Combination Products Regulation – A Guide to Compliance

Abstract

The Food and Drug Administration (FDA or Agency) has issued a regulation on the current good manufacturing practices (CGMP’s) requirements applicable to combination products. The new rule is intended to promote the public health by clarifying which CGMP requirements apply when drugs, devices, and biological products are combined to create combination products. In addition, the rule sets forth a transparent and streamlined regulatory framework for firms to use when demonstrating compliance with CGMP requirements for “single entity”, “co-packaged”, “cross-labeled”, and “investigational crosslabeled” products. New regulations for combination products (new rule) were made effective in July 22, 2013 and are made available in the 21 Code of Federal Regulations (CFR) Part 4. The new rule does not contain new statutes or requirements for the Life Sciences Industry, but encompasses elements from the three existing regulations for drugs, devices and biologics. The purpose is to ensure that an industry manufacturing health products that combine two or more of the aforementioned elements complies with the requirements and has the controls in place to provide a product with the lowest risk to the patient. This is a change in paradigm from the previous ways of the agency where only one of the regulations for drugs, devices, or biologics applied to any given manufacturer, depending on the primary mode of action of their product. The project will focus on the development of a strategy to implement the new combination product regulation in relation to pharmaceutical (drugs) and medical device products that merge to conform a final product. Key Terms and Acronyms: Term Definition FDA Food and Drugs Administration CGMP’s Current Good Manufacturing Practices CFR Code of Federal Regulations QMS Quality Management System CAPA Corrective and Preventive Action HCT Human Cell and Tissue PMOA Primary Mode of Action NDA New Drug Application ANDA Abbreviated New Drug Application IND Investigational New Drug Application AER Adverse Event Reporting BLA Biologics License Application PMA Premarket Approval 510K Pre-Market Notification (equivalence) IDE Investigational Device Exemption MDR Medical Device Reporting CDER Center Drug Evaluation & Research CBER Center Biologics Evaluation & Research CDRH Center Devices & Radiological Health Combination Product A combination product is composed of any combination of a drug and a device; a biological product; or a drug, device, and a biological product. Single entity combination product A product comprised of two or more regulated components, i.e drug/device, that are physically, chemically, or otherwise combined and produced as a single entity Co-pacakged combination product Two or more separate products packaged together in a single package or as a unit and comprised of two or more components, i.e., drug/device Cross-labeled combination product A drug, device, or biological product packaged separately that according its investigation plan or proposed labeling is intended for use only with another approved specified drug, device or biological product