title: Issues and approaches for ensuring effective communication on acceptable daily exposure (ADE) values applied to pharmaceutical cleaning.
abstract: This manuscript centers on communication with key stakeholders of the concepts and program goals involved in the application of health-based pharmaceutical cleaning limits. Implementation of health-based cleaning limits, as distinct from other standards such as 1/1000th of the lowest clinical dose, is a concept recently introduced into regulatory domains. While there is a great deal of technical detail in the written framework underpinning the use of Acceptable Daily Exposures (ADEs) in cleaning (for example ISPE, 2010; Sargent et al., 2013), little is available to explain how to practically create a program which meets regulatory needs while also fulfilling good manufacturing practice (GMP) and other expectations. The lack of a harmonized approach for program implementation and communication across stakeholders can ultimately foster inappropriate application of these concepts. Thus, this period in time (2014-2017) could be considered transitional with respect to influencing best practice related to establishing health-based cleaning limits. Suggestions offered in this manuscript are intended to encourage full and accurate communication regarding both scientific and administrative elements of health-based ADE values used in pharmaceutical cleaning practice. This is a large and complex effort that requires: 1) clearly explaining key terms and definitions, 2) identification of stakeholders, 3) assessment of stakeholders' subject matter knowledge, 4) formulation of key messages fit to stakeholder needs, 5) identification of effective and timely means for communication, and 6) allocation of time, energy, and motivation for initiating and carrying through with communications.
authors.affiliation: SafeBridge Consultants, Inc., USA. Electronic address: michael.olson@safebridge.com.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Olson
authors.affiliation: Janssen Pharmaceutical Company, An Affiliate of Johnson & Johnson, USA.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Faria
authors.affiliation: EPHayes Toxicology Services, USA.
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Hayes
authors.affiliation: Eli Lilly and Company, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Jolly
authors.affiliation: Novartis, Switzerland.
authors.forename: Ester Lovsin
authors.initials: EL
authors.lastname: Barle
authors.affiliation: Mylan, USA.
authors.forename: Lance R
authors.initials: LR
authors.lastname: Molnar
authors.affiliation: Merck & Co., Inc., USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Naumann
authors.affiliation: University of Cincinnati, USA.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Pecquet
authors.affiliation: Pfizer Inc., USA.
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Shipp
authors.affiliation: SafeBridge Consultants, Inc., USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Sussman
authors.affiliation: Genentech, Inc., USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Weideman
mesh_terms: D000818:Animals; D003299:Cooperative Behavior; D004345:Drug Industry / Q000331:legislation & jurisprudence / Q000592:standards; D017408:Guidelines as Topic; D006291:Health Policy; D006801:Humans; D033183:Interdisciplinary Communication; D019055:No-Observed-Adverse-Effect Level; D016273:Occupational Exposure / Q000009:adverse effects / Q000331:legislation & jurisprudence / Q000517:prevention & control* / Q000592:standards; D016272:Occupational Health / Q000331:legislation & jurisprudence / Q000592:standards; D009937:Organizational Objectives; D004364:Pharmaceutical Preparations / Q000145:classification / Q000592:standards; D011050:Policy Making; D016730:Program Development; D018570:Risk Assessment; D018675:Toxicity Tests
chemical_list: D004364:Pharmaceutical Preparations
keywords: Acceptable Daily Exposure (ADE); Communication; Contract manufacturer; Monograph; Permitted Daily Exposure (PDE); Pharmaceutical manufacturing; Regulatory agencies; Stakeholder