Microbiologically Controlled Products: Regulatory Management of Postapproval Changes

The collaborative concepts discussed in this article focus on the global regulatory requirements associated with postapproval changes related to the quality of microbiologically controlled products and their labeled claims.The objectives of this work are to (1) summarize current global regulation and guidance and (2) identify and promote areas for cooperation and innovation between regulators and manufacturers.It is intended to foster agility in regulatory management principles, thereby further enabling industry innovation.This will ultimately result in the efficient and consistent provision of quality products to the healthcare market.The first section provides a review of some of the most widely used guidance documents on postapproval changes and highlights instances in which guidance is given on proposed changes related specifically to microbiological quality.It should be noted that this section is not an exhaustive review, as topic-specific guidance often is provided on a case-by-case basis directly from regulatory agencies in specific countries or geographical areas.In the second section, recommendations are proposed to enhance regulatory management of microbiologically controlled products, with a particular emphasis on the management of postapproval changes.This article has been assembled by the Kilmer Regulatory Innovation Team. 1 The team includes representatives with diverse experience, including microbiology, sterility assurance, sterilization, manufacturing, quality assurance, validation, regulatory affairs, environmental controls, engineering, medical devices, pharmaceuticals, biologics, preserved products, and advanced therapy medicinal products. Summary of Existing and Developing GuidanceMedical Devices European Union.The European Union (EU) Medical Device Coordination Group provides guidance on significant changes regarding the transitional provision under Article 120 of the EU Medical Devices Regulation. 2 The scope includes devices covered by existing certificates according to the EU Medical Devices Directive or Active Implantable Medical Devices Directive.It presents opinions on defining significant changes in design or intended purpose of a medical device that may require regulatory approval.Detailed flow charts are provided on subjects such as device material changes (flow chart D) and changes of sterilization method or packaging (flow chart E).For example, a change in a sterilization method may be considered significant in some cases but not in others.It is important to remember that any changes in the sterilization parameters are always required to be documented in a quality management system (QMS) but do not necessarily require regulatory approval.The Notified Body Operations Group (NBOG) Best Practice Guide 2014-3 3 presents similar guidance on reporting of design changes.In general, any change to the sterilization method or process of a medical device or a change to the packaging for the sterilization of a medical device may be considered a substantial change.It is recommended that manufacturers contact and discuss with their notified body about any questions related to whether the change may be considered substantial, in order to reach a common understanding.In the case of a substantial change, the manufacturer should inform its notified body.