When you are auditing you will often find non-conformities. These occur when the department, process or organisation that you are auditing is not following a requirement of the standard that you are auditing against. For many of you who perform audits in the pharmaceutical industry – the standard that you will audit against is GMP. It is important that any non-conformities are linked with the standard that you are auditing against, so non-conformities against GMP must be linked to the relevant clause of GMP.
The following may be useful to you. It lists a number of common basic audit findings and the corresponding clause in EU GMP that is relevant. Readers should note that there is often some repetition in GMP, so I have tried to find the best single clause – but additional clauses may exist. You should also refer to GMP itself to understand fully the context of each clause.
Not following a procedure
4.1/5.2
Absence of a procedure
5.2
Procedure out-of-date
4.5
Not following a schedule, programme or plan
4.1/5.2
Internal audits schedule late
9.1
Untrained personnel
2.10/2.11/5.1/6.1
No GMP training
2.11
No job specific training
2.11
Item not calibrated
3.41
Poor housekeeping/ cleaning
3.1/3.2
Risk of mix-ups and contamination
3.1/3.7/3.8
Unauthorised entry of personnel
3.5/5.16
Poor design of drains
3.11
Poor temperature control
3.3
Doors and windows left open
3.3/3.4
Incorrect crossing out of data
4.9
Not completing records at the time of action
4.8
Area not identified with batch number, product and activity
5.12
Items not labelled
5.12/5.13
Pipework not labelled
3.42
Damage to facility/ equipment
3.3/5.4
Redundant and broken equipment
3.44
Not using pen
4.7
Use of correction fluid
4.9
No organisation chart
2.2
No job description
2.3
No training record
2.9/4.29
Poor control of deviations
5.15
No CAPAs
1.4xiv
No root cause analysis
1.4xiv
Inadequate change control
1.4xii/1.4xiii
Poor control of suppliers
1.4vi/5.27-5.29
There is no mention in GMP of pen colour, the use of ditto marks, post-it notes or having a specific time and date format. However, if an organisation has a policy or procedure on such things – then they must follow their own system. Otherwise this is a non-conformity against 4.1 and 5.2.
Please feel free to comment. For details of our courses in this area select this link: QMS Courses
THIS ARTICLE WAS FIRST PUBLISHED IN 2012 AND MOST RECENTLY UPDATED IN AUGUST 2022.
Annex 1 has finally arrived, 25th Aug 2022 saw the publication of Annex 1. Normally, updates to GMP chapters and Annexes have a 6-month lead time for implementation. In the case of the new Annex 1, the lead time is 12 months, except for clause 8.123 relating to lyophilization which has 24 months lead time.
Annex 1 was first issued in 1971 as the only annex in the first ever UK guide to Good Manufacturing Practice. Since then, there have been several updates but not full revisions. In 2012 there was a proposal to revise Annex 1 with a re-proposal in 2014 by the UK’s MHRA. At the time, a full rewrite was considered unlikely and instead the intention was to provide a document that would confirm regulatory expectation and as such, not place any new requirements or costs on the pharmaceutical industry.
While this principle, is still upheld, it was clear from the first draft for public comment of December 2017, that a rewrite was being undertaken. The first draft created around 6200 comments coming from regulatory organizations, such as the pharmaceutical cooperation scheme, regulatory bodies outside of the EU, support organizations such as the Parenteral Drug Association, the Parenteral and Healthcare Sciences Society, the Pharmaceutical Microbiology Interest group as well as representatives from the manufacturers within the pharmaceutical industry to name just a few. Rarely do updates require a second public consultation but in the case of the annex 1 update a second draft was issued in March 2020 although this was a more targeted review in terms of the sections and clauses that comment was being sought for.
About the author
Andy Martin
Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.
Training courses on Annex 1
There are a number of half-day workshops organised to take you through the changes in more detail and to look at how they relate to your organisation.
Our 2-day course is updated for Annex 1 changes
Related Articles
Find out about our course ranges
GMP Training
QMS Training
GDP/RP Training
GMP Compliance
QP Training
GDP Compliance
Free Taster courses
To try a free taster of our online courses to see if they are of interest visit this page.
Good one . CAPA details needed for the observations.
You definitely hit on some of the popular findings I see all the time during cGMP audits! I always find it amazing how much we can read between the lines of the regulations. Take for example the US GMP regulation on equipment design which basically states that “equipment shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use.” That simple statement has ballooned into complex equipment validation, detailed change control, and intricate maintenance programs.
There’s a nice newsletter out there called GMP Trends which gives a nice monthly summary of FDA 483 observations.
Really enjoy your blog and look forward to more posts!
Sometimes training records are found to be a mere paper work. During an vendor audit, I found a chemist trained in a particular analysis. When I was asking for how the calculation is arrived at, the concerned p[erson could not reply. Also, for out of specification, different versions are noticed. No common version could be found out. This is because of the complexity of the expressions/terminologies used in making the out of specifications.
I like this article and agree with other commentator regarding business based citations provided sense prevails and the auditor doesnt get too attached to the number he/she generates! These might best be recorded as “Comments”- this is what I have seen done before.
I agree to the above comments. I need to quote one example I came across. The company cleared a regulatory audit a week before. When a QA personnel from some other factory audited the firm for vendor approval, he could generagte around 20 NCs. Ofcourse, 5 of them were major and rest were minor. The firm attributed top the lineant view taken by its employees that they had cleared an international audit. So, people work only for audits. If the system is followed regularly, then there will not be any non-compliant. My boss used to say that we ahve to work as if everyday is an audit day.
Excellent , Thank you for this .
See item 1.b. Post-it’s are typically related to, or considered “scratch paper”
https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2014/ucm409898.htm
There also used to be an FDA guidance that does specifically state records should be in “blue or black indelible ink”, although I can’t recall which one now. Up to you as to which color or either.
And the FDA has preferred dating for expiration dating. They expect you to have defined the date format for your organization and follow whatever you choose to avoid confusion…although I’ve never heard nor seen anyone being written up for using a specific format.
https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM409401.pdf
A lot of the GDP practices you mentioned not being covered by GMPs are considered “implied” since these are legal documents. Try signing a home loan in red or green ink. These may vary by country to country. For example the FDA used to not accept the common Asian practice of using a stamp as a signature, however, they now appear to allow that.
These aren’t covered under GMP, they are extensions of the criminal code in the U.S. Specifically title 18 of the USC, obstruction of justice.