Stability considerations for drug-device combination products-21 CFR part 4 update

ABSTRACT

Combination products are therapeutic and diagnostic products that include two or more of the following: drug, biologic, and device. These products are needed for enhanced clinical outcomes and have more than one Mode of Action (MOA). Therefore, they require a more complex regulatory pathway and compliance with a minimum of two (2) sets of regulatory standards. In 2013, the 21 Code of Federal Regulations (CFR) Part 4 was published to clarify the applicable GMP regulations when drugs, devices, or biological products are included. The FDA (U.S. Food and Drug Administration) released additional guidance in 2017 to streamline the regulatory framework and provide transpar- ency about demonstrating GMP compliance when multiple regulatory standards overlap. This paper summarizes the Current Good Manufacturing Practice (CGMP) requirements for drug-device combination products (Biologic combi- nations are not discussed in this paper). Emphasis is placed on considerations for structuring a compliant drug-device stability program, including the use of bracketing and matrixing the test schedule to support the establishment of the product expiry date and how legacy products can be evaluated to meet current standards.

Keywords Stability, Combination device, Drug-device, Design controls, Quality by design, Bracketing, Matrixing, FDA, CGMP

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Chris Latoz

Stability Manager, Hollister Incorporated

Christopher (Chris) V. Latoz earned his Bachelor Degree in Chemistry and Mathematics from Illinois State University, and his Master’s Degree in Analytical Chemistry from Illinois Institute of Technology. Chris has over 28 years’ experience in the medical device industry (Class I and II devices) working in R&D, Materials Characterization, and Stability. Currently, he is Stability Manager at Hollister Incorporated in Libertyville, Illinois. While at Hollister, Chris has led several process and capacity improvement projects, including: the implementation of a LIMS (Laboratory Information Management System) for stability sample and data management; the construction of new walk-in stability storage chambers; and the implementation of a continuous temperature and humidity monitoring system for stability chambers.

Kim Huynh-Ba

Managing Director, Pharmalytik LLC;
Adjunct Professor, RA-QA, Temple University-School of Pharmacy
Adjunct Professor, Chemistry Department, Illinois Institute of Technology
Council of Experts, US Pharmacopeia

Kim Huynh-Ba is the Managing Director of Pharmalytik, LLC, a consulting and training Kim Huynh-Ba is the Managing Director of Pharmalytik, LLC, a consulting and training organization. She has over 30-years of experience in Validation, Audits, Data Integrity, Quality Systems, CMC, Analytical Lifecycle, and Stability Sciences. She is a Council of Experts of US Pharmacopeia (2015-2025), where she chairs the Small Molecules IV Expert Committee. She is also a member of the USP Drug-Device Combination Products Sub-Committee. Kim is a former President and Distinguished Board Member of the Eastern Analytical Symposium (EAS). She is chairing the American Association of Pharmaceutical Scientists (AAPS) career committee and was named Fellow since 2020. Kim has served on various editorial boards such as AAPS Open and Pharmaceutical Chemistry Journal. Her extensive experience and involvement in various aspects of the pharmaceutical industry highlights her commitment to advance quality standards and best practices in the field.
Kim is an Adjunct Professor at Temple University-School of Pharmacy and Illinois Institute of Technology (IIT), where she teaches GMPs, Quality Audit, ICH quality guidelines, and Pharmaceutical Analysis for their Regulatory Quality and Compliance Programs. She has authored close to fifty articles and is the editor of several book volumes, “Handbook of Stability Testing of Pharmaceutical products,” “Stability Testing to Support Global Markets,” and the textbook “Analytical Testing for the Pharmaceutical GMP laboratories.” Overall, Kim’s multifaceted roles reflect a strong dedication to education, quality, and compliance within the pharmaceutical industry.

Stability considerations for drug-device combination products-21 CFR part 4 update

ABSTRACT

Chris Latoz

Kim Huynh-Ba

Managing Director, Pharmalytik LLC; Adjunct Professor, RA-QA, Temple University-School of Pharmacy Adjunct Professor, Chemistry Department, Illinois Institute of Technology Council of Experts, US Pharmacopeia

Managing Director, Pharmalytik LLC;
Adjunct Professor, RA-QA, Temple University-School of Pharmacy
Adjunct Professor, Chemistry Department, Illinois Institute of Technology
Council of Experts, US Pharmacopeia