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Developmental and Reproductive Toxicology

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Priorities for a Nonclinical Standardization Roadmap

Data Elements Priority

Miscellaneous

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.

Genetic Toxicology

Safety Pharmacology

Pharmacology

Carcinogenicity

General Toxicology

Pharmacokinetics

0 2 4 6 8 10 12 14

Safety Pharmacology

CNS Safety Pharm.

Cardiovascular Safety Pharm.

Renal/Urinary System

Autonomic Nervous System

Gastrointestinal System

Other studies

Pharmacodynamic Drug Int.

Priority (# responses per priority level)

Respiratory Safety Pharm.

0 2 4 6 8 10 12 14

Pharmacokinetics (PK)

Analytical Method/Valid. Report

Absorption

Distribution

Metabolism

Excretion

PK Drug Interactions

Other Pharmacokinetic Studies

Priority (# responses per priority level)

0 2 4 6 8 10 12 14

Genotoxicity (in vitro)Bacterial Reverse Mutation Assay (Ames)

E. coli Reverse Mutation Assay

Mammalian Chromosome Aber. Test

Mammalian Cell Gene Mutation Test

Mammalian Cell Micronucleus Test

Sister Chrom. Exchange Assay in Mamm.

Genotoxicity (in vivo)

Mamm. Erythrocyte Micronucleus Test

Mamm. Bone Marrow Chrom. Aber. Test

Liver Unsched. DNA SynthesisTg. Rodent Som. & Germ Cell Gen Mut

In Vivo Comet Assay

Priority (# responses per priority level)

Pharmacology Studies

Primary Pharmacodynamics

Secondary Pharmacodynamics

0 2 4 6 8 10 12 14

Priority (# responses per priority level)

0 2 4 6 8 10 12 14

Other Nonclinical Topics / Data Elements

Historical Control Data

Clinical Signs

Study Design and logistics

Formulation Data (Lot/Study linkages

Device combinations

In vivo efficacy studies for FDA's Animal Rule

Biomarker incorporation

Study Tags (pharm class, etc)

Elements of Interconnectivity

Image data (e.g. X-ray of NHP bone develop.)

Cell line descriptions (i.e. for in vitro studies)

Sample/specimen descriptions, ex vivo study

Metadata/context , (Connectivity across data, documentation of

study design, tool development, etc)

Priority (# responses per priority level)

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Medium

Low

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Local Tolerance

Other Toxicity Studies (if available)

Antigenicity

Immunotoxicity

Mechanistic studies (if not elsewhere)

Dependence

Metabolites

Impurities

Mitogenicity

0 1 2 3 4 5 6 7 8 9 10

Receptor Screens

Priority (# responses per priority level)

SummaryThe 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.

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.

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.

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_Roadmap or responding to the survey at this link: http://www.phusewiki.org/wiki/index.php?title=File:Roadmap_Prioritization_PDF_V10.pdf.

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.

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