Are You Still Evaluating CMOs When You Really Need A CDMO?

By Ivan Di Bonaventura

Outsourcing is a growing trend in the pharmaceutical industry and shows no signs of slowing down. The global CMO market was valued at $92.42 billion in 2018 and is projected to reach $188.07 billion by 2026.

Increasing regulatory requirements, market fluctuations, and technological advancements are making it more challenging for companies to manage everything in-house. From innovative biotech to major pharmaceutical companies, the technical expertise and manufacturing capacity and capability of contract organizations have valuable roles to play.

Classical examples of this are the high demand for GLP-1 for obesity treatment and for antibody-drug conjugates (ADCs) in the clinic and in the market to treat different kinds of cancers.

As a result, many firms are turning to outsourcing to supply their active ingredients, drug products, and packaging solutions.

What's A CMO?

A contract manufacturing organization specializes in services to help pharmaceutical and biotechnology companies to manufacture their innovative pharmaceutical products. They focus mainly on large-scale manufacturing for products already marketed or close to market, which includes high-volume ones.

They also help improve manufacturing processes to reduce costs, manage raw materials sourcing, and ensure manufactured products meet regulatory requirements in different countries. CMOs can help save pharmaceutical and biotechnology companies money since they provide the cutting-edge equipment and highly trained employees that are essential when manufacturing new commercial products or generics, whether from small or large molecules.

What's A CDMO?

A contract development and manufacturing organization, or CDMO, provides end-to-end, fully integrated drug development and manufacturing solutions and services to biotechnology and pharmaceutical companies.

Specifically, the wide range of CDMO offerings include formulation development, specific analytical development and testing, midsize commercial production, product packaging, and technology transfer solutions.

Different from CMOs, CDMOs act as strategic partners to customers, enabling them to focus on research and commercialization while outsourcing critical development and production tasks. This is particularly useful for smaller biotech firms without the infrastructure for GMP manufacturing.

Making The Right Choice: CMO Or CDMO?

While outsourcing can minimize capital and labor costs, the challenge lies in the process of evaluating and selecting the right external partner.

There are different aspects to examine as part of the sourcing process, such as:

• Confidentiality, communication, flexibility, and costs
• Reputation and personal experience, which may not exist or be well established
• Geographical presence
• CMO experience with certain technology or types of products
• Batch size and number of lots to be provided
• Manufacturing and analytical capacity and capability
• Special handling, such as managing exposure limits and implementing a containment strategy in ADC manufacturing
• Presence of stability chambers and how controls prevent temperature excursions

Meanwhile, operational and business points must play a major role, quality considerations must be included in the selection process. Unfortunately, amid the myriad other considerations that come with hiring a CMO or CDMO, some key factors are often overlooked until later or when they become a problem. These issues, which affect even the most established manufacturing organizations, can interrupt development and production timelines and, in the worst cases, delay deliveries.

Here are a few quality points to consider when assessing your potential contractor:

• How robust is their quality management system?
• Does their GMP inspection history include recalled products and major observations?
• Does their infrastructure and quality culture align with your product and needs?
• Procedures for nitrosamine and genotoxicity of starting material
• Do their cleaning validation procedures meet your standards and expectations?

Product-Specific Considerations

CDMOs will often work with their customers to develop ideas for new products or make changes to existing ones. In contrast, most CMOs focus more on producing the best possible outcome, concentrating on delivery.

A CMO, moreover, already may have several clients and a small window in which to produce. This usually results in capacity reservation fees or equipment purchase to manufacture products with specific processes. In this regard, major consideration also must be given to the analytical capacity, which may impact analytical methods development and validation and release activities.

Assessing Your CMO’s or CDMO’s Capacity

When courting your new contract manufacturer, whether CMO or CDMO, it’s important to assess their capacity and fully investigate any weak links in their supply chain.

When supply chain constraints hamper deliveries, it can trigger many problems, including limited patient access to essential medications, delayed drug launches to specific markets, and increased costs.

Drug manufacturing bottlenecks occur due to various factors that hinder the smooth flow of production processes in the pharmaceutical industry. Root causes include:

• Quality issues: such as major deviations and/or inadequate quality control measures
• Regulatory hurdles: complex regulatory requirements and lengthy approval processes, such as unique specifications or manufacturing procedures for specific countries
• Inadequate manufacturing and analytical capacity at CMO/CDMO: insufficient resources of equipment and skilled labor
• Inconsistent access to critical raw/starting materials: immature supplier network without redundancies

Despite major initiatives, most CMOs nowadays face lack of capacity and capabilities due to high volumes requested, short timelines to deliver products, and manufacturing processes that don’t scale adequately.

To overcome these bottlenecks, it is crucial to first understand their root causes and the impact they can have and, secondly, understand how to mitigate them.

Conclusion

Overall, selecting the right external partner to drive CMC activities is not an easy task and often results in major problems. Assuring the contract organization has the right capacity and resources can be challenging and time consuming. Pros and cons should be carefully evaluated before undertaking major commitments.

About The Author:

Ivan Di Bonaventura, Ph.D., is a scientist and outsourcing expert with a decade of experience in pharmaceutical manufacturing, including peptide drugs and antibody-drug conjugates. His experience includes management positions with Seagen, now part of Pfizer, and AC Immune. He received his Ph.D. from the University of Bern.