The MHRA has taken a different approach this year in the publication of the GMP deficiencies for drug product issued during inspections in 2018 and published in October 2019. In 2015 and 2016, MHRA provided approximately 100 slide decks with tables, figures, and text from deficiencies against the requirements in the Chapters and Annexes. No data were published for 2017. The MHRA published a 6,200-plus line excel spreadsheet of their 2018 GMP inspection data so that individuals can parse and present the data according to their needs.
This article is data-dense and includes many figures in three sections, published here in a three-part series. (Note: clicking images will enlarge them.)
- Section I begins with a high-level overview of the 2018 data including additional trends from the two most recent MHRA reports, 2015 and 2016.
- In Section II we identify and evaluate the critical and major deficiencies from 2018. This section identifies the Chapters and Annexes associated with critical and major deficiencies. For critical deficiencies citing Chapter 1 and Annex 1, we identify the specific paragraphs and requirements with which they are associated.
- In Section III we present the ten most frequently cited paragraphs for the ten Chapters and Annexes with the most frequently cited deficiencies identified in Section I, Figure 5 (found in Part 1).
- Section IV provides conclusions.
In Part 1 of this series, we covered Sections I and II. In Part 2, we present and analyze five of the top ten most frequently cited paragraphs for the Chapters and Annexes identified in Part 1, Figure 5. Part 3 will cover the remaining five paragraphs as well as conclusions to the data.
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III. Specific Deficiencies in the Top Ten Annexes/Chapters
In the following section, we take a granular look at individual Chapters and Annexes identified in Part 1, Figure 5 and how the deficiencies are divided among the various paragraphs. We address Chapters 1, 3, 4 and 5, 6, 7, 8 and Annexes 1, 11, and 15. These are provided in decreasing order of deficiencies as in Part 1, Figure 5. This post will cover the top five Chapters and Annexes, and Part 3 will cover the remaining five. We provide the top ten citations for each, or more in the two instances where there are ties for this honor. Each figure is followed by the short version of text of the top citations. The previous reports from MHRA in 2015 and 2016 include text from actual inspections as examples, but that is not provided this year.
Figure 1 shows the top ten citations from Chapter 1 and Figure 2 provides the short text of the requirements, along with the number of times each was cited. The top two citations address problems with investigations and root cause analysis which is not a surprise. This topic is among the most frequently cited FDA inspection observations. These two citations constitute 48 percent among the top ten citing Chapter 1 and 29 percent of the total number of deficiencies citing Chapter 1. Also notable are the two citations associated with management oversight, paragraphs 5 and 6, which together constitute 12 percent of the total number of the top ten and 7 percent of all deficiencies citing Chapter 1.
Figure 1: Top Deficiencies Citing Chapter 1
Figure 3 and Figure 4 address the ten most frequently cited requirements in Chapter 4. The most frequent citation addresses contemporaneous documentation of data and information, and the requirement that these actions are traceable. Document management is also among the most frequent citations.
Figure 3: Top Deficiencies Citing Chapter 4
Figure 5 and Figure 6 identify the ten most frequent deficiencies that cite Chapter 5. Many of the requirements are cited with a similar frequency, thus no single requirement stands out as with some other areas.
Figure 5: Top Deficiencies Citing Chapter 5
Figure 7 and Figure 8 show the ten most frequent requirements cited in Annex 15. The most frequently cited requirement includes the need to identify and investigate deviations including failures to meet acceptance criteria, once again emphasizing the importance of this area which is also identified as the most frequent citation of Chapter 1 requirements.
Figure 7: Top Deficiencies Citing in Annex 15
Figure 9 and Figure 10 identify the ten most frequent deficiencies in Chapter 3. The three most frequently cited requirements include the need to have adequate storage areas with appropriate environmental controls, secure storage of highly active materials and the need to calibrate and maintain weighing and measuring equipment.
Figure 9: Top Deficiencies Citing Chapter 3
In Part 3, we will continue with a granular look at the last five individual Chapters and Annexes identified earlier and review conclusions from all 2018 data.
[NOTE: No need to wait for Part 3—download the full, 16-page copy of this report for yourself now!]