APR Nov/Dec 2022 - 54

» MANUFACTURING
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process validation records, standard operating procedures, and
product complaints, among many other examples.
FDA has stated it will use a risk-based approach to determine which
establishments to initiate or request RRAs, considering " firm location,
inspection history, complexity of product and process, and travel
restrictions. " 27
serious problems prior to FDA inspections, and recommended that
FDA should adopt a pilot plan for unannounced foreign inspections to
ensure inspection integrity.36
Arriving unannounced, particularly after
FDA has also begun factoring more up-to-date data
from its quality metrics program and other sources in its risk-based
inspection prioritization system since the pandemic.28
Historically, FDA
has relied only on facility scores (which consider factors such as type
of establishment, number of products manufactured, and inspection
history), product scores (which consider factors such as type of
product, dosage form, and sterility), and time since last inspection
in determining which sites to inspect.29
Due to decreased resources
and opportunities during the pandemic, FDA has sped up modifying
its risk-based inspection scheduling model to incorporate risk scores
that rely on additional quality metrics and other data, such as more
precise facility types, geographical locations with higher compliance
rates, recall and inspectional history, and results from inspections
conducted by foreign regulators.30
Second, FDA began to increasingly rely on information and reports
from international regulatory bodies. FDA is statutorily authorized to
rely on information and observations collected by competent foreign
regulatory authorities through mutual recognition.31
While mutual
recognition has existed in the U.S. since 2014 and for longer in the
European Union, the agency rarely relied upon mutual recognition
prior to the COVID-19 pandemic.32
Mutual recognition provides
regulators greater efficiency and allows agencies to synchronize
inspection schedules and allocate sufficient resources toward higher
risk inspections, without duplicating efforts. Because of these strategic
benefits, FDA will likely continue to take into account inspections
conducted by other international regulators, and companies should
prepare for all inspections with the same level of readiness. The
expansion of mutual recognition is part of FDA's larger goal to globalize
its inspection program, by facilitating greater coordination and
oversight of medical products among foreign regulatory bodies.33
FDA
believes that information sharing with competent foreign regulatory
bodies will allow it to become " more efficient " and the " industry can
implement innovations and quality systems in a more rapid and
effective manner. " Going forward, FDA is considering expanding the
scope of mutual recognition with the UK and EU to include vaccines
and plasma-derived pharmaceuticals.34
Third, FDA has begun conducting unannounced inspections of foreign
manufacturers. Prior
to the COVID-19 pandemic,
facilities based
outside of the U.S. were typically provided with advance notice of
an upcoming inspection, sometimes as much as three months' time.
FDA initially began performing unannounced foreign inspections
during the pandemic following criticism from the industry that
notice to international facilities can " harm an FDA inspector's ability
to get transparent information about a company's standard operating
practices. " 35
A report from the U.S. Government Accountability Office
( " GAO " ) noted the issue of establishments quickly fixing potentially
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the long the delays in time between inspections due to the pandemic,
certainly bolsters the credibility of the foreign inspection program.
In response, FDA has begun to conduct unannounced inspections
in India, with plans to expand to China, where FDA already has field
offices and inspection staff.37
FDA stated the unannounced inspection
program was launched in India first since foreign inspections in certain
parts of China are still paused due to local COVID-19 restrictions.38
Regarding other parts of the world, in January 2022, the Creating
Efficiency in Foreign Facility Inspections Act, S. 3509 was introduced in
the United States Senate, proposing to expand FDA's ability to perform
unannounced inspections of foreign facilities. While this would
strengthen FDA's mandate, logistical challenges for FDA investigators
such as arranging travel and securing visas would remain.
Now that the COVID-19 pandemic has begun to subside in 2022 and
public health measures such as travel restrictions are largely lifted,
FDA has resumed onsite inspections. However, the agency continues
to use the inspectional techniques it piloted during the pandemic
and rely on updated quality data metrics to focus its resources on
inspections of highest risk to the public health.39
The new approach
offers significant advantages which FDA can benefit from beyond the
pandemic for all types of FDA-regulated products. FDA has stated that
its revised approach will enhance oversight and " improve [...] the
efficiency of how [they] operate, furthering [their] mission to protect
the public health. " The adoption of these inspection techniques also
reflects FDA's " modernization effects " in implementing " advanced
tools, including technology. " 40
Conclusion
In light of FDA's updated inspectional approach, pharmaceutical
manufacturers should also update and revise their standard operating
procedures on inspection management. With increased visibility to
manufacturers through remote review and information sharing, it
is highly likely that an FDA investigator's first impression of a facility
will occur before their arrival. This also means that documents such as
manufacturing and data integrity-related investigations and reports,
which are typically viewed onsite, are now particularly susceptible
to advance review. Regulators may use these documents to prepare
for an upcoming inspection or base regulatory decisions solely on
them. Manufacturers should, as a result, consider creating or updating
policies
related to FDA record requests and remote interactive
evaluation requests. Companies should prepare in advance for the
disclosure of challenging manufacturing deviations discovered
over the past few years and be in position to explain the corrective
and preventive measures taken to demonstrate sustainable cGMP
compliance. Finally, practicing how to handle, manage, and respond
to an unannounced inspection helps, and companies should conduct
regular " mock audits " and document reviews to stay in a state of
APR Nov/Dec 2022

Table of Contents for the Digital Edition of APR Nov/Dec 2022
