ASVCP Pre-Meeting Workshop

8:00a.m. - 8:10a.m.
The ASVCP Regulatory Affair Committee: Focus on Best Practices in Toxicologic Clinical Pathology
Lindsay Tomlinson, DVM, DVSc
Pfizer Inc.
Anne Provencher, DVM, MS
Charles River Laboratories

8:10a.m. - 9:30a.m.
Routine Laboratory Investigations: Hematology, Coagulation, Clinical Biochemistry, and Urinalysis

The core clinical pathology panel recommended for laboratory animal toxicity and safety studies consists of well-characterized hematologic, blood chemistry, and urine analyses that inform on general body homeostasis and organ function and/or injury. Minimal testing recommendations have historically been broad or intentionally vague, to provide flexibility for appropriate study design, and to remain relevant and withstand the rapid pace of growth in biomarker capabilities. Our recent poll of routine testing practices in companies across industry suggests that standard testing panels have evolved along with technologic advances. Current standard panels, as indicated by survey respondents, generally followed or exceeded current guidelines. In this section of the symposium, we will present survey data for current standard panels, we will examine the appropriateness of current practices and guidelines in the context of existing knowledge and testing capabilities, and we will discuss whether there is a need for updating guidelines.

Lila Ramaiah, DVM, PhD
Huntingdon Life Sciences

Mehrdad Ameri, DVM, MS, PhD
Amgen

9:30a.m. - 10:00a.m.
PANEL DISCUSSION

10:00a.m. - 10:15a.m.
BREAK

10:15a.m. - 11:00a.m.
Non Routine Laboratory Investigations: Bone Marrow, Cytology, Endocrinology and Others
Denise Bounous, DVM, PhD
Bristol-Myers Squibb Co.

Clinical Pathologists and clinical pathology laboratories in pharmaceutical companies are increasingly expanding to include more than the routine biomarker panels in their repertoires. Bone marrow cytology, fluid cytology, and new biomarkers and platforms are utilized in many investigative studies. These are areas in which clinical pathologists are traditionally trained, but in pharmaceutical and toxicology studies this requires a different perspective than the more traditional diagnostic role. This expansion of traditional training further integrates the clinical pathologist into a role of consultant and advisor for interpretation of data in investigative studies for drug development.

11:00a.m. - 11:45a.m.
Instrument and Method Validation

Standard procedures for instrument and method validation are well established and described in text books and online references. In well established industry laboratories under the supervision of specialized clinical pathologists state of the art procedures are practiced and documented for all instruments and methods. However, in smaller laboratories without previous exposure to standard validation procedures or in a non GLP environment it may not always be possible to perform and document a complete package of validation procedures due to shortages in resources and personnel. The presentation will discuss basic validation procedures based on a number of real life problems encountered in environments without standardized instrument validation. In addition, practical examples will propose possible approaches for method validations in toxicologic clinical pathology.

Barbara Von Beust, Dr. med. vet., PhD
Labor am Zugersee

11:45am - 12:45pm
LUNCH

12:45p.m. - 1:45p.m.
Points to Consider for Identification, Qualification and Implementation of New Biomarkers

Interest in biomarker development in both the clinical and nonclinical setting has led to the increasingly widespread use of novel biomarkers for evaluation of target organ injury or drug target pharmacology. While the process for analytic validation of new parameters is both well understood and broadly implemented, characterization of unique biological aspects of these novel markers is often less comprehensively performed. Biomarker qualification involves biologic or physiologic characterization, with understanding of biologic variability, pre-analytic variables, as well as consideration of species-relevance and specificity for target organ or pharmacology. Novel biomarker qualification also involves pathophysiologic characterization, with consideration of relationship of novel marker changes to histopathologic findings or disease state, chronology and reversibility. Lastly, evaluation of diagnostic performance across a variety of treatments or experimental conditions in meta-analyses is a critical aspect of the biologic qualification of novel biomarkers that is increasingly being performed. This presentation will provide an example-based overview of key considerations for the application and development of novel safety markers in preclinical studies.

Daniela Ennulat, DVM, PhD
Glaxo SmithKline

1:45p.m. - 3:00p.m.
Data Analysis / Interpretation of Data

The final determination of compound-related and adverse effects in nonclinical studies requires the integrated assessment of clinical pathology data with concurrent pathology findings, in-life observations, exposure and metabolism data, and anticipated pharmacological effects of the test compound. Importantly, the approach to the interpretation of nonclinical data cannot be prescribed to cover all potential scenarios. Rather, the clinical pathology data should be evaluated on a case-by-case basis using a subjective “weight of evidence” approach. Toxicological pathologists, particularly clinical pathologists, are the best individuals for the interpretation and reporting of the clinical pathology data. In this session, general guidelines for interpreting and reporting clinical pathology data will be presented. Additionally, important tools in the interpretation and reporting of clinical pathology will be discussed to include statistical analysis, the peer review process, and the use of reference intervals.

Laura Boone, DVM, PhD
Covance Inc.

Overview of Roles and Responsibilities, Laboratory Personnel, and Report Process

Veterinary clinical pathologists are individuals with a doctorate in veterinary medicine plus formal training and board certification in clinical pathology. Did you know that approximately 70% of companies surveyed reported employing a total of 40 individuals with DVMs acting as clinical pathologists. Additionally, 85% percent of companies reported having minimal qualifications for laboratory professionals processing clinical pathology specimens. In this session we will explore how different companies utilize clinical pathologists and laboratory professionals among the surveyed companies and investigate the various roles they play in drug development. Finally we will identify emerging and recommended best practices surrounding industrial clinical pathology personnel and their roles and responsibilities.

Kelley Penraat, MS, DVM, MVSc
Alpha-Omega Vet Consultant Services

3:00p.m. - 3:30p.m.
PANEL DISCUSSION

3:30p.m. - 3:45p.m.
BREAK

3:45p.m. - 5:00p.m.
Beyond CBC and Chemistry Panel: The Expanding Roles of the Clinical Pathologist in Drug Development

Veterinary clinical pathologists have a thorough understanding of comparative biology, physiology, pharmacology, and pathology which positions them well to contribute to drug discovery and development in industry. There is increased recognition that clinical pathologists are necessary for the efficient operation and interpretation of clinical pathology in standard drug discovery and development studies. Beyond this recognition, there is a growing awareness of the breadth and versatility of these individuals throughout industry. However, there are still many situations in which veterinary clinical pathologists could be further utilized, such as in translational medicine. Translational medicine, which includes animal model work and biomarkers translatable to the clinic, is an area in which veterinary clinical pathologists can have substantial impact. Nontraditional roles in industry will be explored with examples of clinical pathology leaders in biomarker development, drug safety, immunotoxicology, pharmacovigilance and as liaisons to medical and research institutions.

Lindsay Tomlinson, DVM, DVSc
Pfizer Inc.

Conferences

ASVCP Pre-Meeting Workshop