French Medicines Agency Voices Support for ISPE’s Risk – MaPP Guide Principles

by Rochelle Runas, ISPE Technical Writer

Representatives from the French Medicines Agency (AFSSAPS) have voiced support for risk-management principles that underpin ISPE’s upcoming ISPE Baseline® Guide Volume 10: Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP).

“AFSSAPS is in favor of a risk-management method,” said Vincent Gazin, Head of the Clinical Toxicology Unit, AFSSAPS, at the ISPE 2008 Washington Conference: Engineering Regulatory Compliance, held June 2 – 5 in Washington, D.C., USA. “We agree to have a scientific discussion more than an interpretation of regulatory text.”

The need for dedicated facilities for the manufacture of certain classes of high hazard compounds has been the subject of much debate in recent years. The rationale for separating certain compounds has not always been clear and regulators in the US and Europe are working on revisions to parts of their Good Manufacturing Practice (GMP) guidelines addressing this issue.

The ISPE Risk-MaPP Baseline® Guide shows how the rational use of a science-based risk assessment process can be used to assess compounds, on a case-by-case basis, to support manufacturing strategies that allow for the use of multi-product facilities.

In January the EMEA released a “State of the Status of the Revision of Chapter 5 of the GMP Guide Concerning “Dedicated Facilities,” indicating that the EMEA will provide a list of products that mandates “dedicated facilities.” The development of this list is pending input from toxicological/pharmacological experts, including Gazin.

The EMEA anticipates that a text will be submitted to the European Commission at the end of 2008 or the beginning of 2009 for public consultation.

At the ISPE educational session, “Risk-MaPP: Application of the new ISPE Baseline® Guide Volume 10: Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP),” Gazin and Nicolas Chauviere-Courcol, Mechanical Engineer, gave a presentation on how risk management principles are applied in the toxicological unit of AFSSAPS.

While AFSSAPS has not yet officially reviewed the Risk-MaPP Guide, Gazin’s comments during his presentation indicated his support for the Guide’s principles.

Gazin commented on the following text taken from the Risk-MaPP draft September 2007:

Pharmacological and toxicological descriptions (dose-response, no-observed-adverse-effect level (NOAEL) and ADI) should be used to assess compounds instead of hazard labels. Terms such as potent, cytotoxic, cytostatic, and other product class definitions tend to induce an emotional response that might imply that these compounds are always difficult to handle and require the highest level of control.

“Emotional responses should be rationalized,” said Gazin. “Toxicity depends on the quantity as well as on the duration and the route of exposure. NOAELs and usual toxicological reference values should be integrated in a risk management program. But the choice of NOAELs and toxicological reference values (such as ADI) could be different among toxicologists.”

“The objective is to have harmonization between assessors,” said Gazin. “When we are talking about scientific data, it is easier to have harmonization.”

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