Whitepaper: CMC Regulatory Considerations for Successful Submission Planning

Combination Products: Understanding and Appreciation of CMC Regulatory Considerations for Successful Submission Planning Whitepaper

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Combination products have emerged as powerful technologies for delivering novel molecules and modernizing traditional therapies to make them more effective and safer. A combination product is comprised of one or more regulated different classes of medical products (ie, drug, device, or a biologic) that are intended for use together as a therapeutic or a diagnostic human medicine. The medical device and medicinal product constituents are regulated per se by regulatory authorities, like the US Food & Drug Agency (FDA) and the EU European Medicines Agency (EMA), within developed regulatory frameworks. Even so, regulatory challenges arise in product development strategies for manufacturers and review management policies for regulatory authorities when the individual elements are combined to form more complex and diverse drug device systems.

One of the main challenges lies within the demarcation between medical devices and medicines. It is for the manufacturer to initially determine the classification regarding with regards to the primary function of a combination product. FDA and EMA guidance documents include definitions, and examples as well as laying out regulatory provisions for the manufacturer.

Secondly, depending on the regulatory pathway, various regulatory requirements need to be fulfilled for each component of the drug device combination with respect to preclinical testing, clinical investigation, manufacturing and quality control, adverse event reporting, promotion, advertising, and post approval changes.

Lastly, regional differences in regulatory requirements of combination products add another layer of complexity for product developers planning to launch combination products in multiple regions. These regional differences are yet unharmonized despite a few existing initiatives. As a whole, manufacturers in combination product space need good understanding and appreciation of regional regulatory considerations for successful submissions.

This white paper aims to provide baseline knowledge on comparative regulatory requirements by FDA and EMA with a primary focus on Chemistry, Manufacturing and Controls (CMC) and quality aspects of developing combination products. Starting off with basic definitions and examples of common drug device combinations, we navigate through regulatory pathways by providing key steps and tips on how to prepare content in electronic submissions. Strategic topics addressed in this paper aim to provide practical help to sponsors interested in the submission of combination product filings in the US and the EU.

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