ProRelix Research offers customized, end-to-end services for clinical trials of a broad range of biological products to help bring both innovator biologics and biosimilars to the market in a timely and cost-effective manner. We ensure compliance with regulatory requirements in all operations to facilitate a smooth transition of your product from bench to bedside. Our experts can help develop strategies to overcome difficulties in trial management of biologicals by partnering with facilities equipped for biologicals assays and analysis.
Biological products are isolated from natural sources such as humans, animals, or microorganisms or can be produced by biotechnology methods. They include vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologics have been approved for the treatment of several autoimmune diseases and inflammatory diseases such as Crohn’s disease and ulcerative colitis (adalimumab, golimumab, infliximab), rheumatoid arthritis (adalimumab, etanercept), and cancers (vaccines, chimeric antigen receptor (CAR) T-cell therapy, monoclonal antibodies). Unlike small-molecule drugs that are chemically synthesized and have a well-defined and reproducible structure, biologicals are large, complex molecules. Being natural in origin, biologicals exhibit inherent variability and exist as complex mixtures and therefore cannot always be accurately identified and characterized. Manufactured biologicals exhibit some degree of batch-to-batch variation which is acceptable by regulatory agencies provided that the manufacturer delineates the appropriate manufacturing controls. Thermal sensitivity and propensity for microbial contamination of biologicals requires strict controls on the manufacturing process and storage conditions.
Despite the problems associated with handling and characterizing biologicals, often they represent the only means of treatment for several diseases necessitating their availability to patients. Like small molecule drugs, new biologicals must undergo rigorous preclinical and clinical evaluation before marketing to ensure safety, efficacy, and quality to patients. Furthermore, just as ‘generics’ are copies of synthesized drugs, biosimilars represent the generic equivalent of innovator biologicals. However, in contrast to generics which are identical to the innovator drug, biosimilars are ‘highly similar’ and have no clinically meaningful differences from the reference biological. Biosimilars also have an abbreviated pathway for their approval based on a shorter timeline and fewer clinical and nonclinical studies like an abbreviated new drug application (ANDA) for generics.
Biologicals also require Investigational New Drug (IND) submission to the FDA before the initiation of first-in-human trials. Phase I and II trials assess the pharmacology and safety of the biological and Phase III is focused on demonstration of efficacy and safety in a larger patient population. Like a new drug application (NDA) which is submitted to the FDA following the spectrum of clinical studies, marketing of biologicals requires submission and approval of a biologics license application (BLA). The BLA is a comprehensive document that contains information on manufacturing processes, chemistry, nonclinical pharmacology and toxicology, human pharmacokinetics and bioavailability, and clinical pharmacology. Biosimilars approval can be attained through an abbreviated pathway that may not require all clinical studies to be performed and can shorten timelines for approval considerably.
Under the Public Health Service (PHS) act there are two approval pathways for biological products
- Traditional pathway or Full BLA Section 351(a): this application is submitted for innovator biologicals and must contain all the safety and efficacy information. It is also known as a ‘standalone’ application as it contains new information on the biological product.
- Biosimilar BLA Section 351(k): this application is submitted for biosimilar products and can draw from information submitted for the innovator or reference biological.
Biosimilarity can be based on data from analytical, animal, and clinical studies. Clinical studies should be designed to demonstrate the safety, purity, and potency of the biosimilar product to the reference through immunogenicity, pharmacokinetic (PK), pharmacodynamic (PD), and comparative clinical studies. The FDA decides studies to be included in the final application following a thorough assessment.
Broadly clinical trial phases are similar between small molecule drugs and biologicals, however, there are some details that need to be considered when conducting clinical trials for biologicals. Unlike chemically synthesized drugs, biologicals have the potential to elicit allergic reactions, immunogenicity reactions, and other unexplained side effects due to their complex structure requiring a strict and continuous safety monitoring program for patient safety. The physical instability of biologicals is another issue that makes it essential for proper handling and storage of these products to prevent changes in potency and degradation.
Keeping in mind the special needs for clinical trials of biologicals, ProRelix research is your ideal partner throughout your clinical trial journey from IND approval to Phase III studies for innovator biologicals and biosimilars. We provide the following services:
- Study protocol development and design
- Participant selection and recruitment
- Investigational product handling: adequate storage, transport, and dispensing to maintain product integrity under sterile conditions
- Site identification and qualification
- Ongoing safety monitoring programs
- Design of immunogenicity studies: population, dose, sampling schedule, development and validation of antibody assays
- Site management and study monitoring: Study startup, interim and close-out visits
- Compliance with Good Clinical Practice (GCP) and other relevant regulatory guidelines
- Obtaining ethics committee approval
- Writing services: Investigator’s brochure, informed consent forms, case report forms
- Pharmacovigilance programs for reporting adverse reactions
- Implementation of a quality management system and standard operating procedures (SOPs)
- Database lock and data archival
- Statistical data interpretation and analysis, creation of statistical analysis report
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