BioC Conducts Thermal Analysis During Clinical Phase for a Small Biotechnology Company
Our client’s lyophilized new drug product successfullly completed early clinical testing and their production date for Phase 3 clinical supplies was set. However, Phase 2 study results established their product required five times the dose given at one thrid the frequency for Phase 2 studies. To provide clinical supplies, they needed a new presentation capable of delivering the higher dose. But there was a potential glitch – they has conflicting development history data and theories regarding the formation of crystalline mannitol during lyophilization and its role in solubility, reconstiution, and product stability. Early studies indicatied a relationship between lyophilized plug dimensions relative to vial dimensions and crystalline mannitol formatoin. However, the product formulation, lyophilization cycle and vial presentation had remained the same since preclinical development and cGMP clinical production had delivered acceptable product quality, reconstituion, and stability results. therefore, no additonal development studies had been performed to prove or disprove the theory regarding crystalline mannitol formaton. To develop a new larger dose presentation, they needed to understand the intersection of these key product design parameters for their current formulation and presentation.
Thermal Analysis During the Commercial Phase for a Large Global Life Sciences Company
Our client’s lyophilized protein diagnostic product had been successfully launched and sales exceeded expectations. Therefore, they were facing the decision whether to expand their lyophilization capacity (and by how much) to meet demand. However, they suspected their formulation and lyophilization cycle had not been optimized due a low collapse temperature of -48°C and lower than expected yields during commercial production. They sought a collaborative partner who could assess their current lyophilization cycle and recommend meaningful (rather than small incremental) changes. They wanted to minimize formulation changes, reduce cycle length, increase yields and improve quality. Because the partner would be suggesting changes to a top selling product, they realized choosing a reputable partner was key to making their case for improvement to internal stakeholders.
Thermal Analysis During the Preclinical Phase for a Contract Manufacturing Company and their Client
Our client was collaborating with another firm in early development of their new product’s lyophilized presentation. They needed to ascertain the critical design parameters to conduct further lyophilization cycle development in order to produce engineering and then clinical batches. As is often the case during preclinical periods, they were under significant time, monetary and drug substance supply constraints.
Determine critical thermal properties of the formulation, including glass transition or eutectic melting temperature, and/or collapse temperature by differential scanning calorimetry (DSC) and freeze dry microscopy (FDM).