FDA CFR Part 4 compliance

for combination products

The rapid development of combination products—biologics, pharmaceuticals and their devices—provides great opportunity for technological advancement, opening new doors for patient health and improved compliance with administration requirements. The complexity of these systems often requires the device to be developed alongside the drug that it will contain. Whether wearables, injectables or transdermal delivery systems, concerns of maintaining a firm grip on quality and stability throughout the design, manufacturing and product lifecycle process means understanding the GMP requirements of each component. Both are critical to product and compliance success.

Definition of combination product

As set forth in part 3 (21 CFR part 3), a combination product is a product composed of two or more different types of medical products (i.e., a combination of a drug, device, and/or biological product with one another).5 The drugs, devices, and biological products included in combination products are referred to as “constituent parts” of the combination product.

Which products are affected?

Combination drug/device products as defined by FDA’s 21 CFR part 3 must comply with 21 CFR part 4 subpart A, current Good Manufacturing Practice (GMP) requirements for combination products (see January 2017 Final Guidance, Current Good Manufacturing Practice Requirements for Combination Products). Whether approved by CDRH, CDER or CBER, (generally only one approval is required based on the product’s most “significant” attribute or mode of action), device design controls (21 CFR part 820.30) and other main CFR part 820 requirements must confirm there are no negative interactions between constituent parts and assure the combination product is safe and effective, performing as expected.

Additionally, pharmaceutical quality must also address product design and development procedures, so it is critical that both sets of requirements are coordinated in the design and development stage. A reminder that cGMPs are minimum standards by which products shall be manufactured

It is imperative that management are actively engaged in oversight of the quality system and demonstrate an active, ongoing commitment to the quality system’s development and implementation. 

Particularly in the case of combination products, understanding how to comply with both sets of cGMPs and which should take precedence can be confusing at best and warrant and injunction order at worst.

As your product development team begins the process of creating or reviewing policies and procedures that ensures operation under the correct GMP systems, invite both the drug and device side of the business to the table so that each set of regulatory requirements is met or exceeded, and done so with integrity.

How can we help?

GemarMed’s, experts have specific expertise to define the provisions from the device QS regulation in accordance with 21 CFR 4.4(b)(1) (drug cGMP-based streamlined approach) OR Device QS regulation may use the following provisions from the drug cGMPs in accordance with 21 CFR 4.4(b)(2) (device QS regulation-based streamlined approach). Particular expertise is provided by our experts in the definition of Design History File  for the combination products, along with FDA Regulatory requirements.

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