During the revision of the WHO's Technical Report Series in June 2010, a number of annexes was also revised (also see our News from 14 July 2010, and the News from 2 July 2010), among others the "Good manufacturing practices for active pharmaceutical ingredients". This revised Annex 2 replaces the annex dating back to the year 1992 and is identical to the ICH Q7 Guideline. However, the WHO added two more appendices to this Annex 2:
- A list with references to a number of corresponding WHO guidelines or Technical Report Series
- A list of explanations and clarifications on various paragraphs of Annex 2
This list of explanations refer to the following issues, which need to be clarified according to the WHO specialists since they often played a role in inspections:
- Definition of the API starting material
- Role of the management in the introduction of a quality management system (Paragraph 2.11)
- Delegating responsibilities in the production area (Paragraph 2.3)
- System for qualifying suppliers of critical substances
- Examination of containers or groups of containers after receipt and before acceptance
- Batch identification
- Retention samples
An interesting feature of this list is the very strict definition of the starting material. According to the WHO, the starting material must
- be fully characterised with regard to identity and purity
- be a synthetic precursor one or more synthetic steps prior to the actual API
- be an isolated and purified substance with a fully elucidated structure
- have a well-defined specification related to one or more specific identity tests as well as tests and limits for efficacy and the impurity profile
It is the manufacturer's duty to define the starting material and to lay down a corresponding rationale in writing that can be produced to the inspector in case of a WHO inspection.
It is a fact that the wording of Annex 2 is absolutely identical to that of the ICH Q7 Guideline. However, the recently conducted revision of Part II of the EU GMP Guide, which comes into force on 31 July 2010 and will afterwards no longer be identical to ICH Q7, has not been taken into account. This means that Paragraph 2.19 requiring the application of the quality risk management principles, which has recently been introduced into Part II (see also our GMP News from 7 July 2010), will not be present in the new WHO Annex 2.
Here you can find the original text of Annex 2 to the WHO Technical Report 957.
Please note: A WHO representative deals with this topic at this year's "European Conference on Active Pharmaceutical Ingredients" by APIC in Barcelona, Spain, from 27-29 October 2010.
Dr Gerhard Becker
On behalf of the European Compliance Academy (ECA)