title: Guidance on the establishment of acceptable daily exposure limits (ADE) to support Risk-Based Manufacture of Pharmaceutical Products.
abstract: Health-based limits for active pharmaceutical ingredients (API) referred to as acceptable daily exposures (ADEs) are necessary to the pharmaceutical industry and used to derive acceptance limits for cleaning validation purposes and evaluating cross-carryover. ADEs represent a dose of an API unlikely to cause adverse effects if an individual is exposed, by any route, at or below this dose every day over a lifetime. Derivations of ADEs need to be consistent with ICH Q9 as well as other scientific approaches for the derivation of health-based limits that help to manage risks to both product quality and operator safety during the manufacture of pharmaceutical products. Previous methods for the establishment of acceptance limits in cleaning validation programs are considered arbitrary and have largely ignored the available clinical and toxicological data available for a drug substance. Since the ADE utilizes all available pharmaceutical data and applies scientifically acceptable risk assessment methodology it is more holistic and consistent with other quantitative risk assessments purposes such derivation of occupational exposure limits. Processes for hazard identification, dose response assessment, uncertainty factor analysis and documentation are reviewed.
authors.affiliation: University of Medicine and Dentistry of New Jersey, School of Public Health, Piscataway, NJ, USA. evsargent@gmail.com
authors.forename: Edward V
authors.initials: EV
authors.lastname: Sargent
authors.forename: Ellen
authors.initials: E
authors.lastname: Faria
authors.forename: Thomas
authors.initials: T
authors.lastname: Pfister
authors.forename: Robert G
authors.initials: RG
authors.lastname: Sussman
mesh_terms: D004305:Dose-Response Relationship, Drug; D004345:Drug Industry; D006801:Humans; D019055:No-Observed-Adverse-Effect Level; D009784:Occupational Diseases / Q000209:etiology / Q000517:prevention & control*; D016273:Occupational Exposure / Q000009:adverse effects*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*; D017410:Practice Guidelines as Topic; D018570:Risk Assessment; D035501:Uncertainty
chemical_list: D004364:Pharmaceutical Preparations