Advanced therapies (ATs), defined for this article as cell and gene therapies, are pushing the frontiers of medicine because they can potentially improve quality of life by eliminating disease. Whereas traditional small molecule or biopharmaceutical therapies treat the symptoms of a disease, ATs restore or establish normal function through the modification of human cells (cell therapy), or of DNA or RNA (gene therapy).
 
The FDA has approved 17 ATs¹ to date, and the number of ATs in development is rapidly growing as they are applied to additional diseases. Currently, the majority of ATs focus on oncology, as the rates of most cancers are on the rise and there is a great unmet need in this area (Figure 1).

AT trials are intensely complex; they come with requirements and considerations above and beyond what is typical for traditional clinical trials. Sponsors face major challenges, particularly site selection, navigating additional regulatory requirements, and managing logistical demands of the AT manufacturing process, the AT itself, and any associated biospecimen handling. These must each be addressed directly to increase the chance of clinical success.
 
Steering through the site selection process
Site selection for AT trials requires finding a suitable institution, one that can handle the required coordination and integration of efforts from specialized disciplines. Biotech companies should prepare to invest extra time during qualification and initiation visits to confirm that sites are truly prepared to handle their studies.
 
There are several ways to search for potential sites. A good place to begin is to explore Foundation for the Accreditation of Cellular Therapies (FACT) accredited institutions, which have built up their infrastructure and capabilities to meet globally recognized advanced therapy standards. Sponsors can also use a CRO-partner database or subscription database to gain insight into a site’s past performance. Finally, call on investigator relationships, thought-leader support, and specialized networks to choose sites best suited to the clinical trial.
 
Maneuvering through regulatory requirements
Before enrolling patients, AT trials must gain regulatory approval for the investigational product, protocol, genetic tests, raw materials, and lab assays to be used in the study, which may vary by region. In addition to seeking standard approvals (e.g., from an Institutional Board Review and the FDA) and adhering to guidelines for the global International Conference Harmonization Good Clinical Practice, AT trials are also evaluated by country standards and specialized committees. There are global and regional standards to be met for every aspect of a trial, and they do not always match up across borders. ATs are a relatively new field of study and – in an effort to improve oversight, improve AT handling, and to uphold public safety – regulations have and will continue to evolve. When planning an AT trial, biotech companies should ensure that for the foreseeable future, their technology will be accepted in all countries in which they plan to operate to minimize expense and maximize safety of a trial.
 
Coordinating logistics
While an AT trial is under way, sponsors must meet massive logistical demands to successfully collect biospecimens from patients and run the manufacturing supply chain. Accurate communication and logistical planning are essential throughout the trial for maintaining compliance, tracking, and risk mitigation.

Whether ATs are autologous (personalized therapies manufactured from a patient’s own cells) or allogeneic (small batch therapies made from a donor), manufacturing ATs follows a web-like supply chain. From starting material to final product, ATs are highly perishable and require intricate storage, labeling, traceability, packaging, and shipping and release requirements. Once an AT therapy has been administered, adhering to frequent biospecimen collection ensures safety, evaluates kinetics, and determines function or efficacy. Biotechs must have a predetermined protocol for how, when, and in what quantity biospecimens must be collected for the trial, as well as a plan to store, transport, and assay them.
 
CROs can ease these complexities
CROs can help sponsors overcome an AT trial’s many operational complexities, and support biotechs through the ever-changing AT regulatory landscape. For example,the imminent EU Clinical Trial Regulation (EU CTR 536/2014) will launch some of the most significant changes to clinical trial regulations in Europe in over a decade, introducing new procedures for clinical trial applications and protocols for notifying authorities and committees that oversee all interventional trials. These changes may incite uncertainty for smaller biotech companies with limited resources but, backed by a CRO with knowledge of the regulatory landscape, sponsors can navigate these developments with confidence.
 
As advanced therapies evolve, we predict that administering them will become less complex and more universal. As the current manufacturing and regulatory processes become more established, sites beyond academic and high-powered medical institutions may one day be able to offer ATs. Although a shift toward more widely available advanced therapies may come with a host of additional complexities, this shift will bring these therapies to more patients who need them.

Reference:
1. U.S. Food and Drug Administration, “Approved Cellular and Gene Therapy Products.” https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products. Accessed 8 August 2019.2.

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Erin Finot is the Global Head of Immuno-Oncology at IQVIA Biotech and is regionally based in Charlottesville, Virginia. Mrs. Finot has 18 years of experience in clinical research and provides exceptional global knowledge of the drug development process, including an emphasis and fluency in adoptive cellular trials. She is responsible for the strategic direction and leadership of the team and oversees the delivery, quality, and services provided to the Immuno-Oncology portfolio. Mrs. Finot holds a BA in biology from the University of California, Berkeley, an MS focused in Immunology from the University of Virginia, and an MBA in Finance and Accounting from the University of Louisiana, Shreveport.