Emergency Hand Sanitizer Production – Regulations, Requirements and Manufacturing Opportunities
The current public focus on personal hygiene and cleanliness can present a significant revenue opportunity for businesses that have the flexibility to manufacture hand sanitizer. Conceptually, the Big Message from FDA is simple; assist in COVID-19 prevention by making hand sanitizer, and FDA will not pursue enforcement actions.
In the guidance document released by FDA on April 15, 2020, Temporary Policy for Preparation for Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19) Guidance for Industry, FDA has officially announced relaxed enforcement (“enforcement discretion”) of the Adulterated Drugs and Devices (21 USC 351) chapter of the Federal Food, Drugs and Cosmetic Act.
The purpose of this article is to provide background information on the scope of federal emergency action, to identify relevant sections of public acts and laws which provide immunity from liability, and finally to discuss the requirements in the FDA’s guidance document on emergency manufacture of hand sanitizer.
Background on Scope of Federal Emergency Action
There are several bureaucratic layers to peel back in order to understand a company’s responsibilities and risks from taking part in the emergency manufacture of hand sanitizer. The following is relevant background information to clarify the authority of the FDA versus HHS in this health crisis.
There are states of emergency and there are public health emergencies (PHE). The two are not the same. While they can occur simultaneously, one does not necessitate the other and each opens its own set of bureaucratic doors. Different governmental bodies are responsible for activating these states.
A public health emergency is declared by Health and Human Services (HHS). It is a tool with statutory and regulatory weight and reference. It is also specifically identified in the Federal Food Drug and Cosmetic Act and recognized by the FDA. This statutory condition paves the way for emergency use of medical products, emergency development and review of medical products, and priority review to encourage treatments for agents that present national security threats. (These are all sections under 21 USC Chapter 9 Subchapter V, parts A and E.)
The guidance document states clearly the relaxed oversight will last for, “…the duration of the public health emergency as declared by the Secretary of Health and Human Services (HHS) on January 31, 2020,” (Food and Drug Administration, 2020). The PHE for the COVID-19 outbreak was declared January 31, 2020, and was retroactive to January 27, 2020. Per 42 USC 247d, the Secretary may extend the public health emergency for up to 90 days. On April 26, 2020, Secretary Azar of HHS made the first extension of the public health emergency. It is likely the PHE will be extended again on or around July 26, 2020. A comparable example of the duration of a public health emergency is the H1N1 flu outbreak in 2009.
HHS declared a public health emergency related to H1N1 which lasted from March 22, 2009, through June 22, 2010. If this is the case with COVID-19, companies new to the world of FDA regulated manufacturing may have over a year to learn, implement and optimize this stream of revenue before becoming concerned about enforcement activities from FDA.
HHS Public Act and Declaration Providing Immunity from Liability
Another important detail of the PHE and the supporting bureaucracy is that the PREP Act (aka Public Law 109-148) has been declared applicable to this crisis. The PREP Act was written and signed into law in 2005. Division C of the Act provides immunity to manufacturers acting in good faith to address public health emergencies. The Secretary of HHS may (and has for the COVID-19 outbreak) issue a declaration to provide:
“…liability immunity to certain individuals and entities (Covered Persons) against any claim of loss caused by, arising out of, relating to, or resulting from the manufacture, distribution, administration, or use of medical countermeasures (Covered Countermeasures), except for claims involving “willful misconduct” as defined in the PREP Act,” (Health and Human Services Department, 2020).
An advisory opinion issued by HHS on April 14, 2020 cites the PREP Act and specifies covered countermeasures include, “…any other drug…used to treat, diagnose, cure, prevent, or mitigate COVID-19….” (Department of Health & Human Services, 2020). As FDA classifies hand sanitizer as an Over-The-Counter (OTC) drug product, it falls within the definition of a covered countermeasure and as such immunity from liability is applicable. It is important to reiterate immunity does not apply in the face of willful misconduct which is clearly defined in the PREP Act (Public Law 109-148 section 319F-3(c), Definition of Willful Misconduct).
During the declared PHE, companies still have a responsibility to manufacture products ethically and honestly. Once this relaxed oversight ends, companies will be expected to strictly adhere to FDA regulations for manufacturing OTC drug products.
Emergency Provisions to Manufacture Hand Sanitizer in the FDA Guidance Document
As mentioned, hand sanitizer is classified as an Over-the-Counter (OTC) drug product. Production is normally regulated by 21 CFR 330. As a drug product, it is also normally subject to the regulations commonly referred to as current Good Manufacturing Practices (cGMP) captured within 21 CFR 210 and 211.
Even though a PHE has been declared, and FDA has specifically stated it does not intend to take action against firms for the duration of the emergency, 21 CFR 210, 211, and 330 still do apply. Companies should adhere as best as possible to these regulations when starting emergency manufacturing for hand sanitizer. As enforcement is presently relaxed, this is a prime opportunity to begin ethical manufacturing while simultaneously developing processes and procedures to ensure strict FDA compliance for when the PHE is lifted.
Nine circumstances are needed to be able to manufacture hand-sanitizer for public use:
- Permission/Firm registration
Firms need to register with FDA. An electronic registration system exists. Instructions to register can be found here: https://www.fda.gov/drugs/drug-registration-and-listing-system-drls-and-edrls/electronic-drug-registration-and-listing-instructions
This link will direct businesses wishing to register to a webinar created by FDA that guides a company through the registration process.
Bear in mind, hand sanitizer is considered a drug/drug product. It may be confusing to see this language in relation to hand sanitizer, however, it is industry ‘lingo.’
The recipe/formulation is limited to 4 ingredients in proportions following the World Health Organization (WHO) guidelines. The FDA guidance document linked at the beginning of this article provides the formulation details. This means scents/flavors must be excluded from the formulation.
The finished product concentration cannot be below 80% for ethanol-based and 75% for isopropyl alcohol (IPA) based sanitizers. Specific grades of ingredients required and identified in the guidance document.
Ethanol and IPA are the only two alcohols identified by WHO and acceptable per the guidance document. Be cautious to avoid using any ingredients listed under 21 CFR Sec. 310.545 as anything listed there requires approval for use via a New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) and are outside the scope of FDA’s enforcement discretion for emergency hand sanitizer production. The attachment at the end of this article identifies the section of 310.545 specific to hand washes and provides a link to yet another FDA guidance document on hand cleansing products.
- The alcohol used must be denatured. The guidance document identified several acceptable denaturants. Additionally, the CARES Act (H.R. 748 Section 2308) declared a temporary exemption from excise tax for alcohol used to produce hand sanitizer.
- Batches need to be tracked.
Even though FDA has indicated it does not intend to take enforcement action, batch records, and by inference, Good Documentation Practices (GDP) still apply. Simple forms are acceptable to track batches. Each batch should have a traceable lot number.
- The hand sanitizer should be manufactured under sanitary conditions using appropriate equipment. If manufacturing lines are being converted from another product, care should be taken to avoid cross-contamination with that other product. Per the guidance document, insanitary conditions must be prevented.
- Businesses must test and verify the final alcohol concentration. The guidance document identifies a few means considered acceptable to accomplish this.
- Relaxed guidance is limited to one formulation.
Foams, aerosols, etc., cannot be manufactured under this emergency guidance document. This is because other formulations may contain more than the 4 ingredients identified by WHO.
- Adverse event reporting mechanism
Firms must have an adverse event reporting mechanism in place. At this point it does not need to be complex. However, it is recommended to concurrently author/issue an SOP that will identify the business approach to address reporting adverse events. When the public health emergency ends, this requirement will need to be part of routine manufacturing.
Any adverse event reported to the business will also have to be submitted to the FDA per the MedWatch Adverse Event Reporting program.
Specific labels identified and templates are included in the temporary guidance document. Additionally, specific packaging requirements that prevent alcohol evaporation are called out. The guidance document defers to the Department of Transportation (DOT) guidelines for transportation, stating DOT hazmat transport includes separate requirements for, “…classification, packaging, marking, labeling and other requirements relevant to transportation,” (Food and Drug Administration, 2020).
As stated at the beginning of this article, the Big Message from FDA is make hand sanitizer ethically and in good faith, and enforcement actions will not be taken against a firm. It appears this public health emergency is changing and shaping mindsets for the future. Routine production of hand sanitizer is likely going to become a significant revenue stream for enterprising companies willing to learn to navigate FDA regulations. Once the public health emergency ends, strict FDA compliance will be required. Automated Systems, Inc. has the experience and resources available to assist with a seamless transition into OTC manufacturing.
Department of Health & Human Services. (2020, April 14). Advisory Opinion on the Public Readiness and Emergency Preparedness Act and the March 10, 2020 Declaration Under the Act. Washington, District of Columbia. Retrieved from https://www.hhs.gov/sites/default/files/prep-act-advisory-opinion-april-14-2020.pdf
Food and Drug Administration. (2020). Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19). Silver Spring, MD: FDA.
Health and Human Services Department. (2020, April 15). Amendment to Declaration Under the Public Readiness and Emergency Preparedness Act for Medical Countermeasures Against COVID-19. Public Readiness and Emergency Preparedness Act, Public Law 109-148. Washington, District of Columbia. Retrieved from https://www.federalregister.gov/documents/2020/04/15/2020-08040/amendment-to-declaration-under-the-public-readiness-and-emergency-preparedness-act-for-medical#pri
- FDA final rule on ingredients considered generally recognized as safe (GRAS):
Safety and Effectiveness of Consumer Antiseptic Rubs; Topical Antimicrobial Drug Products for Over-the-Counter Human Use, A Rule by the Food and Drug Administration on 04/12/2019
Some ineligible active ingredients (listed below) require approval under NDA or ANDA
(e.g.: In today’s final regulation we finalized the FDA’s previous determination that 28 active ingredients, including triclosan and benzethonium chloride, are not eligible for evaluation under the FDA’s OTC Drug Review for use in consumer antiseptic rubs*)
- From the regulations:
|21 CFR Sec. 310.545 Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses.|
|(a) A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses:|
(27)Topical antimicrobial drug products –(iii) Consumer antiseptic hand wash drug products. Approved as of September 6, 2017.
Iodine complex (ammonium ether sulfate and polyoxyethylene sorbitan monolaurate)
Iodine complex (phosphate ester of alkylaryloxy polyethylene glycol)
Nonylphenoxypoly (ethyleneoxy) ethanoliodine
Phenol (greater than 1.5 percent)
Phenol (less than 1.5 percent)
Poloxamer iodine complex
Povidone-iodine (5 to 10 percent)
Undecoylium chloride iodine complex
(b) Any OTC drug product that is labeled, represented, or promoted for the uses specified and containing any active ingredient(s) as specified in paragraph (a) of this section is regarded as a new drug within the meaning of section 210(p) of the Federal Food, Drug, and Cosmetic Act (the Act), for which an approved new drug application under section 505 of the Act and part 314 of this chapter is required for marketing. In the absence of an approved new drug application, such product is also misbranded under section 502 of the Act.
(c) Clinical investigations designed to obtain evidence that any drug product labeled, represented, or promoted for the OTC uses and containing any active ingredient(s) as specified in paragraph (a) of this section is safe and effective for the purpose intended must comply with the requirements and procedures governing the use of investigational new drugs set forth in part 312 of this chapter.
(d) Any OTC drug product that is not in FDA compliance with this section is subject to regulatory action if initially introduced or initially delivered for introduction into interstate commerce after the dates specified in paragraphs (d)(1) through (d)(42) of this section.
- FDA News Release (04/11/2019) FDA issues final rule on safety and effectiveness of consumer hand sanitizers:
“At this time, three active ingredients—benzalkonium chloride, ethyl alcohol, and isopropyl alcohol—are being deferred from further rulemaking to allow for the ongoing study and submission of additional safety and effectiveness data necessary to make a determination regarding whether these active ingredients are generally recognized as safe and effective for use in OTC consumer antiseptic rub products. Their status will be addressed either after completion and analysis of the studies or at another time, if these studies are not completed. At this time, the FDA does not intend to take action to remove hand sanitizers containing these three active ingredients from the market.”
 42 USC 247d.(a) “…Any such determination of a public health emergency terminates upon the Secretary declaring that the emergency no longer exists, or upon the expiration of the 90-day period beginning on the date on which the determination is made by the Secretary, whichever occurs first.”
 It is strongly recommended to read this publication by HHS to further understand liability and immunity as outlined in the PREP Act: https://www.hhs.gov/sites/default/files/prep-act-advisory-opinion-april-14-2020.pdf