Analysis of GMP Inspections by MHRA

 
Due to the Freedom of Information Act (FOI), the FDA makes theirinspection results available to the public. Very rarely, however, thepublic gets informed about inspection results of European supervisoryauthorities. The MHRA is a very positive exception from this rule. JohnTaylor from the British supervisory authority MHRA presented inspectionfindings of his authority at the ECA event "How to Pass EU and FDAInspections - GMP Compliance Auditor", held in Barcelona from 04 to 06October 2006.

The MHRA set the frequency of inspections of UK manufacturers (700) to2 years and that of third-country manufacturers (300) to 3 years.

Inspection findings are classified by the MHRA into the categories"critical", "major" and "others". Here, "critical" characterises adeficiency which has produced, or leads to a significant risk of producingeither a product which is harmful to the human or veterinary patient. Acombination of "major" deviations indicating a critical system error arealso classified as "critical".

A "major" deficiency could or would produce a product that is not incompliance with the marketing authorisation. Or it stands for acombination of "other" deviations indicating a system error or repeated"other" deviations. A deficiency related to a Qualified Person failing tocarry out his/her legal responsibilities is also rated "major".

In the category "other", deficiencies can be found which cannot beclassified as "critical" or "major", but still indicate a departure fromGMP.

In the top-ten list of "critical" and "major" deviations found in allinspected areas (including third countries, wholesalers, contract labs),findings regarding the quality system rank first and second (seeillustration 1). This is similar to recent FDA findings.

Illustration 1

Examples for critical GMP deficiencies have been for example:

• Potential for microbial and non-microbial contamination
• Product is inspected and released by the warehouse supervisor whohas a stamp of the QP's signature
• Batch number and expiry date checks are no longer carried out by adesignated responsible person

John Taylor also presented a trending for all sectors inspected(Illustration 2)

Illustration 2

GMP deviations in third countries are often rooted in the ignorance ofEuropean GMP rules. Illustration 3 lists these deficiencies, illustration4 shows their trends.

Illustration 3

Illustration 4

Another interesting fact are the serious Good Distribution Practicedeviations. As in the previous years, temperature control and monitoringhad the most deficiencies.

Illustration 5

With regard to deficiencies in the manufacture of investigationalmedicinal products, the QM system is also listed in the top 3 (seeillustration 6).

Illustration 6

In 2005/ 2006, the MHRA conducted 15 inspections based on part 2 of theEU GMP Guide. The top 5 major deficiencies were:

• Laboratory Controls
• Process Equipment
• Quality Management
• Materials Management
• Production and In-Process-Controls
   

The European Compliance Academy organises seminars on all frequent GMPdeviations.Click here to view a list of events.

 
Author:
Wolfgang Schmitt
On behalf of ECA