By Ajay Pazhayattil
The successful vaccination drives in the U.S. and other countries were backed by the incredible efficiency in COVID-19 vaccine production. It is time to recognize the diligent efforts of the individuals employed at material suppliers and CMOs who worked through the peak pandemic months just like frontline healthcare professionals.
The immediate future now presents opportunities with the launch of new streams of biopharmaceutical product pipelines. CMOs are creating manufacturing capacities based on newly emerging treatment pathways and practices of medicine. While it is an exciting time of expansion, commissioning projects during a restrictive atmosphere presents challenges. Here, we discuss how drug sponsors and service providers can work together to continue down the path of outsourcing success.
CMO Success Formula
The 2020 McKinsey survey, “COVID-19 And Cell And Gene Therapy: How to Keep Innovation On Track,” identified attributes such as regulatory compliance, awareness of customer requirements, segment experience, industry reputation, cost, and assurance of safeguarding IP as the top factors for choosing your CMO. Post engagement, attributes such as transparency, responsiveness, and meeting delivery commitments become important as well. Informed CMOs put in immense efforts to go above and beyond client expectations on the listed attributes. To meet these client desirables, CMOs are developing capabilities that provide high flexibility with a higher degree of automation. Employing customer transparency technologies and maintaining high customer satisfaction are priorities. Processes are available for CMOs to ensure integrity of data, proprietary data privacy, and security. Maintaining a steadfast CMO industry reputation is achieved through attributes such as quality of work, reliability, etc., and it also depends on the organization’s success in being relevant by continually innovating and showcasing those manufacturing innovations at major industry virtual events and webinars and in publications. Competitive costing of CMO services is becoming commonplace, requiring agile costing models and options. Differentiating themselves and offering value-added services, developing payment models, and providing dedicated client support are other activities CMOs are focusing on.
The FDA has published recommended quality metrics for drug manufacturing, such as LAR (lot acceptance rate), PQCR (product quality complaint rate), and IOOSR (invalidated out-of-specification rate). Whether or not the FDA intends to make reporting mandatory and publish them, such metrics can now be mandated by clients. CMOs, in order to successfully meet such metrics, are automatically obligated to maintain quality cultures, high compliance, and integrity. Checks and balances to minimize compliance risks and maintain operational excellence and strategies to maintain high service levels are built-in traits of CMOs targeting high facility EBITDA.
Being A True Partner
A CMO provides its manufacturing services amid varying levels of customer expectations. Clients can range from clinical to commercial organizations. To be effective, client points of contact must be aware of the CMO’s multiclient, multiproduct operational circumstances. Constantly being cognizant about the boundaries goes a long way in solidifying the client- CMO relationship. CMO departments are normally mandated to allocate project hours to a specific project activity. Hence, preplanning sessions for smart use of your CMO’s interaction time and tracking of those interaction sessions can be effective in improving efficiency of knowledge transfer activities, when required. Agreements need to establish the number of on-site visits/audits. However, added layers of compliance monitoring can disrupt operational efficiency as CMOs do receive a large number of pre-engagement and routine client audits in addition to the mandated regulatory audits. Rather, clients may consider a full-time person-in-plant working side-by-side with CMO employees for specific phases of a project. Client organizations increasingly use consultants for CMO management, which can cause an added layer of complexity. In cases where more parties are involved, the delivery timeline metric should be carefully monitored so those delay factors are captured.
The CMO’s activities involving a range of diverse projects provide an excellent opportunity for CMO employees to gain valuable experience. The fast-paced nature of the CMO’s work develops SMEs, but they get very little opportunity to reflect on how their contributions help in bringing critical medicines to the market. Presentation sessions providing product insights and direct-to-employee gratitude events at your CMO’s site will be highly appreciated by the employees. It is important to establish an incentive plan as soon as you engage with a CMO. For example, organizations that perform consistently on product quality, delivery, responsiveness, etc. need to be significantly rewarded with more autonomy, such that it results in further excellence benefiting the product. Your CMO and its internal resources are your manufacturing quality and operational excellence SMEs that you need to rely on.
A lot of planning goes into making a single batch of product. For instance, a fill/finish operation includes timely sourcing of raw materials and components, line scheduling, storage, change parts, cleaning, testing, documentation, training, resource planning, assuring utility availability, calibration, qualification, gowning, maintaining room grade, dispensing, formulation, sterilization, filtration, transfers, environmental sampling, testing and monitoring, filling, primary packaging, controlled chamber storage, secondary packaging, inspection, decontamination, waste management, and cold-chain shipping activities. Since aligning the activities and executing the manufacturing steps involves meticulous coordination, swift batch injections and last-minute change orders from clients can affect the operational performance level of the entire facility, thus impacting other client products. CMOs develop SOPs that are fit for the facility’s activities. They may not always align with client procedures. The procedures are, however, designed to meet regulatory and general client expectations. Client-specific procedures for general activities may be developed if necessary; however, that comes with the risk of failure to execute, especially if the execution is nonroutine. Critical failure investigations are handled and justified per CMO procedures. When additional testing or more time for investigations is needed, providing the CMO with a batch order for a nonimpacted process/product line will be desirable. When needed, a client’s technical team’s hands-on involvement during brainstorming and root cause analysis is certainly an advantage. While the CMO leads the investigation, any support, such as statistical data analysis and external testing, may be provided to accelerate investigation completion and establish the findings.
Just like monitoring a CMO’s performance, it is also important for the client to gauge the performance of its own internal point of contacts. The source data for such assessments should be routinely (anonymously) sourced from your CMO partner. Special attention may be given to aspects such as the expertise level on the activities performed, responsiveness, input and collaboration, cycle time, and engagement etiquette. Such data can help in developing and maintaining an effective external manufacturing operations team.
Acknowledge Your CMO’s Capabilities
The CMO’s documentation and data are your evidence of successful batch execution, which is available for regulators’ verification during submission or on-site inspection. Developing a cordial give-and-take relationship with your CMO is critical. Supporting the CMO’s teams in the ways mentioned in this article yields positive results. Continually communicating the importance and value of the product manufactured at the CMO and building employee ownership of the product and process have been seen to be effective. The goal should be to focus on patient safety and efficacy, followed by compliance, since CMOs must assure regulatory compliance for their own continued existence. Acknowledgement of your CMO’s management of diverse lifesaving products and clientele will lead to developing approaches that support their operating model. Rather than taking non-issue CMOs for granted, developing incentives for such performers can only create a special affinity and encourage them to maintain their service levels.
About The Author
Ajay Pazhayattil is a management consultant supporting clients to achieve their business goals while adhering to global regulatory mandates. He has contributed to strategic organizational transformations as part of senior management at major CDMO and generic organizations in North America.