Chain of Custody (COC) is a common topic within cell orchestration discussions. But what is COC and why is the Chain of Custody important within cell and gene supply chains? This article will discuss its significance and the consequences of disrupting it. Additionally, we will explain how you can incorporate accurate COC tracking.
- Chain of Custody (COC) Definition
- What is COC within Cell & Gene Therapies (CGT)?
- COI vs COC, what is the difference?
- Why is the Chain of Custody important?
- How is the Chain of Custody created?
- Why is it important to maintain the Chain of Custody?
- What happens if the Chain of Custody is broken?
- Reporting and auditing the Chain of Custody
- How to implement accurate Chain of Custody tracking?
Chain of Custody Definition
COC is the record that tracks how human tissues and cells exchange custody throughout the supply chain process. It can be defined as the contemporaneous, permanent, and auditable record that documents the possession of a CGT product – from its origin right through to its final disposition. When we refer to COC, we mean the record of who was responsible for cells at every stage of the process. So, why is this so important within CGT?
What is COC within Cell & Gene Therapies (CGT)?
COC is often linked to Chain of Identity within personalized medicines; but COC and COI are different and are tracked separately. Most importantly, both are required for regulatory compliance and to demonstrate best practice for Advanced Therapy Medicinal Product (ATMP) supply chains.
COI vs COC, what is the difference?
Essentially, Chain of Identity (COI) is a control placed to ensure that the correct patient receives the correct therapy. Typically, a patient is allocated a unique COI code which spans the whole supply chain ensuring that their materials and data are tied to them. This is critical because within personalized medicine, an error resulting in a patient receiving another patient’s therapy could be fatal. You can read more about COI in our “What is COI?” blog.
Why is the Chain of Custody Important?
As the less frequently discussed element of the COI COC debate, it’s easy to underestimate the importance of Chain of Custody. However, there are both operational and regulatory reasons for accurately recording who is responsible for tissues, cells, or drug products as they move within the supply chain.
Additionally, the Chain of Custody also has important implications with drug product security. And depending on process requirements is often tied to data records of storage conditions such as temperature.
There are regulatory requirements in relation to COC in certain jurisdictions. These include the Human Tissue Act 2004 in the UK, which prevents unauthorized trafficking or use of human tissues. Under this act it is important to be able to demonstrate that cells have only been handled by authorized parties. Additional regulations governing the handling of human cells include FDA 21 CFR 1271 and DIRECTIVE 2004/23/EC.
It is a key ethical concern to ensure that cells are only being used for purposes the donor has consented to. Whilst these challenges might be partially addressed via COI, COC records have a critical role in demonstrating full compliance.
How is the Chain of Custody Created?
Like Chain of Identity, the COC is a complex record collating details from multiple sources, documents and providers into a Chain of Custody log. This log details all the tissue or cell’s movements and responsible parties throughout its journey along the chain.
Chain of Custody was traditionally seen as an historical record, compiled retrospectively. It was created by collating shipping documents and other records from the various sites and partners that held them. The effort needed to compile the Chain of Custody log manually limited its usefulness. Making it a tool to support investigations into errors, process failures, and a compliance record for human tissue and transplant legislation.
The complexity of compiling Chain of Custody records can be increased by the disparate locations of supporting documents. With records held by multiple parties in multiple places throughout the supply chain.
Typically, a recipient signed paperwork to show that the cells had been transferred and accepted. These documents and their copies would then be stored with supply chain partners or at remote sites. Collating involved scanning or sending to a central location to be associated with a specific patient’s therapy journey.
More recently, electronic Chain of Custody logs have become powerful, pro-active components of the supply chain. This methodology can vary in complexity. For example, Chain of Custody documents can be exchanged via partner portals or emails, and collated in one place. This could be done by using Chain of Custody tracking, or orchestration software, that can gather documents in real time.
Within CGT, cells often have a shelf life as short as 48-72 hours even with temperature-controlled shipping and storage systems. Real-time tracking of the location and custodian of a shipment helps ensure cells are viable when they reach their destination. Delays or problems can trigger real-time alerts that prompt mitigation actions. Making a Chain of Custody compiled in real-time a tool that can improve patient experience, minimize loss, and reduce costs.
Why is it important to maintain the chain of custody?
Beyond basic compliance, the bottom line is that many of these treatments have a high value both financially and ethically. Delays that result in cells losing viability, or drug products being lost/destroyed could cost millions – even for a single dose. But more importantly, they could cost the life of a patient.
CGTs are often the last treatment option a patient has. Those based on cells extracted from the patient can take weeks or months to manufacture. For autologous therapies, the manufacturer’s ability to produce to release specifications is dependent on the quality of the starting material. Controlling chain of custody decreases the risk of excursions damaging starting material, increasing the chance the therapy will meet release specification.
In the event of errors, delays, or ‘near misses’, a record of who had custody at the point of failure is essential for effective corrective actions. It can also be used when looking at optimizing the process timings and improving efficiencies – e.g., optimal logistic routing.
As more organizations investigate sophisticated planning tools, having the data to drive the models that are used can be extremely informative. Processes are often built on tolerances or averages, but specific, real-life data is invaluable for time sensitive CGT logistics.
What happens if the chain of custody is broken?
This is a complex question, and much depends on the process and the material type that you are dealing with. It is possible that if nothing else goes wrong (e.g., temperature and tracking is intact), a COC snag may be just an administrative issue. However, if critical parameters or the authorization status of those who have handled the cells is unverified, they may be unusable.
Growing focus on drug product security and the need to verify handling and donor consent for human tissues, mean demand for real-time COC tracking is increasing. And this is gaining an additional financial driver. Whilst CGTs are curative or life changing, they often have an extremely high cost per dose. This means that new reimbursement models for commercializing CGTs are emerging.
Some of these models tie financial compensation to the treatment and aftercare schedule of the patient. In these cases, Chain of Custody records help determine when a treatment has been administered and the ’compensation countdown’ begins. For drug developers, a system that issues an alert when treatment is completed reduces admin, and speeds up financial settlement.
Reporting and auditing the Chain of Custody
A key issue in traditional Chain of Custody tracking was consolidating the records that support the audit trail. As COC generally tracks physical movement of goods through partner organizations, supporting documents can be spread across the supply chain.
These documents, or copies of them, then must find their way back to be associated with the central patient record. This might mean several stakeholders having to submit documentation accurately. This is usually a complex and manual process which is open to errors and delays. Alternatively, a central stakeholder accessing multiple records, partner portals or systems, may be trying to collate records.
Digital Cell Orchestration Systems (COS), are a type of Chain of Identity and Chain of Custody tracking software. A configured COS will automatically compile Chain of Custody reports and collate supporting documents from integrated parties (e.g. couriers). They create a searchable Chain of Custody record that can be audited by authorized users during or after the process.
How to implement accurate COC tracking
CGT developers are increasingly regarding digital COS as standard for tracking Chain of Identity, Chain of Custody and Chain of Compliance. This is in part due to the fact that they facilitate scale-up far better than a manual system. With this in mind, when choosing a Chain of Custody software solution, it’s important to consider both future and current requirements.
With OCELLOS by TrakCel, you can fully track COC, and COI throughout the entire supply chain. These reports are available both during and after the therapy journey and can be downloaded in an easy-to-read PDF. Making it easier than ever to demonstrate a fully compliant Chain of Custody log for your advanced therapies.
Do you want to know more about setting up COC supply chain tracking for your cell and gene therapies? If so, reach out to our team for a free demonstration.
Article by Helen Hopkins - 25 Apr 2023