A logical first step in selecting a CMO involves making an assessment of internal capabilities, strengths, and needs that can then be overlaid on anticipated external requirements. A company with marketed products and established infrastructure for manufacturing, testing, packaging, and distribution must identify pockets of supply-chain weakness and then evaluate the financial benefit of outsourcing. If the assessment identifies large-volume under capacity for a product or product line, consideration of a large offshore CMO could represent a cost-effective solution, provided there are no extenuating circumstances associated with product release or distribution. In other cases, the assessment could lead to a decision to outsource processes that require specialized expertise. The CMO choice in that scenario would be made based on an evaluation of the sponsor company's ability to manage the interface with the CMO.
CMO selection is one of the most critical decisions made by companies with limited internal resources dedicated to production, testing, and control of pharmaceutical products whose definition includes development compounds, clinical trial material, and commercial active pharmaceutical ingredients and products. This article describes a systematic supplier selection approach taken by a company with operations outside the US, but with a commitment to develop, manufacture, and gain approval to market a specialized drug product using a completely outsourced model for manufacture and testing of this product in the US.THE CHALLENGE
The company wanted a CMO with capability to fill ampoules and vials with a sterile emulsion containing a potent drug substance whose stability is affected by exposure to elevated temperature, but not sufficiently to preclude the requirement to terminally sterilize finished dosage units. Phase 1 lots of this drug product were manufactured and tested by a reputable pharmaceutical company with primary operations in Asia. A specific homogenization technology was used to make the emulsion, which is commonly found in the US food industry, but is not as common in the pharmaceutical industry. The sponsor company did not wish to change homogenization technology because of the potential impact on emulsion properties.
The supplier selection process began with detailed review of process data from the original clinical trial material manufacturing process. The review revealed specific homogenization parameters and identified two critical features of the process that would be important for technology transfer to the CMO. The first issue was the need to use a rotating autoclave with capability to heat up and cool down quickly to preserve emulsion properties. The second issue related to equipment cleaning, but was not considered a limiting factor in the CMO selection process.
A checklist of optimum supplier attributes was developed from the data review to be used as a guideline for preliminary supplier screening. The prerequisites included:
Initial CMO screening was conducted using hardbound and Internet-based directories to identify potential candidates. Benchmarking exercises were completed by contacting development staff employed at companies that market specialized emulsion formulations. Concurrently, the manufacturer of the desired homogenization technology was contacted to determine a potential list of contract manufacturers who purchased the specific technology needed for the sponsor company's product.
The result of initial screening was a list of 10 CMOs who could potentially handle the sterile emulsion project. A general product information sheet was developed as a tool to facilitate telephone conversations with technical and business development staff at the 10 shortlisted CMOs. Some CMOs were immediately eliminated from the list because their capabilities did not meet the criteria for the project. Other suppliers were eliminated from further consideration because of conflicting requirements associated with a potential business relationship. Ultimately, a short list of five CMOs was developed.