Vaccines, Blood & Biologics

Lot Release


What is lot release?

What happens before the biological product is licensed?

What happens after the biological product is licensed?

Is there other information that applicants should know about the lot release process?


Lot Release

What is lot release?
Lot release is a mechanism that provides FDA with a real-time system to continuously monitor product quality, through review and testing, of many of the biological products that it regulates.

Biological products licensed under the Public Health Service Act are subject to the lot release requirements of Subpart A of 21 C.F.R. Part 610 (General Biological Products Standards):

  • 21 C.F.R. §610.1 provides that “[n]o lot of any licensed product shall be released by the manufacturer prior to the completion of tests for conformity with standards applicable to such product . . . “
  • 21 C.F.R. §610.2(a) and (b) provide that “[s]amples of any lot of any licensed product together with the protocols showing results of applicable tests, may at any time be required to be sent to the Director [of the Center for Biologics Evaluation and Research or the Center for Drug Evaluation and Research, as appropriate] . . . Upon notification by the Director . . . a manufacturer shall not distribute a lot of a . . . product until the lot is released by the Director . . .

What happens before the biological product is licensed?
As part of the approval of many biologics license applications (BLAs), the responsible Center (the Center for Biologics Evaluation and Research (CBER) or the Center for Drug Evaluation and Research (CDER)) works with the applicant to develop a lot release protocol that will be used for each lot of product post-licensure. The Center also develops a test plan for independent confirmatory testing by the Agency.

What happens after the biological product is licensed?
Once the Agency has licensed such a biological product, for each product lot, the applicant must submit materials relating to that lot to the Agency before the lot can be released.

  • What lot release materials must the applicant submit to the Agency?
    • Protocols: The applicant must submit the protocols that contain the agreed-upon tests.
    • Results: The applicant must submit the results of the testing performed by the applicant.
    • Samples: The applicant generally must submit samples of the product from the lot in question in order to permit the Agency to perform confirmatory testing.
  • How should the applicant submit the lot release materials to the
    Agency?
    • Electronically: The Agency encourages applicants to submit lot release protocols and results to the Agency electronically through the Gateway, which facilitates the lot release process.(Currently, over 55% of lot release protocols are submitted electronically.)Interested applicants should first contact the Sample Custodian at the address below.
    • Samples: should be submitted by courier to the Agency’s Sample Custodian. An applicant seeking to submit protocols and results by mail or courier should direct these to the Agency’s Sample Custodian, as well. Note that applicants should send protocols, results, and samples for CDER-regulated products, as well as for CBER-regulated ones, to the Sample Custodian at the following address:

      Sample Custodian
      Center for Biologics Evaluation and Research
      Food and Drug Administration
      10903 New Hampshire Avenue
      WO75-G707
      Silver Spring, MD 20993-0002

  • What happens after the applicant has submitted the lot release materials to the Agency?
    Once the Agency has reviewed the lot release protocol, completed any testing of samples, and has found the results acceptable, the Agency will notify the applicant that that lot has been released.
  • How long will it take for a product lot to be released by the Agency?
    Please note that there is no required timeframe for lot release. However, the Agency strives to release lots within 30 business days once a complete and accurate submission has been received. This is the length of time that the Agency generally expects to need in order to review the data and multiple test results contained in a protocol and conduct confirmatory testing. If it becomes necessary for the Agency to resolve an issue with a protocol, or request the submission of a corrected protocol, the lot release process may take longer.
    • In situations of true product shortages, an expedited release may be requested. A request should be made to CBER’s Product Shortage Coordinator at cbershortage@fda.hhs.gov.

Is there other information that applicants should know about the lot release process?
Yes. Please note that lots that are submitted in support of an application or a prior approval supplement (PAS) cannot be released until the application or supplement is approved.

Contact FDA

(800) 835-4709
(240) 402-8010
Consumer Affairs Branch (CBER)

Division of Communication and Consumer Affairs

Office of Communication, Outreach and Development

Food and Drug Administration

10903 New Hampshire Avenue

Building 71 Room 3103

Silver Spring, MD 20993-0002

Page Last Updated: 02/07/2017
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