The U.S. Food and Drug Administration (FDA) issued a guidance in June 2020 that sets forth recommendations for manufacturers of drug and biological products to ensure compliance with current good manufacturing practice (cGMP) requirements in response to employees who test positive for COVID-19, including implementation of manufacturing controls, risk assessment of impact on drug safety and quality, and measures for maintaining continuity in drug supply.

This guidance is relevant for all drug and biological product manufacturing entities that are registered with FDA and are subject to cGMP requirements, including:

• Facilities that make human or animal active pharmaceutical ingredients (APIs), prescription drugs, over-the-counter drugs, or biological drug products;
• Outsourcing facilities registered with the FDA under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act), and
• Compounding pharmacies regulated under section 503A of the FD&C Act.

This guidance does not apply to state-licensed compounding pharmacies and federal facilities that are not required to register with the FDA, although the FDA recommends that such compounders to also implement additional controls and processes to prevent and correct potential contamination and insanitary conditions.

For facilities that are registered with the FDA and subject to the cGMP requirements, the FDA sets forth various recommendations, including the following:

I. Manufacturing controls to prevent contamination of drugs and biologics

• Monitor employees who perform manufacturing functions for COVID-19 (regardless of symptoms) and restrict or exclude such employees from production areas until the criteria for discontinuation of isolation for persons with COVID-19, as described in an interim guidance by the Centers for Disease Control and Prevention (CDC), have been satisfied and in consultation with a healthcare provider.
• Ensure that employees are practicing good sanitation and hygiene habits, including compliance with personnel duties and hygiene requirements under cGMP regulations such as 21 CFR 211.28(d) and 21 CFR 600.10(c)(1).
• Evaluate the adequacy of cGMP controls to protect materials, components, drug container closures, in-process materials, and/or drugs from sick employees.
• Risk assessment of current viral control strategy and, if needed, implement more stringent viral controls for biological products, including whether cell bank and harvest testing for viral contamination would detect the COVID-19 virus, or SARS-CoV-2, potential for cell lines to replicate SARS-CoV-2, and effectiveness of viral clearance and inactivation steps for SARS-CoV-2.
• Implement more frequent cleaning, sanitization, and/or sterilization procedures for production areas and surfaces as well as non-production areas.
• Expand the use of gloves, face masks, and/or gowning where such measures were not previously required.
• Further restrictions on employee access to manufacturing area to prevent or mitigate potential contamination.

II. Risk assessment of COVID-19 impact on drug safety, quality, and disposition

• Evaluate whether COVID-19 poses new risks in the context of manufacturers' specific drugs, facilities, processes, and manufacturing controls, including taking into consideration known characteristics and studies of viruses within the same family as well as drug types and characteristics.
• Ensure that all such evaluations and risk assessments, follow-ups, and changes are approved by the manufacturer's quality unit and documented within the quality management system.
• Implement procedures for determining lots or batches of components, drug product containers and closures, in-process materials, APIs, or drug products that are adversely affected in terms of safety and quality and proper disposition of such products (e.g., quarantine for re-evaluation, reprocessing, or rejection).

III. Continuity of manufacturing operations

The FDA also reminds that employees of drug manufacturers have been deemed essential critical infrastructure workers during the COVID-19 public health emergency and cites various resources and guidance documents from the CDC, Environmental Protection Agency (EPA), and Occupational Safety and Health Administration (OSHA) regarding general strategies for minimizing exposure and transmission in the workplace and safety practices for critical infrastructure workers, including:

The FDA recommends manufacturers of medically necessary human drugs to implement contingency plans in the event of high absenteeism during the COVID-19 public health emergency, as described in its 2011 guidance. For example, quarantined and recovering employees may be permitted to work remotely on certain manufacturing functions if the manufacturer's data and record management system supports such remote functions, e.g., batch record and analytical record review and investigations.

FDA also provided email addresses for drug shortage notification and reminds manufacturers to contact the agency immediately if measures taken to prevent or mitigate adverse effects on safety and quality of drugs are likely to lead to a disruption in the drug supply, e.g., rejection of lots or recalls.