Current thinking of the Food and Drug Administration (FDA or Agency). The guidance discusses the notification requirements under section 506C of the Federal Food, 22 Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 356c) and FDA’s regulations.
Who Must Notify FDA and What Products are Subject to the Notification Requirements:
- Applicants with approved new drug applications (NDAs) or approved abbreviated new drug applications (ANDAs) for certain finished drug products.
- Applicants with approved biologics license applications (BLAs) for certain finished biological products other than blood or blood components.
- Applicants with approved BLAs for blood or blood components for transfusion that manufacture a significant percentage of the U.S. blood supply.
- Manufacturers of certain finished drug products marketed without approved NDAs or ANDAs
The notification requirement regarding discontinuances and interruptions in manufacturing of API under section 506C of the FD&C Act applies only to the manufacturers that are listed above; other entities in the supply chain for a drug, including third-party API manufacturers and suppliers, are not required to submit such notifications.
The finished products for which notifications must be submitted under section 506C of the FD&C Act are prescription drugs and biological products (including blood or blood components for transfusion) that are:
- (1) life supporting, life sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition, including any such product used in emergency medical care or during surgery or any such drug that is critical to the public health during a public health emergency declared by the Secretary under section 319 of the Public Health Service Act; and
- (2) not radiopharmaceutical drug products or any other products designated by FDA.21,22 In addition, the manufacturers listed above must submit notifications under section 506C of the FD&C Act for API of covered finished products
When To Notify FDA:
In general, manufacturers of covered finished products must submit a notification to FDA at least 6 months in advance of
- (1) a permanent discontinuance in manufacturing of a covered finished product,
- (2) an interruption in manufacturing of a covered finished product that is likely to lead to a meaningful disruption in supply of the product in the United States,
- (3) a permanent discontinuance in manufacturing of API for a covered finished product, or
- (4) an interruption in manufacturing of API for a covered finished product that is likely to lead to a meaningful disruption in supply of the API for the product
However, if 6 months’ advance notice is not possible, the notification must be submitted as soon as practicable thereafter; furthermore, a notification concerning a permanent discontinuance or interruption in manufacturing of a covered finished product must be submitted no later than 5 business days after the discontinuance or interruption in manufacturing occurs.
Failure To Notify FDA?
If a manufacturer fails to provide notification with respect to covered finished products or API, as required by section 506C(a) of the FD&C Act and in accordance with the timelines set forth in section 506C(b) and the implementing regulations, FDA will issue a letter to that manufacturer stating that the applicable notification requirement was not met (a “noncompliance letter”).
Note that if FDA determines that an applicant experienced a reportable interruption in manufacturing that it could not reasonably anticipate 6 months in advance, but the applicant failed to notify FDA “as soon as practicable,” FDA will issue a noncompliance letter.
The manufacturer must respond to FDA’s letter not later than 30 calendar days after its issuance, providing the reason for noncompliance and the information on the discontinuance or interruption required under section 506C(a) of the FD&C Act.
Not later than 45 calendar days after the issuance of the noncompliance letter to the manufacturer, FDA will post that letter and any response received on FDA’s website, with appropriate redactions to protect trade secrets or confidential commercial information.
Please contact info@fwqrc.com for
- What Information to Include in Notifications About Discontinuances or Interruptions in Manufacturing of Covered Finished Products and API
- How To Notify FDA?
