FDA’S CDER LISTING OF TOP EIGHTEEN OBSERVATIONS FOR 2013

TOP FOUR OBSERVATIONS INCREASE SIGNIFICANTLY OVER 2012

Each fiscal year the FDA issues the various FDA 483 Observations from the various Centers to include CBER, CDER, CDRH, etc.  This Blog focuses only upon those issued by Center for Drug Evaluation and Research (CDER) and will concentrate upon those found within 21 CFR Part 211.  Interestingly, while the order of the Observations has remained constant within the top four, the number of Observations has markedly increased in numbers (from 340 in 2012 to 491 in 2013).  Of particular interest to my readers should be 21 CFR 211.113 (b) which pertains to the manufacture of sterile drug products.  In 2012 this Observation was considerably lower in terms of numbers of Observations noted (<43).

One should also be aware that the FDA, and CDER, in particular, use an internal electronic system to assist in positioning an Observation.  This system called TURBO EIR is designed to provide the most pertinent Observation vs. the information collected by the FDA auditor.  While this system is “painted” by the FDA as providing the most fool-proof method of providing the correct citation, it is especially notable within the area of microbiology that this often does not occur and one should question the number of microbiological citations, i.e., 21 CFR 211.113 (a)/(b) – especially when one studies 21 CFR 211.192 and recognizes that several of citations should not have been “192”, but 211.113(b).

Ref   No	Frequency	Short   Description
21 CFR 211.22(d)	155	Procedures not  in writing,   fully followed
21 CFR 211.192	131	Investigations of discrepancies,   failures
21 CFR 211.100(a)	106	Absence of Written Procedures
21 CFR 211.160(b)	99	Scientifically sound laboratory   controls
21 CFR 211.67(b)	77	Written procedures not   established/followed
21 CFR 211.113(b)	76	Procedures for sterile drug   products
21 CFR 211.67(a)	71	Cleaning / Sanitizing /   Maintenance
21 CFR 211.165(a)	66	Testing and release for   distribution
21 CFR 211.110(a)	65	Control procedures to monitor and   validate performance
21 CFR 211.166(a)	62	Lack of written stability program
21 CFR 211.100(b)	59	SOPs not followed / documented
21 CFR 211.68(a)	56	Calibration/Inspection/Checking   not done
21 CFR 211.188	56	Prepared for each batch, include   complete information
21 CFR 211.84(d)(2)	53	Reports of Analysis (Components)
21 CFR 211.63	49	Equipment Design, Size and   Location
21 CFR 211.25(a)	44	Training–operations, GMPs,   written procedures
21 CFR 211.198(a)	44	Complaint Handling Procedure
21 CFR 211.113(b)	43	Validation lacking for sterile   drug products