the most problematic one, is the one who says, “Doctor, we authorise you to do whatever you feel is best for me … we trust you” without understanding anything of the trial. The second type is at the other extreme end; patients who www.expresspharmaonline.com

Dr VK Chopra , Director Heart Failure Programme, Medanta Heart Institute Gurgaon getting more benefits than the placebo, they can stop the trial and say that it is unethical to withhold the trial. This board meets once in three months and will have acces to all 700 sites.

They are responsible for ensuring the safety of the patients.

Patient speak: 60-year-old Madhu Gupta, a resident of Gurgaon, is diabetic since the last ten years. Gupta says, “I know that research is being done on me, and if this drug works in 1000 people, me and others like me can use this, as it comes to the market. shalini.g@expressindia.com

sion, whether to participate or not. With the third group, it usually comes down to a judgement call by the investigator who needs to take a call. We need to understand that it is practically impossible for a patient to understand every single minute detail of a trial. What is important is that he/she understands the basic information that this is part of research and not routine medical care, the types of treatment involved, the possible side effects, the possible benefits and risks of participating. I would not be comfortable trying too hard to convince a patient to join a trial when the patient is ambivalent. viveka.r@expressindia.com EXPRESS PHARMA

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'GCP strived hard to impart quality pharmacy education' Government College of Pharmacy Bangalore is going to celebrate its golden jubilee.

Dr S Shashidhara, Principal, Government College of Pharmacy Bangalore in a chat with Usha Sharma, talks about the institutions journey so far and plans for the celebration INTERVIEW

Tell us about GCP’s journey so far. What are the courses you offer?

The institution was started in 1963 by KN Shanbogue, the then drugs controller general of Karnataka. This marked the initiation of pharmacy education in the state. The institution started working as an impetus for various private pharmacy institutions to come in the state. Throughout its journey of 50 years, GCP strived hard to impart quality pharmacy education, without compromising the ethics of the profession. The faculty, non-teaching staff and the student’s fraternity have put up continuous efforts in upholding the pharmacy education in particular and pharmacy profession in general in the state.

The alumni of GCP are now at the helm of the affairs in various facets of pharma profession and contributing in evolving pharmacy profession. Now GCP is the brand name, which has secured a place within the 25 best institutions in the country. The college offers courses like D Pharm, B Pharm, M Pharm (in four specialisations) and PhD programmes.

What agenda have you set for GCP’s golden jubilee celebration? Also, tell us about the venue?

The golden jubilee celebrations have been planned keeping in mind the following agenda” i. To develop interaction between the alumni and present students so as to evolve a strong professional guidance platform ii. To develop alumni network iii. To discuss present day challenges of pharmacists iv. To come out with effective strategies to convert challenges into opportunities through focused discussions and interactive sessions v. To discuss about challenging technologies with moving times for students and alumni to update information vi. To install golden jubilee scholarships, provide research assistance to stu-

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dents of our college.

The two-day event will be organised in NIMHANS convention centre and provisions have been made for the alumni to visit the campus during these two days. Golden jubilee lecture series will be organised in the campus.

GCP's slogan states Suvarna Sambhrama. Can you elaborate more on this concept?

Suvarna means gold and Sambhrama means celebrations and hence this title has been given. Actually the slogan states “GCP: Glorious 50 years in shaping the talented pharmacy professionals.” This slogan is self-explanatory.

Throughout the year, attempts will be made to create a common platform for the alumni and budding pharmacists and to bridge the gap. There will be sessions for alumni and present students to reminisce their golden memories, exchange of professional ideas, technical knowledge, etc.

GCP also plans to honour college faculties and invited drug controllers for the event.

In case of GCP, the untiring and selfless efforts of the former principals and teachers is immense and it is just a token of respect and gratitude that we would like to show to the mentors of this institution.

Even many alumni are eager to honour their revered teachers to express gratitude.

What are the programmes planned for motivating the existing students?

Scientific sessions have been planned and the speakers have been told to motivate our existing students. A session has been scheduled to bridge the generation gap of alumni and existing students.

In addition, year-long lecture series have been designed to inspire and motivate our students and to expose them to the latest trends in the profession.

Can you share some success stories of the college?

There are several success stories of the institution and also of our alumni, to mention a few: The institution is the brand name in the field of pharmacy education in the state. In PG CET exams conducted by RGUHS, six to eight of first 10 ranks are bagged by www.expresspharmaonline.com

our students and students choose our institution as the matter of first choice. Today, the institution is in first 25 best colleges list.

When it comes to the success stories of our alumni: Professor SK Kulkarni was raised to the level pro-chancellor of Punjab University.

Professor Srikant Murthy also the pro-chancellor of Drexel University, US; Prof B Suresh, Vice-chancellor of JSS University, Mysore and President of Pharmacy Council of India. Dr Jagashetty B R is the present Drugs Controller and Raghuram Bhandari is the present additional drugs controller.

In addition several former drugs controllers from the state of Karnataka namely, Anand Rajshekhar, Premanand Shetty, Ram Murthy, Sripathy Rao, etc were all our alumni. Further, Dr SK Kulkarni, Dr B Suresh were the presidents of Indian Pharmaceutical Association.

Many have become entrepreneurs, in top positions in the pharma industries, etc.

Dr Bharatesh Jagashetty is holding the drug controller position in Karnataka.

Would you like to comment on his academia and professional career?

Dr BR Jagashetty is our distinguished alumni, having studied B Pharm. and M Pharm from our institution.

His zeal in attaining the higher education and enhancing the understanding of conceptual aspects of profession made him to pursue his higher studies, while in very responsible position in drugs control department. He has degrees M Pharm, LLB and PhD. in Law. All these speak volumes about his penchant desire for learning. He was awarded with best drugs controller officer in India.

Besides Jagashetty, how many people have achieved success like him?

There are many such alumni success stories in India and abroad. These people have carved niche for themselves and also for the institution. Therefore, proudly we call all our alumni as our “Brand Ambassadors”.

How do experts (Ex-students) of the college help in the growth of the college and helping enrolling

students?

They are our brand ambassadors. Regularly our alumni visit the college, deliver scientific lectures, help in imparting new techniques and assist in research activities. It is noteworthy to mention that the American Association of GCP Alumni is sponsoring PG research projects for our M Pharm students. The association has instituted STAR awards for the achievers in the field of pharmacy education and research.

Our alumni are acting like live link between the modern trends in the field and the college students.

What are your responsibilities and how are you managing it?

Heading a government institution is different. It has a major advantage of being independent and not bound by pressure of improving the financial resources as observed in many of the private institutions. However, it has a few disadvantages of not being independent with respect to utilisation funds and facing difficulties at different levels for introduction and development of new schemes and management of human resources.

True challenges are here.

Accomplishment of success in good performance with constant motivation, overcoming the difficulties and convincing all other concerned to improve academic, infrastructural and development are some of the important challenges.

Whats your message for the academy and industry?

Though it is a feeling of many that facilities and governance in government institutions will not be up to the mark, GCP has shown that conduct of examination for all diploma colleges in Karnataka and also in our college has been outstanding. The performance of our students in post graduate entrance examination conducted by the University has been remarkable and also the performance of students in diploma examinations has been excellent.

Overall it is a feeling in academia, industry and research departments that GCP is brand name for indication of standard in pharmacy education. u.sharma@expressindia.com May 16-31, 2013

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NEWS Sciformix Corporation celebrates founding day by volunteering at local charities in India and Philippines Announces Social Impact Initiative day

May 16-31, 2013

ciformix Corporation, a world leading Scientific Process Organization (SPO), celebrated Sciformix’s 6th inception day and announced the introduction of a Social Impact Initiative day. The day involved over 400 Sciformix employees moving away from their offices and volunteering their time to local charities to work at the ground level setting up medical camps, giving health awareness presentations and spending time with aged people and orphans in Pune and Mumbai, India and Manila, the Philippines.

During the Social Impact Initiative (SII) day all Sciformix employees spent their time with various charities such as Tunga Gaon

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Charitable Trust, Mumbai, where qualified medical practitioner employees opened a clinic for slum dwellers. In Pune, Sciformix teams supported Maher Ashram, a Non Government Organization (NGO) for destitute children, providing them with health and eye check-ups. Additional teams spent time distributing food and drink and taking part in social activities across various charities including Asha Daan, Dhanvantari Trust and Jhanvi Trust.

The Social Impact Initiative day was incepted

by Manish Vinayak Soman, President and Chief Executive Officer, Sciformix.

Soman said, “While Sciformix is succeeding in our chosen area of expertise

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it is equally important for us, as an individual and as an organisation, to grow and succeed from within. In the present connected and global world, success is defined not only by our business achievements but also how well we serve our communities and enrich our ecosystem and together, our employees can experience the happiness of giving through our Social Impact Initiative day.”

“We live our mission of helping people live healthier lives; and our values of integrity, commitment, focus, innovation, diversity, excellence and teamwork every day, in everything we do. Giving, volunteering and business innovations are the ways in which we live our

mission and respond to the needs of our communities.

Each is important; together they become a powerful commitment to improving health, people’s lives and communities,” says Soman.

Sciformix, headquartered in the US, with operations in India and the Philippines, partners with clients through the entire drug development cycle, to provide a full range of services from study design to post marketing surveillance and commercialisation support. Areas of specialisation include safety and risk management, clinical research and post approval support services, medical affairs, scientific writing and regulatory affairs.

EP News Bureau-Mumbai

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AWARDS Pharmasynth wins Rajiv Sandhi National Quality award Receives award in drug and food category

elhi-based pharmaceutical company P h a r m a s y n t h Formulations has been selected as the winner of Rajiv Gandhi National Quality Award in food and drug category for the year 2011. This award was given by Prof KV Thomas, Union Minister for Consumer Affairs, Food and Public Distribution, at an event held at NDMC Convention Centre, New Delhi.

The award is instituted by the Bureau Of Indian Standards in 1991 to give special recognition to those who are considered to be the leaders of quality movement in India. This is a national award of international repute, assessed in line with Malcolm Baldrige National Award of USA, Deming Prize of Japan and European Quality Award.

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According to AK Gupta, Managing Director, Pharmasynth Formulations, “Fulfillment of environmental & social responsibilities are also the integral part of quality.” As part of CSR, the company participates in 'Ganga Safai Abhiyan', 'Beti Bachao Abhiyan' and runs its own

NGO and a Bharat Mata Mandir (a museum of Freedom Fighters) in Dilshad Garden, Delhi.

The appreciable aspect of this event is that Pharmasynth has donated the reward money of Rs 50,000 to the 'Prime Minister’s Relief Fund', at the

award ceremony itself. The company has also given an increment of Rs 500 per month to all its employees, on this occasion. The field force and dealers of the company celebrated this occasion with great enthusiasm, all over the country..

EP News Bureau-Mumbai

Venus Remedies bags award for Elores Receives gold medal for being the best Innovation of 2013 enus Remedies has been awarded gold medal by DST-Lockheed Martin India Innovation Growth Program – 2013 for Elores, a drug designed to fight multi drug resistant ESBL and MBL producing gram negative ICU infections to which other antibiotics failed to respond.

Dr Manu Chaudhary, Director Research, Venus Medicine Research Centre received the award from Montek Singh Ahluwalia, Deputy Chairman, Planning Commission of India, in an award ceremony recently held at FICCI office in New Delhi.

More than 1500 technologies took part in the programme this year.

Participants were adjudged under various parameters like novelty, innovativeness, technical strength and commercialisation potential by a team of experts from Stanford Business School, US, IC2 University of Texas, Austin,

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US, Lockheed Martin foundation in collaboration with DST under Indo-US joint science and technology innovation programme, 2013.

Chaudhary on receiving the award said, “The award from DST-Lockheed Martin Foundation in the first year of www.expresspharmaonline.com

launch of Elores is a matter of great pride for the team VMRC. Gold medal is a recognition of VMRC’s innovations, its credibility and competitive edge in research.”

Elores is capable of addressing multi drug resist-

ant ESBL/MBL producing gram negative infections which constitute 25 per cent of this market creating an opportunity of more than 11 billion in coming five to six years. Elores has patent for product, method of treatment and use protected from 45 countries including the US, India, Australia and Europe.

Elores was launched in Indian market in early this year and has received tremendous response from medical fraternity.

Venus has already filed CTD for this product in Europe, and is planning to take this product to other International markets with the support of Lockheed Martin Foundation, DST, FICCI and all the associated bodies. With its ability to reduce the cost of therapy to patient to >50 per cent and offers more than 30 per cent faster cure rate besides improving hospital ecology.

Elores can become a block buster product in times to come.

EP News Bureau-Mumbai May 16-31, 2013

REGD.WITH RNI NO.MAHENG/2005/21398 REGD.NO.MH/MR/SOUTH-77/2013-15, PUBLISHED ON 5TH & 20TH EVERY FORTNIGHLY & POSTED 6-7-8 & 21-22-23 OF EVERY FORTNIGHLY. AT IND.EXP.PSO.