Gregg Bodnar
Gregg Bodnar

Standardization in the cell and gene therapy industry is not easy. Stakeholders from across the industry must come together to develop, agree on, and adopt a standard because standards must reflect the needs of the industry, not just one segment.

That does not mean standardization—when possible—is not necessary or achievable. Using starting material collection as an example, the status quo of having slightly different auditing, collection bag labeling, and chain-of-identity requirements for each product is not sustainable when more therapies enter clinical trials and gain regulatory approval.

For several years, industry stakeholders—including cell and gene therapy developers, apheresis collection centers, manufacturers, clinical sites, accrediting agencies, and more—have worked together to develop and implement standards for cell and gene therapies.

Representatives from three organizations instrumental in facilitating standardization efforts—the Standards Coordinating Body (SCB), the Foundation for the Accreditation of Cellular Therapy (FACT), and the Deloitte NextGen Therapies Industry Working Group (IWG)—came together at The ONE Forum 2022 in November. They offered an overview of the benefits of standardization, where standardization is today, and where it is going.

Standards can improve efficiency in meeting regulatory requirements

As Dawn Henke, senior scientific program manager for the SCB, said, “Regulatory agencies prefer the use of standards because it helps accelerate your review process.” Indeed, the U.S. Food and Drug Administration (FDA) released a draft guidance in 2022 for a voluntary consensus standards (VCS) recognition program for regenerative medicine therapies (RMTs) at the Center for Biologics Evaluation and Research (CBER). RMTs include cell and gene therapies.

The draft guidance states that “the use of recognized VCS can assist stakeholders in more efficiently meeting regulatory requirements and increasing regulatory predictability for RMT products.” CBER recognizes that voluntary consensus standards play a role in product development by “reducing the need to develop unique methods for individual products.”

The draft guidance closed for public comment in September 2022. After releasing the final guidance, the FDA plans to publish and maintain a list of vetted standards on its Regenerative Medicine website.1

Although the VCS recognition program is still under development, Phyllis Warkentin, MD, chief medical officer for FACT, said that some companies have approached the organization to determine how FACT accreditation and voluntary standards can be incorporated into IND or BLA submissions as evidence sites are qualified to perform specific activities.

The current state of auditing and apheresis site qualification is not sustainable

Accreditations, like those from FACT, can also create efficiencies post-IND or -BLA.

The SCB, FACT, and the NextGen Therapies IWG have all been involved in initiatives to streamline and standardize requirements for apheresis centers, particularly in apheresis site qualification and auditing. Apheresis centers collect source material for autologous and allogeneic cell and gene therapies.

Warkentin explained that multiple manufacturers often audit a single site because each audit is product specific. Some manufacturers conduct separate audits of the same site for each product. The same is true for site qualification.

As groups like FACT and the NextGen Therapies IWG reviewed audit and site qualification requirements, they found that significant overlap exists from company to company and between audits and accreditation standards.

Finding common ground and accepting an accreditation report, for example, could reduce audit and site qualification inefficiencies while also leaving space for companies to conduct audits and qualifications for the therapy-specific portion of requirements.

According to Warkentin, some cell and gene therapy companies have already accepted the FACT-accreditation report and conducted reduced-scope site qualification and auditing. This decreased duplicative work and increased site satisfaction.

Jen Rabin, project advisor for the NextGen Therapies IWG, also shared that the group’s cross-functional site certification workstream has spent 18 months drafting a risk-based assessment design for companies to use as a site certification approach. Although the assessment design is not yet ready for release, its goal is clear: companies should, for the most part, comply with shared requirements for site certification while still allowing for a smaller number of therapy-specific requirements.

Product labeling standards can improve patient safety

A new standard for labeling products collected for further cell therapy manufacturing exemplifies what can result when industry stakeholders collaborate.

Apheresis centers often collect source material products for multiple clinical trial sponsors or manufacturers. Those sponsors and manufacturers have different requirements for the label attached to the collection bag.

That label is critical for chain of identity and patient safety. Autologous cell therapies originate from and are returned to a specific patient. Many patients may receive an allogeneic cell therapy manufactured from the cells of a single adult donor or cord blood unit.

Multiple label formats increase the error potential. A mislabeled product can result in a patient not receiving the needed treatment.

Gene Cell Therapy Standards Label
Figure 1. Example of the new standard label for use on products collected for further therapy manufacturing. [ISBT 128 STANDARD Labeling of Collection Products for Cellular Therapy Manufacturing]

A group of industry partners—including sponsors and manufacturers, FACT, the Association for the Advancement of Blood and Biotherapies, the National Marrow Donor Program/Be The Match BioTherapeutics, the SCB, and the NextGen Therapies IWG—collaborated with the International Council for Commonality in Blood Banking Automation (ICCBBA) to develop a new standard label specifically for use on products collected for further manufacturing for therapies to be used in clinical trials or commercially (Figure 1).

The label builds on an existing cell therapy labeling standard called ISBT 128, which is managed by the ICCBBA. ISBT 128 is widely used internationally for labeling cell therapy products.

The new label uses the same dimensions as the ISBT 128 label for ease of implementation at centers. The left side of the label contains the standard ISBT 128 information used for traceability; the right side of the label contains the information specific to the clinical trial or manufactured product.

The information included on the right side is flexible but presented in a standardized way.2

In addition, the ICCBBA has a new Chain of Identity (COI) identifier standard in development. The public comment period for the standard closed in September 2022. The COI identifier would be used in cases when a therapy for a single patient requires more than one collection. It allows those collections to be linked and provides a single identifier for downstream manufacturing.3

Be The Match flow chart
To conduct allogeneic cell sourcing for cell and gene therapies, Be The Match BioTherapies takes extensive steps from donor outreach to donor follow-up. These steps—and the various steps in between—are summarized in this diagram.

The ICCBBA used requirements collaboratively defined by SCB working groups to develop the data structure and elements of the COI identifier.

Standards development takes everyone

For standardization to become a reality, experts in every area of cell and gene therapy must get involved by providing input and feedback. Opportunities to get involved include:

  •  Joining an SCB working group or the NextGen Therapies IWG.
  •  Commenting on draft documents when standards are released for public comment.
  •  Using the searchable Regenerative Medicine Standards Portal from the SCB to find standards that have been published as well as those in development.

Just as important as getting involved, companies must adopt the standards into their practices. While standardization is not easy, the accomplishments over the last few years demonstrate that, with support from across the industry, it is possible.



1. U.S. Food and Drug Administration. Voluntary Consensus Standards Recognition Program for Regenerative Medicine Therapies—Draft Guidance for Industry. Accessed November 10, 2022.
2. ICCBBA. ISBT 128 STANDARD Labeling of Collection Products for Cellular Therapy Manufacturing. Accessed November 10, 2022.
3. ICCBBA. ISBT 128 STANDARD Chain of Identity (CoI) Identifier—Draft. Accessed November 10, 2022.

Gregg Bodnar is director of client engagement and account management, Be The Match BioTherapies

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