STP Best Practices for Evaluating Clinical Pathology in Pharmaceutical Recovery Studies

Tomlinson, Lindsay; Ramaiah, Lila; Tripathi, Niraj; Barlow, Valerie G.; Vitsky, Allison; Poitout-Belissent, Florence; Bounous, Denise I.; Ennulat, Daniela

doi:10.1177/0192623315624165

Cited by 17 publications

(8 citation statements)

References 31 publications

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“…Current standards in validation for clinical pathology and biomarker methods commonly include testing sample stability under a variety of conditions (eg, room temperature [20-25 °C], refrigerated [3 to 4 °C], frozen [−20 to −70 °C], after ≥1 freeze thaw cycle, etc). 34 -36 Clinical pathology laboratories may perform various elements of this stability testing in house during method validation, particularly for routine clinical pathology analyses, and/or may refer to the literature for information on expected stability duration.…”

Section: Survey Results: Current Practices and Rationale For Retentio...mentioning

confidence: 99%

Scientific and Regulatory Policy Committee Points to Consider: Biological Sample Retention From Nonclinical Toxicity Studies

Harbison

Aulbach²,

Bennet

et al. 2021

Toxicol Pathol

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Samples of biologic specimens and their derivatives (eg, wet tissues, paraffin-embedded tissue blocks, histology slides, frozen tissues, whole blood, serum/plasma, and urine) are routinely collected during the course of nonclinical toxicity studies. Good Laboratory Practice regulations and/or guidance specify minimum requirements for specimen retention duration, with the caveat that retention of biologic specimens need not extend beyond the duration of sample stability. However, limited availability of published data regarding stability for various purposes following storage of each specimen type has resulted in confusion, uncertainty, and inconsistency as to the appropriate duration for storage of these specimens. To address these issues, a working group of the Society of Toxicologic Pathology Scientific and Regulatory Policy Committee was formed to review published information, regulations, and guidance pertinent to this topic and to summarize the current practices and rationales for retention duration through a survey-based approach. Information regarding experiences reaccessing biologic specimens and performing sample stability investigations was also collected. Based on this combined information, the working group developed several points to consider that may be referenced when developing or revising sample retention practices. [Box: see text]

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Section: Survey Results: Current Practices and Rationale For Retentio...mentioning

confidence: 99%

Scientific and Regulatory Policy Committee Points to Consider: Biological Sample Retention From Nonclinical Toxicity Studies

Harbison

Aulbach²,

Bennet

et al. 2021

Toxicol Pathol

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“…However, the number of CP time points required for a given study can be minimized using information gained in earlier, preliminary studies. Exclusion of testing during a treatment‐free period is another option, if these are not found to be necessary after evaluation of the end of dose data . However, this practice is of limited utility in terms of blood volume reduction (except in mice which would require an additional cohort) because of the larger sample volumes that can be collected at necropsy.…”

Section: Opportunities For Reducing Animal Usementioning

confidence: 99%

Reducing blood volume requirements for clinical pathology testing in toxicologic studies—points to consider

Poitout-Belissent

Aulbach

Tripathi

et al. 2016

Veterinary Clinical Pathol

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In preclinical safety assessment, blood volume requirements for various endpoints pose a major challenge. The goal of this working group was to review current practices for clinical pathology (CP) testing in preclinical toxicologic studies, and to discuss advantages and disadvantages of methods for reducing blood volume requirements. An industry-wide survey was conducted to gather information on CP instrumentation and blood collection practices for hematology, clinical biochemistry, and coagulation evaluation in laboratory animals involved in preclinical studies. Based on the survey results and collective experience of the authors, the working group proposes the following "points to consider" for CP testing: (1) For most commercial analyzers, 0.5 mL and 0.8 mL of whole blood are sufficient for hematology and biochemistry evaluation, respectively. (2) Small analyzers with low volume requirements and low throughput have limited utility in preclinical studies. (3) Sample pooling or dilution is inappropriate for many CP methods. (4) Appropriate collection sites should be determined based on blood volume requirements and technical expertise. (5) Microsampling does not provide sufficient volume given current analyzer and quality assurance requirements. (6) Study design considerations include: the use of older/larger animals (rodents), collection of CP samples before toxicokinetic samples, use of separate subsets of mice for hematology and clinical biochemistry testing, use of a priority list for clinical biochemistry, and when possible, eliminating coagulation testing.

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“…Though one dose group should suffice, it is important that a relevant dose group is used, and this may not always be the highest dose group (e.g., low dose may be more appropriate for biologics to avoid oversaturation of the target). However, it can also be questioned whether a control group is always necessary, since the purpose of the recovery groups is to assess recovery from treatment-related effects that requires comparison between main study animals with recovery animals of the same dose ( Konigsson 2010 ; Sewell et al 2014 ; Tomlinson et al 2016 ). This may be more applicable to studies with short recovery periods and with sexually mature nonrodents, where there is minimal risk of age-related phenotypic drifts.…”

Section: Recovery Animalsmentioning

confidence: 99%

Opportunities to Apply the 3Rs in Safety Assessment Programs

Sewell

Edwards

Prior

et al. 2016

ILAR J

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Before a potential new medicine can be administered to humans it is essential that its safety is adequately assessed. Safety assessment in animals forms an integral part of this process, from early drug discovery and initial candidate selection to the program of recommended regulatory tests in animals. The 3Rs (replacement, reduction, and refinement of animals in research) are integrated in the current regulatory requirements and expectations and, in the EU, provide a legal and ethical framework for in vivo research to ensure the scientific objectives are met whilst minimizing animal use and maintaining high animal welfare standards. Though the regulations are designed to uncover potential risks, they are intended to be flexible, so that the most appropriate approach can be taken for an individual product. This article outlines current and future opportunities to apply the 3Rs in safety assessment programs for pharmaceuticals, and the potential (scientific, financial, and ethical) benefits to the industry, across the drug discovery and development process. For example, improvements to, or the development of, novel, early screens (e.g., in vitro, in silico, or nonmammalian screens) designed to identify compounds with undesirable characteristics earlier in development have the potential to reduce late-stage attrition by improving the selection of compounds that require regulatory testing in animals. Opportunities also exist within the current regulatory framework to simultaneously reduce and/or refine animal use and improve scientific outcomes through improvements to technical procedures and/or adjustments to study designs. It is important that approaches to safety assessment are continuously reviewed and challenged to ensure they are science-driven and predictive of relevant effects in humans.

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STP Best Practices for Evaluating Clinical Pathology in Pharmaceutical Recovery Studies

Cited by 17 publications

References 31 publications

Scientific and Regulatory Policy Committee Points to Consider: Biological Sample Retention From Nonclinical Toxicity Studies

Scientific and Regulatory Policy Committee Points to Consider: Biological Sample Retention From Nonclinical Toxicity Studies

Reducing blood volume requirements for clinical pathology testing in toxicologic studies—points to consider

Opportunities to Apply the 3Rs in Safety Assessment Programs

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