From a regulatory standpoint, Sponsors are required to conduct a risk assessment or qualification audit during the CDMO selection process to understand if CDMO can maintain regulatory requirements and if there are any associated risks. Qualification audits help identify low-risk and high-risk CDMOs and to develop adequate risk mitigation plans. Most of the CDMOs have the basic quality management systems in place, therefore they pass qualification audits. However, It is prudent to conduct thorough due diligence during the qualification audits to develop an adequate CDMO monitoring plan. The CDMO monitoring plan will be different for high-risk CDMO vs low-risk CDMO, depending on the risks identified. Low-risk CDMOs need less monitoring whereas high-risk CDMOs need continuous monitoring.
There are a few key points to review while qualifying the CDMO for outsourcing, in addition to routine Quality System audit. For example, manufacturing experience and product type, compliance history, staff turnover rate, etc.
High-Risk CDMO vs Low-Risk CDMO
The following are some of the few differences between high-risk and low-risk CDMO.
High-Risk CDMO
- No FDA Licensed products
- New Foreign Manufacturers
- Only Clinical Manufacturing Experience
- Communication barriers due to different time zones and language barriers
- High turnover of staff
- Poor quality culture
- Noncompliance with the Quality Agreement
- Numerous critical/major audit/inspection observations
- Poor customer service
- Backlogs
- Rapid growth of products and hiring spur
- Sterile products with complex manufacturing
- Poor customer service
Monitoring Plan for High-Risk CDMO
For high-risk CDMOs, a high level of oversight is needed. For example:
- Detailed batch record review
- Review and approval of all deviation and change controls
- Annual audits and targeted audits of a high-risk area
- Review of all analytical data for each batch
- Multiple face-to-face meetings
- Establish a Quality review board to discuss the investigations.
- Have a Person in Plant for a deep dive review.
- Stringent Quality agreements
- The clear expectation for complying with GMP in QTA
Low-Risk CDMO
- Extensive Clinical and Commercial Manufacturing Experience
- Routinely inspected by various regulatory agencies and customers
- Distribution to Global Market
- In-house QP
- Mature Quality Systems
- Excellent Quality Agreement Compliance
- Considered Strategic Partner
- Robust Quality Culture (Robust Quality Program, empowered employees to initiate deviation/CAPA/Change Controls, accountability for not complying with SOP, rewards for excellent compliance and everyone’s own quality)
- Counterpart quality groups are well-connected and aligned.
Monitoring Plan for Low-Risk CDMO
For low-risk CDMO, the monitoring will be minimal. For example:
- Risk-based batch record review
- Review of major and critical deviations only
- Random checks for analytical data review but not reviewing all the data.
- Risk-based audits every 2-3 years
- Sponsor approval is needed for major/critical deviations and change control only.