6 BioPharm International eBook September 2019 www.biopharminternational.com
Regulatory Sourcebook Compliance Report Card
months of FDA's fiscal year 2019
(ending September 30).
The spike in recalls may be par-
tially attributed to the identification
of trace nitrosamine contamination
in three commonly used medicines
during the past year: angiotensin
II receptor blockers in 2018, the
diabetes treatment pioglitazone in
April 2019, and rantidine, a hista-
mine-2 blocker in September 2019.
Inspections are the primary method
regulatory authorities use to identify
manufacturing and quality prob-
lems. Bet ween 20 09 –2018, FDA
inspected, on average, more than
4500 drug and biologics facilities
annually. For fiscal year 2019, the
number of inspections appear to be
down, with only 2733 inspections
reported through early August 2019.
The number of inspections at
domestic drug facilities has declined
since 2010; from 2010 –2012, an
average of more than 2000 annual
inspections were conducted. Only
1325 inspections of US-based drug
facilities were reported in 2018.
The number of foreign inspections
almost doubled from 541 in 2009
to 1005 in 2018; however, fewer
than 600 foreign inspections had
been conducted through the first 10
months of FDA's fiscal year 2019.
Meanwhile, the number of FDA
inspections of biologics facilities—
both domestic and foreign—has
held steady for the past 10 years,
and these biologics facilities out-
performed drug facilities in inspec-
tion results. More than 80% of
inspections at biologics facilities
resulted in no action indicated
(NAI) classification; less than 1%
of facilities inspected were classi-
fied as official action indicated. For
drug facilities, only 47% received
an NA I classif ication; a similar
number received a voluntary action
indicated (VAI) classification.
Overall, US-based facilities man-
ufac t ur ing dr ugs and biolog ics
outperformed foreign facilities. Two-
thirds of US facilities received a NAI
classification compared with 42% of
foreign facilities. More than half of
the foreign facilities received a VAI
classification; more than 5% were
cited for official action indicated.
NEW INSPECTIONS AND PROTOCOLS
Recog ni zing t he need to sta n-
dardize its inspection data col-
lection and analysis, FDA, in late
2018, announced a New Inspection
Protocol Project (NIPP), that uses
standardized electronic inspec-
tion protocols to report the data
from surveillance and pre-approval
inspections (3).
S t e r i l e d r u g p r o d u c t s w e r e
selected for the first NIPP due to
ongoing quality issues with the
manufacture of this dr ug t y pe.
The agency conducted pilot stud-
ies and incorporated feedback to
develop protocols to cover critical
areas of sterile drug manufacturing
and provide data to quickly support
quality decisions. Other programs
will address non-sterile tablets/cap-
sules; bulk powders; transdermal
drug delivery; creams, ointments,
and solutions; metered dose inhal-
ers; terminally sterilized drugs; and
active ingredients.
ESTABLISHING
A QUALITY CULTURE
When a drug company is cited for
a quality violation, the blame often
is directed to the quality team or
offending manufacturing, mainte-
nance, or analytical unit. A qual-
it y c u lt u re shou ld be adopted
throughout an organization, said
Patrizia Cavazzoni, deputy direc-
tor of operations at FDA's Center for
Drug Evaluation and Research at the
PDA/FDA conference (4).
Executive management is ulti-
mately responsible for assuring reli-
able manufacturing operations and
high-quality standards. Inspections
reveal a "notable difference: when
top management embraces qual-
ity," Cavazzoni said.
Organizations should plan for
and design quality into all systems,
invest in manufacturing technolo-
gies, guard against decay in opera-
tional effectiveness, and ensure
suppliers are aligned with your
quality practices, she recommended.
ABOUT THIS EBOOK
U n d e r s t a n d i n g — a n d k e e p i n g
informed—about the many regu-
lations, compendial requirements,
and guidelines present challenges
for bio/pharmaceutical companies.
In the premiere issue of this
BioPharm International Regulatory
S o u r c e b o o k , t h e e d it o r s p r e s -
ent recent regulatory trends and
enforcement actions, a critique of
the effectiveness of good manu-
fac t ur ing prac tices reg ulations,
and insight on biosimilar quality
requirements. A focus of this ebook
is the first installment of a com-
prehensive series on compendial
compliance, including a detailed
analysis of the impact of pharma-
copoeia requirements, challenges
with compliance, and why harmo-
nization is needed.
The ebook also includes links
to pertinent guidance documents,
contact information for global reg-
ulatory authorities, and other tools
to aid in compliance.
REFERENCES
1. 2019 PDA/FDA Joint Regulatory
Conference, Washington, DC, Sept. 16,
2019.
2. FDA, Data Dashboard, https://
datadashboard.fda.gov/ora/index.htm,
accessed Sept. 19, 2019.
3. FDA, "Statement from FDA Commissioner
Scott Gottlieb, M.D., on New Steps to
Strengthen and Modernize Agency's
Oversight and Reporting of Inspections
for Sterile Injectable Drugs," www.fda.gov,
Nov. 9, 2018.
4. P. Cavazzoni, "Advancing Drug Innovation
Through Investment in Quality,"
Presentation, 2019 PDA/FDA Joint
Regulatory Conference, Sept. 16, 2019,
Washington, DC.
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