Be the Match/National Marrow Donor Program (NMDP) Offers Validation Protocol to Apheresis Collection Facilities Implementing ISBT 128 Label for Collection for Further Manufacture
Don’t let the new ISBT 128 apheresis collection split label leave you with a split-ting headache! ICCBBA has recently released the ISBT 128 Standard Labeling of Collection Products for Further Manufacture (ST-018) for use on apheresis collection products. To facilitate implementation, Be the Match (NMDP) has developed a validation protocol for collection centers that plan to utilize the new labels. This will allow users to more readily implement ST-018, which provides standardized, consistent labeling to all apheresis collection bags destined for further manufacturing by a sponsor/manufacturer. Please reach out to Tamara Lengacher at NMDP (tlengach@NMDP.org) for questions and/or to request the protocol. Questions about the ST-018 standard should be sent to ICCBBA’s help desk at support@istb128.org.
DUE JUNE 30, 2022: Standards Coordinating Body Seeks Comments on Chain of Identity Identifier Definitions and Requirements
The Standards Coordinating Body (SCB) assembled a multi-stakeholder working group, including FACT, to develop proposed definitions and requirements for Chain of Identity (COI) identifiers titled, “Key Requirements and Definitions for Chain of Identity Identifier.” Standard definitions and requirements have become increasingly important as the number of players in the cellular therapy supply chain has increased and become more diverse. FACT strongly recommends its accredited organizations and inspectors review the draft and submit comments. Comments are due by June 30, 2022.
As SCB explains in the draft, COI identifiers are essential to demonstrating adequate control of biological material. FACT-accredited organizations have expressed concern about the challenges of implementing several identification systems at a single institution and how they pose risks of mix-ups. These definitions will hopefully lead to consistent use of COI identifiers and potentially allow the development of common COI identification systems for multiple cellular therapy products.
Please review the draft and submit your comments via the commenting template to Dawn Henke at dhenke@regenmedscb.org.
Read the draft Key Requirements and Definitions for Chain of Identity Identifier
Download the Commenting Template
Examples of Label Reconciliation Methods to Prevent Mix-Ups of Cellular Therapy Products
Label reconciliation is now required in the eighth edition of the FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration. Specifically, Standards CM7.2.2.1, C7.2.2.1, and D7.2.3 state: “A system of label reconciliation shall be used to ensure the final disposition of all labels allocated to a specific product is documented.”
The purpose of this requirement is to prevent cellular therapy product mix-ups. As the FACT-JACIE Hematopoietic Cellular Therapy Accreditation Manual states, “The purpose of reconciliation is to ensure that all labels have been accounted for and no mix-up occurred. A system for label reconciliation that documents the number and type of labels received by the Collection/Processing Facility, the number of labels used, and the number of labels passed to the Processing Facility or destroyed shall be used.” The scope includes labels with unique identifiers of final products. It does not include labels for patient demographics or internal tracking numbers if they are not uniquely identifying a product, though these labels must still be controlled.
Print-on-demand systems for labels reduce risks of label mix-ups; however, there are instances in which a batch of labels is printed to facilitate processes. Label reconciliation does not need to be performed in real-time but should at least occur at the end of a process (for example, during cleanup of a processing procedure.)
In addition to the labeling operations requirements outlined in the FACT Coding and Labeling Cellular Therapy Products sections of the Standards (CM7, C7, D7), the following are example methods that may facilitate label reconciliation:
- Keeping labels in a batch record.
- Limiting the number of labels that are printed at a given time, and defining in policies what the use of each label will be.
- Utilizing a form that details the number of labels printed or received, used, passed to another unit, or destroyed. This could be on a collection form or a separate label reconciliation form.
- Affixing unused labels to the relevant form and crossing through or annotating labels that will no longer be used.
- Numbering labels (e.g., for 12 labels, label them 1 of 12, 2 of 12, and so on) to facilitate documentation of which label was used where.
ICCBBA Releases Registration and Licensing Information for ISBT 128
Interest in the new ISBT 128 coding and labeling standard, Labeling of Collection Products for Cellular Therapy Manufacturing, has led to many inquiries to ICCBBA regarding registration and licensing. To assist entities with determining how the standard applies to their scope of work and the applicable fees, ICCBBA created a flyer that outlines this information. There are also step-by-step registration instructions on its website.
We are encouraged by this interest in this new standard to improve efficiency and patient safety. Further questions can be directed to the ICCBBA help desk at iccbba@iccbba.org.
Step-by-step registration instructions
Now Published: ISBT 128 Labeling Standard for Collection for Cellular Therapy Manufacturing
It is official! The final ISBT 128 Labeling of Collection Products for Cellular Therapy Manufacturing Standard is published.
Following multistakeholder efforts to standardize labels for cells collected for further manufacturing, and two rounds of public input, ICCBBA has finalized this ISBT 128 labeling Standard. The Standard is for use only in situations where the sponsor or manufacturer has adopted it.
This Standard may reduce the variations in labeling requirements for apheresis collections for different sponsors or manufacturers, minimizing the risk of errors and increasing patient safety. ISBT 128 is a well-established and international coding and labeling system. Standardizing labeling requirements using this system enhances cellular therapy product traceability and reduces the number of systems that must be adopted, implemented, validated, and maintained at health care institutions.
FACT-accredited apheresis collection facilities are encouraged to review this Standard, work with their ISBT 128 vendors regarding implementation and validation, and inquire with clinical trial sponsors and manufacturers about their intentions for adopting it.
ISBT 128 Labeling Standard for Cells Collected for Cellular Therapy Manufacturing: Comments Due October 18th
Thanks to the teamwork of several stakeholders in apheresis cell collection, the field is one step closer toward label standardization. Comments are needed in the most recent draft ISBT 128 label published by ICCBBA by October 18, 2020.
As reported in previous Just the FACTs newsletters, a multi-stakeholder working group led by the Standards Coordinating Body and the Deloitte NextGen Industry Working Group, consisting of industry, registries, accrediting organizations, technology providers, and apheresis and quality subject matter experts, released a draft standard labeling proposal for collected cells.
Public comments following the release of that draft indicated support for ISBT 128 labeling for starting material intended for further manufacturing. After reviewing these comments, ICCBBA has released a draft Standard for Labeling of Collection Products for Cellular Therapy Manufacturing.
This Standard builds on existing ISBT 128 standards, including compatible label dimensions and essential traceability information, but also accommodates sponsor/manufacturer information. As stated by the ICCBBA website, “it is for use only in situations where the sponsor/manufacturer has adopted this standard and has provided the necessary information to populate the sponsor/manufacturer section of the label.” Although the standard was written with apheresis in mind, the label could be used on products collected from other sources and intended for further manufacturing.
Draft Labeling of Collection Products for Cellular Therapy Manufacturing
Heat-sealing label in cryopreservation bag pouch meets definition of “Affix”
Written by Sarah Litel-Smith, BSMT (ASCP), Accreditation Services Supervisor
The Accreditation Committees recently affirmed that inserting a label into a cryopreservation bag pouch and heat sealing the pouch would categorize the contents (label) as affixed. When the definitions of “affix” and “attached” were written, the goal was to distinguish labels connected to the bag with a physical intermediary device (e.g., plastic, string, or metal linkage) from a label that was integral to the bag (e.g., direct bag to label contact). While glue is the most common method, we interpret that a sealed portion of the bag containing the label is equivalent to secure direct contact between bag and label.
Affix: To adhere in physical contact with the cellular therapy product container.
Attach: To fasten securely to the cellular therapy product container by means of a tie tag or comparable alternative. Any information required to be attached to a cellular therapy product container may alternatively be affixed.
Clinical Trial Product Labeling: What is it, whose is it, and where is it going?
Programs must be confident in the identity of a clinical trial product. Programs have reported near misses due to labels on clinical trial products that use ambiguous identifiers, are handwritten illegibly, or do not link identifiers on the collected “starting material” with the final product that is returned to the program. When labeling is performed appropriately, clinical sites should be able to follow the chain of custody from collection to administration confirming exactly what the product is and the identity of donor and recipient.
What is it?
Cellular therapy products start with a collection (autologous or allogeneic), which is delivered either fresh or frozen to a manufacturing facility for processing, and then sent to the clinical site for administration to a recipient. This means there are at least three main points (but usually more) at which the identity of the product could be compromised. Unclear labeling of the product may result in undue delay or the inability to administer the product. Some manufacturers have agreed to use the ISBT 128 donation identifier (DIN), which can be assigned at collection and used throughout the manufacturing and administration processes.
Whose is it?
Cellular therapy (even in the case of many allogeneic cell therapy products) is personalized medicine. It is critical to get the right product to the right patient. Ambiguous identifiers prevent programs from linking a product to the correct patient. Many manufacturers have requested that only the study identifier be used on a product label. A study identifier is typically insufficient because 1) it is not unique to a specific product, 2) the meaning of the identifier is not typically known by personnel administering the product, and 3) various manufacturers may use similar or duplicative identifiers.
Where is it going?
In addition to knowing where a product is going, it is important to know where it has been. This is another purpose of unambiguous identifiers. Identifiers must allow collection facilities and manufacturers to proactively prevent product mix-ups and retroactively review records.
What does FACT expect?
FACT’s longstanding guidance on labeling of clinical trial products is that programs should comply with the IND as required, but FACT requirements that are not forbidden by or in conflict with the IND should be followed. Labels submitted as part of the Chemicals, Manufacturing, and Controls (CMC) section of Investigational New Drug (IND) applications or equivalent are approved by the appropriate regulatory authority (e.g., Food and Drug Administration [FDA] in the United States).
The seventh edition of the FACT-JACIE Hematopoietic Cell Therapy Standards requires full implementation of coding and labeling technologies using ISBT 128 or Eurocode. FACT believes the use of ISBT 128 is the most effective coding and labeling system that can be used for any type of cellular therapy product. Many research labels approved by regulatory authorities will not fully utilize this system.
However, the use of the donation identifier (DIN) at a minimum can be useful. The DIN is currently used on two commercially available chimeric antigen receptor (CAR) T-cell products, which demonstrates its effectiveness and feasibility as an identifier for commercial products.
It is understood that some manufacturers’ approved IND (or equivalent) labels must be used, but FACT-accredited programs are expected to use ISBT 128 to the extent possible. Accredited programs must define labeling responsibilities with commercial manufacturers and may wish to negotiate the use of ISBT 128. Programs may have different quality assurance approaches, and negotiations between a manufacturer and a program will often be site specific. However, patient identification procedures for almost any delivery of health care require two patient identifiers. In the absence of ISBT 128 coding and labeling, FACT encourages the use of at least two patient identifiers. Patient name and date of birth are acceptable identifiers for autologous products. Programs may have stricter requirements. In some cases, this may require that IND labels be supplemented with an additional identifier(s). The patient identifiers may be attached or on paperwork that closely accompanies the product.
We encourage clinical sites to work with commercial manufacturers to establish labeling procedures that will serve manufacturers’ needs while ultimately protecting the health and safety of the intended recipients of cellular therapy products.
