If you are a party A, how can you choose and evaluate the reliable Party B? What do you need to ask during the audit and selection process to ensure that your clinical or commercial program does not derail due to quality-related issues?
The Pharmaceutical Development Corporation (Sponsors / also "Party A") may consider that performance of quality commitments is an inherent part of the operations of each contract development and manufacturing organization (CDMO / also "Party B"), simply because product quality is essential to ensuring patient safety. Of course, each CDMO claims to fulfill its promise of quality. But CDMO has many companies, mixed, how can we accurately evaluate? Answers include a thorough on-site quality audit, asking the right questions and requesting detailed information. The responses, data and documents provided by the CDMO will reveal whether it has a robust quality management system and quality culture.
You have to act like an FDA, an inspector
The CDMO shall welcome Party A to conduct an on-site audit of its facilities and operations. If the CDMO is reluctant to accept an audit, it is certainly a questionable red flag.
If Party A is a small startup company or has limited audit experience, then an experienced company can be hired as a third party to perform the inspection, and, ideally, with a member of party A's own team involved.
If Party A performs the audit, it may follow the FDA quality system inspection technology to ensure that all aspects of the system have been covered by the inspection. The FDA guidance describes how six systems should be inspected: systems related to quality, facilities and equipment, materials, production, packaging and labeling, and laboratory controls. The above methods should be used and the following key questions should be raised and some corresponding information should be requested.
What do you understand the structure of party B's quality team?
Like any drug manufacturer, the CDMO must have the right quality structure and staffing. First, the CDMO is requested. If the organization chart shows the quality team reporting to the production team, then this is a problem. The quality team must be independent from the potential impact of business problems. Then, beyond the reporting structure, to ensure that the quality personnel do not take too much responsibility, the same personnel shall not participate in the production supervision, review the quality control (QC) test data, and then approve the QC test results.
Next, ask, " What is the percentage of quality people in your team?"Depending on the capacity of the facility and the number of projects undertaken, the organization must have sufficient quality personnel. Even well-trained employees make mistakes if they take too much responsibility and, worse, they may cut corners.
Then ask about the background of the quality team. Record the names of key players during the factory visit and then review their resume later. Quality-critical personnel must have the right educational background, training and relevant experience, or a combination of all three to perform the assigned functions. While education and training are important, nothing can replace many years of experience.
A diverse experience can also make a quality team strong. Do quality employees only work in CDMO, or have they also worked in Party A? With their experience in Party A, they will better understand the customer's concerns. Does the Quality Assurance Supervisor (QA) work only in QA or in the production workshop or QC? With practical experience in performing quality-related tasks, QA supervisors can better monitor these GMP activities and know where errors are most likely to occur.
If your company is a start-up, make sure the CDMO quality personnel have experience manufacturing drugs for clinical trials. A quality team with only experience in GMP commercialization may increase the burden on the early clinical drug manufacturing process, as GMP is expected to be not as high as in the early clinical stages. They should have a GMP experience suitable for the clinical stage.
You will have to ask questions about the quality management system
The CDMO shall be willing to share information about its Quality Management System (QMS) and its Corrective and Preventive Action Procedures (CAPA). Party A may request a list of deviations from the past two years. If there is a strong quality management system, managed with advanced software, they should be able to provide this list in a few minutes, so with a long delay, it would be a red flag.
Ask about investigations of bias, including how they handle these issues. If the record repeats the same error, it indicates that they never identified or investigated the root cause.
Ask them how often they perform an internal quality audit, and who is involved. The answer will also be a good indication of the company management's commitment to quality and the overall quality culture of continuous improvement by CDMO.
Request a list of standard operating procedures (SOPs). And then asked how the documents were prepared, including who was involved, and the frequency of reviews. Party A may require the production workshop or QC staff to guide you to complete a procedure while you follow the standard operating procedures. Observe if the operator skips any steps and ask why. The response may be that these steps are redundant; if so, investigate the validity of this statement. If these steps are indeed unnecessary, ask why the SOP was not modified to reflect this.
You have to ask how the supplier qualification confirmation is done?
Another key aspect of the quality system is the qualification confirmation of the suppliers. Just as pharmaceutical companies are responsible for the quality of its CDMO production, CDMO is responsible for the quality of materials and services it receives from suppliers. First ask how CDMO reviews vendors. Ask the CDMO team to share their bill of materials and qualified supplier lists. Then ask how they performed the vendor audit. In general, pharmaceutical makers can follow a risk-based approach to manage the quality of suppliers, with more rigorous reviews of the most critical components, components or services.
As part of this process, supplier audits can be conducted on site or remotely, depending not only on the degree of product or service critical, but also on the development phase and regional requirements. EU regulations require on-site audits of critical suppliers, even in the early stages of drug development. The FDA regulations are less specific and allow manufacturers to conduct adequate audits based on risk assessments, including decisions about conducting on-site audits.
In any case, CDMO should conduct a field audit of its most critical suppliers, such as those supplying active substances (i. e., API and excipients). If CDMO outsources any laboratory testing, the analytical testing provider is also a key supplier and must conduct an on-site audit. In addition, drug manufacturers must regularly monitor supplier performance through regular audits.
sum up
Through the above activities and feedback, drug development companies and even a small biotech company can gain confidence in whether CDMO has the necessary quality system and quality culture to ensure product quality and thus ensure patient safety. This evaluation process will take some time and effort, but it is an appropriate input of resources that will pay off in the long run. Insufficient emphasis on CDMO audit quality poses the risk of selecting CDMO partners, which may cause significant problems or even catastrophic losses for the company. A popular maxim, often regarded as the Benjamin Franklin, captures the fact: " The bitterness of poor quality remains long after the sweetness of low price is forgotten.(The sweetness of the low price quickly passes, but the bitterness of the inferior quality is long unforgettable)."Quality is not cheap, but ensuring the return on the quality of drugs will help the company go further.
