Selecting a contract research partner to help your biopharmaceutical process development

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By: Amy Friesen

You’ve discovered a new biopharmaceutical product. You used milligrams of material for a proof-of-concept study, but now you need much more for doing additional pre-clinical work.

You’re also thinking ahead about how to manufacture the protein for clinical trials, but aren’t ready to invest in cGMP manufacturing. By the time your contract manufacturer gets started, you’ll have been waiting for months.

Before you start investing in laboratory equipment to do process development beyond bench-scale and produce pre-clinical material, consider a contract research organization (CRO) to become your partner.

In the pharmaceutical world, CRO commonly refers to organizations that organize and manage clinical trials. A broader definition is an organization that performs contract research of any kind on behalf of a company. A process development CRO in the biopharmaceutical industry is a business that can develop manufacturing processes for production of proteins, vaccines, and other biopharmaceuticals.

Most CROs are not cGMP-certified, so they operate less expensive facilities.

Using a CRO, such as the Saskatchewan Research Council (SRC), to work on your process development needs can be a strategy to reduce your company’s cash burn rate. For example, if you want to compare three different ultrafiltration methods for downstream processing, you could ask your CRO if they have the equipment to do a project for you rather than investing in the equipment and the time to set it up and learn to operate.

A well-equipped facility will have a variety of equipment choices for different scales and types of development. In many cases, it is ideal to have small-scale fermentors develop basic growth parameters and a larger vessel for scale-up.

By using a contractor, you pay only for using the equipment and facilities as long as you need them. You also share the cost of maintenance, training, and validation with the service provider and their other clients, saving hundreds of thousands of dollars or more.

Aside from saving capital investment in facilities and equipment, hiring a CRO means that you have a whole team of experts at your disposal. An organization doing biopharmaceutical process development likely has a team of microbiologists, biochemists, and engineers working together to solve development problems.

The size of the organization can determine who might be on your project team. In addition to biologists and chemists, your process might require the expertise of process engineers and instrumentation specialists, and easy access to this know-how can decrease the time and money in process development.

Once a manufacturing protocol is developed and demonstrated by your process development partner, it may be ready for contract manufacturing. If a robust process has been developed and documented well, transfer to your cGMP manufacturer should be seamless.

At this point, your CRO partner can work closely with the contract manufacturer to ensure the smooth transfer. Better yet, introduce both partners to each other as early as possible. If your process development team knows limitations and requirements of the manufacturing site, it can save your company money and time.

When choosing a contract research partner, it’s important to find the right fit between your company and their organization. Process development needs to be a collaborative process and there are questions to ask to determine whether there is a good “fit”.

How does the contract research organization work?

You should ask questions about what processes are in place to make sure that the project is of the highest quality and delivered on time and on budget. Most organizations claim to practice project management, but the processes vary and asking a few questions about it will determine whether their standards are rigorous enough for your product.

The quality management system that is in place in a contract organization can also make a difference. While GMP is not required for process development, you should still ask about good documentation practices. If you are not familiar with the system, make time to plan a visit to the research organization and do an audit of their standard operating procedures and other documentation.

Similarly, you should expect the CRO to ask questions about your company’s and product’s needs. The better information you can provide about the work that has already been done and your expectations, the more likely it is that you will get what you want out of the relationship.

What is the organization’s track record?

You might want to consider how long the organization has been operating and how much experience its project team has acquired.

You should start by asking what other products have been developed. If you have an unusual expression system for your product, you want to be reassured that your process development partner is prepared for the unexpected. It is desirable to collaborate with an organization that understands technology transfer and that has a clear knowledge of manufacturing. It is also ideal to work with a diverse team that brings many perspectives to the table.

After all, you are paying this organization to solve a problem for you and you want to make sure you receive a resourceful solution.

How flexible is the contract research organization?

No one knows your product better than you do, so it makes sense for you to be a critical part of the project team. You might choose to work on different parts of the project yourself. For example, it might make sense for product assays to be developed in-house while contracting out scale-up and downstream processing. Or, you may want your own scientists or engineers to learn about the process along with your CRO. Ask questions about on-site agreements and other arrangements that will enhance the working relationship.

If the project is large, it will help to develop a stage-gated contract that allows project progress to be reviewed and evaluated at every step. If a project needs to move in a different direction, renegotiating the agreement takes valuable time. Make it easier on yourself and your partner by breaking the contracts into smaller pieces.

How well will the organization communicate?

At the end of the day, the success or failure of a project depends on communication between the client and the contractor. Choosing a research partner is like dating—once established, the relationship takes work from both sides.

You should feel welcome to visit your partner on site to discuss the project’s progress. Regular communication should be planned and incorporated into the project.

These can be monthly visits, weekly phone calls or daily emails when the project is at its busiest. While this can seem inconvenient at times, it pays back the first time something unexpected comes up in the project (and in development, there are plenty of surprises!) and a crisis is averted.

Sometimes, manufacturing costs enter into how a process is developed. For example, you might require a protein that is 95% pure, but 99% is more desirable. The material and labour cost to remove the last 4% of impurities may not be economical. A “perfect” process might be the goal, but not if the cost is too great. By communicating your specific needs, your process will be designed around your requirements.

Occasionally, a client is reluctant to tell the whole story to a CRO, but it is important to put your cards on the table.

Confidentiality agreements and intellectual property agreements can help information flow more freely in both directions. Was something tried in the past that did not work? Is your development budget severely limited? Are you having trouble developing an assay? A CRO partner has likely worked on dozens of products in the past and may have a creative solution to these problems.

Amy Friesen is a research scientist with SRC’s Health and Food Business Unit, which provides contract manufacturing and contract research. SRC works with clients from scale-up to production on a range of fermentation applications. It operates a world-class Biosafety Level 2 Fermentation Pilot Plant and is Canada’s only contract research organization with a Canadian Food Inspection Agency license to produce animal vaccines.