FDA’s CDER LISTING OF TOP NINETEEN OBSERVATIONS FOR 2014

TOP FOUR OBSERVATIONS REMAIN SIMILAR IN NUMBER TO 2013

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 the 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 relatively constant within the top four, the number of Observations has markedly increased in numbers (from 340 in 2012 to 491 in 2013 to 645 in 2014).  This appears to be partially because of the large number of Form FDA 483s arising from citations at various compounding facilities.

21 CFR 211.192 was listed as two sets of Observations.  The first, which was ranked third in 2014, was defined as “investigations of discrepancies/failures” (94 Observations), while the second set was defined as “written record of investigation incomplete” (38 Observations).

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) than 2014 when a total of 109 Observations were recorded.  Please note that within 21 CFR 211.113(b) that two different sets of Observations were recorded wherein 72 referenced “procedures for sterilizing drug products” and 37 referenced “validation lacking for sterile drug products”.

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).

Â	    Reference Number	Short Description	Â	Frequency
	21 CFR 211.22(d)	Procedures not in writing, fully followed		145
	21 CFR 211.160(b)	Scientifically sound laboratory controls		109
	21 CFR 211.192	Investigations of discrepancies, failures		94
	21 CFR 211.100(a)	Absence of Written Procedures		87
	21 CFR 211.67(b)	Written procedures not established/followed		72
	21 CFR 211.113(b)	Procedures for sterile drug products		72
	21 CFR 211.165(a)	Testing and release for distribution		64
	21 CFR 211.67(a)	Cleaning / Sanitizing / Maintenance		63
	21 CFR 211.68(a)	Calibration/Inspection/Checking not done		54
	21 CFR 211.166(a)	Lack of written stability program		51
	21 CFR 211.110(a)	Control procedures to monitor and validate performance		51
	21 CFR 211.198(a)	Complaint Handling Procedure		47
	21 CFR 211.25(a)	Training–operations, GMPs, written procedures		46
	21 CFR 211.100(b)	SOPs not followed / documented		43
	21 CFR 211.188	Prepared for each batch, include complete information		43
	21 CFR 211.42(c)(10)(iv)	Environmental Monitoring System		42
	21 CFR 211.63	Equipment Design, Size and Location		41
	21 CFR 211.192	Written record of investigation incomplete		38
	21 CFR 211.113(b)	Validation lacking for sterile drug products		37