AABB24: Managing Vendor-Specific Requirements for Cell and Gene Therapy Work

As of August 2024, 38 cell and gene therapy (CGT) products had been approved by the Food and Drug Administration (FDA), and hundreds (perhaps thousands) of additional products are in clinical trials. Unlike blood components, these CGT products are each unique regarding the contracting, onboarding and operational processes to be managed by the blood center or hospital performing the collection, processing, labeling, auditing and analysis of the new products.

Attendees at the Sunday session “Lessons Learned Onboarding Cell and Gene Therapy Vendors and Clients in the 21st Century” were treated to an inside look at these issues by presenters with first-hand experience.

How Do We Simplify This Complexity?
Program Chair Kevin Land, MD, CABP(H), from Vitalant in Tempe, Ariz., provided an overview of the CGT products in the pipeline and noted some issues that must be addressed, including the following:

• An increasing focus on nonhematologic and allogeneic-derived therapies
• FDA submission requirements with more flexibility
• Streamlined requests for proposals (RFPs), onboarding (tech transfer) and decentralized manufacturing
• Use of existing audits, accreditation visits and facility-established processes

Land also touched on the overwhelming estimate of the patients who might be helped through CGT products, asking the audience by a show of hands how many commercialized or clinical trial CGT products they support in some capacity. Of those who responded, most were supporting more than 20 different products, with at least two supporting around 50, highlighting the need for standardization.

Land then observed that most programs involve hospitals in densely populated parts of the country, where only half of the population lives. He stressed that as more and more CGT products continue to be developed, we need to provide diverse and equitable access to care, and we will need to work together as a network of providers to meet the patients where they live.

Contracting Is New Territory
Not all blood centers and hospitals have experience working as a contractor for a commercial firm, so the terminology used may need some explanation. Kate Brown, PhD, from CooperSurgical Inc. in Tucson, Ariz., reviewed three such terms. She detailed the Master Service Agreement (MSA, covering the overarching responsibilities), the Statement of Work (SOW, project-specific and detailed breakdown) and the Quality Agreement (the quality standards and regulatory requirements agreed upon to ensure compliance with current good manufacturing practice regulations).

She also explained how the AABB standards committee has been working to update the Standards for Cellular Therapy Services to meet the challenges of a rapidly changing field. She described how the agreements section of the current edition was significantly revised to reflect the increasing number of stakeholders and organizations involved at each step.

Brown further emphasized that contracting establishes a relationship between the organization that performs the work and the client organization that receives the product for further manufacturing or provision to the end-user. The key to success is to be clear, specific and detailed in objectives and expectations from the beginning. With such clarity in both outcomes and timelines, pitfalls (surprises, renegotiations, reworking, missed targets, etc.) can be avoided.

A Closer Look at RFPs
Laura Staller, MLS(ASCP), from the National Marrow Donor Program in Minneapolis, Minn., detailed the five major steps in the RFP process as follows:

• Start at the end. First, determine the need to perform the activity and any associated expansion of capabilities. Then, identify the current business partners and how closely they match the desired attributes. Close with an evaluation that limits subjectivity.
• The request process. This step combines two aspects—recipient considerations and a short checklist. Recipient considerations include the expected timeline, information to be shared and any required documentation. The short checklist items include a gap analysis, the possibility of site visits or demonstrations and identification of key personnel and their roles.
• Partner considerations. The three major issues are 1) the basics (accreditation, financial viability and regulatory compliance), 2) variations (geography, hours of availability and technical competency of staff) and 3) the future (scalability, experience and strategy).
• Selection. Selection of a successful candidate organization is a balance of many factors including, but not limited to, costs, expected level of involvement and maintaining good interorganizational relationships.
• Onboarding. This can be an arduous process. The tension can be eased by the use of standardization where possible, flexibility by both parties and development of a detailed process flow. Also helpful are the review and discussion of lessons learned at the particular facility and other organizations, implementation of process improvement techniques and the use of metrics to measure and repeat success.

Operational and Quality Assurance Processes
Given the overwhelming number of CGT products in clinical trials, it is unlikely that a blood center or hospital would invest in biotherapy collection and processing for just one product or vendor. One of the most challenging aspects of the entire biotherapy “environment” is managing multiple vendors/clients. Robert Marriott and Melissa Marlowe, CHS, MBA, from Vitalant in Tempe, AZ, addressed this issue, with Marlowe focusing on the operations aspect and Marriott focusing on the quality aspects. They emphasized crucial questions such as the following:

• Will the donor history questionnaire for blood components be adequate?
• What additional risks should be explained during the consent process?
• Are you operating as a single site or will your activities be occurring in multiple locations?
• Have you and the vendor/client defined and agreed upon specifications and formulations?
• Do you have the capacity to create stand-alone procedures for each product or manufacturing type?
• Is your quality management system ready?
• Which procedures will be used—yours, the vendor/client’s or a partner organization’s?
• How will you manage subtle differences in procedures, requirements and nuances in practice between sponsors?
• Is the SOW detailed and complete with no gaps?
• Have you determined where you can be flexible and where you need to hold your ground?
• Can your current cryopreservation process meet the requirements of the vendor/client?
• Is the collection goal realistic? If not how much retooling would need to be done?
• Will the facility be able to meet the requirements for humidity, HVAC, aseptic and open vs. closed manufacturing considerations?

Even if your facility is performing the same processing for different vendor/clients, the operational and quality processes will be more challenging than the more standardized processes for blood component collection and processing. The keys to successful onboarding and long-term biotherapy partnerships are flexibility and communication.
Practical Examples

The information-packed session concluded with two scenarios that involved audience participation. In the first scenario, the attendees considered outcome metrics other than engraftment, because CGT engraftment is not always the desired outcome. Collection time, total cells collected, meeting minimal dosing requirements and viability were among the audience responses.

In the second scenario, attendees were asked to identify which stage of the onboarding process best demonstrates that all elements of the technology transfer is understood in sufficient detail to be successful. The audience members agreed that it is really a two-part answer where the completed SOW and Quality Agreements represent the first part and successful completion of a mock run represents the second part.