FDA reiterates guidance plans on distributed and point-of-care manufacturing

The US Food and Drug Administration (FDA) this week reiterated its plan to issue draft guidance spelling out how it intends to regulate distributed manufacturing (DM) and point-of-care (POC) manufacturing of drugs and biologics. FDA expects that issuing such guidance may clear up regulatory ambiguities and spur the adoption of these technologies.

The plan was set out in a Center for Drug Evaluation (CDER) report summarizing stakeholder feedback on an October 2022 discussion paper on DM and POC manufacturing (RELATED: FDA releases discussion paper on distributed and point-of-care manufacturing, Regulatory Focus 14 October 2022).

The impending draft guidance was included in the agency’s semiannual agenda, published in July (RELATED: Labeling, DTC advertising and compounding rules make FDA’s semiannual regulatory agenda, Regulatory Focus, 27 July 2023).

The discussion paper was developed as part of the CDER’s Framework for Regulatory Advanced Manufacturing Evaluation (FRAME) initiative. Under the program, launched in 2021, CDER is examining its statutory authorities, regulations, and guidance to support a regulatory framework for advanced manufacturing technologies, including DM and POC technologies.

DM is defined in the discussion paper as “decentralized manufacturing strategy consisting of a manufacturing platform comprising manufacturing units deployed to multiple locations.” One use can include units located within manufacturing facilities operating within the host’s pharmaceutical quality system.

POC is defined as a “subset of DM that uses manufacturing units distributed to host sites in proximity to patient care (e.g., healthcare facilities) where drugs are intended to be administered to patients and manufacturing units are neither intended for personal, in-home use nor drug compounding.”

In the report, stakeholders identified areas where additional regulatory clarity regarding DM technologies for drugs and biological products was needed. Respondents also expressed the need to harmonize the regulation of DM technologies with other health authorities to facilitate their use.

FDA reiterated in its action plan that it would “develop guidance, as appropriate, to clarify areas of regulatory uncertainty. This would include a draft guidance on “Considerations for Complying with 21 CFR 211.110, Approaches to Meeting CGMP Requirements for Distributed Manufacturing, and Advanced Manufacturing Technologies Program Designated Technologies in Drug and Biological Products.”

The agency also committed to undertake a review of current regulatory requirements that could cover DM strategies and announced plans to coordinate efforts to promote the global adoption DM with its other regulatory partners.

PhRMA and ISPE want greater clarity   

Two major pharmaceutical industry groups, Pharmaceutical Research and Manufacturers of America (PhRMA) and the International Society for Pharmaceutical Engineering (ISPE) told FDA that additional guidance was needed to clear up ambiguities with how DM will be regulated.

In responding to the agency’s question on whether new regulations or guidance would be needed for DM, both groups recommended that FDA retool its earlier SuPAC (Scale Up and Post Approval Change) guidance to incorporate manufacturing changes for DM technologies, or those technologies that do not fit in the traditional manufacturing paradigm.

“PhRMA recommends that FDA update scale-up and post-approval change (SUPAC) guidances to accommodate scenarios where a site “change” (e.g., relocation or replication to add a new unit) presents less risk than a traditional site change based on the nature of the change and/or the manufacturer’s PQS. These changes should have fewer documentation requirements, or a lesser SUPAC “level” and accompanying recommended filing documentation, as set forth in the relevant SUPAC guidances, may be acceptable.”

The group added FDA “can implement this concept under the same regulations as mobile assets or create a separate guidance for the scale-out fleet concept. The guidance should include the expectation for control of the fleet for initial and future qualifications.”

ISPE wrote that “lack of clarity on regulatory acceptability will inhibit the utilization of the technology. In particular, the SUPAC guidance should be updated to accommodate scenarios where the risk of a site ‘change’ (e.g, relocation  or replication to add a new unit) is less than a traditional site change, and lesser documentation requirements, or less SUPAC ‘level’ where appropriate.”

PhRMA also encouraged FDA to harmonize these regulatory approaches with other health authorities. The group “believes that globally harmonized approaches towards innovative manufacturing regulation will help ensure these advances provide their intended benefits. To that end, we encourage the agency to work together with MHRA and EMA to harmonize definitions, approaches towards quality systems, and other elements raised in the Discussion Paper.”

Distributed Manufacturing of Drugs: Stakeholder Feedback and Action Plan

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