With the Coronavirus Disease 2019 (COVID-19) pandemic the new reality for hospital pharmacies across the globe, the need for hand sanitizer plays an important role in hand hygiene when coupled with proper hand washing practices. Hand washing may not always be feasible or available in certain situations; therefore, access to hand sanitizer is crucial to promote compliance with proper hand hygiene and to prevent the spread of infection. Alcohol-based hand sanitizer is the only known means for rapidly and effectively inactivating a wide array of potentially harmful microorganisms on hands.1
During a worldwide pandemic of an infectious disease, such as COVID-19, the demand for hand sanitizer exponentially increases, leading to widespread stockouts and complete unavailability. This presents an unsafe condition for health care workers and first responders who are treating patients with the disease to protect themselves and others from spreading the infection. In these scenarios, hospital pharmacies are well equipped to compound hand sanitizer to prevent the spread of disease in health care settings. (See the SIDEBAR1-6 for information on regulatory policy and guidance on compounding hand sanitizer.)
Hand Sanitizer Ingredients
Each ingredient in hand sanitizer is added for a specific purpose1:
The final preparation is a solution with a very low viscosity. This is advantageous, as it is easier to compound in large batches, mix, transfer, and verify alcohol content, and also facilitates a final preparation dispensed as a spray application or from a pour spout.
Formulation, Ingredients, and Other Considerations
Evaluating the regulatory policies and guidances, several options exist for the compounder with regard to the active ingredient used (ie, ethanol or isopropyl alcohol), and the grade of ingredients (ie, USP, National Formulary [NF], Food Chemicals Codex [FCC], etc). In order to ensure a quality product as well as employee/consumer safety, a multitude of other factors should be considered by the pharmacy department prior to engaging in compounding hand sanitizer (see TABLE 2).
Compounding Hand Sanitizer in the Pharmacy
The 831-bed Moses H. Cone Memorial Hospital in Greensboro, North Carolina, recently began a program to compound hand sanitizer for use throughout the Cone Health System. When initiating a hand sanitizer compounding program, the first consideration was identifying the location in which to compound the hand sanitizer to ensure proper worker safety and quality of the preparation. Undiluted alcohol is highly flammable and may ignite at temperatures as low as 10°C (50°F). WHO identified the flashpoints for diluted ethanol 80% (v/v) and isopropyl alcohol 75% (v/v) to be 17.5°C (63.5°F) and 19°C (66.2°F), respectively.1 Therefore, it was essential to choose a well-ventilated and air-conditioned room for preparation of hand sanitizer. Flash points (eg, open cup, closed cup) are the result of empirical testing, rather than fundamental properties of the tested substance.7 It is important to verify the tested flash points with the Certificate of Analysis (COA) or Safety Data Sheet (SDS) of each sourced alcohol manufacturer.
In reviewing the SDS of available alcohol stock, isopropyl alcohol was identified as our alcohol of choice for use in the hand sanitizer formulation, as it had a higher flash point compared to ethanol. The negative pressure, nonsterile compounding room was selected as the location for compounding hand sanitizer due to the room being externally exhausted, as well as the fact that the room is humidity and temperature controlled (set point 64°F). WHO advises that batches not exceed 50 L at a time to further mitigate accidental fires.
Storage of the undiluted alcohol was identified as an additional risk point. Therefore, a large, flammable liquid cabinet within the negative pressure nonsterile compounding room was used for storage of undiluted alcohol stock. Should the capacity of the cabinet be exceeded, excess stock is stored in the alcohol vault in the hospital’s laboratory department.
To mitigate alcohol vapor exposure to the compounder, several mask choices were evaluated. It was determined that surgical masks would not protect compounders from the vapors produced from isopropyl alcohol. Therefore, the R-95 mask was chosen as it provides the same protection as an N-95, but also blocks oil (and other organic) vapors. The service life of our stocked R-95 is 8 hours of use before it loses integrity, whereas an N-95 has a service life of 40 hours. Reusable goggles were obtained to protect the compounder from accidental splashes of ingredients into eyes and to minimize exposure to vapors.8
Considering the higher flash point of isopropyl alcohol, the WHO formulation, which produces an isopropyl alcohol 75% final concentration, was chosen (see SIDEBAR1-6 for more information about the different formulations). Furthermore, since isopropyl alcohol is already denatured, this formulation is easier to produce compared to the ethanol formulation. For efficiency, batch sizes were set at 50 L, which roughly equates to 10 gallons of undiluted isopropyl alcohol.
Product shortages required ordering through multiple vendors to obtain USP grade pharmaceutical products. Source containers of isopropyl alcohol 99%, USP (1 gallon), anhydrous glycerin, USP (16 oz), hydrogen peroxide 3%, USP (16 oz), and sterile water for irrigation, USP (1 L) bottles were obtained for the preparation of the hand sanitizer. A Master Formulation Record was created to ensure safe and accurate preparation of the hand sanitizer formulation (see MASTER FORMULATION RECORD).
Through a conversation with the FDA on a public conference call regarding compounding hand sanitizer, the FDA commented that at this time they were not enforcing the policy of placing an expiration date on compounded hand sanitizer formulations. Normally, manufacturers of hand sanitizer must provide data and evidence supporting an expiration date of 3 years. Given the shortages of hand sanitizer and the exponential increase in demand, it is expected that any product being compounded will be used in a short period of time. Furthermore, the final product is noted to be self-preserved and the addition of hydrogen peroxide in the formulation helps to eliminate any spores when product is quarantined for 72 hours prior to use. The quality of the water was deemed an important factor to ensure the final product does not contain contaminants. Therefore, our water source used in the formulation was commercially available sterile water for irrigation, USP. This was selected over other methods to minimize opportunity of introducing contaminated water into the formulation.
The original distribution plan was to dispense 50 mL bottles with dispensing lids for personal use and 1000 mL spray bottles for departmental use throughout the entire health system. It was quickly apparent that a multitude of batches were needed urgently to meet the demand. The Materials Management department assisted in distributing the product to the areas most in need as it became available. The hand sanitizer was also added to the hospital materials ordering system to support requisitions for additional quantities.
Because most of the necessary compounding equipment was non-standard, it had to be purchased. We partnered with a local home brewing product supplier to obtain an alcohol meter, large plastic stirs, a 15-gallon kettle with spigot, a dispensing nozzle, and an oversized funnel. The kettle contained a tight-fitting lid with a small opening for adding ingredients via the funnel. The other supplies were obtained through our normal compounding supplier and included 3,500 mL beakers, a 500 mL conical beaker, glass stirring rods, spatulas, and 100 mL and 250 mL graduated cylinders.
A repeater pump was used to enhance the efficiency of the unit dosing process for the 50 mL bottles. This helped increase the accuracy and speed of filling the containers. It was determined that three workers were needed to ensure maximum efficiency: one person running the pump, one person capping the bottles, and one person labeling the product. This strategy supported the production of 1,800 x 50 mL bottles per shift. As this process was the rate-limiting step in production, the addition of two more repeater pumps were added to further increase throughput.
Multiple challenges appeared at the outset, impacting product sourcing, unit dosing, final alcohol concentration verification, and communication/staff education.
The most significant challenge encountered was the limited availability of the materials needed to produce hand sanitizer in large quantities. Empty plastic bottles, acceptable dispensing lids/caps, and spray nozzle containers were in extremely short supply. To obtain the quantities needed, multiple distributors and manufacturers were utilized to meet the demand. The lag time in arrival was anywhere from 4 days to 3 weeks. Through discussions with the distributors, it was discovered that the majority of the supplies were made outside the United States and were difficult to obtain quickly.
Several ingredients used in the preparation of the hand sanitizer were also in short supply. Obtaining sufficient quantities of undiluted isopropyl alcohol required placing orders through six different distributors and manufacturers. Serendipitously, we discovered an alternative vendor that routinely supplies USP-grade isopropyl alcohol to the cytology department within the health system. Purchasing alternative ingredient bottle sizes was required to ensure a consistent supply of incoming ingredients.
Staffing the unit dose production required foresight. With the highly laborious task of filling, capping, and labeling thousands of bottles, additional staff was required while we were simultaneously experiencing an FTE reduction due to callouts and quarantined staff. Therefore, student pharmacy interns were assigned to the unit dosing process, averting the need to pull operational staff from essential pharmacy operations.
After completing the first day, it was clear that the capping process was laborious and likely to cause repetitive stress injuries. The solution was to use channel lock pliers to cap the bottles without straining the hands. This increased efficiency and reduced the wrist twisting motion.
Final Alcohol Concentration Verification
Creating a safe and adequate quality control measure for the alcohol concentration within the hand sanitizer was an additional challenge. The WHO guidelines recommend the use of an alcohol meter. Because it is calibrated for ethanol and not isopropyl alcohol, we needed to determine the reading for isopropyl, as it has a different specific gravity. The WHO guidelines provide documentation that an isopropyl alcohol 75% concentration within the final hand sanitizer formulation would display as 77% +/- 1%. It was noted that different manufacturers’ certificates of analysis listed slightly different starting concentrations of the undiluted isopropyl alcohol. Therefore, a second quality assurance measure was added that included checking the alcohol percentage of the undiluted alcohol product prior to compounding, and the formulas were adjusted accordingly as needed.
It was quickly apparent that communication and education regarding hand sanitizer availability and proper use was required. In the past, the health system used a gel hand sanitizer throughout the facility, so education needed to be provided that the compounded hand sanitizer was now being provided as a solution. Thus, we created and distributed a flier that provided key product information and explained the ordering process (see FLIER).
The final challenge was efficiently identifying areas in need of hand sanitizer and distributing the product as it became available throughout the health system, which comprises well over 12,000 employees and is spread across numerous hospitals, clinics, surgery centers, cancer centers, outpatient pharmacies, home care, and other locations. To service all these locations, the compounded hand sanitizer was added to the Materials Management requisition software so departments could use their normal ordering process to obtain it. Partnership with Materials Management was essential to provide efficient delivery of the hand sanitizer to the areas most in need.
The inpatient pharmacy department is well equipped to compound alcohol-based hand sanitizer to meet demand during supply disruptions and global pandemics. Through proper planning, a focus on safety and quality, and flexibility in the face of ingredient/supply shortages, the guidance from WHO, FDA, USP, and state boards of pharmacy can be applied successfully in the preparation of alcohol-based hand sanitizer. To date, the inpatient pharmacy at Moses H. Cone Memorial Hospital has successfully compounded and distributed over 1,000 L of hand sanitizer throughout the Cone Health system.
Kevin N. Hansen, PharmD, MS, BCPS, BCSCP, the assistant director of pharmacy at Moses H. Cone Memorial Hospital (MCMH), provides oversight and leadership for pharmaceutical compounding and perioperative services pharmacy. He graduated from the Lake Erie College of Osteopathic Medicine with a Doctor of Pharmacy degree and received an MS in Pharmaceutical Sciences from the University of North Carolina Eshelman School of Pharmacy.
Christopher J. Boiallis, PharmD, BCSCP, the quality assurance pharmacy coordinator at Moses H. Cone Memorial Hospital, graduated from St. John’s University College of Pharmacy with a Doctor of Pharmacy degree and was one of the first to obtain his Board Certification in Sterile Compounding.
Regulatory Policy and Guidance for Compounding Hand Sanitizer
The World Health Organization
In 2009, the World Health Organization (WHO) developed guidelines on hand hygiene in health care.1 The guidelines provide specific formulations and details for local production of hand sanitizer as an alternative when suitable commercial products are unavailable or are too costly. The formulations provided are evidence-based, suitable for use in resource-limited areas, economical, and designed with safety, cultural, and religious factors in mind. Furthermore, to minimize the risk of allergic reactions, the formulations contain no dyes or fragrances. Two formulations are provided with different active ingredients and concentrations (see TABLE 1).1
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) state that for health care workers, unless hands are visibly soiled, an alcohol-based hand rub is preferred over soap and water in most clinical situations due to evidence of better compliance compared to washing with soap and water. Hand rubs are generally less irritating to hands, and in the absence of a sink, are an effective method of cleaning hands. The CDC also provides guidance for health care workers on clinical scenarios where hand sanitizer or hand washing should be performed.2
The Food and Drug Administration
Due to the COVID-19 pandemic, the Food and Drug Administration (FDA) has released a policy titled Policy for Temporary Compounding of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency, which went into effect immediately following publication in March 2020.3 The document outlines FDA’s expectations for how compounding pharmacists in various settings can safely and effectively compound alcohol-based hand sanitizer to meet their needs when commercial products are unavailable. FDA outlines that compounders, relative to untrained consumers, are more familiar with standards and methods for producing drug products and discourages consumers from producing their own hand sanitizer using non-proven methods. The policy gives additional guidance on ingredient quality or grade, denaturing ethanol, approved formulations (consistent with WHO guidelines), verifying ingredient amounts, preparation conditions, and labeling. The agency also released an additional policy titled Temporary Policy for Manufacturer of Alcohol for Incorporation Into Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19), which provides details specifically related to the manufacturing of ethanol, including processes to denature the alcohol for use in production of hand sanitizers.4
The United States Pharmacopeia (USP)
The Compounding Expert Committee within USP has created a document outlining recommendations intended to address shortage of alcohol-based hand sanitizers.5 The document includes three formulations with appropriate ingredient substitutions based on shortage issues for key ingredients used in the production of hand sanitizer. USP outlines that compounders are expected to follow USP General Chapter <795> Pharmaceutical Compounding – Nonsterile Preparations for compounding hand sanitizer.5 Specifically, the following are recommended:
National Alliance of State Pharmacy Associations
For state-licensed pharmacies, it will be prudent to verify rules, regulations, policies, and guidances from specific state boards for compounding hand sanitizer. The National Alliance of State Pharmacy Associations (NASPA) has compiled state actions affecting compounding hand sanitizer. Some states make direct reference to FDA, USP, or WHO guidance, while others provide their own specific guidance.6 More information is available at: https://naspa.us/resource/compounding-hand-sanitizer/