Read All About it: CDER’s Framework for Regulatory Advanced Manufacturing Evaluation (FRAME) Initiative and its Regulatory Framework for Distributed Manufacturing and Point-of-Care Manufacturing of Drugs

October 26, 2022By Holly N. Brevig, Senior Regulatory Device and Biologics Expert

During last year’s 2021 Pharmaceutical Quality Symposium, CDER described the development of a regulatory framework called FRAME –Framework for Regulatory Advanced Manufacturing Evaluation, to accommodate innovation expected in the next 5-10 years with a focus on 4 technologies: End to End Manufacturing, Distributed Manufacturing, Point-Of-Care, and Artificial Intelligence.  On October 17, 2022, FDA finally published a webpage officially describing FRAME.  In addition to describing FRAME’s technology focus, the webpage includes descriptions of its priorities to develop a regulatory framework for advanced manufacturing technologies:

  • Seek and Analyze Input: CDER plans to solicit stakeholder feedback by releasing discussion papers and holding a public workshop on regulatory areas of consideration for advanced manufacturing technologies.
  • Address Risks: Through FRAME, CDER is evaluating our existing risk-based regulatory framework as it applies to these technologies to enable timely adoption of advanced manufacturing technologies.
  • Clarify Expectations: As a result of FRAME, CDER may issue new or updated guidance to explain the current thinking on a regulatory issue.
  • Harmonize: The FRAME initiative is aligned with FDA’s efforts to work through the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) to develop international guidelines related to advanced manufacturing technologies, such as continuous manufacturing, the subject of a new ICH Q13 guideline.

For the Seek and Analyze Input priority, CDER is seeking input from stakeholders on its recently published a discussion paper on Distributed Manufacturing and Point-of-Care Manufacturing of Drugs.  For the purposes of the discussion paper, CDER and CBER define Distributed Manufacturing (DM) to be a decentralized manufacturing strategy consisting of a manufacturing platform of manufacturing units deployed to multiple locations; Point-of-Care (POC) manufacturing is defined as a subset of DM that uses manufacturing units distributed to host sites in proximity to patient care ( e.g., healthcare facilities).  The discussion paper describes regulatory areas of consideration for an applicant’s ability (human drugs and biologics) to comply with the current regulatory framework or FDA’s assessment of a marketing application when using distributed manufacturing (DM) and point-of-care manufacturing (POC).  FDA included questions for each technology (DM and POC) to facilitate public comment.  For example, are there additional aspects of the current regulatory framework that may affect DM or POC that should be considered by the FDA; are there new regulations or guidances that should be considered; what are the necessary steps for demonstrating quality or comparability of product quality, etc.  The commenting period for this discussion paper ends December 13, 2022 (FDA docket FDA-2022-N-2316).  Interested stakeholders may also provide input at the FDA/PQRI Workshop on the Regulatory Framework for Distributed and Point of Care Pharmaceutical Manufacturing:  An Opportunity for DM/POC Stakeholder Engagement on November 14-16, 2022.  According to the website, the Workshop aims to facilitate interaction among DM/POC stakeholders on critical areas for development and implementation of these technologies including terminology, technical challenges to adoption, operation of Pharmaceutical Quality Systems, good manufacturing practice expectations, and the unique challenges and considerations that apply to complex biologics.