Leveraging Transformative Technologies to Improve the Vein-to-Vein Supply Chain | Hogan Lovells
Two transformative technologies
ATMPs, including gene therapy drugs, somatic cell therapy drugs, and tissue-engineered drugs, may offer the potential for truly personalized medicine and viable treatments for diseases that are currently nearly incurable, including hematologic cancers, sickle cell disease, and spinal muscular atrophy. Development and commercialization of new ATMPs is currently a high priority for both authorities and the pharmaceutical sector. In the UK, which currently hosts around 12% of ongoing ATMP trials, approximately £3.8 billion has been invested since 2012 to support ATMP development.
Blockchain, meanwhile, offers the ability to store and transfer data in a decentralized and real-time manner. While the focus of many blockchain implementations to date has been in the financial sector, there is growing recognition that blockchain can provide security in recording transfers of assets in a wider range of sectors, including the unique and specialized ATMP production and supply process.
The challenges of the ATMP supply chain
The creation of an ATMP involves the collection or “donation” of human tissue from an individual. The donated tissue is usually then modified, engineered or manufactured into a therapy for delivery to either the same patient (an “autologous” therapy) or another patient (an “allogeneic” therapy). This complex production and delivery model is known as the “vein-to-vein supply chain”.
ATMPs have not yet been adopted on a large scale due to a combination of clinical, regulatory and cost-related obstacles. Currently, ATMP supply chains are necessarily bespoke and costly. However, given the potential presented by ATMPs and the current focus on developing them, it seems likely that they will form an integral part of future therapies. As ATMPs become more widespread, ensuring the ongoing integrity of their supply chains will be of utmost importance.
The role of blockchain
There is a growing recognition that blockchain can help solve many of the key challenges facing ATMP supply chains due to its inherent characteristics:
- Consensus – for a transaction, or a new data set, to be registered in a blockchain database, this transaction must be validated through an agreed consensus mechanism. This mechanism will often include the validation of new entries by a subset of participants in accordance with the rules of the blockchain network. There are a number of consensus mechanisms, and since all participants have the same copy of the database, this ensures a high degree of confidence that the data recorded in the database is accurate and valid.
- Origin and immutability – all transactions on a blockchain ledger are permanently recorded so that all changes over time can be seen. Once a transaction is recorded in the ledger, it cannot be changed or deleted. It is therefore not possible for participants to tamper with data registered in the ledger, which increases confidence in, and enables traceability of, this data.
- Finality – the blockchain ledger is a single source of truth for all participants in the blockchain network. Any participant operating a node (which is a device that will receive real-time validated updates of data added to the blockchain) and has rights to read data on the blockchain will be able to see transaction data and can have confidence that data is valid.
- Safety and reliability – there is no single point of failure in the operation of a blockchain network. The participants each operate their own node; if one node fails, this should not prevent the operation of other nodes. Due to the nature of consensus mechanisms, any attempt to tamper with a blockchain would require a bad actor to take control of the entire consensus mechanism.
- Decentralization – given the decentralized nature of blockchain networks, the ledger provides complete openness and sharing of data, and transparency.
In short, transactions recorded on the blockchain are secure, authenticated and verifiable. This is relevant for ATMPs because:
- Given their nature, ATMPs are sensitive to the environment
Blockchain, in combination with other technologies (such as Internet of Things (IoT) devices) can be used to monitor and verify temperature and other environmental requirements, as well as provide real-time updates to enable hospitals to prepare planning and resource allocation. IoT devices can be used to track changes in temperature or other measurable variables, such as geolocation, and regular data streams can be transferred from the device to the blockchain ledger. Participants will then be able to track the location of ATMP throughout the supply chain, ensuring that the environment in which ATMP has been stored at each stage of the chain is compliant.
- ATMPs are subject to complex regulatory requirements
The regulation of ATMP is complicated by the production process and the nature of the final product. Donated tissue used as the basis for an ATMP may be regulated by the EU Tissue and Cell Directive, the EU Blood Directive or other regulation, depending on the source (human or animal) and type (tissue, cells or blood) of the donation. Where the donated tissue is subsequently engineered and/or undergoes a functional change, the resulting ATMP may be regulated and administered to patients as a medical device, investigational drug, or a licensed or unlicensed/”specialty” drug. In the UK, the regulation of ATMP across the supply chain involves a number of separate regulatory bodies, including (depending on the ATMP in question): the MHRA, the Human Tissue Authority, the Human Fertilization and Embryology Authority and the Health Research Authority.
Integrating blockchain technology into the ATMP supply chain can facilitate regulatory engagement in a number of ways, for example by enabling regulators to: (i) access the blockchain platform, possibly through a visible-only node operated by the regulator; (ii) track products and coordinate with other stakeholders in real time through the blockchain network; (iii) assess and confirm compliance via the publication of zero-knowledge evidence (whereby a party can demonstrate that a given claim is true without disclosing the data that proves it); and (iv) have access to a permanent and immutable regulatory audit trail in the form of the blockchain ledger itself. This integration can save regulators and commercial parties time and costs.
- There are many different actors within the ATMP supply chain
Blockchain allows efficient coordination between stakeholders – for example, all participants can monitor updates to the ledger in real time, and all (or a subset) of participants can also request uploading of data to the ledger. Lack of coordination and transparency with regard to data is a major barrier to existing technologies (which are often developed for individual manufacturers such as a centralized database); this barrier can be solved through the implementation of a blockchain network. However, implementing a blockchain network can present challenges around the control of data (ie a decentralized blockchain network does not allow a single actor to withhold data).
A blockchain solution
As illustrated in this paper, various barriers to the widespread use of ATMPs can be addressed by the introduction of a blockchain network for supply chain management. In the UK, we have already seen a blockchain-based platform that manages supply chains for ATMPs that is intended to be fully integrated with NHS IT systems. In addition, IBM has also developed a “Personalized Medicine Platform”, a blockchain platform that provides tracking and tracing of CAR T-cell therapies.
Key considerations in implementing the blockchain network will include how to: (i) decide how the network will be run, and by whom (usually a consortium of interested parties will establish the network and may set up a dedicated entity to manage day-to-day operations; this may creating the need for complex contractual arrangements from the outset); (ii) forming contracts between various stakeholders, including whether smart contracts can be used; (iii) evidence of regulatory compliance; and (iv) ensure data security and privacy – important design choices in relation to data placement, processing and storage must be made at the start of any ATMP blockchain project.
