Gone is the era of the blockbuster drug with straightforward manufacturing, distribution, and simple, well understood reimbursement practices. The changes, coupled with rapid advances in basic science, are driving the pharmaceutical industry toward drug targets and treatment regimens that are far more sensitive to the impacts of temperature and transportation, namely novel biologic and regenerative therapies. Cell and gene therapy is now considered “the third pillar” of healthcare—along with traditional pharmaceuticals and biologic drugs.

As with any new paradigm, the push into more advanced biologic and regenerative therapies has its challenges. One critical element which is rapidly manifesting itself as a significant challenge in the commercialization of such therapies is the very complex logistics needed to support such programs. Movement of these sensitive biomarkers, therapies, and patient samples, all require exact, time-limited logistics support. It is not atypical to see 3 to 4 different temperature requirements for a single supply chain for a regenerative therapy; some transportation requirements must be met within hours, not days or weeks. Additionally, the samples being moved are often patient-specific, and require distinct, independent, ID codes specific to the patient, also requiring compliance with HIPAA and other global regulatory standards.

The success of these clinical trials critically depends on achieving and maintaining optimal performance conditions for these temperature-sensitive biomarkers, patient samples, and therapies throughout the trial. Careful planning of all packaging, transport, storage, and handling steps, as well as strict adherence to planned processes, is needed to ensure that delays and/or temperature excursions do not jeopardize the quality of any of the materials transported in support of the program and, thus, the results of the clinical trial. Manufacturers work very hard to produce high-quality products which meet exacting standards applied to every stage of the production process and these exacting standards should extend beyond the manufacturing site to the packaging, shipping and storage of these valuable lifesaving products.

Regulatory bodies are starting to take notice and are intent on establishing specific criteria related to the storage and distribution of these types of therapies. The International Organization for Standardization (ISO) is currently reviewing guidelines for their storage and distribution. ISO /TC 212 and ISO/TC 276 will be the standards by which all regulations are likely to be established. It is anticipated that part of the standards being developed will dictate the limits of environmental excursions
acceptable during distribution of these therapies and the level of detail required for the packaging qualification and validation. It is extremely likely that, in the future, it will be standard practice to be able to correlate historical performance of a particular piece of packaging equipment to any given shipment.

The industry is starting to respond to the challenge presented by this emerging field of therapeutics. Companies are bringing logistics support planning into the clinical trial design process and in many cases giving it equal weight. Additionally, active research into the impact of time, temperature, and handling on the stability, efficacy, and viability of these samples is currently being conducted by many companies in advance of initiating clinical programs.

Moreover, fully integrated payer processes are being designed and integrated into the clinical and manufacturing processes to support patient specific manufacturing and distribution. Overlaying all of these developments are rapidly evolving software platforms that track patient enrollment, clinical scheduling, transportation—inbound and outbound—manufacturing, release, distribution, storage, and reimbursement.

Informatics will be the key to the success of ensuring patient access to these therapies. Complete integration of the entire supply chain processes, linking them to the data supporting regulatory needs and quality considerations, as well as automating complex patient reimbursement processing is an absolute requirement. The ability to correlate and analyze the data from a single patient process through enrollment, testing, clinical procedures such as apheresis, transport—chain of condition and custody data—manufacturing, release, storage, distribution, administration, and reimbursement will be the difference between success and failure. This is due to the fact that something as simple as a clinical sample missing a flight due to aircraft maintenance could impact either the manufacturing scheduling or patient procedures supporting therapy administration, both of which could be significant to the success or failure of the therapy.

The complexity of supply chains for the next generation of therapies in development worldwide is rapidly increasing. A proper cold chain logistics strategy, processes, and informatics to support the complex movements and activities of these types of programs will dictate success or failure. Companies must integrate strategic logistics considerations into the clinical design process and ensure they have set aside appropriate resources to the development of the systems, partnerships, and informatics to support success. 

---

Mark W. Sawicki, Ph.D., is chief commercial officer at Cryoport. With more than 15 years of business development and sales management experience in senior leadership roles, he has a proven record of consistently delivering on corporate revenue and market share goals in the pharmaceutical and biotechnology industries. Dr. Sawicki can be reached at msawicki@cryoport.com.