March 2023: From the Editor

The first event that we editors attend each year usually is the annual WCBP (Well-Characterized Biopharmaceutical Products) conference hosted by CASSS, formerly the California Separations Science Society. Held in Washington, DC, each January, the meeting is prefaced by a day-long offering of two CMC Strategy Forums. The combined event brings together scientists and regulators from around the world to explore current issues in biopharmaceutical development from a chemistry, manufacturing, and controls (CMC) perspective. Presentations often include updates and progress reports on regulatory harmonization toward making and marketing life-saving therapies for a global patient population.

The best practices highlighted at those events tend to preview what will arise in other meetings throughout the year, so we watch this program closely for high-priority topics. For example, the industry has been buoyed by the rapid success of mRNA vaccines as well as established methods and comfort levels working with monoclonal antibodies. Speakers are advancing their work with emerging modalities by drawing from experiences with the well-characterized paradigm. Key topics this year included the progress of novel formulations and delivery methods, adenoassociated virus (AAV) analytics, ongoing efforts to implement process analytical technologies (PATs) in commercial manufacturing, and the status of international regulatory documents.

Companies increasingly are experimenting with novel formulations and delivery devices. Some speakers presented work with coformulated or coadministered recombinant proteins and highly concentrated formulations. We also learned about progress toward designing prefilled syringes for highly viscous and concentrated formulations. Of special interest to me, having read so much over the past 30 years about obstacles to delivery of large-molecule drugs, were experiments with spray drying and spray freeze-drying technologies for dry-powder formulations of proteins (either for reconstitution at the point of care or for inhaled delivery).

The capabilities and applications of PATs are increasing — but they still are used mainly for development work and not as much for commercial-scale processes. The industry needs tools that can gather and present data almost instantaneously at the needed scales. Otherwise, on-line analysis doesn’t work fast enough to enable real-time adjustments to processes. And companies still need options for AAV analytics that reduce cost- and time-intensiveness for insight into a drug’s exposure to and its clearance rate from the body.

Regulatory updates were presented specific to ICH Q12 and a new quality guideline for analytical development (ICH Q14) along with a November 2020 revision of ICH Q2. The latter introduces regulatory tools and principles for managing postapproval CMC changes both predictably and efficiently. Increasing transparency between industry and regulatory authorities will go far to support innovation and continuous improvement. As described in Q12, the successful use of flexible approaches for management of CMC changes is predicated on proper implementation of established conditions, product life-cycle management, postapproval change management protocols (PACMPs), an effective pharmaceutical quality system (PQS), and other tools. ICH Q12 was created to simplify the complex process of making postapproval changes to provide a clear path for implementation of improved technologies and continual improvement over the life cycle of a drug. Participants discussed how the guidance is being interpreted and applied. Questions concerned the benefits and complications of implementation, the data that companies can use to justify their identification of established conditions, and the effects of implementation on risk management systems, development strategies, control strategies, and quality systems. Case studies included presentations from Health Canada and Genentech/Roche on implementing the pilot program’s key initiative on established conditions and PACMPs.

The new harmonized quality guideline draft for analytical development (ICH Q14) and a complementary revision of ICH Q2(R1) for validation of analytical procedures received much attention because product owners need guidance on enhanced approaches to analytical method development and validation. No details of postapproval changes to analytical procedures are required currently except to provide justification for changes to category classification. Revisions to ICH Q2(R1) will link to the Q14 principles and clarify existing guidelines for method validation and transfer while providing guidance for emerging analytical control techniques such as spectroscopy. The resulting combination should facilitate selection and application of enhanced development approaches that could reduce the risk incurred by postapproval changes to analytical procedures discussed in ICH Q12.

The COVID-19 pandemic demonstrated that international collaboration among companies and global health authorities is achievable and essential, enabling the best use of available resources and expertise. Regulators and industry collaborated to expedite streamlined product development and decision-making processes to enable treatment availability at an unprecedented pace, scale, and geographical reach. As reflected at the CASSS meetings, companies and regulatory agencies now have exciting opportunities to leverage experiences gained during the pandemic to streamline development, harmonize systems, and speed products to approval.