Regulatory Update on GMP in response to COVID-19

FDA published guidance to address the COVID-19 public health emergency – “Good Manufacturing Practice Considerations for Responding to COVID-19 Infection in Employees in Drug and Biological Products Manufacturing”

The Guidance was issued to provide recommendations for following.

  • Manufacturing controls to prevent contamination of drugs: Drug manufacturers are expected to prevent or mitigate potential adverse effects on the safety and quality of drugs from an infected or potentially infected employee engaged in drug manufacturing. During the COVID-19 public health emergency, drug manufacturers should review the following current good manufacturing practice (CGMP) regulations and recommendations regarding restriction of sick employees from production areas.
  • For drug products, 21 CFR 211.28(d), “Personnel responsibilities,” requires that: Any person shown at any time (either by medical examination or supervisory observation) to have an apparent illness or open lesions that may adversely affect the safety or quality of drug products shall be excluded from direct contact with components, drug product containers, closures, in-process materials, and drug products until the condition is corrected or determined by competent medical personnel not to jeopardize the safety or quality of drug products. All personnel shall be instructed to report to supervisory personnel any health conditions that may have an adverse effect on drug products.
  • For active pharmaceutical ingredients (API), the ICH guidance for manufacturing of API is same as drug products requirements in the US Code of Federal Regulations.
  • For positron emission tomography (PET) drugs, 21 CFR 212.30, “What requirements must my facilities and equipment meet?” states: (a) Facilities. You must provide adequate facilities to ensure the orderly handling of materials and equipment, the prevention of mix-ups, and the prevention of contamination of equipment or product by substances, personnel, or environmental conditions that could reasonably be expected to have an adverse effect on product quality.
  • For biological products, 21 CFR 600.10(c)(1), “Restrictions on personnel – (1) Specific duties,” states: Persons whose presence can affect adversely the safety and purity of a product shall be excluded from the room where the manufacture of a product is in progress.

The guidance also recommends that Drug manufacturers should vigilantly monitor employees who perform drug manufacturing functions and have been exposed to others with confirmed or suspected COVID-19 for symptoms of COVID-19 infection.

  • Risk assessment of SARS-CoV-2 as it relates to drug safety or quality: The guidance recommends to follow the quality risk management principles in accordance with ICH Q9.
  • Review cleanroom process controls such as air filtration, positive air pressure and movement of air to ensure proper function.
  • Consider the likelihood of contamination or cross-contamination to other drugs in the facility
  • Current microbiological controls, if strictly implemented (e.g., employees only work in area with closed system processing), may be sufficient to protect the drugs and materials used to make them from SARS-CoV-2 contamination.
  • For biological products where manufacturing processes or materials are more susceptible to viral contamination, manufacturers should already have stringent viral control strategies in place. Potential risks from SARS-CoV-2 are likely to be mitigated by existing viral control strategies.
  • To help prevent transmission among employees and contamination of drugs/materials by a COVID-19-infected employee engaged in drug manufacturing at the workplace, drug manufacturers should:
  • Clean and sanitize nonproduction areas (such as offices, elevators, break rooms, changing rooms, and restrooms) more frequently.
  • Update existing procedures to institute more frequent cleaning, sanitization, and/or sterilization of surfaces in the production areas, particularly surfaces that are contacted frequently, such as door handles, equipment latches, bench/counter tops, and control panels. Special attention should be paid to sanitizing/sterilizing equipment and product contact surfaces.
  • Consider expanding existing procedures to include using gloves, face masks, and/or gowning where such measures were not previously required.
  • Consider further restrictions on employee access to any manufacturing area, beyond that required by CGMP regulations and recommended by Agency guidance and normal practice, to limit the possibility of contamination.
  • Continuity of manufacturing operations: To maintain the drug supply, the drug product manufacturers need to take necessary steps recommended steps to prevent any contamination from COVID-19. If steps taken to prevent or mitigate adverse effects on safety and quality of drugs (e.g., rejected lots or recalls) are likely to lead to a disruption in the drug supply, drug manufacturers of human drugs should immediately contact FDA.