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Looking at the FDA’s 1998 Draft CMC Guidance for MDI and DPI Drug Products with a 2016 Combination Products Mindset

Berger RL.

Respiratory Drug Delivery 2016. Volume 1, 2016: 237-240.

Abstract:

The Center for Drug Evaluation and Research (CDER) issued ‘DRAFT’ CMC (Chemistry, Manufacturing and Controls) Guidance on Metered Dose Inhalers (MDI) and Dry Powder Inhalers (DPI) Drug Products nearly two decades ago in 1998. Since its issuance, many MDI and DPI drug products have received market authorization by CDER using this Draft Guidance as the basis to assess CMC quality. Guidance documents are supposed to represent the Agency’s current thinking on a particular subject but this Draft Guidance has remained unchanged for nearly two decades, although a revised version is scheduled to be issued in 2016 to reflect the FDA’s current thinking with respect to these inhaled dosage forms. The introduction and application of the combination product regulations has caused ambiguity within the industry and within the Agency with respect to how exactly to appropriately implement the rules to the development, manufacture, and control of combination products. It has also created the need for companies to retrospectively apply these rules to legacy MDI and DPI drug products whose review, pre-approval inspections, and market authorizations were granted by the FDA as drug products, and not as combination products (despite the fact that combination products were defined and a process for inter-center review was established). The complete application of drug and medical device quality systems is complex and it is relevant to consider the specifications and studies outlined in the Draft Guidance within this new context of medical device design controls (21 CFR 820.30). Using the example of a device-metered DPI, the FDA proposed drug product characterization studies, container closure system, and drug product specifications outlined in the 1998 Draft CMC Guidance will be reconsidered within the context of the medical device design controls for the device constituent part of the DPI. Specifications and characterization studies will be recast in terms of: 1) an approach to how they might apply to the device and drug constituent parts of the DPI; 2) how these might be addressed as design inputs, design outputs, design verification, or as design verification during development; and 3) a streamlined approach to control combination products post-commercialization, as both a drug product under 21 CFR 210 and 211 and in some cases as a device under 21 CFR 820.