Chemical Engineering March 2014 - 48

TABLE 1. OBsErvATiOns frOm fDA inspEcTs -
numBEr Of fOrm 483s issuED By yEAr
TABLE 2. fOrm 483s issuED
483 Totals
year
2010 2009 2008 2007 2006
Sum product area 483s from system1 5,306 4,612 4,307 4,630 5,383
Actual total of 483s in system2
Total 483s for fiscal year3
Total number of inspections/year
NOTES:
Foods
4,804 4,122 3,805 4,079 4,747
6,695 5,449 4,764 4,826 5,507
17,635 15,170 14,318 14,594 16,525
1. This table does not represent the complete set of Form 483s issued during the fiscal year as some
483s were manually prepared and not available in this format. The sum of Form 483s for all product
areas will be greater than the actual total Form 483s issued during the fiscal year since a Form
483 may include citations related to multiple product areas, and counted more than once, under
each relevant product center.
2. This is the actual total number of Form 483s issued from this system, and that are represented
in this Table.
3. This is the count of the total number of Form 483s issued in and out of the system during a oneyear
period.
taken to correct the listed deficiencies.
Should those fifteen working
days be exceeded with no effort at
a response from the notified company,
then any penalizing action
described in the warning letter will
go into effect.
Form 483 statistics
Referring to Table 1, in the five-year
period from 2006 through 2010,
there were a total of 78,242 FDA
inspections encompassing eleven
manufacturing categories. These
inspections resulted in 27,241 Form
483s being recorded. Figure 1 represents
a portion of those statistics,
with four of the higher-ranking
manufacturing categories providing
a comparison between the four
being represented. As readily seen,
the food processing category far and
away seems prone to attract the
most FDA citations.
FDA inspection and enforcement
falls under the responsibility of the
FDA's Office of Regulatory Affairs
(ORA). While the majority of Form
483s are generated through the
electronic TurboEIR (Turbo Establishment
Inspection Report) form
reporting system, which is reflected
in the data used for Table 1 and
Figure 1, there are some instances
in which these forms are filled out
manually and are therefore not
represented in these statistics. TurboEIR-generated
483s are categorized
in the following manner:
* Biologics
* Drugs
* Devices
* Human tissue for transplantation
* Radiological health
* Parts 1240 & 1250
* Foods (includes dietary supplements)
*
Veterinary medicine
* Bioresearch monitoring
* Incidental text
* Special requirements
Table 2 reflects, by category, the
number of Form 483s issued from
the TurboEIR system in descending
quantity by category from October
1, 2009 through September
30, 2010.
Interpreting FDA regulations
The FDA inspectors, working
through the ORA, are guided by
three resources: The regulations set
forth under Title 21 of the Code of
Federal Regulations (CFR); its law
enforcement counterpart Title 21
Chapter IX of the U.S. Code (USC);
and their FDA training guidelines.
Training for FDA inspectors plays
a big role in how they perceive, not
only the rule of law under the USC,
which by necessity is writ black and
white, but to also understand the
nuances and implications of the unwritten
variants within the many
complex guidelines and laws the
manufacturer is obliged to follow
under CFR Title 21.
One of the difficulties lies in the
fact that many regulations governing
the manufacture of food, drugs
and cosmetics are, in many cases,
intentionally vague. This is due in
large measure to two basic facts:
1. Much of manufacturing is proprietary
and specialized. It would
be impossible to write detailed
requirements that would apply
to all manufacturing without
constraining or interfering with
development and inhibiting new
concepts.
2. The criteria that the inspector
must base their field analysis on
is relative by nature and is subject
to a subset of nuances that
would be impossible to capture in
Devices
Drugs
Incidental text
Bioresearch monitoring
Veterinary medicine
Biologics
Parts 1240 & 1250
Human tissue for transplantation
Radiological
health
Special requirements
Total
Total number of inspections
same period
10/1/2009 ThrOugh 9/30/2010
category
2,496
817
646
303
282
232
224
169
111
16
10
5,306
17,635
% Inspection having 483s 30%
words, making broad statements
in the CFR a necessity.
This is why, in Title 21 Chapter I
Subchapter C Part 211 Subpart D,
you will find such vague requirements
as in Section 211.63, which
states the following:
" 211.63 Equipment design, size,
and location. Equipment used in
the manufacture, processing, packing,
or holding of a drug product
shall be of appropriate design, adequate
size, and suitably located
to facilitate operations for its intended
use and for its cleaning and
maintenance. "
The FDA cannot regulate the
design of equipment, the size of
equipment, or its location within
a facility or its approximation to
other equipment.
Another example of a vague requirement
is in Section 211.67
where it states, in part:
" 211.67 Equipment cleaning
and maintenance. Equipment
and utensils shall be cleaned, maintained,
and, as appropriate for the
nature of the drug, sanitized and/or
sterilized at appropriate intervals to
prevent malfunctions or contamination
that would alter the safety, identity,
strength, quality, or purity of the
drug product beyond the official or
other established requirements. "
In stating such a vague requirement,
the FDA is leaving the design
and procedural elements to
industry. Without knowing a particular
process, the FDA cannot
possibly know the specific needs of
its cleaning requirements. Instead,
what is available for the engineer
ChemiCal engineering www.Che.Com marCh 2014 49
Quantity
issued

http://www.Che.Com

Chemical Engineering March 2014

Table of Contents for the Digital Edition of Chemical Engineering March 2014