In our GMP News from 10 April 2013, we reported about FDA's new GMP regulations for Combination Products (combination of a medical device with another product, e.g. a drug). These regulations came into force on 22 July 2013 as 21 CFR 4. The scope of these GMP provisions is relatively "light" and has been drafted in a kind of Question & Answer form. Now, the FDA has released the draft of Guidance on GMP requirements for Combination Products.
The document - composed of 46 pages ist pretty extensive. It is divided into 6 chapters:
III General Considerations for CGMP Compliance
IV What do I need to know about the CGMP requirements specified in 21 CFR 4.4(b)?
V Application of CGMP requirements to specific types of combination products
VI Contact Us
The introduction briefly outlines the content of the document. The definition of Combination Product is given in the background (Chapter 2) which provides an overview of 21 CFR 4. In Chapter III the draft deepens definitions like the term "manufacturer" and gives general explanations about which GMP requirements apply to a product or a manufacturing facility. Comparable to 21 CFR 4, the explanations are also presented in a Question & Answer system. An individual subchapter addresses the topic Change Control to a combination product (not in the Question & Answer system in this case).
The content of Chapter IV concretely goes into the specifications of medical devices (from a drug manufacturer perspective). For example the responsibilities of the management (21 CFR 820.20) or the topic Design (21 CFR 820.30) are addressed - i.e. provisions which aren't regulated as medical devices in the drug environment. Conversely - from a medical device manufacturer perspective - provisions specific to drugs (e.g. on stability testing, 21 CFR 211.166 and reserve samples, 21 CFR 211.170) are explained in detail. In addition, the draft specifies Compliance requirements when the medical device is combined with a biological product (21 CFR 600-680) or tissue (21 CFR 1271).
Chapter V is of utmost interest: it describes detailed regulations e.g. also a risk analysis as part of the design process. However, these detailed regulations refer to only three product groups:
1. Prefilled syringes,
2. Drug-coated meshes and
3. drug-eluting stents.
The document ends with the contact data of the respective Offices (CDER, CBER, CDRH and Office of Combination Products) and a list of references to relevant FDA documents for medical devices, drugs, biological products, tissues and combination products.
Conclusion: although it is only a draft, Chapter 4 with its detailed regulations i.e. cGMP requirements reveals to be interesting. Yet, they only address explicitly prefilled syringes, drug-coated meshes and drug-eluting stents.
The draft guidance entitled "Current Good Manufacturing Practice Requirements for Combination Products" can be commented on within 60 days.