Transcript Slide 1

Priorities for a Nonclinical Standardization Roadmap
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.
High
Medium
Low
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
High
High
Carcinogenicity
General Toxicology
Developmental and Reproductive Toxicology
High
Historical Control Data
Medium
Study Design and logistics
Safety Pharmacology
Low
Clinical Signs
Formulation Data (Lot/Study linkages
Safety Pharmacology
High
Respiratory Safety Pharm.
Biomarker incorporation
Medium
Cardiovascular Safety Pharm.
Medium
Low
CNS Safety Pharm.
Renal/Urinary System
Autonomic Nervous System
Gastrointestinal System
Metadata/context ,
(Connectivity across data, documentation of
study design, tool development, etc)
Sample/specimen descriptions, ex vivo study
Study Tags (pharm class, etc)
Pharmacodynamic Drug Int.
Elements of Interconnectivity
Other studies
Cell line descriptions (i.e. for in vitro studies)
0
2
4
6
8
Priority (# responses per priority level)
10
12
14
Device combinations
Pharmacokinetics
Image data (e.g. X-ray of NHP bone develop.)
Medium
Low
Low
Medium
In vivo efficacy studies for FDA's Animal Rule
High
Pharmacokinetics (PK)
Metabolism
PK Drug Interactions
Distribution
Other Nonclinical Topics / Data Elements
0
2
4
6
8
10
12
14
Priority (# responses per priority level)
Absorption
Analytical Method/Valid. Report
Excretion
Other Pharmacokinetic Studies
0
2
4
6
8
10
12
14
High
Priority (# responses per priority level)
Genetic Toxicology
Miscellaneous
High
Immunotoxicity
High
Medium
Medium
Receptor Screens
Low
Low
Mechanistic studies (if not elsewhere)
Medium
Low
Genotoxicity (in vivo)
Genotoxicity (in vitro)
Bacterial Reverse Mutation Assay (Ames)
Mammalian Cell Micronucleus Test
In Vivo Comet Assay
Mammalian Chromosome Aber. Test
Mamm. Erythrocyte Micronucleus Test
E. coli Reverse Mutation Assay
Mamm. Bone Marrow Chrom. Aber. Test
Mammalian Cell Gene Mutation Test
Sister Chrom. Exchange Assay in Mamm.
Tg. Rodent Som. & Germ Cell Gen Mut
Liver Unsched. DNA Synthesis
0
2
4
6
8
10
Priority (# responses per priority level)
12
14
Metabolites
Local Tolerance
Impurities
Antigenicity
Pharmacology
Dependence
Mitogenicity
Medium
Primary Pharmacodynamics
Low
Secondary Pharmacodynamics
Low
High
Pharmacology Studies
Other Toxicity Studies (if available)
0
0
2
4
6
8
10
12
14
1
2
3
4
5
6
7
8
Priority (# responses per priority level)
9
10
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_Roadmap or responding to the survey at this link: http://www.phusewiki.org/wiki/index.php?title=File:Roadmap_Prioritization_PDF_V10.pdf.