The US FDA has released the draft norms which explains the current good manufacturing practices (cGMP) for combination products. Prior to issuance of the final rule, although cGMP regulations were in place to establish requirements for drugs, devices, biological products, and human cells, tissues, and cellular and tissue-based products, there were no regulations to clarify and explain the application of these requirements for  combination products.

The final rule was intended to provide such clarification and specify how compliance with applicable cGMP requirements may be demonstrated.   As set forth in 21 CFR part 3, a combination product is a product composed of any combination of a drug, device, or biological product. These are referred to as ‘constituent parts’ of the combination product.

Under 21 CFR 3.2(e), a combination product includes two or more regulated components. They could be  physically, chemically, or otherwise combined or mixed and produced as a single entity such as a prefilled syringe or drug-eluting stent.

It could also be two or more separate products packaged together in a single package such as a surgical or first-aid kit.

The final rule clarifies that the cGMP requirements that apply to each of the constituent parts apply to the combination product.

For single-entity and co-packaged combination products, offers two ways to demonstrate compliance with cGMP requirements. Under the first option, manufacturers demonstrate compliance with all cGMP regulations applicable to each of the constituent parts included in the combination product.

Under the second option, manufacturers implement a streamlined approach, demonstrating compliance with either the drug cGMPs (21 CFR part 211) or the quality system (QS) regulation (21 CFR part 820) rather than demonstrating full compliance with both, when the combination product contains both a drug and a device, under certain conditions. These conditions include demonstrating compliance with specified provisions from the other of these two sets of cGMP requirements.

According to Prema Desai, consultant auditor for pharma plants, the norms  serve as  guidance  for Industry and FDA staff. Once implemented, this will be a good guidance for all the industries involved in manufacturing any of the combination products described in the guidance. This guidance explains the final rule on cGMP requirements for combination products for a product composed of any combination of a drug, device, or biological product.

“Though cGMP regulations are in place to establish requirements for drugs, devices, biological products, and human cells, tissues, and cellular and tissue-based products (HCT/Ps), there are no regulations to clarify and explain the application of these requirements to combination products. Now the guidance  provides such clarification and specifies how compliance with applicable cGMP requirements may be demonstrated by combination product manufacturers,” she added.