Transparency is something that regulatory agencies need to get better at, both in sharing more and doing it in a timely manner. The fact that the 2019 data from the MHRA was released in October of 2020 is pretty poor. As a reference, the FDA releases their data pretty reliably at the end of the calendar year for the given year.
Been evaluating the MHRA’s 2020 data on Chapter 4 Documentation, which is the 2nd largest category of observations in 2019 (and in 2018 before it).
80 different inspections cited comments against the Principles section
Good documentation constitutes an essential part of the quality assurance system and is key to operating in compliance with GMP requirements. The various types of documents and media used should be fully defined in the manufacturer’s Quality Management System.
Documentation may exist in a variety of forms, including paper-based, electronic or photographic media. The main objective of the system of documentation utilized must be to establish, control, monitor and record all activities which directly or indirectly impact on all aspects of the quality of medicinal products. The Quality Management System should include sufficient instructional detail to facilitate a common understanding of the requirements, in addition to providing for sufficient recording of the various processes and evaluation of any observations, so that ongoing application of the requirements may be demonstrated.
There are two primary types of documentation used to manage and record GMP compliance: instructions (directions, requirements) and records/reports. Appropriate good documentation practice should be applied with respect to the type of document.
Principles, Chapter 4 Documentation
Suitable controls should be implemented to ensure the accuracy, integrity, availability and legibility of documents. Instruction documents should be free from errors and available in writing. The term ‘written’ means recorded, or documented on media from which data may be rendered in a human readable form.
The Principles section then goes on to lay out the required document types.
I would love to see more. Is this 80 companies who don’t known what a SMF is? Good documentation practices? Don’t have SOPs and batch records? Have errors in their documents? Don’t approve them? More transparency would be valuable here.
We can learn more by drilling down in the document.
- There are 87 inspections with 4.1 in section “Generation and Control of Documents”. 1 is critical and 25 are major. Here we see failures in understanding types of documents and controlling them, or maybe just having them in the first place.
- The 82 against 4.2 (1 critical and 20 major) are more about having the manufacturing and testing process defined (and matching the filing).
- 103 inspections with observations against 4.3 (23 major) show companies that do not have appropriate approval and release controls
- 14 for 4.4 (6 major) means there are 14 companies out there who can’t write a good process and procedure. 4.4 has one of my favorite requirements “written in an imperative mandatory style”
- 60 against 4.5 (13 major) demonstrates a lack of review and keeping documents up-to-date.
- 12 companies (6 major) have terrible handwriting and cannot stick to ballpoints, yes in fact 4.7 states “Handwritten entries should be made in clear, legible, indelible way.”
- 103 against 4.8 (1 critical and 28 major) is ALCOA focused on contemporaneous, attributable and accurate.
- 18 for 4.9 (6 major) is for not correcting data correctly. That’s right 18 companies do not know how to comment correctly.
- 22 for 4.10 (1 critical and 9 major) is for not clearly laying out the manufacturing records and keeping them for the retention period.
- 19 for 4.29 (5 major) is a lack of process and procedure for a grab-bag of quality processes from change control to equipment management to cleaning
There are more, but we are in single digit observation territory.
Useful things to be evaluating in your own organization. As a good place to start, here are some questions to ask when contemplating data integrity.