BioC Develops Enabling Formulation for Animal Health Client
The client was in early stage development for a drug product to be used to treat a condition commonly seen in a large food animal. This condition causes several problems for these animals and their producers including increased waste, decreased production, extra labor, and costs associated with these issues. The client is evaluating a new administration form of the drug product to treat this condition. To begin they only had an API and no existing formulations. The client came to BioConvergence to develop and evaluate possible formulations, and to optimize the formulations for several factors including viscosity, density, freezing point depression, drug delivery, and pH, while keeping in mind and avoiding possible manufacturing hurdles.
BioC Innovates Labeling Process for Animal Health TAS Study
The client submitted one of its products with its promising data to the CVM for approval to begin Target Animal Safety (TAS) studies within the European Union. The product is administered using a syringe, where one syringe equals 1x the dose concentration. To achieve higher dose strengths for the study such as 2x and 3x, the client planned to use multiple syringes (i.e. 2x strength would be 2 syringes for the target animal). However, the CVM requested that another dose strength be administered, 2.5x, as an additional data point in the safety study. The TAS study was already scheduled and the target animals had been purchased and prepared for the study to start, in which the timing was critical. The client had limited options in order to come up with the additional data. They could either reformulate and manufacture the product so that they could have a syringe with 0.5x strength (costing them several thousands of dollars and setting them back for their study timeline) or come up with a creative solution to develop a 2.5x strength dose, keeping the end-user in mind and not compromising the integrity of the study. Additionally, they needed the syringes of each dose strength to be labeled, kitted, and delivered to the international site on time.
Strengthening the Supply Chain through Partnership
As a partner in the pharmaceutical supply chain, it is our responsibility to have expertise in the many aspects of procurement, development, manufacturing, storage, and distribution to properly serve clients. In addition to our own expertise, we must also rely on our external partners’ expertise, to provide the highest level of service possible; it is the collective expertise of both parties which provides the greatest benefit to the client and the end-user (the patient).
Here’s the method we used to strengthen our supply chain partnerships (which contributed to yielding a 99.7% excursion-free rate):
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).