FDA/PQRI Workshop on the Regulatory Framework for DM and POC Manufacturing – Day 3

FDA/PQRI Workshop Organizing Committee – Diane Paskiet

The current regulatory framework includes requirements intended to ensure product quality, such as the testing of input components (e.g., raw materials) prior to manufacture and testing of the finished product. Challenges may arise if a DM or POC technology or host site do not contain a traditional quality control laboratory. This session will explore potential strategies for ensuring drugs and biologics manufactured using DM/POC technologies meet the established specifications and potential alternatives to traditional analytical testing approaches. 

J. Christopher Love, Ph.D., Professor, Massachusetts Institute of Technology (MIT); Chairman Sunflower Therapeutics

Therapeutics and vaccines that rely on proteins as the active drug substance are conventionally produced in large manufacturing facilities designed to segregate individual production steps and require many operators to implement processes. As a result, control strategies to assure quality of the protein emphasize elements of the building, the process controls, and final measurements of quality attributes. This talk with consider 1) how control strategies may differ for distributed and point-of-care manufacturing, 2) what technologies, biologies, processes and analytical approaches could enable alternative, fit-for-purpose control strategies, and 3) provide examples of support for these new paradigms that can enable high-quality protein production with new manufacturing capabilities.

Thomas D. Roper, Ph.D., Professor, Department of Chemical and Life Sciences Engineering, School of Engineering, Virginia Commonwealth University

The current regulatory framework for small molecule supply to patients assumes a traditional approach wherein a central manufacturing facility produces the material and ensures the quality meets the specification prior to distributing to patients. The realization of the potential for small, modular, and mobile production facilities as well as the need to protect against supply chain risk offers the opportunity for a much more distributed pharmaceutical supply chain than in the past. This presentation will focus on the options for modifying the current product control strategies and product testing regimes to a more distributed paradigm. Examples of how traditional release testing may be re-envisioned will be presented for discussion.

Registrants will breakout into several concurrent breakout sessions to facilitate small group discussions

CBER has encountered the rapid emergence of advanced manufacturing technologies in various investigational biological products, such as cell-based and tissue-based advance therapy products, intersecting with critical areas associated with DM and POC manufacturing. While CDER & CBER both regulate biological products, CBER biologics are generally more complex with undefined critical quality attributes and often have different manufacturing paradigms. This is particularly true for cellular and gene therapy products and tissue-engineered products. The aim of this session is to discuss the unique challenges and considerations that apply to these products.

Laura M. Ricles, Ph.D., Chief, Tissue Engineering Branch, Division of Cellular and Gene Therapies (DCGT), Office of Tissues and Advanced Therapies (OTAT), CBER/FDA

This presentation will discuss CBER’s experience with distributed manufacturing and point-of-care manufacturing of complex biologics, including cellular and gene therapy products and tissue-engineered products. The current regulatory framework for these CBER-regulated medical products will be presented and discussed in the context of distributed manufacturing and point-of-care manufacturing.

Laura Sands, MSc, Head of Regulatory Affairs, Bioscience and Personalized Medicine, Lonza

For autologous cell therapies, proximity to patients matters; however, the complexity of Cell and Gene Therapies as compared to traditional biologics and small molecules creates unique product quality considerations during implementation of distributed manufacturing models. This talk will review some of the challenges specific to autologous cell therapies and highlight industry needs for successful application of distributed manufacturing.

Richard McFarland, Ph.D. MD, Chief Regulatory Officer, Advanced Regenerative Manufacturing Institute (ARMI)

Cell and Gene Therapy (CGT) products constitute a diverse group of products in commercial use with many more in research and development. This group is heterogeneous and includes most of the products classified under regenerative medicine including both in vitro and in vivo gene therapies, cell therapies of all types, and tissue engineered medical products and engineered organs. In addition, unlike traditional biotech products where the cells and gene are ‘biofactories’ and the therapeutic products are either secreted or extracted from the cells, the cells and genetic material are the final products. This situation tends to make in process control during manufacturing even more challenging than traditional biotech as a result of the fact that given our current understanding of ex vivo biology it is often not possible to control their responses to seemingly trivial changes of their microenvironments. As a result, it is difficult to offer precise, well-defined proscriptive solutions to the design of quality systems for CGT manufacturing under conventional conditions, much less distributed and point of care manufacturing models (DM/POC). However, the general tenets of distributed PQS with respect to data integrity, security, and degree of centralized control that are being established for other drug and biologic products should also be applicable. There are many logistic and patient care benefits of DM/POC that should lead to increased use in CGT manufacturing as increased process analytical technology allow for more robust application of QbD principles to CGT manufacturing.

• • Laura M. Ricles, Ph.D.
  • Laura Sands, MSc
  • Richard McFarland, Ph.D., MD
  • Steven S. Oh, Ph.D., Deputy Director, DCGT/OTAT/CBER/FDA

Registrants will breakout into several concurrent breakout sessions to facilitate small group discussions