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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5335_Библиотеки_им_академика_М_И_Перельмана.pdf
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Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
Associate Professor Chan Lai Wah, BSc (Pharm) (Hons), PhD
Department of Pharmacy, National University of Singapore,
18 Science Drive 4, Singapore 117543
References
This article has 83 references which can be found at https://gabijournal.net/manufacture-and-regulation-of-cell-tissue-and-genetherapy-products-global-perspectives-challenges-and-next-steps.
html.
Chapter 13
Hand Sanitizers
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13.1. What are Hand Sanitizers?
and sanitizers are rub-on formulations for the purpose of inactivating microorganisms on the hands.
They typically come in gel, liquid, or foam forms and
H
hand sanitizers may be loosely categorized as alcohol-based and
non-alcohol-based.
13.2. Composition and Eectiveness of Hand Sanitizers
Alcohol-based hand sanitizers commonly contain ethanol or isopropanol, while non-alcohol-based sanitizers usually contain benzalkonium chloride or chlorhexidine gluconate. In relation to the
may contain alcohol as the active ingredient. Hence,
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Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
Stationary bottle of hand sanitizer
Portable bottle of hand sanitizer
COVID-19 pandemic, the World Health Organization recommends
alcohol-based sanitizers as they are more eective against viruses
than the non-alcohol-based ones. Benzalkonium chloride and chlorhexidine gluconate are more eective against bacteria than against
fungi and viruses, destroying bacteria by disrupting their plasma
membrane. Compared to alcohol, they are less fast-acting but they
have greater residual activity. Besides the active ingredient, hand
sanitizers may also contain other additives. These include:
Hand Sanitizers
• emollients (for example, glycerol) to prevent dry skin;
• antimicrobial preservatives (for example, hydrogen peroxide) to
prevent the growth of contaminating bacterial spores;
• bittering agents (for example, methylethylketone and denatonium benzoate) to make the product less palatable and thus
reduce the risk of ingestion; and
• fragrances to enhance product appeal.
However, the eectiveness of the active ingredients may be reduced
by the additives. Currently, there is no single international standard for testing the eectiveness of hand sanitizers. So, how do you
really know what is really in the bottles of hand sanitizers and what
“germs” do they actually kill? Are the chemicals even safe for frequent and long-term use on skin? Unfortunately, there is no clear
answer for the consumers or users. There are many dierent formulations on the market, their labeling is often incomplete, and most
countries do not regulate these products. Hand sanitizers typically
contain antiseptic substances to kill “germs”, including viruses,
bacteria and fungi. But these germs are very dierent from one
another and react dierently to antiseptics. Globally, the emergence
of safety threats and inappropriate manufacturer claims also suggest that regulatory frameworks are insucient in ensuring optimal eectiveness and safety standards for hand sanitizers.
395
13.3. Microbiological, Scientific and Regulatory
Perspectives of Hand Sanitizers
With the recent COVID-19 pandemic, a surge in the manufacturing, sale and use of hand sanitizers had been observed. However, the
eectiveness and safety of hand sanitizers are not well understood
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Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
by the public. Therefore, the usage of hand sanitizers may not confer adequate protection and may even pose safety threats.
Studies have shown that washing hands with soap and water kills
germs more eectively than using hand sanitizers. As such, hand
sanitizers are just a stopgap when soap and water are not available.
Another misconception is that the higher the alcohol content, the
better. The US Food and Drug Administration recommends 60–95%
levels of alcohol for hand sanitizers. Beyond 95%, the rate of kill
decreases rapidly as the alcohol evaporates too quickly. Alcohol acts
by denaturing proteins, which does not occur easily in the absence
of water. Pure alcohol is completely ineective, as the alcohol needs
water to do its job.
Furthermore, manufacturers of hand sanitizers often claim kill
rates in excess of 99%. For example, 99.99% means that out of a million germs on your hands, just 100 of them will survive the sanitizer.
But these surviving germs continue to pose a health hazard as they
can multiply again when conditions are favorable. Product claims
may mislead people into thinking the sanitizer will kill everything
and there is no more need for good hand hygiene.
13.4. Published Article and Commentary on Hand Sanitizers
Since COVID-19, hand sanitizers have become part of everyday life,
an instant and convenient way to wash your hands to prevent the
spread of the coronavirus and other micro-organisms. Although this
is commonly believed, is this really so in practice? This prompted
the authors to conduct scientific research, and to publish an article
Hand Sanitizers
in GaBI Journal (Volume 10 / 2021 / Issue 3) which is entitled “Micro-
biological, scientific and regulatory perspectives of hand sanitizers”. Copyright © 2021 Pro Pharma Communications International.
The article has been reproduced with permission from the publisher
of GaBI Journal, and it appears immediately after this introduction.
The article presents an overview of the activity of antimicrobials as
active ingredients in hand sanitizers and the principles of test methods to evaluate their eectiveness. Dierent antimicrobials confer
dierent activities, rendering some more useful than others. There
are also no specific compendial tests for ecacy of hand sanitizers
and the choice of test method is left to the discretion of manufacturers. It has also been reported that a significant number of hand
sanitizers were improperly labeled or had inappropriate claims.
Implementing a tighter regulatory framework, developing pharmacists’ knowledge and capabilities, raising consumer awareness and
debunking common myths are some possible solutions to address
the problems encountered.
397
A commentary was also published on 4 March 2021 in TODAY Online.
This commentary, with the caption “What’s really in that bottle of
hand sanitizer?”, was contributed by the author Chan Lai Wah and
her final year student Tan Ying Ting. Amongst some scientific and
general knowledge about hand sanitizers, it also highlights some
facts and myths, and emphasizes that hand sanitizers are not magic
bullets. They come in handy during times of illness outbreaks or
when access to soap and water is limited, providing a convenient
and eective way to maintain hand hygiene. They are commonly
used in healthcare settings, public places, and by individuals to help
prevent the transmission of germs and diseases. It is available to
read for free at https://www.todayonline.com/commentary/whatsreally-bottle-hand-sanitiser.
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Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
Microbiological, scientific and
regulatory perspectives of
hand sanitizers
Adjunct Associate Professor Sia Chong Hock1, BSc Pharm, MSc; Tan Ying
1
Ting
, BSc Pharm (Hons); Associate Professor Chan Lai Wah1, BSc Pharm
(Hons), PhD
Hand sanitizers are rub-on formulations for the purpose of inactivating microorganisms on the hands. With the recent COVID-19
pandemic, a surge in the manufacturing, sale and use of hand sanitizers is observed. However, the eectiveness and safety of hand
sanitizers are not well understood by the public; thus, hand sanitizer usage may not confer adequate protection and may pose safety
threats. Globally, the emergence of safety threats and inappropriate
manufacturer claims also suggest that regulatory frameworks are
insucient in ensuring optimal eectiveness and safety standards
for hand sanitizers. This paper presents an overview of the activity of
antimicrobials as active ingredients in hand sanitizers and the principles of test methods to evaluate the eectiveness of hand sanitizers.
Dierent antimicrobials confer dierent activities, rendering some
more useful than others. There are also no specific compendial test
for ecacy of hand sanitizers and the choice of test method is left to
the discretion of manufacturers. It has also been reported that a significant number of hand sanitizers were improperly labelled or had
inappropriate claims. Implementing a tighter regulatory framework,
Hand Sanitizers
developing pharmacists’ knowledge and capabilities, raising consumer awareness and debunking common myths are some possible
solutions to address the problems encountered.
Keywords: Eectiveness, hand sanitizers, myths, regulatory framework, safety, standards
Introduction
Globally, millions of people suer from healthcare-associated infections (HCAIs) each year [1]. HCAIs occur in patients while receiving
care for another medical condition [2] and one identified cause is
poor hand hygiene [3]. Recently, the emergence of Coronavirus Disease 2019 (COVID-19) poses an unprecedented challenge to healthcare globally. In light of persistent HCAIs and this public emergency,
strategies to mitigate infectious spread are crucial.
399
According to the World Health Organization (WHO), the most crucial measure towards mitigating the spread of harmful microbes is
practicing proper hand hygiene [4]. Following COVID-19, the Center
for Disease Control (CDC) recommends the use of alcohol-based
hand sanitizers as a substitute to hand-washing with soap and water
[5, 6]. Consequently, the sale, supply and use of hand sanitizers have
skyrocketed. Hand sanitizers are rub-on formulations [7] categorized as alcohol-based (ABHS) or non-alcohol-based (NABHS). ABHS
contain alcohol and components, such as water and humectants
[8]. The alcohols commonly used include ethanol (ethyl alcohol)
and iso- propyl alcohol [9]. NABHS, also known as “alcohol-free
hand rub”, commonly contain benzalkonium chloride, chlorhexidine gluconate, hydrogen peroxide or iodine [9]. Hand sanitizers
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Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
may be liquids, gels or foams used to inactivate or suppress the
growth of microorganisms found on hands [8].
Many manufacturers claim that their products kill 99.9% of microbes
eectively. Such claims have become common practice [10] and have
misrepresented the eectiveness of hand sanitizers because the percentage of kill claimed is specific to the microorganisms used in the
test method. Currently, the US Food and Drug Administration (FDA)
allows manufacturers to produce hand sanitizers without formal
approval [11]. This may encourage the rise of ineective hand sanitizers by unethical manufacturers. In fact, the lack of tighter regulatory
controls has compromised safety, as evident in recent cases of methanol poisoning due to the use of methanol-contaminated hand sanitizers [12]. More regulatory oversight is warranted to ensure safety
checks and balances are in place to avoid safety threats.
With the perceived ‘shortage of supply’ of hand sanitizers amid the
COVID-19 pandemic, consumers have become less discerning. They
may also hold misconceptions regarding hand sanitizers which hinder them from receiving the desired protection. The misconceptions
have resulted in safety issues for consumers. In this regard, there is
a need to debunk these myths, raise consumer awareness and promote consumer education.
Studies have investigated the ecacy of using hand sanitizers vis-
a-vis handwashing with soap and water [13, 14]. Some studies have
also compared the ecacies of dierent hand sanitizer brands [15–
18]. As there is no specific compendial test for ecacy of hand sanitizers, various methods have been used and the results obtained
may not be comparable or may not provide useful information.
Hand Sanitizers
There is also a lack of studies to investigate the multitude of factors
that can aect the ecacy of hand sanitizers and to debunk the
misconceptions regarding their activity and safety. To date, there is
no reported survey on the quality, safety and ecacy of commercial
hand sanitizers available to consumers.
This paper aims to highlight useful antimicrobial compounds and
provide a better understanding of the dierent test methods. It also
aims to debunk myths and identify factors that aect the activity
and safety of hand sanitizers, and consequently, pro- pose solutions
to educate consumers. Last, but not least, a regulatory framework
for control of hand sanitizers, is proposed.
The microbiology of bacteria, fungi and viruses
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To evaluate the eectiveness of hand sanitizers, it is necessary to
understand the nature of microorganisms, which are targets of
hand sanitizers. Microorganisms are tiny living things not visible to
the naked eye unless they proliferate to form a mass. Scientifically,
bacteria and fungi are considered microorganisms, but viruses are
not because viruses exist in sub-micron size and are non-living outside of a host [19]. However, manufacturers of hand sanitizers have
often claimed that their products kill 99.9% of microorganisms
[10, 20] which is perceived to include viruses. Moreover, common
ecacy tests employed consist of methods developed for bacteria
and fungi, suggesting that viruses are not covered.
Bacteria are prokaryotes with each cell consisting of a double-stranded
DNA (dsDNA), plasmids and ribosomes in the cytoplasm surrounded