AGC Biologics: how to optimize early phase manufacturing

BPR: What role can outsource partners play in optimizing early-stage biologics development?​

 By outsourcing to a CDMO, drug developers of all sizes get access to the latest technologies, such as expression systems, platform processes, including antibodies and viral vectors, and CMC expertise which only helps accelerate timelines and increase reliability.

Larger companies with in-house manufacturing capacity can turn to global outsourcing partners like AGC Biologics because they are hoping to mitigate risk for their products, seeking more capacity to help get their products to late-phase stages and wanting access to historic scientific expertise and a worldwide network of resources. The added benefits for small companies are savings in building and maintaining manufacturing facilities and analytical equipment.

 Biologics can be challenging to manufacture, and a partner that has experience with a range of molecules besides monoclonal antibodies offers trusted scientific expertise and experience with optimizing early-stage projects, guiding the customer through phase-appropriated activities for every stage of the project.  At AGC Biologics, our teams of scientists at our seven sites across the globe have seen and developed custom programs for the most complex molecules (from coagulation factors to cell therapies) for 25+ years, and that knowledge and acumen gets passed down to any new customer that chooses to work with us.  

BPR: What types of technology can play a role in supporting this process optimization?  ​

Single-use bioreactor technology offers greater flexibility. Single-use technology and materials allow you to change the configuration of a manufacturing line, exchange or add unit operations, and cover various scales of operation - adding flexibility for developers at early stages. For example, at AGC Biologics, we can configure our single-use bioreactors to help us vary the batch sizes in the same manufacturing line by combining harvests of parallel 2,000L single-use bioreactors (scaling out the process).

 The flexibility helps our customers seeking to build clinical manufacturing programs by giving them the possibility to hold off on scaling their drug product in early development stages until demand is well understood, saving them internal resources, time, and money. The benefits also extend to later stages - developers can scale out based on need and demand.

New Innovations in downstream purification. Even the well-established monoclonal antibody platform processes can benefit from modernized technologies. Through a new partnership with W.L. Gore, AGC Biologics is working on scaling up and implementing a new disposable membrane-based protein A capture device for antibody purification in its protein biologics manufacturing network. We are finding this innovative technology can reduce the cost of the protein A purification step, remove storage and bioburden challenges, and condense the overall manufacturing footprint.

For the early-stage developer, the Gore purification devices increase flexibility and lower clinical and commercial manufacturing costs by helping to create a complete single-use technology platform process (when paired with single-use bioreactor technology systems). There is potential for the technology to replace standard resin chromatography for this critical step in the development process, which is very costly to purchase and is hard to store and maintain for multiple uses.

BPR: What are the biggest thing researchers should keep in mind when developing a drug for clinical trials?​

Two considerations AGC Biologics focuses on with drug developers of any size are process robustness and reducing timelines. These are considerations in the early phases that we advise developers to focus on.

How robust the manufacturing process and the analytical methods are can often be neglected in the early part of development to reduce costs and increase speed. Researchers and drug developers must consider manufacturability earlier in the process development phase. At the same time is important to keep the development of the process appropriate to the clinical phase, so there is no waste of resources and time.

Too often, the manufacturing process is purely laboratory-focused without more considerations for manufacturability when a product needs to be transferred and scaled up. Failing to consider manufacturability in the lab can cause delays and longer timelines for getting into the clinic and require conducting new steps for the first time at scale, which poses a risk if your outsourcing partner has inexperienced personnel.

BPR: Do you have any tips or considerations for better development you see being frequently overlooked by clients that come to you?​

Increase your transparency with your outsourcing partner. Some customers are reluctant to share some process details, particularly when transferring the process from another CDMO. In addition, create proper handling notes. Detailed handling notes with information such as stability to temperature, pH, concentration, etc., are particularly critical to create when developing the product and have clearly defined for an outsourcing partner. Our job as a CDMO is to get our customers to succeed and that goal is achievable when the customers and the CDMO foster an open and transparent exchange of data.

Do not underestimate the importance of process robustness. Some customers are overly focused on timelines and while speed is relevant, so too is developing a process that is reproducible. A good CDMO-customer partnership should hold space to discuss how to find a balance between speed and process robustness.

You must understand how development activities are phase appropriate. Developers should know, or work with the CDMO to determine, which aspects of process development they need to focus on for early clinical development vs. more extensive development activities that will be needed as they enter late-stages.  Such conversations could have a positive impact on the project timeline as well as allowing for the developer to plan for long-term financial commitments.

Create collaboration with technical teams and subject matter experts. It is important that your subject matter experts and the CDMO's subject matter experts have close conversations to share process issues and solutions. It is important that you consider this during the CDMO selection process and find a CDMO that supports these types of conversations.