Bringing a new drug to market is one of the most demanding undertakings in modern medicine. The process of taking a promising compound from the research lab to a therapy available on a pharmacy shelf is a long one that requires years of careful work, the expenditure of vast amounts of capital, and a whole series of processes that have to go flawlessly. Specialized Contract Development and Manufacturing Organizations, or CDMOs, are partners that are essential to the process for many pharmaceutical and biotech companies, especially those that are smaller without the in-house infrastructure to complete all the steps.

The job of CDMO is not just about work outsourcing. The best of them possess deep technical expertise, purpose-built facilities, regulatory experience, and are really able to deliver a compression of time and enhanced likelihood of clinical success. To understand how they do that, it’s necessary to get into the details of why drug development stalls out and why specialization alters the game.

Does that sound like a big problem with you?

It is a phenomenon that big pharmaceutical firms have always endeavored to keep all the control over their development and manufacturing pipelines. The principle is correct – if you can make some of the processes there tighter, there must be fewer delays, better quality, and less reliance on third parties. But in real-world situations, in-house staff may be constrained by capacity, equipment, or lack of knowledge, resulting in delays when they are needed the most.

The dilemma is more acute for biotech start-ups and mid-sized companies that are working on new Cell and Gene Therapy. They have clinical candidates and the availability of the manufacturing infrastructure to produce the clinical-grade material in the needed quantities for trials, which is often unavailable. It will cost hundreds of millions of dollars and years to build that infrastructure from scratch, and it doesn’t make any sense when the compound has not yet been cleared for Phase I.

The problems are solved by CDMOs

Instead of the drug developer having to develop and construct their own manufacturing and development facilities, the CDMO model provides a shared infrastructure that is maintained as a specific facility but is available to multiple clients as needed.

If you’re considering a college degree, you should understand what a specialization is.

CDMOs are not all the same, and there is a difference between a generalist contract manufacturer and a really specialized CDMO that can make a huge difference in clinical development.

A CDMO specializes in a certain class of molecules, dosage forms, or technologies. Others focus on biologics, which are monoclonal antibodies, fusion proteins, and complicated cell-based processes that require producing them. Some have specialized knowledge in using very powerful active pharmaceutical ingredients that demand containment and handling technologies and procedures that would not be safe at a general facility. Others are working on formulations of lipids, gene therapy, oligonucleotides, or special solid oral dosage forms with more complex release profiles.

The focus this creates is tangible and can mean the difference. A CDMO with hundreds of bioreactor campaigns with mAbs has process knowledge that cannot be quickly learned by a new team that has just begun. They have overcome more failures, fixed more issues, and devised more successful protocols than a large organization that is handling many molecule types at a time. That institutional depth speeds up troubleshooting, minimizes deviations in the process, and decreases the time it takes from initial production of material for the first time in human clinical studies to a stable and consistent clinical manufacturing process.

Regulatory Fluency as a Speed Driver

Accumulated regulatory experience is one of the most important ways that specialized CDMOs can speed clinical development. The regulatory submission documents, such as IND applications, IMPDs, and CMC sections of clinical trial applications, are technically challenging documents that are required to comply with strict standards by the agencies such as the FDA, EMA, etc., of different countries. If there are any errors or gaps in these submissions, a clinical hold or request for information can result, which can cause months of delay to a program.

The CDMO has extensive experience in preparing dozens or even hundreds of regulatory packages for similar molecular types, and thus has a working vocabulary with the regulators. They understand the types of data points that are closely reviewed, how to convey manufacturing controls in a manner acceptable to the agency, and potential areas to watch out for on any given class of therapy. That familiarity doesn’t mean to say that there is approval, but it definitely decreases the ping-pong effect that stalls out less experienced organizations.

A few specialised CDMOs also keep in regular contact with the regulatory authorities via pre-submission meetings and involvement in industry working groups. The link ensures they stay up to date on changing expectations, especially in rapidly changing fields such as cell and gene therapy, where the regulatory landscape is rapidly evolving.

Compressed Timelines Using Parallel Processing

Traditional drug development is generally done linearly. The work of process development is completed first, before formulation work is started. The formulation work is completed before the beginning of the analytical method development process. Each handoff involves a waiting period, and the total waiting period is a development timeline that is much longer than the work itself.

Many of these workstreams can be performed concurrently by specialized CDMOs, especially those that can provide integrated development and manufacturing Process Development Services. It is possible to develop and optimize the process and formulation at the same time. Early batches may be used for the development of an analytical method without awaiting finalization of the process. Stability studies may be started on a representative material, while at the same time, further optimization of the process is in progress.

This is a parallel process that needs tight collaborative work and communication between teams, and can save 6–12 months of development time. That time compression is a real asset in a competitive therapeutic area, where several players are pushing for similar clinical outcomes.

Technology platforms that help to eliminate early uncertainty

The number of CDMOs that have developed their own technology platforms that provide their clients with a competitive edge. A client can license or purchase an existing manufacturing platform and customize it to the particular molecule.

For instance, in the biologics arena, a CDMO with a high-performance cell line development platform can provide a manufacturing cell line in just a few months, whereas a de novo development effort would take. For oral solid dosages, existing hot-melt extrusion or spray drying platforms enable a quick screening of formulations for poorly soluble compounds, without the months of basic research required with a new platform.

The technology platforms do not replace development activities, but they significantly shorten the exploration phase and enable development teams to proceed to optimization and scaling up at a more rapid pace.

Conclusion

The process of moving from a promising clinical candidate to an approved therapy has always been a difficult one and is unlikely to be easy. New modalities make the science more complicated; regulations are continually getting tougher, and the pressure to get products to market is as strong as ever. In this challenging landscape, niche CDMOs have developed a business beyond contract manufacturing.

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