Having a clear clinical strategy early on can shave time off overall development projects.

Early Strategizing Tightens Development Timelines

With recent approvals of bispecific antibodies, these complex molecules are fast moving out of the research box and into clinical pipelines.

Bispecific Antibodies are Moving from Research to Clinical Development

Extensive work has greatly expanded the possibilities for fetal bovine serum sourcing.

Considerations for US Fetal Bovine Serum Sourcing

Thanks to technological advances, process chromatography challenges are surmountable, but increasingly complex therapies in the pipeline will demand more efficient processes in the future.

Advancing Process Chromatography in DSP

The complex nature of biologics creates challenges for GMPs in sterile manufacturing, and the EU’s Annex 1 is making an impact.

GMPs for Sterile Manufacturing of Biologics

Precompetitive consortiums seek solutions to industry-wide challenges.

Coming Together to Enable Cell and Gene Therapy Manufacturing

When considering whether to outsource work to a CRO, there are a number of factors to assess, including the type of work that may be outsourced, regulatory considerations, and needs for the study.

When Is It Appropriate to Outsource Bioanalysis Work to a CRO?

Validair Diamond Scientific (VDS) has invested in a new cleanroom at its Chester-le-Street headquarters. The in-house facility was designed to meet exacting requirements for research and fault-finding, as well as for use as a hands-on training resource.

VDS worked with Total Clean Air to design the cleanroom to be flexible in its performance and functionality, allowing for new experimentation, testing, and training processes. The cleanroom’s control system can be set to underperform, which will make the room fail and replicate real-life critical issues that may arise, allowing the field service teams to develop strategies and resolve these issues. The cleanroom will also be used to conduct research of fault-finding, rectification works, and test methodology comparisons.

"The room was installed in early June and is already helping us to improve procedures, refine techniques, and perform experiments and case studies that support our UKAS accreditation," said Steve Ward, managing director at Validair Diamond Scientific, in a press release.

Articles

Validair Diamond Scientific has installed a new cleanroom for in-house testing, research, and training. 

Validair Diamond Scientific Installs New Cleanroom

Charles River announced on August 9, 2022 that it has received approval from the European Medicines Agency (EMA) to commercially produce allogeneic cell therapy drug products for distribution in Europe. Its contract development and manufacturing (CDMO) facility located in Memphis, TN received Good Manufacturing Practice (GMP) certification, joining the company’s existing GMP license for Investigational Medicinal Product (IMP) production.

The Memphis facility can now manufacture and ship drug products intended for distribution in the European Union, making it the first CDMO in North America to be awarded the license to do so. The approval follows an inspection by the cell and gene therapy experts from the Italian inspectorate, Agenzia Italiana del Farmaco (AIFA), performed on EMA’s behalf.

“We are incredibly proud that our Memphis facility has received EMA approval to commercially manufacture an allogeneic cell therapy,” said Birgit Girshick, corporate executive vice president & chief operating officer, Charles River, in a company press release. “We are looking forward to continuing close partnerships with our clients, and supporting future commercial projects, bringing these potentially curative therapies to patients, sooner.”

Charles River has received approval to commercially produce allogeneic cell therapy products for distribution in Europe from EMA. 

Charles River Receives EMA Approval to Commercially Produce Allogeneic Cell Therapy Drug Products

Novartis announced on Aug. 11, 2022, that the United Kingdom’s Medicines & Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for Pluvicto (lutetium (177Lu) vipivotide tetraxetan) for the treatment prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in adult patients who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy or who are not medically suitable for taxanes.

An emerging therapy approach, radioligand therapy may offer an alternative treatment option for some cancer patients, by combining a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle). It is administered via the bloodstream and delivers targeted radiation to cancer cells in the body while aiming to limit damage to surrounding tissue.

“Far too many people are still dying each year from prostate cancer. Tragically, those diagnosed with metastatic prostate cancer will only have about a 1 in 2 chance of surviving 5 years,” said Steve Allen, acting chair of Tackle Prostate Cancer, in a company press release. “Today’s announcement of marketing authorization for lutetium treatment is another positive milestone for eligible patients and their families. There continues to be a real and pressing need for better treatments for people with advanced prostate cancer. This new approach is very welcome.”

The UK’s MHRA has granted marketing authorization for Novartis’ radioligand therapy, Pluvicto, for the treatment of advanced prostate cancer in Great Britain. 

UK Grants Marketing Authorization for Novartis’ Radioligand Therapy for Advanced Prostate Cancer 

Séverine Allard is Head of Global Regulatory Affairs at RegCMC Vaccines.

Thierry Gastineau is Global Head of Quality Advocacy, Culture, & Innovation at Sanofi.

Post-approval changes (PACs) are inevitable and necessary throughout the lifecycle of pharmaceutical products—to implement new knowledge, maintain a state of control, and drive continual improvement.

This One-Voice-Of-Quality (1VQ) for Post-Approval Changes (PAC) position paper is part of a series of industry case studies intended to demonstrate the standard application of the principles outlined in the publication “Effective Management of Post-Approval Changes in the Pharmaceutical Quality System (PQS)–Through Enhanced Science and Risk-Based Approaches: Industry One-Voice-of-Quality (1VQ) Solutions” (1)

Furthermore, this 1VQ for PAC position paper provides a practical application of the concepts described in International Council for Harmonisation (ICH) Q9 (2), 

Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management 

(4) to PACs that bring an additional restriction on the product compared to registered conditions.

The conclusion drawn from this case study is that those changes present a very low risk, and therefore, can be downgraded from a prior-approval to a notification after implementation and managed in the PQS with immediate implementation effect.

, Annex 1 describes potential opportunities to enhance science and risk-based regulatory approaches to PACs as follows: When a company can “demonstrate effective PQS and product and process understanding” this is an opportunity to 

optimize science and risk-based PAC processes to maximize benefits from innovation and continual improvement

 Current regulatory mechanisms and guidance for PACs do not consider the company’s latest product and process knowledge when determining the type of filing required to implement the change. Further, the application of ICH Q9, 

 or the effectiveness of the company’s PQS to manage PACs is not considered during the assessment of individual PACs, or during inspections. Demonstrating a detailed understanding, effective implementation, and compliance with ICH Q10, will allow companies to overcome barriers to continual improvement and innovation. Additionally, it will help mitigate drug shortages in the global pharmaceutical supply chain by allowing faster implementation of PACs and reduce the burden on both industry and regulators.

This specific example of PACs that bring an additional restriction on the product compared to registered conditions,has demonstrated the application of the principles outlined in ICH Q9, Q10, and Q12 irrespective of current national or regional reporting category and concluded that it could be managed as a notification after implementation.

This PAC example and the 1VQ for PAC Initiative is sponsored by the Chief Quality Officer’s from more than 20 pharmaceutical companies (5).

Description of current state for changes that bring an additional restriction on the product compared to registered conditions

Putting additional restriction(s) on the drug product or vaccine compared to registered conditions does not affect compliance to the license as it is produced and controlled under more stringent conditions than the ones registered in the approved Marketing Authorization Application (MAA, NDA [new drug application], BLA [biologics license application], or similar, depending on country/region of approval). As a company generates new product and process knowledge during commercial manufacturing and testing, it may decide to tighten or add certain operational parameters to reduce process variation and/or tighten manufacturing and testing controls. Such continual improvement activities should be encouraged.

Specific examples of PACs that add restriction(s) on the product compared to registered conditions are:

 of acceptance criteria on manufacturing process ranges or test methods performed on the product, materials, or excipients

 of a test method performed on the product, materials, or excipients as long as it is not necessitated by a change in a critical process parameter (CPP)

 of a validity criterion for an analytical method

 of a CPP in the master batch record of the product, without any change in the manufacturing process.

For any such change mentioned above, the company should provide rationale for the change and supporting documentation in their PQS. These changes do not have a negative impact on the critical quality attributes (CQAs) of the product, and consequently on quality and safety. However, in certain countries, these changes require prior-approval by the regulatory authority.

Table I lists countries requiring prior-approval for PACs to drug product. These additional examples of restriction(s) compared to the registered conditions according to regulations or experience, are based on Sanofi Vaccines experience.

Companies are confronted with the following dilemma: implement continual improvements with no negative impact to patients as soon as possible after gaining new knowledge vs. wait for approval by regulatory authorities requiring prior-approval even though the PAC provides more stringent conditions than those in the approved Marketing Authorization.

By definition, more stringent conditions fall within the registered parameters and thus, comply with the Marketing Authorization.

As part of the company’s change control process, a science and risk-based approach with appropriate justification and documentation must be documented in the PQS when evaluating the changes mentioned in this document.

This document applies to PACs that bring an additional restriction on the product compared to registered conditions for commercial drug substances and products (chemical and biological/biotechnological products including vaccines).The principles and quality risk management approach described in this document are intended to apply globally to all regulatory authorities.

This risk-based approach applies to PACs which fulfill the following conditions:

The change brings an additional restriction on the product compared to registered conditions.

The change does not have any impact on the CQAs of the product, and consequently on product quality and safety.

Industry 1VQ for PAC position for a change that brings an additional restriction on the product compared to registered conditions

echnical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

 provides regulatory flexibility for PACs to the product, or its manufacturing process, based on latest product and process knowledge, sound scientific and risk-based approaches (4).

A PACwhich brings an additional restriction on the product compared to registered conditions with the appropriate supporting data (e.g., validation of the analytical method for an additional test, process validation for an additional monitored CPP) can be managed within the PQS, leveraging the principles outlined in ICH Q9, Q10, and Q12. This type of change may only be managed under the PQS and/or be reported to the regulatory authorities within ICH, Pharmaceutical Inspection Co-operation Scheme (PIC/S) and World Health Organization (WHO) member countries through annual reports or notification after implementation.It should not require prior-approval from the regulatory authorities. This will facilitate use of new knowledge and continual improvement efforts to increase the level of control of products in a timely fashion, including the potential to reduce process variability by implementing additional restriction on the product compared to initial registered conditions.

Figure 1 describes the risk-based approach for assessment of a PAC which brings an additional restriction on the product compared to registered conditions. Such PACs do not increase risks beyond current levels. 

Figure 1: Risk-based Assessment of PACs and Determination of Regulatory Reporting Category

When a PAC that brings an additional restriction on the product compared to registered conditionsis proposed and entered into the change management system, the potential quality, safety, efficacy (QSE) and legal/regulatory impact of the change needs to be considered during the initial high-level impact assessment. This impact can be assessed by using the following risk questions: What might go wrong when changing from the current situation to the proposed one? Why or how could this happen? This initial impact assessment should consider existing product and process knowledge (including process performance and variability) and current control strategies, as follows:

 There is no potential QSE risk associated with a PAC that brings an additional restriction on the product compared to registered conditions given that the product is manufactured and controlled according to restricted specifications, and providing that data supporting the change are assessed and readily available.

 If there is a regulatory impact per local/regional regulation, a more detailed risk assessment needs to be performed to define the reporting category of the change. In this example, some countries require prior-approval of the PAC despite there being no potential QSE risk.

The initial impact assessment concluded that there is no potential QSE risk associated with this change of additional restrictions on the product compared to registered conditions. In the case, when the change was triggered by recurring events or negative trends arising during manufacture and testing, the assessment should ensure that the relevant PQS requirements have been appropriately followed for managing this change (e.g., appropriate corrective and preventive actions [CAPA], deviation management).

Therefore, no additional risk assessment is required for this low-risk PAC, and the change can be managed within the company’s PQS and implemented immediately without the need for a regulatory prior approval.

Steps 3 and 4: Change implementation, review, and closure. 

Change implementation, review, and closure should be performed according to the change management process. The outcomes of the impact and risk assessments (if needed) will be integrated into the change implementation plan. After implementation of the change, residual risks should be assessed and managed to acceptable levels prior to change closure; any unintended consequences or risks introduced as a result of the change should be evaluated, documented, and handled adequately through effectiveness verification mechanisms. In case several changes are introduced at the same time or related to each other, the company should assess cumulative effect of the changes.

Demonstrating effective management of a change that brings an additional restriction on the product compared to registered conditions within the PQS

The following risk control elements have been considered for ensuring effective management of such PACs within the PQS:

No impact on the CQAs of the product, and consequently on quality and safety

No change to in-place analytical methods or system suitability

Validation is adequately performed and documented.

This change should be included in the Annual Product Quality Review and reported to concerned regulatory authorities through the annual or periodic regulatory reporting mechanism as appropriate or through notification after implementation.

How to Evaluate and Demonstrate the Effectiveness of a Pharmaceutical Quality System in Relation to Risk-based Change Managemen

t (6) provides a practical checklist tool that can be used by the company to evaluate the effectiveness of its risk-based change management process.

This 1VQ for PAC position paper provides a standard and enhanced risk-based approach within the framework of an effective PQS that can be utilized by any company to gain regulatory flexibility, reduce the burden and global complexity, and enable faster implementation of a PAC that brings an additional restriction on the product compared to registered conditions, without increasing risk to the patient and/or product quality, safety, and efficacy.

The benefits of practical application of the principles of ICH Q9, Q10, and Q12 as described in this document are:

Continual improvement with timely (weeks or months vs. years) implementation of such PACs

Enhancing product availability and mitigating potential drug shortages

Focusing regulatory resources on PACs that may have a potential to impact product quality as it relates to safety and efficacy

Reducing the regulatory approval burden for medium and low-risk changes

Faster implementation of new knowledge and innovative technologies (e.g., new test).

Many PACs require regulatory agency approval by individual countries before implementation. Because of the global regulatory complexity, individual PACs usually take years for full worldwide approval even when they reduce patient risk, improve compliance, or enhance the manufacturing process or test methods.

Senior Quality leaders (chief quality officers and heads of quality) from more than 20 global pharmaceutical companies are speaking with “One-Voice-Of-Quality” (1VQ) to advocate for an effective management of specific PACs that currently are handled as a prior-approval change in some countries, but where a standard science and risk-based approach concludes that these should be downgraded to a notification or handled only in the PQS. This benefit would be a reduction of the implementation timeline from years to months with no increased risk to product quality or patient safety.

Thank you to the following Chief Quality Officers (CQOs) for their endorsement of this example and for their continued sponsorship of the 1VQ for PAC Initiative:

Kunihiko Kokubo (Astellas, CQO at time of completion of example), Jackie Elbonne (Amgen), Anthony Mire-Sluis (AstraZeneca), Oliver Brehm (Bayer), Melissa Seymour (Biogen), Lothar Halmer (Boehringer Ingelheim), Kerstin Koenig (Bristol-Myers Squibb), Laura O’Brien (CSL Behring), Valerie Brown (Gilead), Paul Daly (GSK), Anil Sawant (Merck Sharp & Dohme Corp.), Dirk Bissinger (Merck Healthcare KGaA), Maria Soler (Novartis, CQO at time of completion of example), Christine Møller-Jensen (Novo Nordisk), Andi Goddard (Roche), Philippe Germanaud (Sanofi), Scott Gunther (Catalent)

The authors wish to acknowledge Mic McGoldrick (Merck & Co, Inc), Leader of IFPMA VSRWG (Vaccines Scientific and Regulatory Working Group) and members of the 

 team who contributed to development of this manuscript.

E. Ramnarine et. al., "Effective Management of Post-Approval Changes in the Pharmaceutical Quality System (PQS) – Through Enhanced Science and Risk-Based Approaches. Industry One-Voice-of-Quality (1VQ) Solutions,”

PDA Journal of Pharmaceutical Science and Technology

Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

E. Ramnarine and A. Vinther, “Solving the Global Continual Improvement and Innovation Challenge: How an Effective Pharmaceutical Quality System Can Transform Post-Approval Change Management; One-Voice-of-Quality Concept Paper,” 

 How to Evaluate and Demonstrate the Effectiveness of a Pharmaceutical Quality System in Relation to Risk-based Change Management

, 2021. Available at: https://picscheme.org/docview/4294

The authors declare no conflict of interest related to the content of the article.

A case study discussing why post-approval changes present a very low risk, and therefore can be downgraded from a prior-approval to a notification after implementation and managed in the PQS with immediate implementation effect. 

Changes That Bring an Additional Restriction on the Product Compared to Registered Conditions

The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) announced on August 15, 2022 that it has approved a bivalent version of Moderna’s COVID-19 vaccine that targets both the original and Omicron strains of the virus. The decision follows an endorsement of the booster from the UK’s Commission on Human Medicines, the government’s independent scientific advisory board.

According to an agency press release, the decision was based on a clinical trial which demonstrated that the booster triggers a strong immune response against the original COVID-19 strain and BA.1, the first Omicron strain. It also demonstrated a good immune response against Omicron sub-variants BA.4 and BA.5. Side-effects and overall safety profile were found to be the same as those in the original vaccine.

“The first generation of COVID-19 vaccines being used in the UK continue to provide important protection against the disease and save lives,” said June Raine, chief executive, MHRA, in the release. “What this bivalent vaccine gives us is a sharpened tool in our armory to help protect us against this disease as the virus continues to evolve.”

“The virus, SARS-CoV-2, is continually evolving in order to evade the immunity provided by vaccines,” said Munir Pirmohamed, chair, Commission on Human Medicines, in the release. “This novel bivalent vaccine represents the next step in the development of vaccines to combat the virus, with its ability to lead to a broader immune response than the original vaccine.”

The United Kingdom has approved Moderna’s bivalent COVID-19 vaccine, which targets the original variant and Omicron.

UK Approves First Bivalent COVID-19 Booster Vaccine

CYTENA, a BICO group company and supplier of high-precision laboratory equipment for handling biological cells, recently unveiled the next generation of B.SIGHT, a fully automated single-cell dispenser. The B.SIGHT instrument is designed to streamline single-cell isolation in microbiology research, with emphasis placed on handling bacteria, yeast, and other microorganisms.

“The new B.SIGHT brings isolation of bacteria and yeast to the next level,” said Julian Riba, CEO, CYTENA, in an Aug. 8, 2022 company press release.. “This second generation single-cell dispenser is really the outcome of a great collaboration between our team and our customers.”

“The new instrument provides more automation, faster processing speeds, higher resolution, and precise dispensing,” said Hussein Hamzeh, the product manager in charge of B.SIGHT, in the release. “Researchers using the B.SIGHT not only will be able to accelerate microorganism isolation workflows but also significantly reduce plastic waste.”

CYTENA’s B.SIGHT cell dispenser is designed to streamline single-cell isolation in microbiology research.

CYTENA Unveils Fully Automated Single-Cell Dispenser for Microorganisms

New England Biolabs (NEB), a supplier of enzymes for molecular biology applications, announced the release of the Faustovirus Capping Enzyme (FCE), a messenger RNA (mRNA) capping solution, on Aug. 9, 2022. FCE is designed to improve capping efficiency and scalability for mRNA manufacturing workflows, including vaccine generation.

FCE is a single-subunit enzyme that contains the enzymatic activities to achieve a Cap-0 structure, which is necessary in eukaryotic mRNA maturation. According to a company press release, FCE is active over a broader temperature range (20 °C–55 °C) than traditional enzymatic capping approaches and demonstrates increased capping efficiency across a variety of mRNA 5´ structures.

"The biological versatility of mRNA continues to propel its rise as a therapeutic modality within infectious disease, oncology, and beyond," said Breton Hornblower, product portfolio manager, NEB, in the press release. "We are very excited to introduce FCE—an enzyme discovered at NEB—to our portfolio of products for mRNA synthesis. This new product offers a streamlined, scalable, and cost-effective solution for mRNA capping for both research and therapeutic applications."

"For large-scale mRNA production, I have always favored post-transcriptional enzymatic capping due to the significant advantages in terms of yield," said Andrew Geall, chief development officer, Replicate Bioscience, in the release. “This new enzyme with improved activity at lower temperatures promises great utility for the production of our large (9–16 kb) self-replicating RNA vector.”

According to the release, FCE is manufactured through environmentally friendly manufacturing practices, avoids the use of organic solvents and without producing significant volumes of hazardous waste. A good manufacturing practice-grade format of the enzyme will be available in early 2023.

The Faustovirus Capping Enzyme launched by New England Biolabs is designed to increase capping efficiency and scalability of mRNA manufacturing workflows.

New England Biolabs Releases Novel Enzymatic mRNA Capping Solution

Moderna announced on August 9, 2022 an amendment to its agreement with the European Commission (EC) to convert contractually agreed doses of Moderna’s COVID-19 vaccine to its Omicron-containing bivalent vaccines for supply in 2022, pending regulatory approval. The EC has also agreed to purchase an additional 15 million doses of the Omicron-containing vaccine booster candidates from Moderna.

Under the agreement, all remaining contractually agreed doses of Moderna’s SPIKEVAX will be converted to Omicron-containing bivalent vaccines, pending approval by the European Medicines Agency (EMA). Contractually scheduled doses in July and August of SPIKEVAX will be deferred to later in 2022.

"The European Commission and Moderna have been steadfast partners in the fight against the COVID-19 pandemic. This agreement highlights the EC's trust in our mRNA platform and next-generation bivalent COVID-19 vaccines," said Stéphane Bancel, CEO of Moderna, in a press release. "Participating member states will now have access to Omicron-containing vaccine booster candidates, and protection against COVID-19, heading into the winter season."

Moderna and the European Commission have amended their agreement to convert contractually agreed doses of Moderna’s COVID-19 vaccine to the company’s Omicron-containing bivalent vaccines for supply in 2022.

Moderna and European Commission Amend COVID-19 Vaccine Agreement

Roche announced on August 12, 2022 that FDA has approved a supplemental New Drug Application for Xofluza (baloxavir marboxil) for the treatment of acute uncomplicated influenza in otherwise healthy children aged five to less than 12 who have been symptomatic for no more than 48 hours. FDA also approved the treatment for prevention of influenza in children of this age group following contact with someone with influenza.

According to a company press release, baloxavir marboxil is the first single-dose oral influenza medicine approved in the US for children in this age group. Prior to this announcement, the medicine was also approved for use in people aged 12 and older who are otherwise healthy or at high risk of developing influenza-related complications.

“Despite the ongoing COVID-19 pandemic, influenza continues to be a threat to public health, and effective influenza antivirals remain critical to alleviating the burden on healthcare systems,” said Levi Garraway, chief medical officer and head of Global Product Development. Roche, in the press release. “[Baloxavir marboxil] has proven to be an important tool in fighting and preventing influenza in adults as well as adolescents, and we are pleased to now offer households and younger children our single-dose oral treatment.”

Roche announced that FDA has approved Roche’s Xofluza (baloxavir marboxil) to treat influenza in children aged five years and older.

FDA Approves Roche’s Influenza Treatment for Use in Young Children

FDA approved Daiichi Sankyo’s Enhertu (fam-trastuzumab-deruxtecan-nxki), an IV infusion for the treatment of patients with unresectable or metastatic HER2-low breast cancer. Fam-trastuzumab-deruxtecan-nxki is the first therapy that specifically targets the HER2-low breast cancer subtype, a newly defined subset of HER02 negative breast cancer that describes breast cancers that have some HER2 proteins on the cell surface, but not enough to be classified as HER2-positive.

FDA stated in an August 5, 2022 press release that the approval is based on the findings ofDESTINY-Breast04, a randomized, multicenter, open label clinical trial that enrolled 557 adult patients with unresectable or metastatic HER2-low breast cancer. 373 randomly received fam-trastuzumab-deruxtecan-nxki, while 184 received the physician’s choice of chemotherapy — eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel. The results demonstrated improvement in both progression-free survival and overall survival in patients with unresectable or metastatic HER-2 low breast cancer.

“Today’s approval highlights the FDA’s commitment to be at the forefront of scientific advances, making targeted cancer treatment options available for more patients,” said Richard Pazdur, director of FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in FDA’s Center for Drug Evaluation and Research, in the press release. “Having therapies that are specially tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments.”

Daiichi Sankyo’s Enhertu (fam-trastuzumab-deruxtecan-nxki) is the first targeted therapy for HER2-low breast cancer.

FDA Approves First Targeted Therapy for HER2-Low Breast Cancer

Merck, known as MSD outside of the United States and Canada, and Cervance, a Boston biotechnology startup, announced that they have entered a strategic research collaboration on August 9, 2022. The deal will see the companies work together to identify novel targets for Alzheimer’s disease via Cerevance’s Nuclear Enriched Transcript Sort sequencing (NETSseq) platform.

NETSseq isolates cell populations from human brain tissue with the aim of exposing biological pathways underlying neurodegenerative and psychiatric diseases that may be difficult to see in animal models or differentiated human stem cells. According to a company press release, Cerevance will receive a $25 million upfront payment from Merck for the rights to use the platform. Cerevance is also eligible to receive development and commercial milestone payments, totaling approximately $1.1 billion, as well as additional royalties on sales of approved products derived from the collaboration.

“The establishment of this collaboration with Merck, which comes on the heels of our positive Phase 2 data for CVN424 in patients with Parkinson’s disease, represents a significant milestone for Cerevance and reinforces the promise of our NETSseq technology platform,” said Mark Carlton, chief scientific officer, Cerevance, in the release. “We believe we are well-positioned to identify novel targets for neurodegenerative diseases and look forward to collaborating with Merck to potentially bring forward transformative therapeutics for patients with Alzheimer’s disease.”

“Progress in our understanding of the biology of neurodegenerative diseases continues to reveal compelling new mechanisms for potential therapeutic intervention,” said Jason M. Uslaner, vice-president and head of neuroscience discovery, Merck Research Laboratories, in the release. “We look forward to advancing the discovery program as well as taking advantage of the NETSseq platform to identify new targets with the team at Cerevance.”

Merck, known as MSD outside of the United States and Canada, will collaborate with Cerevance to identify novel targets for Alzheimer’s disease.

Merck Enters Alzheimer’s Collaboration with Cerevance

B.S Sathya Durga is Director at Acute Market Reports.

India, the home of more than 10,000 pharmaceutical manufacturing sites, is a major player in the global pharmaceutical market. The country manufactures the majority of the world's active ingredients for generic drugs, is the source of more than 90% of the medications used by Americans, and accounts for more than 60% of global vaccine production, according to data from US Pharmacopeia.

Consequently, India has an ambitious vision: to grow its pharma business to a value of $130 billion by 2030. According to a report from 

, the Indian pharmaceutical business was worth $42 billion in 2020 and is set to grow at a compound annual growth rate of 12% from 2020 to 2030. However, while the Indian pharmaceutical industry is the third largest in terms of volume, it ranks at just fourteenth in terms of value.

To enable rapid growth, India must advance its value proposition amidst intense cost pressures and competition. To stimulate the anticipated growth, it is evident that India needs to undergo a significant transition from generic drug producer to a producer of novel molecules and biosimilars through rigorous R&D initiatives.

Modern technologies are critical in facilitating advancement of India’s pharmaceutical manufacturing industry, as they can enable many crucial process improvements:

Virtual product design allows products to be produced, tested, or assessed virtually without physical prototypes, minimizing research time.

Robust tracking systems automatically alter production to reduce logistics failures.

Intelligent sensors and a connected value chain enable data interchange from design to production and supplier/customer integration.

Autonomous robots provide flexible and adaptive production lines for many models and small customized lots, improving performance.

Predictive maintenance links wirelessly to the cloud for big data and analytics, reducing downtime and improving maintenance.

The organizations that are most likely to have a competitive advantage in the Indian pharma manufacturing market are those who continuously adopt new technology, find ways to harness the technology, and promote business integration. Consequently, significant advancement is predicated on modernization of the complete pharmaceutical manufacturing process.

Technology First Approach – The Need of the Hour

Indian pharmaceutical companies are prioritizing technology to maintain and enhance their market position. All new pharma plants must meet standards set by FDA, World Health Organization, and Pharmaceutical Inspection Co-operation Scheme.

Similarly, an increasing number of Indian pharmaceutical companies are deploying cloud computing, as well as technologies like artificial intelligence/machine learning (AI/ML) and robotic process automation (RPA). This allows them to modernize supply chain processes, extract better insights from data, conduct modeling/simulations more quickly, accelerate the drug development process, and save significant time in drug commercialization.

As a result of the COVID-19 pandemic, Indian companies have adapted to the speed of global digital transformation adoption and increased supply chain efficiencies. Information Technology (IT) companies have been offering different subscription models to the pharma industry that best suit their payment structure. For instance, the “pay as you use '' model charges companies based on usage, making it ideal for expenses like utility bills.

Pharma 4.0 allows pharma businesses to leverage the internet of things (IoT), Cognitive Science, AI/ML, blockchain, and RPA in tandem, utilizing the digital cloud as a foundation. This helps pharma companies enhance distribution and supply chain management by accelerating production and reducing errors. Currently, a medium-sized IT company in India enables more than 150 to 200 pharmaceutical companies to modernize the pharma manufacturing process at some level.

Shifting Priorities to Create Smart Factories

The production capabilities of firms need to be increased in order to create more value-based pharma products. Existing operations in India need to be automated and digitized so that the companies can adhere to the appropriate standards and maintain precise control over the product's quality.

The front-end priority has always prevented Indian companies from focusing on shop-floor technologies, but upgrades to these technologies are increasingly becoming more global. The shop floor is undergoing transformation as a result of developments in the IoT, AI/ML algorithms, 3D printing, machine vision, advanced physical robotics, and parametric optimization.

Development of integrated production capabilities would provide Indian businesses, industries, and the country as a whole with a significant and long-lasting competitive advantage. Existing process technologies need to be scaled up for industrial application so that prices can be reduced. For instance, the University of Calicut discovered a promising method of producing penicillin from wasted fruit by using solid state fermentation rather than submerged fermentation technology. If that technologies like this could be enabled on a widespread scale, it could prove critical to widespread process improvements; the pharmaceutical industry in India must evaluate smart factory developments.

The Indian government has been actively partnering with pharma companies and has been allotting considerable funds for the construction of new pharma facilities, pharma research, healthcare schemes, and so on. These initiatives open new doors for the acceptance of technologies to enhance production efficiency like never before.

However, while technologies such as cloud AI are extensively deployed in the U.S. and Europe, in India modernization of pharma manufacturing is still in its infancy. Companies are finding use cases in many commercial operations and manual procedures to eliminate human interaction and improve accuracy.

As the labor costs in India are lower than in other countries, cost sensitivity must be considered a prime factor. Pharma companies are beginning to use AI and ML, but it's still in the proof-of-concept stage. India is only starting to utilize blockchain for transparent data sharing between contractors and suppliers. While skill and labor aren't a significant issue in India, unstable prices and policies impede sector expansion.

With the current pace and ambitions, active government involvement, and strategic collaborations, it is anticipated that in the coming decade India will grow to adopt advanced modernization technologies in the pharma manufacturing segment to be at par with the developed economies.

Guest contributor B.S. Sathya Durga discusses the importance of modernizing India's pharmaceutical manufacturing industry.