Understanding Pathways to a Paradigm S hift in Toxicity Testing - PowerPoint PPT Presentation

Understanding Pathways to a Paradigm S hift in Toxicity Testing and Decision Making Jim Jones, EVP , Consumer S pecialty Products Association

cience Fact ors in Int egrat ing 21 st Non S Cent ury S cience int o regulat ory decision making: EDS P  Context  Program  Key Factors Organizational S kill mix S takeholders Policy Choices S ummary

Cont ext of Endocrine Disrupt or Screening Program (EDSP)  EDS P assay development post FQP A occurs from 1998 (after getting advice from EDS TAC) through 2008. It took a decade to develop the battery of 11 tier 1 assays to screen for estrogen, androgen, and thyroid disruption.  April, 2009 EP A issues test orders for the first 67 chemicals for Tier 1 screening.  Data is submitted and reviewed by 2013- 4 years after assays are required.  Early in the process (1998) EDS TAC advised EP A that high throughput methods were not scientifically robust enough for screening.

Cont ext  R esearch by EP A ’s Office of R esearch and Development and its National Center for Computational Toxicology (NCCT), creates the potential for high throughput techniques to replacing some EDS P assays but not all. (Estrogen and Androgen related assays in particular).  The question for EP A: Does it move away from an approach that took years to develop for an alternative approach that still requires further scientific development. If so, how does it manage this “ pivot” ?

Cont ext : Jim’s Hierarchy of Applicat ion (fit for purpose and problem formulat ion)  Prioritization and S creening  Integrate with animal data (WOE)  Custom design a chemical data set  R eplacement  Risk Assessment

Organizat ional Issues  Multiple organizations involved: R esearch (ORD); EDS P program office (OS CP in OCPPS ), OPP (in OCS PP): Each has different cultures and obj ectives with respect to how to implement the Endocrine mandate.  ORD focused on the use of cutting edge research.  OS CP has spent 10-15 years on a framework j ust finalized and beginning to be implemented. Vested in that framework.  OPP is focused on its deadline to re-review all pesticides by 2022 and trying to ensure whatever approach is selected allows them to meet their statutory deadline.

Skills mix  Underlying some of the organizational issues. There are varying degrees of expertise in understanding computational techniques.  Highly trained individuals who are national and international experts at hazard assessment, exposure assessment and/ or risk assessment under that traditional animal based framework may not have the same status under the new framework.  The individuals with the most experience in the new techniques often don’ t have expertise in risk assessment and other aspects of regulatory decision making

St akeholders  It is necessary but not sufficient for stakeholders to understand the basis of decision making. To its credit EP A ’s ORD NCCT held monthly calls open to all stakeholders in an open forum to discuss ToxCast. OCS PP (the program office) relied on traditional means of getting stakeholder input/ buy in: Peer R eview, Policy FACA (PPDC), Notice and comment on program implementation. .  Peer R eview: EP A peer reviewed approaches to use HTS s before deploying several times (one scheduled next week).  PPDC: EP A routinely used its FACA advisory group to inform and get advice on its plans routinely.  EP A took comment through FR Notices on its planned approach.

Policy Choices  When and how t o “ pivot ” from t he old approach (11 t ier 1 assays) t o a new approach?  By June 2015, EP A was comfort able t hat HTS from ToxCast were adequat e t o replace 3 of t he Tier 1 assays (relat ed t o Est rogen).  EP A at t hat t ime said it would accept t he HTS as replacement s.  Should EP A cont inue t o issue orders before t he ot her 8 assays could be replaced?  Ult imat ely EP A decided not t o cont inue issuing orders but t o focus on science development of High Throughput t echniques.  Next week EP A will present t o a peer review HTS t echniques t hat may allow for replacement of some of t he Androgen relat ed assays.  In t he short t erm we’ ve delayed t he screening of chemicals wit h t he plan t hat moving t o HTS will ult imat ely lead t o much fast er screening of t he universe of 10,000 chemicals ident ified for screening.  EP A has also det ermined t hat it could use ToxCast and ExpoCast t o det ermine t he order of screening chemicals (priorit y set t ing)

Summary  There are numerous non technical factors that are important to manage when attempting to integrate new science into a regulatory process.  Arguably, priority setting is the most straightforward from both a scientific and programmatic implementation perspective.  EDS P offered a very challenging context although the upside was so big (the science was well under way and the status quo would take decades to implement).  S enior level engagement is critical.