Sponsor-CMO Conflict Management for Clinical-Phase Biologics - The authors present the CMO's perspective on various potential sources of sponsor-CMO conflicts. - BioPharm International


Sponsor-CMO Conflict Management for Clinical-Phase Biologics
The authors present the CMO's perspective on various potential sources of sponsor-CMO conflicts.

BioPharm International Supplements
Volume 24, Issue 3, pp. s4-s8

GMP manufacturing of clinical batches

Risk assessments should be performed before initiating GMP manufacturing to ensure that product quality will be met. The CMO is responsible if it chooses to go ahead with GMP production when the risk of batch failure is high. Reasons for anticipated failure can include a lack of process robustness, insufficient process knowledge, and analytics' undemonstrated fitness for purpose. At this point, additional development activities must be discussed to avoid overpromising. Finally, both parties should agree on the product specifications in accordance with regulatory requirements as well as the procedures and the method of production before starting GMP manufacturing. Target production yields and the customer's needs to supply the clinic should be in good agreement with development data or process history upon normal operating conditions.

Following the risk assessment, the process is transferred to the GMP manufacturing facility. The technical transfer should never be jeopardized. The CMO is responsible for allocating all resources necessary so that the technology transfer is successfully achieved. The technology transfer should be documented, and the sponsor should be informed of the transfer's completion and any issues encountered. Likewise, the quality system in place must ensure the following points during the production of the GMP batches:

  • The GMP personnel are adequately trained
  • Equipment is qualified
  • Operations are traced, recorded, and checked
  • No cross-contamination occurs in a multiproduct facility.

Conflict resolution in GMP manufacturing of clinical-phase biologics

Figure 2. Conflict resolution protocol
Outsourcing biologics manufacturing is costly, and dealing with conflicts that involve financial arbitration is always challenging. This statement is particularly true when GMP batch quality specifications are not met or production yields are not achieved (see Figure 2). Identifying financial responsibilities in these situations is often stressful and contentious. Senior management and appropriate decision-makers for both parties should immediately be informed of the issues and should take time reaching their conclusions following a thorough investigation. The investigation should be structured and systematically documented and should address the following technical and quality questions:
  • Are the people trained in all affected operations?
  • Is the equipment qualified?
  • Are there any major or critical deviations in the method of production?
  • Is the process robust or validated?
  • Are critical steps identified or operating ranges well defined?
  • Is the issue related to cleaning or cleaning validation?
  • Are release specifications accurate with respect to product knowledge?
  • Was an out-of-specification investigation opened by the quality-control laboratory?
  • Is the out-of-specification root- cause assignable to a laboratory error?
  • Are in-process controls as expected with respect to historical data?

This investigation should allow the development of a rationale for discussing the financial responsibility of both parties. In every case, successful conflict resolution depends on the quality of the investigation at the CMO and the sponsor's understanding of the issue and root cause. Videoconference or face-to-face meetings are helpful in clarifying perceptions and promoting dialogue between the sponsor and the CMO. Generally, good conflict resolution, supported by facts and documented evidence, should benefit both parties and strengthen the partnership.

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