Ensuring the Safety of Locally Sourced Alcohols for Hand Sanitizer Production During the SARS-CoV-2 Crisis: A Comprehensive Impurity Analysis

Abstract

Amid the early 2020 SARS-CoV-2 crisis, severe hand sanitizer shortages led to OMS local production recommendations, inviting a diverse array of alcohol producers to contribute. However, not all followed mandatory controls for API-grade alcohol. We conducted a study to ensure the safety of the received alcohols, focusing on methanol and acetaldehyde levels. All samples were well below Ph. Eur guidelines, affirming their safety for use. Furthermore, no additional impurities were detected, reinforcing the quality and safety of the assessed hand sanitizers. Our findings, amidst the scarcity of the SARS-CoV-2 era, highlight the importance of rigorous safety assessments during local hand sanitizer production.

Introduction

As the world grapples with the enduring challenges posed by the SARS-CoV-2 pandemic, it is opportune to revisit a critical aspect of the crisis that emerged at its outset. In the early days of the pandemic, the shortage of essential supplies, including alcohol-based hand sanitizer (ABHS), was keenly felt. The demand for ABHS soared, driven by its pivotal role in limiting the transmission of SARS-CoV-2. ¹

The pandemic compelled international health organizations, notably the World Health Organization (WHO), ² to underscore the significance of ABHS in infection prevention. WHO guidelines encouraged the frequent use of ABHS, especially following patient interactions, handling of potentially contaminated surfaces, exposure to bodily fluids, and glove removal. ³ Healthcare facilities and community settings witnessed an unprecedented surge in ABHS consumption, challenging the capacity of established supply chains. ⁴

In response to the severe shortages, both the WHO and several countries, including France and the USA, advocated for local ABHS production, aligning with WHO formulations. ³ France, one of the countries profoundly affected by the pandemic, harnessed its diverse ethanol industry, encompassing beverages like beer, wine, and spirits, as well as cosmetics such as perfumery. This resulted in a remarkable mobilization of diverse suppliers, including those not conventionally associated with ABHS production, to meet the escalating demand, particularly within healthcare facilities.

The production of safe and effective ABHS hinges on stringent standards for ethanol suppliers, encompassing biocide grade requirements (eg, European regulation of spirit drinks) or Pharmacopeia grade specifications. ⁵ These standards encompass not only the ethanol concentration but also the control of impurities such as methanol and acetaldehyde. Accordingly, methanol and acetaldehyde must not exceed 200 and 10 ppm, respectively, for Canadian guidelines ⁶ and European Pharmacopeia (Eur Ph). ⁵ Elevated concentrations of methanol can lead to headaches and cough, similar to some Covid-19 symptoms, ⁷ while excessive acetaldehyde can cause irritant contact dermatitis or skin sensitization. ⁸ The latter could also lower ABHS compliance.

As we reflect on the enduring legacy of the SARS-COV-2 pandemic and the strategies employed to navigate its complexities, it is crucial to revisit the early challenges, including the ABHS shortage. With the passage of 3 years since the onset of the pandemic, we propose to reexamine the state of ABHS production and its safety. Specifically, we revisit the levels of methanol and acetaldehyde in locally produced ABHS and their implications for public health. This investigation was launched because a supplier (rejected by Toulouse Hospital pharmaceutical team) repurposed ethanol solution with methanol concentrations above the Eur Ph regulation cut-off, underlining the need for ongoing vigilance and quality control in ABHS production.

Material and Methods

Concentrations of methanol and acetaldehyde were measured in ABHS made from four ethanol suppliers (A, B, C and D), including three local producers (Table 1). One supplier had an ethanol solution of Pharmacopeia grade (A; pharmaceutical supplier), while the others provided biocide grade (Table 1). Ethanol was produced from plants (samples A-C) or yeast (sample D) (Table 1).

Table 1.

Semi-quantification of Methanol and Acetaldehyde in Four ABHS Formulations Produced From Different Ethanol Solutions.

Sample	Producer	Grade of ethanol solution	Ethanol source	Rectified/denatured ethanol	Methanol concentration (ppm)	Acetaldehyde concentration (ppm)
A	Pharmaceutical	Pharmacopeia (EU)	Plant (sugar cane or beet)	Rectified	Presence	Presence
					<100	<10
B	Perfumer	Biocide (WHO)	Plant (wheat or corn)	Denatured	Presence	Presence
					<100	<10
C	Perfumer	Biocide (WHO)	Plant (wheat or corn)	Rectified	Presence	Presence
					<100	<10
D	Industrial	Biocide (WHO)	Yeast	Rectified	Presence	Presence
					<100	<10

Note. EU = European Union; WHO = World Health Organization.

Methanol and acetaldehyde were semi-quantified using a static headspace-gas chromatography-mass spectrometry (GC-MS) method and based on a declaration of conformity for acetaldehyde measurement from ethanol solution. Full-scan screening was also performed on a GC-MS system to identify impurities in the ethanol solutions.

Thresholds of 200 and 10 ppm for methanol and acetaldehyde are based on Canadian guidelines ⁶ on ABHS formulation and Eur Ph guidelines. ⁵

Results

Methanol and Acetaldehyde Concentrations

Analysis of the ABHS samples from four ethanol suppliers (A, B, C, and D) revealed methanol and acetaldehyde concentrations that met safety standards. The concentrations of methanol and acetaldehyde in all samples were found to be well below the regulatory limits defined by the European Pharmacopeia (Eur Ph) guidelines, ⁵ which set the thresholds at 200 parts per million (ppm) for methanol and 10 ppm for acetaldehyde. These results affirm the compliance of the tested ABHS products with established safety criteria, ensuring their suitability for use in healthcare and community settings (Table 1).

Impurity Screening

In addition to the targeted analysis of methanol and acetaldehyde, a comprehensive full-scan screening for impurities was conducted using gas chromatography-mass spectrometry (GC-MS). This screening encompassed a wide range of potential impurities that could compromise the quality and safety of the ABHS products. Encouragingly, no other impurities, such as benzene or furfural, were detected in any of the tested samples. These findings further reinforce the safety and purity of the ABHS formulations examined in this study.

Discussion

The results of our study have substantial implications for the safety and quality of alcohol-based hand sanitizers (ABHS) used in healthcare facilities and, by extension, in community settings. Notably, our investigation did not reveal elevated concentrations of methanol or acetaldehyde in the different samples, and no other impurities were detected, aligning the tested ABHS formulations with Canadian and European guidelines.

It is essential to recognize that acetaldehyde, a natural component of ethanol solutions, was present in the tested samples at levels comparable to, or even lower than, those found in alcoholic beverages such as beer, wine, or liquor. The traditional process of ethanol production, involving fermentation using brewing yeast or plant-derived sources, inherently involves the reduction of acetaldehyde. While it is reasonable to assume that ethanol may not significantly impact the transcutaneous passage of acetaldehyde, a threshold of 1% (volume/volume) acetaldehyde has been proposed by the “European Union Scientific Committee” to avoid skin irritation. ⁸ However, applying this threshold to hydrated and/or occluded skin (eg, immediately after ABHS application when gloves are worn) may require further investigation, as such conditions could alter skin permeability. ⁸

On the other hand, oral ingestion of ABHS could lead to acute intoxication, mainly related to ethanol. ¹ An increase in oral intoxication, already observed with healthcare workers, could be related to its increased availability, at a low cost, outside healthcare facilities. ⁹ Since the denatured-ethanol sample in our study did not contain more methanol, acetaldehyde or impurities, it could be interesting to promote using denatured ethanol for ABHS production to prevent intoxication.

While the ABHS solutions used in healthcare facilities are typically accompanied by a declaration of conformity, ensuring the conformity of raw materials remains the responsibility of ABHS producers. Our study, though reassuring in its findings, featured a limited number of ABHS suppliers, and it is imperative to extend impurity screening to ABHS intended for use in community settings. Recent reports of ABHS products with egregiously high methanol content underscore the need for vigilance (one contained 81% (v/v) methanol, without any ethanol, and the other 28% (v/v) methanol), especially given the potential for serious health risks.^{10 -12}

In conclusion, our study provides reassuring initial data on the absence of excessive methanol and acetaldehyde in selected biocide grade and Eur Ph ethanol solutions, supporting the safe use of ABHS. However, continuous monitoring of the quality and safety of ABHS, particularly in community settings, is of paramount importance as the ongoing fight against infectious diseases, including SARS-COV-2, demands unwavering attention to product integrity and public health.