I
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.
That
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.
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.
Most
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.
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.
FDA
told the company dominating the HIV treatment market that their response was
inadequate because:
told the company dominating the HIV treatment market that their response was
inadequate because:
·
Your
rationale was incomplete
Your
rationale was incomplete
·
You
do not have justification
You
do not have justification
·
You
provide no timeframe
You
provide no timeframe
·
You
provide no details
You
provide no details
·
You
did not specify how you intend to document
You
did not specify how you intend to document
·
You
did not provide the scientific rationale
You
did not provide the scientific rationale
·
You
did not describe how you will evaluate
You
did not describe how you will evaluate
It
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.
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.
More
specifically, Anita Richardson, Associate Director for Policy, Office of
Compliance and Biologics Quality, has given suggestions for writing an
effectiveresponse.2
specifically, Anita Richardson, Associate Director for Policy, Office of
Compliance and Biologics Quality, has given suggestions for writing an
effectiveresponse.2
It’s
like being given answers in the back of the book, except it’s not just the
answers to the odd-numbered problems.
like being given answers in the back of the book, except it’s not just the
answers to the odd-numbered problems.
So
take notes, class. Ms. Richardson says:
take notes, class. Ms. Richardson says:
1.
Include
a commitment/ statement from your senior leadership
Include
a commitment/ statement from your senior leadership
2.
Address
each observation separately
Address
each observation separately
3.
Note
whether you agree or disagree with the observation
Note
whether you agree or disagree with the observation
4.
Provide
corrective action accomplished and/or planned. Tell the FDA the
plan.
Provide
corrective action accomplished and/or planned. Tell the FDA the
plan.
a.
Be
specific (e.g., observation-by-observation)
Be
specific (e.g., observation-by-observation)
b.
Be
complete
Be
complete
c.
Be
realistic
Be
realistic
d.
Be
able to deliver what you promise
Be
able to deliver what you promise
e.
Address
affected products
Address
affected products
5.
Provide
timeframes for correction
Provide
timeframes for correction
6.
Provide
method of verification and/or monitoring for corrections
Provide
method of verification and/or monitoring for corrections
7.
Consider
submitting documentation of corrections where reasonable and
feasible
Consider
submitting documentation of corrections where reasonable and
feasible
8.
BE
TIMELY (Ms. Richardson’s emphasis.)
BE
TIMELY (Ms. Richardson’s emphasis.)
Unfortunately,
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:
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:
1.
Have
the communications department write a sincere cover letter for the president to
sign.
Have
the communications department write a sincere cover letter for the president to
sign.
2.
Never
agree with the observation, as this will be interpreted as admitting
guilt.
Never
agree with the observation, as this will be interpreted as admitting
guilt.
3.
Respond
as general as possible to allow maximum flexibility.
Respond
as general as possible to allow maximum flexibility.
4.
Don’t
look anywhere else other than the specific problem cited in order to limit our
liability.
Don’t
look anywhere else other than the specific problem cited in order to limit our
liability.
5.
Do
not give lot numbers of potentially affected product, since this will provide
the seizure list to FDA.
Do
not give lot numbers of potentially affected product, since this will provide
the seizure list to FDA.
6.
Don’t
put anything in writing because documents are legally
discoverable.
Don’t
put anything in writing because documents are legally
discoverable.
7.
Don’t
provide additional documents, as this gives the FDA more material to find
objections.
Don’t
provide additional documents, as this gives the FDA more material to find
objections.
Ms.
Richardson’s advice is excellent, and my parody—although followed by some
firms—just calls fire on your position.
Richardson’s advice is excellent, and my parody—although followed by some
firms—just calls fire on your position.
In
summary, count the F’s:
summary, count the F’s:
For
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.
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.
Responders
with correct answers will be announced ([email protected]).
with correct answers will be announced ([email protected]).
No,
really.
really.
1
Gilead Warning Letter, San Dimas, CA, September 21, 2010
Gilead Warning Letter, San Dimas, CA, September 21, 2010
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm227649.htm
2
Richardson,
Anita, Writing an Effective 483
Response
Richardson,
Anita, Writing an Effective 483
Response
http://www.fda.gov/downloads/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/UCM102921.pdf
About The QA
Pharm:
“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
you have a passion for the value and the direct relationship that quality
assurance and current Good Manufacturing Practices have to your patients and
your business, you will find a kindred spirit here.” For more insight from The
QA Pharm visit his blog here.
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