Oct - Nov 2021 Edition by Pharma Machines

Vol - 17 / Issue - 4 / Oct - Nov 2021

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Vol - 17

Issue - 4

Oct - Nov, 2021 PUBLISHER & EDITOR

Dear Pharma Pals,

Harjit Singh Dhaul

To be in the business, we need to continuously innovate by responding to market demand. This has been Clearpack strategy from beginning, adapting to market needs by implementing latest technological development with continuous engagement with its suppliers. Today, Clearpack supplies very highspeed, fully automatic packaging lines from primary filling all the way to end-ofline palletizing, and is always prepared for tomorrow's challenge.

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The exclusive in this issue of Pharma Machines & Technology is on Clearpack, the packaging automation partner for the pharmaceutical industry. Read exclusive interviews with Govind Bhandari, the CEO of Clearpack Group, a passionate engineer with incredible energy and insatiable ambition, and Piyush Bhandari, Sales Head – India.

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The article in this issue by world-renowned author Dr. Tim Sandle on fungi in cleanrooms, its types, origins, and decontamination strategies, is highly educative. Cleanrooms and controlled environments are at risk from fungal spores. Fungi can present health hazards to operators and pose potential contamination risks to medicinal products. The article considers the types of fungi that might be recovered from cleanrooms and looks at the mechanisms by which they might enter a facility.

Website: www.pharmamachines.com All rights reserved. Reproduction in any manner is prohibited. PHARMA Machines & Technology takes no responsibility for validity of claims in advertisement and articles published. Printed & Published by: Harjit Singh Dhaul on behalf of Global Vision and printed at Hariom Printers, C/70, Akurli Industrial Estate, Akurli Road, Kandivali East, Mumbai 400 101, and published at 26-B, Rebellow Cottage, Gaon Devi Road, Poinsur (E), Kandivli 400 101. Editor Harjit Singh Dhaul.

The automations of QA systems and processes are becoming of prime importance these days. The article by Chetananand Pathak, Director - Corporate Quality & Compliance, Emcure Pharmaceuticals Ltd, analyses the success and failures of automation in Indian pharma industry. Track & Trace system plays a vital role in preventing counterfeiting during trading, assisting in optimizing monitoring at each level of supply chain and maintaining integrity of the product while dispensing to the customer. However, the entire process is full of challenges. The article by Navdeep Singh Kathuria, General Manager - Packing, Aurobindo Pharma Ltd, talks on the challenges in implementing track and trace systems in pharmaceutical packaging.

DEPUTY EDITOR Byju Bhaskaran

Harjit Singh Dhaul

CO N T E N TS

EDITORIAL ASSISTANT Ravlin Kaur

Publisher & Editor

EXCLUSIVE • 'Packaging automation has become lean, smart, data oriented and driven by AI’ Exclusive interview with Govind Bhandari, CEO, Clearpack Group • Complete Primary Packaging Solution for Pharma Industry • 'Always prepared for newest challenges’ Exclusive interview with Piyush Bhandari, Sales Head India, Clearpack • Need of Robotics Automation in End of Line Packaging • Tablet Bottle Line Automation with Track and Trace • What gets measured, gets improved using IoT and i4.0

Articles

REVIEW

Automation in Indian Pharma Industry: Analysing Success vs Failures By Chetananand Pathak, Director - Corporate Quality & Compliance, Emcure Pharmaceuticals Ltd

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Fungi in Cleanrooms: Types, Origins, and Decontamination Strategies Article by world-renowned author Dr. Tim Sandle Track & Trace Systems Implementation in Pharmaceutical Packaging By Navdeep Singh Kathuria, General Manager Packing, Aurobindo Pharma Ltd

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INDIA PHARMA 8 GLOBAL PHARMA 10 DID YOU KNOW? 12 TECH NEWS 14

INDIA PHARMA

Rise in raw material prices stifles India pharma Drug manufacturing in India has become expensive due to steep rise in raw material prices. The prices of APIs, excipients, glass vials and packaging material, among other inputs, have escalated over the last three months. The situation is largely due to factory shutdowns and production cuts in China, the main source of APIs and key starting materials for Indian companies.

Made in India kits offered world class virus testing Cheap, and sometimes free RT-PCR tests in the country have allowed millions of Indians a chance to access world class virus testing. More than a million tests are still being administered in the country daily, and 80% of the test kits used are now completely manufactured in India. India expanded from 14 laboratories capable of conducting Covid-19 tests in February 2020 to more than 1,500 over the next six months. The country now has nearly 3,000 such labs. Most Indians can access RT-PCR tests at a fraction of the cost due to a large-scale public-private partnership, known as InDx, that set up the local know-how and infrastructure to manufacture these tests within India.

Penal provisions may go in new laws As the government starts framing new laws for medicines, cosmetics and medical devices, it is looking at removing penal provisions where a drug or a medical device has not harmed a patient. The existing Drugs and Cosmetics Act, 1940 is prosecutable. Any drug/cosmetic deemed to be adulterated or spurious is punishable with imprisonment and fine too. The ministry of health and family welfare had in September set up the expert committee to frame new laws for medicines, cosmetics and medical devices in a bid to replace the existing drugs and cosmetics Act which was enacted in 1940. The eight-member committee will have to submit the draft laws by November 30.

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The price rise has particularly hit the micro, medium and small pharma companies. The prices of all APIs have risen by 25% to 300% over the last few months. For instance, paracetamol prices have risen to be in the 840-1,000 per kg range, up from around 300 per kg before the Covid-19 outbreak. The prices of excipients and solvents, including propylene glycol and glycerin have also gone up. Packaging material, another key material for the pharma industry, has become expensive, too.

Indian firm starts making ingredient for Covid-19 drug India's Everest Organics Ltd has started making the API for a generic version of Merck & Co's experimental antiviral drug molnupiravir to treat mild to moderate Covid-19. The Indian bulk drugs manufacturer joins Divi's Laboratories Ltd as an API maker for Merck's experimental oral drug. Merck has separately entered into voluntary licensing agreements with at least eight Indian generic drugmakers for molnupiravir, with an aim to turn the country into a manufacturing hub for the drug. Merck has sought U.S. emergency use authorisation for the drug. The U.S. authorisation application was based on data released earlier this month by Merck and partner Ridgeback Biotherapeutics. The data showed molnupiravir nearly halved the risk of hospitalisation or death in at-risk nonhospitalised patients with mild-to-moderate COVID-19.

INDIA PHARMA

US company plans radiotherapy facilities in govt hospitals Varian Medical Systems, the US-based provider of radiation oncology treatments and medical software has reached out to several Indian states with a high burden of cancer to set up radiotherapy centres at district government hospitals under the public-private partnership (PPP) model. In this model, the state is expected to provide space in their hospitals, where a private clinical service provider will set up the radiotherapy centre to treat patients at a cost agreed with the state. Varian has also reached out to the Central government to develop a policy document for developing radiotherapy centres based on the PPP model. Out of the 718 districts in India, radiotherapy facilities are available in less than 100. This results in only 18 to 20% of patients being able to access radiotherapy treatments. India has only 0.45 linear accelerators or radiotherapy systems per million in comparison to a world average of 1.84.

Ayush Ministry simplified granting of licence The process for granting licenses for manufacturing Ayurveda, Siddha and Unani (ASU) drugs has been made swift, paperless and more transparent by bringing the application system online. The manufacturers will now be saved from the trouble of being physically present at the office of the licensing authority and can apply for the license online at www.e-aushadhi.gov.in/"www.eaushadhi.gov.in. The Ministry of Ayush issued a gazette order notifying the implementation of the Drugs (4thAmendment) Rules 2021, with effect from October 1, 2021. The license of ASU drugs has been made perpetual i.e. with one-time registration fee, the license of the product will be valid lifetime subject to online submission of self-compliance declaration every year or unless suspended or cancelled.

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Eye care chain plans to expand presence Chennai-based specialty eye care chain Dr Agarwals Eye Hospital has said it is in talks for Series-D funds, as it plans to spend Rs 1,000 crore over the next three years to add dozens of hospitals across the country and abroad. The plan is to open over 100 eye hospitals and 500 outreach clinics. About 20% of the new expansion will be outside of India. The company will earmark about Rs 300 crore for expansion in Maharashtra alone. Dr Agarwals operates 100 eye hospitals, of which 86 are in India and the remaining in Africa. It has clinics in Mauritius, Mozambique, Tanzania, Rwanda and Uganda. The company has also acquired Mumbai-based Aditya Jyot Eye Hospital, the largest eye care centre in Mumbai headed by ophthalmologist Sundaram Natarajan.

'One Health' consortium for surveillance of bacterial, viral infections The Department of Biotechnology has launched a 'One Health' consortium that envisages carrying out surveillance of important bacterial, viral and parasitic infections of zoonotic as well as transboundary pathogens in the country. The project also looks into the use of existing diagnostic tests and the development of additional methodologies for the surveillance and understanding the spread of emerging diseases. The 'One Health Consortium consisting of 27 organisations led by DBT-National Institute of Animal Biotechnology, Hyderabad, is one of the biggest health programmes launched by the government in post-Covid times. The consortium consists of AIIMS, Delhi, AIIMS Jodhpur, IVRI, Bareilly, GADVASU, Ludhiana, TANUVAS, Chennai, MAFSU, Nagpur, Assam agricultural and veterinary university and many more ICAR, ICMR centres and wildlife agencies.

with continued protection for more than six months," said Mene Pangalos, executive vice president, biopharmaceuticals R&D at AstraZeneca AstraZeneca is also developing the drug cocktail as a therapy to protect people who do not have a strong enough immune response to COVID-19 vaccines. It requested emergency approval from U.S. regulators for its use as a prevention drug last week. To develop cell therapies for rare metabolic disorders

Potentially dangerous chemical detected in BP drugs The new chemicals detected are called azido impurities and regulatory authorities say they're mutagenic, meaning they can change someone's DNA and potentially increase cancer risk. The impurities were found in blood pressure drugs which have been recalled in Canada as well as Europe earlier this year. U.S. officials helped lead the way in the 2018 recalls of the same type of drugs tainted with the probable carcinogen N-Nitrosodimethylamine, or NDMA, though they have yet to pull any for containing the azido impurities. Drug regulator Health Canada announced recalls of valsartan, a type of drug called an angiotensin II receptor blocker or ARB, in May for elevated levels of azido impurities. Over the next few months, other drugs in the same class, losartan and irbesartan, were recalled for the same impurities. Drug cocktail to treat Covid-19 succeeds in study AstraZeneca's experimental Covid-19 antibody drug cocktail has succeeded in reducing severe disease or death in non-hospitalised patients in a late-stage study. The drug, called AZD7442, reduced the risk of developing severe Covid-19 or death by 50% in patients who had been symptomatic for seven days or less, meeting the main goal of the trial. "An early intervention with our antibody can give a significant reduction in progression to severe disease,

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Immusoft has signed a research and licensing agreement with Takeda Pharmaceutical for cell therapies in rare inherited metabolic disorders that lead to complications in the central nervous system (CNS). The collaboration will see the discovery, development and commercialisation of cell therapies. The cell therapies will be developed using Immusoft's Immune System Programming (ISP) technology platform. This ISP platform changes the B cells of a patient and instructs the cells to produce gene-encoded therapies. This partnership is aimed at providing protein therapies across the blood-brain barrier. Founded in 2009, Immusoft is also developing new approaches to modify cell therapies to be more durable and redosable. This advances Immusoft's leadership position in B cells as biofactories for therapeutic protein delivery, a novel approach that it has pioneered. This partnership provides Immusoft with significant resources to further develop its Immune System Programming (ISP) technology platform and therapies in diseases for which patients have limited options According to the agreement, Takeda has options to exclusively license programmes at the pre-clinical stage while Immusoft is entitled to get tiered royalties on commercial products developed from the partnership. Additionally, Takeda will handle the preclinical and clinical development, as well as the commercialisation of the products.

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Second-generation mRNA vaccine candidates German biopharmaceutical company CureVac has decided to abandon its Covid-19 vaccine de velopment and focus on its collaboration with GlaxoSmithKline (GSK) to develop secondgeneration messenger RNA (mRNA) vaccine candidates. The company will also withdraw the application to the European Medicines Agency (EMA) for the approval of its first-generation Covid-19 vaccine candidate, CVnCoV, due to potential overlap with timelines regarding approval for a secondgeneration candidate. The earliest potential approval of CVnCoV is expected in the second quarter of next year, by which time the candidates from the company's second-generation vaccine programme are expected to have progressed to late-stage clinical development. In the coming months, CureVac and GSK expect to enter clinical development and expedite the development and manufacturing of the broad second-generation programme. The companies aim to secure regulatory approval for an improved Covid-19 vaccine next year.

Combination therapy to treat Covid-19 Brii Biosciences has filled an emergency use authorization (EUA) application with the USFDA for its combination therapy, BRII-196/BRII-198, to treat Covid-19 patients. BRII-196/BRII-198 is a SARS- CoV-2 neutralising monoclonal antibody combination therapy , which is intended to treat non-hospitalised Covid-19 patients at high risk of clinical progression to severe disease. The EUA submission is based on the positive Phase III results obtained from the ACTIV-2 clinical trial that was announced in August. Funded by the National Institutes of Health (NIH),

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the trial was conducted at clinical trial sites worldwide that include Brazil, South Africa, Mexico, Argentina, the Philippines and the US. The data showed that the combination therapy provided a 78% statistically significant decline of relative risk of hospitalisation and death compar ed to placebo. It has also demonstrated that BRII-196/BRII-198 improved safety and zero deaths by day 28 of the trial in non-hospitalised Covid-19 patients . The company stated that the clinical data to support the EUA submission is planned to be submitted to the US FDA on a rolling basis.

$500m vaccine manufacturing facility in Africa Moderna plans to invest $500m to build a state-ofthe-art mRNA facility in Africa, capable of producing up to 500 million doses of vaccines in the continent each year. The announcement comes amid a fierce patent waiver debate between pharma companies, governments, and charities. The WHO and rights groups like Amnesty have said vaccine makers should share doses and technology with lowincome countries, which have received disproportionately low supplies of Covid-19 vaccines compared to wealthier nations. The world's leading Covid-19 vaccine manufac turers, including Moderna, have so far refused to transfer their vaccine know-how into WHO's Covid19 technology access pool – and are opposed to a patent waiver that would allow vaccine mak ers in poorer countries to domestically produce approved Covid-19 vaccines. The pharma industry has argued that waiving intellectual property rights would remove the incentive for drugmakers to innovate. Some companies have also insisted that the technology needed to produce their vaccines is too complex to simply transfer over to other manufacturers.

DYK

DID YOU KNOW? Indian pharma industry, currently valued at $41 billion, is expected to grow to $65 billion by 2024 and $120130 billion by 2030. PharmaJet, a needle-free applicator for painless intradermal vaccine delivery penetrates the cell membrane, and a single dose is spread into two shots across two arms. The adenoviral intranasal vaccine BBV154 from Bharat Biotech is the first of its kind Covid-19 vaccine which has been undergoing human trials in India. India has conducted more than 580 million Covid-19 tests, and 80% of the test kits used are now completely manufactured in India. Strongyloidiasis, an intestinal roundworm infection affects an estimated 30 to 100 million people worldwide. Rabies is present on all continents, except Antarctica, with over 95% of human deaths occurring in the Asia and Africa regions. Globally, the economic burden of dog-mediated rabies is estimated at US$ 8.6 billion per year. Every year, more than 29 million people worldwide receive a post-bite vaccination. Ischaemic heart disease was the top cause of death in both 2000 and 2019. It is responsible for the largest increase in deaths – more than 2 million – over the last two decades. Colorcon Inc., a global leader in pharmaceutical film coatings and specialty excipients, has acquired Mumbaibased Ideal Cures, which supplies coatings for tablets and capsules to pharmaceutical and allied sectors. Merck & Co's experimental antiviral drug molnupiravir to treat mild to moderate Covid-19 is on course to become the first oral antiviral medication for the pandemic. Globally, life expectancy has increased by more than 6 years between 2000 and 2019 – from 66.8 years in 2000 to 73.4 years in 2019. Anaemia is a serious global public health problem that particularly affects young children and pregnant women. WHO estimates that 42% of children less than 5 years of age and 40% of pregnant women worldwide are anaemic. Antibiotic resistance is one of the biggest threats to global health, food security, and development today. WHO has declared that Antimicrobial resistance (AMR) is one of the top 10 global public health threats facing humanity. One billion people need assistive products today and more than two billion people around the world are expected to need at least one assistive product by 2030.

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ARTICLE

Automation

AUTOMATION IN INDIAN PHARMA INDUSTRY Analysing Success vs Failures By Chetananand Pathak The automations of QA systems and processes are becoming of prime importance these days in Indian pharma industry. A polling done on LinkedIn recently to see how many people in Indian pharma could successfully implement the automation without much obstacles indicated that out of 200 people voted across the industry, 48% agreed that they could implement automations in rst attempt. This indicates a good change in the industry in recent years, because 10-12 years back there were very few Indian pharma organizations who were trying to automate their QA systems and processes, and many of them struggled to be successful in the rst attempt due to multiple reasons. Despite this fact many of us learnt through initial failures and slowly started adapting automations with a fresh thought. If we analyse the second part of polling, where 52% people across industry said that they could not implement automations in rst attempt, we may get multiple reasons.

ased on my experience and discussions with senior professionals from diﬀerent pharma companies who were involved in automation, I could list the following most common reasons: 1. Management thought process: It is important to understand what the management thought process is, and what they are visualizing as digitalization. There can be two thought processes predominantly: a. A few organizations in the enthusiasm to do modernization and automation proceeds to automate everything. b. A few organizations may also want to present in regulatory inspections the best picture of their existing controls in their processes to avoid human errors or human interventions Industry experts say that irrespective of the thought process of the organization management, if the convenience to users and proper assessment of user acceptance is lacking the eﬀorts may not be successful. 2. User thought process: It is also important to understand

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ARTICLE

Automation

automation of their QA systems and what the users feel as more processes. Following are few key convenient. Are they aspects to be taken care: comfortable with automation? Normally user nds diﬃculty to a. What is the user requirement switch over from paper based speci cation (URS): User system to digital products due to

troubleshooting expertise whenever required, etc. Again, experts say that vendors for any digitalization or automation in the pharma industry can be either

image courtesy: einfochips.com

requirement must be clear and their psychological attachment speci c. For example, whether for many years with paper organization wants full records. Users may feel more automation or semi automation, comfortable while reviewing whether they want to interphase paper records. They have a multiple automated permanent attachment with systems/softwares with each paper. Simple example of this is a other? If something in the newspaper in metro housing manufacturing process goes societies, where even today we wrong, whether they want to will nd multiple people buying have automated blocking of the newspaper daily even when outcome or auto rejection of the every news comes at our product, etc? ngertips on mobile. Exactly same may be the situation with b. Vendor Selection: Once the mainly document reviewers in vision of the organization is clear, pharma who are more they need to select a vendor comfortable nding mistakes in who is technically strong. The paper documents rather than in vendor evaluation may also software. include evaluation of his experience in digitalization of 3. Visualization of the similar processes, validation Management: It is important to expertise available, quality of know what organization post sales services, management visualizes as

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locally developed or a globally known branded digital products. · Developing a local vendor: Some organizations prefer to choose local vendors for automations due to multiple bene ts as listed below: a. Local vendors can sit with the user and understand user requirement very well. b. They can customize the digital product as per the user convenience and try to make the product more user-friendly. c. Such product is economical as it saves lot of cost compared to globally known digital products. The post-sale service cost or annual maintenance cost is low. The license cost and also the cost towards any modi cations required after implementation of

ARTICLE

Automation

pharma industries. As learnt through Covid-19 pandemic · Globally known branded there is also a need to develop product: In contrast to local vendors within the country vendor if we select globally thereby contributing to nation's known brand for implementing development, and in such case if digital products, it may have very local vendors need hand holding high cost, sometimes as high as to make them understand the 10 times compared to that paid global standards or regulatory to a local vendor. But such requirements as Indian industry globally known product has we should de nitely do that. certain advantages as listed below: To a question recently asked in a such digitalization is low.

LinkedIn poll on the choice of vendor for automation of processes and QA systems in Indian pharma industry, 45 % professionals mentioned that internationally b) The regulatory agencies know known product will be preferred, the top branded digitalization and 29 % mentioned that they will products in the global market choose local vendor, while 25% and they know how they are developed at the level of global people said that they will develop from their in house team. So it is standards. This may give some bene t in regulatory inspections organization speci c choice as to to give regulators the con dence what they want, but the trend in that an organization is following Indian pharma seems to be more on getting readymade products global standards. known globally. c) Another bene t of such globally known product is their post sales 4. Cost considerations: services, which are available 24 x Organization has to visualize cost at 7 in most of the cases. the beginning as well as cost post Finally, it is up to each organization implementation. For example, as to decide what exactly they want – mentioned under vendor selection, cost of licenses, annual whether they want to invest more maintenance cost and cost of and want comfort during regulatory inspections by following modi cations after implementation, if not visualized initially, becomes a global standards, or they want to huge burden and organization may save cost by choosing a local vendor to meet their speci c needs. nd it less feasible to continue with such recurring cost. Nowadays we are also observing that a lot of Indian vendors are also 5. Running parallel systems: getting developed and selling their Some organizations decide to digital products or software even in implement automation and run the international markets for previous non automated system a) The automation product is developed considering global standards rather than industry speci c user requirements.

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parallel for few months to gain con dence. But in doing so, the user gets overloaded following two parallel systems, and if the same continues for long time users start feeling inconvenience. Summary I tried to share my experience in this article. Experience involves discussions with other senior colleagues in Indian pharma industry. Most of the organizations implement automation of their processes and QA systems, and as they get experienced on it they learn many things. Many organizations even learn through failures to implement and nally they choose some product best suited for their organization culture. Whatever they choose, the most common success stories de nitely indicate importance of user convenience.

Chetananand Pathak has 26 years of experience in Quality Assurance and Corporate Quality within pharmaceutical manufacturing environment. As site QA head, led multiple successful regulatory inspections and was involved in selection and implementation of automations in processes and QA systems. Has been a speaker on Digitalization in Pharma. Currently working as Director Corporate Quality & Compliance with Emcure Pharmaceuticals Ltd.

ARTICLE

Cleanrooms

Fungi in Cleanrooms: Types, Origins, and Decontamination T Strategies

By Tim Sandle

his article considers the types of fungi that might be recovered from cleanrooms and looks at the mechanisms by which they might enter a facility. The article concludes with some considerations for fungal remediation.

Cleanrooms and controlled environments are at risk from fungal spores, should they enter the facility (1). Fungi can present health hazards to operators and pose potential contamination risks to medicinal products. The presence of fungi in the processing areas of pharmaceutical and healthcare products manufacturing facilities is normally regarded as an indication of a control breakdown, such as one relating to air handling or with the transfer of materials (or people) into the manufacturing area. The risk exists because most fungi produce spores, for reproduction or for survival, and such spores are relatively easy to disperse in the form of bioaerosols. These biologically dynamic particles can cover relatively wide distances and, unlike bacterial spores, fungal spores are found in relatively high numbers. The risk of spore dispersal can be enhanced based on air ow dynamics, the ambient temperature and humidity, plus water availability.

18 PHARMA machines & technology 24

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Tube ﬁller Cartoner Bundler Case packer & End-of-line Automation

ARTICLE

Cleanrooms

Types of fungi recovered from cleanrooms Fungi are structurally complex organisms, showing a variety of reproductive structures associated with sexual and asexual processes, in addition to vegetative, nonreproductive elements and hyphal structures. Their diﬀerentiation into genera, species, and varieties is made, in a large part, on a morphological basis — especially morphology of the reproductive structures.

Cladosporium growing on TSA, isolated from a cleanroom (Image by Tim Sandle)

There is a huge diversity of fungi on the planet. Mycologists have identi ed about 100,000 to 120,000 species of fungi, yet this 100,000 or so is only a fraction of the 1.5 million species of fungus probably present on earth.New cultureindependent approaches to determine microbial diversity, such as next-generation sequencing methods, are greatly broadening our view of fungal diversity (2). The number of diﬀerent fungal species associated with the as-built environment is somewhere between 200 and 250, with the majority requiring aerobic conditions for growth (3).

26 PHARMA machines & technology

While there are geographical variations in terms of what might be isolated (4), the species of Aspergillus, Cladosporium, Penicillium, Alternaria, Curvularia and Fusarium are the most predominant fungal isolates from pharmaceutical processing environments (based on a review undertaken by this author) (5). These fungi present a hazard and a challenge to contamination control practices. This is not least because spores of fungi can be found in dust particles in the atmosphere or on oors, work surfaces or equipment. Fungi come from many sources in the cleanroom, including door kick plates, bags, incubators, boxes, markers, intervention equipment, cartwheel, ceiling tiles, poorly maintained ooring, vibrations from construction, and in some cases, high-pressure impingement application devices for applying cleaning solutions.

cleanrooms. Variations with the environment, such as increases in ambient temperatures, together with items brought into cleanrooms, are also contributors. Overall, there are probably two main types of breaches: the ingress of un ltered air (where atmospheric air poses the greatest risk), such as from faulty Heating, Ventilation and Air Conditioning (HVAC systems); and with the ingress of water, such as a leak from a pipe (6). Other factors include transfer via personnel, where gowning can present a particular concern (the toe area has the highest population of fungi on the human body and the greatest varieties of fungi are found on the heel of the foot) (7). These points of origin are revisited in the section below about prevention of fungal contamination.

How fungi enter cleanrooms Fungi come from many sources in the cleanroom, including door kick plates, bags, incubators, boxes, markers, intervention equipment, cartwheel, ceiling tiles, poorly maintained ooring, vibrations from construction, and in some cases, high-pressure impingement application devices for applying cleaning solutions. De cient room pressurization, vibrations from construction, poor engineering designs related to sprinkler systems and light xtures have also been the cause of fungal outbreaks in

Oct - Nov 2021

Ochroconis fungus by methylene blue stain, x 100 objective (Image: Tim Sandle)

Fungal spores and dispersal Fungal spores are the reproductive mechanism for fungi. Fungal spores are either unicellular or multicellular, developing into a number of diﬀerent phases through the complex life cycles of the fungi.

ARTICLE

Cleanrooms

For example, with lamentous fungi the process of growth is through the production of hyphae (tubular branches), which expand as a mass (called the mycelium) in multiple directions. The production of aerial hyphae is an important mechanism for spore dispersal (8). In the cleanroom environment, the physical determinants in relation to each Heating, Ventilation and Air Conditioning (HVAC) unit will introduce air vector variabilities. In terms of the way spores may be distributed within the cleanroom

Penicillium fungus, methylene blue stain x 100 objective (Image: Tim Sandle)

Overall, there are probably two main types of breaches: the ingress of un ltered air (where atmospheric air poses the greatest risk), such as from faulty Heating, Ventilation and Air Conditioning (HVAC systems); and with the ingress of water, such as a leak from a pipe. Other factors include transfer via personnel, where gowning can present a particular concern (the toe area has the highest population of fungi on the human body and the greatest varieties of fungi are found on the heel of the foot).

28 PHARMA machines & technology

environment, with either sexual or asexual reproduction, the spores that disperse from the parent organism will do so either by either air currents or hitching a ride on a moving person or object. As well as dispersal mechanisms of the fungus itself, spores can move by water droplets. In terms of settling, sedimentation at terminal velocity under gravity is an important factor. Where spores are kept in suspension and removed from the controlled environment, the risks are lower; where spores settle the risk of germination exists, depending on those con uence of the necessary factors designed to promote germination (as discussed in this chapter). With the sedimentation of fungal spores, different types of spores do not equally remain in air. The deposition of a given spore is in uenced by their terminal velocity and aerodynamic characteristics. In general, large conidia and spores will settle faster than smaller ones. The objective of most fungal spores is reproduction. Fungi are often classi ed according to their sporeproducing structures, for example, spores produced by an ascus are characteristic of ascomycetes. Different factors will in uence the germination process, especially temperature which has a marked effect on the spherical growth rate of spores and their eventual size. The temperature will need to be optimal for the fungal species. A second important factor is with humidity. Germination is also mediated by surface topography, hydrophobicity, and physical and chemical signals (9). If conditions are not favorable, such as a low

Oct - Nov 2021

relative humidity, the spore will remain in dormancy (10). As well as reproduction, some fungi produce spores to survive unfavorable environmental conditions (such as hot and dry environmental conditions, lack of nutrients, alterations to osmolarity and hostile pH levels and chemicals), these are termed chlamydospores (a chlamydospore is the thick-walled large resting spore of several kinds of fungi. Why fungi survive in cleanrooms Upon entry of viable fungal propagules from outdoors, the fungus most probably becomes attached to a susceptible substrate (11). If fungi enter the cleanroom, the prevailing conditions of temperature, water availability and the state of the fabric are key determinants of whether the fungi will survive and colonize. If colonization occurs, it tends to follow the pattern: vegetative growth will commence if the appropriate environmental conditions exist. These conditions include suﬃcient free water and a susceptible substrate that can provide the necessary nutrients for fungal growth. If the conditions are suitable, the fungus will release extracellular fungal enzymes into the immediate environment, from which nutrients are absorbed and for which the presence of water is important (12). The indoor accumulation of water is the primary predisposing factor for indoor fungal colonization (and the subsequent biodeterioration of building materials). This is why fungi can regularly be recovered from wet-areas and wash-bays (and

ARTICLE

Cleanrooms

The objective of most fungal spores is reproduction. Fungi are often classi ed according to their spore-producing structures, for example, spores produced by an ascus are characteristic of ascomycetes. Diﬀerent factors will in uence the germination process, especially temperature which has a marked eﬀect on the spherical growth rate of spores and their eventual size.

activity). Ensure that cardboard never enters the cleanroom. 2.

consequence the controls leading into and out of these areas are critical). Water is the solvent that needed by all fungi in order to grow (while some fungi can survive with very low levels of water activity 4. (xerophilic organisms), the typical lower level for most species is an aw of 0.80 - examples include species of Aspergillus and Penicillium, which can grow slightly below 0.80; and species of Altemaria and Cladosporium which prefer the range 0.8 to 0.90 aw) (13). Water 5. activity (aw) is diﬀerent to water availability and it refers to “free” water available for microbial Preventative measures There are several preventative measures to reduce the likelihood of fungi being present in cleanrooms. These are (14, 15):

1. Control the delivery of items into the cleanrooms, such as ensuring items are dry and multi-wrapped (and that a layer is removed prior 7. to entering the cleanroom, together with a disinfection

30 PHARMA machines & technology

gowning must be practiced.

8. Use effective disinfectants. The variations between different Control of air, ensuring that the room HEPA lters are functioning species of fungi can be shown as designed. One common through assessments of the source of fungi is the interior Minimum Inhibitory surface of air ducts. Concentration (MIC) of different biocides.The disinfectant used Ensure good air ow within the must have proven properties cleanroom. Many cleanrooms are against a range of fungi. Often designed as turbulent ow areas, different contact times are they can move fungal spores required to eliminate spores over a wide area. The success or (fungal and bacterial) than are failure of the cleanroom design, used for standard disinfection including the ability to keep cycles.To kill spores – both particles suspended and the bacterial and fungal – a sporicide number of air exchanges needs to be used. As well as (determining how quickly air is killing spores, a sporicide is removed from the cleanroom) expected to also kill all vegetative can in uence whether fungal cells. Examples of suitable spores settle onto new surfaces. disinfectants are ones that is An important determinant is with chlorine based, or peracetic acid the materials used for cleanroom based, or hydrogen peroxide, or a construction; while modern blend of peracetic acid and cleanrooms are constructed of hydrogen peroxide). materials that are not intended to encourage fungal growth, this is Assessing the presence of fungi in pharmaceutical cleanrooms not always the case with aging requires an effective environmental facilities). monitoring regime that is capable Maintaining areas in a dry state is of detecting fungi consistently. The important. As dry states prevent frequency of monitoring should be fungal growth (although fungi sufficient as to allow trending to will often survive they are less take place. In terms of detection, likely to reproduce). thought needs to be given to the Minimize dust levels. Dust culture medium (either a general presents an interesting substrate, agar designed to recover bacteria and it plays a role in spore and fungi, or a speci c mycological dispersal dust can sometimes medium) and the incubation contain the nutrients derived conditions (16). Giving thought to from dead microbes, providing a this is important since there is an nutrient source for the association between the failure to organisms. detect fungi in the environment Fungi can be carried in by and the contamination of personnel, therefore effective healthcare products (17).

Oct - Nov 2021

ARTICLE

Cleanrooms

Conclusion

Tim Sandle is the author of the book Digital Transformation and Regulatory Considerations for Biopharmaceutical and Healthcare Manufacturers, Volume 1: Digital Technologies for Automation and Process Improvement, available via the PDA Bookstore: https://www.pda.org/bookstore/pro duct-detail/5897-digitaltransformation-volume-1

Fungi pose a risk to pharmaceutical cleanrooms, given their ability to survive for long periods of time and their rapid growth once conditions are optimal (especially given the right levels of water activity). In addition, fungi can be easily spread in the air, where the diﬀerent parts of the fungus can serve as reproductive propagules: conidia (asexual), spores (asexual or sexual), and hyphal fragments. Each of these can establish growth at a new nutrient source. In addition, spores often have the ability to remain dormant for substantial time periods. Due to the risks presented by fungi, this means that assessing fungal populations in cleanrooms becomes an important part of the environmental monitoring program using both air and surface methods. Once fungi have been detected in high numbers, steps need to be taken to eliminate the population. This generally relates to eliminating water sources; repairing damage; and eﬀectively disinfecting the area. This article has considered some of the contamination control and fungal spore risks within controlled environments. Understanding these risk factors will help to construct a contamination control strategy.

References 1. Sandle, T. (2014) Fungal contamination of pharmaceutical products: the growing menace, European Pharmaceutical Review, 19 (1): 68-71 2. Kousser, C., Alam, F. and Hall, R. (2019) Fungal interactions in health and disease, Microbiology Today, 46 (2): 95-97 3. Flannigan B, Samson RA, Miller JD. (2002) Microorganisms in Home and Indoor Work Environments: Diversity, Health Impacts, Investigation and Control. London: Taylor and Francis 4. Taylor JW, Turner E, Townsend JP, Dettman JR, Jacobson D. (2006) Eukaryotic microbes, species recognition and the geographic limits of species: examples from the kingdom Fungi. Philos Trans R Soc Lond B Biol Sci. 361:1947–1963 5. Sandle, T. (2011): A Review of Cleanroom Micro ora: Types, Trends, and Patterns, PDA Journal of Pharmaceutical Science and Technology, 65 (4): 392-403 6. Sandle, T. (2018) Investigating and Addressing Fungal Contamination in Pharmaceutical Cleanrooms, Journal of GxP Compliance, 22 (1): 1-10 7. Sandle, T. (2015) “From Head to Toe: Mapping Fungi across Human Skin”. EC Microbiology 2.1: 211-213 8. Wosten, H.A., Schuren, F.H., Wessels, J.G. (1994) Interfacial self-assembly of a hydrophobin into an amphipathic protein membrane mediates fungal attachment to hydrophobic surfaces, EMBO J, 13: 5848-5854 9. Osherov, N. and May, G.S. (2001) The molecular mechanisms of conidial germination, FEMS Microbiol Lett , 199: 153-160 10. El-Enshasy, H. A. (2007) Filamentous Fungal Cultures – Process Characteristics, Products, and Applications. In Yang, S. A. (Ed.) Bioprocessing for Value-Added Products from Renewable Resources: New Technologies and Applications, Elsevier, New York, pp225-261 11. Money, N. P. (2016) The Fungi, 3rd edition, Chapter 3 - Spore Production, Discharge, and Dispersal, Academic Press, New York, pp67-97 12. Cundell T (2014) Microbiology: mould contamination in pharmaceutical drug products and medical devices. Eur Pharm Rev 18(3):67–75 13. Cundell, A. M. (2009) Chapter 9: Eﬀects of Water Activity on Microorganisms In Cundell, A. M and A Fontana (Editors) Water Activity Application in the Pharmaceutical Industry Davis Horwood/PDA 14. Sandle, T. (2013). 'Dimorph and Filamentous Fungi'. In Mascellino, M. T. (Ed.) Bacterial and Mycotic Infections in Immunocompromised Hosts: Clinical and Microbiological Aspects, OMICS Group Inc.: Henderson, NV, USA E-book at: http://www.esciencecentral.org/ebooks/bacterial-mycotic-infections/pdf/bacterialmycotic-infections.pdf 15. Vijayakumar, R., Kannan, V.V., Sandle, T. and Manoharan, C. (2012). In vitro Antifungal Eﬃcacy of Biguanides and Quaternary Ammonium Compounds against Cleanroom Fungal Isolates. PDA Journal of Pharmaceutical Science & Technology, 66 (3): 236 – 242 16. Sandle, T. (2014) Examination of the order of incubation for the recovery of bacteria and fungi from pharmaceutical cleanrooms. Int J Pharm Compd 18, 242–247 17. Ahearn D.G. and Stulting, R.D. (2014) Fungi associated with drug recalls and rare disease outbreaks, J Ind MicrobiolBiotechnol 41: 1591 – 1597

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REVIEW

Webinar

AI and Mathematical Modelling in Pharma The webinar by MathWorks covered important and relevant topics: How to hybridize data from many data streams; optimize pharmaceutical production through process engineering; perform modeling and simulation for drug discovery and development; design, implement, and deploy code to control new medical devices; etc.

cientists and engineers in the biotech and pharmaceutical industries experience day to day scenarios related to multidisciplinary data analysis, industrial data communication, quality and process control followed by yield optimization, mechanistic models, and hybrid approaches to be implemented as end-to-end workflows. A multifaceted platform promoting early as well as easy prototyping enables engineering teams to move from internal research and development to design and implementation in a single environment. MATLAB from MathWorks offers a complete end-to-end solution for biopharma and can be scaled seamlessly from development on the desktop to deployment in the cloud or on premises high

34 PHARMA machines & technology

performance clusters. This language is robust and largely backwardscompatible owing to the vigorous design and testing environment at MathWorks. MATLAB supports deep and machine learning routines out of the box. Command-line and appbased workflows support users of all development styles and capabilities. It also supports numerous file and data types, including genetic, image, and bio signal, allowing many different data streams to be analyzed (or even combined) in the same software package. MATLAB is also easy to learn but does not sacrifice computational sophistication in its simplicity. There are many learning resources available for free through the MathWorks website. The talk from the Industry expert covered an interesting example on the field of pharma manufacturing, where the goal was to take pharmaceutical manufacturing from 'reactive state' to 'proactive' and further to 'predictive state'. Cipla Manufacturing Science and Technology Group have developed models using machine learning tools and deployed them on server which are used for predictive modelling by shopfloor personnel. Using Apps the shopfloor personnel can perform root cause analysis, can predict if the raw material is suitable for processing, if

Oct - Nov 2021

the processed batch will comply to the specifications and what improvements must be done for the next batch to get good results. Further the webinar delved deeper into mechanism based mathematical model informed artificial intelligence approach. Modelling is used in different phases of drug development processes to answer phase specific questions from choosing the right target, dose, patient and the safety and efficacy thresholds. As pharmacokinetics (PK) focuses on determining concentration profiles and the fate of drug molecules in the body, pharmacodynamics (PD) examines the effect of the drug on the body and then the possibility of combining models with greater complexity than the PK or PD models. Other than virtual bioequivalence studies relevant to the Indian context, the webinar also explored AI trends since the Bayesian framework of pharmacometrics ensures a natural evolution to embrace AI/DL/ML The presenters at the webinar were: Vaidehi Soman, Senior Manager, Cipla; Dr. Rob Holt, Bioscience Manager, MathWorks; and Dr. Shayoni Dutta, Senior Application Engineer, MathWorks.

CLEARPACK EXCLUSIVE

Packaging Automation PARTNER FOR PHARMA

Read the CLEARPACK EXCLUSIVE in the following pages...

Visit us at

24 - 26 November 2021 Expo Mart, Greater Noida Hall No. 14, Booth No. B10

Aggregation

Track & Trace

Serialization

Vision Systems

EXCLUSIVE

Inter view

Packaging automation has become lean, smart, data oriented and driven by AI Setup in 1994 in India with a dream to build a great packaging automation company, Clearpack is currently a 500+ people strong, stable, and well-organized group with network of oﬃces, R&D and production facilities and a dedicated team of packaging professionals across Southeast Asia, India, China, Middle East, Americas and Europe.

GOVIND BHANDARI CEO of Clearpack Group a passionate engineer with incredible energy and insatiable ambition speaks to Pharma Machines & Technology in an exclusive interview.

37 PHARMA machines & technology

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EXCLUSIVE

Inter view

What has been the nature of technological developments in packaging automation in the last thirty Q. years of Clearpack? Over the last thirty years, packaging automation has become lean, smart, data oriented and driven by AI. I A. still remember the solutions that were very complex in the early days when we were building machines and now everybody can easily make them. So, it's great that we've moved up in the value chain and welcomed the technology, which can provide more complex solutions.

Q. What has been your role and contribution to packaging automation in all these years? Packaging automation is core of our business. We started in this domain 30 years ago when packaging A. automation was not high on agenda for many companies. Our role has been to help our customers identify bottlenecks in their packaging lines, suggest optimum automation solutions to overcome the same and prioritise implementation of these solutions. In terms of contribution, we have always remained mindful of aﬀordability and ROI for our customers, incorporated latest technologies in our solutions and use non-proprietary standard OEM components to ensure that our customers always have access to parts from multiple sources. Our solutions are designed in Europe (Italy) by our partner companies and we build, assemble and test these machines in our factories in Greater Noida, India and Kuala Lumpur, Malaysia under their supervision to ensure same performance level and reliability, while keeping solutions aﬀordable. Last but not the least, we have built well trained teams of service technicians and engineers in all the markets we operate in to be able to support the solutions we supply and train our users. To be in the business, we need to continuously innovate by responding to market demand. This has been Clearpack strategy from beginning. This also opens new market and less competition. Clearpack has been leading this upgradation from front. We adapt to market need by implementing latest technological development with continuous engagement with our suppliers. We always keep our door open for new concepts/ designs and at any given time we would be working on an average 20 percent on such projects.

Q. Why and how Clearpack is the clear choice for packaging automation? With our vast industry experience, we provide aﬀordable solution for our customers based on line-speed, A. available workspace, product shape, size and future requirement. Clearpack works as a single source supplier with proven expertise to design, integrate and install complete packaging lines leading to high eﬃciency, cost and time saving. These world class machines are now made in India and backed by strong network of experienced service engineers. All the critical spares are available at our factory to serve and deliver the spares in fastest timeline to ensure minimum downtime and low maintenance cost.

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Oct - Nov 2021

Inter view

The pandemic has changed the world a lot in the last two years, Q. how challenging has it been for Clearpack and how did you take on it? The pandemic has disrupted business on many fronts. Nevertheless, A. Clearpack resumed its operations following the local authorized guidelines and protocols. Our eld-service teams have been working on-site, or remotely, to support the market. We tried to minimize service disruptions to our clients and worked hard to give them packaging automation solutions to assist manufacturers keep their workers socially distanced more safely on the factory oor without hampering overall productions. What are the safe, hygienic, and cost eﬀective packaging Q. automation solutions you oﬀer to pharma industry? Our solutions can be broadly categorised into Primary Packaging (like A. Filling, Capping, Sachet machines) and End-of-Line Packaging (like Shrink bundling, Case packing, Palletizing machines). Our solutions conform to the necessary ISO and EN standards and documentation to meet the safety and hygienic standards, and where necessary regulatory requirements speci ed by our customers.

We've partnered with suppliers who understand our requirements very well and have built very close relationships with them. Clearpack doesn't like to make anything that can be done by other companies more eﬃciently or better. We concentrate on what we do best and outsource whatever else can be done more competitively by our partners, so that we can provide optimum solutions to our customers.”

different is catering to pharmaceutical industry compared Q. toHowconsumer-packaged goods (CPG)? We all know that the primary objective of consumer packaging is to A. protect the contents from microbiological, chemical, physical, and atmospheric contamination and preserve the contents and thereby protect consumer's health. Packaging is essential and critical for promoting food safety, extended shelf-life and thereby enhancing food security. The quality of the packaging of pharmaceutical products plays a very important role in the quality of such products. It must protect against all adverse external in uences that can alter the properties of the product, e.g., moisture, light, oxygen, and temperature variations, and therefore the packaging components so used need to protect at each stage: · Protect against biological contamination, protect against physical damage. · Carry the correct information and identi cation of the product. · The kind of packaging and the materials used must be chosen in such a way that the packaging itself does not have an adverse effect on the product (e.g., through chemical reactions, leaching of packaging materials or absorption). · The product does not have an adverse effect on the packaging, changing its properties or affecting its protective function. The resulting requirements must be met throughout the whole of the intended shelf-life of the product.

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Packaging development has become an integral part of pharmaceutical drug development and manufacturing. The pandemic, COVID-19 has further strengthened the collaboration between the pharmaceutical industry, packaging technology suppliers, and regulatory authorities, creating a solid network for speed and eﬃciency in development and supply of safe and eﬀective medicines in the future.

EXCLUSIVE

Inter view

Is pharma industry lagging behind other high-risk industries in terms of innovation? What are your Q. comments? pharma industry has been under a constant pressure to provide packaging components which are inert A. inThenature. In other words, that do not have any reactions whatsoever with the medicine over the entire shelf life of the drug substance and beyond. All this can be achieved through the long term and accelerated stability studies that are a part of the drug substance development and release, etc. Packaging development has become an integral part of pharmaceutical drug development and manufacturing. The pandemic, COVID-19 has further strengthened the collaboration between the pharmaceutical industry, packaging technology suppliers, and regulatory authorities, creating a solid network for speed and efficiency in development and supply of safe and effective medicines in the future. In my opinion, it would be an error to say that the pharma industry is lagging behind. Of course, in some areas like injectable dosage forms where the interacting packaging components that come in direct contact with the drug substance and have immense importance over the other dosage forms. All those need to be selected based on the extensive stability studies of being inert in terms of chemical reactivity of the interacting surfaces. We have been supplying packaging machines for close to three decades. Now, in addition, we have smartfactoryworx system to monitor the line performance of existing or new production lines and to improve over-all line equipment effectiveness (OEE) while reducing maintenance costs by predicting and avoiding breakdowns. The solution includes invisible supervision on each machine, recording bottlenecks of production lines, automatic alerts, and more. Realtime data is generated for the improvement of the efficiency of the production lines. This has helped many of our customers to improve their OEE and reduce production downtime.” Minimizing rejects is a major challenge in pharmaceutical packaging. How are you addressing this Q. issue? is a major challenge for any industry including pharma. Rejections could be due to quality issues A. inRejection packaging materials or with machine related issues. Clearpack is working with our customers to understand the limitation from packaging materials and designing the machine which can work within max input quality deviation. In addition to this, Clearpack is constantly engaged in research and innovations to improve the machine performance adopting to latest technologies. We have also prepared our machine for industry 4.0 and offer a performance monitoring solution to identity the areas leading to maximum rejects. Speed gets faster and faster, and technology is constantly changing, it is extremely challenging to Q. be in the business of packaging automation. What has been the Clearpack strategy? To be in the business, we need to continuously innovate by responding to market demand. This has been A. Clearpack strategy from beginning. This also opens new market and less competition. Clearpack has been leading this upgradation from front. We adapt to market need by implementing latest technological development with continuous engagement with our suppliers. We always keep our door open for new concepts/designs, and at any given time we would be working on an average 20 percent on such projects.

Q. How important and effective are building partnerships and acquisitions in your kind of business? Today, we supply very high-speed, fully automatic packaging lines from primary lling all the way to end-ofA. line palletizing to the top consumer companies in the world. Our decision to acquire and start factories in Europe, especially in Switzerland and Italy, was very important because we are seeing the ywheel effect now – even though it took a lot of hard work to get started, it takes much less effort to keep it moving.

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Oct - Nov 2021

Inter view

Today, we supply very high-speed, fully automatic packaging lines from primary lling all the way to end-of-line palletizing to the top consumer companies in the world. Our decision to acquire and start factories in Europe, especially in Switzerland and Italy, was very important because we are seeing the ywheel effect now – even though it took a lot of hard work to get started, it takes much less Brief about your Industry 4.0 readiness, and your Q. SmartFactoryWorx? Clearpack is industry 4.0 ready. We have been supplying packaging A. machines for close to three decades. Now, in addition, we have smartfactoryworx system to monitor the line performance of existing or new production lines and to improve over-all line equipment effectiveness (OEE) while reducing maintenance costs by predicting and avoiding breakdowns. The solution includes invisible supervision on each machine, recording bottlenecks of production lines, automatic alerts, and more. Real-time data is generated for the improvement of the efficiency of the production lines. This has helped many of our customers to improve their OEE and reduce production downtime. What does it mean for your company to be named one of the Q. top 50 SMEs in the E50 Awards this year, especially amidst the challenges of Covid-19? is a great honor to be A. Itawarded as one of the top 50 SME’s in Singapore in such a challenging year, especially as we enter our 30th year of being in the industry this year. We view this as a recognition of our agility to be able to change our approach to the market quickly despite challenges faced last year. It is also a recognition of our team members across the region who work tireless to ensure customer delight.

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Oct - Nov 2021

Clearpack is working with our customers to understand the limitation from packaging materials and designing the machine which can work within max input quality deviation. In addition to this, Clearpack is constantly engaged in research and innovations to improve the machine performance adopting to latest technologies. We have also prepared our machine for industry 4.0 and oﬀer a performance monitoring solution to identity the areas leading to maximum rejects.

EXCLUSIVE

Primar y Packaging

Complete Primary Packaging Solution for Pharma Industry The quality of the primary

Rinsing Machines

packaging of pharmaceutical

products plays a very important role in the quality and shelf life of nal product packs. It must protect content against all adverse external in uences that can alter the

ORQ Range of Rotary Rinser meets the 21 CFR part 11 compliance by pharmaceutical industries and provides required cleaning for the interior of the containers in medicines production lines before for the next step of liquid lling. TORQ range of Rinser machines can have multiple cleaning treatments, like blowing with clean air, blowing with ionized air, vacuum suction, cleaning with water / cleaning solutions.

properties of the product, e.g., moisture, light, oxygen and temperature variations, biological contamination etc. Commitment to good manufacturing practices (GMP) compliance as required by pharma industry is the topmost priority of Clearpack. Here is a glimpse of popular solutions:

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Oct - Nov 2021

Primar y Packaging

Salient Features: - Suitable for Glass / PET / HDPE Bottles of diﬀerent shapes & sizes - Compact Design in SS304 construction with safety interlock - Multiple Treatments possible for bottle cleaning - Air Blowing, Suction, Liquid Rinsing - Dive in nozzle option available - Star wheels provided with clutch mechanism - Drainable machine frame - ease of Rinsing Mechanism: cleaning - Bottles to be loaded on conveyor, complete rinsing operation is automatic - Used water can be recycled if needed - Motorized Turret up/down movement - Machine comprised with Conveyor motor and Main motor - both with AC Drives

· Rinser with Air Blowing Treatment: The Rinser is equipped with Compressed Air Filtering system composed of Oil removing ltration degree of 0.6 μm. As well as nal lter equipped with ltration degree of 0,003 μm (air or gas). · Rinser with Suction Treatment: Each nozzle is surrounded by a slight vacuum chamber (suction cup) and is positioned, during the blowing phase, close to the bottle mouth. These cups relate to a central rotating manifold by a timing ring. During the working cycle, a side channel exhaust fan removes contaminants and air from the bottles by vacuum.

· Rinser equipped with Air Ionizing treatment: Each nozzle is equipped with a high-tension ionizer (8 kV) and blows ionized air inside the bottles. Ionized air blown into bottles allows the detachment of the - Operator friendly Customized HMI dust particles from the inner surface of the bottles. The supply includes touch screen the AC high voltage (8 kV) feeder.The ionization device is controlled - No bottle no Liquid discharge from the operator panel. - Various models designed to cover · Rinser equipped with Water Rinsing treatment: It is possible to production range from 50 bpm to provide a recovery tank that can be used for recirculating the liquid for 600 bpm. cleaning purpose.

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Oct - Nov 2021

EXCLUSIVE

Primar y Packaging

Linear Flow Meter Filling Machine The LFM series of lling machines are inline intermittent machines equipped with ow meter technology (volumetric measuring principle). For the liquids that are conductive, Magnetic Flow Meters

are employed for each nozzle. For liquids that are non-conducive, Mass Flow Meters are used for each nozzle. Both the Magnetic and Mass Flow Meters are applied for measuring the liquid with recipebased control system (from HMI) for accurate and repeatable lling of both large and small volumes.

Soft/Multi-Push Reject

Capping Solution for Pharma Industry TORQ provides a complete range of Capping solutions starting from linear Single Head Servo Capper for low speeds to Rotary Cappers with 3 to 20 capping heads. The machines are capable of handling Glass, PET, HDPE all kind of bottles for speed ranging from 15 to 400 bpm. TORQ capping machines are suitable for handling all types of closing applications; press-on Caps, Aluminium screw, CRC Caps, Prethreaded, oriented, dispenser, pump, and triggers.

Salient Features:

(product dependent)

· Various model ranging from 5 nozzles to 14 nozzles in a single frame

· Hygeinic non-contact lling

· To cater for Glass, PET, HDPE bottles for production speed up to 200 bpm · Bottle transfer by Servo driven timing screw · Nozzle Up/Down movement by Servo motor · Foamy liquids handled by Servo Driven Dive-in Nozzles · Liquid circuit supplied with gravity or pressurized tank

44 PHARMA machines & technology

· The liquid circuit is comprised with Automatic CIP function · Soft-push Rejection System to reject bottles that are out of ll volume tolerance · The machine is designed considering CIP operation to be carried out from HMI · State-of-the-art HMI with internal diagnostic & alarms · Monobloc execution of Filler with Single Head Capper is possible for lower speeds

Oct - Nov 2021

Primar y Packaging

Depending on the type of Cap, the machine can be equipped with special capping heads: · ROPP caps Chuck with thread forming and crimping wheels · For Screw Caps Machine comes with standard Magnetic clutches for normal torque range or with Hysteresis clutch (washable execution) with high torque accuracy · Pressure head with axial spring (diﬀerent measures) to apply the correct vertical load · Positive gripper chuck with mobile grippers controlled by a cam, for shaped caps

Salient Features: ·

SS Construction HMI panel designed for easy Operator Interface with display of SKU, alarms history and production data.

Capping heads rotation speed controlled by induction or brushless motors.

Orientation of Caps with respect to Bottle front / back face is by Vision Camera & Servo Motor

Remote assistance with Ethernet connection / Vision Camera for checking the correctness of capping

Quick change over and automatic regulation with recipes

TORQ machines are customized according to the pharma requirements always ensuring construction quality of the highest level

Product contact parts in AISI304 with AISI316l option

IES (Inox External Surfaces) and Washable execution machines are available

· Special chucks with vacuum or with grippers

Clearpack manufactures Torq Rinsing, Filling & Capping Machines in India under license manufacturing

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Oct - Nov 2021

Visit us at

24 - 26 November 2021 Expo Mart, Greater Noida Hall No. 14, Booth No. B10

EXCLUSIVE

Inter view

Always prepared for newest challenges In an exclusive interview

PIYUSH BHANDARI Area Sales Head - Clearpack speaks to Pharma Machines & Technology on the challenges in building automation solutions for pharma industry, how Clearpack keeps a close watch on the market and consumer behaviour and prepare itself for the new challenges, and on the newest solutions Clearpack oﬀers to pharma industry.

47 PHARMA machines & technology

What are the challenges in building automation solutions for pharma industry, compared to CPG?

For pharma, a great level of attention and detail must be on hygienic design, material selection, validation, documentation, and control as compared to CPG. I must add that many CPG products also demand high hygienic design, so we are quite familiar with these requirements.

The fast-changing pharmaceutical industry calls for newest packaging solutions. Is the packaging industry equipped? What are your comments?

At Clearpack, we keep a close watch on the market and consumer behaviour and prepare ourselves for the new challenges. Pharmaceutical industry demands innovative automation solution given the nature of the product and added by tough regulatory requirements. These requirements keep changing based on the country where these products are exported and hence the solutions that we provide should be extremely exible and easy to adapt to change with minimum cost implication. Clearpack is always prepared for tomorrow's challenge, and we believe this is the only way to grow with the time.

Investing in the right technologies has become an integral part of pharma industry's eﬀorts to prepare for the future. How do you help the industry out?

. Innovation is the key here. They can be either driven by our customer or by the technology provider like us. We closely work

Oct - Nov 2021

EXCLUSIVE

Inter view

Pharmaceutical industry demands innovative automation solution given the nature of the product and added by tough regulatory requirements. These requirements keep changing based on the country where these products are exported and hence the solutions that we provide should be extremely exible and easy to adapt to change with minimum cost implication. Clearpack is always prepared for tomorrow's challenge, and we believe this is the only way to grow with the time.”

In recent years, we have seen exponential growth in automation adoption and expanded our factory in 2016 in India. Last year, amidst COVID lockdown, the company saw further growth potential in India and accelerated its expansion plans to support the increasing production demand. We also established our sister concern Smart Factory Solutions Pvt Ltd to oﬀer Eﬃciency Improvement Solutions – a must have tool to monitor and improve overall productivity of production lines.”

48 PHARMA machines & technology

with our customer in developing a solution from concept. In many cases these investments may not lead to an immediate business, but Clearpack consciously spends time and resource in these developmental works as we believe this is the road map for innovations and thereby, we can prepare the industry for future.

It is said that the growth rate of technology has been much faster than the overall growth of pharma industry. What are your comments?

The trends in technology development have indeed taken enviable strides over the overall growth. But this has been fast tracked by the pandemic and the technology has been close behind to address the requirement of providing the vaccine in a record time of 15 months bringing it down from 5 to 8 years or more.

Brief about your oﬃces, factories and people strength globally?

Clearpack was setup in 1994 in India with a dream to build a great packaging automation company. We are currently a 500+ people strong, stable, and well-organized group with network of offices, R&D and production facilities and a dedicated team of packaging professionals across Southeast Asia, India, China, Middle East, Americas, and Europe. In recent years, we have seen exponential growth in automation adoption and expanded our factory in 2016 in India. Last year, amidst COVID lockdown, the company saw further growth potential in India and accelerated its expansion plans to support the increasing production demand. We also established our sister concern Smart Factory Solutions Pvt Ltd to offer Efficiency Improvement Solutions – a must have tool to monitor and improve overall productivity of production lines.

Q. A.

Oct - Nov 2021

What are the newest solutions you oﬀer to pharma industry? We have developed new solutions and models in both Primary Packaging and End-of-Line space. In Primary Packaging, from pharma standpoint, our new solutions are Linear Filling technology using Flow meters with full CIP capability, Hygienic nozzle, and high lling accuracy (0.3%), Net weight Rotary Filling machines and Servo cappers with full Torque control. In End-of-Line space for bundling and case packing, we have developed several new and compact solutions around Vision and Robotics integrated with Track and Trace. These solutions have high degree of exibility with quick changeover for formats. These could be particularly interesting for pharma sector.

Visit us at

24 - 26 November 2021 Expo Mart, Greater Noida Hall No. 14, Booth No. B10

EXCLUSIVE

End of Line Packaging

Need of Robotics Automation in End of Line Packaging

Industrialization of consumer goods companies are moving into next phase of automation in the form of End of line automation. Increased throughput, labor shortage, quality and consumer complaints, supply chain automation demand are the few important factors pushing this automation.

ne of the key factors pushing end of line automation in most of the industry is need for boosting eﬃciency and there by output. This is a key factor driving the end-of-line packaging market. While new production lines are being set up, there is also great need to automate existing low to medium speed lines. Customer desire to modernize the manufacturing plants will bene t the market in general and the technology provider in speci c. While calculating the return on investment for automation, it is very important to know the total cost of ownership (TCO) of the equipment. This is as important as the initial automation acquisition cost as this is recurring cost over the period of equipment lifetime. TCO should consider utilities, labor costs, spare and service cost spread along the length of the life cycle. Any robotic automation for end of line gives excellent bene t in terms of TCO due to its low spare part and maintenance cost due to time tested robots which have very high MTBF records. Robotic automations are deployable with some modi cation to do a totally new task. This gives high exibility and low redundancy factor. Clearpack has been working with leading companies in the region in developing various robotic based applications.

50 PHARMA machines & technology

Primary Packaging

Bottle Unscrambling Depalletizing Bottle Feeding

Pick & Place Tray Loading & Unloading

End of Line Packaging

Carton loading Case packing

Case sealing Palletizing

Oct - Nov 2021

Visit us at

24 - 26 November 2021 Expo Mart, Greater Noida Hall No. 14, Booth No. B10

EXCLUSIVE

Case Study

Single Source Responsibility For Your Packaging Lines Tablet Bottle Line Automation with Track and Trace Pharma companies often face problem with space for end of line equipments. In addition to length and width of the area, roof height also a concern in many companies. 1. Automatic lane division /collation system with Shrink bundling 2. Cobot case erector and packer 3. Check weigher and Rejector 4. Labelling Machine 5. Label Inspection Machine 6. Case Sealer 7. Cobot Palletizer

52 PHARMA machines & technology

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ne of the leading pharma company in India had similar problem. But this was not a deterrent for them to completely automate their end of line operation. They also had to include product serialization and aggregation. Clearpack came up with a unique solution which can very well t in the space provided. Solutions were based on robotics which helped optimize the footprint of the equipment. Clearpack jointly worked with a leading track and trace solution provider to put in place a complete line, taking care of all critical interface points between diﬀerent partners of the project. This helped customer getting a completely engineered and tested solution from a single source without worrying about integration. Bene ts to customer: – Fully automated solution with no manual intervention – 100 % Track and Traceability integration to the manufacturing process and visibility in the entire supply chain – Overcoming challenges of unstable bottles after application of PIL (Patient Information Lea et) – Collaborative operation – Easy integration with the existing line – Low operating costs – Safe & hygienic packing – Faster ROI – Small Footprint – Flexible and durability of machinery for long run – Real time monitoring of OEE – Accurate results and fast output

Visit us at

24 - 26 November 2021 Expo Mart, Greater Noida Hall No. 14, Booth No. B10

EXCLUSIVE

Efficiency Improvement Solutions

What gets measured, gets improved using IoT and i4.0

industry 1.0

industry 2.0

industry 3.0

industry 4.0 industry 5.0

Digitizing machine, Clearpack provides: 1. Line loss analysis

With IoT and i4.0 there is no

2. Yield of the material used

excuse now not to digitize the machine in real time and improve labour productivity,

3. Labour productivity A typical 8-hour shift will it look as below with OEE of 56%

asset monitoring, % yield of the material, and environment.

Helps to get breakdown of the idle time as below:

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Oct - Nov 2021

Efficiency Improvement Solutions

All the dashboards and reports are action driven:

Some of the important stoppages that are most detrimental to OEE are: 1. Minor stoppages 2. Changeover time

Clearpack will provide: 1. Continuous monitoring of OEE 2. Stoppages alerts

Report:

The OEE analysis is based on DIN 8743

Each month there is performance improvement summary. This will give what action needs to taken, and where there has been improvement. With IoT and i4.0 there is no excuse now not to digitize the machine in real time and improve: – Labour productivity – Reject / rework – Asset monitoring – % Yield of the material – Environment With ROI of less than 2 months, would you not try one of the lines? Reach Clearpack today. 55 PHARMA machines & technology

Oct - Nov 2021

ARTICLE

Track & Trace

Track & Trace Systems Implementation in Pharmaceutical Packaging A Major Challenge Track & Trace system, nowadays, plays a vital role in preventing counterfeiting during trading, assisting in optimizing monitoring at each level of supply chain and maintaining integrity of the product while dispensing to the customer. However, the entire process is full of challenges, although continuous measures are being taken by both manufacturer and service provider to minimize the errors while transit at various levels of supply chain as well as packing operations and to ensure minimum impact on the productivity.

By Navdeep Singh Kathuria

The pharmaceutical industry around the world has gone through tremendous challenges for the past few years since introduction of Track & Trace systems to comply with the medicinal products veri cation requirements to prevent counterfeiting and falsi cation at all levels of product supply chain starting from manufacturer and ending upto the dispensing counter of pharmacist. To implement the controls, the key importers of medicinal products (USA, UK and Europe) around the globe had formulated the laws and guidelines time to time to ensure correct supply of medicinal products in their respective territories. A. The Drug Supply Chain Security Act (DSCSA) – United States To prevent illegal trading, an act (Ordinance H.R. 3204) to supply medicinal products in USA was

56 PHARMA machines & technology

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formulated by experts and was signed by the then President in November 27, 2013, which was de ned under two diﬀerent titles at initial stage. i) Title I: The Compounding Quality Act which contains important provisions relating to the oversight of compounding of human drugs. ii) Title II: The Drug Supply Chain Security Act which outlines critical steps to build an electronic, interoperable system to identify and trace prescription drugs as they are distributed in the United States. On January 01, 2015, the act was amended by the mandatory implementation of product veri cation as all trading partners were supposed to have 'Pass and Accept' Transaction Information (TI), Transaction Statements (TS), and Transaction History (TH) with all sales. (Dispensers shall not accept

ARTICLE

Track & Trace

transaction without TI, TS, TH after 1 July 2015). The act was further amended on November 2017 to incorporate 'Unique Product Identi er' by Supply Chain trading partners and be able to verify the products legitimacy by following dates: •

Manufacturers: November 27, 2017

•

Repackagers: November 27, 2018

•

Wholesale Distributors: November 27, 2019

•

Dispensers (Clinics, Retail): November 27, 2020

Unit level Traceability has still been targeted to November 27, 2023, which will enforce the manufacturer to have an aggregation facility on serialized packs as a mandate. B. Falsi ed Medicines Directive (EUFMD)

and medical devices in the UK, including diazepam, moda nil and dermal llers. Worldwide, the annual Operation Pangea exercise, which was initiated by the MHRA in April 2006, netted potentially dangerous medicines and medical devices worth around £10.9 million and led to the closure of 123 websites, the removal of 535 online adverts. Looking into the scenario, it was a high time to frame drug regulations to prevent counterfeiting for which 'EU Falsi ed Medicines Directive' (2011/62/EU) (FMD) was adopted in 2011 and introduced new harmonised measures to ensure that medicines in the European Union (EU) are safe and that trade in medicines is properly controlled. The nal part of the Directive, the 'safety features' Delegated Regulation (EU) 2016/161) comes into force on 9 February 2019. It is worth noting that according to EU rules, a falsi ed medication is any medicinal product which has been falsely presented in

In October 2018, the MHRA reported that since 2015 it had seized almost 10,000 unsafe I) Identity of the product, sexually transmitted infection (STI) including its packaging, and human immuno-de ciency labelling, name, or its' virus (HIV) test kits that could give ingredients list, including false negative results leading to an excipients, and the strength of increase in diseases such as those ingredients, or, chlamydia, syphilis, and gonorrhoea, as well as HIV. Many of ii) In regard to the country of origin, including the the potentially unsafe kits were manufacturer, country of being sold online. Later that month, manufacture, and the holder of in a report on Interpol's globally cothe marketing authorization, as ordinated Operation Pangea annual well as the history of medicine's initiative that involves 116 trading, including the records countries, the MHRA and its UK and documents related to the partners reported that between used channels of distribution. 9–17 October 2018, they had seized more than £2 million worth of This de nition does not include unintentional quality defects falsi ed and un-licensed medicines

58 PHARMA machines & technology

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and is without prejudice to infringements of intellectual property rights. Apart from a unique identi er, the directive recommends implementing a mandatory security measure located on the external package (tamper evident feature) to protect the drug against undesired opening. The veri cation process – authentication - will therefore be nothing other than a basic element of pharmaceutical care, optimizing pharmacotherapy and increasing the level of patient safety. The EU FMD introduced harmonised European measures, which applied from 2013, to help identify and remove falsi ed medicines from the legal supply chain. The Directive amended the Human Medicines Regulations 2012 to require the introduction of two new safety features: i) A unique identi er (UI) in the form of a Data Matrix (2D barcode) and human readable information, comprising: a product code identifying the medicine, pharmaceutical form, strength, pack size and type; a unique randomly generated serial number; batch number; expiry date and ii) an anti-tampering device (ATD) on the outer packaging of almost all prescriptions. At the European level, this is EMVO (European Medicines Veri cation Organization), and at the national level - NMVO (National Medicines Veri cation Organization) and their main task was to create data repositories necessary to

ARTICLE

Track & Trace

authenticate individual drug packaging.

least recommends it looking into its complexity of identi cation.

line

C. Challenges faced by

2. Artwork revisions

requirements (Print, inspect and

pharmaceutical industry during

To comply with the space related

aggregate) by diﬀerent customers

transition phase

constraints on secondary

for diﬀerent pack sizes, frequent

If we review the history of

packaging materials to incorporate

changeovers and start up time was

implementation of the serialization

all details in the form of readable

also increased which had a direct

standards, major key challenges

data apart from 2D code data

impact on operational eﬃciency of

were faced by every manufacturer

matrix (GTIN, batch numbers, expiry

the plant. Bollino label was a perfect

during transition phase, and it took

date and unique serial numbers), it

example which was aﬃxed

a plenty of time to come out of the

became mandatory to revise

manually, and the process was

situation with new resolutions,

existing artworks to accommodate

automated later.

reworks, implications, and

all relevant information. Existing

6. IT Infrastructure overhauling

strategies:

stock with old artwork was

Installation of independent

1. Diverse regulatory norms

supposed to be discarded or was

production server and its

packed with tamper evident sticker

maintenance, storage of billions of

for European markets. Brexit further

events, data backup, secure data

added to the complexity.

exchange and data protection

they never come to a single

3. Integration with existing line

along with system updating

platform to draft universal norms.

equipment

became additional requirements

The lack of which complicated the

Synchronization of existing line

adding to the considerable cost to

manufacturer to comply the

components for compatibility with

the manufacturer.

country requirements individually.

serialization requirements was

7. Multiple service providers and

Italy already had introduced a

another challenge due to variety of

their approach

tracking system a long back

machine suppliers. Removal of

Not a single solution provider had

through forming an act (Law 39,

existing equipment and addition of

100% workability about their

Mar 1st. 2002, Art. 40) through

new automated equipment to

systems. Some vendors kept on

generating A.I.C. code of the drug

achieve targets was another factor

upgrading systems due to multiple

package that is the authorization

which added to the company's

issues like duplicate serial codes

number issued by the Italian

cost.

generations, serial code mismatch

Medicines Agency (AIFA) for

4. Space constraints on packing

etc., which is still a big source of

commercialization, the label, which

shop oor

alerts and complaints raised in

Due to diﬀerent regulatory requirements by regulatory authorities anywhere in the world,

Due to variety of serialization

to be aﬃxed on secondary package, Design of shop oor in packaging

Europe market.

known as Bollino.

area became mandatory to modify

8. Regulatory compliance and

NTIN (National Trade Item number)

to accommodate serialization and

data integrity

is still required by Nordic countries

aggregation components.

Key regulatory authorities like

having Nordic Article Number,

5. Multiple packaging

USFDA, MHRA and EMA had a key

however Global standards (GS1)

con guration on same packing

focus on data integrity also along

60 PHARMA machines & technology

Oct - Nov 2021

visit us at

24-26 November 2021 Expo Mart, Greater Noida, Delhi NCR

Hall-10. Stand-B31.

ARTICLE

Track & Trace

with serialization requirements that was a challenge for manufacturer to comply both regulatory as well as cGMP requirements during regulatory inspections.

house complaints during packing operations looking into the complexity and budgetary implications.

After passing through a long

awareness at user end also plays a

transition period, still aggregation

crucial role which further adds to

(Parent child relationship) is still

the human errors and serialization

under transition phase in Indian

alerts for which manufacturer needs

At present, lack of training and

pharmaceutical industry by most of to focus on continuous monitoring the manufacturers besides its to optimize the entire process and bene ts of reducing alerts and in-

reduce reworking.

References "European Medicines Agency - Public health threats - Falsi ed medicines". www.ema.europa.eu. Retrieved 23 June 2017. https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Pha rmacyCompounding/ucm376732.htm "H.R. 3204 - Summary". United States Congress. Retrieved 15 November 2013

Navdeep Singh Kathuria is General Manager - Packing, Aurobindo Pharma Ltd. He is working on implementing lean methodology along with automation of process equipment. Started his career with Tablet manufacturing, his additional area of expertise is Track & Trace systems and simpli cation of documentation on shop oor by means of replacing manual recording into the electronic form (EBMR).

visit us at 24-26 November 2021 Expo Mart, Greater Noida, Delhi NCR

Hall-12 - Stand No. D17

62 PHARMA machines & technology

Oct - Nov 2021

IN FOCUS

Uhlmann

Cristian Reiter takes over as Chief Technology Officer

at Uhlmann Pac-Systeme Cristian Reiter, who served as Vice President Packaging Systems at Uhlmann Pac-Systeme GmbH & Co. KG, has taken over as Chief Technology Officer (CTO) from October 1, 2021.

"We are very happy to have such a valuable addition to our experienced management team, joining from within the Uhlmann management board. Cristian Reiter has been with our company since 2019 and has already demonstrated his comprehensive expertise, for example by reorganizing his business unit or with important strategic projects in the new machine business. We have a lot planned for the coming years and I am certain that Mr. Reiter will have a leading role in implementing our ambitious corporate strategy," explains Prof. Dr.-Ing. Matthias Niemeyer, CEO of the Uhlmann Group and Uhlmann Pac-Systeme. Before joining Uhlmann, Cristian Reiter worked in mechanical and plant engineering for more than 15 years, most recently as a Executive Vice President and Managing Director of Homag Automation GmbH. "I am really looking forward

64 PHARMA machines & technology

CTO, and our current managing to this new challenge and to directors Prof. Dr.-Ing. Matthias actively contributing to the future of the company," says Cristian Reiter. Niemeyer (CEO), Michael Mrachacz (CSO) and Alexander Schöllhorn Mr. Reiter succeeds Tim Slomp, who (CFO), will continue to do contributed his development and outstanding work for our business." production expertise to great Uhlmann Pac-Systeme GmbH & Co. success at Uhlmann over the past KG is a global leader in providing four years. He also played a systems for packing particularly important role in pharmaceuticals in blister effecting structural and packaging, bottles and cartons. In organizational change and in addition to its innovative packaging comprehensively implementing lines, Uhlmann offers consultation, lean management. project management, extensive "We would like to thank Tim Slomp services and digital solutions from a for the trusting cooperation, his single source. The company is part great commitment and his valuable of the Uhlmann Group, which contributions over the past years. achieved a turnover of €423 million We wish him all the best for his in the 2020/21 business year with private and professional endeavors," around 2600 employees. Other says Tobias Uhlmann, Chairman of companies in the Uhlmann Group the Supervisory Board of the are KOCH Pac-Systeme, Cremer Uhlmann Group and Uhlmann Pac- Speciaalmachines, Wonder Packing Systeme. Machinery, and Axito. "Our management board, which now consists of Cristian Reiter as

Oct - Nov 2021

Find out more at: www.uhlmann.de and at www.uhlmann-group.com

REVIEW

PharmaLytica 2021

PharmaLytica 2021 successfully returns in a Hybrid Format The 7th edition of PharmaLytica organised by Informa Markets in India successfully concluded in the physical format at the Hitex Exhibition Centre on 14th August 2021.

his year, PharmaLytica, for the first time in a Hybrid format, witnessed a substantial turnout from buyers and sellers of the Pharma industry offline and online. The live in-person event was held from 13-14 August 2021, at the HITEX Exhibition Centre, Hyderabad and online from 13th -20th August 2021.

including the Pharmaceutical Export Promotion Council of India (Pharmexcil) and Confederation Of Indian Pharmaceutical Industry (CiPi).

The pharma industry needs to be in a state of continuous, steady improvement to spur medical advances. And, as the life sciences industry evolves, advancements in The two-day in-person event was lab equipment too will see a boost. inaugurated by Shri Ravi Uday Pharma labs will have to be at the Bhaskar, Director General, cutting edge of science and Pharmaceuticals Export Promotion technology to be more efficient, Council of India; Shri Chakravarthi improve time-to-market and AVPS, Global Ambassador, World reduce costs. As a result, the Packaging Organisation; Shri Madan demand for sophisticated Mohan Reddy, Whole Time Director, equipment and instruments to aid Aurobindo; Mr Muhd Suleman Kakar, and accelerate the process of drug Consul General of Afghanistan; Mr discovery, development, analysis Yogesh Mudras, Managing Director, and modelling of the compounds Informa Markets in India and Mr will continue to grow. Adding to Rahul Deshpande, Group Director, the industry's woes, packaging and Informa Markets in India. freight costs have also increased manifold. The show, along with its PharmaLytica enables the knowledge forum, aimed at finding pharmaceutical community to solutions for these industry issues. procure the current industry trends, innovations and conduct business Speaking at the success of with Analytical, Laboratory, PharmaLytica 2021, Mr Yogesh Machinery, Packaging and other Mudras, Managing Director, Informa allied Industries. The Expo is well Markets in India, said, “We are supported by associations, delighted with our return to

66 PHARMA machines & technology

Oct - Nov 2021

physical shows once again, commencing with PharmaLytica, at a time when the pharma industry is facing a massive transformation. The industry support and encouragement that we have received for putting up this show now creates added morale and determination to strongly bring back face-to-face shows in the pharma and other sectors. The pharma industry is projected to reach $65 bn by 2024 and $120 bn by 2030. This year, PharmaLytica, in its Hybrid format, focused on the lab and analytical equipment, pharma packaging solutions and pharma machinery subsectors. With future labs coming into place, the industry anticipates a boom in the pharma lab equipment market in the coming years.” “Innovation-led research and development, healthcare delivery (R&D), manufacturing and supply chain, and market access are the opportunities that have recently emerged and evolved to accelerate the growth of Indian pharmaceutical and healthcare industry. This can help to move up

REVIEW

PharmaLytica 2021

different cities, including the recently held PharmaLytica and the Biopharma networking series in Ahmedabad, strictly adhering to our Informa AllSecure Standards and commitments. India's share of trade in value. Like Witnessing such a great response every year, we at Informa Markets in and support from the industry, we India are committed to are looking forward to taking this encouraging novelty in products prestigious platform to the next level and exchanging ideas within the in the coming years. We thank framework of our exhibitions, be it offline or online. Significantly, a firm Pharmaceutical Export Promotion Council of India (Pharmexcil) and belief and conviction in our industry and its purpose also goes a Confederation Of Indian Pharmaceutical Industry (CiPi) for long way. Since the pandemic, we supporting us with this Re-Start 2.0 have delivered 8 live events in 6

68 PHARMA machines & technology

Oct - Nov 2021

of exhibitions.” He further added. The two-day conference had an exciting line of speakers that include – Dr Pallavi Hajela, Dr Tom Van Wijk, Dr George Johnson and Dr Harish Shandilya and many more. The Expo saw participation from companies such as Pacmac Solutions, Span Automation, Sachin Industries, Kinam Engineering, Agilent Technologies, Merck, Nichrome India and Thermo Fisher Scientific, Komal Scientific, Sun Teknovation, Omega Scientific, Smart Labtech, Conation India to name a few. Informa Markets is owned by Informa PLC, a leading B2B information services group and the largest B2B Events organiser in the world. Informa Markets in India

Technology Updates

run data. New high power lamps and software improvements enhance overall performance for faster evaporation rates.

TECH NEWS

Evaporator range to accelerate breakthroughs SP Industries (SP) has announced the launch of its new SP Genevac EZ-2 4.0 Benchtop Evaporator series for the fast, safe and environmentally-friendly removal of all commonly used solvents and acids.

The new EZ-2 4.0 also offers greater versatility for additional applications. Now with EXALT technology, crystallization studies such as polymorph screening can be conducted with ease. In addition, by preventing any vapor from escaping, the SpeedTrap means the EZ-2 4.0 can be used even without a fume hood, so this highly compact system can be readily located anywhere within a laboratory. The EZ-2 4.0 has also been redesigned to minimize its environmental impact, with low Global Warming Potential (GWP) refrigerant, a standby mode to help save energy, and reduced use of plastic throughout. The packaging is also recyclable.

The new EZ-2 4.0 centrifugal evaporator makes evaporation effortless, even for the less experienced user. Operators can simply load, set and walk away without any Three low maintenance models, need for specialized training. with HCl compatible and IGP (Inert SP has redesigned its highly Gas Purge) options, ensure that any regarded EZ-2 series based on solvent and application can be decades of advanced expertise in accommodated. The EZ-2 Standard evaporation science and feedback is ideal for solvents with boiling from bench scientists. To support points up to 120°C. The EZ-2 Plus or high performance and routine use, Elite are used for those with boiling the chemically resistant, glass points between 120°C and 165°C. SpeedTrap™ condenser jar is now The EZ-2 Elite is also optimized to located at the front for easy visibility, work with difficult solvents with and simple removal and replaceboiling points above 165°C, like ment. The new intuitive DMSO and NMP. It also features an touchscreen interface enables external low maintenance, dry scroll 'press-and-go' operation with at-apump for an even deeper vacuum glance monitoring of operational parameters, more pre-set methods that, combined with its auto defrost and draining condenser, enables for frequently used protocols, a methods guide, and recording of all fast lyophilization of HPLC fractions.

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Designed for challenging shear requirements The ROSS Inline Ultra High Shear Mixer 700 Series is designed for challenging shear requirements, a more efficient alternative to colloid mills which generally suffer from low throughput. Depending on the application, it can replace high pressure homogenization; or serve as a premixer to high-pressure homogenizers to mitigate clogging and inconsistent feed quality issues. To meet the specific demands of niche processes in the adhesive, chemical, cosmetic, food, beverage, pharmaceutical and plastic/composite industries, ROSS developed the QuadSlot rotor/stator for demanding applications where conventional rotor/stator mixers fall short but do not require the intensity of other ROSS 700 Series ultra-high shear designs, namely the X-Series and Mega Shear. By exposing product to four successive stages of increasing shear, the QuadSlot often provides a perfect balance of shear and flow capacity in the inline processing of emulsions, agglomerate size reduction and gas-liquid mixing. The washdown-duty Model HSM706Q-40 shown below features a 40-horsepower motor with a 6” QuadSlot rotor that runs at tip speeds over 11,000 fpm. This mixer is easy to clean and sanitize in place, saving time and allowing for longer production runs.

Technology Updates

Machine learning support to data include Insight Ventures, Saudi Aramco Energy Ventures, Altira science innovation Group, Chevron Technology Seeq Corporation, a leader in Ventures, and Cisco Investments. manufacturing and Industrial Seeq's strategy for enabling Internet of Things (IIoT) advanced machine learning innovation analytics software, has announced provides end user access to the expansion of its efforts to algorithms from a variety of sources, integrate machine learning rather than forcing users to rely on a algorithms into Seeq applications. single machine learning vendor or These improvements will enable organizations to operationalize their platform. This addresses the data science investments, and their diversity and types of algorithms available to organizations. open source and third-party machine learning algorithms, for The Seeq initiative also address the easy access by front-line employees. critical 'last mile' challenge of Seeq customers include companies scaling and deploying algorithms in manufacturing organization by in the oil and gas, pharmaceutical, chemical, energy, mining, food and putting data science innovation in the hands of plant employees in beverage, and other process industries. Investors in Seeq, which easy-to-use applications: Seeq Workbench for advanced analytics, has raised over $100M to date,

Organizer for publishing insights, and Seeq Data Lab for ad hoc Python scripting. This is in addition to Seeq support for the foundational elements of success with machine learning. This includes access to all manufacturing data sources—historian, contextual, and manufacturing applications—for data cleansing and modeling, support for employee collaboration and knowledge capture, quick iteration, and performance-based continuous improvement workflows. Seeq first shipped machine learning features in 2017 in Seeq Workbench, and then in 2020 introduced Seeq Data Lab for Python scripting and access to any machine learning algorithm.

First to Market : A fully synchronized ointment filling line.

PacMac

Aptitude for perfection

SINGLE HEAD TUBE FILLING

visit us at 24-26 November 2021 Expo Mart, Greater Noida, Delhi NCR

Hall-9 Stand-A04

CARTONER MACHINE

End to end ointment filling machine solution Wide range (60 to 200 tubes per minute)

Best ointment filling line available in India. Almost 100 % repeat order from all the buyers.

PacMac Solutions Pvt. Ltd. A-109, Dadra Industrial Estate, Opp. Dadra Check Post, Silvassa, U.T. of Dadra & Nager Haveli. Tel: +91 9819950900/9427468575 Email: thakkar@pacmac.co.in Website: www.pacmac.co.in

72 PHARMA machines & technology

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www.pacmac.co.in

Technology Updates

Addressing liquid pharma challenges Mettler-Toledo Product Inspection has launched new checkweigher and track and trace technologies to address liquid pharma challenges. The Mettler-Toledo StarWeigh™ Checkweigher is designed to provide laboratory accuracy of fill levels at production throughputs for small, instable or lightweight products, such as glass and plastic bottles, vials and ampules used in liquid pharmaceuticals. Up to four load cells can be fitted, including Mettler-Toledo's next-generation FlashCell™, capable of delivering highly accurate weighing results (+/- 5mg) at speeds of up to 300 products per minute.

74 PHARMA machines & technology

subsequently serialized. Manufacturers can save time and money by having fewer labeling and packaging processes. In addition, these technologies are backed-up by the company's global network of service experts, providing remote and on-site To help liquid pharmaceutical support, as well as proven solutionmanufacturers comply with based project management regulatory demands, Mettler-Toledo expertise in integrating OEM and has also launched the T60 proprietary technology into existing Integrated 360 Series systems for production lines. Mark & Verify, Serialization and Aggregation of round objects such The products can be immediately as bottles and vials. The T60 integrated into all applications Integrated 360 Series offers the where the production process ability to control third-party systems needs to conform to that print codes directly onto pharmaceutical requirements such bottles and vials versus the typical as 21 CFR part 11, with full processes where bottles are traceability, audit trail and validation inserted into cartons which are supporting documentation. StarWeigh™ is a compact checkweigher that can be installed within existing production lines and features customizable 'starwheels' to fit different package shape requirements and enable quick product changeovers.

Oct - Nov 2021

Technology Updates

To develop next-generation biomanufacturing technologies National Resilience, Inc. (Resilience) has announced a strategic collaboration with Children's Hospital of Philadelphia (CHOP) to implement next-generation biomanufacturing technologies and capabilities aimed at accelerating the creation of impactful therapies and technologies for the benefit of patients. As part of the multi-faceted strategic alliance, Resilience plans to work with CHOP's scientific and clinical teams to meet their biomanufacturing needs, and work to develop new cell, gene, and nucleic acid therapies and

biomanufacturing innovations, including novel delivery vehicles, next generation quality systems and novel approaches for scaling manufacture of such therapies. The organizations also plan to look for opportunities to collaborate on creating new ventures based on these technologies.

Resilience plans to support CHOP in fostering the next generation of biotechnology leaders, through education programs including symposia, student skill development, hackathons and internships.

Resilience is a manufacturing and technology company dedicated to broadening access to complex The collaboration also provides a medicines and protecting framework for CHOP principal investigator sponsored and external biopharmaceutical supply chains against disruption. Resilience aims Good Manufacturing Practice to free partners to focus on the production contracts to move from discoveries that improve patients' in-house early phase lives. manufacturing to full commercial CHOP is a center of excellence for production with streamlined tech the invention and translational transfer between CHOP and development of cell and geneResilience. based therapies, to help bring new In addition to the above work, complex medicines to patients.

AMS GLOBAL ENGINEERING CO.

76 PHARMA machines & technology

Oct - Nov 2021

PREVIEW

APE 2022

The 13th ASIA PHARMA EXPO 2022 (APE 2022) & ASIA LAB EXPO 2022, international exhibitions on pharma manufacturing technologies are scheduled during March 3 to 5, 2022 at ICCB, Dhaka, Bangladesh. of pharmaceutical industry.

The Bangladesh local pharma market is valued at around Taka 40,000 crore. More than 300 pharmaceutical companies of Bangladesh with current exports worth USD 72+ million are expected to take country's pharma formulation exports to USD 60 billion by 2021. Hon. Prime Minister Sheikh Hasina has already announced the pharmaceutical industry as a promising sector, as it is contributing much to the improvement of country's economic growth.

expected to exhibit their latest The exhibition is helping to develop technologies to upgrade the pharma manufacturing standards of the pharmaceutical industry of Bangladesh to a newer height. Bangladesh and making significant contribution to Bangladesh The 2020 edition was attended by economy. The exhibition, organized 11,748 trade visitors to explore the jointly by the Bangladesh complete spectrum of latest Association of Pharmaceutical pharma manufacturing Industries and GPE EXPO PVT LTD technologies and products on (India), offers an unparalleled display - processing machineries for international trade and formulation and API manufacturing, technologies platform specifically packaging machineries and to the entrepreneurs materials, cleanroom and utility manufacturing and exporting the equipment and services, water

Bangladesh has undoubtedly emerged as one of the fastest growing pharma economy in global markets. The momentum of growth is further accelerated by 17 years long extension till year 2033 by WTO / TRIPs to continue the patented pharma formulations. More than 47 units are coming up at API Manufacturing Park near Dhaka. The Bangladesh pharma industry now meets around 98% of the local demand for medicines, which is a milestone in the history

pharma engineering machineries and pharma bulk active chemicals to explore the business with the Bangladesh pharmaceutical industry. An overwhelming response by the local business associates as well technology solution providers from outside Bangladesh is noticed.

78 PHARMA machines & technology

At ASIA PHARMA EXPO 2022 / ASIA LAB EXPO 2022, more than 600 exhibiting companies from 29 countries across the world are

Oct - Nov 2021

treatment and management systems, analytical and biotech lab instruments, project consultants and turnkey contractors, API, pharma bulk actives, excipients, additives and many more. The focused industry segments are: Pharmaceuticals, Healthcare, Biotech, API, Neutraceuticals, Personal Care, Cosmetics, Beverages, and Distilleries. For more information about the exhibition, email to mail@AsiaPharma.org.

visit us at 24-26 November 2021 Expo Mart, Greater Noida, Delhi NCR

Hall-9. Stand- C25

4100