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EMA issues draft guidance on shared facility risks

pharmafile | January 17, 2013 | News story | Manufacturing and Production | EMA, manufacturing

The European Medicines Agency has issued draft guidance to help drug manufacturers avoid cross-contamination of products made in shared facilities.

The document – which is open for comment until 30 June – is designed to prevent situations in which residual active substances from one product end up contaminating another, potentially placing patient safety at risk.

The guidance suggests that drugmakers should develop a ‘threshold value’ for each of their products – either a permitted daily exposure (PDE) or threshold of toxicological concern (TTC) – which would be based on pharmacological and toxicological data from non-clinical and clinical studies.

If PDEs or TTCs cannot be drawn up for a product due to a lack of data, the drug will have to be made in a dedicated facility, says the EMA. This is already a requirement for some drug classes, such as certain antibiotics and high-potency compound such as cytotoxics.

The draft defines a PDE as “substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed at or below this dose every day for a lifetime”.

A TTC is expected to be used when the active substance being made is genotoxic, so any level of exposure carries a risk. It represents the genotoxic impurity exposure level associated with a theoretical cancer risk of one additional cancer in 100,000 patients exposed over a lifetime.

The document is designed to bring EMA guidance into alignment with revisions to its Good Manufacturing Practice (GMP) guidelines, which have introduced the concept of toxicological evaluation to establish threshold values for risk identification.

The guide also provides guidance on how the PDE and TTC data should be presented in reports to regulatory inspectors and provides a suitable template.

The new guidance applies to all commercial and investigational human and veterinary medicinal products, as well as all active substances, that are made in shared facilities.

Phil Taylor