Pharmatech Associates articles: technical expertise for the regulated life science industry

The combination of regulatory flexibility, improved process efficiencies, and technological innovation will define the future of biologics manufacturing. Whether through N-1 continuous perfusion for faster production scaling or PAT-driven MCC for higher yields and purification efficiency, the industry is moving toward a more agile, cost-effective, and high-quality production landscape. The continued evolution of bioprocessing will improve drug availability and create a more sustainable and resilient global supply chain for critical biologic therapies.

A new article from Dr. Paschal Iwuh of Pharmatech Associates compares the methodology for equipment and process validation used for a conventional bulk drug substance biotech facility with a personalized medicine tissue engineering facility. Because this area of biotechnological innovation emphasizes cell manipulation, the equipment, systems, and material methods for a state-of-the-art tissue engineering facility are markedly different from a conventional biotechnology facility.

Dr. Iwuh explains how commissioning and qualification (C&Q) activities are conducted and details the validation costs attributable to each type of facility. To determine the costs and types of validation methodology needed for each facility, future operators or owners should understand the main differences.

In part two the article explores what it will take for domestic companies to be self-sustaining and the role of advanced technologies in reshoring and onshoring.

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Last year, the Brookings Institute convened a group of experts from academia, industry, government and nonprofits to explore technology options for improving the resilience of generic drug manufacturing. During the workshop, generic drug leaders voiced concerns that the cost efficiencies captured by continuous manufacturing still fall short when compared with current models for generic drug production, including sourcing from foreign producers.

… continuous manufacturing proponents, Chatterjee among them, insist that with technology costs coming down and regulatory uncertainty surrounding those technologies lessened, there is a role for continuous to play in generic drug manufacturing.

“There’s a wealth of generic drugs out there that could benefit from continuous, but it’s just that activation energy to get management to realize that the upside far outweighs the downside,” says Chatterjee. “The government is trying to incentivize folks to push in that direction to overcome their fears.”

Featuring Pharmatech Associates’ expertise, Brian Glass’ new article “Assessing pDNA Purity for Cell & Gene Therapies” has published in Cell & Gene magazine.

Because plasmid DNA suppliers have been taking different approaches to manufacturing and applying different specifications, Brian Glass of Pharmatech Associates takes a closer look at ways to assist manufacturers of gene therapy drug substances and drug products in building a control strategy for the plasmid DNA used as a starting material.

Brian Glass gives a framework for applying development principles of small molecules to large molecules and refers to USP’s proposed chapter <1040>. The goal of this general chapter is to describe considerations for the manufacture and release of plasmids for use as starting materials in the manufacture of cell and gene therapy drug products.

CPhI Online is publishing a series of “behind the scenes” interviews with the people at the heart of pharma, the individuals who work day-to-day in pharma companies to bring better healthcare to the population. This month’s column features Pharmatech Associates’ Bikash Chatterjee.

Louis Garguilo, chief editor, Outsourced Pharma "In preparation for the recent webinar Outsourced Pharma Live – Strategies For Today's Top Quality & Regulatory Outsourcing Challenges, Bikash Chatterjee, Chief Science Officer, Pharmatech Associates (a USP company), sent notes worthy of extrapolating and relating to readers."  

https://www.outsourcedpharma.com/doc/a-new-context-for-quality-and-regulatory-professionals-0001

On FDA’s QMM initiative: “Quality is a huge issue. It affects access and availability…QMM is a great initiative that looks at culture approaches, fostering a mindset of continual improvement that we hope will result in fewer backend issues that require corrective actions at a huge cost for all involved.”

For generics manufacturers: …”Investing in quality upfront from design to implementation and doing it in a way that takes business processes into account, quality must be at the center of every decision. From product yields, product control, and process control, better yields are a big part of the pharmaceutical endeavor. Yields and quality go hand in hand. Thus, investing in quality becomes a competitive advantage.”

On PCM: "Continuous manufacturing can be one of the ways to lower costs and be more efficient, and we’re seeing that already on the API side. While end-to-end continuous manufacturing is harder and more expensive, there are some processes that are conducive to pharmaceutical continuous manufacturing. The adoption of continuous flow reactors for APIs is being led in India, and generics will most likely follow, although slowly at first."

Lawrence De Belder: "Quality traps exist because with batch processing, you check the quality after you have finished a batch. Imagine that you have made several batches and, only after they are all done, you realise some of them don't meet the required specifications. That is a problem, because you have to toss out entire batches.

In continuous manufacturing (CM), it is a whole different ball game. You can identify or even predict issues with product quality while the process is ongoing. If there is a problem, you can fix it in real time, and you won't end up throwing away whole batches. With CM, it is not about checking quality after the fact; it is about designing quality into the process from the get-go.

In batch processes, there is also this assumption that raw materials and APIs stay the same throughout production. But what if there are tiny, unnoticed variations in your materials that can affect the final product's quality? Batch processes may miss these issues, but CM keeps an eye on everything, constantly measuring and adjusting."

Adequately dissolved CO2 is paramount for the health of cultured cells used for biologics, viral vector, and cell therapy products. Apurv Puri of Pharmatech Associates takes a closer look at quality implications and equipment selection, reviewing measurement principles for sensor technologies—whether for single use, small scale wave bioreactors, or inline sensors for larger custom bioreactors. (See BioProcess Online https://www.bioprocessonline.com/doc/how-to-achieve-consistent-quality-with-carbon-dioxide-sensing-in-bioreactor-applications-0001)

Pharmatech Associates' Janette Buechler debunks the most common myths associated with working in a multi-generational workplace.

In Cell & Gene Therapy Review, Claudia Lin writes: "Developing a control strategy for a new CGT product requires bringing together substantial scientific, technical, GMP quality system knowledge and experience. A firm’s regulatory strategy and interactions with the regulators must be part of this systematic approach. To solve the CMC bottleneck for CGT product realization and commercial viability, control strategy is a critical link to exciting new manufacturing solutions for CGT that assure safety and efficacy of the product at different stages of the clinical development, leading to higher confidence in regulatory approval."

Integrating new tech into manufacturing and QC testing
The huge promise of CGT to treat serious, and often life-threatening diseases has so far not achieved widespread commercial success due to challenges in reliable GMP manufacturing and high costs of QC testing. Industry’s efforts to improve manufacturing processes by including new technologies and automation will determine the viability of CGT as next generation medicine. Adopting technological innovations, however, brings challenges in demonstrating and achieving product quality. Quality risk assessment, along with QbD tools, will help establish the control strategy for new processes. Reliable quality systems with QC strategies and method suitability will ensure quality and regulatory compliance are achieved. Integration of new manufacturing technologies under such quality management measures can ensure product success, manufacturing efficiency improvement, and cost reduction.
• Claudia Lin, Ph.D., Executive VP, Pharmatech Associates – a USP company

In a new article in Pharmaceutical Online, Richard Steiner of Pharmatech Associates discusses pharmaceutical continuous manufacturing (PCM) solutions and best practices to ensure content uniformity, applying QbD principles to achieve real time release testing -- an opportunity for drug sponsors to reduce costs. 

Pharmaceutical Manufacturing magazine features a two-part series by Karen P. Langhauser, chief content officer, that assesses pharma’s reshoring progress, including efforts to establish a reshoring list, the importance of ongoing government support and the role of advanced technologies. The author interviewed and cites a number of pharma experts: Bikash Chatterjee, president and chief science officer at Pharmatech Associates, a USP company; Marta Wosińska, senior fellow at the Brookings Institution Center on Health Policy; Kevin Webb, chief operating officer at the API Innovation Center (APIIC); Eric Edwards, co-founder and CEO at Phlow Corp.;  Salvatore Mascia, founder and CEO of CONTINUUS Pharmaceuticals; Sarah Lieber, Sanofi’s North America head of global regulatory affairs.

As Mark Twain once said, “During the gold rush it’s a good time to be in the pick and shovel business.” And for the handful of pharma stakeholders willing to get on board with the reshoring effort, the government — through the Department of Health and Human Services’ (HHS) Administration for Strategic Preparedness and Response (ASPR) — has offered lucrative incentives. ASPR’s Biomedical Advanced Research and Development Authority (BARDA) has awarded contracts totaling more than $2.1 billion to expand domestic production of pharma ingredients and related supplies for pandemic response and build future capacity. ASPR’s newly created Office of Industrial Base Management and Supply Chain (IBMSC) has invested over $17 billion across 87 contracts to expand the U.S. industrial base for key materials and products.

“There’s certainly a lot of activity in this space right now and a tremendous amount of money that’s being thrown at it. And you’re seeing bits and pieces of it take hold,” says Bikash Chatterjee, president and chief science officer at Pharmatech Associates, a USP company.

In this interview, Stephanie Gaulding, CQA, CPGP,  Managing Director, Pharmatech Associates a – USP Company, tells us about her day, the path she took to her current role including her inspirations, and how things have changed since she wanted to be a vet as a child. She gives points of advice for people seeking to enter the field.

Pharmatech Associates Stephanie Gaulding, John Aikens, and Bikash Chatterjee weigh in with industry leaders on best practices for outsourcing -- and how risk-sharing partnerships with CDMOs are essential to smooth, efficient operations over the pharmaceutical supply chain.

American Pharmaceutical Review, Pharmaceutical Outsourcing, and Tablets & Capsules magazines spoke with Bikash Chatterjee, Michael Kopcha of the FDA, and other industry experts to discuss how the pharmaceutical industry is working toward building a better tablet to ensure the viability of oral solid dosage forms well into the future.

Stephanie Gaulding’s article discusses the emerging trend toward competency-based learning and how it is adapted to the modern learner.  Competency-based learning builds on formal training and hands-on experience with an increased emphasis on social learning that improves business all around.

Regulatory actions in recent years have brought the focus to quality and compliance, said Sireesha Yadlapalli, CEO of the life sciences consultancy Pharmatech, at the ongoing CpHI Europe conference. During the panel session “What’s next for the generic drug market?” Yadlapalli and other experts outlined the key trends expected in the generic drugs market, including the growing scrutiny on quality and the balance between outsourcing and reshoring efforts.

Big tech and big pharma partnerships involving AI are becoming a dominant feature of the landscape and could mean a huge boost in revenue in this area, with a wider impact on the global economy.

Bikash Chatterjee, President and Chief Science Officer of Pharmatech Associates, a USP company, stated: “A recent study estimated that global GDP could be up 14% higher in 2030 as a result of AI – the equivalent of an additional $15.7 trillion – making it the biggest commercial opportunity in today’s economy.”

The benefits on a more patient-centric level for the incorporation of AI are also clear, with potential uses in cell and gene therapies and clinical trial selection and analyses, adding to its appeal for pharma companies looking to improve their offerings in the future. 

Pharmatech Associates' Moria Feighery-Ross writes about the many ways to reduce costs in designing, building, and qualifying a CGT facility. She says that the most important thing to consider is this: You can adopt any number of interesting solutions as long as you have a thorough, documented risk assessment and rationale for the risks you are accepting.

Richard Steiner of Pharmatech Associates makes the case for pharmaceutical continuous manufacturing (PCM) supporting specific business needs and the way to implement it. He writes that it remains a deeply entrepreneurial decision whether to implement PCM, as each level in the organization and each step in the value-adding process is involved.