In our GMP News from 4. July 2012 we reported on a publication on the results of inspections carried out by the MHRA (Medicines and Healthcare Products Regulatory Agency, MHRA). MHRA is the authorisation and GMP regulatory agency in the United Kingdom. The report covers the period April 2011 to March 2012 and describes anomalies found in 303 inspections. In total 26 critical and 644 major observations were made.
It is worthwhile to take a look at this publication beyond the actual top ten list of deficiencies, since there are relatively few publications on GMP deficiencies by European authorities.
The following observations focus on the topics process validation/equipment qualification/calibration.
Already beginning with position 10 "Process Validation" in the list of deficiencies, interesting observations are reported. There are quotations concerning the topic risk assessment ("...same score were prioritised within the group", "...no risk assessment available..."). Among other things it was criticised that the protocols were not linked to the Site Validation Master Plan. Some deficiencies concerned the topic revalidation and recalibration (e.g. of blister processes) or the assessment of validation statuses (PQR). Remarkable are the deficiencies that in fact should be part of the separate category "qualification" (referred to as "equipment validation" in the report). The MHRA criticised among other things that the IQ/OQ for a mixer did not contain sufficient details with regard to the acceptance criteria. Furthermore deviations were not further dealt with ("no explanation or impact was documented"). It was also criticised that there was no requirement within the IQ/OQ documentation to identify and include the calibration and or maintenance requirements within the maintenance system. Further "classics" as concerns validation are lack of a pre-authorised validation protocol, lack of a validation report, lack of a formal conclusion of validation.
It is also very interesting to see how the top ten list continues with regard to the topics validation/qualification/calibration.
11. Design and Maintenance of Facilities
13. Design and Maintenance of Equipment
15. Validation Master Plan and Documentation
25. Qualification ("Equipment Validation")
40. Cleaning Validation
43. Computerized Systems - Validation
47. Computerized Systems - Documentation
49. Analytical Validation
60. Process Validation - Rework/Reprocessing
The deficiencies concerning "technical GMP-aspects" are striking. Positions 11 and 13 are taken by deficiencies concerning design and maintenance of facilities and equipment. Deficiencies with regard to qualification and calibration are ranging on positions 25 and 32. "Relatively" far behind are deficiencies in connection with the cleaning validation (position 40), computerized systems (positions 43 and 47) analytical validation (position 49) and deficiencies concerning rework and reprocessing (position 60). The latter are indicated separately although being part of process validation.
Details and quotations concerning the observations can be read in MHRA's report "Deficiency Data Review - April 2011 to March 2012.
Compiled by Sven Pommeranz
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)