June July 2022 Edition

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Vol - 17

Issue - 2

June - July 2022

Dear Pharma Pals,

PUBLISHER & EDITOR Harjit Singh Dhaul

Why is QRM important for a pharmaceutical organization? What's an efficient

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QRM program? How QRM is implemented and applied across the product life

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cycle? How to plan a QRM program that is practical to maintain? How to manage

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a QRM program efficiently and effectively? How to embed QRM in all levels of the

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pharmaceutical organization? What is the correct way of implementing QRM?

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QRM expert Kate Coleman, Senior Director and Principal Consultant, PharmaLex, gives conclusive answers in an exclusive interview with this magazine. Quality


Risk Management (QRM) is important as it ensures that we place the risk to the

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patient and risk to product quality at the centre of each decision that we make. A

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QRM program can only be efficient when the information gathered through the

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Always keep in mind that QRM is not a tool for justifying bad practice or justifying

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deviations from GMP. QRM programs become inefficient and resource hungry

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when risk assessments are performed every time something goes wrong instead of performing them at the start when you have a chance to mitigate risk and prevent issues. Kate categorically states that if there is a culture of justification of current practice

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.

through risk assessment, an organisation will not improve or progress and will still have to waste resources in the management of deviations and issues that could have been foreseen and prevented with a good QRM program. Also read in this issue Natoli's initiative to minimize the gap between academics and the industrial aspect of pharmaceutics, and make the students industry ready. Yasar Shaikh, Director - International Business, Natoli Engineering Inc, USA, conducted a training program on tablet compression at Bombay College of

DEPUTY EDITOR Byju Bhaskaran

Pharmacy. Harjit Singh Dhaul



Publisher & Editor

Book Review


Blue Ocean of Compliance The best seller book on Amazon by Dr. Rupali Paranjape

11th Annual Innopack Pharma Confex Innovation and Sustainability Paving the Way Forward

Quality Risk Management


Exclusive interview with QRM expert Kate Coleman, Senior Director and Principal Consultant, PharmaLex.


From connecting devices to human value Jekson Vision presents ReeSmart, based on Industry 4.0 principles

Exclusives QRM

Tablet Compression Tooling – How it affects Tablet Properties Natoli training program conducted by Yasar Shaikh, Director- International Business, Natoli Engineering Inc, USA





Excellence in Packaging Automation Clearpack wins Excellence in Packaging Automation Award at Innopack, India Packaging Awards


A new consolidated team Brio Pharma Technologies and Marchesini Group India





India's first Covid-19 vaccine for animals Anocovax, developed by Haryana-based ICARNational Research Centre on Equines, is India's first home-grown Covid-19 vaccine for animals. Anocovax is an inactivated SARS-CoV-2 Delta (Covid -19) vaccine for animals. The immunity induced by Anocovax neutralises both Delta and Omicron variants of SARS-CoV-2. The vaccine contains inactivated SARS-CoV-2 (Delta) antigen with Alhydrogel as an adjuvant. It is safe for dogs, lions, leopards, mice and rabbits.

Top 300 drug brands shortlisted for QR codes India's drug pricing authority has shortlisted the top 300 brands of drugs including widely used analgesics, pain relievers, anti-platelet, vitamin supplements, blood-sugar lowering medicines and contraceptive tablets which will have to put QR codes to their packages, in a bid to ensure authenticity and enable tracing. The brands identified by the National Pharmaceuticals Pricing Authority (NPPA) include Dolo, Saridon Fabiflu, Ecosprin, Limcee, Sumo, Calpol, Corex syrup, Unwanted 72 and Thyronorm. The government has been trying to introduce QR codes since 2011. Pharma companies and lobby groups had expressed concerns over multiple sets of directions regarding tracing and tracking being issued by various departments and had asked for a single QR code system.

Drug major to expand field force in India Sun Pharma has announced plans to increase its field force in the domestic market by 10 per cent in the current fiscal in order to drive twin objectives of brand focus and geographical expansion. The Mumbai-based drug major, which is the fourth largest specialty generic drug maker in the world, currently employs around 11,000 Medical Representatives (MRs) and related staff in the country. Supported by more than 40 manufacturing facilities, Sun Pharma caters to more than 100 countries across the globe. In FY22, the company's topline has crossed the USD 5 billion milestone while the adjusted net profit has gone past the USD 1 billion mark.


PHARMA machines & technology

June - July 2022

Besides Anocovax, India has launched the 'CANCoV-2 ELISA kit' – a sensitive and specific nucleocapsid protein-based indirect ELISA kit – for antibody detection against SARS-CoV-2 in canines. Surra ELISA kit, a suitable diagnostic assay for 'Trypanosoma evansi' infection in multiple animal species, is also launched. Surra is one of the most important haemoprotozoan diseases of the different livestock species caused by Trypanosoma evansi. The disease is prevalent in all the agroclimatic parts of India.

16 common drugs under over-the-counter category Government of India is planning to list the commonly used drugs for cough, cold, pain and skin irritation such as paracetamol, nasal decongestants and antifungals under the over-the-counter (OTC) category. The Union Health Ministry has suggested amendments to the Drugs Rules, 1945, to bring 16 such medicines under Schedule K for providing exemptions from requiring a doctor's prescription so that they can be sold over-the-counter by retail sellers under a valid license. Those 16 medicines include Povidone Iodine, an antiseptic and disinfectant agent; Chlorohexidine mouthwash for gingivitis, Clotrimazole an antifungal cream; Dextromethorphan Hydrobromide lozenges for cough; analgesic ointment Diclofenac; Benzoyl peroxide which is an antibacterial for acne; Diphenhydramine capsules, an antihistaminic and antiallergic drug; Paracetamol; some nasal decongestants and laxatives.


Pharma firm launches OTT platform for doctors Mankind Pharma has launched Docflix, an OTT (over-the-top) platform for doctors. With the launch of the OTT platform, the company said it is taking steps to deliver engaging scientific content created by doctors specialised in their fields, in short, video formats. The company claims to have partnered with doctors in the cardiovascular segment to build authentic content, seeking to help doctors in making clinical decisions faster. The company said the platform will have 20 different shows on varied subjects, a few shows include science simplified, legend inside the white coat, stitch in time, cardio Unflip, medico-legal cases in India and much more. Additionally, the company has also hired the National Institute of Design's pass-out team to ensure the representation of data and figures, directors and scriptwriters who can form science into a story to deliver the message. The team is also building an AI-enabled personalised interface to deliver individual experiences on the platform.

India's first mRNA-based Covid-19 vaccine Subject expert committee (SEC) of the India's drug regulator will soon review Pune-based Gennova Biopharmaceuticals' application seeking emergency use authorisation (EUA) for India's first mRNA-based Covid-19 vaccine. Gennova had in April submitted interim data on its indigenously developed mRNA Covid-19 vaccine to the Central Drug Standard Control Organisation (CDSCO). Gennova has conducted phase-2/3 trials to evaluate the vaccine's safety, immunogenicity and tolerability on 4,000 participants. As the vaccine would not require sub-zero temperature for storage, it would make its rollout in India easy. While India's eligible population has received the primary dose of the Covid-19 vaccines, the mRNA platform continues to be important in the medium term, near future and beyond.

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Serum Institute of India plans African plant The Serum Institute of India (SII), the world's biggest vaccine maker, plans to set up its first manufacturing plant in Africa as it looks to expand globally after its success in selling Covid-19 vaccines. Africa was the only continent that did not have its own manufacturing capacity for Covid vaccines during the worst phases of the pandemic in the last two years, and depended on suppliers from overseas, including the SII. Apart from Covid vaccines, the SII's Indian plants make vaccines for diphtheria, BCG, measles, rubella and other conditions. SII has sold more than 1.5 billion doses of Covishield in India and exported millions more. But as demand has now waned, the company is putting its Indian Covishield facilities on standby. However, it is still making millions of doses of a version of the Novavax Covid vaccine for India and other countries.

Antibody drug for breast cancer launched Swiss drugmaker Roche Pharma has made the breast cancer antibody cocktail drug PHESGO available in India, which will be priced 20% less and more convenient to administer than the existing therapy. PHESGO is the world's first fixed dose combination of two monoclonal antibodies Perjeta (pertuzumab) and Herceptin (trastuzumab) in Oncology for the treatment of HER - 2 positive breast cancer. About 20-30% of all breast cancer cases are related to the HER-2 subtype, which is considered aggressive. PHESGO will come in a single vial for subcutaneous (under the skin) injection compared to existing therapy where Perjeta and Herceptin come in as two separate drugs, and are to be given through intravenous infusion (IV). While Roche follows differential pricing in India and offers its medications under our Blue Tree Patient Assistance Program at substantial discounted price on case-to-case basis for patients who can't afford, the MRP of Perjeta is 2.75 lakh and that of Herclon or Herceptin is 65,556.

The team from the Nuffield Department of Clinical Neurosciences of Oxford initially compared genetic variation in samples obtained from more than 1,000 subjects from Colombia in a two-part study to see if there were any genetic variants more common in individuals with higher pain wind-up. Researchers found a substantial difference in variants of one specific gene, the protein Sodium Calcium exchanger type-3, NCX3. The latest findings showed that any drugs that can boost NCX3 activity could potentially lower pain sensitisation in humans. HLA-G targeted CAR T cell therapy for solid tumours The University of Texas MD Anderson Cancer Center, Invectys and the Cell Therapy Manufacturing Center (CTMC) have entered a strategic partnership to codevelop a compliant and mountable process for human leukocyte antigen (HLA)-G targeted chimeric antigen receptor (CAR) T cell therapy to treat solid tumours. The partnership will be based on Invectys's HLA-G platform to progress new CAR T cell therapies until the preclinical development stage with CTMC into initialphase clinical trials at MD Anderson. Furthermore, the alliance will combine the technology of Invectys with the cell therapy development and manufacturing capabilities of CTMC and MD Anderson's clinical trial knowledge. The HLA-G molecule is a key modulator of the human immune system that is usually found during pregnancy when it works to offer protection for the foetus from rejection by the immune system of the mother. However, it is unusually expressed in cancer, making it a desirable tumour-specific antigen as the tumour cells suppress the innate immune responses of the patient. Gene linked to chronic pain discovered Researchers at the University of Oxford in the UK have identified a gene that regulates pain sensitisation by augmenting pain signals within the spinal cord. This offers an insight into the key mechanism underlying chronic pain in humans and provides a new therapeutic target.

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This is the first time that the researchers have been able to study pain in humans and then to directly demonstrate the mechanism behind it in mice, which provides a broad understanding of the factors involved and how they can begin developing new treatments for it. New treatment to prevent cardiovascular events The UK National Institute for Health and Care Excellence (NICE) has recommended Amarin's icosapent ethyl (Vazkepa) for reducing the risk of cardiovascular events, such as heart attacks and strokes, in adults with increased levels of triglycerides, a type of blood fat. According to the published final draft guidance, icosapent ethyl is indicated for use in adults with cardiovascular disease and controlled low-density lipoprotein cholesterol (LDL-C) levels taking a statin but are at residual increased risk of cardiovascular events and have elevated triglyceride levels. With the latest development, the new treatment will benefit nearly 425,000 individuals. Icosapent ethyl is said to be the first licensed therapy that demonstrated to reduce the risk of heart attack and stroke in individuals with controlled LDL-C or 'bad' cholesterol who are on a statin and have raised triglycerides. According to clinical trial data, icosapent ethyl showed to lower the risk of cardiovascular events in people by more than a quarter versus placebo in individuals with evaluated triglyceride levels, LDL-C levels controlled by statins and cardiovascular disease.

Researchers discover genes linked to Covid-19 Scientists from the University of Sheffield in the UK and Stanford University in the US have identified certain genetic signals in individuals who de velop severe Covid-19 infection. The team leveraged machine learning and discovered more than 1,000 genes associated with se vere Covid-19 cases that needed breathing support or were fatal. Furthermore, the team detected specific kinds of cells in which these genes ac t up. This research is claimed to be one of the first studies to establish a relation between coronaviruslinked genes and particular biological functions.

the in vivo effects of SFX-01 in models of colorectal cancer. Utilising normal and malignant patient-derived organoids and tumour tissue, the mechanism of action and impacts of SFX-01 on organoid growth, morphology, stemness and inflammator y markers will be analysed. The company anticipates the preliminary findings at the end of next year. A clinical-stage drug development firm, Evgen focuses on the development of sulforaphane-based therapies to treat cancer and other indications. Its core technology is Sulforadex, a technique to synthesise and stabilise the naturally occur ring compound sulforaphane and new analogues based on sulforaphane.

To unravel the genetics behind severe Covid-19, the researchers utilised various large data sets. The first data set included genetic information from lung tissue of healthy humans.

To develop gene therapy manufacturing processes

This data aided in detecting gene expression in 19 separate lung cell types, including epithelial cells. These cells line the respiratory tract and serve as the first line of defence against infection.

Coave Therapeutics and contract development and manufacturing organization (CDMO) ABL have signed a strategic partnership for developing gene therapy manufacturing processes.

Other data came from the COVID-19 Host Genetics Initiative, a genetic study of critically ill Covid-19 patients.

Under the two-stage partnership, Coave and ABL will merge their complementar y capabilities in the initial stage to jointly develop manufacturing technologies for AAV-based gene therapy products.

The team analysed genetic hints in the data such as DNA mutations known as single nucleotide polymorphisms, which could show if someone is at an increased risk for severe Covid-19.

Partnership to study colorectal cancer asset Evgen Pharma has entered a partnership with the University of Michigan in the US to analyse the potential anti-tumour effects of the company's lead asset, SFX-01, for colorectal cancer. SFX-01 is a patented composition of synthetic sulforaphane and alpha-cyclodextrin. In prior studies, the compound demonstrated in vivo and in vitro efficacy in various types of cancer cells including breast cancer, glioblastoma and certain blood cancers. Under the latest partnership, the parties will assess

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The process development teams of the companies will work together in the GMP facility of ABL in Lyon, France. The partnership's second phase will offer an exclusive option for Coave to obtain process development capacity and laboratory space within the plant of ABL. This will aid Coave to continue the development and scaling up of manufacturing technologies for AAV-based products, including the next-generation AAV-Ligand Conjugate vectors (ALIGATER) platform of the company. The latest partnership will also bolster the potential of Coave to produce large-scale and high-quality gene therapy products based on this new generation of advanced AAV vectors.



DID YOU KNOW? India has the largest Bio Safety Level 3 (BSL-3) laboratories facility in the world, used to study infectious agents that can be transmitted through air. Injuries (including road traffic injuries and drowning), violence, self-harm and maternal conditions are the leading causes of death among adolescents and young adults Half of all mental health disorders in adulthood start by age 14, but most cases are undetected and untreated. The harmful use of alcohol is a causal factor in more than 200 disease and injury conditions. Overall 5.1 % of the global burden of disease and injury is attributable to alcohol. The lower the levels of air pollution, the better the cardiovascular and respiratory health of the population will be, both long- and short-term. Dog bites account for tens of millions of injuries annually; the highest risk is among children. Misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens. Without effective antimicrobials, the success of modern medicine in treating infections, including during major surgery and cancer chemotherapy, would be at increased risk. Globally, more than 1 billion people need 1 or more assistive products. Hearing aids, wheelchairs, communication aids, spectacles, prostheses, pill organizers and memory aids are all examples of assistive products. Most asthma-related deaths occur in low- and lower-middle income countries, where under-diagnosis and under-treatment is a challenge. Birth defects become a larger proportion of the cause of neonatal and under-5 deaths. The most common severe birth defects are heart defects, neural tube defects and Down syndrome. Cervical cancer is the fourth most common cancer in women after breast, lung and colorectal cancer. India reports 80,000-90,000 cases of cervical cancer every year. Globally, at least 2.2 billion people have a near or distance vision impairment. In almost half of these cases, it could have been prevented or has yet to be addressed. Clostridium botulinum is a bacterium that produces dangerous toxins (botulinum toxins) under lowoxygen conditions. Botulinum toxins, one of the most lethal substances known, block nerve functions and can lead to respiratory and muscular paralysis. As of the end of 2020, there were 7.8 million women alive who were diagnosed with breast cancer in the past 5 years, making it the world's most prevalent cancer. Brucellosis is found globally and is a reportable disease in most countries, causing flu-like symptoms, including fever, weakness, malaise and weight loss.

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Inter view

QRM Quality Risk Management • Why is QRM important for a pharmaceutical organization? • What's an efficient QRM program? • How QRM is implemented and applied across the product life cycle? • How to plan a QRM program that is practical to maintain? • How to manage a QRM program efficiently and effectively? • How to embed QRM in all levels of the pharmaceutical organization? • What is the correct way of implementing QRM?

QRM expert Kate Coleman, Senior Director and Principal Consultant at PharmaLex, a global organization, speaks to Pharma Machines and Technology in an exclusive interview. Kate has worked in quality roles in the pharmaceutical industry up to management level for 20 years, covering several platforms including biologics, sterile ll nish, vaccines, and oral dose. Kate is a practicing QP, Principal Consultant, a quali ed Lead Auditor and an SME in Quality Risk Management, New Facility Design/Start Up, QC and Sterility Assurance.

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Inter view

Why is QRM important for a pharmaceutical organization?

Quality Risk Management (QRM) is important as it ensures that we place the risk to the patient and risk to product quality at the centre of each decision that we make. It provides a mechanism for us to identify and understand the true risk associated with our course of action, whether that is related to the design of our facilities and processes, the management of change, the assessment of deviations and unplanned events or in the design of our Quality Management Systems.



What's an efficient quality risk management (QRM) program?

A Quality Risk Management program can only be efficient when the information gathered through the risk assessment process is revisited regularly and used to drive decision making. Prospective risk assessments should be in the majority, so that risks and their consequences can be mitigated and avoided before they occur and before there is a need for resources to be spent on xing problems that could have been avoided.

If a Quality Risk Management program is efficient there will be a smaller number of risk assessments that are prospective, prevent risks, and are revised regularly e.g. when a Change Control is proposed or an OOS or Deviation occurs. They are living documents and should also be driver for knowledge retention and management. Inefficient Quality Risk Management programs do not de ne the boundary of each risk assessment appropriately and contain risk assessments that are performed to 'tick a box' or satisfy inspectors rather than to drive improvement and risk reduction.

How QRM is implemented and applied across the product life cycle?

At the design phase, for a product, process or facility, the potential risks should be identi ed and controls de ned for each risk within the context of the risk question (s). These controls are then incorporated into the design and Quality Management System, documented and detection mechanisms are identi ed to monitor the effectiveness of the controls.

When the detection indicates that a control is not performing as expected, or a risk is realized, the risk assessment is reviewed, revised and updated with additional controls until the risk is managed and only residual risk remains. This process is continued throughout the lifecycle of a product, process or facility and following the implementation of the Quality Management System, each Change Control and Deviation should trigger a review of the relevant risk assessments.

Quality Risk Management (QRM) is important as it ensures that we place the risk to the patient and risk to product quality at the centre of each decision that we make.


Why is planning important?

Planning is important to: 1) ensure that the key risk assessments For example, if a Change is proposed in a process, the relevant process step should be reviewed in each relevant risk assessment and the change required in the Quality Risk Management plan are identi ed assessed against the impact it will have on the current controls or methods of detection at that process step. Likewise, when a deviation and 2) to ensure the appropriate occurs, this is an indication that something has gone wrong, i.e. a risk has scope and risk question is identi ed occurred that wasn't prevented by the Quality Risk Management program. for each risk assessment identi ed. This prevents the performance of Investigation of the deviation should identify why the risk had not been multiple risk assessments that do foreseen or if it had, why the controls had failed to prevent the risk occurring. Any resulting CAPA actions should be included in the relevant not have clear direction or a risk assessments as controls on conclusion of the investigation and de ned risk question. implementation of the resulting CAPA plan. The risk question should always tell you the type of risk being assessed, A Quality Risk Management program can only be efficient when e.g. quality risk, contamination risk the information gathered through the risk assessment process is etc., and what the risk is being revisited regularly and used to drive decision making. assessed against. For Quality Risk

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Inter view

Management, the risk question should always be the assessment of the de ned risk to the product quality or patient safety. Business or safety risk does not fall within the scope of Quality Risk Management. It is also important to plan each risk assessment so that the purpose of the risk assessment is clear and to provide the opportunity to identify the correct tool for documenting the risk assessment. Risk Assessment tools do not drive the risk assessment, this is the function of the risk question, they are there to help the clear documentation of the risk assessment. Inefficient QRM programs do not de ne the boundary of each risk assessment appropriately and contain risk assessments that are performed to 'tick a box' or satisfy inspectors rather than to drive improvement and risk reduction.



When planning the Quality Risk Management program, it is important to remember that the purpose of risk management is to help you identify the true risks that are present in your processes so that they can be mitigated and prevented.

Quality Risk Management is not a tool for justifying bad practice or justifying deviations from GMP. Many companies skip the planning process and implement risk assessment as a method for impact assessment after the fact. This is not the intention of Quality Risk Management. The risk assessments that will help you to constantly monitor, assess and mitigate the quality risks in your process need to planned and identi ed so that they can prevent issues before they occur. To plan your Quality Risk Management Plan you must be aware of the following: • What risks are you concerned with in terms of quality, e.g. microbial contamination, impact to CQA, particle contamination, etc. • What are your processes and have you de ned all of your process steps that could be impacted by risk. • What regulatory requirements do you need to meet in terms of Quality Risk Management, e.g. nitrosamines, excipient risk assessment, contamination control risk assessment, etc. • Where will risk assessment help you to prevent issues from occurring in the future, e.g. process FMEA, Contamination Control Risk Assessment, GMP Design Risk Assessment, System Risk Assessment for CQV, etc.

QRM should bring efficiency and economy, how to plan a QRM program that is practical to maintain?

The key to efficiency and economy is having a small number of key prospective risk assessments that are revised regularly as new information becomes available through process improvement, change control and deviations. QRM programs become inefficient and resource hungry when risk assessments are performed every time something goes wrong instead of performing them at the start when you have a chance to mitigate risk and prevent issues. Each risk that you identify and prevent reduces the resources spent on issues and deviations and xing mistakes.

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What are the key considerations while planning?

June - July 2022


What if QRM is not working for a company, nor deriving value from it?

This usually occurs if QRM and its function are not well understood or if risk assessments are reactive tools to problems rather than used to proactively prevent issues. This also occurs when the QRM program is not integrated nor informed by other elements in the Quality Management System as mentioned previously. QRM needs to be an ever evolving tool that keeps us informed of the detail of our current process, how that process is performing, how our controls are performing and areas where there is risk that we can prevent from occurring. Planning is important to: 1) ensure that the key risk assessments required in the Quality Risk Management plan are identi ed and 2) to ensure the appropriate scope and risk question is identi ed for each risk assessment identi ed.



Inter view

How to manage a QRM program efficiently and effectively?

It is also important to plan each risk assessment so that the purpose of the risk assessment is clear and to provide the opportunity to identify the correct tool for documenting the risk assessment.

To manage a QRM program, its function needs to be understood by everyone in the organisation, at all levels and there needs to be an open culture that welcomes the identi cation of risk so that it can be mitigated and prevented. If there is a culture of justi cation of current practice through risk assessment, an organisation will not improve or progress and will still have to waste resources in the management of deviations and issues that could have been foreseen and prevented with a good Quality Risk Management program.

Also, the emphasis is often incorrectly placed on risk management tools and implementation of complex tools that are poorly understood. The emphasis should always be simpli ed and brought back to the questions, “What can go wrong, what is the likelihood it will go wrong based on the current controls in place and how will I detect if it goes wrong or if my controls fail?” As long as we answer this question comprehensively across our operations, we are performing Quality Risk Management and the method for documentation of this thought process is just that, a method for documentation.


How to embed QRM in all levels of the pharmaceutical organization?

Ensure that all levels in the organisation understand the following:

• Quality Risk Management is only concerned with risk to product quality and patient safety • Quality Risk Management is working if it saves time and resources dealing with issues by identifying and preventing those issues before they occur.

Quality Risk Management is not a tool for justifying bad practice or justifying deviations from GMP. Many companies skip the planning process and implement risk assessment as a method for impact assessment after the fact.

• Quality Risk Management should not increase but decrease workload once it has been implemented properly • Quality Risk Management is a method for documenting our knowledge of our processes, our controls and our methods of monitoring. • Everyone naturally thinks in terms of Quality Risk Management in our daily lives, it is how we keep ourselves safe and out of harm's way. Quality Risk Management in industry is just a way of using that inherent thought process to protect our patients rather than ourselves. QRM programs become inefficient and resource hungry when risk assessments are performed every time something goes wrong instead of performing them at the start when you have a chance to mitigate risk and prevent issues.

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What is the correct way of implementing QRM?

Training, planning, implementing and maintenance. If risk assessments are not revisited every time there is a deviation or change control, the system isn't working!

June - July 2022

QRM needs to be an ever evolving tool that keeps us informed of the detail of our current process, how that process is performing, how our controls are performing and areas where there is risk that we can prevent from occurring.


Natoli Training

'TABLET COMPRESSION TOOLING - HOW IT AFFECTS TABLET PROPERTIES' Natoli Engineering Inc, USA, conducted a training program on tablet compression at Bombay College of Pharmacy on 21st May 2022, as part of its initiative to minimize the gap between academics and the industrial aspect of pharmaceutics, and make the students industry ready.

Mr. Yasar Shaikh, DirectorInternational Business, Natoli Engineering Inc, USA, gave a detailed talk to students of Bombay College of Pharmacy, mainly for the nal year and PhD students, and students who are involved in tablet compression.

tooling manufacturing, to minimize the gap and make students industry ready.

Natoli conducts several training programs and seminars all over the world for this purpose. Bombay College of Pharmacy invited Mr. Yasar Shaikh from Natoli headquarters in USA to conduct It was a new experience for the this program. He is a Mechanical students as there is a major gap Engineer (Mumbai) and has 23+ between academics and the industrial aspect of Pharmaceutics. years' experience working with This is one of the initiatives taken by multiple tablet compression Dr. Dale Natoli, President for Natoli tooling companies internationally. He is actively involved in training in Engineering, the global leader of the subject of tablet tooling at tablet compression

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various universities and industries across the globe. Bombay College of Pharmacy (BCP) is a 64 year old pioneering pharmacy institute offering B.Pharm, M.Pharm and Ph.D courses. The college is affiliated to Mumbai University, and has been granted autonomous status by UGC in 2019. BCP has several collaborations with industry and has been recipient of several grants and awards from Government and Industry. The students from T.Y. B.Pharm, F. Y. M.Pharm and Ph.D scholars and

• Cartoner • Bundler • Case packer & End-of-line Automation

To find out how we can help you with secondary packaging solutions for your injectables email us at : hello@avishmachines.com


Natoli Training

The impact of working length to tablet thickness, hardness, weight variation and the relevance of working length matching report to minimize issues related to tablet hardness and weight variation were described. The considerations and solutions for problems regarding sticking and picking were explained, covering logo picking, thermal related issues and ways to minimize their effects.

Pharmaceutics faculty, as well as industry person, Mr. Samir Vasavada attended the session. The aim of the guest lecture was to equip students with the basic points on tablet tooling and how this affects the tablet properties. The session started with an introduction of rotary tablet press tooling, covering commonly used tool con gurations and new trends in tooling such as Segments and Special tooling types. After covering common con gurations, the tooling standards were discussed. TSM (US) and EU (European) tooling standards are established in the industry to provide standardisation in tooling speci cation. TSM and EU

con gurations are very similar to each other but do have some differences that restrict their interchangeability. The two most common tooling con gurations are B and D types. The students were also introduced to common tool terminologies such as Head Flat, Working Length and Tip Relief. The basics of compression cycle, dwell time, key angular orientation were explained. The common tablet compression problems related to weight variation, thickness, hardness, sticking, picking, capping and lamination were addressed, followed by ways to counter them.

In the end, different types/grades of steel used in tooling like S7, M 340 etc. and protective items like dust caps and bellows were briefed. Overall, it was a very informative and interactive session where students gained rst-hand knowledge about tablet tooling, its importance, and applications. The session was concluded with a vote of thanks and presentation of memento to the speaker by Dr. Mala Menon, Adjunct Professor at BCP. Some excerpts of feedback of the lecture session from Faculty and students: “The lecture on tablet tooling and compression by Mr. Yasar Shaikh gave an in-depth information on the various facets of tablet compression and the signi cance of punch and die tooling in yielding a compressed tablet with desirable parameters. It also gave information on various types of punches and dies offered by Natoli Engineering to the pharma industry.” - Dr. Harita Desai, Assistant Professor of Pharmacy “The session elaborated about the basic concepts related to tablet tooling. Emphasis was given on troubleshooting during

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+91-79400 54255




Natoli Training

obtain the desired product. This understanding will also help us troubleshoot any problems during large-scale product production. A lot of research is involved in the machinery and Mr. Yasar Shaikh gave a bird's eye view of the tablet compression tooling with great enthusiasm!” - Ms. Isha Naik, Ph.D Scholar Pharmaceutics

compression and how to overcome the same.”

and I am very excited to practice on online simulator!”

- Ms. Rashmi Dinesh Singh, FyMpharm Pharmaceutics Dept

- Mr. Aditya More, T.Y.B.Pharm

“The seminar was extremely bene cial for pharma students and has given students a great opportunity to learn. Sir did a great job of teaching all the necessary fundamentals of tableting.”

“Numerous properties affecting tablet compression tooling which we not even once thought would in uence tablet compression. This would help us in future from the point of view of academic and industry knowledge.” - Ms. Rutu Patel, T.Y.B.Pharm

- Ms. Anjali Kuril, FyMpharm Pharmaceutics Dept “The seminar was very insightful and informative. The speaker provided very up-to-date knowledge about the recent developments and tooling machines used in manufacturing.” - Ms. Yashita Jain, T.Y.B.Pharm “What an amazing and wide application and innovative equipment of tablet compression

“The lecture by Natoli on tooling was very informative. We had learnt about the basic mechanism of tableting. However, this lecture gave us more clarity about the machinery involved in tablet compression. The lecture made me realize that, along with the knowledge of excipients, the understanding of the machinery involved in the process is also very important to

“Mr. Yasar Shaikh gave us a great learning and informative lecture, touching upon tablet compression and various tablet toolings; how different steel affects tableting, tablet defects and robotic tablet manufacturing. He explained the various causes of tablet defects and their solutions, control, and how to minimize them. Also enlightened on B-type and D-type tool con gurations in TSM (American) & EU (European) formats, and novel toolings.” - Mr. Pankaj Sontakke, Ph.D Scholar Pharmaceutics “The session on tablet tooling by Mr Yasar Shaikh was very informative and very interestingly presented to the students with practical examples. Tablet tooling is not touched upon in depth in our curriculum, and hence it was very new knowledge for the students! This could be an opportunity to introduce a new elective subject for our students, in the coming years.” - Dr. Mala Menon, Adjunct Professor – Pharmaceutics With inputs from the report compiled by Ms. Pradnya Petkar and Ms. Rashmi Singh, F.Y. M.Pharm students, Bombay College of Pharmacy.

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Blue Ocean of Compliance

Blue Ocean of Compliance Holistic Approach towards Achieving Regulatory Compliance for Pharmaceutical Industries with No-Observation

Are you struggling to solve the problems of non-compliances on your site? Even with putting your best technologies, knowledge, and efforts do you feel clueless? If you want to protect your site from risks and huge losses due to non-compliances, if you want to know the thought process and path which would lead you to qualifying a regulatory inspection with noobservation in cost effective way, then do not miss "Blue Ocean of Compliance", the best seller book on Amazon by Dr. Rupali Paranjape.

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Dr. Rupali Paranjape Winner of Women Excellence Award in the Healthcare Industry

“Blue Ocean of Compliance” is a book employing a one-of-a-kind thought process for achieving compliance with no-observation. It takes you through a guide of regulatory inspections elaborated with the US regulatory market regard. This book will not only equip you with regulatory knowledge but will also empower you to solve complicated non-compliances, in the context of factors that we do not even think of. The ideas in this book are very simple to understand. They will imbibe in you the seeds of "acting to win" instead of only being good enough to survive. If you are a Founder, a CEO, an entrepreneur, or anyone in the pharmaceutical industry really: if you are a part of the pharmaceutical industry or even are just starting out, this book is a treasure for you.

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Blue Ocean of Compliance

Regulatory Actions; Impact of the Regulatory Actions; Criminal Fines Chapter Five - Part I: Wisdom is to for Food, Drug and Cosmetic Act learn from other's mistakes. (This Violations; FDA Forms 483; Areas Chapter contains 12 Case Studies of where 483s are given; Warning Warning Letters) Letter; Injunction; Warning Letter Chapter Five - Part II: Wisdom is to Close-Out Letter Program; learn from other's mistakes. (This Prosecution; Criminal prosecution; Chapter contains 492, 483s for 4 Seizure; Types of Seizures; Mass and years and comparative presentation Open-ended Seizures; Multiple of these 483s.) Seizures; Mass Seizure; Recall and eld correction; Recall policy; Chapter Six: Blue Ocean of Understanding Recall Classi cation; Compliance (New thought process) Recall Events; Recall Products; First Chapter One Alert; Alerting the Public; Effectiveness Checks; Recall This chapter covers: Classi cation; FDA-regulated; • History and story behind Products Subject to Recall; Field regulations and guidelines with a Alert; Import Alert; What are the few examples types of import alerts?; What is a red, green, and yellow list?; Drug • Why are Regulatory Audits Product Debarments; FDA happening? Debarment List; Notations; OIG • Types of Applications in the US Exclusions; and Types of Market Debarments: Mandatory Debarment; Permissive • Investigational New Drug Debarments. Application (IND) Chapter Four: Actions to be taken

Why you must read this • By reading and implementing this you will be able to avoid more than 492, 483s on your site. • You will be able to avoid many circumstances that lead to Warning letters. • You will become more familiar with the enforcement actions, reasons of non-compliances and ways to overcome them in costeffective ways. You will come to know many factors which might not be discussed before to solve the non-compliance issues on the site. • You will know one new thought process “Blue Ocean of Compliance” • At the end of each chapter, Practical Assignments: Exercise is given for implementation. The beautiful part of the book is that, it is written by an experienced doer that has spent years on shop oor, in a very simple manner, in easily understandable language with examples, case studies, 492 FDA 483 observations, and many Warning Letter Case studies and much more. Chapters

• New Drug Application (NDA) • Abbreviated New Drug Application (ANDA) • Biologics License Application (BLA) • Drug Applications for Over-theCounter (OTC) Drugs • Drug Master File (DMF)

Chapter One: Why Regulatory Inspections?

• Orange Book Chapter Two

Chapter Two: Types of Regulatory Enforcement Actions and Regulatory Actions on NonCompliances and Devastating effects for the Pharmaceutical Industry due to non-compliances

Types of Regulatory Enforcement Actions and Regulatory Actions on Non-Compliances and Devastating effects for the Pharmaceutical Industry due to non-compliances.

Chapter Three: Reasons for NonCompliances

This chapter covers: cGMP Violations category; Types of

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To book your copy, visit the link below: For India: https://www.amazon.in/BlueOcean-Compliance-RupaliParanjape/dp/9390617014/ For Abroad: https://www.amazon.com/Blue-OceanCompliance-Rupali-Paranjapeebook/dp/B09XMLFK7B Contact details of Author Dr. Rupali Paranjape: Mail: mail@drrupaliparanjape.com Website: www.drrupaliparanjape.com Catch her on: LinkedIn: https://www.linkedin.com/in/dr-rupaliparanjape/ YouTube Channel: https://www.youtube.com/channel/UC7B Z0Scd3LjccScLipUVUVQ


Jekson Vision

From Connecting Devices to Human Value INDUSTRY

ReeSmart is the tool developed based on Industry 4.0 principles and it helps in analyzing the process and identifying the problem areas affecting the utilization of the machines.

Manufacturing industry is using a traditional way of manual calculation of efficiencies over the years. There are lots of techniques developed to manage such calculations. Waste of time and overworked staff are common issues faced by any manufacturing company. Overall Equipment Effectiveness is a technique to measure the effectiveness of a machine, staff and it truly reduces complex production problems into simple and intuitive presentation of information. ReeSmart uses software and

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By Rajan Sundavadra

hardware together using Industry 4.0 principles to measure the Overall Equipment Effectiveness of a machine to automate the process of its calculation and to identify the losses associated with equipment effectiveness.

senses the data, captures it and communicates using secure internet connectivity with cloud for analytics.

ReeSmart cloud does big data analysis on large amount of data using modern AI techniques to ReeSmart is a tool based on derive value out of it, which drives Industry 4.0 principle which collects analysis to action and inform right the data from shop oor equipment group of users with right and synchronize those counters information. This would allow with could so that production line stakeholders to abort un-planned efficiencies can be calculated. It stoppages in no time and help connects with IoT based devices them take corrective action to avoid using embedded intelligence for simple and secure connectivity. It production downtime.

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Jekson Vision

offering From connecting devices to human value

How ReeSmart Works ReeSmart works in 5 simple principles, which are: 1. Data Intake: ReeSmart collects the data from the sensor/devices environment or PLC's. To ensure the data security, protocols such as HTTPS, OPC, UA, MQTT, etc. are used. 2. Data Transmission: The data is transmitted to the cloud via gateways using both the cellular as well as the satellite communication. 3. Data Processing: Once data gets into ReeSmart cloud, it will be processed to calculate efficiencies. 4. Data Visualization: Processed information is made useful to the end user by providing alerts, emails. 5. Data Analysis and Prediction: Use data analytics to make use of historical data for actionable insights. You can make intelligent business decisions based on insights and predictions from generated data.

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Jekson Vision

ReeSmart Architecture ReeSmart architecture is quite simple. Wherever Jekson Vision inspection systems are already installed, those can be connected with ReeSmart cloud directly without any modi cation on line level equipments. To ensure signal point of connectivity with cloud with security – a middle layer called as “Service Gateway” is used which runs behind site rewall and only communicates with cloud bidirectionally.

If lines do not have a Jekson Vision inspection system installed, those can be connected using Jekson Iot Box which collects data from existing sensors to share it with cloud. In case lines has modern PLC already installed, a wide variety of industry standard protocol such as OPC UA, MQTT, Modbus, ODBC are already supported for taking out data from lines with reasons and

synchronize it with ReeSmart Cloud. The data which ReeSmart collects and analyzes is very much useful to provide an insight to manufacturers about much better planning to schedule their upcoming production. It also gives a real time visibility about production status to plant level user to have a real time tracker about production status to keep an eye on timely delivery.

Salient Features OEE as a Service: Installed on Microsoft Azure cloud fully managed by Jekson. No Investment with full performance. Equipment Connectivity: Jekson equipment data is exibly captured without any modi cation and extra cost. Real-time Analysis with Responsive UI: Productivity and stoppages are recorded in real time. OEE Summary: In-depth details in real-time graphs and detailed analysis plant wise, line wise, shift wise and date wise. Line Display: Real-time production data on screen, including delays for operator to focus on job, live OEE Factors, total run time against remaining time, good quantity produced versus total quantity to be produced.

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Jekson Vision

Downtime classi cation: Stoppage summary, including master con guration for better classi cation. OEE Live: In-depth details of running job with OEE trend analysis, reject count summary, accept/reject trend, shift wise OEE, and device wise OEE. Getting Started within Weeks Jekson vision offers a three-phase approach to implement ReeSmart quickly and efficiently. This approach includes: Phase 1 as pre-assessment review of site infrastructure study, equipment study, connectivity study, pilot line identi cation and prepare impact assessment. Phase 2 is proof of concept which connects the pilot lines with ReeSmart cloud and master data setup. Phase 3 is validation of cloud and pilot line connectivity using protocols like installation quali cation and operation quali cation. User training is also given as part of Phase 3 as a go live activity. All Jekson Vision Inspection System can be connected without any modi cation with ReeSmart cloud. All this exercises can be completed within 3 weeks' time in total. Once 1st pilot line is connected, other lines will be connected in 3 days per each line.

Return of Investment ReeSmart offers signi cant cost saving up to 35 % by improving machine and labour efficiencies. How ReeSmart achieves it? Here it is: Increase throughput by identifying hidden stoppages automatically from shop oor equipment with reasons. Reduce downtime by real-time alerts to responsible persons. Equipment maintenance strategy by managing equipment wise preventive schedule maintenance con gurations. Data accuracy by capturing accurate and validated inputs. Real time work progress by visualization of graphs on screen.

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About the Author Rajan Sundavadra is Product Architect at Jekson Vision, leading the software development team for more than a decade and delivered highly-functional and integrated systems. Rajan has a Masters of Computer Applications degree together with close to 15 years of experience in developing diverse products for pharmaceutical industry.

Technology Updates

Incorporating smart technology into packaging According to experts, smart technology such as Near Field Communication (NFC), Bluetooth, and QR codes can redefine the packaging of pharmaceutical products by adjusting demand levels and inventory. Another area of packaging that may benefit from the use of new technology is protection by identifying damaged drugs.


The fact that users can monitor temperature by incorporating Bluetooth within the system will be especially important in the transportation of temperature-sensitive drugs. QR codes and NFC allow items within proximity to communicate with each other.

Polylactic (PLA) acid packaging Polylactic (PLA) acid packaging is one of the important solutions that can help the pharmaceutical industry minimize emissions and manufacture more sustainable goods. The packaging has been found to reduce emissions and produce even more sustainable products. Other characteristics that make it suitable are its ability to control the temperature of goods in transit and use 65% less energy during production. Polylactic acid belongs to the family of aliphatic polyesters commonly made from –hydroxyl acids, which include polyglycolic acid or polymandelic acid, and are considered biodegradable and compostable. PLA is a thermoplastic, highstrength, high-modulus polymer that can be made from annually renewable resources to yield articles for use in either the industrial packaging field or the bio-compatible/bio-absorbable medical device market.

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To combat counterfeit drugs, smart packaging can incorporate holograms and microtext. Holographic technology is constantly developing, making it very challenging for counterfeiters to replicate them on packaging. Smart packaging technology is being incorporated into caps, labels, folding cartons, and flexible packaging materials. These formats offer high potential for patient compliance, safety, and therapeutic success.

Use of AI in drug discovery and development Companies are exploring the use of technologies like artificial intelligence (AI) to address the various challenges in the pharma industry, such as automation and optimization of the manufacturing processes, as well as designing effective marketing and post-launch strategies. Patient identification is a crucial step in the drug discovery and development process, especially for conducting clinical trials. AI simplifies the identification of eligibility criteria and the inclusion of patients and also makes the identification process faster and cheaper. Unsupervised AI algorithms are used to identify patient cohorts for drug discovery, clinical trials, and real-world evidence (RWE) studies. The machine learning-based software scans through electronic health records (EHR) and unstructured doctors' notes to find the right patients based on phenotypes. Also explored are different machine learning approaches, such as few-shot learning, reinforcement learning, active learning, and representation learning, to aid the drug discovery process. The deep learning solution uses small and noisy datasets to predict and optimize potential drug candidates, further eliminating the need for large datasets.

June - July 2022

Technology Updates

Benefit-risk considerations for product quality assessments The FDA’s Center for Drug Evaluation and Research (CDER) has released for public comment 'Benefit-Risk Considerations for Product Quality Assessments: Guidance for Industry'. The purpose of this guidance is to describe the benefit-risk principles applied by the FDA when conducting product quality-related assessments of chemistry, manufacturing, and controls (CMCs) when information is submitted to the FDA for an assessment as part of

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original new drug applications (NDAs), original biologics license applications (BLAs), or supplements to NDAs or BLAs, in addition to other information available (enforcement actions, adverse reactions, recalls, etc.). This guidance discusses how the FDA considers and assesses risks, sources of uncertainty, and possible mitigation strategies for product quality-related issues and how unresolved product quality issues may be addressed. The FDA uses product quality assessments to determine whether an applicant’s product development studies, manufacturing process, and process control strategy will consistently result in finished

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product of acceptable quality. The FDA considers the overall benefit(s) and risk(s) identified for the product, including any residual risk related to unresolved product quality issues, regarding the regulatory approval of an NDA or BLA. The foundation for FDA’s regulatory evaluation of human drugs and biological products are benefit-risk assessments. The FDA considers regulatory approval of BLAs based on a demonstration that the biological product and the facility in which the biological product is manufactured, processed, packed, or held is designed to ensure the biological product is safe, pure, and potent.

Technology Updates

Single-use bioreactors Single-use bioreactors are gaining popularity as they reduce downtime and increase productivity. These bioreactors achieve this by eliminating complex steps like cleaning and validation between separate production stages. New types of bioreactor systems and continuous manufacturing processes address the increasing focus on biopharmaceuticals. In addition to eliminating downtime, continuous manufacturing has low energy needs, achieves high productivity, and minimizes the amount of waste.

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Single-use airlift bioreactor system uses bubbles instead of mechanical mixing to move cells and nutrients. The reactor comes with disposable bioreactor bags, an integrated heater, and offers precise regulation of biochemical parameters such as pH, dissolved oxygen, and temperature. The single-use system can be used for a variety of cell cultures and fermentation.

body responds to drugs. This knowledge, along with advanced manufacturing methods such as additive manufacturing, is making personalized medicine a reality. Drug exposure models determine the pharmacokinetic and pharmacodynamic properties of drugs for arriving at the right dosage for drugs based on age, sex, comorbidities, and other clinical parameters.

Precision medicine

Software solutions for simulating the effects of drugs in a patient's body make use of population pharmacokinetics, as well as scientific literature data, for realtime prediction of efficacy and drug interaction, on each individual.

Precision medicine comes from the idea of treating each patient as a unique individual. Advancements in omic and data analysis are providing new insights into how the human

June - July 2022