Struggling to make sense of the world’s varied guidance on postapproval changes for microbiologically controlled products? The Kilmer Regulatory Innovation Team has sought to address this and more in a special review article published in BI&T, the journal of health technology and sterilization, published by AAMI.
This review of widely used guidance on postapproval changes, as well as several key recommendations, is published as “Microbiologically Controlled Products: Regulatory Management of Postapproval Changes.”
“The objectives of this work are to summarize current global regulation and guidance and identify and promote areas for cooperation and innovation between regulators and manufacturers,” the authors reported. “It is intended to foster agility in regulatory management principles, thereby further enabling industry innovation.”
The review opens with a summary of some popular guidance on postapproval changes as they are used around the world. Of note, the authors describe how the U.S. Food and Drug Administration (FDA) may or may not require a changed device to undergo premarket review once more depending on both the extent of the change and the nature of the device’s existing approval or clearance.
The innovative devices that earn 510(k) premarket clearance, for instance, typically do not need to resubmit for 510(k) clearance once more when they undergo a change. However, the FDA guidance Deciding When to Submit a 510(k) for a Change to an Existing Device does describe how a 510(k) may be required “when a change or modification in the device significantly affects the safety or effectiveness of the device.”
Changes to how a product is cleaned or sterilized may only need to be noted in a product’s quality management system, but when changes affect a product’s biocompatibility “further regulatory approvals may be required,” the authors note.
In a similar example, the EU Medical Device Coordination Group describes how “a change in a sterilization method may be considered significant in some cases but not in others,” creating a need for detailed flow charts, which the group provides.
Through the many examples the authors provide, a pattern becomes clear. While a postapproval change may or may not call for regulatory review, changes associated with the microbiological quality of a product, such a change in its sterilization process, should be documented as part of a quality risk management (QRM) program.
“The objective of regulatory postapproval change requirements is to ensure that process changes do not adversely affect a product’s quality and safety. This is the same objective as manufacturer’s QRM programs,” the authors note. “The premise is that well-planned, per- formed, and scientifically documented risk analysis and controls can be used to demonstrate that risks associated with changes are adequately mitigated. Therefore, opportunities exist for reducing the regulatory impact and burden of postapproval change submissions and/or approvals internationally.”
This isn’t the first time the Kilmer Regulatory Innovation Team emphasized that words matter. In late 2021, this group of passionate experts began seeking harmony in microbiological quality definitions by providing a glossary of common terms, which was published as McDonnell et al, 2021, “Words Matter: A Commentary and Glossary of Definitions for Microbiological Quality,” an open-access document in BI&T.
The authors, hailing from the medical packaging industry, engineering, and medical device standardization, conclude their review by exploring how both manufacturers and regulators can work together to “reduce the overall burden of postapproval changes” by better defining what should be considered major, moderate or minor changes to microbiological quality.
Additionally, they describe how a systemic approach to acquiring, analyzing, storing and disseminating information related to products, manufacturing processes and components can help establish such an essential consensus.
“Manufacturers, regulators and standards development organizations can collaborate to develop more detailed examples of what changes would be considered critical or noncritical … in manufacturing situations for aseptic and terminal sterilization. Requirements for associated postapproval changes and submissions in these cases can be defined, where appropriate,” they suggested while highlighting a gamut of opportunities for improvement.
“Microbiologically Controlled Products: Regulatory Management of Postapproval Changes,” was featured in volume 57, Issue 1, of BI&T, the journal of health technology and sterilization, published by AAMI. The review was assembled by the Kilmer Regulatory Innovation Team and authored by Gerald McDonnell, a senior director of microbiological quality and sterility assurance at Johnson & Johnson; Hal Baseman, the chief operating officer and a principal at ValSource; and Lena Cordie-Bancroft, a sector lead for medical devices at BSI in London.
