Development of analytical methods for hand sanitizer OTC products: Regulatory considerations for safety and product quality

PURPOSE:
To help ensure the safety and effectiveness of hand sanitizer products the FDA has published a temporary guidance for industry detailing the preparation of alcohol-based hand sanitizer products. The temporary guidance on hand sanitizer products states that formulations should include 80% ethanol (v/v) or 75% isopropanol (v/v). In addition, the temporary guidance lists 12 impurities and their concentration limits that should be avoided in the final hand sanitizer products. To assist the Agency with the hand sanitizer product quality testing, OTR’s scientists developed and validated headspace (HS) gas chromatography-mass spectrometry (GC-MS) methods to test hand sanitizer products for ethanol, isopropanol, and impurities. The developed methods were designed to ensure the efficacy and safety of over the counter (OTC) hand sanitizer products.

METHODS:
The HS GC-MS methods were validated according to ICH Q2 R1 for specificity, linearity, range, quantitation limit, accuracy, precision, and robustness. Spike recovery and stability studies were conducted. 2 active ingredients and 12 impurities were evaluated using the respective the HS GC-MS methods. Sample preparation was dependent on the hand sanitizer formulation matrix. Calibration standards were used for determining the concentration of analytes in hand sanitizers. A spike recovery assay was performed by spiking known concentrations of standard analytes into the hand sanitizer samples.

RESULTS:
HS GC-MS methods for hand sanitizer products were successfully validated according to the ICH Q2 (R1) guidelines and passed all the set criteria. All validated analytes maintained their reported linearity with coefficients of determination (R²) greater than 0.99. Inter-day percent accuracy and precision of the tested analytes for the four levels all met the specifications within 80-120% accuracy and ≤ 5% RSD. Spike recovery in hand sanitizers was within the specification of 80-120% recovery for all analytes at three different spiking concentrations and precision was below 10% for samples in triplicate.

CONCLUSIONS:
The successful analytical method development in complex product matrices by the agency scientists and the testing of hand sanitizer products provided regulatory science data to CDER that assisted with regulatory actions helping to best ensure the safety and efficacy of hand sanitizer products for use by the American public.