Warning Letter to Canadian Manufacturers of Injectable Homeopathic Products

On June 11, the FDA published a Warning Letter to 8046255 Canada Inc. DBA Viatrexx, a manufacturer of homeopathic products intended for use by injection. It is interesting to note that the underlying inspection took place at the end of 2019 and resulted in a 483 letter from the FDA. The Warning Letter can be understood as the reaction to the company's response. It is also interesting to note that a number of violations of various sections of the 21 Code of Federal Regulations (CFR) as well as of sections 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355 and 301 of the FD&C Act, 21 U.S.C. 331 are listed. The FDA describes this in its letter:

"These products are of particular concern from a public health perspective because injectable drugs may carry the risk of serious harm to consumers; these risks are less likely to occur with topical or ingested products, i.e. those that are applied to the skin or taken by mouth. Injectable products are delivered directly into the body, sometimes directly into the bloodstream, and therefore bypass some of the body's main defences against toxins and micro-organisms that can lead to serious and life-threatening conditions. Their injectable products are also of concern because they are labelled to contain potentially toxic or otherwise harmful ingredients such as "Nux Vomica" (contains strychnine), "Rectum" and "Belladonna", which poses an additional risk of serious harm to patients if they are released directly into the body...".

The Warning Letter details these violations and documents a number of deficiencies :

Lack of definition, validation and documentation of adequate procedures to prevent microbiological contamination of allegedly sterile medicinal products

• Lack of definition and implementation of process simulations (media fills)
• Unsuitable filters for sterile filtration
• Missing filter integrity test
• Incorrect aseptic techniques/personnel behaviour in manual filling

At this point the connection with the previous Form 483 also becomes clear:

"On October 14, 2019, your company recalled all sterile injectable drugs manufactured by you. However, the corrective measures you proposed allowed the continued use of an unsuitable filter to sterilize your drug. Nor did your response address the frequency with which the media is filled."

As a result, the FDA defines very specifically what they expect from the manufacturer, in particular with regard to the risk assessment of

• All human interactions within the ISO 5 range
• Device placement and ergonomics
• Layout of the facility
• Staff and material flows (through all rooms used to perform and support sterile operations)

and the measures to be derived from it. Also with regard to the sterilization processes, a corresponding change in the choice of materials and a comprehensive validation including complete documentation is expected.

At this point the Warning Letter has already exceeded the length of many other Warning Letters, but this is followed by the description of deficiencies in the following areas.

Manufacturing

• No cleanroom-compatible clothing and lack of qualification of the changing room process
• Inadequate monitoring of environment and processes
• Frequency and documentation of cleaning and disinfection

Laboratory/Quality Control

• No validation of the sterility test
• no suitable media for the test
• no endotoxin test
• no particle check

Accordingly, the FDA has defined an import alert for various of the company's products, i.e. the agency believes that the products have safety deficiencies. As a result of an import alert, the FDA will automatically detain the products at the border.

For more details, see the Warning Letter directly on the FDA³s website.