Poor OOS Review Leads Causes of FDA Citations
Philadelphia, PA (Oct. 24)—Failures to review batch failures and unexplained discrepancies are the leading causes of US Food and Drug Administration
Form 483 observations and Warning Letter citations issued to pharmaceutical companies. Violations of the review requirement
(21 CFR 211.192) accounted for 16.3% of 818 observations in the 2006 fiscal year, pushing the category into first place from eighth
on last year's list.
Kristen D. Evans, a senior regulatory operations officer in the Office of Compliance at FDA's Center for Drug Evaluation and
Research, offered a summary of the 2006 compliance statistics during his keynote address at the Institute of Validation Technology's
Warning Letters and GMP citations
In Evans's analysis of Warning Letters and GMP citations (see Table I and Figure 1), 21 CFR 211.192 failures were followed by 2005's leading citation: shortcomings in the performance of the quality-control unit (21
CFR 211.22[d]). Poor in-process sampling and testing (21 CFR 2110[a]) followed. These categories accounted for 44% of the citations analyzed.
Table I: Causes of Form 483 and Warning Letter citations based on 818 FY 2006 citations.
Failures to follow sampling procedures (21 CFR 211.100[a]), validate production procedures (21 CFR 211.100[b]), or establish proper laboratory controls (21 CFR 211.160[b]) followed on this year's list, each accounting for ~10% of citations.
Rounding out the top ten were lapses in testing and release (21 CFR 211.165[a]), batch- record review (21 CFR 211.188), personnel qualifications (21 CFR 211.25[a]), and equipment cleaning and maintenance (21 CFR 211.67[a])
Evans summarized the causes of 215 of the year's 361 product recalls (240 of prescription products and 121 of over-the-counter
medications; see Table II and Figure 2). Subpotency was the most common reason (prompting 16% of recalls), followed by container
defects, impurities and degradation products, and poor assurance of sterility (each of which caused about 12% of the recalls).
Other causes included CGMP deviations, labeling errors, microbial contamination of nonsterile products, nonsterility, dissolution-test
failure, and failure of stability data to support the stated expiration date.
Table II: Causes of recalls based on 215 FY 2006 recalls.