Questions You Should Know about Drug Substance CDMO Services

The biologics contract development and manufacturing organization (CDMO) selected for a given product or program is critical to an innovator's ability to deliver a drug product safely, on time, and on budget. While some considerations are universal to nearly every CDMO selection effort, innovators must thoroughly and honestly evaluate their requirements for an outsourcing partner.

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For instance, a small, emerging biologics organization utilizing a novel modality will likely need a CDMO partner capable of supporting timeline flexibility, ample process development support, and a white-glove project management approach. On the other hand, an established innovator might require specific data integration capabilities, experience working with international regulatory bodies, and the ability to implement established protocols.

While far from a comprehensive list, this article discusses six questions an innovator should consider when evaluating a biologics CDMO partner. The presented questions reflect critical issues and are listed in no particular order, with communications being the exception. While compliance, a culture of quality, and supply chain management are all vital, a program can only succeed if communications are properly aligned between an innovator organization and its CDMO partner.

1. Are the communication style and project management capabilities of the biologics CDMO under consideration a good match?

The need for transparent and free-flowing communications is well-understood but is a characteristic that is often challenging to evaluate. Clearly, it is a warning sign if communications are not satisfactory during the request for proposal (RFP) process. If it takes weeks to get an RFP, that could be a warning sign that your program will not be prioritized.

However, highly effective communications from a business development team do not necessarily indicate that an innovator can expect the same from the CDMO's operational, quality, and biologics development teams. That's why you'll want to communicate with the CDMO's subject matter experts and program management teams as early as possible before making your final selection.

Additionally, for innovators with fewer internal resources, ample project management capabilities and a CDMO with a consultative approach will provide significant value. Biomanufacturing is never a cookie-cutter approach, so you'll want to ensure your CDMO can advise and be flexible.

2. Does the executive management of the biologics contract development and manufacturing organization foster a culture of quality?

Famously, President Harry S. Truman featured a sign on his desk that read 'The Buck Stops Here,' reflecting his belief that he was ultimately responsible for his administration's actions. The same commitment is needed from a CDMO's leadership.

Every CDMO in the pharmaceutical industry has a statement relaying their commitment to quality, but a passage on their website does not indicate a genuine quality culture. To determine if a CDMO is truly committed to a culture of quality, you must evaluate the statements and actions of the organization's leadership. Does the company's CEO regularly mention quality in their internal and external communications, like speeches, business updates, and interviews? How has the CEO responded to quality issues in the past?

3. Are the biologics CDMO's manufacturing facilities and operations all compliant with applicable GMP regulations and guidelines?

cGMP refers to the Current Good Manufacturing Practice regulations enforced by the FDA. GMP creates a structure that assures proper design, monitoring, and control of biopharmaceutical manufacturing facilities and processes. Adhering to cGMP regulations ensures that regulators, patients, and healthcare professionals can be confident in a drug's identity, strength, quality, and purity by requiring manufacturers to control manufacturing operations carefully.

GMP compliance is all-encompassing, including factors such as:

• Proper equipment selection, qualification, maintenance, and calibration
• Personnel training and qualification sufficient for their respective roles
• Adequate cleaning and sanitation of equipment and facilities
• Effective environmental monitoring programs that ensure control of the manufacturing environment
• Existence of an internal quality/GMP audit program
• Establishment of analytical and testing procedures to ensure specifications of raw materials, containers, packaging, in-process materials, and finished product

While virtually all of a biologics CDMO's operations are related to GMP, look closely at quality systems, documentation and record keeping, supply chain management, regulatory records, and continuous improvement efforts.

4. Does the CDMO have robust quality systems?

The discussion of a pharmaceutical quality system references the ICH Q10 model, which refers to the 'need for one comprehensive model based on International Organization for Standardization (ISO) quality concepts, includes applicable good manufacturing practice (GMP) regulations and complements ICH 'Q8 Pharmaceutical Development' and ICH 'Q9 Quality Risk Management.'"

In practice, a CDMO must embed quality in everything they do. Due to the complexities of working with living systems, there is occasionally a need to reactively respond to a quality incident, even within the best-run operations. That's why, when considering a CDMO partner, there should be strong evidence of a proactive approach to quality.

Proactive quality system improvements must be based on audits, process data analysis, equipment condition, preventative maintenance efforts, and other relevant information sources.

Ultimately, a CDMO must be dedicated to identifying risks, then prioritizing and addressing them in a manner aligned with their threat to product quality. The following are just some of the characteristics of a robust quality system:

• Dedication to closing out quality events like change controls, corrective and preventive actions (CAPAs), and formal deviations promptly
• An established internal audit program
• Effective change control and deviations management
• Continuous improvement efforts that enhance quality and efficiency
• Accurate, completed, and properly stored batch records
• Proper establishment, validation, and documentation of all testing procedures
• Robust system for handling out-of-specification results or non-conforming materials

5. Does the biopharmaceutical CDMO effectively manage its role(s) within the supply chain?

CDMOs play a vital role in the pharmaceutical supply chain; therefore, it is critical to determine a potential partner's ability to respond to an innovator's specific needs. For instance, the demands on a CDMO for a high-volume drug product with highly predictable demand will be quite different than if the program has volatile and difficult-to-predict demand.

A good CDMO partner will have the financial resources to procure materials and significant storage capabilities. Regardless of the demand and volume profile of the drug in question, some of the biologics CDMO supply chain considerations include:

• Proper storage, labeling, and identification of raw materials
• Robust supplier qualification and evaluation approaches
• Ability and willingness to procure and store sufficient raw material buffer stock
• Adherence to all serialization and traceability laws and requirements
• Storage and distribution capabilities

6. What is the CDMO's regulatory track record and experience working with regulatory bodies?

Not only does a biologics contract development and manufacturing partner need to have a strong regulatory track record and reputation, but it also needs appropriate regulatory experience.

For example, if a drug will be distributed and marketed in multiple global markets, the selected CDMO in the US must be familiar with each market's regulatory framework and have experience working with (and being audited by) the relevant regulatory bodies.

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