remember a class exercise in “Quality School” in which you counted the number of
F’s in a paragraph. Remember? The one where you got a different number with each
try? The point was to illustrate: one hundred percent inspection does not detect
defects one hundred percent of the time.
exercise came to mind again when I tried counting how many times some form of
the word “inadequate” appeared in the recent Gilead Warning Letter1.
I think it was eighteen times. But—I’m not absolutely sure.
likely eighteen is not the record, but the point is not lost on the reader: the
Gilead response to their FDA483 was—shall we say—inadequate.
told the company dominating the HIV treatment market that their response was
rationale was incomplete
do not have justification
provide no timeframe
provide no details
did not specify how you intend to document
did not provide the scientific rationale
did not describe how you will evaluate
seems to me that we should have a pretty good idea of how to respond to FDA483’s
by now, since the FDA has been publicly pointing out inadequate responses to
FDA483s in Warning Letters on their website since 1996.
specifically, Anita Richardson, Associate Director for Policy, Office of
Compliance and Biologics Quality, has given suggestions for writing an
like being given answers in the back of the book, except it’s not just the
answers to the odd-numbered problems.
take notes, class. Ms. Richardson says:
a commitment/ statement from your senior leadership
each observation separately
whether you agree or disagree with the observation
corrective action accomplished and/or planned. Tell the FDA the
specific (e.g., observation-by-observation)
able to deliver what you promise
timeframes for correction
method of verification and/or monitoring for corrections
submitting documentation of corrections where reasonable and
TIMELY (Ms. Richardson’s emphasis.)
by the time an FDA483 response filters through layers of management and the
legal department, some industry responses read as though the following
principles had been applied:
the communications department write a sincere cover letter for the president to
agree with the observation, as this will be interpreted as admitting
as general as possible to allow maximum flexibility.
look anywhere else other than the specific problem cited in order to limit our
not give lot numbers of potentially affected product, since this will provide
the seizure list to FDA.
put anything in writing because documents are legally
provide additional documents, as this gives the FDA more material to find
Richardson’s advice is excellent, and my parody—although followed by some
firms—just calls fire on your position.
summary, count the F’s:
faring fine in the future with our federal friends, firms must faithfully follow
forthright fundamentals. Felonious firms finesse and finagle forgetting that
forthwith our federal friends will find and fine them.
with correct answers will be announced (firstname.lastname@example.org).
Gilead Warning Letter, San Dimas, CA, September 21, 2010
Anita, Writing an Effective 483
About The QA
“I am an observer of the pharmaceutical industry from inside and
out with over 30 years experience from the lab bench to the management board. If
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QA Pharm visit his blog here.
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