Two transformative technologies

ATMPs, including gene therapy medicines, somatic-cell therapy medicines and tissue-engineered medicines, could offer the potential for truly personalised medicine and viable treatments for diseases which are currently near-incurable, including haematological cancers, sickle cell disease and spinal muscular atrophy. The development and commercialisation of new ATMPs is a high priority for both governments and the pharmaceutical sector at present. In the UK, which currently hosts around 12% of ongoing ATMP trials, approximately £3.8bn has been invested since 2012 to support ATMP development.

Blockchain, meanwhile, offers the ability to store and transmit data in a decentralised and real-time manner. Whilst the focus of many blockchain implementations to date have been in the financial services sector, there is an increasing recognition that blockchain could provide certainty when recording transfers of assets in a wider range of sectors, including the unique and specialised ATMP manufacturing 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 generally then modified, engineered or manufactured into a therapy for delivery to either the same patient (an “autologous” therapy) or another patient (an “allogenic” therapy). This complex manufacturing and delivery model is known as the “vein-to-vein supply chain”.

ATMPs have not yet been adopted on a large scale basis due to a combination of clinical, regulatory and cost-related hurdles. At present, 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 prevalent, ensuring the ongoing integrity of their supply chains will be of paramount importance.

The role of blockchain

There is an increasing recognition that blockchain could help to resolve many of the most significant challenges facing ATMP supply chains due to its inherent characteristics:

1. Consensus – for a transaction, or new data set, to be recorded on a blockchain database, that 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, as all participants have the same copy of the database, this ensures a high level of trust in the data that is recorded on the database being accurate and valid.
2. Provenance and immutability – all transactions on a blockchain ledger are permanently recorded so that all changes over time can be seen. Once a transaction has been recorded on the ledger, it cannot be altered or deleted. It is therefore not possible for participants to tamper with data recorded on the ledger, therefore increasing trust in, and allowing traceability of, that data.
3. Finality – the blockchain ledger is a single source of truth for all participants in the blockchain network. Any participant that operates a node (being a device which will receive real-time validated updates of data added to the blockchain ledger) and has the rights to read data on the blockchain ledger will be able to view transaction data and can have confidence that the data is valid.
4. Security and reliability – there is no single point of failure in the operation of a blockchain network. Participants each operate a 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 ledger would require a bad actor to assume control of the entire consensus mechanism.
5. Decentralisation – given the decentralised nature of blockchain networks, the ledger allows for complete openness and sharing of data, and transparency.

In short, transactions recorded on blockchain are secure, authenticated and verifiable. This is relevant to ATMPs because:

• Given their nature, ATMPs are sensitive to their environment

Blockchain, when combined 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 for scheduling and resource allocation. IoT devices may be used to track changes in temperature or other measurable variables, such as geolocation, and regular data feeds may be transmitted from the device to the blockchain ledger. Participants would then be able to track the location of the ATMP through the supply chain, and ensure that the environment in which the ATMP has been stored at each stage of the chain is compliant.

• ATMPs are subject to complex regulatory requirements

The regulation of ATMPs is complicated by the manufacturing process and the nature of the end product. Donated tissue used as the basis for an ATMP could be regulated by the EU Tissue & Cells Directive, EU Blood Directive or other regulation, depending on the source (human or animal) and type (tissue, cells or blood) of donation. Where the donated tissue is then engineered and/or undergoes a functional change, the resultant ATMP could be regulated and administered to patients as a medical device, investigational medicinal product or a licensed or unlicensed/“special” medicinal product. In the UK, the regulation of ATMPs across the entire supply chain involves a number of separate regulatory bodies, including (depending on the ATMP in question): the MHRA, the Human Tissue Authority, the Human Fertilisation and Embryology Authority and the Health Research Authority.

Integration of blockchain technology into the ATMP supply chain could facilitate regulatory engagement in a number of ways, such as by enabling regulators to: (i) access the blockchain platform, possibly through a view-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 publication of zero-knowledge proofs (whereby a party can demonstrate that a given statement is true without revealing 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 could save regulators and commercial parties time and expense.

• There are many different players within the ATMP supply chain

Blockchain allows efficient coordination between stakeholders - for instance, all participants can monitor updates to the ledger in real time, and all (or a sub-set) of participants may also request the upload of data to the ledger. A lack of coordination and openness with regard to data is a key barrier faced by existing technologies (which are often developed for single manufacturers as a centralised database); this barrier could be addressed through the implementation of a blockchain network. However, implementation of a blockchain network could present challenges surrounding control of data (i.e., a decentralised blockchain network does not allow any one player to withhold data).

A blockchain solution

As illustrated in this article, various barriers to the widespread use of ATMPs could be resolved by the introduction of a blockchain network for supply chain management. In the UK we have already seen a blockchain-based platform managing supply chains for ATMPs which is intended to fully integrate with NHS IT systems. Additionally, IBM has also developed a ‘Personalized Medicine Platform’, a blockchain platform providing track and trace management of CAR T-cell therapies.

Key considerations when implementing the blockchain network will include how to: (i) decide how the network will be operated, and by whom (typically, a consortia of interested parties will establish the network and may set up a dedicated entity to manage day-to-day operations; this can create the need for complex contractual arrangements from the outset); (ii) form contracts between different stakeholders, including whether smart contracts may be used; (iii) evidence regulatory compliance; and (iv) ensure security and privacy of data – important design choices in relation to data location, processing and storage must be made at the outset of any ATMP blockchain project.

Next steps

We routinely advise on supply chain and other complex transactional matters across the life sciences and health care sector.

Please contact the authors or the Hogan Lovells attorneys with whom you regularly work for guidance on your specific product needs.

Authored by Penny Powell, Bea Watts, Alice Russen, and James Sharp