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Current Good Manufacturing Practices in the Time of COVID-19: FDA Announces New Expectations on Risk Assessment and Risk Management

FDA recently published its “Good Manufacturing Practice Considerations for Responding to COVID-19 Infection in Employees in Drug and Biological Products Manufacturing Guidance for Industry” (“Guidance”) which provides suggestions on managing the potential risk of products being contaminated by SARS-CoV-2, the virus behind COVID-19 infections for drug and biological product manufacturers, 503B outsourcing facilities, and 503A compounding pharmacies.

The Guidance builds on the current Good Manufacturing Practices (cGMPs) regulations for drugs and biological products, which require personnel with an illness that could adversely affect drug safety or quality be excluded from direct contact with drugs and drug components used in manufacturing.[1]  As the Guidance states, preliminary research indicating that SARS-CoV-2 “is stable for several hours to days in aerosols and on surfaces,” and that it has an incubation period of 2 to 14 days, which are both factors that increase the risk of spread and introduction into products.  The actual health risk is hard to calculate – FDA itself notes that there have not been documented transmissions through pharmaceuticals to date.  The regulatory risk, however, is an easier formula – FDA has a clear expectation that drug and biological product manufacturers evaluate the potential for COVID-19 contamination of their products under existing controls, or risk being out of compliance with cGMPs.

The Guidance focuses heavily on undertaking a risk assessment of current systems to understand how effectively the firm can manage the risk of SARS-CoV-2 contamination, and augmenting systems as necessary to minimize risk.  Key recommendations from the guidance are summarized below.

  1. Documentation is essential. FDA makes a point to emphasize the risk assessment and risk management activities that are being done to address COVID-19 should be documented consistent with cGMP requirements.  The emphasis on this point could foreshadow FDA investigators looking into COVID-19 responses on their next visit.

  2. Manage personnel appropriately. Remove individuals who have or are most likely to have COVID-19 from activities where they could contaminate products and equipment, or make other employees ill.  For those who have been potentially exposed to an infected individual, continued monitoring of health is crucial.  Although not stated in the Guidance, an element of monitoring could be establishing a COVID-19 screening program on-site or in conjunction with a clinical laboratory.

  3. Evaluate the adequacy of the cGMP controls already in place. These controls limit contamination and cross-contamination of drug components as the result of SARS-CoV-2 transmission from employees.  This should include a review of controls related to facility and equipment cleaning and sanitation and other controls that ensure materials, APIs, components, drug product containers and closures, in-process materials, and drug products are safe and meet their quality requirements.  For example, reviewing cleanroom process controls such as air filtration, positive air pressure and movement of air to ensure proper function, and current microbiological controls would all be essential.

Manufacturers of biological products – which are naturally more susceptible to viral contamination – may be ahead of the curve in terms of having systems in place, but a thorough evaluation is recommended for all manufacturers.

  1. As needed, in addition to any other gaps that are identified, consider taking the following steps to improve cleaning, sanitization and personnel management:

    1. Clean and sanitize nonproduction areas (such as offices, elevators, break rooms, changing rooms, and restrooms) more frequently.

    2. Update existing procedures to institute more frequent cleaning, sanitization, and/or sterilization of surfaces in the production areas, particularly surfaces that are contacted frequently, such as door handles, equipment latches, bench/counter tops, and control panels. Special attention should be paid to sanitizing/sterilizing equipment and product contact surfaces.

    3. Expand existing procedures to include using gloves, face masks, and/or gowning where such measures were not previously required.

    4. Further restrict employee access to any manufacturing area, beyond that required by cGMP regulations and recommended by Agency guidance and normal practice, to limit the possibility of contamination.

Although not discussed in the Guidance, environmental testing programs, which look for SARS-CoV-2 in high-touch areas also could be helpful to managing risks.

The Guidance addresses actions that manufacturers should take if lots or batches of product are determined to be adversely affected by SARS-CoV-2, although FDA recognized that it is not aware of any such contamination to date.

Further, the Guidance addresses steps that manufacturers should take to mitigate the risk of product shortages due to an outbreak, including requiring social distancing and allowing recovering personnel to perform certain functions remotely (e.g., batch record review).

Though the focus of the Guidance is on traditional manufacturers that are subject to cGMP requirements, FDA also makes a point of reminding 503A drug compounding facilities that even though they are not subject to cGMP requirements, their products are subject to the general adulteration provisions against contamination.  Given that compounded medications are often produced “on-demand” and used soon after preparation while live virus could be present on products, limiting the risk of contamination could be very important, and the guidance from FDA helpful in that regard.

[1] See, e.g., 21 CFR 211.28(d).

©2020 Epstein Becker & Green, P.C. All rights reserved.National Law Review, Volume X, Number 181


About this Author

James Boiani Healthcare Attorney Epstein Becker Green Law Firm
Member of the Firm

JAMES A. BOIANI is a Member of the Firm in the Health Care and Life Sciences practice, in the firm's Washington, DC, office. He has extensive experience in FDA and CLIA legal and regulatory matters, having worked with large and small medical device companies (including many in vitro diagnostic companies), pharmaceutical companies, clinical laboratories, and trade associations in the life sciences industry on a variety of FDA- and CLIA-related issues.

Mr. Boiani's practice focuses on the following:

  • Advising on FDA compliance matters, with an...

DELIA A. DESCHAINE is a Member of the Firm in the Health Care and Life Sciences practice, in the firm’s Washington, DC, office. Named to the Washington DC Rising Stars list (2018-2020) in the areas of Food & Drugs and Cannabis Law, Ms. Deschaine understands the most significant U.S. Food and Drug Administration (FDA) and U.S. Drug Enforcement Administration (DEA) legal and compliance risks that her clients face and knows how to address them. Her advice is informed by a background in defending clients in government enforcement actions and challenging unlawful government conduct.

Ms. Deschaine’s experience includes:

  • Counseling pharmaceutical and biotechnology companies, such as manufacturers, wholesalers, pharmacies, researchers, and others on their regulatory obligations under the federal Food, Drug, and Cosmetic Act (FDCA) and the Controlled Substances Act (CSA), including compliance with current Good Manufacturing Practices (cGMP) and the DEA's expectations related to suspicious order monitoring, registration, recordkeeping, security, and reporting
  • Advising clients on the federal and state regulation of cannabis, including hemp and hemp-derived products
  • Counseling clients on the federal and state regulation of controlled substances, with a focus on the manufacture, distribution, and dispensing of opioids, and assisting clients in controlled substance scheduling-related matters
  • Helping clients respond to problematic FDA inspections, including responding to Form FDA 483s and Warning Letters
  • Assisting clients in developing, implementing, and managing corrective action plans
  • Counseling on the requirements of cGMP as they apply to aseptic processing, quality risk management, supplier management, and data integrity, and conducting cGMP compliance audits
  • Advising clients on compliance with state pharmacy laws, including licensing requirements
  • Conducting internal investigations, and defending clients in administrative, civil, and criminal investigations under the CSA, the Combat Methamphetamine Epidemic Act (CMEA), and the FDCA
  • Performing regulatory due diligence, and reviewing and revising agreements in corporate transactions

Before joining Epstein Becker Green, Ms. Deschaine was a pharmaceutical and biotechnology regulatory lawyer at an international law firm. Previously, she was an attorney at a prominent boutique FDA regulatory law firm in Washington, DC, where she represented pharmaceutical, medical device, and biotechnology companies in FDA and DEA enforcement actions and litigation. Earlier in her career, through the U.S. Attorney General’s Honors Program, she served as an Attorney Advisor for the DEA, where she received a Performance Award in 2011.

In law school, Ms. Deschaine served as a lawyer advocate for a public interest organization, focusing on remedying the legal and systemic barriers that prevent access to addiction treatment services. She was also a legal intern for Magistrate Judge Susan K. Gauvey of the U.S. District Court for the District of Maryland.