By Carla Reed, president, New Creed LLC
Life sciences companies engaged in the transition from clinical to commercial scale are challenged by the ability of current suppliers to meet the demand for materials and services as the volume of source ingredients is increased and production capacity and yield are stabilized. In the case of cell and gene therapies, and related personalized medicines, these source materials directly correlate to specific patient populations, with related constraints.
In addition, in most cases the clinical production — and the ongoing commercial production — takes place through outsourced partners and service providers. This includes a complicated network of many small entities, in many cases geographically dispersed. This increases the complexity, with related requirements to develop supply chain models that can scale. Each of the critical stages needs to be planned for — from acquisition of source material through each of the steps until final delivery of a specific compound at the point of patient.
- Source Materials – In the case of these therapies the source ingredient is a live cell — blood, tissue, or other element. The collection process for these materials needs to be scheduled ahead of time, taking into account each of the process steps from the arrival of the patient — or donor — at the clinical site where this material needs to be drawn, carefully labeled, packaged for transportation, and handed over to the appropriate transportation provider for delivery to the production location.
- Production of Drug Substance and Related Drug Product – The steps in the transformation of source materials into the therapeutic compound frequently take place across a network of contract manufacturing providers. This adds complexity when transporting these fragile compounds, most of which have specific environmental risk factors.
- Packaging, Labeling, and Final Distribution to Point of Patient – Each step in this process needs to be carefully planned for, ensuring compliance with global regulations for item-level serialization, authentication, and association to each unique patient.
While each of these requirements and constraints adds time and cost during the development of the supply chain strategy and implementation process, there are additional benefits that can be derived.
Creating Digital DNA
The information related to the item, trading partner, transportation unit, patient — all the entities that are part of each unique product life cycle — is now available in digital format. This provides many opportunities beyond compliance. The concept of command and control — sometimes referred to as control tower — is being addressed by a variety of software and service providers using “orchestration platforms” that coordinate and consolidate information into actionable information for monitoring and remediation.
The next generation of information technology solutions, one of which is the growing trend toward blockchains, is of great interest to those faced with global supply chain challenges. Adopted and endorsed by Walmart for its fresh produce supply chains, blockchains are an opportunity to create secure digital data across the transaction life cycle for a single shipment. Frank Yiannis — previously an advocate of blockchain at Walmart — is now with the FDA, where he is introducing this concept to an even more complex supply chain environment.
In the simplest terms, a blockchain is a digital ledger, a shared platform for either a private community of entities engaged in a series of transactions or a public platform for a broader community. Each blockchain provides a single record of transactions and reported events that take place from initiation to disposition, across a network of partners in the chain of custody. This creates a single version of the truth for the participants in this specific transaction and community.
Blockchain As A Solution For Cell And Gene Supply Chains
During the discovery process and through to clinical trial stages, relationships are developed with a variety of entities, including material suppliers, clinical sites, transportation providers, contract research and production companies, and third-party logistics partners. This community fits the requirements for a private blockchain:
- Building upon existing relationships and using digital data that is already generated through transportation, manufacturing, and financial transactions, the blockchain platform can be leveraged to create a secure virtual ledger.
- Additional security can be achieved through encryption technologies, in addition to the fact that each transaction cannot be changed once recorded in the blockchain.
- Serialization at the unit and item level is already required and this detail, through association with the transactional data, provides the “digital DNA” that is unique for each series of events, across the product and shipment life cycle.
- Packaging components, including specialized packaging for environmental monitoring and control, contribute to the data, providing digital records related to the location, state, and control across the chain of custody.
Blockchain is a solution that has already been successfully adopted in a variety of industries, such as food and automotive. The FDA is actively supporting blockchain initiatives for the life sciences industry in the U.S., announcing in June 2019 that it will be sponsoring a pilot for a public, permissioned blockchain to track, trace, and authenticate life sciences materials and products.
Participants in the pilot include IBM, KPMG, Merck, and Walmart. The objective of this pilot program is to develop a digital, interoperable platform for participants to share data across the transaction life cycle. This is in support of the objectives of the Drug Supply Chain Security Act (DSCSA), put in place to ensure safety and security of medications, providing visibility, traceability, and authentication across the chain of custody in the U.S. Each participant in the pilot brings expertise to the project, representative of different stakeholders in the life sciences supply chain.
The implementation of a permissioned blockchain framework will enable the secure sharing of real-time data, providing visibility to products as they move through each of the links in the chain. Data shared and made available will include time and temperature data, providing an immutable audit trail at the item and product levels. This provides a permanent record at the participant and transaction level that can be integrated with and enhance capabilities of related supply chain and serialization and traceability solutions already in place.
Barriers To Adoption Of Blockchain
As with the introduction of any new technology, there will be constraints and issues that need to be addressed. One of the key challenges is to achieve consensus among key stakeholders in terms of the process models that will be supported by the blockchain platform. This requires trust and open sharing of data between all participants in the chain of custody, from acquisition of materials through production, storage, and distribution.
A further challenge relates to the personal and cost data that is generated and would form part of a permanent digital record. During the process, there are transactions that are recorded in the blockchain that include data that could identify a specific patient — particularly for autologous therapies. The information that is shared and subsequently stored in the digital ledger is immutable — it cannot be amended or deleted. This raises questions of how long personal data could be stored and if there are potential conflicts with the General Data Protection Regulation (679/2016/EU) that came into effect across the EU in May 2018. Although encryption technologies can be integrated into the blockchain implementation, these are considerations that need to be addressed, potentially by retaining patient confidential data “off the ledger,” where it can be deleted as appropriate.
Getting Started — One Step At A Time
Participants in the supply chain for cell and gene therapies are defined early in the discovery and clinical trial phases. These participants work closely together as co-development partners (to an extent), which addresses one of the first challenges for a blockchain platform — that of trust and transparency. Another plus for cell and gene therapy is the clarity in terms of patient locations; in many cases these are aligned with the clinical sites for clinical trials and subsequent dosing regimens. As such, some of the constraints faced by other types of supply chains are less relevant for cell and gene therapies. What remains is to focus on the sequence of activities and the participants and put this into a structured framework that can provide a blueprint for each of the blocks in the blockchain.
The first step in evaluating how blockchain can be used to monitor and manage the complexity of the supply chain for cell and gene therapies is to define the operational environment. This includes:
- The Players – Supply chain partners that contribute to and share data could be part of a blockchain implementation. The participants include, but are not limited to, healthcare providers, hospitals, transportation and logistics partners, contract research organizations, clinical trial site management, production partners, healthcare agencies, specialty distributors, and specialty pharmacies.
- The Process – It is critical to develop a unique process map for each and every unique supply chain channel. Define each of the steps that take place from beginning to end, across the specific product and shipment life cycle.
- The Technology – There are many different technologies that can be adopted when leveraging a blockchain platform. Start with what is already in place and work with current partners to establish what else is needed.
There are many steps on the road to discovering a life-changing molecule. Understanding the impact and requirements for a clearly defined supply chain strategy and implementing this into the complex environment of cell and gene therapies is not a simple task. It requires dedication and participation from all the stakeholders across the development to delivery life cycle. All the details need to be defined, simulation models developed, and risk assessed — and remediation plans put in place. At times, it is necessary to change plans, change partners, and change direction. But the promise of medical breakthrough is irrefutable — no matter how challenging bringing these compounds to the point of patient may be.
About The Author:
Carla Reed is a supply chain professional with more than 25 years of experience providing leadership and program management across a variety of functional areas for the life sciences industry. Her broad range of experience and expertise has provided solutions for pharmaceutical and biotech companies challenged by the growing complexity of extended supply chain environments. Her firm, New Creed LLC, provides change leadership to facilitate sustainable solutions, providing hands-on experience in all aspects of supply chain operations. You can email her at firstname.lastname@example.org or connect with her on LinkedIn.