A Success Story on Partnership -  the Invisible Superpower in CDMO Projects

At ProBioGen, we have always believed that the key to success in the complex world of biopharmaceuticals lies in forming strong, hands-on partnerships. We have had the privilege of working closely with one of our clients on a project that perfectly exemplifies how such a partnership can make all the difference in the world of Contract Development and Manufacturing Organizations (CDMOs).

The Foundation of Success: Partnership

In an industry where the demand for new biopharmaceutical products never ceases, CDMOs like ProBioGen play an essential role. We provide biotech companies with tailored services across the entire value chain, from cell line development and clone selection to process development, non-GMP, and GMP manufacturing, as well as analytical development and routine testing. The expectations are high – flexibility, efficiency, reliability, and holistic consulting are non-negotiable. However, it is the invisible superpowers of mutual partnership, trust, open communication, and equal-footed project management that truly influence the success of a CDMO project.

Thinking Beyond Size: A Case with Ridgeline

Our recent partnership with a start-up built through Ridgeline Discovery, a forward-thinking Versant Ventures Discovery Engine, demonstrated how well managed collaboration can significantly improve patient outcomes and advance biopharmaceuticals.

Together, we embarked on the development journey of an IgG1 antibody, a novel monoclonal antibody designed to treat autoimmune and certain cancer indications.

When selecting the right CDMO, various factors are significant, such as expertise, experience, and resources. Ridgeline's decision to work with ProBioGen was not only influenced by these factors but also by our shared company culture and size. As Ridgeline’s operated company is a start-up, they appreciated our experience and reputation, coupled with our manageable size.

"ProBioGen is not a massive CDMO, but it is highly experienced and reputable. The company's size was particularly appealing to us and our Portfolio Company. We do not get lost among the giants' clientele. It just fit very well, and the spirit was fantastic," said Kai Rosport, Vice President CMC for Protein Therapies at Ridgeline Discovery.

The Steps to Success in CDMO Projects

Producing high-quality therapeutic antibodies involves a meticulously orchestrated process, from pharmaceutical cell line development to large-scale GMP production. Collaborating with CDMOs streamlines this process for biopharmaceutical companies. At ProBioGen, the following process steps are considered standard in antibody projects:

• Pharmaceutical Cell Line Development: The journey begins with selecting the right host cell line, often Chinese hamster ovary (CHO) cells, known for their productivity and suitability for biopharmaceutical manufacturing. We believe in starting right by using an excellent expression system – our CHO.RiGHT® expression system, based on our proprietary CHO DG44 cell line. This cell line, continuously optimized over the years and cultivated in our proprietary chemically defined media platform, undergoes genetic engineering through stable transfection, ensuring highly efficient expression of the desired antibody gene.
• Clone Selection: After transfection, we isolate and evaluate individual cell clones to identify high-producing candidates. Key parameters, such as antibody expression levels, growth characteristics, and stability are assessed under defined conditions to select the most promising clones for further development and master cell banking.
• Process Development: Once we have clone pools, we initiate first material production to kickstart process development. Collaborative work with our partners is crucial as we define critical quality attributes and process expectations. High throughput analytics play a significant role in selecting the right clone and ensuring the development process results in a highly pure and active product. An integrated approach for cell line and process development is crucial to minimize unwanted variants from the beginning and maximize production yield – especially nowadays in respect to new antibody formats. The downstream process shall remove unwanted product related variants further but also impurities originating from the upstream process like Host Cell Protein and DNA. Together with the usual optimization of cell culture conditions, including feeding strategies, and bioreactor parameters, the productivity is maximized and a robust and scalable process for consistent large-scale manufacturing is established.
• GMP Manufacturing: Following material production for toxicological studies, we move on to GMP manufacturing of clinical material. The process is scaled up and optimized to meet strict regulatory standards, ensuring the integrity, purity, and efficacy of the final product - laying the foundation for successful clinical trials and commercialization.
• Product Characterization and GMP Compliance: Throughout the process, we implement strict quality control measures to ensure product consistency and compliance with GMP regulations. We conduct extensive tests to evaluate the antibody's identity, potency, purity, and safety. Since biological activity is a key quality attribute, potency testing is an essential part of quality control and release testing. Our dedicated bioassay department has extensive experience with such activity assays and is able to develop bioassays from scratch to address specific customer needs as a CDMO.

In-house Solutions for Success

Our goal as a CDMO is to be a reliable partner, offering integrated solutions across the entire value chain. In-house analytics and bioassay development capabilities enable streamlined processes and efficient data-driven decision-making. We believe in comprehensive analyses to ensure that molecules perform in practice as expected, consistently meeting high-quality standards.

In our eyes, this integrated approach is the only way a CDMO can shorten overall timelines.

Challenges Faced and Overcome

“Open communication and honesty are extremely important in CDMO projects. Unexpected challenges often occur, which must be addressed directly to find effective solutions.”

Even in seemingly standard projects, unforeseen challenges arise, often stemming from the unpredictable nature of living organisms or modern technology. Such challenges can lead to delays and increased costs. However, flexibility and creativity are our allies, allowing us to adapt and overcome.

In our journey with Ridgeline, we encountered unforeseen technical obstacles during early material production. A delay in material delivery could have jeopardized the entire project. Working closely with Ridgeline, we adjusted internal processes, established workarounds, and made a concerted effort to deliver the product on time. It is often this one extra mile that is required for success. With solution orientation and partnership as two of our values, this willingness to go the extra mile is deeply rooted in our work.

Reliability and Planning Security: The Heart of Collaboration

In our industry, multiple service providers often collaborate simultaneously. Timeliness is paramount, and all parties must work reliably and punctually for seamless operations.

Ridgeline Discovery's project management recognizes this: "From the beginning, the timeline for Drug Substance Release was tight, but despite that and additional obstacles, ProBioGen delivered precisely on the designated day. I was genuinely surprised by their turbo timelines. It's really important for us to have deadlines met as agreed initially, as we build the further project upon that.”

Effective Communication and Skillful Project Management

For CDMO projects to succeed, effective communication and skillful project management, with ideally scientific background and substantial experience, are essential. Our collaboration with Ridgeline was leaded by two experienced, scientifically based women. Perhaps "women's power" is another superpower that should be mentioned. Nevertheless, this project involved mutual appreciation, the ability to challenge each other, and honesty in interactions. A strong partnership goes beyond the minimum requirements, questioning material and actual requirements to optimize the process.

For example, we collectively asked whether a Phase-1 product could be adequately purified with two chromatography steps instead of the usual three during the GMP process. Testing and discussions led to a fearless decision: two chromatography steps were sufficient. This decision resulted in significant cost savings for Ridgeline and reduced our workload. The key is to make agreements quickly and personally and to rely on both solution orientation and mutual trust.

„We could engage in very constructive discussions on an equal footing and challenge each other. That is good and important in order to make projects a success and thus to bring medicines to patients," Kai Rosport from Ridgeline Discovery said about the project with us.

In conclusion, our partnership with Ridgeline highlights the incredible results achievable when CDMOs and biopharmaceutical companies unite their strengths, expertise, and commitment. Our journey together displays the power of collaboration in bringing innovative therapies to patients efficiently and effectively. We look forward to many more successful partnerships on the horizon.

Want to learn more about our Services for Proteins an Antibodies? Learn more by clicking on the following Button: