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/)
Posted by Dr. Tim Sandle
