WHITE
PAPER
Data Integrity Is At The Heart Of Laboratory Compliance
Authors
Angelo Filosa, Global Head of Scientific Services
Paul A. Coombes, Global Product Manager, OneSource
Qualification Services
Jim Willis, Director Validation and Compliance Services, Americas
PerkinElmer, Inc.
“Prove It,” Regulators Say
Walter Deming, the legendary physicist and management
consultant, once described research this way: “Uncertainty
makes research predictable, but you still need proof to satisfy
everyone else.”1 In a sentence, Deming perfectly describes why
compliance management in government regulated industries
such as food, pharmaceuticals, biologics, cosmetics, and medical
devices is now so dependent upon metrology, or the science of
measurement. When it comes to manufacturing products that
can affect public health, scientists need to prove the integrity
of their data or risk having their laboratories cited or even shut
down, as occurred with a number of offshore pharmaceutical
companies in 2013.2
Thanks to evolving and oftentimes complex guidelines at
global regulatory agencies such as the U.S. Food and Drug
Administration (FDA), the UK’s Medicines and Healthcare
Products Regulatory Agency (MHRA), and the European
Medicines Agency (EMA), analytical laboratories are encountering
a whole new regulatory mindset during the audit process.
Last year, for instance, the FDA reviewed thousands of analytical
reports, conducted hundreds of on-site inspections, and took
action against more than 200 out-of-compliance companies
for a variety of reasons.3
says it stands for ‘current’ and requires companies “to use
technologies and systems that are up-to-date in order to
comply with the regulations.”5 What was state-of-the-art only
a few years ago may now be inadequate by today’s standards,
the FDA advises… and there lies the rub. There are differing
interpretations of what “current” really means and there are no
definitive resources available to settle the inevitable disputes.6
Paper versus computer data is a perfect example. Over the
past few years, regulatory agencies have determined that
electronic data is more secure and less likely to be manipulated
when tracking the lifecycle of products and processes. On the
other hand, it may be simpler to print out chromatograms to
paper, but these are no longer considered by the FDA as a
“true copy” or “exact and complete” record of the entire
electronic raw data, since it does not capture all the required
raw data and metadata.7
Even electronic lab data can have its problems. It needs to be
compliant to the USA law 21 Code of Federal Regulations Part 11
and the European Union law EDQM Annex 11. Good Automated
Manufacturing Practice (GAMP5) is useful industry-written
guidance for computer system validation practitioners. Among
other common errors labs make with electronic data include:
According to one industry expert, the preparations that labs
have traditionally taken in preparing for these audits are no
longer adequate. The focus is increasingly shifting beyond the
validation of procedures, instruments, and personnel training
and towards the integrity of data. The “who,” “what,” “when,”
and “where” of that data’s development are now all fair game
for probing regulators intent on detecting fraud of any kind at
any stage in a product’s development.4
• Access control errors (login, password, etc.),
Defining “Current”
Any one of these can lead to information gaps that may be
difficult, if not impossible, to explain to auditors.8
If that all seems a bit intimidating, it certainly can be if FDA
auditors believe that a lab is out of compliance with Current
Good Manufacturing Practice (cGMP) regulations. In many
respects, it actually all starts with the “C” in cGMP. The FDA
• Lack of permissions,
• No audit trails,
• No electronic signatures,
• Improper or no back up,
• No disaster recovery.
The Importance Of Transparency
No one ever said it was easy. Regulators are constantly
issuing draft guidance directives with major implications on
pharmaceutical research, production, control, and, inevitably,
human health.9 Many of these directives are general in their
wording—some say even vague—to accommodate the vast
number of different companies and exceptions to the rule
within the industry.10
In 2011, for example, the FDA issued guidance for process
validation to clarify its expectations on pharmaceutical production
and control processes. In doing so, it allowed companies to
develop what works best in their particular circumstances so long
as regulatory standards are met. Most Big Pharma companies
responded with the adoption of comprehensive suites of
instrument qualification and software validation protocols to
provide more transparency into their own research practices,
manufacturing processes, and product outcomes. While companies
and their customers benefit from the added insights these
systems provide, their primary objective remains clear: help meet
regulatory requirements and reduce the risk of FDA action.11
The Human Equation
Experience shows that turning promises into common practices is
easier said than done. Most companies, in fact, admit that they
execute change poorly and that most change initiatives fall short
of their goal.12 The reasons why usually have nothing to do with
technology and everything to do with how people implement
and react to change. Some lab scientists, for example, like to do
things their own way, new protocols or not. They may continue
to see paper as raw data, despite what the auditors say. Still
more may simply ignore the goings on outside of their labs for
lack of interest, training, time–or a combination of all three.
What they may not realize are the hidden costs in time, money,
and yes, even their credibility when such behaviors are exposed
through an FDA audit.13
Adopting A Risk-based Approach To Compliance
Industry leaders are no longer leaving compliance to chance.
Increasingly, they are turning to companies such as PerkinElmer
OneSource® Laboratory Services to lead the way in developing
automated and traditional protocols, conduct expert training
and repair services, and even provide turnkey services that
enhance scientific workflows while keeping labs on the path to
an unblemished compliance record. In the lab, it might be as
simple as introducing electronic recordkeeping, automatically
affixing data time stamps to ongoing projects, or validating
analytical instruments, computer systems, and software.14
On the enterprise level it could also lead the way to a more
productive and profitable approach to doing business. That
2
requires the adoption of a globally comprehensive risk-based
approach to compliance that builds quality into procedures and
products rather than “inspect” them in later.
As the world of drug development becomes more complex, it
raises new challenges in the oversight process involving such
variables as personnel, practices, treatments, and geographic
dispersion. With the expertise of OneSource®, companies are
deploying proven solutions to mitigate and even prevent risk
as they streamline their validation efforts to be in line with
global guidance. Staff scientists no longer need to tinker with
hardware, software, or validation procedures in hopes of
remaining compliant. That is part of the OneSource solution.
It is based on centralized monitoring activities and continual
improvement processes that allow scientists to what they do
best – pursue science with integrity.15
Reference
1.http://self.gutenberg.org/articles/Edward_Deming
2.http://www.cbsnews.com/news/ranbaxy-whistleblowerreveals-how-he-exposed-massive-pharmaceutical-fraud/ .
See also, http://www.ft.com/cms/s/0/aad84e64-574c11e3-b615-00144feabdc0.html
3.http://www.accessdata.fda.gov/scripts/inspsearch/results.
cfm?start=401&end=500&textSearch=&classification=&stat
e=&project=&inspDateEndFrom=01/01/2014&inspDateEndT
o=12/31/2014&classificationDecision=&country=&city=
&zip=&center=&sortBy=&district= ; see also:
http://www.accessdata.fda.gov/scripts/inspsearch/results.cfm
4.http://www.pharmtech.com/data-integrity-analyticallaboratory?rel=canonical
5.http://www.fda.gov/Drugs/DevelopmentApprovalProcess/
Manufacturing/ucm169105.htm
6.http://www.pharmtech.com/data-integrity-analyticallaboratory?rel=canonical
7.http://www.fda.gov/Drugs/
GuidanceComplianceRegulatoryInformation/Guidances/
ucm124787.htm
8.http://www.fda.gov/ICECI/Inspections/InspectionGuides/
ucm074918.htm
9.http://www.fda.gov/ICECI/Inspections/InspectionGuides/
ucm074918.htm
10.http://npalliance.org/blog/2014/08/29/fda-draft-guidancedistribution-risk-information-pharmaceutical-companiesfalls-short-ensuring-patient-safety/
11.http://www2.emersonprocess.com/siteadmincenter/
PM%20Articles/ART-Trust-but-Verify.pdf
12.http://www-935.ibm.com/services/us/gbs/bus/pdf/
gbe03100-usen-03-making-change-work.pdf
13.http://www.genengnews.com/gen-articles/a-new-approachto-laboratory-efficiency-on-site-instrument-conciergeservice/5296/
15.http://www-935.ibm.com/services/us/gbs/bus/pdf/
gbe03100-usen-03-making-change-work.pdf;
see also, http://www.pharmtech.com/data-integrityanalytical-laboratory?rel=canonical
14.http://www.fda.gov/downloads/Drugs/Guidances/
UCM269919.pdf
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