The Series of Warning Letters to Manufacturers of Hand Sanitizers does not stop

Background

In the past, we have reported on FDA Warning Letters related to hand sanitizers that were outside of specifications in terms of active ingredient content or contaminated with genotoxic or carcinogenic substances such as benzene, acetaldehyde, and acetal in unacceptable amounts. The FDA has emphasized the need for necessary analytical tests.

Contamination with Acetaldehyde

The latest published FDA Warning Letters include a case of hand sanitizers sold in the over-the-counter consumer market that are contaminated with potentially genotoxic and/or carcinogenic substances. The Synergy Hand Sanitizer (HS) Alcohol Antiseptic 80% Topical Solution and Synergy Hand Sanitizer with Aloe (HSA) Alcohol Antiseptic 70% Topical Solution produced by Superior Glove Works, Ltd., Canada were contaminated with acetaldehyde based on the analysis certificates of the ethanol active ingredient used. This substance appears to be genotoxic and potentially carcinogenic when in direct contact with tissue. The active ingredient used contained acetaldehyde in unacceptable amounts (205 ppm) and the sum of all contaminants was 2,846 ppm.

After a telephone consultation with the FDA, it was recommended to recall all batches on the market that may have been manufactured using the ethanol active ingredient that contained contaminants in unacceptable amounts.

On September 1, 2022, a nationwide voluntary recall of a batch of Synergy Hand Sanitizer (HS) Alcohol Antiseptic 80% Topical Solution was initiated due to the presence of acetaldehyde contaminants and the sum of all contaminants in unacceptable amounts.

Further Requirements

For the FDA, this incident was the reason for the current Warning Letter, as it suggests that the company failed to establish and implement the necessary control and analytical measures to prevent contaminated active ingredients and raw materials from being used. The manufacturer did not conduct its own analysis or identity verification of the raw materials. A test for methanol content was not performed. Although the incoming materials, such as the ethanol active ingredient, were accompanied by a CoA, these CoAs did not contain data/specifications for contamination tests (benzene, methanol, acetal, acetaldehyde, etc.) or specifications such as contamination values for acetaldehyde max. 900ppm and sum of all contaminants max. 5000ppm that exceeded the permissible values. These are described, for example, in the United States Pharmacopeia (USP). Alcohol that does not meet the specification for acetaldehyde and acetal is considered to be misbranded according to Section 501(b) of the FD&C Act. Therefore, as ethanol is a fundamental component of hand sanitizers, the manufacturer must have a specification for acetaldehyde and acetal according to 21 CFR 211.160(b).

In addition to the missing specifications and testing, the FDA found that the company's quality control system was inadequate, including the following points:

• The batch numbers of the materials were not always recorded.
• The quantities used in the batch were given as ranges in some cases.
• Equipment identification numbers were not recorded.
• Mixing speeds/times were not recorded.
• Operator and verifier initials for weighing and material addition steps were missing.

Accordingly, the FDA requires submission of

• A comprehensive, independent review of your material system to determine if all suppliers of components, containers, and closures are qualified and the materials have appropriate expiration or retest dates.
• A description of how each component batch is tested for conformance to all appropriate specifications for identity, strength, quality, and purity
• A summary of the results obtained from testing all components to assess the reliability of each component manufacturer's COA.
• The chemical and microbiological quality control specifications used to test and release each incoming component lot for use in production
• A complete assessment of the documentation systems of the entire production and laboratory operation to evaluate potential gaps and develop an appropriate corrective and preventive action (CAPA) plan.

More details can be found directly in the FDA  Warning Letter from 16 Dezember.