In 1959 Dinah Washington sang ‘What a difference a day makes, twenty four little hours’, you’ll have to indulge the reference to a jazz classic but time can be of the essence for the delivery of advanced therapy products.
Since TrakCel’s inception in 2012 I’ve seen a trend developing for cell and gene therapy companies supplying autologous therapies. The first few autologous treatments to be mapped and defined by TrakCel’s Process Analysts were all time-dependent, unstoppable processes, this dependency was not in recognition of the patient’s fragile condition but a reflection of the stability data (or lack of) for starting material and drug product. In a rush to demonstrate the efficacy of these novel treatments, little consideration was made to the practicalities of commercializing these treatments. In 2019, all therapies managed by TrakCel’s software have at least one cryopreservation step. This is providing flexibility of supply, making manufacturing assets easier to manage, allowing physicians to select convenient days for starting material collection and product administration, providing more time for QC analysis and QA release.
In 2019, all therapies managed by TrakCel’s software have at least one cryopreservation step.
Cryopreservation allows a pause in the supply cycle of autologous cell therapies, makings logistics easier and less likely to cause out of specification shipments (as a rule, the colder a shipment, the easier it is to maintain the shipping specification). Importantly, the reduction in time sensitivity of these advanced therapies (and in some cases starting material) provides time for patients to recover from temperature spikes and other complications which may delay them from receiving their therapy.
TrakCel’s cell and gene therapy software was initially designed to manage ‘fresh in, fresh out’ products, perhaps the toughest supply paradigm, orchestrating all parts of the supply cycle to manage therapies with limited stability data and challenging specifications. Sadly there are several cases of patients not surviving long enough to receive their therapy after donating starting material; take CAR-T treatments, these are currently administered when conventional standard of care has failed, so recipients of these therapies can be gravely ill. So despite an industry-wide move away from fresh in, fresh out’ reducing vein to vein time for treatments is a strategy being pursued across the cell therapy industry.
TrakCel’s cell and gene therapy software was initially designed to manage ‘fresh in, fresh out’ products, perhaps the toughest supply paradigm, orchestrating all parts of the supply cycle to manage therapies with limited stability data and challenging specifications
Today, TrakCel is being used worldwide to optimize the supply cycle of autologous, allogeneic and personalized vaccines; the experience gained in the company has been invaluable to its users, helping to reduce ‘vein to vein’ time, and simplifying the management processes of these products.
While much has changed in the advances of personalized medicine since Dinah Washington’s 1959 hit, the importance of timely and effective treatment is as crucial today as it was then.
The advanced therapy industry is constrained by its focus on manufacturing. The drive to reduce COGS, close and automate processes, create assay platforms, etc. are all critical.
However as advanced therapies increasingly reach market authorisation they need to utilise a logistics platform that connects patients to therapies.
I was asked recently by a senior executive of a cell therapy developer to summarise ‘Why TrakCel?’. He wanted to share this with some of his colleagues that had not been involved directly with us to date. The organisation was clear on the business value of introducing a cellular orchestration platform so ‘Why a COP?’ wasn’t the exam question. It allowed me to reflect honestly on what TrakCel has achieved over the last few years and what is truly important to our customers.
TrakCel has a Released Product. It may sound an overly simple place to start but this industry is unfortunately not immune to the smoke and mirror sale pitches from the ghosts of software (sometime in the) future. We are installed and validated at Sponsors, Clinical Sites, CMOs & Logistic Partners across North America & Europe. That last sentence is simple to say and understand but is not straightforward to achieve. We have a mature operation that has been built since 2012 solely to focus on cell and gene therapies. Being ‘live’ in a complex industry with complex supply chains is, not surprisingly, complex. But TrakCel ticks that box.
TrakCel is ready for commercial scale. The industry is evolving, the Alliance of Regenerative Medicine estimated that there were 804 clinical trials underway by the end of 2016 (2015: 631). The ratio of trials to approved therapies means that our clients are utilising our cellular orchestration during the clinical phase but with the standalone cell and gene biotech market leaders commanding market capitalisations of between $3.2b to $6.3b then it is all about the pathway to approval and commercialisation. TrakCel is built for scale, it has been pushed to volumes that if this industry achieved would make those market caps look like chicken feed. Again, we’re not marking our own homework here but have had these load tests undertaken by 3rd parties including one of world’s largest CROs.
TrakCel is open and agnostic. With the word ‘complex’ being mentioned 3 times in one sentence earlier the need for visibility, control and simplification is paramount. A supply chain, as the name implies, should be a number of interconnected links that provide consistency of process and data, and joined in an efficient manner. I don’t subscribe to the Internet of (every)Thing – does my toaster really need internet access? – but identifying and delivering true business value from system and equipment integrations across the supply chain ecosystem can be transformational. TrakCel takes an open and agnostic approach to this which means that our clients select their preferred best of breed partners (couriers, shippers, manufacturing systems and equipment). The only proviso is that we will always push to ensure that business value is at the forefront rather than just connecting because we can.
TrakCel was not built in isolation. Building a new software platform for a new industry is not always straightforward. Building in isolation is a recipe for disaster. Building alongside an initial high profile anchor client is also full of traps and risk (usually around over-customisation and stretched resources under unrealistic time constraints). TrakCel identified in 2013 a collaboration partner. Not a client, not someone to just get some insight from but a formal collaboration agreement with a big pharma company that truly saw the value in the future of cell and gene therapies and wanted to see an orchestration platform developed to support the upcoming trials and commercialisation of product. Ensuring that TrakCel owned the resulting intellectual property was key for us as a business and testament to the partner’s desire to see the results as being for the market as a whole. Iterative development of a platform built by the cell and gene industry for the cell and gene industry.
TrakCel can support our customers’ urgency. The market is bounding forward with July’s FDA Advisory Committee recommendation for approval of Novartis’s CAR-T cell therapy CTL019 as another milestone moment. The desire for companies, now with added confidence of being allowed to achieve the milestones ahead, to implement a comprehensive platform to support flawless delivery of therapies is increasing. Although we continue to build functionality we are not building ‘version 1’, we therefore are set up to match the deployment urgency of our clients.
For me the last 6 months has seen an awakening in our clients (and future clients) to the realisation that early supply chain strategy roll out and control, implemented during early clinical trial phases will expedite the route to commercialization. The early conversations around ‘I see the value of a COP but come back to me in 12 months’ are frequently replaced by ‘Will you help us now to put in the foundations upon which traceability and scalability can be achieved’. The same approach is not adopted by all companies but increasingly the market is becoming laser focused on what future success looks like and how it can be achieved.
TrakCel is built for purpose. As in other industries that I’ve worked in then there can sometimes be suggestions from proactive internal IT functions that they are willing to add software or system integration design & development to the core skills of the enterprise by building a platform from within. Clarity and focus on an organisation’s core purpose and objectives provides the best chance of success. Big pharma rarely has a well resourced aim to become a software platform developer. A market developed platform, like TrakCel’s, offers our clients continued access to the substantial research and development we invest in new functionality, identification / creation and ongoing alignment to industry standards and uninterrupted support for a core application. Also with the industry full of partnerships, licensing agreements and future divestments and acquisitions, internally developed applications cause unnecessary complexity to support a changing commercial landscape.
TrakCel provides simplicity and choice. When it comes to the deployment of the platform then TrakCel provides simplicity and choice. We are cloud based and provide secure access from a browser or mobile device. A single instance of the platform for each client (but which can run multiple therapies) for security and regulatory safeguards that can be hosted in either public or private cloud depending upon the capabilities and requirements of our clients. The multi tenanted SaaS model that insists all clients take upgrades at the behest of the provider is not workable here – this isn’t a one size fits all salesforce.com model.
TrakCel has a blended team of Experts. We have, what I know from meeting other providers, a truly unique mix of experience across Clinical Operations, Process Development, CMO, Cold Chain Logistics and Enterprise Software Development. Clarity of strategy, followed by uncompromising talent acquisition and development, is a key ingredient to our market leading position and will ensure we continue to lead, innovate and evolve. We have global coverage, currently 60 employees in multiple territories with 2 US and 1 EU office.
TrakCel has clear respect and demarcation of each client’s own Intellectual Property. TrakCel is cognisant of the importance of trade secrets and proprietary IP especially in the young, competitive cell and gene therapy market with valuations and future funding being directly linked to future success. A platform for an industry must respect the need for market standardization but allow for the protected differentiation that the winners will be built on.
There is absolute clarity between TrakCel’s generic IT building blocks and our clients’ intellectual capital. These should never be compromised. Our platform, interaction with clients and contractual agreements are designed to support this. Importantly, TrakCel doesn’t build a library of its clients’ process and knowledge for the future reuse with their competitors. Sounds odd having to state that really.
Somehow for my client I did manage to get this summarised onto the one slide they requested but I felt my reflections on TrakCel’s approach and achievements, and importantly why they directly support the ambitious objectives of our clients was useful to share wider. We’re motivated by the journey so far and excited by the one ahead. We look forward to working with our existing and future clients to make a truly positive difference.
Cellular Orchestration Platforms (COPs), such as TrakCel, are designed to improve supply chain performance for cell and gene therapies (CGTs).
This is achieved by:
· Providing full traceability of therapies from donor to recipient – this is especially important for autologous cell therapies, where following modification and expansion at a manufacturing site, starting material derived from a patient must be infused back into the same patient. As the number of therapies being received, processed and shipped by clinical sites, manufacturers and logistics providers grows this will become increasingly challenging.
· Driving compliance with regulations, the trial protocol and Sponsor SOPs at clinical sites, through the implementation of prescriptive 21 CFR Part 11 compliant workflows. Again, as the number of parties involved in cell therapies grows in late stage clinical development and commercialisation, the need for consistency and control increases.
· Capturing Data from multiple parties in the supply chain, giving Sponsors a single-system view of needle-to-needle supply chain performance allowing for analytics and performance optimisation.
· Scheduling of activities in the supply chain to ensure upstream tasks occur only when there is downstream capacity available for subsequent process steps. For example, providing apheresis centres with visibility of manufacturing capacity so starting material is collected only on days when capacity is available for cell modification and expansion.
· Simplifying QA release processes and supporting product quality by providing Quality Staff with all the information on a product’s chain of custody required to certify it is safe for infusion into a patient.
Through the above functionality, COPs can significantly reduce Costs of Goods during clinical development as illustrated below. Savings in this table are based on the following estimated costs for a clinical trial[i] (based on standard pharmaceuticals/biologics – for CGTs, we would expect the cost to be at the high end of this scale, if not higher):
· Phase I $1.4M – $6.6M
· Phase II $7.0M – $19.6M
· Phase III $11.5M – $52.9M
Major cost drivers include clinical procedure costs (15-22%), study administration costs (11-29%) and clinical site monitoring (9-14%). For illustrative purposes, and based on the complexities of CGTs, we will use the higher figure in these ranges for CGTs.
Further supply chain challenges, and associated costs, need to be captured in each therapy’s Cost of Goods (COGs). While a COP may not directly impact on these processes per se, data captured by the system allows Sponsors/Developers to take a holistic view of their supply chain and identify opportunities for optimisation.
· Logistics – COPs can provide logistics providers visibility to future needs, allowing for better forecasting and utilisation of courier services and improved management of specialised shipping system inventories, which in turn can reduce costs. Also, data captured can be used to analyse courier performance, route selection and potential points of failure.
· Manufacturing/QC testing – In many cases, scheduling is performed manually across the supply chain. Automating this process can enhance utilisation of manufacturing assets, which has a significant impact on the cost of goods. Integration with manufacturing equipment allows for a more efficient review of manufacturing data at the time of release.
· QA/QP release – This is a major cost and process bottleneck for even traditional pharmaceutical manufacturers. Capturing data and documentation across the entire supply chain, from multiple sources (as is often the case for CGTs) can be challenging and adds significantly to release timelines – particularly for initial batches. By capturing key data, COPs can help alleviate this – one QP we spoke to quoted up to 40 man hours at a cost of $10,000 to release a first batch of product when compiling data from multiple stakeholders, which can fall by around 85% if all information is available in a single system.
TrakCel’s experience to data has been focused on supporting our clients’ products through clinical development. We are well aware of the challenges ahead when products are commercialised. One client we spoke to when compiling this paper cited that, in order to justify their current market capitalisation, larger autologous CGT developers will need to sell 5-10,000 treatments per year. This in turn equates to 40-60 batches of product released every day. How is this going to be possible using manual traceability and supply chain orchestration? What will the labour cost of achieving this, let alone the risk of product failures in terms of lost material and damaged reputations, amount to? COPs were developed to enable cell therapies to reach their potential – this will not happen without traceability, consistency across all stakeholders, automation and holistic data-driven decision making across the supply chain provided by these systems.
Recently I had the opportunity to participate in the Hanson Wade Future Cell Therapy Commercialization Event in Boston, MA which was overall, a fantastic event. A big thanks to the organizers. With logistics being a cornerstone to the future success of cell therapy commercialization, a significant portion of the overall discussion was focused on supply chain challenges associated with the delivery of autologous therapies.
Due to TrakCel’s well established US and EU compliant, Cloud-based Cellular Orchestration Platform (COP) that pioneers the space and was first to market in 2012, Hanson Wade provided TrakCel and myself the opportunity to help assemble and moderate a panel titled, “Leveraging Cellular Orchestration Platforms and Other Systems to Support the Cell Therapy Supply Chain.”
For those that were not able to attend, this blog post is a summary of the three main takeaway messages of the presentation:
- What is a Cellular Orchestration Platform?
– Where does a Cellular Orchestration Platform fit amongst other IT systems?
– How to go about implementing a Cellular Orchestration Platform?
What is a Cellular Orchestration Platform?
Over the past several months it’s been evident that the cell therapy community has an acute awareness of Cellular Orchestration Platforms (referred to as COP here forward) but somewhat of an obtuse understanding around what exactly these systems do – hence the intention and main focus of the panel.
As the name suggests, these systems are designed to orchestrate, or manage processes and workflows across the entire supply chain, often driven by various third parties that lie outside the control of drug developers, including collection centers, couriers, manufacturers and infusion centers. To do so, these systems must have flexible configurations that yield prescriptive workflows as well as detailed rules and constraints that are specifically engineered to match the cell therapy company’s product portfolio.
The end result provides cell therapy developers a standardized, automated and controllable needle-to-needle supply chain with functionality including automated scheduling/resource alignment, notifications/alerts, capacity management and customizable dashboards for core users.
When complete, these systems become a drug developer’s “Control Tower” view and the thread that ties the overall process together. By doing so, the COP system provides developers a complete and regulatory compliant electronic record for chain of identity and chain of custody from collection through to infusion.
Where does a Cellular Orchestration System Fit Amongst Other Systems?
Another major topic discussed by the panel was around where a COP fits within the universe of IT systems.
Primarily, a COP should not be compared against more traditional internal systems such as ERP, MES or LIMS which are of course intended to support more internal enterprise and manufacturing efforts. This is something that’s often misunderstood by our industry and understandable considering the new and unique manufacturing requirements of autologous cell therapies. Even though when one compares a COP against a more traditional manufacturing system and finds overlap in functional capabilities (such as barcoding, traceability, scheduling, etc.), the environments for which they are intended and the implementation efforts and expertise required are very different.
The second major message was that a COP does not, and should not, interfere with the implementation of customer relationship, enterprise, manufacturing and laboratory related management systems. Too frequently companies feel that major internal systems should be implemented before considering a COP when the strategy should be the exact opposite! Those that have managed mid to late-stage autologous trials understand firsthand how labor intensive and inefficient management of the autologous supply chain can be.
While the traditional systems mentioned above have their place in the commercial environment, COP becomes instrumental early in clinical development when patient numbers are in the 10s, not 1000s. This leads to the last major topic of the presentation, implementation strategy.
When and How to Implement a Cellular Orchestration Platform
Stage 1 – Build the Foundation
So, what’s the first step to implementation? Like building a house, the first effort should be focused on building a solid foundation. In the world of COP implementation that means establishing clinical site workflows for both collection and infusion, generating both starting and final drug product labels, courier integrations and milestone reporting within manufacturing environments.
A successful COP foundation establishes the pathway and major processes conducted across the supply chain while also pinpointing each step in the process where custody of the product is exchanged and/or chain of identity verification if required.
To garner maximum value from the COP, implementation efforts should begin early in clinical development when the number of clinical sites are limited (during Phase I/II trials). This early implementation allows for a validated system to be in place to support mid-stage trials, when clinical site numbers begin to expand and manual in-house systems begin to break down. At this stage of implementation, the combined value of the COP along with the costs saved via introducing the system during early to mid-stage clinical onboarding efforts (instead of onboarding and then backtracking clinical efforts to introduce the COP) can immediately justify investment with a measurable return on investment.
Stage 2 – Incorporate Scheduling
Once the foundation is in place, the next stage of implementation should be focused on scheduling. The simple reason for this is based on the fact that tracking/traceability (established in the foundation) and scheduling are inherently interconnected and dependent on each other.
As patient numbers increase and manufacturing capacity utilization quickly reaches the upward limits of the cleanroom environment, the scheduling system must accurately assess and book capacity while also being able to cancel or reschedule without breaching the limitations of the third-party environments. To do so, implementation of scheduling requires careful analysis of all stakeholders and resources involved in the supply chain followed by applying detailed rules and constraints that subsequently ensures alignment of resources for collection, manufacturing, transportation and infusion.
As we all know too well, Murphy is alive and well in cell therapy – if something can go wrong…it will go wrong. For this reason, the scheduling system must be adaptable to manage change. Lastly, implementation of a scheduling system often requires a detailed understanding of the treatment regime and the manufacturing process.
For this same reason, a COP provider must have a detailed understanding of the collection, logistics, manufacturing process and administration (including patient preparation) of each cell therapy it manages. Without this experience, rules could be built into the platform that would plague the utility of the system.
Stage 3 – Establish Commercial Integrations to Maximize Efficiencies
With the bulk of COP functionality now in place from the Stage 1 and Stage 2 implementations, developers are well positioned to provide an electronic audit file demonstrating chain of identity and chain of custody while also demonstrating capacity management for BLA application. This leads us to the final implementation stage (recommended to occur during Phase III trials) that is focused primarily on the integration of commercial systems to maximize efficiencies across the supply cycle. On the front end of the supply cycle, integrations may occur between the customer relations management software (CRM) – often the initial system used by patient case managers to gather preliminary patient enrollment related information and benefit verifications – with the COP.
To further information automation in the ultimate effort to streamline visibility into the needle-to-needle supply, integrations during Stage 3 may also occur between ERP, MES, QMS and LIMS systems as each system may have independent yet important data to contribute to the COP. The COP then becomes the tool that weaves several standalone systems together to provide the detailed view of the patient and the drug product journey. It can also become an interface for the patient and the physician to provide visibility into the progress of the life-saving therapy. Beyond infusion, drug developers are also considering the lifecycle of the COP to go beyond the delivery of the drug and become a vital tool for the long-term tracking of the patient for reimbursement, therefore requiring integrations with potential downstream payor-related systems. In the end, COP can become the overarching platform that tracks and manages the overall patient journey from identification to final reimbursement for the therapy.
The bottom line message is that Cellular Orchestration Platforms play an instrumental role in cell therapy – especially for autologous therapies. While the functionality they deliver is undoubtedly needed in the commercial setting, I hope this blog emphasizes the incredible value these systems provide in early clinical development and why it makes sense to begin implementation efforts as early as possible. As a final point, Steven Buckanavage one of the panelists, who led commercial efforts at AstraZeneca, GSK and most recently Celyad and now President at Mentoris Advisors, emphasized several times that we as an industry must have flawless execution every time to be commercially successful.
We at TrakCel see COP systems as a vital tool in the effort to bring Six Sigma level of quality to cell and gene therapy.
If you have any further questions or would like to learn more about TrakCel’s Cellular Orchestration Platform please email me at firstname.lastname@example.org.