Cell and gene therapy innovators are scaling up and out to reach more patients. Clinical Trials Arena spoke to the team at Oximio (formerly the SMO Group) to discuss market developments.
Most advanced therapy medicinal products (ATMPs, also known as cell and gene therapies) address the clinical needs of “orphan” diseases (very rare conditions, where patients are so thinly spread globally that in some markets it becomes difficult or uneconomical to deliver treatments). Because of this, there are advantages to running trials across additional markets, providing access to more of the right patients.
ATMP studies have typically been designed to bring patients to a designated dosing facility, meaning they were likely to have treatment in the country where a clinical trial was running, close to where the drug was manufactured. However, therapy innovators are increasingly considering how to scale-up, run multi-country trials and bring therapies to patients, giving the opportunity for a wider group to access treatment.
Focus on geography
The US continues to be the industry front runner, with nearly half (550) of all 1,220 global ATMP trials ongoing in 2020. Studies initiated in Europe have remained flat year-on-year, from 2014 to 2018, but we see evidence of the emergence of multi-country trials in the region.
Highly complex logistics
A major factor for selecting a clinical trial site or country are the expertise and skills of the clinical centers and healthcare professionals, followed closely by the speed of approval by regulatory authorities in country (figure 2).
Logistics planning and stakeholder coordination is also a critical factor in ensuring the success of advanced therapy trials. ATMP supply chains are complex, and logistics is the element that is relatively immature, given the diversity of ATMP starting materials and the final product.
ATMPs have a variety of manufacturing strategies (centralized vs decentralized), various product characteristics (autologous vs allogeneic, fresh versus frozen) and different clinical utilizations (out-patient vs in-patient, surgical vs non-surgical). This means that bespoke logistics schemes must be created, considering specific drug characteristics, geographical coverage and the regulatory landscape.
Case study: Bespoke ATMP supply chain in action
A developer created an allogenic cell therapy to be shipped fresh from the manufacturing site in in the EU to clinical centers in Israel. Timing was the main challenge – temperature-controlled shipping (15-25°C) for the product, across the ocean and into a patient within 72 hours. To add to the complexity, the administration was not an infusion, but surgery.
Documentation requirements were stringent too and included
- Certificate of analysis (CoA) – to acknowledge the quality assurance for each batch produced
- Drug pedigree documents – to account for the product as it passes from manufacturer through to the eventual user
A QP release would normally be evaluated post manufacture, but ahead of the trial. The product could be held in safe controlled storage while the evaluation was completed, but that wasn’t possible with a 72-hour shelf life.
There were number of supply chain stakeholders too; the manufacturer in the EU, international transport with import and customs teams, the local delivery teams, those receiving the goods, the pharmacy and the dispensing personnel, plus a team of doctors ready to perform surgery, all of whom needed to play their part within a 36 hour window.
According to Samuel Gal Alterovich, director of strategic services and alliances at Oximio, their role was to act as a “professional integrator” between these parties. “You need a strong team of people who are knowledgeable about the challenges of clinical trial regulations in general and then specifically in the market concerned (in this case, Israel),” Alterovich explains. “But you also need someone knowledgeable about logistics, who is also able to advise on the pharmacy side and be able to prove cold chain GMP-compliant activity.”
Oximio drafted a clear standard operating procedure including the manufacturer, the global courier, the CRO and the local medical team. “We came up with a protocol in which the roles of each of the parties was very clearly articulated and so it was very clear who needed to do what and when. It all had to go like clockwork,” says Alterovich.
To make it possible, normally sequential processes had to happen in parallel. As soon as the drug was manufactured, the QP and pharmacist were ready to receive the CoA. They reviewed it while the product was on its way. And those documents – CoA and pedigree – were reviewed in real time, so any problems could be communicated, and action taken.
Upon arrival in Israel, a dedicated import team made sure the shipment was covered, that authorities were aware of it, and that the release needed to be hassle-free.
Then came the last-mile delivery, where the Oximio team was on hand to work with the local clinicians to create a GMP-like environment in the medical facility.
Oximio developed tightly focused schemes to ensure that the product reached the patient in the same condition it reached the manufacturing facility, resulting in nearly 30 treatments delivered safely and on time to patients in Israel, with many more expected as the project continues.
Extending the footprint of advanced therapy logistics trials
Oximio’s capability to extend ATMP trials means partners benefit from local expertise and knowledge, including that of regulatory frameworks and culture, to facilitate improved patient access. This ability to interact with the key players in a wide range of territories, including regulators, highlights one of Oximio’s strengths – its network of local market experts. This, combined with dedicated project management in every market, makes Oximio well placed to support ATMP trials in established locations, as well as across a network of smaller, less developed markets.
Whether it’s bringing patients to advanced therapies, or bringing therapies to patients – through the establishment of additional dosing centers and communication with regulatory authorities, to the training of site staff, as well as support at import, export, domestic distribution, storage, and arrival stages – Oximio can build supply chain strategies for the success of your ATMP trial.
 The Alliance for Regenerative Medicine, accessed 02/09/21: http://alliancerm.org/wp-content/uploads/2021/03/ARM_AR2020_FINAL-PDF.pdf
 The Alliance for Regenerative Medicine, accessed 02/09/21: http://alliancerm.org/wp-content/uploads/2019/10/Trends-in-Clinical-Trials-2019-Final_Digital.pdf