{"id":7689,"date":"2024-06-20T11:33:22","date_gmt":"2024-06-20T16:33:22","guid":{"rendered":"https:\/\/labtesting.\/?p=7689"},"modified":"2024-06-20T11:33:30","modified_gmt":"2024-06-20T16:33:30","slug":"unlocking-the-potential-navigating-non-toxicology-programs-for-biotherapeutics","status":"publish","type":"post","link":"https:\/\/labtesting.\/2024\/06\/20\/unlocking-the-potential-navigating-non-toxicology-programs-for-biotherapeutics\/","title":{"rendered":"Unlocking the Potential: Navigating Non-Toxicology Programs for Biotherapeutics"},"content":{"rendered":"\n
As the field of biopharmaceuticals continues to expand, drug developers are faced with the critical task of planning non-toxicology programs for biotherapeutics. These programs play a pivotal role in ensuring the safety and efficacy of novel drugs before they reach clinical trials. Here, we explore the essential considerations that underpin successful non-toxicology programs, guiding drug developers through Investigation New Drug (IND) applications and Clinical Trial Applications (CTA).<\/p>\n\n\n\n
The decision to engage a toxicology consultant often stands overlooked amidst the flurry of drug development activities, particularly in teams that don\u2019t have in-house toxicology expertise. A toxicology consultant can help guide your nonclinical toxicology strategy for your product, including important decisions about nonclinical species selection and selection and engagement of a laboratory testing partner to conduct the in vitro<\/em> and in vivo<\/em> toxicology studies, helping to avoid any unforeseen pitfalls. A toxicology consultant offers invaluable insights, aiding in navigating regulatory expectations, defining study timelines, and steering the program toward success.<\/p>\n\n\n\n Before first-in-human (FIH) clinical trials can begin, regulatory guidelines require in vivo<\/em> toxicology studies, complying with Good Laboratory Practice (GLP) standards. While early exploratory toxicology studies and dose range-finding studies are typically not conducted under GLPs, it is always best to conduct all assays associated with GLP toxicity studies. In some cases, an exception can be made, and an assay can be qualified but not conducted under GLP (i.e., specialty immunophenotyping or cytokine endpoints). These exceptions will be noted in study protocols and final reports submitted to health authorities.<\/p>\n\n\n\n On the other hand, in vivo<\/em> pharmacokinetics (PK) studies are not required to be conducted under GLPs. Pharmacokinetic\/toxicokinetic assessments (drug concentration and anti-drug antibody [ADA] assays) conducted as part of a GLP toxicity study do require validated assays and must meet GLP standards.<\/p>\n\n\n\n A toxicology consultant can help guide which in vivo<\/em> or in vitro<\/em> studies regulators require to be conducted under GLPs and the level of characterization of the drug substance necessary to support non-GLP and GLP studies. By aligning with regulatory standards, drug developers bolster the integrity of their non-toxicology programs, laying a solid foundation for subsequent clinical translation.<\/p>\n\n\n\n The development of critical bioanalytical reagents and assays is too often deprioritized. However, bioanalytical assay (PK and ADA assays) method development, and qualification to support the nonclinical program, should begin well before any PK and toxicology studies start, including any non-GLP studies. Drug developers need to account for the several months that it can take to develop critical reagents and methods, while also qualifying the methods for use on the PK and dose-range finding studies. <\/p>\n\n\n\n Bioanalytical assays results are essential when designing subsequent toxicology studies and interpreting data. These results are important when selecting the starting dose, dosing regimen, and dose escalation scheme for the FIH clinical trials.<\/p>\n\n\n\n Preparing for an IND submission requires a nuanced understanding of the differences between regulatory bodies, as each has distinct guidelines and pre-IND interaction protocols.<\/p>\n\n\n\n For most protein-based biotherapeutics, including monoclonal antibodies, derivatives, fusion proteins, endogenous replacement therapies, and nanoparticles, the primary regulatory guideline is ICH S6(R1): Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals<\/a>. A pre-IND meeting provides further guidance on the nonclinical, clinical, and CMC aspects before the IND submission.<\/p>\n\n\n\n For bacterial and viral products, blood and blood products, and vaccines, the main guideline is “Preclinical Assessment of Investigational Products.” Numerous regulatory guidelines support the nonclinical development of these diverse products.<\/p>\n\n\n\n Regardless of the regulatory body, pre-IND meetings offer invaluable opportunities for clarification and guidance, ensuring alignment with regulatory expectations and smoothing the path to successful IND submission.<\/p>\n\n\n\n2. \u00a0Follow regulatory guidance<\/h3>\n\n\n\n
3. Time bioanalytical assays carefully<\/h3>\n\n\n\n
4. Navigate regulatory interactions skillfully<\/h3>\n\n\n\n
5. Decide how \u2018global\u2019 you want to go \u00a0<\/h3>\n\n\n\n