A comprehensive GMP Intelligence program includes monitoring of health authority enforcement actions, including:
- FDA forms-483
- Establishment Inspection Reports
- Warning Letters
- Import Alerts
- Consent Decree Agreements
- EU Reports of GMDP Noncompliance
This 3-part article series presents recent publications of GMP drug product inspection data from CDER and MHRA:
- The CDER data are from drug inspections conducted in FY2017
- The MHRA data come from inspections conducted in 2016
- We include a total of 5 years of data for FDA
- 2 years for MHRA as we identify trends in areas of enforcement for both health authorities
- The CDER drug inspection observations supplement the information we previously published describing CDER Drug GMP warning letters issued in FY2017.
Raw data regarding FDA inspections come from the FDA website. But the presentation of data herein differs from that generated by the FDA:
- I combine the number of all observation listings that cite 21 CFR211.192 into a single value.
- In contrast, the FDA data present 5 line-items for 211.192, and each identifies the number of times FDA cited the regulation.
- Consolidating the citations leads to different conclusions.
- In the FDA listing, the most frequently cited item is 211.22(d), ‘procedures not in writing, fully followed.’
- Considering the total number of times that FDA cited 211.192, 211.188, and 211.160(b), they become number 1, 2, and 3 respectively with 211.22(d) becoming the 4th most frequent citation.
- FDA uses the term ‘frequency’ which appears to be the number of times they identified a specific citation in the forms 483 in the FDA tabulation.
FDA’s data include only forms-483 issued through their electronic system; it does not include forms-483 issued to API manufacturers or issued outside of the electronic system. Thus, the data do not represent FDA’s complete collection of inspection observations.
We also present GMP inspection data from MHRA. They recently published a 100-slide deck that provides GMP Inspection Deficiency Data Trends for 2016 for dosage forms. The MHRA provides a graphic representation of the deficiencies linked to the governing Chapters or Annexes. All MHRA data come from their slide deck.
- The number of forms-483 included in this analysis remained reasonably consistent over the past 5 fiscal years — ranging between 645 and 694 inspections. (Table 1, Row 2)
- The number of observations citing investigation of discrepancies (211.192) remains at the top of this list over the past 5 years though it tied for 1st place last year with 211.42(c). We as an industry cannot seem to get this investigation activity quite right. (Table 1)
- In general, the regulations cited and their relative order has remained reasonably constant over the past fiscal years. 5 areas saw a marked change, either increases or decreases, between FY2016 and FY2017. (Table 2 and Figure 2)
- The MHRA issued 143 ‘critical’ deficiencies in a total of 324 inspections of which 82 (25%) were overseas and 242 (75%) were UK inspections in 2016. The number of critical deficiencies identified in 2016 represents an almost 3-fold increase in the number identified in 2015. (MHRA 2016 Slide Deck, Slide 5 and MHRA Slide Deck 2015 Slide 5)
- Critical deficiencies cited in 2016 identify Chapters 1, 2, 3, 4, 5, 6, 8, and Annexes 1, 11, and 15 in the EU GMP Guide and represent a dramatic increase from last year in the number of Chapters and Annexes identified and the distribution of the critical deficiencies. (Table 3 and Figure 4)
- The MHRA cited a total of 4,974 deficiencies among the top 10 Chapters and Annexes in 2016. Critical deficiencies constituted 3% of the total compared to 2% last year; Majors were 29% compared to 29% in 2015 and Others were 68% compared with 69% in 2015. (MHRA 2016 Slide Deck, Slide 5 and MHRA Slide Deck 2015 Slide 5)
Go to for Part 2 to see the tables & figures that back these conclusions…
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About the Author
Barbara W. Unger is Govzilla’s Quality Expert and Editor-in-Chief of GMP Regulatory Intelligence. She formed Unger Consulting, Inc. in December 2014 to provide GMP Quality consulting services to the pharmaceutical and biopharmaceutical industry. At Amgen, she led the segment of the Corporate GMP Audit group at Amgen focused on API manufacturers, Quality Systems and Computers. She developed, implemented and maintained the GMP Regulatory Intelligence program for 8 years at Amgen Inc. This included surveillance, analysis and communication of GMP related legislation, regulations, guidance and industry compliance enforcement trends. This was an essential service and tool within the Corporate Audit function.
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