Key Takeaways
Cell and gene therapy supply chains require strict temperature control, validated shipping, and coordinated clinical-site handling.
Autologous cell therapies depend on continuous chain of identity and chain of custody from patient collection through infusion.
Radiopharmaceutical logistics must account for radioactive decay, fixed expiration times, isotope availability, and regulated handling.
Treatment-center readiness, contingency planning, and qualified storage are essential components of advanced-therapy supply chain resilience.
Digital traceability systems help maintain unique patient and product identifiers across collection sites, manufacturers, logistics providers, and healthcare organizations.
Resilience Begins Before Shipment
Advanced therapy logistics cannot be treated as a downstream distribution activity that begins once manufacturing is complete. The relevant supply chain may begin with collection of patient-derived starting material or access to an isotope precursor and continue through manufacturing, quality release, transportation, clinical-site receipt, storage, preparation, administration, and final disposition. Each handoff introduces conditions that can determine whether the product remains suitable for use.
The distinctions become clear when specific products are considered. KYMRIAH must be stored in a monitored system at or below −120 °C, and once an infusion bag has been thawed and reaches room temperature, it must be infused within 30 minutes.1 LUXTURNA and its diluent must be stored at or below −65 °C, while preparation must occur within four hours of administration under aseptic conditions before the product is delivered to the surgical suite.2 PLUVICTO has a shelf life of 120 hours from the date and time of calibration and cannot be used after the expiration date and time printed on its label. These are not variations on a single cold-chain problem.3 They are different operating models defined by the product, the treatment pathway, and the time available for use.
For advanced therapies, resilience therefore means more than maintaining inventory or adding transportation capacity. It means preserving the conditions that must remain true for the product to reach the correct patient in a usable state. Those conditions differ by modality, and they often extend well beyond the walls of the manufacturing site.
The Patient Is Part of the Cell Therapy Supply Chain
Autologous cell therapies create a closed-loop supply chain in which the patient is connected to both the starting material and the finished product. Chimeric antigen receptor T (CAR-T) cell manufacturing can involve multiple biological materials and complex, multistep procedures, creating the potential for lot-to-lot variability. Process controls, in-process testing, and lot-release testing are therefore central to maintaining consistency.4
That control begins with leukapheresis material. Shipping procedures must address temperature control, the performance of the shipping container, temperature monitoring, transport validation, and the stability of the starting material under the intended shipping conditions. The collection-to-manufacturing journey is not simply a courier movement. It is the first controlled stage of the manufacturing pathway, and any weakness in labeling, packaging, timing, or receipt can affect what follows.
Physical custody alone is not sufficient. For autologous products, chain of identity must be maintained from collection through administration. The product must remain permanently associated with the intended patient, and labeling should include at least two unique identifiers together with identity checks at appropriate stages. This requirement changes the nature of supply chain risk. A shipment may arrive at the correct facility, at the correct temperature, and within the intended transit time, yet still be unusable if the patient association cannot be confirmed.
KYMRIAH illustrates how identity and cryogenic logistics converge. The product is prepared from an individual patient’s leukapheresed cells, cryopreserved, and released for shipment in patient-specific infusion bags. It travels directly to the infusion center’s associated cell laboratory in a liquid-nitrogen Dewar. On receipt, the patient’s identity must be confirmed, and the product must remain in a monitored system at or below −120 °C until use. Once thawed and brought to room temperature, the bag must be infused within 30 minutes.1
The contrast between fresh and cryopreserved CAR-T products further demonstrates how product design shapes logistics. Fresh products may have limited shelf lives, requiring close coordination among release testing, quality review, shipment, receipt, and administration. Cryopreservation can provide additional time for release testing and greater scheduling flexibility, but it replaces one set of constraints with another, including the need for validated cryogenic transportation, appropriate on-site storage, controlled thawing, and rapid administration after thaw.1,4
A resilient cell therapy network must therefore control two parallel journeys. The first is the physical movement of starting material and finished product. The second is the continuous movement of identity information that links both to the patient. Neither can be treated as secondary to the other.
Contingency Planning Must Be Designed into Distribution
The standard shipping pathway may work under normal conditions, but resilience depends on what happens when the expected route, timing, or patient schedule changes. For immune effector cell products shipped over extended periods, applicable temperature ranges should be established through standard operating procedures, written agreements, and manufacturer instructions. The need for continuous temperature monitoring must also be assessed. Transit times should remain within limits determined jointly by the distributing and receiving facilities.5
These controls require collaboration before shipment. The sending organization cannot define the operating window in isolation if the receiving site lacks the storage capacity, staffing, or procedural readiness to accept the product. The two parties need a shared understanding of allowable transit duration, delivery timing, receipt procedures, and escalation pathways.
Within the immune effector cell accreditation framework, contingency plans must provide alternative means of transport or shipping during an emergency. A backup route cannot be improvised effectively after a delay has already consumed part of the product’s allowable time or compromised the original delivery plan.
Responsibilities become more complex when third parties participate in collection, transport, storage, or distribution. Policies, standard operating procedures, and written agreements should define who maintains traceability and chain of custody, who controls storage and transportation, who distributes the product for administration, and who verifies product and recipient identity. The goal is to remove uncertainty at organizational boundaries, where each party may otherwise assume that another has responsibility for a critical step.
BREYANZI offers a product-specific example of contingency planning when a patient will not be ready before the shipping container expires. A qualified infusion site may transfer the product to on-site vapor-phase liquid-nitrogen storage. If the site is not qualified for on-site storage, it must contact Bristol Myers Squibb to arrange return shipment. The approved pathway therefore includes more than delivery and infusion. It also includes a controlled decision tree for temporary storage or return when the original schedule cannot be maintained.6
Contingency planning is most effective when it is integrated into the operating model rather than treated as an exception. Alternative transport, qualified storage, return procedures, and clear ownership of decisions all need to be defined before the product begins its journey.
Treatment-Center Readiness Extends the Supply Chain
Delivery to the treatment center does not mark the end of the supply chain. The site must be able to receive, store, prepare, administer, and monitor the therapy within the conditions established for the product. For cell therapies, this requires more than access to freezer space or a trained courier at the receiving dock.
For accredited immune effector cell programs, participating clinical sites are expected to operate with common staff training, protocols, standard operating procedures, and quality systems. The designated team includes a program director, a quality manager, and an additional physician trained or experienced in cellular therapy. These accreditation expectations are not universal statutory requirements, but they show the breadth of infrastructure involved in reliable treatment delivery.5
Site readiness also includes round-the-clock pharmacy availability, prompt access to medications needed for expected complications, and nurses trained to administer cellular therapies and recognize and manage treatment-related complications. These capabilities matter because the timing of administration cannot be separated from the capacity to manage the patient immediately afterward.
BREYANZI again provides a product-specific illustration. Tocilizumab and emergency equipment must be available before infusion and during recovery, and no more than two hours may elapse between removal from frozen storage and administration to the patient. After infusion, patients are to be monitored daily for at least seven days for signs and symptoms of cytokine release syndrome and neurologic toxicities and instructed to remain near a healthcare facility for at least two weeks.6
The regulatory context has changed in an important respect. In June 2025, the Risk Evaluation and Mitigation Strategies (REMS) for the affected autologous CAR-T cell products were eliminated. This removed requirements that dispensing hospitals and associated clinics be specially certified under those REMS and have immediate on-site access to tocilizumab as a REMS condition. Product-specific prescribing information, institutional procedures, and accreditation standards may still establish operational expectations, so removal of the REMS should not be interpreted as removal of the need for treatment-center preparedness.5–7
The receiving site is therefore an active part of the supply chain. A network cannot be considered resilient if its transportation plan is robust but its treatment centers cannot consistently assume custody, maintain the product, complete preparation, and support administration within the required window.
Digital Traceability Must Survive Every Handoff
Patient-specific therapies require data systems that preserve identity across organizations as reliably as the physical systems preserve the product. Chain of custody refers to permanent, auditable documentation of guardianship from origin through final disposition, while chain of identity refers to the permanent association of a cell or gene therapy’s unique identifiers throughout its life cycle. The ISBT 128 Chain of Identity Identifier supports a bidirectional link between donor or donors and intended recipient or recipients.8
The identifier uses a Facility Identification Number to support global uniqueness across organizations, and issuing organizations must control identifier assignment to preserve that uniqueness. This is particularly important when collection centers, manufacturing facilities, logistics providers, and healthcare organizations all participate in the same patient-specific pathway. A local naming convention may function within one institution but become ambiguous when transferred across a broader network.
The standard also supports automatic identification and electronic exchange. The identifier can be encoded in a standardized machine-readable format and transmitted as a defined data field between electronic systems. Electronic messages containing the identifier can transfer associated product data among collection sites, manufacturing sites, and healthcare organizations.8,9
Electronic traceability creates its own continuity requirements. Critical electronic records should be backed up regularly, and a validated alternative system should permit operations to continue if the primary system is unavailable. Relevant staff must also be trained to use that alternative. A digital system that works only under ideal conditions does not provide meaningful resilience when an outage occurs during collection, release, shipment, or receipt.5
These standards support consistent identification, data exchange, backup, and continuity. They do not, on their own, establish quantified reductions in errors, delays, or administrative workload. The strongest case for digital traceability is therefore the control it provides over identity information and the ability to maintain that control across organizational and technological boundaries.
Gene Therapy Control Continues to the Bedside
Gene therapy logistics extend through the clinical site and into the final preparation and administration steps. Chemistry, manufacturing, and controls information for an investigational gene therapy should describe shipping and storage conditions, product expiration, chain of custody, receipt and handling at the clinical site, and activities performed before administration. Those activities may include thawing, dilution, preparation of a delivery device, and transportation to the bedside.10
For multicenter studies involving collected human cells, standardized collection and handling procedures across sites are critical to product quality, safety, and control of the manufacturing process. Relevant documentation may include storage, shipping, labeling, tracking, hold times, and transportation conditions. The challenge is not simply to create a compliant procedure at one center but to ensure that each participating site performs the same critical steps consistently.
LUXTURNA demonstrates how final preparation becomes part of the supply chain design. The product and its diluent are stored at or below −65 °C. Preparation must occur under aseptic conditions within four hours of administration, after which the prepared product is delivered to the surgical suite at room temperature in secondary containment. The site must therefore coordinate frozen storage, aseptic preparation, internal transport, surgical scheduling, and administration within a single controlled sequence.2
This requirement differs from the patient-specific identity model of autologous cell therapy, but the underlying principle is similar: control cannot stop at the receiving dock. For gene therapies, the final stages of storage, preparation, device readiness, and movement to the administration setting are part of the product’s validated pathway.
Individualized Medicines Require Control at Very Small Scale
Individualized medicines create a different form of supply chain pressure. Individualized antisense oligonucleotide (ASO) drug products may be designed for a unique genetic variant for which typically one or two individuals have been prospectively identified. These programs are not expected to follow traditional clinical development phases. These regulatory recommendations remain in draft form.11
The small number of patients does not remove the need for repeatable manufacturing and storage controls. Later batches used for continued treatment are generally expected to comply with 21 CFR part 211. Stability should also be monitored under the proposed storage conditions, with stability protocols and data covering the ready-to-administer product. These expectations remain in draft form.
The resilience challenge in this setting is not broad distribution across a large treatment network. It is maintaining sufficient process, batch, and stability control for a product serving one or a very small number of patients, including when additional batches are needed. Because development and treatment may be closely linked, any delay in repeat manufacturing, release, storage, or preparation can directly affect an individual patient’s treatment pathway.
This model shows why advanced therapy resilience cannot be reduced to volume or geographic reach. A supply chain can be operationally complex even when it supports only one or two patients, particularly when each batch must be managed with the same attention to quality, stability, and readiness for administration.
Radiopharmaceutical Supply Chains Operate Against Decay
Radiopharmaceuticals introduce a time constraint that differs from conventional stability dating. Their usable life is shaped by radioactive decay and a product-specific expiration time. PLUVICTO is shipped in a Type A package with the vial enclosed in a lead-shielded container. Its labeled shelf life is 120 hours from the date and time of calibration, and it cannot be used after the expiration date and time shown on the label. Storage and disposal must comply with applicable local and federal laws governing radioactive materials.3
These requirements connect transportation, shielding, receipt, storage, scheduling, administration, and waste management. A delay does not simply create a service problem. It consumes part of the usable treatment window. Medical radiopharmaceuticals with very short half-lives may require the shortest and fastest transport route, while shipment denials and delays remain recognized international coordination issues.12
The evidence does not establish a formal requirement for backup carriers or alternative routes for radiopharmaceuticals, but it does support the need to plan transportation around speed, access, and the consequences of delay. The chosen route must align with the product’s calibration and expiration timing, while the receiving site must be ready to accept, store, handle, and administer the material within the remaining window.
Radiopharmaceutical resilience also begins upstream. Actinium-225 has been described as being in short supply because its current production process is complicated, while a scalable accelerator-based production method has been established.13 Ytterbium-176, which is used to produce lutetium-177, has also been characterized as being in short supply, alongside efforts to expand production capacity.14
This creates two linked planning horizons. The first concerns access to the therapeutic isotope or precursor material needed for production. The second concerns movement of the finished radiopharmaceutical within its labeled expiration window. Strengthening only the downstream route cannot compensate for an upstream material constraint, just as securing isotope supply cannot compensate for a delayed or unprepared treatment site.
Building a Modality-Specific Resilience Model
The evidence across these modalities points to a common set of design questions, but not to a uniform operating model. The first question is what must be preserved. For autologous cell therapies, that includes patient identity as well as product condition. For gene therapies, it includes the preparation and administration pathway at the clinical site. For individualized ASOs, it includes repeat-batch and stability control at extremely small scale. For radiopharmaceuticals, it includes both isotope access and delivery within a fixed radioactive expiration window.
The second question is where control changes hands. Collection centers, manufacturers, quality units, logistics providers, pharmacies, laboratories, surgical suites, and treatment teams may all participate in the same pathway. Written agreements and standard operating procedures should assign responsibility for custody, identity verification, storage, transportation, receipt, preparation, and release for administration.5
The third question is how the system responds when the expected pathway fails. Within immune effector cell accreditation, resilient systems require alternative transportation plans, defined transit limits, and continuity arrangements for electronic records. Product-specific instructions may add options for temporary cryogenic storage or controlled return shipment. These measures are most useful when decision rights and escalation pathways have been established before a disruption occurs.5,6
The final question is whether the receiving site can execute the last stage of the product journey. That may require cryogenic storage, aseptic preparation, device readiness, emergency medication, trained staff, patient monitoring, radioactive-material controls, or coordination with a surgical suite. Supply chain design must therefore include treatment-center capabilities rather than assuming that delivery completes the task.2,3,5,6
Resilience Must Follow the Product
A 30-minute post-thaw infusion window, a four-hour preparation window, and a 120-hour radioactive shelf life describe three different logistical realities. None can be managed through transportation capacity alone. Each requires an operating model built around the product’s identity, condition, timing, preparation, and administration requirements.
Advanced-therapy supply chains are extensions of manufacturing and clinical control. Their resilience depends on preserving the information and conditions that make treatment possible across every handoff. The strongest systems will not force cell therapies, gene therapies, individualized medicines, and radiopharmaceuticals into a common template. They will identify the critical constraints for each product and build the network, agreements, contingencies, digital systems, and treatment-site capabilities needed to keep those constraints under control.
References
1. “KYMRIAH® (tisagenlecleucel) Suspension for Intravenous Infusion: Full Prescribing Information.” U.S. Food and Drug Administration. Jun. 2025.
2. “LUXTURNA (voretigene neparvovec-rzyl) Intraocular Suspension for Subretinal Injection: Full Prescribing Information.” U.S. Food and Drug Administration. May 2022.
3. “PLUVICTO® (lutetium Lu 177 vipivotide tetraxetan) Injection, for Intravenous Use: Full Prescribing Information.” U.S. Food and Drug Administration. Apr. 2026.
4. Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products: Guidance for Industry. U.S. Food and Drug Administration. Jan. 2024.
5. “International Standards for Immune Effector Cells.” Foundation for the Accreditation of Cellular Therapy and Joint Accreditation Committee–ISCT and EBMT. 3rd ed., version 3.1. 17 Dec. 2025.
6. “BREYANZI® (lisocabtagene maraleucel) Suspension for Intravenous Infusion: U.S. Prescribing Information.” Bristol-Myers Squibb Company. Feb. 2026.
7. “FDA Eliminates Risk Evaluation and Mitigation Strategies (REMS) for Autologous Chimeric Antigen Receptor CAR T Cell Immunotherapies.” U.S. Food and Drug Administration. 27 Jun. 2025.
8. Ashford, Paul, Karen Moniz, and Beth Gardner, eds. “ISBT 128 Standard Chain of Identity (CoI) Identifier.” Version 1.1.0. ICCBBA. Jun. 2025. Tracking No. ICCBBA ST-028. ISBN 978-1-957177-19-9.
9. Agy, Erica, et al., eds. “Implementation Guide: Using the ISBT 128 Chain of Identity (CoI) Identifier.” Version 1.0.0. ICCBBA. Dec. 2023. Tracking No. ICCBBA IG-050.
10. Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs): Guidance for Industry. U.S. Food and Drug Administration. Jan. 2020.
11. IND Submissions for Individualized Antisense Oligonucleotide Drug Products for Severely Debilitating or Life-Threatening Diseases: Chemistry, Manufacturing, and Controls Recommendations: Guidance for Sponsor-Investigators. U.S. Food and Drug Administration. Dec. 2021.
12. “Facilitation of Safe and Secure Transport of Radioactive Material.” International Atomic Energy Agency. Accessed 3 Aug. 2026.
13. “Groundbreaking Cancer Therapy Clinical Trial with U.S. Department of Energy’s Accelerator-Produced Actinium-225 Set to Begin This Summer.” U.S. Department of Energy, Office of Science. 18 Jun. 2025.
14. “New Batch of Ytterbium-176 Now Available.” U.S. Department of Energy Isotope Program. 23 Feb. 2024.
