As Salamandra’s Senior Consultant, Nonclinical, Melissa brings a wealth of regulatory experience and scientific depth to help clients navigate the complex landscape of drug development.
Before joining Salamandra, Melissa served as a Nonclinical Team Lead and Reviewer in the Division of Hematology Oncology Toxicology at the FDA. There, she reviewed pre-IND meetings and IND, NDA, and BLA applications across a broad range of product types – including small molecules, monoclonal and bi-/tri-specific antibodies, oligonucleotides, fusion and recombinant proteins, antibody-drug conjugates, and other novel modalities. She applied her immunology and oncology expertise to tackle challenging safety issues around immune-modulating drugs and led initiatives focused on identifying opportunities to reduce animal use in regulatory testing.
At Salamandra, Melissa leverages this regulatory insight and scientific rigor to support clients across all stages of the drug life cycle. She provides strategic advice on nonclinical aspects of regulatory submissions, helps design toxicology studies and safety assessment strategies, authors key sections of regulatory documents, and supports meetings and interactions with regulatory authorities. Her work ensures nonclinical programs are scientifically sound, globally aligned, and built to support successful development.
Melissa’s background spans both bench science and regulatory review. She helped develop CAR-T cell therapies at the National Cancer Institute and studied therapeutic protein stability and immunogenicity at FDA. She received her PhD training in immunology at the University of Alabama at Birmingham, where she focused on the role of myeloid cells in health and disease.
She enjoys working with Salamandra’s collaborative, multi-disciplinary team to solve unique and complex challenges across a wide range of product types and therapeutic areas – all with the goal of supporting the development of new patient treatments.
In her spare time, Melissa enjoys spending time outdoors hiking and camping (especially with her dogs), traveling, and cooking new recipes. She particularly loves finding ways to combine hobbies and has trekked an active volcano and the Swiss Alps.
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“I chose this picture because I have always been fascinated by the ocean and marine life, particularly sea turtles. The natural beauty, vastness, and diverse life of the ocean evoke a deep sense of wonder.”
3 October 2025
KEY TAKEAWAYS
Nonclinical studies bridge a drug from discovery to the clinic and inform on safety at all stages of clinical development.
In addition to being used to determine a safe first-in-human (FIH) starting dose, nonclinical data are used to predict adverse events and identify appropriate monitoring plans for a clinical trial.
The types of nonclinical studies needed are determined by the type of product, proposed indication, and clinical trial design.
When changes occur during clinical development, such as formulation changes or changes to the route of administration, nonclinical data can often be used to identify potential risks and develop mitigation strategies.
Transitioning a new drug candidate from discovery to the clinic is a significant leap, and a strong nonclinical development plan is critical to success. The ultimate goal of a nonclinical program is to identify and characterize potential risks to humans in a clinical trial. After the initial discovery phase, nonclinical experts work collaboratively with clinical, chemistry, manufacturing, and controls (CMC), and regulatory colleagues to ensure the nonclinical development program is appropriately designed to align with clinical development objectives and to satisfy regulatory requirements. In addition to generating data that can be used to determine a first-in-human (FIH) starting dose, nonclinical studies should support the intended dosing schedule and guide appropriate safety monitoring in a clinical trial. Insight gained from a robust nonclinical development program not only enables the safe progression of an investigational drug into the clinic but also guides strategies for future clinical and nonclinical testing, regulatory meetings and submissions, and eventual marketing applications.
A nonclinical program usually includes pharmacology, pharmacokinetic, and toxicology studies. However, the exact studies that are needed depend upon several factors, such as the type of product, proposed indication, route of administration, dosing regimen, and duration of dosing. For example, nonclinical development of a monoclonal antibody product intended to treat lung cancer will look quite different from a small molecule drug being developed for the treatment of rheumatoid arthritis. A general timeline of nonclinical studies is provided below in Figure 1; however, the exact timing of studies may vary based on overall development goals and regulatory requirements for a therapeutic product.
Figure 1: General Overview of Timing of Nonclinical Studies
Among the first nonclinical evaluations to be conducted are pharmacology studies, including primary, secondary, and safety pharmacology assessments. Primary pharmacology studies, typically conducted during the discovery phase, are important to understand the mechanism of action for a drug and demonstrate proof-of-concept, i.e., initial efficacy. These studies can be used to provide insights into important aspects of future nonclinical and clinical studies, such as doses to be evaluated, combinations of drugs, and selection of biomarkers. Thus, it is important to select the most appropriate and relevant models to evaluate pharmacologic activity and the potential for efficacy based on the target of the drug and proposed therapeutic indication. While primary pharmacology studies focus on the intended therapeutic effect, secondary pharmacology studies can help understand aspects of the drug’s safety profile by elucidating off-target effects; these studies will generally include large panels of kinases, enzymes, receptors, ion channels, and other proteins. The core battery of safety pharmacology studies includes assessments of a drug’s effects on cardiovascular, central nervous, and respiratory parameters; these assessments are evaluated using in vivo and in vitro studies, such as human ether-a-go-go-related gene (hERG) assays to evaluate potential for cardiotoxicity. While in vivo safety pharmacology studies can be stand-alone studies, these endpoints are often incorporated into the Good Laboratory Practice (GLP)-compliant repeat-dose toxicology studies to streamline development. Overall, findings from pharmacology studies characterize the intended and unintended activity of a drug and support the assessment of safety in humans.
Nonclinical pharmacokinetic (PK) studies collect data on the absorption, distribution, metabolism, and excretion (ADME) of a drug. PK is evaluated with both in vitro (i.e., blood and tissue samples from animals), and in vivo methodologies. These studies provide valuable information on systemic exposures that may be achieved clinically, and in combination with findings from pharmacology studies, can help establish an exposure-response relationship to predict doses that result in a therapeutic effect. A limited evaluation early in development can be sufficient to support species selection for toxicology studies by comparing metabolite profiles in animals versus humans, but further evaluation should proceed in parallel with GLP toxicology studies and initial clinical development.
GLP-compliant toxicology studies to support drug development should generally be conducted in two species, one rodent and one nonrodent. Study design is an important consideration and should support the intended route of administration and dosing regimen for the proposed clinical trial. Critical factors in the design of these studies include species selection, dose levels, and dosing duration:
Species selection should be based on scientific knowledge of the pharmacology, toxicity, and PK profile of a drug; it is important that adequate systemic exposure to parent drug and human-relevant metabolites are achievable in the selected species to enable the establishment of safety margins. Rats are commonly selected as the rodent species, and dogs or nonhuman primates (usually cynomolgus monkeys) are frequently used as the nonrodent species. While this approach applies for many new investigational drugs, there are situations where studies in two species may not be needed. For example, because antibody-based therapeutics bind very specific targets, toxicity testing for these products should be conducted in a relevant species that expresses the intended target and in which the drug is pharmacologically active. If only one such species is identified, then conducting toxicity testing in a single species may be considered appropriate.
Careful consideration should be given to dose levels evaluated in a toxicology study. Doses should be selected to allow for characterization of clinically relevant toxicities, and studies should generally include more than one dose level to enable identification of dose-dependent responses. A control group should be included in the design of the toxicology study to aid in determining whether findings are related or unrelated to treatment with the investigational drug. Any adverse findings observed in the toxicology studies should be carefully evaluated in the context of the proposed clinical trial to identify the potential risks to human participants; this information can also be used to determine the appropriate monitoring that may be needed to ensure safety. Additionally, a no-adverse-effect-level (NOAEL) should be identified to support selection of clinical doses; for a FIH study, the NOAEL in the most sensitive species should provide a safety margin at least 10-times higher than the proposed clinical dose.
The duration of the nonclinical toxicology studies is related to the size, duration, and therapeutic area of a clinical trial but, in general, should be equal to or exceed the duration of a proposed clinical trial. Single dose (acute) and/or short-term repeat-dose toxicology studies may support a FIH clinical study or other early phases of clinical development where exposure is limited. Sub-chronic and/or chronic toxicology studies that evaluate dosing for longer periods (up to 6 months in rodents and 9 months in nonrodents to support clinical dosing for 6 months or longer) must be submitted prior to Phase 3 clinical studies or studies intended to support a marketing application.
In addition to general toxicology studies, genetic toxicology studies should also be conducted prior to testing in humans. An assay for gene mutation, such as an in vitro bacterial reverse mutation assay (i.e., Ames assay), is expected to support single-dose clinical trials. In vitro and in vivo assays to detect chromosomal damage, including chromosomal aberration and micronucleus assays, are needed to support clinical trials evaluating multiple doses. A complete battery of genetic toxicology studies should be completed before initiation of Phase 2 clinical trials. If these studies return positive results, additional follow-up testing may be needed to further evaluate risks.
While a nonclinical program is heavily focused on supporting safety during early stages of development, nonclinical studies can be informative throughout the entire drug development life cycle, including through submission of a marketing application. Initial Phase 1 trials are conducted in a small number of participants over a limited treatment duration, often starting with doses resulting in relatively low systemic exposure in healthy volunteers; these are followed by clinical trials that expand in size of the exposed population and duration of treatment. As development proceeds, other types of toxicology studies are required to support the expanded scope of clinical investigations, including reproductive and developmental toxicology, phototoxicity, and/or carcinogenicity studies. Additional immunotoxicity studies may also be needed for immune-modulating drugs.
Safety issues and concerns that may arise from findings across disciplines are often evaluated and mitigated based on data from nonclinical studies. Changes to a program once studies are initiated, such as a change in route of administration or modifications to the active pharmaceutical ingredient (API) or formulation that lead to an altered impurity profile or the use of novel excipients, may result in the need for nonclinical studies to support the change. It is also important to remember that data generated early in development may be used at later stages, including to support a marketing application and proposed labeling.
Though the general components of a nonclinical program have been outlined above, there are situations where abbreviated programs may be acceptable. Regulatory flexibility in nonclinical requirements may apply in certain circumstances, including for drugs intended to treat life-threatening or serious conditions; as such, the types of studies needed to support clinical trials for drugs with oncology indications differ from non-oncology indications. Further, the array of targets, indications, novel drug structures, and drug combinations being evaluated clinically continues to grow, and it can be challenging to determine what types of studies are informative and what types of studies are not necessary. There are also ongoing efforts across consortia, regulators, and other interest groups to continue to optimize and refine nonclinical testing to maximize useful data while minimizing unnecessary animal use and costs.
Salamandra is actively following these evolving industry-wide efforts to streamline and strengthen nonclinical approaches. Given these shifts in data expectations and study requirements, expert insight can be instrumental in guiding your nonclinical development program. If you have questions about nonclinical development programs or need assistance in evaluating nonclinical data or developing a nonclinical regulatory strategy, Salamandra’s experts are here to support you. Contact us at hello@salamandra.net to learn more.
This article is Part 2 of a series to explore expectations and requirements for early drug development from the nonclinical, clinical pharmacology, clinical, and CMC perspectives.
