West Pharmaceutical Services, Inc

Li Chen

Biologics Delivery Champion

Li Chen currently serves as Vice President at West Pharmaceutical Services. She oversees the development and execution of strategies and plans within the organization. Also she establishes guidelines, policies and protocols to promote efficient operations.

1. In your opinion, how has the Immunotherapy landscape evolved over the years? What are some of the advantages of the current technological evolution?

Technology development for immunotherapy has evolved in several ways. The technology behind life changing living drugs (CAR T-cell therapies) innovated from the need to track their manufacturing and transportation activities, and medical devices fit-for-use for advanced therapies in containment and delivery. Each of these aspects of technology development must integrate with each other to realize the industry’s goal of affordable, curative therapies for all to access equally. In this light, administration technology is behind the biological technical revolution and could evolve from a simple syringe, flexible bag, and cannula to a more personalized device tailored to meet patient needs and the various demands on healthcare staff.

Additional cell-based immunotherapies are also in development, aiming to provide treatment options to those who currently have none or patients who are not able to achieve complete response from existing treatment.

Cancer often develops mechanisms to evade immune response. One such mechanism engages the natural breaks on T-cells to stop it from attacking. Today, the best-known immunotherapy is designed to release the breaking mechanism, called checkpoint inhibition, which allow T-cells to go at full speed to destroy what shouldn’t be in the body. This has worked wonders and we’ve seen continuously expanding indications to pair the monoclonal antibody with various chemotherapy and targeted therapy to treat various solid tumor conditions. Traditionally, the checkpoint inhibitors are administered intravenously. Because of its widespread use, several drug companies are looking at subcutaneous dosing which can give the patients back some cumulative time required for repetitive IV infusions and improve quality of life. Gene-based immunotherapies in the pipeline are also looking to time release molecular therapy which has been especially difficult to achieve for certain disease areas, such as brain cancer.

Releasing the T-cell breaking mechanism is only one of the ways to utilize immune response in the battle against cancer. CAR T-cell therapy is another, where the T-cells are armed to identify cancer and actively pursue its target. Several CART-cell therapies had been approved to treat hematological tumors and were able to show significant efficacy in patients who experienced relapse after chemo and monoclonal antibody. Similarly, personalized mRNA therapy is hoping to address the evolving nature of a tumor and to provide the custom[1]tailored therapy based on the tumor’s makeup at a given time and, therefore, provide efficacy in cases where the tumor does not respond.

2. What according to you are some of the challenges plaguing the Immunotherapy landscape and how can they be effectively mitigated?

Patient selection has always been very challenging. Drug companies have generally needed to come up with companion diagnostics to help select the subgroup of patients who are most likely to benefit from the combination of drugs.

Another challenge is manufacturing of cell-based therapies. 

We have witnessed the successful maturation of manufacturing procedure for small molecule chemotherapeutic agents, and recombinant protein drugs such as monoclonal antibodies and cytokines. We also saw autologous immunotherapies take off when scientists armed patient white blood cells with Chimeric Antigen Receptors (CAR) ex-vivo to allow these gene-modified T cells to recognize their tumor antigens, a therapy widely known as CAR-T cell therapy. The high manufacturing complexity drives the exploration in the development of allogenic cell therapy and in vivo genomic modification. The risks of bringing the new immunotherapy to market are high but can be mitigated by working with industry advocate groups who are defining the regulatory paths necessary for such a task.

3. Which are a few technological trends influencing Immunotherapy today? What are some of the best practices businesses should adopt today to steer ahead of competitors?

For small molecule and biologics developers, the availability of on-body injections opens up a new route of administration and may be desirable to maturing checkpoint inhibitors that can benefit from slowing down its pharmacokinetics. For the advanced therapy developers, many will seek to manipulate the expression of genes or alter the biological properties of living cells. FDA guidance for industry document on Chemistry, Manufacturing, and Controls (CMC) for Human Gene Therapy investigational new drugs (INDs) should be taken into considerations as soon as IND filing is in sight.

For cell therapies, the technological trends are still developing but remain adhered to improvements in unit processes that can be modified without changing the entire manufacturing setup. Process intensification is another hot topic within advanced therapies as time in production ultimately influences cell therapy efficacy. Again, I stress the interaction between therapy developers and technology developers to ideate industry[1]wide solutions and to mitigate potential risks as they occur. Everyone in the industry has a high demand for current knowledge, so staying current is the best way to stay ahead of competitors.

4. Do you have any advice for industry veterans or budding entrepreneurs from the Immunotherapy space?

Immunotherapy, whether it’s in the form of checkpoint inhibitor or advanced therapy, is evolving to the point where combination of multiple technical competencies becomes necessary. While the drug developer needs to focus on showing efficacy and safety in the clinical trial, it may be much easier operationally to achieve the goal by business alliance. Especially because the immunotherapy clinical endpoints may have a shorter timeline, it does not hurt to consider late-stage development and scale up sooner.

The best, and hardest, path to success is hiring the right leadership and attaining the right knowledge. Advanced therapies, such as immunotherapies, require knowledge to be translated to products quickly and effectively while supporting the very needs of the industry. To do so requires deep industry knowledge, expertise, and vision to help all patients ultimately win their battle with cancer.