News in Depth

The role of ICH M4Q and M16 in creating a more efficient, effective and globally aligned CMC regulatory process that can help release the potential of digitization and advanced data management technologies including artificial intelligence (AI) drew active dialogue from key thought leaders at the concluding session of the 2026 CASSS Well Characterized Biotechnology Product (WCBP) Symposium, which took place in Washington, DC in late January.

The biomanufacturing wing of the European Federation of Pharmaceutical Industries and Associations (EFPIA) Manufacturing & Quality Expert Group (MQEG) is heavily focused on how to gain more leverage from platform technologies, prior knowledge and risk-based tools in streamlining and harmonizing the regulatory expectations for assessing comparability, specification conformance, and lifecycle management for the expanding universe of biotech products.

The issues involved in adapting regulatory processes to make them more innovation supportive across the development and manufacturing spectrum for advanced biotech therapies and vaccines were in focus at the EFPIA satellite session that preceded the October 2025 CASSS Europe CMC Strategy Forum, held in Basel, Switzerland. At the session, representatives from the biomanufacturing team provided status updates, shared data, and outlined emerging concepts and proposals from the team’s ongoing activities.

At the September 2025 PDA Regulatory Conference held in Washington, DC, two prominent experts on FDA inspections examined why data integrity (DI) failures continue to surface across the product life cycle and what it will take to build more resilient governance systems that prevent them. The second-day plenary session on ‘Data Integrity at the Next Level’ provided the opportunity for Live Oak Quality Assurance President and former FDA investigator Peter Baker and CDER Office of Compliance (OC) Division of Drug Quality I Director Carmelo Rosa to share their complementary perspectives. The presentations were followed by an extended Q&A, moderated by industry consultant Sue Schniepp.

Complementing the perspectives offered by regulators from Canada, Japan and Chile at the CASSS Summer CMC Strategy Forum on bioconjugates and multispecifics were presentations by former FDA reviewers Marjorie Shapiro and Katherine Duncan, who drew on their extensive regulatory experience and learnings in discussing the CMC challenges that these products present and the pathway forward in addressing them.

The excipient and formulation challenges associated with lipid nanoparticle (LNP) delivery systems are emerging as a pivotal issue in advancing the mRNA field beyond vaccines for infectious diseases into broader therapeutic applications including protein replacement therapy and gene editing. The functional performance of LNP lipids is deeply interdependent with the nanoparticle’s composition and structure – differentiating them from traditional excipients and making them more like “functional excipients” in their impact on product performance.

The DIA/FDA conference on oligonucleotide therapeutics, held in Washington DC in October 2024, provided an opportunity for industry and agency experts to exchange insights on how the knowledge gained in addressing the CMC challenges of mRNA COVID-19 vaccines can be leveraged in the therapeutics arena.

At a session of the conference focused on “CMC considerations in the development of mRNA-based therapeutics,” participants highlighted the common structural characteristics and processes between mRNA vaccines and therapeutics, which offer the potential to extrapolate CMC learnings involving purity/impurity profiles and other CQAs, lipid nanoparticle (LNP) stability, phase appropriate specifications, and shelf-life.

Among the focus areas of the European Federation of Pharmaceutical Industries and Associations (EFPIA) Manufacturing and Quality Expert Group (MQEG) for 2025 is engaging with regulators on the issues around using the mass spec (MS)-based multi-attribute method (MAM) as a QC tool.

MQEG leaders had the opportunity to explore the group’s priorities for the coming year at the traditional EFPIA satellite session accompanying the CASSS CMC Strategy Forum Europe, held in mid-October 2024 in Rotterdam, The Netherlands.

A “Quality Business Leadership Summit” (QBL), held in Dublin, Ireland in May 2024, brought industry, regulator and academic experts together to explore how to speed up pharma’s progress from a compliance to a quality investment value modus operandi that better drives innovation, financial performance, and supply chain resilience. At the summit, hosted by the Pharmaceutical Regulatory Science Team (PRST) at the Technological University (TU) Dublin, prominent leaders in the quality regulatory dialogue from the US and Europe took stock of where the pharmaceutical industry is on this journey, where the constraints and hurdles now lie, and what needs to be done to make this “fundamental shift” a reality.

The industry/FDA dialogue at an August meeting in Washington, DC, sponsored by the Duke-Margolis Institute for Health Policy resulted in some substantive ideas on how the communication pathways could be broadened to facilitate a more efficient CMC review process and improve outcomes for biological license applications (BLAs) submitted to the Center for Drug Evaluation and Research (CDER). Explored were the communication pathways between sponsors and FDA and the increased communication challenges that result from CMO participation in the manufacturing process.

Increasing experience in developing and reviewing synthetic peptide and oligonucleotide therapeutics is providing the foundation for more concrete guidance and standards for these rapidly expanding product classes.

Peptides and oligos present unique regulatory challenges that may not be covered under the guidance and support umbrella in place for either conventional small molecule or biological products. They are complex molecules that are prone to impurities and are difficult to synthesize and characterize. The rapid innovations in the field, including novel modifications, new formulations, and the emergence of platform technologies, are also a challenge to keep pace with.

Leading regulatory agencies and pharmacopeias like FDA and USP are working hard to meet these challenges and help expedite bringing peptide and oligo products to the market.