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  1. Compliance Actions (Biologics)

The Center for Biologics Evaluation and Research (CBER) may issue several types of regulatory action letters. These letters are ordinarily issued to biological product manufacturers in the effort to stop practices found to be in violation of the regulations and to promote corrective action. Examples of regulatory action letters issued by CBER include:


Warning Letters

A Warning Letter is an informal, advisory correspondence, issued to achieve voluntary compliance and to establish prior notice. Typically, a Warning Letter notifies a responsible individual or firm that the Agency considers one or more products, practices, processes, or other activities to be in violation of the Federal Food, Drug, and Cosmetic Act, its implementing regulations and other federal statutes. A Warning Letter is one of the Agency's principal means of achieving prompt voluntary compliance with the Act. Warning Letters are issued only for violations of regulatory significance.

Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (NIDPOE) Letters

A NIDPOE letter informs the recipient clinical investigator that FDA is initiating an administrative proceeding to determine whether the clinical investigator should be disqualified from receiving investigational products pursuant to the Food and Drug Administration's regulations. Generally, FDA issues a NIDPOE letter when it believes it has evidence that the clinical investigator repeatedly or deliberately violated FDA's regulations governing the proper conduct of clinical studies involving investigational products or submitted false information to the sponsor.

Untitled Letters

An Untitled Letter is an initial correspondence with regulated industry that cites violations that do not meet the threshold of regulatory significance for a Warning Letter. Examples when CBER has issued an Untitled Letter include after its review of a manufacturer's advertising and promotional labeling, after an inspection under CBER's bioresearch monitoring program or by Team Biologics, and as a result of internet website surveillance.

Administrative License Action Letters

License Revocation is the cancellation of a license and the withdrawal of the authorization to introduce or deliver for introduction, biological products into interstate commerce. Unless in the cases of license suspension (see below) or willful violations, CBER will issue a Notice of Intent to Revoke License letter and will provide an opportunity for the manufacturer to demonstrate or achieve compliance before initiating revocation proceedings and issuing a License Revocation letter.

License Suspension is a summary action and provides for the immediate withdrawal of the authorization to introduce or deliver for introduction, biological products into interstate commerce when there are reasonable grounds to believe that any of the grounds for revocation exist and that by reason thereof there is a danger to health. In such cases CBER will issue a License Suspension letter to the licensed manufacturer notifying them of the suspension of license.

Orders of Retention, Recall, Destruction, and Cessation of Manufacturing Related to Human Cell, Tissue, and Cellular and Tissue-Based Products (HCT/Ps)

An Order of Retention, Recall, Destruction, or Cessation of Manufacturing may issue when any of the following conditions exist:

  • There are reasonable grounds to believe that an HCT/P is a violative HCT/P because it was manufactured in violation of the regulations in this part and, therefore, the conditions of manufacture of the HCT/P do not provide adequate protections against risks of communicable disease transmission; or
  • The HCT/P is infected or contaminated so as to be a source of dangerous infection to humans; or
  • An establishment is in violation of the regulations in 21 CFR part 1271 and, therefore does not provide adequate protections against the risks of communicable disease transmission.

Of note, FDA does not issue orders for the destruction of reproductive HCT/Ps, nor will FDA carry out destruction of reproductive HCT/Ps.

An Order of Retention, Recall, Destruction, or Cessation of Manufacturing generally would be issued where violations create an urgent situation involving communicable disease transmission, because an establishment is in violation of the regulations and, therefore, does not provide adequate protections against the risks of communicable disease transmission.


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Division of Communication and Consumer Affairs
Office of Communication, Outreach and Development
Center for Biologics Evaluation and Research
Food and Drug Administration
10903 New Hampshire Ave WO71-3103
Silver Spring, MD 20993-0002

ocod@fda.hhs.gov

(800) 835-4709
(240) 402-8010

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