Issue link: https://www.e-digitaleditions.com/i/1411460
6 Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2021 P h a r mTe c h . c o m Regulatory Oversight Lambert (Pharmatech Associates): In the [United States], a combination product is assigned to an agency or lead center that will have primary ju- risdiction. The lead center is determined based on the primary mode of action of the combination product. If the sponsor is unclear on the primary mode of action, they can submit a request for des- ignation (RFD) to the office of combination prod- ucts at FDA to receive a binding determination. If the sponsor prefers informal feedback, a pre-RFD can be submitted to FDA. PharmTech: How is FDA's process similar to or dif- ferent from that of the European Medicines Agency (EMA) for drug-device combination products? Lambert (Pharmatech Associates): Submission of a combination product to the EMA is not as clearly defined as submission to the FDA. Fundamentally, if the product is device led, the product is subject to the Medical Device Regulation (MDR) and must bear a CE [Conformité Européenne] mark. The competent medicines authority reviews the medicinal substance and issues a scientific opinion before the notified body can issue the certificate of conformity. If the combination product is drug substance led, the product is regulated under the medicinal products framework. The medical device would be required to conform to the General Safety and Performance requirements of the European Union (EU) MDR. EMA issued a final guideline on quality documentation for medicinal products when used with a medical device in July 2021 (3). The device can be integral, co-packaged, or obtained separately. PharmTech: Are there any other major differences for other regulatory bodies? Lambert (Pharmatech Associates): Regulatory bodies outside the US and EU have significant differences in their requirements for marketing approval of combination products. Japan, China, Brazil, and others all have their own regional specific re- quirements, and it is best to contact those regula- tory bodies directly if marketing authorization is needed. Primarily, development data [are] gener- ally applicable. However, different regulatory bod- ies may have specific development data, or clinical requirements, beyond those asked for in the US and EU. It is best to understand and incorporate regional specific requirements into the product and clinical development early to minimize delays in submissions outside the US and EU. Best practices PharmTech: What are some of the key aspects that drug product or process developers should under- stand about combination products? Lambert (Pharmatech Associates): When developing a combination product, what is critical is to under- stand how the drug/biologic interacts with the de- vice, and to understand how those interactions can impact the performance and quality of the product. I have seen a number of significant setbacks and delays when the drug/biologic/device interactions are not clearly understood and accounted for in the product development/design. One area that re- quires forethought is how an organization will ac- commodate both a drug and a device development program from a quality perspective. US 21 [Code It is crucial to understand how the drug or biologic interacts with the device. —Adam Lambert, Pharmatech Associates