Chemical Engineering March 2014 - 47

Feature Report
Engineering Practice
FDA Form 483: Minimizing
FDA Inspection Citations
One of the paramount
issues related to FDA
regulated products is
that of documentation
and record keeping
related to manufacturing
W. M. Huitt
W. M. Huitt Co.
A
s an owner or manager of a
company whose product is
regulated by the U.S. Food and
Drug Administration (FDA),
you will, at some point, be subjected
to an FDA inspection. And once an
inspection is underway in your facility,
anything affecting the drug or
food product directly or indirectly
in an adverse manner is within the
purview of the FDA inspectors.
If discrepancies are found during
such an inspection, one or more
Form 483 Inspectional Observation
Forms will be submitted to company
management addressing each
discrepancy. These will come at the
conclusion of the inspection process,
and each discrepancy will be discussed
and explained. Keeping in
mind that the majority of discrepancies
will typically be subjective
in nature, they can be wide-ranging
in their impact and implication -
from a housekeeping issue to product
adulteration.
Form 483 is used by the FDA as
a first step in correcting a productrelated
deficiency within a facility.
Deficiencies can be related to
computer programming, productcontact
material of construction,
procedural issues, material handling,
documentation, and on and
on. Anything, as mentioned earlier,
3,000
2,500
2,000
1,500
1,000
500
2006
Foods
2007
2008
Years
Devices
2009
Drugs
that could affect the consistent and
acceptable quality of the product is
fair game.
Rather than cover the broad and
varied manufacturing categories
and subject matter encompassed
by the use of Form 483, this discussion
focuses more pointedly at those
facilities that fall within the characterization
of being included as a
part of the chemical process industries
(CPI).
The notification
As a first-step notification to facility
management, Form 483 is the
FDA's way of identifying and forewarning
a company that certain aspects
of its manufacturing process
are not compliant with FDA regulations.
Upon receipt of a Form 483
notification, the company will have
fifteen working days in which to
respond. This is not a requirement,
but is simply an expectation.
Should a company not respond
within that fifteen-day window, or
should the response be considered
insufficient or inadequate to correct
the deficiency, the second shoe
would fall in the form of a warning
letter being issued.
The warning letter would first
state the issue or issues reiterating
the Form 483 infraction(s), fol48
ChemiCal engineering www.Che.Com marCh 2014
2010
Biologics
lowed by a statement such as: " We
have reviewed your firm's response
of December 12, 2012, and note
that it lacks sufficient corrective
actions. " The letter would then go
on to elaborate, in significant detail,
on why the response was inadequate
and what was required to
rectify the issue.
In many cases, the warning letter
will include a cease-and-desist order,
should its directive go unresolved or
ignored, similar to what follows:
" Until all corrections have been
completed and FDA has confirmed
corrections of the violations and
your firm's compliance with cGMP,
FDA may withhold approval of any
new applications or supplements
listing your firm as a drug product
manufacturer. In addition, failure
to correct these violations may result
in FDA refusing admission of
articles manufactured at ABC Drug
Co., located at 1234 Street, City,
Country, into the United States. "
Note: The above company name
and address is fictitious and is not
intended to apply to any company
in particular.
The letter will finish by giving
the respondent " fifteen working
days " to respond with a clear and
concise description as to what steps
have been taken, or are to be under2,496
2,400
1,873
1,773
1,980
865
628
295
818
559
252
738
470
228
725
550
216
817
646
224
Figure 1. Of
the four categories
shown here, food
processing has by
far received the
most Form 483 notifications
throughtout
the five-year
period plotted here
(see also Tables 1
and 2)
Number of notifications
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Chemical Engineering March 2014

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