Regulatory Actions Issued By CBER
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
- Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (NIDPOE) Letters
- Untitled Letters
- Administrative License Action Letters
- Orders of Retention, Recall, Destruction, and Cessation of Manufacturing Related to Human Cell, Tissue, and Cellular and Tissue-Based Products (HCT/Ps)
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.
Warning Letters - FDA's Electronic Freedom of Information Reading Room
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.
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.
- Advertising and Promotional Labeling Untitled Letters for Approved Biological Products
- Untitled Letters Related to BIMO/Team Biologics/Internet Surveillance/Other
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.
- 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 the risk 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 this part and, therefore does not provide adequate protections against the risks of communicable disease transmission.”
- An Order to Cease Manufacturing would be issued where violations create an urgent situation involving a communicable disease, because an establishment is in violation of the regulations and, therefore, does not provide adequate protections against the risks of communicable disease transmission.