Risk-MaPP — The Overall Goal

In 2010, the International Society of Pharmaceutical Engineers (ISPE) released Volume 7 of their Baseline Guide series: Risk-based Manufacture of Pharmaceutical Products, A Guide to Managing Risks Associated with Cross Contamination, or simply Risk-MaPP. The overall goal of Risk-MaPP is to provide a scientific, risk-based approach to managing the risk of cross product contamination in multi-product facilities.

Determination of Acceptable Daily Exposure (ADE) Limits

One of the key components of the Risk-MaPP approach is the determination of Acceptable Daily Exposure Limits or ADEs. ADEs are based on the toxicological properties and pharmacology of the specific active pharmaceutical ingredient. According to the Risk-MaPP document, the ADE of active pharmaceutical ingredient is the estimated dose that is unlikely to cause an adverse effect if an individual is exposed to the API by any route, at or below this dose every day for a lifetime.

Determination of the ADE should be performed by a qualified toxicologist, and must be science-based and data driven. As indicated on the Risk-MaPP blog, for many years, pharmaceutical companies have used 1/1000^th of the lowest clinical dose or 10 ppm to derive cleaning limits. While in most cases this approach is adequate, for highly potent compounds calculation of an ADE will lead to a lower cleaning limit.

Although not a specific regulatory requirement, regulatory agencies throughout the world are viewing the approach detailed in the Risk-MaPP document as current practice. Pharmaceutical manufacturers and contract manufacturing organizations (CMOs) that handle multiple products can reduce their regulatory compliance risks by adopting the Risk-MaPP process.

Contact Affygility Solutions today

The experts at Affygility Solutions are available for assistance in Risk-MaPP, and ADE determination. Contact us today.