The MHRA has taken a different approach this year in the publication of the GMP deficiencies for drug product. In 2015 and 2016, they provided a full report with tables, figures, and text associated with representative deficiencies against the requirements in the Chapters and Annexes. No data were published for 2017. This year, 2018, the publication is a 6,200-plus line excel spreadsheet so that everyone can parse and present the data according to their needs.
This article provides a high-level overview of the 2018 data, and we will do a later follow-up report including additional granularity and trends over the past few years. The spreadsheet does not include text from deficiencies identified in inspection reports, so in that respect it is more limited than previous publications on the topic.
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Background and Caveats
The “Notes and Guidance” segment of the MHRA spreadsheet is a bit confusing. For example, in rows 2 through 12 of the spreadsheet, column E notes that the inspection resulted in 4 “other” deficiencies, though there are 11 unique references to Chapters/Annexes/paragraphs.
In light of this, here’s how I’ve parsed the data. Each row in the spreadsheet is treated as a unique deficiency, regardless of whether it is a “deficiency” or a “sub-point.” It is not possible to discern which is which in the spreadsheet so I treat them all equally.
The MHRA conducted 286 GMP inspections, both domestic and outside of the UK, in 2018. Inspections outside the UK included ones in Bangladesh, China, India, Japan, Singapore, South Korea, and the United States. Figure 1 identifies the number of drug product inspections performed by the MHRA in 2018 in each of the countries.
Figure 1: MHRA Inspections by CountryThe table with ID 68 not exists.
As in the past, almost all of the MHRA inspections were conducted in the UK. India was the second country with a total of 42 inspections. The remaining 14 inspections occurred in six countries with China and the US each having been the subject of five inspections.
Figure 2 and Figure 3 present the number of line-item deficiencies according to which GMP Chapter or GMP Annex is cited, respectively.
Figure 2: Inspection Citations by GMP Chapter
Chapter 1, Quality Management, with approximately 1,500 citations has more than twice the number of deficiency citations of the nearest chapter. Chapter 4, Documentation, at almost 760 deficiencies is closely followed by Chapter 5, Production, with just over 650, and Chapter 3, Premises and Equipment, at just under 570 citations. Chapters 2, 6, 7 and 8 each had between 200 and 400 deficiencies each and the remaining two chapters had fewer than 50 and 1 citation, respectively.
Figure 3: Inspection Citations by GMP Annex
Annex 15, Qualification and Validation, and Annex 1, Manufacture of Sterile Medicinal Products, take first and second place among the annexes with approximately 600 and 450 deficiencies, respectively. This is followed by Annex 11, Computerized Systems, and Annex 16, Certification by a Qualified Person and Batch Release. All of the other Annexes are associated with double-digit number of deficiencies.
Among the 6,200-plus deficiencies, the critical and major deficiencies cluster in a few Chapters and Annexes. Figure 4 shows the number of critical deficiencies and the Chapters or Annexes which are referenced. Among the critical deficiencies, 38% are associated with Chapter 1 and 22% are associated with Annex 1.
Figure 4: Critical Deficiencies
Figure 5 shows the number of major deficiencies and their associated Annex and Chapter. Among the major deficiencies, 33% are associated with Chapter 1, 11% are associated with Annex 15, 11% are associated with Annex 1, and 10% are associated with Chapter 5.
Figure 5: Critical Major Deficiencies
Overall, in terms of the Chapters and Annexes associated with MHRA-identified GMP deficiencies in 2018, Chapter 1, Annex 1, and Annex 15 are the areas of the drug product GMPs identified most frequently. Critical deficiencies are found mostly associated with Chapter 1 and Annex 1; major deficiencies are found associated with Chapter 1, Annex 1, Annex 15 and Annex 5.
In all cases, total deficiencies, critical deficiencies, and major deficiencies, Chapter 1 is the requirement cited most frequently. It is prudent for drug product manufacturers who sell product in the European market to carefully evaluate their compliance with Quality Management, Aseptic Processing and Validation/Qualification requirements in the EU GMPs.
Remember, these data do not include data from API or API intermediate sites, nor does it include GDP sites.
Stay tuned for a deeper dive into each of the areas, including trends over the past few years, and a more granular look at the paragraphs within the requirements that MHRA cited most frequently.
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