FDA finalizes Guidance for Human Blood and Blood Components Intended for Transfusion or for Further Manufacture

Recommendation

7/8 May 2024

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Regulatory Requirements and Practical Implementation

In December 2014, the Food and Drug Administration, Center for Biologics Evaluation and Research published the guidance on "Changes to an Approved Application: Biological Products: Human Blood and Blood Components Intended for Transfusion or for Further Manufacture". This guidance finalizes the draft of June 2013 and supersedes the 2001 guidance, "Changes to an Approved Application: Biological Products: Human Blood and Blood Components Intended for Transfusion or for Further Manufacture."

As mentioned in our News from July 2013, this document addresses manufacturers of licensed whole blood and blood components intended for transfusion or for further manufacture, including Source Plasma. It is supposed to provide recommendations for assisting them in determining which reporting mechanism is appropriate for submission of changes to an approved biologics license application (BLA) in accordance with the requirements under Title 21 Code of Federal Regulations (CFR) 601.12. (21 CFR 601.12). It further includes recommendations in connection with the applicability and content of comparability protocols under 21 CFR 601.12(e) and labeling changes under 21 CFR 601.12(f).

Under 21 CFR 601.12, you must report each change in the product, production process, quality controls, equipment, facilities, responsible personnel or labeling established in the approved license application to FDA. As defined in 21 CFR 601.12, the change must be categorized in one of the following reporting categories:

• Major Change. A change that has a substantial potential to have an adverse effect on the safety or effectiveness of the product. Major changes require the submission of a Prior Approval Supplement (PAS) to FDA, which FDA must approve before you distribute the product made using the change (21 CFR 601.12(b)).
• Moderate Change. A change that has a moderate potential to have an adverse effect on the safety or effectiveness of the product. Moderate changes require the submission of a Changes Being Effected in 30 Days Supplement (CBE30) to FDA at least 30 days before you distribute the product made using the change (21 CFR 601.12(c)). In certain circumstances, FDA may determine that the product made using the change may be distributed immediately upon receipt of the Changes Being Effected Supplement (CBE) by FDA (21 CFR 601.12(c)(5)).
• Minor Change. A change that has a minimal potential to have an adverse effect on the safety or effectiveness of the product. Minor changes must be described by the applicant in an AR (21 CFR 601.12(d)).

For more details with regard to which submission and reporting category a change to an approved application has to be assigned to, please see the Guidance for Industry "Changes to an Approved Application: Biological Products: Human Blood and Blood Components Intended for Transfusion or for Further Manufacture".