* Carcinogenicity

1. Metadata/context , Sample/specimen descriptions, ex vivo study Cell line descriptions (i.e. for in vitro studies) Image data (e.g. X-ray of NHP bone develop.) Elements of Interconnectivity (Connectivity across data, documentation of study design, tool development, etc) Study Tags (pharm class, etc) Biomarker incorporation In vivo efficacy studies for FDA's Animal Rule Pharmacodynamic Drug Int. Other studies Device combinations Gastrointestinal System Autonomic Nervous System Formulation Data (Lot/Study linkages Renal/Urinary System Respiratory Safety Pharm. Study Design and logistics Cardiovascular Safety Pharm. Clinical Signs CNS Safety Pharm. Safety Pharmacology Historical Control Data Other Nonclinical Topics / Data Elements Other Pharmacokinetic Studies PK Drug Interactions Excretion Pharmacokinetics (PK) High Medium Low **Safety Pharmacology *Carcinogenicity *General Toxicology Pharmacokinetics Genetic Toxicity Pharmacology Priorities for a Nonclinical Standardization Roadmap **DART Debra Oetzman, Covance Laboratories Inc, Madison, WI; Lynda Sands, GlaxoSmithKline, King of Prussia, PA; Robert Dorsam, Food and Drug Administration, Silver Spring, MD; Gitte Frausing, Novo Nordisk, Denmark; Rick Thompson, Janssen Research & Development, Raritan, NJ; Anisa Scott, JMP Life Sciences, SAS Institute, Cary, NC; Lou Ann Kramer, Eli Lilly and Company, Indianapolis, Indiana; Sarah Obbers, Janssen Research & Development, Beerse, Belgium. Disclaimer: The opinions expressed on this poster are those of the authors and do not necessarily represent those of their organizations. Study Group Priority Prioritization of Study Groups. Study groups are listed in order of their priority based on the results of the survey. Single asterisks (*) indicate study groups which have been standardized. Double asterisks (**) represent those study groups currently being standardized. Introduction The Standards Roadmap Team (a subset of the FDA / PhUSE Working Group 6) have forged a collaboration aimed at addressing common issues with data management, data standards, and standards implementation. To support this activity, the group created a survey for members of industry to further understand the priorities of the many stakeholders of nonclinical data. We asked them to consider the entire expanse of nonclinical studies listed for Module 4 of the eCTD. Responders rated the study types and data elements with a scale of high, medium, or low priority and also had the option of leaving it blank (indicating no particular preference). the respondents were provided with a text field where they could provide a rationale for their response. A spot to comment on rationale for the preference was provided, and responders were asked to indicate whether they were responding as an individual or on behalf of their organization. Respondents consisted of both companies/institutions (n=4) and individuals (n=11) throughout industry. Study Type Priority Data Elements Priority Carcinogenicity General Toxicology High Developmental and Reproductive Toxicology Medium High Low Safety Pharmacology High High Medium Low Medium 0 2 4 6 8 10 12 14 Priority (# responses per priority level) Pharmacokinetics High Medium Metabolism Medium Low Low 0 2 4 6 8 10 12 14 Distribution Priority (# responses per priority level) Absorption Analytical Method/Valid. Report 0 2 4 6 8 10 12 14 Priority (# responses per priority level) Genetic Toxicology Miscellaneous High High Immunotoxicity Genotoxicity (in vivo) High Medium Genotoxicity (in vitro) Medium Bacterial Reverse Mutation Assay (Ames) Receptor Screens Low Mammalian Cell Micronucleus Test Low In Vivo Comet Assay Mechanistic studies (if not elsewhere) Mammalian Chromosome Aber. Test Mamm. Erythrocyte Micronucleus Test E. coli Reverse Mutation Assay Metabolites Mamm. Bone Marrow Chrom. Aber. Test Mammalian Cell Gene Mutation Test Sister Chrom. Exchange Assay in Mamm. Local Tolerance Tg. Rodent Som. & Germ Cell Gen Mut Low Liver Unsched. DNA Synthesis Medium Impurities 0 2 4 6 8 10 12 14 Priority (# responses per priority level) Antigenicity Pharmacology Dependence Mitogenicity High PharmacologyStudies Other Toxicity Studies (if available) Medium Primary Pharmacodynamics Low Low Secondary Pharmacodynamics 0 1 2 3 4 5 6 7 8 9 10 0 2 4 6 10 12 14 8 Priority (# responses per priority level) Priority (# responses per priority level) Prioritization of Study Types. Individual study types were rated as high, medium, or low priority by survey respondents. Red Font indicates study groups that have been standardized. Blue font denotes study types that are currently being standardized. Summary The results of the survey indicated that carcinogenicity and general toxicology were the highest priority study groups. Next, developmental and reproductive toxicology (DART) and safety pharmacology were high priorities. DART studies (Segment I, II, III) were similar in their perceived priority, whereas safety pharmacology had both high and low priorities among their study types. Pharmacokinetics studies were medium priority along with genetic toxicology studies. Respondents differed on the utility of pharmacology studies, which received both high and low priority status. A prioritization of several data elements which can be applied across study types is also provided. The Roadmap team recognized value in keeping study types grouped since conventions of standardization may be applied to several study types within a study group. Data utility, accessibility, gaps and complexity along with metadata linkage, resources, timelines and technological advancements in collection and/or reporting systems should be considered and carefully integrated as the roadmap is created. As we continue our work, the Team will use the data collected and presented in this poster to suggest a roadmap for development of nonclinical standards. Contact the Nonclinical Standardization Roadmap Working Group if you are interested in participating in this group at this link: http://www.phusewiki.org/wiki/index.php?title=WG6_Nonclinical_-_Standardization_Roadmapor responding to the survey at this link: http://www.phusewiki.org/wiki/index.php?title=File:Roadmap_Prioritization_PDF_V10.pdf.