Using Risk-Based Quality Frameworks to Fast-Track Biopharma Development: A Q&A with Abzena’s Dr. Jeffrey C. Mocny and Cellares’ Anna McMahon

In this Q&A interview with BioPharm International®, Jeffrey C. Mocny, PhD, vice president of Regulatory Strategy at Abzena, and Anna McMahon, director of Regulatory Affairs at Cellares explore the implementation of risk-based strategies to navigate evolving global regulations and maintain high biopharmaceutical quality standards. Their discussion highlights how FDA guidance changes, adaptive clinical trial designs, and data integrity are transforming the drug development lifecycle. They note how, by embedding quality risk management into initial process designs and leveraging prior knowledge from contract development and manufacturing organizations (CDMOs), the industry can achieve greater manufacturing efficiency, faster innovation, and improved patient outcomes.

BioPharm: How are evolving global regulations shaping biopharma quality standards?

Dr. Mocny (Abzena): There is a shift toward risk-based thinking and leveraging prior knowledge as often as possible. As drug developers, we need to understand the products we manufacture and maintain control over the manufacturing process, materials, and analytical aspects to demonstrate the molecule meets requirements. As regulators adopt this risk-based thinking, leveraging the prior knowledge held by CDMOs offers opportunities to use existing tools in new ways to allow for faster innovation. This reduces development time and allows developers, sponsors, and CDMOs to focus on better patient outcomes and faster-to-market strategies.

What are the benefits of adaptive and Bayesian trial designs in drug development?

Dr. Mocny (Abzena): Safety and risk-based thinking are at the core of these trial models. Trial designs have evolved to improve efficiency and ethical standards by enabling real-time data and informed decision-making. This allows us to leverage prior knowledge and data from other sources to foster faster development and reach go/no-go decisions more quickly. Because clinical trial activities, monitoring, and safety drive the largest portion of drug development costs, economized thinking in these trials is key. Incorporating real-world evidence makes trials stronger and tells a more complete story regarding safety, efficacy, and mechanism of action. This allows products to move through trials quickly based on milestones and an understanding of how the product works.

How do recent vaccine and immunization guidance changes affect compliance?

Dr. Mocny (Abzena): Recent FDA guidance and changes in thinking will change the landscape. Placebo-controlled mandates are beneficial for understanding drug performance, and returning to these clinical trial basics is helpful. Reduced animal testing and the incorporation of real-world evidence offer better chances for novel strategies to reach the market and affect positive health outcomes. From a CDMO perspective, this introduces aspects of supply chain and strategic compliance, such as the BIOSECURE Act.¹ This has caused intensified oversight of local US-based manufacturing operations, which benefits the market by driving the development of high-quality, patient-centric medicines. It also offers CDMOs an opportunity to modernize approaches, be more competitive on the global market, and offer higher-quality materials at lower prices.

What strategies can biopharma companies use to implement risk-based quality frameworks?

McMahon (Cellares): Implementing a robust risk-based quality framework requires integrating risk management into design, not just operations. A common mistake is treating quality risk management as something that kicks in during manufacturing or post-approval; instead, it should be embedded into process design and development from the start. For example, automated cell therapy manufacturing platforms build risk considerations into the engineering requirements of the system to reduce operator intervention and standardize workflows. It is also essential to foster a risk-aware quality culture where personnel are trained on why procedures exist and are empowered to escalate emerging risks. Practically, this means building cross-functional quality review boards where manufacturing, regulatory, and clinical teams collaborate.

Dr. Mocny (Abzena): CDMOs have the luxury of leveraging prior knowledge gained from developing multiple products over many years. For instance, IgG1 [immunoglobulin G1] manufacturing platforms have been used since the 1980s and are well-understood, allowing for predictable and fast-moving strategies. Risk-based thinking involves carefully considering if a platform strategy is best for phase 1 clinical trials while understanding critical quality attributes and manufacturing design considerations. Implementing these frameworks relies on data integrity and control over the processes within the facility. While the expectation of data integrity and control is always present, the level of detail and understanding of the product evolves at each phase of development.

How are regulatory shifts influencing manufacturing and clinical development workflows?

Dr. Mocny (Abzena): ICH [International Council for Harmonisation] Q14 and Q2(R2) have changed the approach to analytical methods, moving away from rigid thinking toward a risk-based understanding of method design and function. Analytical development is now viewed as a continuum that evolves with the product, allowing developers to leverage prior knowledge to streamline validation. Additionally, FDA has moved away from the need for clinical trials for biosimilars, emphasizing robust analytical development programs to demonstrate biosimilarity. This [move] reduces financial barriers and allows products to move to market more quickly.

McMahon (Cellares): FDA-accelerated approval modernization and the FDORA [Food and Drug Omnibus Reform Act]² provisions strengthen the authority to require post-approval confirmatory trials. This leads companies to build commercial-scale manufacturing readiness in parallel with development, rather than sequentially. The agency has also announced more flexible development strategies for cell and gene therapies in areas like clinical development, commercial specifications, and process validation. In Europe, the EU HTA [European Union Health Technology Assessment]³ regulation requires evidence that goes beyond traditional endpoints like overall survival. This means phae 2 protocols must be designed with joint clinical assessment requirements in mind from the outset, requiring early collaboration between regulatory, medical affairs, and market access functions.

What challenges do companies face when aligning evidence generation with modern FDA guidances?

Dr. Mocny (Abzena): A primary challenge is data integrity, as evidence is presented based on collected data. There is a shift toward structured data submissions to regulators, moving away from the written word toward data and numbers. This change offers an opportunity to judge a product's analytical performance against the field and understand how manufacturing fits with clinical activities. Establishing a clear link between manufacturing unit operations and clinical performance demonstrates an understanding of the molecule and consistent manufacturing. As regulators modernize, the shift toward structured data elements and understanding interrelationships will become more prevalent. While AI tools are being developed to help manage this data, FDA still emphasizes the importance of having a human in the mix.

How can quality and compliance strategies improve biopharma development efficiency?

Dr. Mocny (Abzena): Quality is a scientist's best friend. Scientists must understand why they follow specific guidances and how those actions affect the product and the patients. A renewed focus on the purpose behind development activities leads to enhanced efficiency. When an organization understands that everything is done with purpose, it is easier to translate the ‘why’ and ‘how’ of meeting regulatory requirements. Compliance is one thing, but making material with a purpose and maintaining that cultural mindset within an organization is the essence of a successful quality strategy.

Reference

1. U.S. Congress. Senate. S.3469 - BIOSECURE Act of 2025. 119^th Congress (2025-2026). Accessed May 11, 2026. https://www.congress.gov/bill/119th-congress/senate-bill/3469
2. FDA. Food and Drug Omnibus Reform Act (FDORA) of 2022. Accessed May 11, 2026. https://www.fda.gov/regulatory-information/selected-amendments-fdc-act/food-and-drug-omnibus-reform-act-fdora-2022
3. European Commission. New EU rules on Health Technology Assessment open up a new era for patient access to innovation. Published Jan.9, 2025. Accessed May 11, 2026. https://ec.europa.eu/commission/presscorner/detail/en/ip_25_226