FDA drafts guidance on post-approval manufacturing for biologics

The US Food and Drug Administration (FDA) has released a draft guidance in response to an increase in the number of post-approval manufacturing supplements it has received in recent years.

The recommendations are specifically for holders of biologics license applications (BLAs) on the types of minor changes to be documented in an annual report. The changes FDA is recommending are focused on five areas, components and composition; manufacturing sites, manufacturing process, batch size and equipment; specifications and container closure systems.

Many of the changes included, and those yet to be documented in an annual report are either slight modifications or those that would have no impact on the current risks of the manufacturing. The FDA offers the following examples:

Components and composition

The first suggestion was in regards to the elimination or reduction of the overage from the drug product manufacturing batch formula that was previously used to compensate for manufacturing losses, however this does not apply to loss of potency during storage.

Manufacturing sites

The FDA have recommended a change on a manufacturing location can be considered minimal if the manufacturing area is already listed in an approved BLA, the steps are part of a non-sterile production process, and the new location will have no impact on product quality or will lower the risk of contamination or cross-contamination. 

Manufacturing process, batch size and equipment

Small changes in the size of pooled or separated batches have been recommended to perform the next step in the manufacturing process if all batches meet the approved in-process control limits and the critical process parameter ranges for the next step remain unaffected.

Specifications

Addition of tests and acceptance criteria to specification for approved excipients has been suggested, as well as change in the regulatory analytical procedure if the acceptance criteria remain unchanged and the revised method maintains basic test and provides equivalent or increased assurance that the drug substance or drug product will have the characteristics of identity, strength, quality, purity, or potency that it claims to have or is represented to possess.

Container closure system

Changes in the container closure system for the storage of a non-sterile drug substance can be considered minimal when the proposed container closure system has no increased risk of leachable substances, and the new container “offers equivalent or greater protection properties from air and moisture,” noted the FDA.