Today, from Revio, we would like to share with you a review of the Industry Guidance on manufacturing of cellular and gene therapy products (CGT) authorised by the Food and Drug Administration (FDA) during COVID-19 public health emergency.
This piece provides manufacturers with risk-based recommendations to minimize potential transmission of the coronavirus. These recommendations specifically consider the source material (cell and/or tissues) recovered from donor and how the CGT product will be manufactured (e.g., cell expansion in culture, viral reduction steps, formulation).
Respiratory viruses, in general, are known to be transmitted by implantation, transplantation, infusion or transfer of human cells, tissues, and cellular- or tissue-based products (HCT/Ps). FDA is not aware of any CGT products that have been contaminated with SARS-CoV-2 or of information indicating transmission of SARS-CoV-2 via these products. However, is a novel coronavirus and, to ensure compliance with current good manufacturing practice (CGMP) requirements, CGT manufacturers are expected to evaluate whether it poses new risks in the context of their specific products, facilities, processes, and manufacturing controls.
Additional concerns specific to establishments that manufacture CGT products may involve the potential for the unintended expansion of SARS-CoV-19 in autologous or allogeneic infected cells or tissues during the manufacturing process.
Risk assessment and mitigation
CGT manufacturers should review CGMP requirements related to facility and equipment cleaning and sanitation. In addition to other controls that ensure materials, active pharmaceutical ingredients (APIs), components, in-process materials, drug product container and closures, and drug products are safe and meet their quality requirements.
FDA recommends that CGT manufacturers perform a risk assessment and identifies, evaluates, and mitigates factors that may allow for transmission of SARS-CoV-2. The main aspects that should be included in the risk assessment should be:
Manufacturers of CGT products derived for HCT/Ps must determine and document the eligibility of a cell or tissue donor. FDA recommends routine screening measures be considered for autologous HCT/P donors, due to the potential for expansion of SARS-CoV-2 during the manufacturing process.
Manufacturers should consider whether the allogeneic or autologous donor:
- Cared for, lived with or had close contact with individuals diagnosed with COVID-19 infection,
- Had been diagnosed with COVID-19 infection,
- Had a positive test result for SARS-CoV-2 but never developed symptoms.
At this time, FDA recommends that establishments not screen for or defer HCT/P donors who have been vaccinated against COVID-19 with non-replicant, inactivated or RNA based COVID-19 vaccines.
Cellular or Tissue Source Material
Manufacturers should consider whether SARS-CoV-2 can infect and propagate in cells or tissues during certain manufacturing processes (e.g., cell/tissue culture). Manufacturers should also consider the risk of infection of the specific organ system (e.g., respiratory system vs. central nervous system) from which the donor cells or tissues are derived.
FDA recommends that manufacturers provide scientific justification and literature references to support their overall risk assessment and mitigation strategies.
Starting materials, manufacturing process used to control viral spread (e.g., cell expansion in culture, viral reduction steps, producer cell lines, controls for open systems), and contamination risk during manufacturing should be considered. Of note, SARS-CoV-2 has been shown to be capable of infecting and replicating in cells commonly used for vector production (e.g., HEK293 and Vero cells).
Manufacturers may include testing for HCT/P source material, cell banks, intermediates, final CGT products, or other relevant raw materials for SARS-CoV-2 as a risk mitigation strategy based on their assessment of potential risk.
CGT manufacturers must ensure that all evaluation of the production controls, as well as any follow-up and changed, are approved by the manufacturer’s quality unit. In addition, they must be documented in the manufacturer’s quality management system.
This is some of the information you need to know if you are interested in manufacturing of cellular and gene therapy products during this pandemic. Nevertheless, we have launched a dedicated webpage to bring you the latest updates, guidance, and developments. You can also follow us on LinkedIn.
We hope you find this useful and of interest. If you would like to discuss any of these updates with the team at REVIO, please get in touch here.
If you want to know more, check out the official guideline here.