Friday, 26 May 2017

EMA: risk based prevention of cross contamination in production (draft)


The European Medicines Agency has issued a new draft document, with the lengthy title of “Questions and answers on implementation of risk based prevention of cross contamination in production and ‘Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities’ (EMA/CHMP/CVMP/SWP/169430/2012).”

The document deals with highly hazardous products are those that can cause serious adverse effects at low doses and that therefore would benefit from a full toxicological assessment in order to derive a safe Health Based Exposure Limits. A health based exposure limit is a limit (permitted daily exposure (PDE) or equivalent) at which a product is regarded to be safe in humans. It can be based on either clinical dose or non-clinical safety data, depending on which would give the lower exposure limit.

Such products are:


  1. Genotoxic (specifically mutagenic) compounds that are known to be, or highly likely to be, carcinogenic to humans. Compounds of this group are easily identifiable, since genotoxicity would be related to the pharmacology, e.g. as DNA alkylating cytostatics, and their use is usually restricted to oncology indications with respective warning statements in the Summary of Product Characteristics.
  2. Compounds that can produce reproductive and/or developmental effects at low dosages, for example where evidence exists of such effects being caused by a clinical dose of <10 mg/day (veterinary dose equivalent 0.2 mg/kg/day) or dosages in animal studies of ≤1 mg/kg/day.
  3. Compounds that can produce serious target organ toxicity or other significant adverse effects at low doses, for example where evidence exists of such effects being caused by a clinical dose of <10 mg/day (veterinary dose equivalent 0.2 mg/kg/day) or dosages in animal studies of ≤1 mg/kg/day.
  4. Compounds with a high pharmacological potency i.e. recommended daily dose of <1 mg (veterinary dose equivalent 0.02 mg/kg)

Compounds with a high sensitising potential.

The document can be accessed here: EMA



Posted by Dr. Tim Sandle