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.