Advanced therapy medicinal products (ATMPs) industries, including cell therapy and gene therapy, are forecasted to grow at a compound annual growth rate of 22% from 2018 to 2022 [1]. ATMPs are estimated to be a billion-dollar industry and potentially the fourth therapeutic pillar of health care [2,3]. Commercially available ATMPs make up a very small percentage of total patient interventions as compared to the mainstream first- and second-line therapies in the developed markets. However, for cell and gene therapy, they are expected to grow from a few 1000 patients in 2018-2019 globally to possibly 100 million by 2025, as the number of commercially available ATMPs matures [1].

To facilitate the growth of the ATMP sector, the supply chain infrastructure is critical in supporting the industry from clinical trials to commercial distribution of life-saving treatments to more patients in a safer and more secure manner. In addition, compliance with data protection laws (Health Insurance Portability and Accountability Act [HIPAA] in the United States and General Data Protection Regulation [GDPR] in the European Union) comes at a very high cost [4-6]. Without proper encryption and selective data disclosure, everyone in the supply chain will have to be GDPR-compliant. Key to the success of these new treatments will be the safe, secure, and timely delivery of advanced therapies in a highly regulated environment (eg, temperature, tilt, time duration, and location) to ensure transparency and accuracy [7,8].

Current logistics tracking solutions are reliant on paper audit trails and legacy cloud infrastructure and are at significant risk of causing treatment failures. Specific to autologous therapies, the starting material collected from the patients can vary greatly. This can cause the final manufactured product to be of different quality, which may cause it to fall out of specification [9]. For example, Novartis had to write off multiple batches of Kymriah (Novartis) due to out-of-specification products since its launch in August 2017 in the United States [10]. Similarly, during the clinical studies, 7%-9% of patients did not receive the CAR-T treatment due to manufacturing failures [11].

Current solutions based on paper and dated legacy standalone information technology (IT) infrastructure that are being used by bioscience companies during precommercialization may be sufficient during research stages. However, these solutions are likely to fail as their operations scale up and out. They are not designed to be scalable, interoperable, or capable of dealing with the complexity of regulation and process that these ATMPs will incur in the real world of patient care. Batch identification through patient initials and date of birth is considered insufficient due to possible mix-ups, which can be catastrophic for patients. Intuitive labeling methods must be simple enough for use across sites while providing sufficient information about the patient to avoid mix-ups [12]. Companies, including Trakcel, Vineti, Danaher (previously, GE), are using cloud-based solutions for manufacturing ATMPs [13-15]. Although cloud-based solution systems are useful in tracking and tracing products in traditional linear logistic supply chains, data in these centralized systems are highly vulnerable to being tampered with, potentially allowing fraudulent or damaged products to enter the supply chain or data falsification. These systems focus only on the logistics part of the delivery process and fail to address the coordination issues between stakeholders (hospitals, patients, manufacturers, logistics providers, and regulatory authorities) in the advanced therapy delivery process.

As new license indications are achieved, the systems will need to be designed to change and adapt across the whole logistics supply chain. From the collection of source material to manufacturing and final delivery of therapies, there are many handoff points, creating the probabilities of mix-ups and supply chain failure. As most advanced therapies are provided as the last line of treatment for patients with critical illnesses, the failure or delay may cost them their chance of survival.

Blockchain technology is a digital ledger of transactions, agreements, and controls that are stored in a distributed network, removing the need for a centralized database. Due to its distributed and transparent nature, the data stored cannot be tampered with and is transparent, traceable, and secure [16,17]. The benefits of the blockchain technology have been explored in various sectors, including finance, health care, and agriculture [18-20]. One of the most highly discussed use cases of blockchain technology is in supply chain management. Integration of blockchain into supply chain architecture can lead to a more reliable, transparent, and resilient system [21-24]. Specific to ATMP supply chain management, a layered blockchain solution with a smart contracts business logic layer can enable a holistic way of managing various stakeholders, ensure needle-to-needle supply chain integrity, and secure data management. The decentralized nature of blockchain can allow this to happen almost instantaneously across the full ecosystem, including the ability to keep regulators updated by publishing on a public chain with zero-knowledge proofs. Cloud environments cannot provide these facilitations; and thus, require frequent on-site monitoring and auditing by regulators. The protocol of this study will focus on developing a patient-to-patient blockchain-based supply chain system for advanced therapies.

This proposed study protocol will lay the foundation for future grant applications, and its execution will be completed in 2021.

The successful implementation of the integrated blockchain solution to the supply chain and manufacturing of advanced therapies can push the industry standards toward a safer and more secure therapy delivery process and encourage rapid adoption of the innovative technology. Adoption of the innovation in a wider context can reduce the costs of monitoring good manufacturing practices through increased transparency and security of the manufacturing and delivery process. A more transparent process can reduce communication errors and overall time spent, hence reducing health care costs. The integrated platform solution will enable more accurate and transparent tracking at all stages of the needle-to-needle delivery pipeline, allowing treatment-centric care pathways to be truly personalized through a digital evolution in supply chain and manufacturing management.