CGT Apheresis Service Market: Future Challenges

By Sanjay Srivastava, Ph.D., Cell & Gene Therapy Lead, Life Sciences Practice and Vinod Mrithinjayam, Managing Director, Capability Network Life Science and Health at Accenture

Other Contributors: Anuj Gupta, Ainesh Jishnu, Vaibhav Kayathwal, Shruti Nair, Sakshi Guleria, Harsha Agarwal

The Cell and Gene Therapy (CGT) market is poised to grow at a significant rate due to evolving opportunities like drug approvals and strong pipeline of cell and gene therapies. Other favorable factors, which are supporting this market include increasing prevalence of cancer and chronic diseases, rising number of clinical trials for cell and gene therapy and favourable regulatory environment. Hence, this is an exciting time for pharmaceutical companies in the CGT area.

However, this space is also facing certain challenges due to its complex nature. Some of them include complex patient referral pathway, multi-step process of generating autologous products and difficulty in patient evaluation and patient eligibility.  To add to that, the apheresis sites are limited and estimated to grow only at single digit growth rate.  This presents a stark contrast to the overall Cell and Gene therapy space, where patient volume is expected to grow at approximately 20-30% YoY. This implies there could be a potential demand-supply gap in the near future.

Given the dynamics and complexity of CGT, it is imperative for pharma companies to differentiate themselves and enhance the efficiency of the partner apheresis centers. It is extremely crucial to address the operational complexities related to apheresis process by automating supply chains, standardizing audit and trainings, enhancing patient recruitment processes and adopting a collaborative approach.

For improving the overall efficiency of the existing apheresis centers, we must address gaps in the following key areas:

1. Workflow Management:

Having a standardized workflow driven solution helps in managing challenges in routing partners, donors and products through the process. There are three key areas which need to be addressed:

• Patient and Donor Apheresis Schedule: There are fluctuations in Patient and Donor Apheresis schedule. It is also important to capture and manage patient and donor information throughout the workflow. This can be done by choosing digital platforms that demonstrate prior regulatory authority acceptance and performance.
• Data Management Strategy: Traditional data management strategies cannot effectively collect, process, and analyze the quantity of data generated from advanced therapies and thus capturing data at each stage to support quality, traceability and regulatory compliance becomes difficult. This can be resolved by managing real-time information integrated from other departments including insurance status, patient demographic information, laboratory test results, and cellular therapy product availability.
• Stakeholder Management and Complex Workflow: Tracking and managing each step of the workflow becomes difficult. Getting real time access to know where the patient is, in the Cell Journey can help track the workflow.

2. Quality Management:

Cell therapy manufacturers should ensure apheresis collection facilities maintain a comprehensive quality management program. The quality program should ensure process control is maintained during all aspects of the apheresis. The key areas which need to be addressed are:

• Standardization: With so much variation in apheresis and cryopreservation methods, harmonizing the processes and standards is a huge challenge. This can be resolved by developing standardized approaches in cell collection processes. Software platforms for ordering, chain of custody/chain of identity and patient data should be utilized.
• Quality Management Programs: Lack of quality management programs in apheresis centers creates complex challenges. This can be tackled by having defined processes in place for the management of equipment, training, vendors, materials, SOPs, non-conformances/deviations, and validation/qualification programs.
• Ensuring Cell Collection Quality: Ensuring cell collection quality is challenging in advanced therapies due to patient health, inherent variability in human biology, and the unusual origin and complex processes for procuring this key raw material. Well-designed, hands-on training and careful monitoring of sites via the vendor audit process helps in keeping a tab on performance.

3. Audits and Training:

Manufacturers can help ensure consistent process development by standardizing apheresis center training, equipment and protocols and obtaining access to a large, diverse, and reliable donor network. The challenges faced are:

• Multiple quality system audits: As the number of cell therapies in clinical trials increases, the number of audit requests continues to grow. These audits for compliance and regulations are necessary to ensure apheresis centers meet quality standards. This can be done by an Audit Program offering licensed audit results to therapy developers that can streamline the audit process, saving apheresis and cell therapy lab staff a significant amount of time.
• Numerous requests for SOPs: Numerous requests for copies of standard operating procedures (SOPs), as well as revisions to SOPs. This can be addressed by developing a single CAR-T therapy SOP that establishes a framework that can be modified as additional product, such as gene therapies, become a standard of care. 
• Redundant Training: Cell and gene therapy companies often train staff on every aspect of cell collection and processing, including those for which an approved SOP already exists leading to duplicative training. Instead, train staff on the aspects of each protocol that are unique to the therapy. Using a train-the-trainer approach for training to reduce the number of staff members pulled off the unit for training.

4. Logistics:

Supply chain intricacies such as staff handling information, temperature and storage conditions should be managed with advanced technologies. The major challenge is:

• Cold Storage: Cell and gene therapy products often requires products to be stored and processed at ultra-low temperatures (-20 to -80 °C), with the products only being defrosted immediately prior to use. If these products are not kept in exact conditions, they become unusable. There must be Smart Tech to enable efficient supply chain. Development of smart packaging is a critical element of the supply chain solution.

5. Resource Management:

Companies should consider looking at unconventional sources of talent familiar with required technologies and invest in retraining existing staff to meet the needs of CGTs. Following are the key challenges:

• Device Handling: Nurse/Technician/operator may not be suitably equipped to operate apheresis machines and conduct the process with minimum discrepancy. They should be well trained and equipped to anticipate any mobilization-related adverse events, judge the optimal collection timing and be aware of stem cell or immune cell collection target levels as well as collection volume limits.
• Staffing: There should be appropriate methods for ensuring adequate number of staff to meet the needs each day. This can be resolved by effective scheduling which will maximize staffing and improve procedural coverage. Attempts should be made to accommodate flexible staff schedules to the extent HR policies allow, as flexible schedules improve employee satisfaction and retention. HR policies should allow for stagger shifts to accommodate procedures that start early and those that run late. Additionally, there can also be a designated staff rotate on call.

6. Apheresis Collection:

The apheresis collection facilities and methods are key to success of any CGT treatment. The following areas need to be addressed:

• Apheresis Collection Services: Apheresis cell collection variability due to variable cell collection methods and variable personnel collection is a big problem as it effects the end results. Standardization of apheresis center training, equipment and protocols, product QC testing, including safety, purity, identity, and potency parameters can help fix this.

1. Allogenic Therapies: A highly valued trait in apheresis donors is the ability to reliably donate higher blood volumes rich in the target cell population. However, donors with this trait are not always readily available. Since variability among donors cannot realistically be eliminated, along with access to a large, diverse, and reliable donor network new technological advancements in apheresis devices and methods need to counter problems such as low collection volume or low target cell counts with other measures.
2. Autologous Therapies: It can be difficult to meet the number of T cells required for treatment as donors have already been heavily impacted by their cancer. So, obtaining apheresis material with adequate CD3+ T cell is a critical challenge. Companies can try resolving this by using a prediction algorithm and decision pathway can standardize practice and improve outcomes.

In conclusion, for pharma companies and apheresis centers to stay ahead of the curve in CGT space, they must manage Apheresis resources in an optimal manner. The current scenario of Apheresis Centers presents several opportunities for improvement and innovation in all parts of the value chain. They can look at improving logistics, optimizing packaging, differentiating on customer experience, and standardizing in the nascent stage. Most importantly, they must focus on Digital Platforms as technology to cover all gaps and maximize returns for companies.