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FDA Regulatory and Compliance Monthly Recap – February 2021

FDA issues guidance for temporary compounding of alcohol-based hand sanitizer products by pharmacists

The FDA updated its guidance concerning pharmacists and outsourcing facilities temporarily compounding alcohol-based sanitizer products. The guidance was issued in response to difficulties experienced by both consumers and health care personnel in accessing these sanitizers. It was also issued in response to reports that some consumers are producing their own sanitizers for personal use. The FDA also recognizes that compounders, compared to untrained consumers, are more familiar with the standards for and methods of manufacturing these products, and the guidance was issued to communicate its policy for the temporary compounding of hand sanitizers.

As per the guidance, the FDA stated that it does not intend to take action against compounders preparing alcohol-based hand sanitizers for consumer use during the ongoing COVID-19 public health emergency. Compounders will be exempt from FDA action provided a certain set of circumstances are present. The first of these relates to ingredients used in the compounding of the products, which must include only either (i) alcohol that is not less than 94% ethanol by volume or (ii) U.S. Pharmacopeia (USP) grade isopropyl alcohol; glycerin USP or Food Chemical Codex (FCC); hydrogen peroxide; and sterile water. In addition, alcohol that was produced using fermentation and distillation processes in a facility used for producing consumable goods would potentially be considered for use in hand sanitizers, so long as the alcohol meets the interim impurity levels listed in the guidance’s appendix.

The alcohol used must also be denatured either by the alcohol producer or at the point of production. This is important due to reports of adverse events, including death, from ingesting hand sanitizer. The finished hand sanitizer product must also be compounded using the following formula, which is consistent with World Health Organization recommendations:

  • Alcohol (ethanol) (formulated to 80%, volume/volume (v/v)) in an aqueous solution; or isopropyl alcohol (formulated to 75%, v/v) in an aqueous solution;
  • Glycerin (glycerol) (1.45% v/v);
  • Hydrogen peroxide (0.125% v/v); and
  • Sterile distilled water or boiled cold water.

Compounders should also ensure that the active ethanol or isopropyl alcohol ingredient is correct, and the correct amount of the ingredient is used. If the compounder accepts one of these ingredients from another source, the compounder should test the active ingredient to ensure the methanol content does not exceed 630ppm. Further, the hand sanitizer should be prepared under conditions generally used by the compounder to compound similar nonsterile drugs. The product should also be produced as an aqueous solution, rather than a gel, foam or aerosol spray.

FDA implements interim process for communication record request finding

The FDA implemented an interim process to communicate issues identified in record reviews done in place of or in advance of preapproval inspections with drugmakers. Under normal circumstances, the agency would conduct preapproval or prelicense inspections prior to approving new drugs and biologics to ensure the facilities in which they are manufactured comply with current good manufacturing processes (CGMP). However, due to the ongoing COVID-19 pandemic, the FDA postponed most of these inspections, relying instead on alternative methods to conduct facility inspections. The new process was implemented to provide better opportunities for manufacturers to communicate issues arising from reviews conducted using these alternative methods.

The interim process was outlined in a guidance issued by the FDA, which provides answers to common questions regarding changes to the review process in light of the COVID-19 public health emergency. With respect to how the health emergency is impacting the inspection process, the FDA temporarily postponed all domestic and foreign routine surveillance facility inspections. In regard to preapproval inspections, the agency plans to continue using alternative tools and approaches whenever possible, such as requesting existing inspection reports from other trusted foreign regulatory partners, requesting information from applicants, and requesting records and other information directly from facilities and other inspected entities.

Some types of inspections will be deemed “mission critical” by the FDA, which will still be considered for inspection on a case-by-case basis. The agency’s assessment of whether an inspection is considered mission critical takes into account several factors relating to the potential benefits to the public by having access to the product that is the subject of the inspection. The factors include, but are not limited to, whether the product has received breakthrough therapy designation or regenerative medicine advanced therapy designation, or are products used to diagnose, treat or prevent a serious disease or condition for which there is currently no substitute. The agency will also take into account safety concerns in regard to inspectors, facility staff and, when applicable, clinical trial participants.

To ensure the quality of imported products while inspections are on hiatus, the FDA has implemented several alternative tools and approaches. These include physical examinations of products arriving at the U.S. border or product sampling and testing prior to release into commerce. Other methods include reviewing compliance histories of individual facilities and using information from trusted foreign regulatory partners. If a product appears to not meet applicable standards for safety, effectiveness or quality based on these alternative approaches, the FDA has the authority to refuse the product’s admission into the U.S.

The guidance also stresses that the FDA is using all available tools and sources of information to support regulatory decisions on applications that include facilities impacted by the postponement of inspections. The agency will continue quality assessments of all applications as normal for all disciplines. Further, all manufacturing facilities will be evaluated using the aforementioned alternative methods, in keeping with current guidelines. The FDA will also work directly with facilities to communicate any issues identified by such methods. Responses from a facility in regard to these issues will be considered by the agency where feasible, before it takes action on a pending application.