At the end of 2004, APIC (Active Pharmaceutical Ingredient Committee), a
sector group of the European
Chemical Industry Council (CEFIC), published a
"Guidance on Qualification of Existing Equipment". APIC
represents the interests of the industrial companies manufacturing APIs.
This guidance is 13 pages long and has 7
chapters. The first four chapters consist in an acknowledgement,
introduction and scope, as well as a presentation of the regulatory
requirements. Chapter 5, the longest part, is the guidance itself. The
document is rounded off by references, a glossary and a list of
abbreviations.
The target group of this guidance is the
complete API industry including manufacturers of API intermediates, API
starting materials and perhaps even earlier stages.
The (main) chapter "Guidance" begins with the topic of risk
assessment. The authors consider risk assessment to be a very helpful
tool, which can be applied to all kinds of qualification (existing plants,
equipment, systems).
The methods for assessing risks indicated in the text are HAZOP, FMEA, and
decision trees. However, it says that the list is not complete and might
be continued by adding further techniques.
For the risk assessment of unit operations or functions, the document
lists 6 questions that help to assess the criticality with regard to
a loss of quality and/or the occurrence of cross contamination.
If one of these 6 questions is answered in the affirmative, the respective function
is GMP-relevant. Afterwards, the probability of occurrence and the
detectability of a mistake should be considered and measures to reduce the
risk, identified.
The text also gives an example for a technical GMP risk assessment.
A programme with 10 steps guides through the actual qualification
activities:
- Collecting flow charts and matrices as a tool for monitoring and
getting an overview.
- Reference to a matrix giving examples for activities within the
framework of qualification and for documentation.
- Creating a Validation Master Plan (VMP) and/or Qualification Plan
(QP).
- Collecting, reviewing and updating the equipment-related
documentation. The text recommends to use an example documentation
matrix, which helps to find out about the necessity and availability
of the respective documents (e.g. User Requirement Specification,
maintenance protocols) and their numbers in a short time.
- Risk assessment for identifying the necessary qualification
activities.
- Creating a qualification matrix for IQ (the text provides an
example).
- Updating the IQ documents according to the actual on-site
conditions.
- Creating another qualification matrix for OQ and PQ in order to be
able to identify the necessary activities. (The text gives an example
here, too.)
- Conducting OQ and PQ.
- "Ongoing Change Management" after equipment has been
declared qualified and released.
A flow chart helps to clarify the 10-steps programme once more.
Our opinion: We think that this document is very practice-oriented. The
numerous examples help to make the subject of qualification of existing
equipment transparent and understandable. A surprising fact is that risk
assessment itself is not mentioned before point 5 of the 10-steps
programme. However, in the corresponding flow chart, quite sensibly risk
assessment comes second, directly after the Validation Master Plan. So
this is just a minor inconsistency, which does not diminish the quality of
the document.
Author:
Sven Pommeranz
CONCEPT HEIDELBERG
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