Wednesday, 15 July 2020

FDA: GMP and COVID-19


The U.S. FDA has published guidance (dated June 19, 2020) detailing the agency’s recommendations for current good manufacturing practices (CGMP) requirements for addressing COVID-19 infection in employees engaging in drug manufacturing. The guidance was issued to help mitigate and prevent effects on drug safety and quality by employees confirmed to be either infected with COVID-19 or potentially exposed to someone with COVID-19.
According to FDA:

“As with any potential new risk, FDA expects pharmaceutical manufacturers to evaluate whether SARS-CoV-2 poses contamination risks under existing manufacturing controls that prevent drug contamination and whether the virus adversely impacts drug safety or quality should contamination occur”.

Some of the recommendations presented in the guidance document are to prevent contamination of drugs from COVID-19-infected employees include cleaning and sanitizing non-production areas more frequently; updating cleaning and sanitizing procedures for production areas; expanding existing procedures to include gloves, face masks, and/or gowning if not already in place; and restricting employee access to manufacturing areas.

The document is titled ‘Good Manufacturing Practice Considerations for Responding to COVID-19 Infection in Employees in Drug and Biological Products Manufacturing - Guidance for Industry’. At: https://www.fda.gov/media/139299/download

What does it say?

COVID-19 specific:

1.      Each manufacturer must have a COVID-19 risk assessment in place, approved by Quality.
2.      Drug manufacturers must 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.
3.      Personnel who either test positive for COVID-19 (regardless of whether they have symptoms) or have symptoms of COVID-19 must be excluded from drug manufacturing areas.
4.      Employees in ‘1’ or ‘2’ above must practice self-isolation. FDA only accepts CDC measures rather than national health agencies.
5.      All employees must practice good sanitation and health habits.
6.      Each manufacturer must:
a.       Evaluate the adequacy of the GMP controls already in place to protect materials, components, drug container closures, in-process materials, and/or drugs from sick employees in the context of this new coronavirus. 
b.      Manufacturers must review cleanroom process controls such as air filtration, positive air pressure and movement of air to ensure proper function.  This may mean faster responses when cleanroom control measures breakdown.
c.       Manufacturers must consider the likelihood of contamination or cross-contamination to other drugs in the facility. 
d.      Current microbiological controls like closed system processing (isolators) should be sufficient to protect the drugs. Where the is no barrier technology in place, additional controls may be required to eliminate or minimize the risk of contamination.
e.        Potential risks from SARS-CoV-2 are likely to be mitigated by existing viral control strategies.  However, FDA recommends that manufacturers perform a risk assessment of the current viral control strategy in light of SARS-CoV-2 and implement appropriate mitigation strategies.
                                                              i. Drug manufacturers should determine if SARS-CoV-2 could adversely affect the safety or quality of their materials, components, drug product containers and closures, in-process materials, and drugs if they were to become contaminated with the virus. 
                                                            ii. The risk assessment should consider the known characteristics and studies of this family of viruses as well as the drug types and their characteristics (e.g., drug product or API, sterile, non-sterile, solids, powders, liquids, large or small molecule).
f.        Additional controls need to be in place for procedures taking place in open systems (e.g., buffer and culture media preparation areas).
g.      Manufacturers must 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.
h.      Manufacturer must clean and sanitize nonproduction areas (such as offices, elevators, break rooms, changing rooms, and restrooms) more frequently. 
i.        Manufacturers should consider expanding existing procedures to include using gloves, face masks, and/or gowning where such measures were not previously required.
j.        Manufacturers should consider further restrictions on employee access to any manufacturing area, beyond that required by GMP regulations, to limit the possibility of contamination.
k.      If a potential or actual viral contamination event is identified, drug manufacturers must promptly clean, disinfect, sanitize, and if necessary, sterilize affected equipment, surfaces, production areas, and facilities, before resuming manufacturing. 
l.        If supplies of single-use masks and other garb used to control contamination during manufacturing are low, they should be prioritized for use in sterile manufacturing operations.


General advice:

1.      Any person shown at any time shown 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.
2.      All personnel must report to supervisory personnel any health conditions that may have an adverse effect on drug products. 
3.      Companies must provide adequate facilities to ensure the orderly handling of materials and equipment.
4.      Companies must put in place measures to prevent mix-ups.
5.      Measures must in place to prevent the prevention of contamination of equipment or product.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

No comments:

Post a comment

Pharmaceutical Microbiology Resources

Special offers