The success of a biologic drug development program depends on a variety of factors, and is best supported by early consultation with industry experts on the breadth and design of the bioanalysis support required. Given the complexity of such programs, planning the assays that best enable appropriate assessments in pharmacokinetics, pharmacodynamics, and toxicokinetics, and translate from preclinical to clinical human trials, is a crucial step. Critical assays to consider will include biologic quantitation, immunogenic response assessment, cell-based functional assays and biomarkers. Novel or existing bioanalytical platforms and assays can be employed for the development of novel biologics and vaccines, and it is important to understand and be prepared for the challenges that are likely to arise.
A major consideration of any bioanalytical endpoint is translatability from preclinical to clinical trials, thus it is important to know which data you require to complete your submission(s), and which data is interesting but not essential. If your budget is limited, it is helpful to focus resources on the data required for your IND submission, or which can be helpful to facilitate further human studies later. If budget is not a major consideration, you can include endpoints which may not be absolutely necessary, but which do provide a more comprehensive data set.
You can benefit from invaluable scientific and regulatory guidance by partnering with an integrated early phase bioanalytical laboratory that can help you smoothly transition through the phases of your program, saving you both time and money. They can help you develop an effective bioanalytical plan, including the best assay design and timing, critical quality reagents, and sampling requirements, as well as translatability between species.
"As an example of how expert support is invaluable, for some new classes of biologics, specific regulatory guidance is not available, and in those circumstances an experienced provider can offer expert guidance on choices of bioanalytical platforms and fit-for-purpose assay validation criteria", mentions Lynne Le Sauteur, Vice President Laboratory Sciences at Altasciences.
Planning Your Program
Engaging with bioanalytical support partners as early as possible during the biologic development process will provide efficiencies over the longer term, as you can focus on the specific requirements for maximizing translatability of your assays. For example, the research and development assays used during discovery and biomanufacturing could serve as the seeds for appropriate method development that will later be transferred to the bioanalytical laboratory. Early drug quantitation assays from the discovery phase, which do not meet regulatory guidance for GLP studies, are often further optimized, or even modified, and can then be validated to support preclinical and clinical studies. In addition, biomanufacturing characterization assays such as potency assays can be adapted to support pharmacodynamics and cell- or ligand-based neutralizing assays in immunogenicity assessments.
As soon as a lead candidate is identified and toxicology studies are envisioned, bioanalysis support discussions and strategy should be outlined to ensure smooth progression, whether for assay transfers or de novo assay development. The inter-dependence of the preclinical and clinical design with the bioanalysis is paramount, as translatability of appropriate assays, data and biomarkers must be investigated. Elements that should be analyzed and confirmed are availability and stability of critical reagents for the duration of the program, cross-reactivity of reagents between species, and sensitivity requirements for assays based on regulatory guidance. Timely generation of a positive control antibody for immunogenicity testing is also an important step.
Choosing a Partner
Careful selection of an expert partner can provide advantages in efficiency, effectiveness, and acceleration of your drug development program. Danielle Salha, Senior Director, Immunochemistry, Immunology and Ligand Binding Assays states that "Altasciences' experience with biologics and vaccine development allows you to benefit from a broad portfolio of expertise with a range of modalities, including proteins, peptides, antibodies, protein drug conjugates, multifunctional biologics (such as bispecifics), oligonucleotides, and gene therapy, to allow effective development from preclinical to clinical studies. When you need bioanalysis for drug development programs, placed at Altasciences or elsewhere, we have the capabilities and expertise to provide quality data, interpretation and advice for your drug or vaccine development program."
As a closing, and extremely important, thought, good communication with the bioanalytical team is vital. It is beneficial to engage with a bioanalytical partner who will proactively raise important issues, and communicate openly with your experts to arrive at appropriate solutions for the entire lifecycle of your program. Agility, flexibility, and scientific creativity are essential.
Altasciences is a forward-thinking, mid-size contract research organization offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences' integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.