Does Your Existing Combination Product Need Design History Files?

Combination products are defined by the U.S. Food and Drug Administration as products that are some combination of drugs, biological products and/or devices. For instance, a medical device packaged with the drug it administers would be a combination product.

As you design, engineer and manufacture your combination product, one of the most important parts of the FDA’s regulatory process is the design history file (DHF). All medical devices, including combination products, must be submitted for approval with DHFs. These files formally document the creation of the product, from the initial design phases to the manufacturing process.

What DHFs Do You Need for Combination Products?

The FDA generally treats combination products as though they were simply made up of their constituent components. The constituents must be regulated, however, and so to document a combination product you must also document all of the product’s constituents.

Generally, this documentation will consist of the DHFs of each component product used in the combination, as well as an explanation of the design, engineering and manufacturing process that results in the final combination product. However, there are occasional exceptions to this requirement, as in the case of retrospective products.

Retrospective Products

A retrospective product is one that draws on old designs or products in the creation of a new combination product. For example, if you’re combining a thirty-year-old medical device and a thirty-year-old drug into one new combination product, this would be a retrospective product.

Because the retrospective product is a new combination, it must be specially registered by the FDA. But if you are designing a retrospective product, you may not be sure if you need to include documentation for the older portions of the product. Be aware that because the FDA regulates the component parts of all products, even retrospective components must be accounted for in a combination product’s DHFs.

However, you may be able to meet the requirement without supplying a DHF for the retrospective product’s older components. The requirements for DHFs came into effect in 1990. If one of your combination product’s constituents is older than that, then you may not have DHFs on file for the product. Therefore, you may be able to circumvent the DHF requirement if you can prove that the device has a history of being safe and meeting the FDA’s requirements.

This kind of grandfathering is typically decided on a case-by-case basis. Be ready to supply all documentation to prove the product’s safety and efficacy, and be sure that you’re providing DHFs for any newer components to the combination product. If you cannot prove this to the FDA’s satisfaction, you may need to reconstruct DHFs for the product.


Preparing your design history files is one of the most important parts of the regulatory process. Leaving this up to an untrained or inexperienced individual can cause headaches down the road, and in severe cases may cause your combination products manufacturing facility to run into trouble with the FDA.

Remember that regulatory requirements can change quickly, and are much more complicated than can be outlined here. Always consult the most up-to-date documents from the FDA and if possible, work with a combination products specialty consulting partner to help you through the process of creating and modifying DHFs.