Think the Food and Drug Administration’s
February withdrawal of its draft 21 CFR Part 11 guidance
covering electronic record integrity means the agency doesn’t
care about the quality of your records? Think again.
“FDA inspectors are human, and they have different
approaches and styles,” says Ken Miles of the FDA’s
Pacific Region. “But believe me, they’re still
taking Part 11, quality system regulations, and corrective
and preventive action plans quite seriously.”
“I’ve heard straight from dozens of key FDA
personnel and leading consultants in the field that 21 CFR
Part 11 is not going away, and neither is the agency’s
demand for electronic record integrity,” adds Michael
Causey, editor of the industry newsletter Part 11 Compliance
As one consultant put it, “If you don’t care
about the accuracy and efficiency of your electronic records,
then you don’t have to worry about Part 11, quality
assurance or computer system validation.”
The FDA is making no secret of the fact that it still
cares very much about these issues. For example, at an industry
seminar in May, John Murray, the primary adviser to the
FDA’s office of software validation, policy, classification
and Part 11 compliance, stated the agency actually assumes
most computer systems will fail at some point. Murray suggested
the real question firms should be asking themselves is how
a system failure would affect the safety and efficacy of
their product and their record integrity.
Sion Wyn, one of the authors working with the FDA on the
Feb. 20 Part 11 guidance withdrawing the prior draft guidance,
said in an interview with Part 11 Compliance Report: “It
would be a mistake to regard Part 11 compliance as having
a lower priority with the FDA. It’s a matter of a
more appropriate focus. The FDA is looking at all the good
manufacturing practices as part of its risk-based, science-based
21st century initiative. The agency’s objective, in
my opinion, is to develop an approach to using electronic
records and signatures that fits with that initiative. This
balances the need for secure and accurate record keeping--and,
of course, patient safety--with the potential benefits of
Finally, Joe Famulare, director of the FDA’s Division
of Manufacturing and Product Quality, recently said that
industry must remember that the agency’s new risk-based
and narrower interpretation of Part 11 does not mean the
FDA won’t enforce the rule or has lost interest in
it. “The importance of electronic record integrity
is still there,” Famulare says.
“It frankly amazes me: the number of smart pharmaceutical
executives who have told me since February that they don’t
think they need to devote much time to Part 11 and its related
issues now,” notes Causey. “They’re on
the verge of making a big mistake.”
As if the FDA’s seriousness wasn’t enough,
consider what can happen to your firm’s bottom line
and its reputation if you fail to take quality and record
integrity seriously. For example, take a look at the infamous
November 1999 FDA Consent Decree with Abbott Laboratories.
Hard lessons learned about the importance of rigorous quality
assurance still ring true today.
Abbott signed a consent decree of permanent injunction
in which it agreed to stop manufacturing and distributing
many of its in-vitro diagnostic tests until it corrected
manufacturing problems in its Diagnostics Division. In-vitro
diagnostic tests are designed to be performed in laboratories
on samples of patients’ blood, urine, mucous and other
bodily fluids for use in diagnosing and treating diseases.
“Over the past six years, Abbott has failed to comply
with FDA’s good manufacturing practice and quality
system regulation,” the agency reported. “Despite
warnings from [the] FDA, Abbott has failed to correct its
The FDA hit the firm hard both in the pocketbook and on
the production floor. Abbott agreed to comply with the FDA’s
quality systems regulation for these products according
to a schedule approved by the FDA. The firm also agreed
to pay $15,000 per manufacturing process per day (up to
$10 million) for failure to adhere to that schedule.
The firm agreed to pay $100 million to the U.S. Treasury
within 10 days after the court entered the decree. The amount
covered is described in the complaint filed by the court
as the equitable remedy of disgorgement. It set a precedent
as the largest amount of money ever paid by an FDA-regulated
company for a civil violation of the Federal Food, Drug
and Cosmetic Act.
In addition, the company agreed to pay 16 percent of the
gross proceeds generated by the sales of medically necessary
products not brought into compliance within one year after
the court entered the decree, as determined by an independent
Abbott’s manufacturing practices first raised FDA
concern in 1993, when GMP deficiencies were found during
inspections of the firm’s Abbott Park, Illinois, and
North Chicago manufacturing facilities. Violations were
found in process validation, production and process control,
and corrective and preventive action.
After these inspections, the FDA sent a warning letter
to Abbott in March of 1994. Subsequent FDA inspections during
1995, 1996, 1997 and 1998 continued to find the same types
of deficiencies. The FDA tried to work with Abbott to correct
these problems without seeking relief from the courts. However,
when the firm failed to meet promised completion dates and
failed to correct problems adequately, the FDA sent another
warning letter in March of 1999 and re-inspected the facilities
during May, June and July. During that inspection, the FDA
found continuing deficiencies and decided that a court order
would be necessary to ensure that the firm’s processes
were brought into compliance in a timely and orderly fashion.
In addition to the stiff financial penalties in the consent
decree, Abbott also agreed to correct deficiencies in its
manufacturing operations for all other diagnostic tests.
The corrections had to be overseen by an outside expert,
hired by Abbott, who certified to the FDA that the corrections
were made. The FDA had the option to re-inspect Abbott’s
facilities to verify that the products had been validated
and that the manufacturing processes conformed to the QSR.
Once the corrective action was complete, Abbott was allowed
to resume manufacturing and distribution. However, the company
had to hire an independent auditor to conduct audit inspections
of its in-vitro diagnostic device manufacturing operations
at least twice a year for at least four years.
Results of these audit inspections are required to be
reported directly to the FDA. If Abbott fails to comply
with the QSR or the terms of the consent decree, the FDA
may order the firm to again stop manufacturing and distributing,
recall the products, or take other action.
With the seriousness of the Abbott case in mind, it’s
worth looking at how some FDA-regulated life sciences and
biotech firms are changing their approach to quality and
validation since the FDA’s February Part 11 shift.
In truth, they’re not changing much.
“We’re not changing our approach to Part 11
at all,” says Karen Maskell, principal software quality
engineer at device firm Medtronic. Speaking at the Minnesota
Quality Conference in April, Maskell said that Part 11 was
“one of the most demanding regulations in FDA history.”
It’s also interesting to take a closer look at how
other firms are tackling quality, validation and record
integrity issues in the wake of the agency’s Part
11 shift. Understanding that compliance with Part 11, quality
and efficiency are basic requirements in today’s marketplace,
Galderma R&D quality assurance leader Herve Leroy knew
that he had to update his managing audit reports and follow-up
procedures that were based on paper and were frankly “not
Galderma R&D planned to acquire an electronic tool
that would enable the company to build a master audit plan,
schedule individual audits, record and report findings,
get response from audit contacts, allow response delegation
(one level), and monitor post-audit actions and/or other
His new streamlined approach has improved operations at
Galderma in several ways, including:
Management has access to the audit information as soon as
the audit report is issued and can fully manage the audit
contact’s response, which gives it a more active role
as a manager.
The auditor can easily produce an electronic audit report
and follow post-audit actions and due dates, which are dispositioned
to the audit contact.
With one click, the audit contact can delegate each issue’s
response to an assigned delegate and can simultaneously
oversee and endorse the final response.
Quality assurance management can handle problem resolution
and trigger CAPA when audit problems are residual.
Galderma is currently testing the application and expects
to start the performance qualification process later this
Shawn Gould, software compliance specialist for aaiPharma,
a pharmaceutical company based in Wilmington, North Carolina,
says he’s satisfied with the recent draft guidance.
“We’re pleased the FDA narrowed its scope with
the new draft guidance,” says Gould. “It gives
us some breathing room for our legacy systems and allows
us to make decisions based on our own risk analyses.”
There are numerous other systems at aaiPharma that are
Part 11-compliant, and the company’s Part 11 team
holds weekly meetings to discuss ongoing projects and requirements.
It has now put into place a policy that requires all future
purchases to be Part 11-compliant.
“No matter what the final outcome is, it just makes
good business sense to be Part 11-compliant,” says
Ken Miles of the FDA. “I can’t see how companies
can continue to put information on paper when they have
a golden opportunity to automate their processes and improve
their productivity and bottom line.”
Even though numerous companies have invested a considerable
amount of effort, time and money towards compliance with
Part 11, their efforts aren’t wasted. There is a chance
that the FDA will reinstate the guidelines, but more importantly,
these companies will be ahead of the competitive game by
having systems in place that maintain the integrity of their
Tamar M. June is director of marketing at AssurX Inc.,
a provider of CAPA software systems to a variety of industries
including medical device, pharmaceutical, semiconductor,
aerospace and contact manufacturing. She has spent the past
16 years in both manufacturing and information technology.
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