Covid-19: Reference for COVID-19 viral control strategy in the biological manufacturing industry – industry position on the FDA guidance

This paper provides an in-depth exploration of the characteristics of SARS-CoV-2 (the virus) and COVID-19 (the disease). It also discusses how likely these may impact current control strategies that maintain product quality, safety and efficacy in the biopharmaceutical industry. It covers the areas that need to be assessed by biomanufacturers regarding SARS-CoV-2 risks for their patients, employees and products. Mitigation actions for the risks and associated benefits are also proposed. Just as importantly, it also discusses the areas that do not need to be evaluated – as current control strategies for endogenous and exogenous viruses, standards of work and the GMP framework are appropriate to prevent SARS-CoV-2 impacting on product. This is the case when the characteristics of SARS-CoV-2 do not make it unique when compared to the existing controls in place.

The FDA asked the biomanufacturing industry to review these specific topics:

Effectiveness of viral clearance steps and inactivation for COVID-19
Potential for cell lines to replicate COVID-19 (e.g. Vero, CHO, 324-K, MRC5)
Contamination of open process steps by COVID-19
Current methods for testing cell banks and harvest
Control/detection of sickness origin for sick staff (manufacturing and other)
Control/detection of incubation and sickness period for sick and asymptomatic staff
Limiting interpersonal contacts
Intensifying cleaning processes of facilities and equipment
Contamination of non-manufacturing facilities
Access to manufacturing facilities.

The team concluded that the existing controls in place for the first four areas are suitable and address the risk potential of SARS-CoV-2 contamination. This was based on a systematic review of current controls in BioPhorum member organizations and their knowledge of SARS-CoV-2 and COVID-19 in August 2020. However, the final six topics require additional controls and changes to current practices and standards of work, mainly for biomanufacturing sites but also other facilities. These extra controls can be summarized as:

Limiting the number of staff in the facilities
Ensuring staff at manufacturing sites and other facilities wear appropriate PPE (masks, gloves, etc.)
Increasing cleaning and sanitizing procedures and extending these into non-manufacturing areas
Screening individuals (e.g. questionnaires, temperature screening)
Ensuring the appropriate training of all staff
Ensuring appropriate social distancing and workspace design.

The team found that not all biologics pose or are exposed to the same risk of contamination. Those considered to be at a higher risk and requiring mitigations were added to the recommended control strategy.