By Aisha Shakeel and Kieran Reals, PA Consulting
Biotechnology companies understand that a quicker journey from R&D to clinical delivery is a key factor in achieving market success. The importance and possibilities of development and manufacturing scale-up speed were demonstrated most recently during the COVID-19 vaccine programs, with 15.4 billion doses manufactured between December 2020 and October 2022, as reported by UNICEF. CDMOs were fundamental in ensuring these vaccines reached the public quickly.
This article looks at the needs and challenges biotech organizations face during the manufacture of therapies, how they can reduce cost, and how establishing — or not establishing — partnerships with CDMOs can help get their therapies to patients faster.
Automation, Innovation Can Reduce Drug Manufacturing Costs
Many biotech companies are daunted by the cost of manufacturing novel therapies and look to reduce expenses. While some costs, like quality starting materials, are necessary value-adds, cost savings are possible throughout the process. CDMOs provide a route to cost-saving by offering an alternative to in-house deployment of non-scalable processes, run by specialists on capital-intensive equipment.
It is in a CDMO’s best interest to provide innovative technologies to its clients, making large-scale production, training, knowledge transfer, skills development, and data analysis easy and efficient. Introducing automation to reduce manual intervention in the production of biotherapeutics provides three main benefits: reductions in contamination risk, processing time, and cost. Cell processing traditionally occurs as an open system within a laboratory setting and with a considerable number of manual steps. Using a CDMO’s automated, state-of-the-art, closed processing systems (like the CAR-TXpress Platform) can provide a much more efficient, safe, and cost-effective solution.
Automation can also positively impact the technology transfer process. A seamless transfer of assets is essential for reducing time to clinic, but it is often a bottleneck (taking up to four months), with timelines extending if reruns are required for regulatory submission. The main drivers behind the length of this process are the mandatory requirements outlined by the WHO: the technology transfer must follow a logical/standard operating procedure (SOP), have fully traceable documentation, use professional expertise, and occur in accordance with the local regulatory boards.
Aligning tools to those a CDMO already has in-house may smooth this process for a biotech. Adopting commonly used platforms, like Miltenyi MACSQuant for flow cytometry analysis, Cytiva WAVE for cell growth, or a Nuclear Counter 200, or using the CDMO’s from the outset supports the seamless transfer of SOPs and ensures consistency of data in regulatory reports. Consistency of tooling for manufacturing stage gate release is particularly helpful in ensuring alignment between R&D activities and the CDMO, helping with troubleshooting and timely releases.
These capabilities are not a panacea, nor should they be relied on to rescue slow development pipelines. CDMOs are always in high demand, with wait times for dedicated cleanrooms and skilled teams ranging from six to 12 months – a clear challenge for biotechs on accelerated clinical release timelines. Time constraints can be further exacerbated by the high staff turnover that some CDMOs face, with short handover periods to contractors brought in to resolve staffing gaps. The resultant retraining of new team members can result in unexpected delays, significantly impacting compounds with complex, highly tailored manufacturing processes.
Working with a CDMO to automate manufacturing processes should not be viewed as a guaranteed route to cost savings. Although automation can reduce the per-unit production cost, the development of multiple products can still be a large expense for an organization, with CDMOs typically charging for each new product introduced into their system. A new product introduction (including technical transfer, engineering runs, aseptic validation, and clinical runs) may be prohibitively expensive for smaller biotechs, with CDMO costs being reported by A. Sertkaya et al. as ranging from $20 million to $30 million.
CDMOs Can Help Establish Digital Backbones For Multidisciplinary Teams
Collaborating with a CDMO provides an opportunity to design a transparent digital backbone that extends throughout the therapeutic development process. This can enable better collaboration and coordination between the matrixed teams conducting clinical trials and support the information sharing that is essential to achieve a successful IND submission.
The recent introduction of CTIS and EUDAMED in the EU demonstrates the growing desire for electronic submission of regulatory data. A CDMO’s GMP-compliant data capture processes provide time, date, and user stamp details, reducing the burden on internal dossier compilation teams. This information additionally aids auditors, enabling them to extract data sets and track performance of various batches of drug product during initial dosing and stability studies.
Data interoperability is an increasing focus post-launch, especially as more healthcare providers are moving toward decentralized care. Patients increasingly give treatment consent via digital forms and report their health through electronic solutions. This information can be used to monitor adverse events or adjust the next treatment dose to increase efficacy. A combined digital backbone can ensure information is shared transparently and securely across stakeholders, supporting long-term patient care plans and providing stakeholder value from lab to bedside.
Investment in AI tools to support clinical diagnosis is growing; spending on AI in healthcare was projected by Business Insider to grow at an annualized 48% between 2017 and 2023, with organizations like Agilent, Gilead, and Biogen already exploring this opportunity. Proactively designing a platform that can combine machine learning/AI capabilities with integrated treatment and manufacturing data may prove to be essential for long-term patient management and treatment success in the future.
Building a system like this is heavily reliant on both the CDMO and biotech working in good faith toward a long-term vision. If either party contracts without properly discussing their partnership ambitions, it may be too late to change once an unwillingness to collaborate is discovered.
A One-Stop Shop CDMO May Not Be Suitable For All
CDMOs have a global reach, with facilities located across the world. This is attractive for biotechs looking to have therapy manufactured in a specific location but also introduces additional complexities with supply chain management and local regulatory compliance. Currently, several London-based biotechs are running clinical trials across Europe, while contracting CDMOs located in the U.S. These biotechs need to take additional care to ensure that what is being produced in the U.S. meets European regulatory standards.
The turnkey processes offered by a CDMO allow them to act as a one-stop shop solution for biotechs, but they are not the only route. An alternative to traditional CDMOs is represented by partnership development management organizations (PDMOs), such as Ocyonbio, Sterling, and Resilience. When working with CDMOs, therapy developers may find themselves limited by commercial models, restrictive contractual arrangements, or excessive intellectual property controls. PDMOs aim to resolve these issues by offering more flexible partnerships and manufacturing spaces than is possible under the classical CDMO “fee for service” models.
Choosing between in-house process development and manufacturing versus outsourcing to a CDMO or a PDMO is a critical decision for biotechs, with a wrong decision increasing cost and time to clinic. When choosing which route to select and which organization to choose, a biotech should carefully evaluate all the above factors. No universal right solution exists; what is suitable for the product pipeline, business strategy, and operating model of one organization may not be suitable for another. Conducting a thorough evaluation to find the right balance is key to success — and key to the speed of that success.
About The Authors:
Aisha Shakeel is a healthcare and life sciences expert at PA Consulting. She is focused on cell and gene therapies, specializing in oncology and rare disease platforms. She has worked on drugs taken to clinic during her time in pharma and biotech and has real-world experience working with CDMOs. Shakeel has helped identify, develop, and leverage new technologies to solve business needs, as well as improve their innovation and product development processes. She holds a BSc (Hons) in biomedical sciences from London Metropolitan University.
Kieran Reals is an operational improvement expert at PA Consulting. He helps organizations at the intersect of healthcare and life science deliver digital and operational transformation initiatives. A specialist in human-centric trial design, he specializes in radically transforming the planning, design and conduct of clinical trials. Reals holds a MBioSci in biomedical sciences from the University of Southampton.