ISPE publishes new Baseline on the Subject of Risk Management

Dated September 2010, the International Society of Pharmaceutical Engineering (ISPE) has published a new baseline entitled "Risk-Based Manufacture of Pharmaceutical Products" (Risk-MaPP). The title implies a broader field of application than actually described in the baseline. The subtitle reveals the actual topic: "A Guide to Managing Risks Associated with Cross-Contamination." The baseline thus specifically targets the topic of cross-contamination and its prevention.

The baseline is 148 pages long and is subdivided into 16 sections:
1. Introduction
2. Concepts and Regulatory Philosophy
3. Quality System Requirements
4. Risk Assessment
5. Risk Identification
6. Risk Analysis
7. Risk Evaluation
8. Risk Control
9. Risk Reduction
10. Risk Acceptance
11. Risk Management Tools
12. Risk Review
13. Risk Communication
14. Appendix 1 Risk-MaPP Application Examples
15. Appendix 2 - Bibliography
16. Appendix 3 - Glossary

The goal of the document is stated in the introduction (Section 1): the baseline aims to strike an appropriate balance between product safety and personnel safety in terms of the risks of cross-contamination as found within pharmaceutical manufacturing. The methodology adopted is a scientific approach compliant with ICH Q9/Annex 20. This is an ambitious goal, but one to which the baseline does justice.

Interestingly, the original intention of the baseline was to supply a method capable of identifying "highly hazardous components". During drafting of the baseline, however, it became clear that the more appropriate approach would be to identify acceptable risks.

Fundamentally, the concept of cross-contamination risk assessment within pharmaceutical manufacturing is embedded in cleaning validations. Both product residues and cleaning agents are mentioned explicitly. Activities involved in cleaning validations should also be based on risk assessments.

Section 2 gives a general overview of regulatory requirements, also identifying key elements that are then presented in the baseline itself.

Section 3 discusses general aspects of GxP and offers a simple tool - the "logic diagram" - for evaluating processes in relation to the deployment of "dedicated facilities". The aim of this two-part diagram is to evaluate the manufacturing process in terms of its ability to establish the appropriate medium between GxP and work safety. Detailed treatments of the topics of mix-up, air hygiene, particles and personnel matters are presented.

Sections 4-14 then constitute a highly detailed treatment of the risk management process according to ICH Q9/Annex 20, in relation to the content of the baseline. Section 13 provides a sample quality risk management plan in relation to safeguarding products and ensuring work safety. A very interesting document.

Appendix 1 then offers four scenarios that treat the processing of a number of active substances and explore the applicability of the Risk-MaPP tool with a predefined layout, process and production range.  The scenarios relate to criteria that are clearly acceptable in Scenario 1, but clearly unacceptable in Scenario 2. In Scenario 3, the criteria are apparently acceptable (although not in fact) and in Scenario 4 the exact opposite is true (the criteria are apparently unacceptable but in fact the reverse is true). The four scenarios are then used to once again step through the risk management process from ICH Q9/Annex 20. Scenario 4 is extended to include a sample FMEA analysis.

The breadth of both the bibliography and reading list (Appendix 2) is striking. The bibliography takes four pages to cite 62 references and a further 2.5 pages to recommend another 47 sources. This is an important indicator of the high level of detail and the stringent scientific approach adopted by this baseline.

Also noticeable is the recurrence of "Process Capability of Cleaning Procedures" topic at several junctures in the text. The topic of process capability is also currently the subject of heated discussion as regards the new approaches to process validation. This once again demonstrates the baseline's high degree of scientific topicality.

Summary: ISPE's Risk-MaPP Baseline is a comprehensive, highly detailed document composed to stringent scientific standards. The evaluation of (cross-) contamination within pharmaceutical manufacturing is presented in a highly topical manner with reference to the ICH Q9/Annex 20 risk management process. The result is a very extensive, highly-detailed document that represents the current state of the technological art and will have a signal effect on the changes scheduled for dedicated facilities in the EU GMP Guide. Unfortunately, the "Risk-Based Manufacture of Pharmaceutical Products" (Risk-MaPP) is only available for a fee.

Sven Pommeraanz
On behalf of the European Compliance Academy (ECA )

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