Cooperative manufacture of biologics; FDA guide

The US Food and Drug Administration (FDA) feels this guidance is necessary as the complex technology used in the manufacture of biologics has led to the emergence of highly specialised companies.

Cooperative manufacturing arrangements are increasingly attractive to these companies as they seek to combine niche capabilities. However, the establishment of these licensing arrangements can be a time consuming process so the FDA has issued guidance to help manufacturers.

These cooperative arrangements are subdivided by the FDA into short supply, divided manufacturing, shared manufacturing and contract manufacturing.

Short supply arrangements​

When a source material is in short supply a biologics manufacturer may obtain it from an unlicensed facility if the product license holder meets certain FDA conditions.

This places the responsibility on the license holder to ensure that the product manufactured at the unlicensed facility will be made in full compliance with applicable regulations.

Short supply arrangements are applicable to a limited number of materials that only undergo “specified limited processing​”.

Divided manufacturing arrangements​

The FDA allows for two or more companies, each of which is licensed to manufacture a particular product, to collaborate on its production. It is recommended that the steps performed at each facility are detailed in the application.

Approval of the application will depend on numerous factors including the equivalence of the intermediate products and the ability to demonstrate this will remain stable during shipping.

Further considerations include recordkeeping and labeling, with the FDA requiring that: “The name, address, and license number of each participating licensed manufacturer must appear on the package label​.”

Shared manufacturing arrangements​

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The guidance defines shared manufacturing as: “an arrangement in which two or more manufacturers are licensed and responsible for specific aspects of the manufacture of a product but none is licensed for all aspects of the manufacture of the product​.”

An example of this is if one manufacturer is responsible for an intermediate and another for the final product. The FDA’s guidance details what manufacturing processes require separate licensure and which, “even though important to the purity and integrity of the final product​”, do not.

Further extensive guidance is given on dealing with biologic license applications (BLAs), labelling and the responsibilities of each manufacturer.

Contract manufacturing arrangements​

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A fundamental difference between shared and contract arrangements is that in the latter case facilities do not require additional licenses.

This places certain different responsibilities on the license holder and the contract manufacturer, which are outlined in the FDA’s guidance document.

The complete guidance can be found here​.