In August 2010, the WHO published a draft guideline on quality risk management (QRM). With its 24 pages divided into 6 chapters, it is a surprisingly detailed document.
In the introduction (Chapter 1), the WHO points out that it formerly considered the HACCP concept, which comes from the food sector, as a suitable risk management tool. Bit regard to the EU GMP Guide, ICH Q8 and the FDA's risk-based approach, the WHO now sees more pharma-specific concerning QRM. The draft guideline now describes the current WHO approach to QRM, which is now also based on ICH Q9. However, the text underlines the fact that risk management modules other than the one described in ICH Q9 can also be applied. Depending on the process in question, the WHO also sees the emphasis on the individual ICH-Q9 steps as quite different. Yet, the guideline requires that all of the elements from the QRM process of ICH Q9 be implemented. Interestingly, within the framework of QRM, the WHO also sees connections to GCP and GLP. An indirect requirement to use QRM also in those fields?
The second chapter describing QRM considerations for regulatory authorities is also highly interesting. Actually, the descriptions are hidden requirements on a QRM by regulatory authorities directed at marketing authorisation holders and manufacturers. 2.2.1 explicitly includes a checklist for inspecting a QRM, and 2.2.2 lays down the inspection of risk-based decisions.
Chapter 3, in turn, includes highly detailed requirements on QRM for pharmaceutical manufacturers. You can find specifications regarding the topic of training and education, on responsibilities detailed instructions for the initiation of a QRM process up to the establishment of corrective actions and the verification of the QRM plan. A separate part of this chapter is dedicated to the application of QRM in product development and during validation/qualification. Especially with regard to process validation, the guideline refers to the FDA draft on this topic. In a consistent way, dependent on the process knowledge through QRM coming from development, the number of validation or "conformance batches" is not fixed either. A deviation from the classical number three for validation runs is explicitly considered to be possible (e. g. in the validation of the manufacture of orphan drugs).
Chapter 4 is titled "Risk Management Tools". With reference to a document by the Product Quality Research Institute (PQRI), a probability-versus-impact matrix is published. This matrix is meant to facilitate the classification into low, medium or high risks. In this context, the QRM team shall define each status in advance. As a helpful tool, a "consequence table" is also published, giving examples for the classification of probabilities and impacts, e. g. what is marginal impact (no impact on the product). A separate table lists risk management tools and the cases in which they can potentially be applied. Here, the PQRI is also referenced as the source.
A glossary (Chapter 5) complements the other 4 chapters. A salient point is the contents' distinct reference to a Q&A paper by the MHRA on the topic of QRM (see our GMP News from 15 September 2010). Some of the passages were taken over verbatim. Like the MHRA paper, the draft requires a "risk register", too.
Conclusion: The draft shows an astonishing high level of detail and is therefore truly worth reading. It can give guidance also in the preparation for questions regarding the QRM within the framework of an official inspection. Likewise, it provides guidance for initiating a QRM. However, only time will tell whether pharmaceutical companies e. g. in emerging countries can also implement QRM so meticulously. But the document may still be changed within the framework of finalisation in order to facilitate its implementation. The document is said to be available on the WHO web page soon.
Compiled and commented by:
On behalf of the European Compliance Academy (ECA)