Scientific and Regulatory Policy Committee Points to Consider*: Approaches to the Conduct and Interpretation of Vaccine Safety Studies for Clinical and Anatomic Pathologists

Abstract

The design and execution of toxicology studies supporting vaccine development have some unique considerations relative to those supporting traditional small molecules and biologics. A working group of the Society of Toxicologic Pathology Scientific and Regulatory Policy Committee conducted a review of the scientific, technical, and regulatory considerations for veterinary pathologists and toxicologists related to the design and evaluation of regulatory toxicology studies supporting vaccine clinical trials. Much of the information in this document focuses on the development of prophylactic vaccines for infectious agents. Many of these considerations also apply to therapeutic vaccine development (such as vaccines directed against cancer epitopes); important differences will be identified in various sections as appropriate. The topics addressed in this Points to Consider article include regulatory guidelines for nonclinical vaccine studies, study design (including species selection), technical considerations in dosing and injection site collection, study end point evaluation, and data interpretation. The intent of this publication is to share learnings related to nonclinical studies to support vaccine development to help others as they move into this therapeutic area. [Box: see text]

Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities

“…Additional studies acquire knowledge on timing of administrations, total number of doses, and induction (priming) and booster (maintenance) intervals to establish a rationale for an initial clinical schedule. 84,102 A lack of widely accepted allometric scaling approaches to calculate an equivalent dose across species limits translatability, providing only a rough estimate to support clinical trial designs. [103][104][105] The optimal dose in a personalized TCV will likely vary across antigens, and the total antigen dose must ensure delivery of adequate amounts of the less immunogenic antigens.…”

Toxicity and Local Tolerance of COVID- eVax, a Plasmid DNA Vaccine for SARS-CoV-2, Delivered by Electroporation

“…With reference to the injection site, the quadriceps muscle from both sides and from all animals were divided into 3 portions (i.e., cranial, central, distal) and embedded in paraffin. This trimming procedure followed the recommendation of Sellers et al, 18 in order to achieve optimal sampling of the site of injection. From the overlying skin, a single sample was processed, corresponding to the central portion of the skin injection site.…”

“…[12][13][14][15] Since the SARS-CoV-2 vaccines are developed as preventive measures to be administered to a healthy population, it is of utmost importance to properly evaluate the safety of such vaccines in well-designed and GLP-compliant preclinical toxicity studies. [16][17][18] Therefore, the aim of this study was to assess the systemic toxicity and local tolerance of the TKSB01 plasmid in Sprague Dawley (SD) rats, delivered intramuscularly and followed by EP.…”

Review of Current Vaccine Development Strategies to Prevent Coronavirus Disease 2019 (COVID-19)

“…The typical nonclinical toxicity study design, commonly observed findings and risk assessment strategies were discussed in detail in a recently published STP SRPC Points to consider paper on vaccine safety studies. 40 This current review is written with the expectation that it will be read in context with the previously published SRPC manuscript. Since most SARS-CoV-2 vaccine candidates are expected to use platform technologies with previously generated nonclinical and clinical safety data, this review only addresses potential theoretical safety risks associated with SARS-CoV-2 vaccine candidates.…”

“…Regulatory toxicology studies for vaccines generally follow similar study design as small molecule and biotherapeutics, with additional end points to assess acute phase response and immunogenicity of the vaccine antigens. Regulatory guidelines and key aspects of regulatory toxicology studies (study design, study conduct, commonly observed findings, and interpretation) for vaccines were reviewed in a recently published Society of Toxicologic Pathology (STP) Scientific and Regulatory Policy Committee (SRPC) Points to Consider article in Toxicologic Pathology 40 and covered in an STP Continuing Education course in August 2020.…”