FDA Releases Pandemic Recommendations for Cell and Gene Therapy Makers

The FDA is calling for risk assessments by cell and gene therapy (CGT) manufacturers to minimize the potential for transmitting the SARS-CoV-2 virus through their products, according to a new straight-to-final guidance released yesterday.

The agency’s advice specifically relates to source material taken from donors — cells and/or tissues — and how manufacturers produce their cell and gene therapy (CGT) products. The guidance notes that while FDA has not encountered any such products that have been contaminated with the virus, it expects manufacturers to conduct evaluations to find out if the coronavirus poses risks to their products, facilities, processes and manufacturing controls.

Manufacturers should perform a risk assessment aimed at identifying, evaluating and mitigating factors that could allow viral transmission through their products, the agency recommends, adding that the risk assessment and mitigation strategies should be described in investigational new drug applications, biologics license applications and master files.

For example, CGT manufacturers should consider introducing routine screening measures for donors of human cell, tissue, and cellular- or tissue-based products (HCT/Ps). Currently, the agency recommends that manufacturers consider, in the 28 days prior to accepting HCT/Ps, if the donor:

• Cared for, lived with or was in close contact with individuals diagnosed with or suspected of having COVID-19 infection;
• Had been diagnosed with or was suspected of being infected; or
• Had a positive test result from an authorized diagnostic for COVID-19 but never developed symptoms.

The agency says it doesn’t currently recommend screening asymptomatic donors with laboratory tests. If a manufacturer does choose to screen for COVID-19, they should use authorized molecular or antigen tests. Additionally, the agency recommends not screening donors that have been vaccinated against the virus.

Manufacturers should also consider the ability of SARS-CoV-2 virus to infect and multiply in source cells and tissues, as well as whether the virus can infect and propagate in cells or tissues during certain manufacturing processes, such as cell/tissue culture. They should also consider the risk of infection of the specific organ used as the source of the donor cells or tissues.

For manufacturing, firms should consider starting materials, manufacturing processes used to control viral spread (cell expansion in culture, viral reduction steps, producer cell lines and controls for open systems) and risks of contamination. The agency notes that the coronavirus has demonstrated the ability to infect and replicate in cells commonly used for vector production.

The guidance also explains that while the FDA does not have specific recommendations for testing HCT/P source material, cell banks, in-process intermediates, final products or other raw materials for the virus, manufacturers may include such testing as a risk mitigation strategy.

The agency said comments can be submitted on the guidance at any time.

Read the full guidance here: www.fdanews.com/01-20-21-Guidance.pdf. — James Miessler