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EMA/CHMP/CVMP/SWP/169430/2012

Guideline on Setting Health Based Exposure Limits for Use in Risk Identification in the Manufacture of Different Medicinal Products in Shared Facilities

Sets out how to derive a health-based exposure limit — the permitted daily exposure — from toxicological and clinical data, for use in assessing cross-contamination risk where different medicinal products share a facility. Adopted 20 November 2014, effective 1 June 2015.

LAST REVISED
June 2015
PRODUCT AREAS
Solid DoseSterileBiotechApiVeterinary
SOURCE & PROVENANCE
ISSUING BODY
European Medicines Agency
JURISDICTION
European Union
DOCUMENT ID
EMA/CHMP/CVMP/SWP/169430/2012
Official site — European Medicines Agency

Always verify against the current published text before relying on it for a submission or inspection.

Scope & applicability

Shared manufacturing facilities, and the determination of whether dedicated facilities are required. It is the document that moved cleaning-validation limits away from arbitrary conventions such as one-thousandth of a dose or ten parts per million and onto a toxicological basis — which is also the basis on which an occupational exposure limit is derived, from the same underlying assessment.

Key requirements

  • Derivation of a permitted daily exposure from a point of departure with justified adjustment factors
  • Use of the PDE in cross-contamination risk assessment and in setting cleaning acceptance limits
  • Assessment by a person with appropriate toxicological or pharmacological expertise, with the derivation documented
  • Identification of compounds requiring dedicated or segregated facilities rather than shared ones

Implementation tips

  • One toxicological assessment serves two obligations: the PDE that drives cleaning limits and the occupational exposure limit that drives containment. Commissioning them separately duplicates cost and can produce two numbers that disagree
  • The derivation is the deliverable, not the number — a PDE without its point of departure and adjustment-factor rationale cannot be defended or updated when new data arrive
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EMA/CHMP/CVMP/SWP/169430/2012: frequently asked questions

Quick answers to common questions about EMA/CHMP/CVMP/SWP/169430/2012.

What is EMA/CHMP/CVMP/SWP/169430/2012?

EMA/CHMP/CVMP/SWP/169430/2012 — Guideline on Setting Health Based Exposure Limits for Use in Risk Identification in the Manufacture of Different Medicinal Products in Shared Facilities — is a guideline issued by the European Medicines Agency (European Union). Sets out how to derive a health-based exposure limit — the permitted daily exposure — from toxicological and clinical data, for use in assessing cross-contamination risk where different medicinal products share a facility. Adopted 20 November 2014, effective 1 June 2015.

Who does EMA/CHMP/CVMP/SWP/169430/2012 apply to?

Shared manufacturing facilities, and the determination of whether dedicated facilities are required. It is the document that moved cleaning-validation limits away from arbitrary conventions such as one-thousandth of a dose or ten parts per million and onto a toxicological basis — which is also the basis on which an occupational exposure limit is derived, from the same underlying assessment.

What are the key requirements of EMA/CHMP/CVMP/SWP/169430/2012?

EMA/CHMP/CVMP/SWP/169430/2012 requires, among other things: Derivation of a permitted daily exposure from a point of departure with justified adjustment factors; Use of the PDE in cross-contamination risk assessment and in setting cleaning acceptance limits; Assessment by a person with appropriate toxicological or pharmacological expertise, with the derivation documented; Identification of compounds requiring dedicated or segregated facilities rather than shared ones.

When was EMA/CHMP/CVMP/SWP/169430/2012 last updated?

The current version of EMA/CHMP/CVMP/SWP/169430/2012 dates from June 2015.