Tod Borton, VP of technical operations, Aastrom Biosciences
As the development of highly complex regenerative medicines continues to advance, the level of precision and quality necessary in all phases of manufacturing is reaching new heights. At Aastrom, our lead product candidate ixmyelocel-T is a regenerative, patientspecific cell therapy, which is developed using a proprietary production process. We depend on the availability of very high-quality components, including the bioreactors that are essential to the production process for ixmyelocel-T. We have identified the necessary steps to find the optimal CMO partner and to then work in collaboration with the CMO team at every stage to help them understand and meet our requirements in terms of product quality and precision.
Our team recently went through an extensive vetting process to identify a CMO to supply necessary cell development technologies. We also outlined a process to help the CMO team execute the tech transfer and then put into place a range of reporting and monitoring procedures to maintain the necessary levels of quality with our CMO partner.
Keys to Success: Communication, Support, and Clear Instructions
In the first phase of this effort, our internal team developed a comprehensive list of criteria for a CMO partner. We used this to create a short list of potential CMO partners and then individually reviewed the capabilities and experience of each. We toured their facilities and also talked with previous industry partners for insights on CMO strengths and abilities to work in partnership to set up systems and address challenges. We carefully evaluated the depth of experience of all members of the project team and conducted a company audit. In evaluating the project leader, we assessed strengths in several key areas, including communications, project management, validation, and quality control. We also asked the transfer team to review some recent examples of technology transfer and verified the results with end users.
Once we selected a CMO, we began an intensive technical review and training program to bring them fully up to speed. In this effort, we were able to work with a consultant who was a member of our previous CMO team. Based on the complexity of the bioreactor assembly, a clear and open line of communication with the CMO team was essential. We held weekly review meetings to monitor progress and to identify and address any problems early. We also invited the manufacturing team to Aastrom so they could see our production process first hand and fully understand and appreciate the impact that their work has in producing ixmyelocel-T.
Following this phase, we took several steps to make sure that our ongoing relationship with the CMO positioned us to work in an effective, long-term, mutually beneficial partnership. This includes establishing all procedures related to manufacturing and quality testing. We also outlined a strategy and provided all the resources necessary to address any changes to the team working on our program at the CMO and to keep our team at full strength in a transition. All quality issues were entered in both Aastrom’s and the CMO’s quality systems and were reviewed and tracked during our weekly meetings. Constant quality feedback is an integral part of our normal production process. Aastrom team members participate in evaluation of production anomalies, trends, and official reviews of changes in real time with the CMO.
Management of the CMO relationship is a very important function at Aastrom. We have two full-time engineers positioned to manage all aspects of our relationship with our CMO partner, including daily contact to review progress and address technical issues quickly. This close relationship enables our team to continuously work with the CMO to identify strategies to improve production and maintain all standards in quality. They also manage project lists to track all efforts to improve production.
In our experience, the keys to sustaining an effective CMO relationship in regenerative medicine are clearly defined requirements and expectations as well as the resources and support necessary to get the CMO team fully up to speed. This structure will promote the early identification of problems and rapidresponse strategies to address them. We also recognize that both parties have a responsibility to focus on quality and to provide the other party with all of the support necessary to position them to do their jobs and meet their goals successfully.