FDA Warning Letter: Unlicensed biological product, misbranding and many other offences

Between 25 and 29 September 2023, the FDA conducted an inspection at an American company that manufactures a product based on amniotic fluid. The following serious violations were found, which were documented in an official warning letter:

1. Unauthorised drug and unlicensed biological product

The product is classified as a drug under FDA regulations because it is advertised for the diagnosis, cure, treatment or prevention of disease or to affect body structure or function. However, it is neither approved by the FDA nor does it have a required Biologics Licence Application (BLA). Therefore, the marketing and distribution of the product is a violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the Public Health Service Act (PHS Act). The FDA emphasises that an organic product may only be marketed with an approved BLA, which is not the case for this product.

2. Violations of good manufacturing practices (CGMP)

The inspection revealed serious violations of Current Good Manufacturing Practice (CGMP) regulations according to 21 CFR Parts 210 and 211:

2.1 Lack of validation of aseptic processes

• The sterility of the product is not ensured because no aseptic process validations have been performed.
• The company does not carry out regular aseptic process simulations, although the product is sold as sterile.
• The FDA points out that sterility tests alone are not sufficient to rule out microbiological contamination.

2.2 Lack of identity testing and scientifically sound specifications

• The company has not established appropriate laboratory guidelines for identity testing of the product.
• Although there are studies on the composition of amniotic fluid, these are not used for quality control of the end product.

2.3 Insufficient stability testing and false shelf life claims

• The company has not carried out any stability tests to determine a scientifically sound shelf life.
• Product labels and accompanying documents have different shelf life claims that are not supported by data.
• The FDA requires a correct determination of shelf life and action for products already in circulation that are mislabelled.

3. Misleading labeling (misbranding)

The FDA categorises the product as misbranded because false or misleading information is provided on the labels. For example, the product is described in the instructions as a specific type of medical device, although it actually has a different type according to FDA specifications. Furthermore, the different shelf life information causes confusion for users, which can jeopardise safe use. The company stated that the discrepancies were caused by miscommunication with the distributor, but could not provide documented corrective actions.

4. Additional concerns

There are inadequate environmental monitoring measures in the cleanrooms where the product is manufactured.
The company only monitors passive microorganisms, but does not actively monitor the environment or personnel for contamination.

5 Conclusion and FDA requirements

The FDA requires the company to take comprehensive corrective action and demonstrate that the violations are corrected. In particular, the following are expected:

• A valid Biologics License Application (BLA) process for the product 
• The implementation of aseptic process validations
• The introduction of scientifically based specifications and stability testing
• Corrective actions for mislabeled or unsafe products on the market
• Improvements in environmental monitoring at manufacturing facilities

The FDA emphasises that the distribution of the product under the current conditions is illegal and a violation of several federal laws. If appropriate corrective action is not taken, legal action, up to and including a ban of the product, could follow. Read the full warning letter to INCELL Corporation LLC on the FDA website.