BioPharm March eBook - Outsourcing Resources

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Page 28 of 34 March 2018 BioPharm International eBook 29 Outsourcing Resources Analytics Outsourcing nership, he says. "However, there are always times when short-term of spe- cific one-time service agreements are suitable for a program," he adds. Analytical services that are typically the most sought after by clients dur- ing the early drug development phase include bioanalytical services and analytical methods to determine drug substance and drug product stability. "For preclinical and early phase development, the most important criteria are to develop analytical methods that are suitable for release testing of the drug substance and drug product and can be used to pro- vide early stability data," says Wood. "Method validation is not a priority for early phase molecules, but the methods should be shown to be suit- able during the development phase." "Bioanalytical services by far and away are the most sought-after ana- lytical service, second only to the in-life studies that generate the PK [pharmacokinetic] samples for bio- analysis," Hayes says. "Analysis of the dosing material is sometimes required in bridging studies and always required for the GLP [good laboratory practice] drug safety stud- ies. Analysis of the dosing material is most often sourced to the same labo- ratory providing the vivarium ser- vice, as there are significant benefits to having the dosing and the dose analysis in the same facility," he adds. Most researches seek three char- acteristics in analytical services: adaptability, responsiveness, and translatability, according to Kuehl. "Customers look for a group that has the bandwidth to do things quickly, to be responsive and adaptive to the data as they are generated. For exam- ple, it's great if a lab is able to start on a project relatively quickly. Then, as the data are generated, if there are changes in the assay, detection limit, matrix, or sampling process, the ser- vice provider will adapt and make changes quickly, in order to support the overall program. That's where a strategic partnership is such a key part of the success of an analytical program—adapting to the needs of the overall program, not just a small scope of work," Kuehl says. I n add it ion, c ustomers seek translatability, which is the ability to translate methods, assays, find- ings, and other required information from early proof-of-concept studies through to good practices regulated validated studies, Kuehl adds. PLAYING THE LONG GAME As customers move from early phase development to clinical development, their analytical needs can differ. For instance, for molecules in later-phase development, it becomes increasingly important that a more in-depth pro- gram of work is agreed upon between the client and service provider, Wood notes. He suggests that an investment in a quality agreement would be ben- eficial so that both the provider and client understand what is required of each other moving forward. "As the drug progresses through later-phase clinical trials, an assess- ment should be made of any exist- ing analytical methods to ensure they are still relevant in light of any changes to the synthesis of the API or formulation for drug product. Methods may require redevelopment or evaluation depending upon the nature of these changes," Wood says. "Analytical methods will also require validation, and the extent of these validations will increase as the drug progresses to later-phase clinical trials and registration. The impurity profile of the API should be investi- gated, and formation of impurities should be understood in relation to the synthetic route. Finally, specifica- tions for the drug substance and drug product should be finalized and justi- fied," Wood adds. From a drug metabolism and phar- macokinetics perspective, however, customer needs remain the same, Hayes notes. For instance, determin- ing circulating concentrations (expo- sure) of the test article is a constant in almost all of the studies conducted to bridge the drug candidate from discovery through early development (investigational new drug application) and into the first clinical studies. "Safety multiples are often based on dose-exposure relationships, and so bioanalysis is required throughout the progression of the candidate into the clinic. Once in the clinic, safety and tolerability are assessed through single and ascending doses of the drug candidate, and bioanalysis provides the data to generate the dose- exposure relationships in humans. The primary difference is that the concentration of drug is much lower in the clinic that in the animal model safety studies. The bioanalytical methods become more refined as experience is gained with regard to assay robustness and this helps achieve lower detection levels," Hayes says. He also emphasizes that analysis of the dosing material is required throughout the drug safety stud- ies into clinical development. The requirements for analytical method validation and the sophistication of the analytical methods increase as the compound moves from GLP studies into the clinic, eventually requiring full compliance to GMPs. The biggest change that typically occurs during the transition from early development to clinical devel- opment is the change from a devel- opment mindset to a regulatory mindset, Kuehl notes. "In the early phase of the program, the customer needs the service provider to make modifications to assays and detection ranges. Later on, the focus shifts to expeditiously generating and report- ing data in a manner that is ready for regulatory submission, without significant work by the sponsor." 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