San Diego, February 27, 2012: After completing the identification, selection, and supply agreement negotiations with your Contract Manufacturing Organization (CMO), that’s when the REAL work begins! Whether you’re making Clinical Trial Materials (CTM) for your Phase III pivotal trials or preparing to commence full-scale commercial production in anticipation of or after marketing approval of your new drug, you’ll need to apply the appropriate management processes and oversight to ensure a successful start-up and continuing operations.
One of the first steps in the start-up process is the preparation of and hand-off of the Technical Transfer Package (TTP) to the CMO. Some of the typical components contained in a TTP are: the process description, the Bill of Materials (BOM), QA/QC forms, test methods and assays, toxicology data, and more. Some sponsor companies may have well defined processes that have been developed and refined in their own small-scale facilities or pilot plants. Others may only have a rough back-of-the-envelope process flow sketch. In the former case, the sponsor company may just want the CMO to execute on the sponsor’s own Master Batch Record (MBR). In the latter situation, the CMO will be expected to generate the process that best fits their facilities and unit operations. It should be noted that the legal and cost responsibilities of the two above cases are different and should be differentiated accordingly in the contract or Supply Agreement. Additionally, how much hands-on involvement the sponsor company chooses to have in this preparatory phase also has possible legal and contractual implications. For example, if the sponsor company chooses heavy involvement such as co-signing almost all documents generated by the CMO, including SOP’s, then there is more of a shared responsibility for any negative outcomes in the manufacture of the API or drug product.
Moving into the pre-validation phase of the start-up process, you will probably want to produce one or more placebo or engineering batches without consuming costly active ingredients. The protocols for these batches should be reviewed and signed off by the sponsor company. These batches serve to confirm the operational capability or OQ of the typical IQ, OQ, PQ process within the CMO facility. The final step before initiation of commercial production is the PQ step which usually means production of three consecutive validation batches close to the scale of commercial production. When all three of these consecutive batches meet the finished product specifications, they may also be used for commercial launch material. The test results from these batches are critical as well to the qualification of the CMO relative to the Pre-Approval Inspection (PAI). The sponsor company will definitely want to have their representatives, either employees or contractors/consultants present in the plant for the above critical steps. Following the process steps described above are just a few of the things that you can do to ensure a successful start-up at your CMO. In Part II I’ll discuss some of the things that you should consider in managing your products manufacturing at the CMO on a continuing basis.
Global BioDevelopment has the technical expertise and competency to assist you to achieve a successful implementation of manufacturing at your CMO. Our experienced partners can provide everything you need from process development; CM & C section preparation, technical transfer, supply agreement negotiation, and ‘man-in-the-plant’ representation for start-up and ongoing manufacturing at the CMO.
Give Global BDI a call (813-448-3093) or e-mail (info@GlobalBDI.com) and let’s have a conversation about how we can assist you with your drug supply requirements and the use of CMO.