Choosing the correct Contract Development and Manufacturing Organization (CDMO) is crucial for any biotech company, especially for startups.

The CDMO will be a critical partner in the development, production, and regulatory navigation of a product, making the choice pivotal. Sigma Mostafa, Chief Scientific Officer at KBI Biopharma, offers insights into what to look for in a CDMO, key considerations in partnership, and common pitfalls to avoid.

This concept is discussed in greater detail with Jochen Sieck in an episode of the Smart Biotech Scientist Podcast, hosted by David Brühlmann, founder of Brühlmann Consulting.

Key Factors in CDMO Selection

Several important considerations must guide the decision when selecting a CDMO, especially for a biotech startup. These factors will ultimately determine the project's efficiency, quality, and success.

1. Strong Technical Capabilities and Expertise

For startups, access to resources and capabilities is often limited. This makes it crucial to choose a CDMO that possesses deep technical expertise and can guide the company through every stage of development. 

The chosen CDMO should offer:

• Proven success in navigating regulatory challenges
• Expertise in both upstream and downstream processes
• Experience working with the specific asset or technology of the startup

A trusted CDMO partner is not just an executor of a proposal but a collaborator who helps steer the biotech company through technical hurdles, development, and regulatory landscapes.

2. Speed and Scalability

Speed is essential for startups, especially when there are financial pressures. A stable CDMO should be capable of meeting timelines and scaling processes efficiently. Delays or missteps can be disastrous, so partnering with a reliable CDMO that values customer success and delivers on time is vital.

3. Trust and Communication

Effective communication and trust form the bedrock of any successful partnership. Biotech companies should look for CDMOs that prioritize transparent communication, understand the importance of keeping clients informed, and share data promptly. Having a clear risk-sharing philosophy is also crucial in the event of unexpected challenges.

One-Stop Shop vs. Specialized CDMOs

There are two primary models in the CDMO space: one-stop shops and specialized providers. Each has its advantages and disadvantages, and the choice depends on the product's complexity and the biotech company's needs.

One-Stop Shop

A one-stop shop is a CDMO that provides all services under one roof, from early-stage development to full-scale manufacturing. 

This model's main advantage is convenience, as it simplifies management and provides a single point of contact. However, the downside is that not all CDMOs under this model are equally proficient across all areas, which could lead to subpar results in some parts of the process.

To mitigate these concerns, some companies, like KBI Biopharma, partner with other specialized providers for specific needs (e.g., drug product or drug substance manufacturing). This allows for excellence in each area while offering customers a single proposal and point of contact.

Specialized CDMOs

For more complex projects, a specialized CDMO might be preferable. These providers focus on specific aspects of the manufacturing process, such as drug substance production or specialized services. 

Although the client may need to manage multiple relationships, partnering with specialists often ensures higher expertise in particular areas.

I do think that the overarching part though is where often challenges happen is that communication part and building that trust and relationship and sort of a key customer model where customer feels truly valued and feels like they're getting the necessary attention. So to ask those questions upfront and getting a clear answer is important.

Questions to Ask a CDMO

When selecting a CDMO, particularly for startups with limited CMC knowledge, it's essential to ask the right questions. 

Here are some critical areas to inquire about:

• Experience and Success Rate: Ask about the CDMO's experience with similar products and their manufacturing and regulatory approvals success rate.
• Communication Practices: Understand the communication methods the CDMO employs. Do they use a particular electronic platform for sharing data, and how quickly do they inform clients about developments?
• Risk Sharing and Problem-Solving: What is the CDMO's approach to handling unforeseen challenges? A good partner should be willing to share risk and work collaboratively to resolve issues.
• Technical Capability: Ensure the CDMO has the technical expertise to handle scale-up challenges and solve any issues arising during the process.

Common Pitfalls in CDMO Partnerships

While choosing the right CDMO is critical, managing expectations and avoiding common pitfalls is equally essential.

1. Misaligned Expectations

Clearly defining what matters most—cost, timeline, quality, and communication—at the outset is essential. 

Aligning expectations ensures that both parties understand the goals and the challenges that lie ahead. Biotech companies should create a detailed timeline and address any concerns regarding the interconnectivity between different stages of development, such as cell line development and upstream/downstream processes.

2. Lack of Transparency

A lack of transparency and poor communication are two common reasons for failure in CDMO partnerships. The CDMO culture should focus on building relationships and working together to solve problems. The more transparent and collaborative the CDMO is, the more likely the project is to succeed.

3. Failure to Consider All Aspects of the Process

Biotech companies should consider every aspect of the manufacturing process, including regulatory issues, cell line development, and media selection. Ensuring the CDMO understands and can address all facets of the process is key to avoiding roadblocks later in development.

Strategic Considerations for Cell Line and Media Selection

Choosing the right cell line and media is among the most important decisions in bioprocess development, as it has long-term implications for productivity and product quality.

1. Cell Line Selection

The robustness of a cell line is crucial for the success of the bioprocess.

 A strong cell line should have:

• High productivity
• A reasonable doubling time
• A stable distribution for product quality attributes, such as glycans

For instance, KBI BioPharma's cell line boasts a doubling time of 15 to 16 hours, significantly faster than the industry standard of 24 hours. Selecting a robust cell line ensures higher productivity and consistent quality throughout development.

2. Media and Feed Selection

Media and feed have a profound impact on productivity and product quality. Some CDMOs, like KBI BioPharma, have proprietary media and feed options but will also screen external alternatives to find the optimal solution. 

Testing multiple options allows the CDMO to select the best media and feed combination, which is vital for ensuring the highest quality and productivity.

Biotech companies should perform screening studies early, particularly when developing complex products, to determine the ideal combination of cell lines and media. Addressing product quality concerns early prevents issues later on during process development.

In-House vs. Outsourcing: Finding the Right Balance

As a biotech company matures, decisions regarding which capabilities to keep in-house and which to outsource will evolve. Startups often outsource all process aspects, including manufacturing and analytics, which makes sense for their stage. However, companies may build internal capabilities in areas like small-scale analytical testing and process development as they grow and develop a more extensive pipeline.

Eventually, large-scale manufacturing may only make sense to bring in-house if the company has a significant pipeline or is cost-effective. The choice of in-house versus outsourced services highly depends on the company's size, experience, and strategy, such as whether the plan is to keep assets and progress to phase three or sell them earlier.

The Biotech Industry and the Rise of CDMOs

The biotech industry is experiencing significant growth, with Contract Development and Manufacturing Organizations (CDMOs) poised to expand alongside it. 

A key factor driving this expansion is the introduction of new technologies, which opens up numerous opportunities in drug development and molecule production. The growth in the sector highlights the importance of attracting talented professionals who can shape the future of drug development and bring new molecules to market.

Despite potential market downturns, the industry remains optimistic. Technological advancements are moving rapidly, and the new molecules entering the market offer promising, targeted solutions. 

With this diversification of the biotech portfolio, CDMOs and pharmaceutical companies will continue to play a pivotal role, offering the necessary support and technology solutions to facilitate these developments. The future holds great promise for all involved in the industry.

Inside the CDMO: A Look at Tech Transfer

Challenges of Tech Transfer

Tech transfer is a critical process in the life cycle of biomanufacturing, especially when transitioning from one facility to another. Transferring a customer-developed process into a manufacturing facility can be a make-or-break moment in drug development. 

The process may seem straightforward when the CDMO handles both the cell line and process development; however, it becomes more complex when a customer has developed the process on a smaller scale and needs it transferred to a larger manufacturing facility.

For seamless tech transfer, the process typically follows these steps:

• Small Scale: The tech transfer begins with a small-scale (bench scale) transfer from the client to the CDMO facility.
• Pilot Scale: This is followed by a pilot-scale run to prepare the scale-up into the industrial plant.
• GMP Manufacturing: The process transitions directly into Good Manufacturing Practice (GMP) production at large scale, bypassing engineering runs. If it’s an early-phase project, only one GMP manufacturing run may be necessary.

Success Rate: CDMOs with a strong technical foundation boast high success rates in tech transfers, ensuring the transfer is completed without failure. This success can be attributed to a deep understanding of the equipment and the required process conditions.

However, challenges arise when the customer has developed the process on different equipment platforms. If, for example, the customer has used stainless steel bioreactors and the CDMO uses disposable platforms, the CDMO must understand the differences between the two. 

Similarly, transferring processes between bioreactor types, such as Sartorius or Thermo Fisher, requires a thorough understanding of the process parameters and equipment settings. A key aspect of successful tech transfer lies in the availability and quality of process details provided by the customer. 

The more detailed the process information, the smoother the transfer. If the information is sparse, additional studies may be needed to understand how processes impact product quality and identify potential areas of failure.

In addition to process challenges, the supply chain plays a crucial role. The timely availability of the correct materials and completing all preparations are essential for a successful tech transfer. 

This is particularly critical when customers require a fast transition to GMP manufacturing, often within a tight timeframe.

Accelerating Timelines in Drug Development

In the highly competitive biotech industry, time is a critical factor. Strategies employed by CDMOs to accelerate timelines can significantly improve product delivery to market. For example, CDMOs are now able to offer a remarkable timeline of just 12 months from tech transfer to GMP production and even shorter for enabling toxicology material production, which can be achieved in as little as five months.

Several factors contribute to this speed:

• Fast Doubling Cell Line: Utilizing cell lines with fast doubling times and short selection periods can significantly speed development.
• Integrated Departmental Workflow: Starting work on upstream processes while working on the cell line ensures that development continues without delay.
• Efficient Scale-up Process: Confidence in the process's scalability—from bench scale to large-scale GMP production—reduces the time needed for additional steps like engineering runs or multiple scale-ups.
• Risk Appetite for Pooling: Some companies are willing to generate toxicology material from pooled cell lines rather than requiring single-cell clones. Regulatory authorities now accept this approach, which contributes to faster timelines.

Harnessing New Technologies and Data Analytics

The biotech sector is evolving rapidly, driven by new technologies, data analytics, and artificial intelligence (AI) integration. Two notable trends are reshaping how CDMOs operate: the increasing complexity of drug modalities and the integration of advanced technologies like AI and machine learning.

Complex Modalities and Interdisciplinary Collaboration

As biotech moves toward more complex modalities, such as antibody-drug conjugates (ADCs), the demand for cross-disciplinary expertise has never been greater. These types of drugs require not only strong biological understanding but also chemistry expertise to develop and purify the products successfully. Collaboration between biologists and chemists is essential for creating effective drugs and ensuring proper formulation.

The Role of AI and Machine Learning

AI and machine learning are increasingly integral to improving biotech efficiencies. CDMOs are utilizing these technologies in several ways:

• Protein Sequence and Developability: AI tools can assess a protein's developability based on its sequence, identifying potential challenges and guiding the focus of research efforts. This reduces the number of studies required, leading to quicker development timelines.
• Formulation Development: AI also streams formulation development, minimizing the need for extensive screening studies.
• Data Analytics: CDMOs leverage large volumes of technical data to correlate biophysical attributes and process conditions. This allows them to optimize processes and predict outcomes, ultimately increasing the success rate of biomanufacturing efforts.
• Cell Line Improvement: AI and machine learning also extend to improving cell lines. By applying bioinformatics tools, CDMOs identify target regions for cell line enhancements, such as those in Chinese hamster ovary cells, a common host for biomanufacturing.

In addition to AI, CDMOs are investing heavily in automation, robotics, and high-throughput solutions. These investments help to streamline operations, increase efficiency, and reduce human error in the lab.

We are very focused on data analytics in terms of huge volume of data we have from technical data where we are looking at molecule attribute, biophysical attribute outputs from bioprocess studies and being able to correlate those to be able to say this type of molecule, this type of attributes, needs this kind of process. And again, the idea is to reduce the amount of studies being done, but also to increase the success rate.

The Future of CDMOs and Biotech Partnerships

Looking ahead, CDMOs' landscape is likely to resemble that of large pharmaceutical companies, with deeper technological capabilities and more collaborative partnerships. 

As CDMOs continue to innovate and integrate new technologies, they will become even more valuable partners to biotech firms. CDMOs are expected to provide holistic solutions that include not only manufacturing but also regulatory support.

By leveraging their extensive knowledge from handling numerous IND and BLA submissions, CDMOs are well-positioned to assist clients through the regulatory process, offering invaluable insights and support.

Leadership and Building High-Performance Teams

Leadership is critical to building high-performing teams within CDMOs. Successful leadership involves trust and the ability to mentor employees, especially those starting their careers in the industry. Many leaders within CDMOs started in junior positions and grew within the organization, fostering a mentorship and career development culture.

Empowering employees to solve problems while informing them about the big picture is key. Leaders should be transparent about the company's goals and the direction of the industry, allowing employees to see where they fit in and how they can contribute. A collaborative environment where everyone's voice is heard is crucial for fostering innovation and growth.

Ultimately, leadership is about providing guidance, offering support, and allowing employees the autonomy to make decisions while keeping the company's broader goals in mind. Leaders can build strong teams that drive the organization's success by creating a culture of empowerment and transparency.

Final Remarks

The biotech industry is undergoing rapid growth, fueled by advancements in technology and the emergence of new drug modalities. CDMOs play a crucial role in this landscape, providing the technical expertise and operational support necessary to bring innovative therapies to market. 

Simplified tech transfers, accelerated timelines, and the integration of cutting-edge technologies like AI and data analytics are helping to streamline development, ensuring faster and more efficient biomanufacturing. Additionally, strong leadership and fostering high-performance teams are key to building successful organizations that can navigate the complexities of biotech. 

As the industry continues to evolve, the role of CDMOs will only become more integral, offering holistic solutions that encompass manufacturing, regulatory support, and advanced technological capabilities to meet future demands.

About Sigma Mostafa

Sigma Mostafa is the Chief Scientific Officer of KBI Biopharma. A highly experienced biopharmaceutical executive with a track record of driving growth and market expansion, building high-performance organizations, and transforming organizational culture, Sigma has extensive technical and management expertise in cell line and process development, tech transfer, validation, and clinical and commercial manufacturing. 

Before her appointment to CSO, Sigma served as KBI's Senior Vice President and Site Head for its largest site. Sigma earned her Ph.D. in Chemical & Biological Engineering from Northwestern University and her Bachelor’s in Chemical Engineering from the University of Texas at Austin with High Honors.

Connect with Sigma Mostafa on LinkedIn.

David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.

He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.  

Hear It From The Horse’s Mouth

Want to listen to the full interview? Go to Smart Biotech Scientist Podcast. 

Want to hear more? Do visit the podcast page and check out other episodes. 
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