By Rose Pagano and Suzanne M. Sensabaugh, MS, MBA 

Recently, the FDA released the guidance “Manufacturing Consideration for Licensed and Investigational Cellular and Gene Therapy Products During COVID-19 Public Health Emergency.” This guidance is meant to supplement the recommendations to drug and biological product manufacturers stated in the FDA’s “Good Manufacturing Practice Considerations for Responding to COVD-19 Infection in Employees in Drug and Biological Products Manufacturing; Guidance for Industry” that was published in June 2020. These new recommendations are for cells and tissues from donors and the manufacturing of cellular therapy and gene therapy (CGT) products. The products covered by this guidance are CGT products regulated by FDA, Center for Biologics Evaluation and Research (CBER) as biological products under section 351(i) of the Public Health Service Act and drugs under section 505 of the Federal Food, Drug, and Cosmetic Act. Also, the recommendations in this guidance will only remain in effect for the duration of the public health emergency related to COVID-19 that was declared by the Secretary of Health and Human Services.

During the COVID-19 public health emergency, CGT manufacturers need to review Current Good Manufacturing Practice (CGMP) requirements and recommendations related to facility and equipment cleaning and sanitation to ensure materials, active pharmaceutical ingredients (APIs), components, in-process materials, drug product containers and closures, and drug products are safe and meet their quality requirements. Due to COVID-19, the FDA suggests CGT product manufacturers perform a risk assessment to prevent the transmission of COVID-19 by CGT products. The risk assessment should be included in the appropriate submission to the FDA. In compliance with the quality risk management principles, drug manufacturers are supposed to prevent potential adverse effects on the safety and quality of their products. To minimize the transmission of COVID-19 transmission through CGT products, there should be an assessment of donors, cellular and tissue source materials, manufacturing processes, manufacturing facility control, product testing, and the number of subjects that can be treated with the product.

Regarding donor assessment, there should be routine screening measures that are already in place for evaluating clinical evidence of infection in allogeneic human cells, tissues, and cellular or tissue based products (HCT/P) donors. The FDA recommends that manufacturers consider whether, in the 28 days prior to HCT/P recovery, the allogeneic or autologous donor was in contact with someone who had COVID-19 or whether the donor has tested positive for COVID-19.

Concerning cellular or tissue source material, manufacturers should contemplate the characteristics of coronaviruses and their ability to infect and replicate in the source cells and tissues. It is important to consider if the coronavirus can infect and propagate in cells or tissues during processes like cell and tissue culturing. Also, the risk of coronavirus infection of the specific organ system from which the donor cells and tissue are derived from should be investigated. FDA advises that manufacturers give a scientific justification and literature references to support their overall risk assessment and present a proposed risk mitigation strategy.

The coronavirus has been shown to be capable of infecting and replicating in cells commonly used for vector production. To ensure compliance with CGMP requirements. CGT product manufacturers need to ensure employees execute good sanitation and health habits to prevent potential adverse effects on the safety and quality of drugs from an infected or potentially infected employee engaged in drug manufacturing.

Overall, FDA does not have specific recommendations for testing HCT/P source material or other relevant raw materials for SARS-CoV-2. However, manufacturers may include testing as a risk mitigation strategy based on their assessment of potential risk. To comply with CGMP requirements, CGT product manufacturers must ensure all evaluations of the production controls are approved by the manufacturer’s quality unit and documented within the manufacturer’s quality management system. CGT manufacturers should be aware that under section 501 (a)(2) of the FD&C Act, a drug that is not manufactured, processed, packed, or held in conformity with CGMP to assure that the drug meets certain quality standards is considered to be adulterated.


Nitisha Pyndiah - Biotech Consulting Services

Suzanne is the President and Principal Consultant of HartmannWillner LLC. She is an FDA regulatory affairs consultant who assists companies in advancing biologics, biosimilars, and biologic/device combination products through the FDA.

She formed HartmannWillner in 2009 as a regulatory affairs consultant. Since then, Suzanne has:

  • Assisted in the development of over 130 biologics, biosimilars, and biologic/device combination products
  • Conducted over 30 FDA GMP audits, including preapproval inspections (PAI), which allowed for FDA approval
  • Provided GMP compliance consulting to successfully address Form FDA 483 observations and Warning Letters
  • Prepared expert witness opinions and testimony in the areas of FDA regulatory affairs and GMP compliance
  • Wrote and reviewed hundreds of original INDs and BLAs and amendments and supplements