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Examples of challenges in inhalation pharmaceutical development, how they were diagnosed and steps taken to improve confidence in the execution of outsourced studies. Where a long-term workload was expected, functions were brought in-house. Other activities were outsourced, with training provided for the contract research organizations. 12 February 2020 Inhalation Accelerating inhalation product development Choosing between outsourcing and developing internal capabilities Zhili Li, PhD; Donald Chun, BS; Helena Gauani, BS; Veronica Viramontes, BS; Thomas Baker, BS; Adam J. Plaunt, PhD; Vladimir S. Malinin, PhD and David Cipolla, PhD Insmed, Inc. way. erefore, the quality of the CRO and their proce- dures and experiments need to be closely monitored to prevent errors. Furthermore, it is essential to establish a relationship with the CRO professionals responsible for the conduct of studies and provide training on method- ology that may be novel to them. Periodic assessment and refresher training may also be necessary if the pro- cedures are conducted infrequently. 1 In this article, we share a few examples of challenges that occurred at Insmed, Inc. (Bridgewater Township, NJ, US) during inhalation pharmaceutical develop- ment, how we diagnosed the issues and the steps that we took to improve our confidence in execution of those outsourced studies. For activities where we could fore- cast a long-term workload demand, we brought those specific functions in-house to improve the quality and timeliness of execution. In other situations, we contin- ued to outsource activities but invested in the relation- ship with the CRO and provided ongoing training. Bringing the bioanalytical function in-house Initially, Insmed did not have its own biological sam- ple analysis laboratory, as this would have required an upfront investment in costly equipment (such as tandem mass spectrometry) and personnel with exper- tise to develop the analytical methods and operate the equipment. erefore, our historical preclinical studies were outsourced for analysis to avoid that significant start-up expense. However, a downside became apparent: the timelines from contract signing with the bioanalytical CRO, to development and qualification of the methodol- ogy, followed by subsequent analysis of the biological Introduction It is inevitable that small- and medium-sized pharma- ceutical companies outsource key research and chem- istry, manufacturing and control (CMC) functions to contract research organizations (CROs) when it does not make financial sense to build internal capabilities for activities that are infrequent and/or require large capital or headcount investments to establish expertise. Examples of typical outsourced activities include: eval- uation of the preclinical efficacy or pharmacokinetic profile of experimental formulations in in vivo animal studies, quantitation of a drug and its metabolites from these biological samples, characterization studies such as leachables and extractables testing or aerosol perfor- mance testing, manufacturing of drug product, and stability and release testing of that drug product. For inhalation product development, there is additional complexity in the conduct of preclinical animal studies. Many CROs may not have experience specific to repro- ducibly delivering an inhaled product to animals to achieve the target lung dose, characterizing the perfor- mance of an aerosol delivery system, or providing assur- ance that the formulation maintains its performance characteristics throughout the duration of the animal exposure study. In addition, multiple CROs may often be needed to conduct various elements of linked activ- ities; e.g., one to manufacture a formulation, a second to evaluate that formulation in an in vivo animal study, and a third to validate the bioanalysis method and subsequently quantify the drug in the biological sam- ples from those studies. At the end of the study, if the bioanalytical data does not match expectations, the innovator may wonder if the data is indeed reliable or if an error was made at one of the many steps along the