Project agreements

The PAs are annexes to the previously signed MSA and are an important conflict-management tool. The PA should describe the first project-specific tasks outsourced to the CMO by the sponsor. They are part of the legally binding contract. A project can have multiple PAs at the same time. For example, PA-1 can detail the transfer of a fermentation process, and PA-2 can detail GMP cell banking. Each PA should identify in detail the scope of the work to be done, which can be as comprehensive as required, including allocation of human resources, facility resources, deliverables, delivery date, and price. Each PA acts as a yes–no decision point with respect to the general strategy agreed upon in the quotation. The outcome of one phase of the project will determine the scope of subsequent PAs. The content of the PA is often drafted by the various team members: the project manager, the scientists, and project leader, and the appropriate persons directly involved in development and GMP manufacturing. As a legal document, the PA is signed and approved by both the sponsor and CMO before work is begun. The significant advantage of a PA is to be able to define the phases of the project in a scientifically sound manner.

Quality agreement

The QA should define the legal responsibilities of each party with respect to quality matters, such as manufacturing authorizations, audits, and inspections, facilities, staff and training, suppliers, third-party approval, raw materials, records and retention, product manufacture, storage, packaging and shipping, quality controls and out-of-specification management, change control and deviation management, complaints, and product recalls.

Project go-live

Process transfer & development

Once the MSA and PAs are completed, the sponsor and the CMO should agree on preventive actions before development and GMP manufacturing operations are begun. To avoid conflict during process development at an early stage of the project, the CMO should be irreproachable on the competency and expertise of its personnel, the equipment suitability, the quality of the reporting, and communication. Those in charge of development and GMP manufacturing should be aware of the PAs signed by both parties and should be of adequate expertise to lead process development and transfer to the GMP manufacturing facility. Second, the equipment in process development should be of the highest quality and should be comparable to GMP production equipment to ensure that transfer to the GMP production team is smooth and efficient. As a rule of thumb, the equipment should not represent a constraint that forces the CMO to come back to the sponsor with bad news.

Finally, during process development, the sponsor should be kept informed through frequent informal communication and documented reporting. The frequency of teleconferences should be low enough to enable the CMO to ensure data reliability, yet high enough to ensure that the sponsor is sufficiently informed of ongoing progress: weekly communication is generally sufficient. Development reports should keep the sponsor apprised of key outcomes of the development stage and should reflect the scope of the different PAs. Finally, the CMO should share the sponsor's priorities; its development experience should benefit the sponsor.

In spite of clear and careful agreements between the parties, the development stage can nevertheless be frustrating for both parties. Relevant expertise and technical mastery notwithstanding, there is no guarantee the CMO can provide deliverables and meet the sponsor's expectations. It is likely that the parties will lose faith in the partnership. Conflicts that arise at this point are often related to people, time, financial resources, and the CMO's scientific expertise. If a particular PA step does not satisfy the sponsor's target expectations, the development plan should be adapted with respect to the results of the initial PA in a scientifically sound manner. Because the plan entails process development, this adaption may involve extra work and extra cost. In such situations, the following points are crucial:

• There are no questions with regard to the equipment, personnel expertise, and data generated
• Scientifically sound alternatives and their time and cost consequences are presented to the sponsor
• Authorization of a new PA is given by the sponsor before the CMO embarks on alternative development avenues
• The CMO acts with humility and acknowledges its limitations
• The sponsor acts in good faith and acknowledges the work is performed by the CMO, all the more when the product is difficult to handle or timelines are very aggressive.

When advancing in a science-based manner, transparency in communication and detailed reports allow an accurate assessment of the work performed, even when development meets dead-ends.