The U.S. Food and Drug Administration (FDA) recently released a draft guidance document regarding transdermal and topical delivery systems, outlining the agency’s thoughts on process and product development. FDA considers transdermal and topical delivery systems combination products because they contain both device and drug components. Accordingly, manufacturers of these systems must comply with regulations regarding combination products, including current good manufacturing practice requirements for combination products, and should carefully review the standards laid out in the draft guidance.
Transdermal delivery systems are designed to deliver an active ingredient (drug substance) across the skin and into systemic circulation, while topical delivery systems are designed to deliver the active ingredient to local tissue. FDA notes that both types of delivery systems present similar manufacturing and quality control concerns and similar risks to patients. The draft guidance discusses FDA’s current thinking on product design and pharmaceutical development, manufacturing processes and control, and finished product control. It also addresses special considerations for areas where quality is closely tied to product performance and potential safety issues.
The draft guidance first summarizes product development considerations, including the need for a well-developed quality target product profile, a list of potential critical quality attributes and the need to apply the principles of quality by design and elements of pharmaceutical development discussed in the International Conference for Harmonisation guidelines. FDA encourages manufacturers to minimize product complexity where possible, noting that “[l]ess complex products are likely to have fewer potential failure modes than more complex products.”
Furthermore, the draft guidance provides clarity on what information must be submitted with a premarket review application. The requirements include specific information on pharmaceutical development as well as manufacturing processes and process controls. Additionally, applicants will be required to submit stability studies demonstrating product stability under challenging conditions such as temperature excursions, freeze/thaw and/or crystal seeding. Finally, the draft guidance addresses additional special topics such as product adhesion considerations and product storage/disposal labeling considerations.
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FDA is accepting comments on the draft guidance until Feb. 29, 2020. Manufacturers of these products should carefully review the draft guidance to ensure compliance with FDA’s expectations.