In July 2022, PTC’s first gene therapy and disease-modifying treatment for Aromatic l‐amino acid decarboxylase (AADC) deficiency was approved by the European Commission (EC). In this relatively new field of molecular medicine, PTC is one of the pioneers in the gene therapy, being the first therapy to be injected directly into the brain.

Unlike the supply of conventional small molecule drug products and biologics, gene therapies require a different, more complex approach. PTC’s Supply Chain Group in Dublin is responsible for securing the supply chain for multiple commercial products, including gene therapy globally. They had to establish a new, unique patient-centric supply chain model involving multiple stakeholders with highly specialized capabilities to deliver individual gene therapy products directly to pharmacies of selected hospitals just in time for scheduled surgeries.

We asked our Executive Director, Supply Chain and Logistics in Ireland, Karsten Rosdahl, to tell us more about the innovation in the supply chain function.

An innovative product requires an innovative and unique supply chain model, and we are proud to have the capabilities and expertise to deliver such a transformative therapy to patients.

How does a supply chain system for the delivery of a gene therapy work?
The supply chain is highly complex and involves many different stakeholders. Our gene therapy product is manufactured at MassBiologics, Inc. in the U.S. The product vials are then transferred to Ireland for labelling, packaging and serializing. Prior to the scheduled treatment, the finished product is transported under stringent temperature controls maintaining ≤ -65°C at all times and delivered to the hospitals (which are Centres of Excellence (CoE) for gene therapy treatment), for administration to patients via complex stereotactic brain surgery.

Tell us about some of the complexities.
The most significant challenge in this supply chain is maintaining temperature control: gene therapy product must be maintained at ≤ -65°C. If the temperature goes above this level, the quality of the product can be adversely impacted making the product unusable. We have implemented various control factors and capabilities that are critical to ensure no adverse impact on the product during the entire process.

Treatment center readiness is another critical part in our preparation process. Centres of Excellence follow a strict process to ensure proper receipt, handling, and storage of this specialized treatment upon delivery. A unique set of capabilities is required, and we support them through the process.

AADC deficiency is an ultra-rare disease that impacts patients globally across multiple markets, each with their own specific regulatory and technical requirements. Therefore, the complexity resides in the fact that we can’t proactively plan bulk shipments to the pharmacies of the different Centres of Excellence. Shipments need to be done on an ad-hoc basis when the individual patient is eligible for surgery with highly tailored supply chain efforts to make sure the product arrives on time with the right quality attributes.

How do you manage these complexities?
An innovative product requires an innovative and unique supply chain model. Therefore, we were quick to establish collaborations with specialized partners and build the appropriate infrastructure and processes, as well as expertise in-house that supported multiple successful surgeries across geographies to date.

We selected highly specialized partners that have capabilities managing biological/gene therapy products under extreme temperature conditions, as well as experience for both transportation and packaging processes. Almac and World Courier are two key partners that support PTC to safely supply this innovative gene therapy product to patients across Europe and the rest of the world.

We work closely with treatment centers to ensure the product is received and stored correctly prior to administration. Starting with a treatment center qualification process, PTC provides training, education and instruction to the centers on all aspects of product handling. Hospital processes are supported through the use of detailed receipt instructions and tested though mock shipments. This is an ongoing process in building the capabilities of the center.

PTC supply chain performs mock shipments for every new treatment center to test and practice the receipt and storage process at each approved hospital. This takes place prior to the actual shipment of the gene therapy product. Each actual delivery is supported by PTC’s receipt instruction, which explains how to receive the product in the transport case and how to read the temperature logger and handle the temperature data.

What would you say are the success factors?
A close collaboration with all stakeholders is critical to the success. For every shipment, a cross-functional team is assembled within PTC involving multiple departments as well as external partners and Centres of Excellence. Each supply step is managed by the supply chain team in Dublin and covers every aspect, from initial assessment of the treatments center to the final surgery.

Can you share something interesting about the innovation in the supply chain?
When we started the project over three years ago, we worked closely with Almac Pharma services on the labelling and packaging aspects of the process. We conducted many early engineering studies to find a solution whereby labels could be manually applied to the vials over a bed of dry ice whilst keeping the vial within the acceptable temperature range. A system of conditioning each packing component also ensured the vial was not exposed to higher temperatures during the packaging process.

The validation of the entire process was completed successfully, and subsequent packaging stability studies proved that each component, carton, product leaflet, vial label and tamper evident seal was not adversely impacted by the freezer storage condition of -80°C.

What are you most proud of?
Seeing the impact on patients. Several patients have already received our gene therapy treatment to date. PTC supply chain, together with a wider PTC team, have played a critical role in delivering the product to patients across the world and have contributed to transforming their lives.