Logistics by design: framework for advanced therapy developers

Introduction

Logistics is a key part of any advanced therapies supply chain. Failure within it may prevent therapies reaching patients.  Therefore, logistics platforms need to be created early and built alongside the therapies clinical and process development programs.

Logistics by Design (LbD) is a framework for logistics decision making. Using a risk based analysis it identifies the areas within the supply chain that need to be addressed to create a logistics platform that can meet the needs of patients at clinical and commercial scale.

Background

Advanced therapies, of which cell and gene therapies are an integral part, offer a new paradigm for the treatment of unmet healthcare needs. Clinical successes are translating into commercial realisation at ever-increasing rates and the number of new therapies entering trials are growing year on year.

However there are well documented examples of therapies that have struggled (e.g. rise, fall and rise again of Dendreon’s Provenge) or been withdrawn after commercial launch (e.g. UniQures Glybera), meaning there is more to creating a viable therapy than completing commercial trials.
Possible reasons for commercial failure include high manufacturing cost of goods sold (CoGs), lack of adoption by the clinical community, commitment to reimbursement by healthcare providers or the complexity of logistics and supply chain infrastructure. 

Significant manufacturing optimisation has been realised for advanced therapies and, initiatives such as the UK network of Advanced Therapies Treatment Centres, are seeking to address clinical barriers. However, the glue that binds all these elements together, the supply chain, remains relatively immature within the advanced therapy sector. 

The Logistics by Design Framework

Logistics by Design (LbD) seeks to provide structure to, and de-risk, logistics planning and implementation activities and help align it with the development plans of clinical process development teams.

Underpinning LbD is a well-established process development framework. This framework known as Quality by Design focuses on risk mitigation, as opposed to cost reduction. It uses a systematic approach that begins with predefined objectives, emphasizes product and process understanding and process control, and is based on sound science and quality risk management (for further information, download the white paper by completing the form below).

As with clinical and manufacturing development pathways, the key to logistics success is designing in “quality” from the outset. By doing this, challenges in creating a logistics platform can be identified early and allows sufficient time to consult with key stakeholders (e.g. manufacturing, clinical teams and providers). This will help align the various development programs and address any high risk or cost drivers.

To achieve this LbD creates a 6 stage tool kit that aligns with clinical and manufacturing development : -

1. Mapping of and risk identification for the commercial logistics vision - Application of LbD principles
2. Building Collaborations (Technology Selection and Testing)
3. Infrastructure Planning
4. Field Validation
5. Scaling for Commercial Operations
6. Commercial Deployment 

Stage 1 – Logistics mapping and risk identification for the commercial logistics vision - Application of LbD principles

The key is to set pre-defined objectives that capture the commercial vision of the therapy developer. This a Target Logistics Profile (TLP) and defines the overarching objectives of the logistics platform with respect to supporting business goals, supplying market needs, maintaining regulatory compliance and facilitating clinical adoption.

From this a Focused Target Logistics Profile (FTLP) can be established to provide a prospective summary of the logistics platforms traits. Including all components of the value chain, to ensure successful delivery of the therapy to the patient whilst maintaining chain of custody and identity. Thus, the FTLP describes the design criteria for the logistics strategy.

The Critical Logistics Attributes (CLAs) and resulting Critical Logistics Parameters (CLPs) can then be generated.  From this analysis, a developer will then have a clear understanding of the risk points within their supply chain, and start to identify mitigation or removal actions.

Stage 2 – Building Collaborations (Technology Selection and Testing)

Having defined and identified all the logistic activities required to execute the complete value chain, this stage of the framework builds, and manages, collaborations essential to creating a viable logistics platform.

Logistic providers should be viewed as technical experts, with “joint planning” and “collaborative” relationship levels sought for complex and high-risk elements of the logistics chain. Their expertise and experience can then be harnessed to add maximum value. Furthermore, by having this level of co-engagement and investment in the therapy, providers can appreciate the landscape ahead and “co-evolution” of companies can occur, amplifying the probability of success.

Part of these collaborative working relationships will include the selection and testing of specific technologies, whether it be the physical product shippers or complex integrated data management systems. If selected early in the development lifecycle, they can be assessed within early stage clinical trials and a logistics platform built, tested and optimised alongside the clinical and manufacturing teams.

Stage 3 – Infrastructure Planning

Early insight into the challenges and technological feasibility of the proposed commercial logistics platform, as provided in stages 1 and 2 of the framework above, will provide developers with an opportunity to revisit any of the original decisions based on data driven assessments of performance.

Once the agreed pathway is defined, then planning can commence for establishing the required infrastructure to support field validation (stage 4) as part of pivotal clinical studies and ultimately full-scale commercial deployment (stage 6).

Activities included at this stage of development may include for example the identification and sourcing of appropriately located warehousing capability within a specific geographic footprint. 

For example, having an allogeneic off-the-shelf cryopreserved product for an acute clinical condition such as stroke, where it may be important to administer the therapy within a small timeframe window (<12h), means it may be more desirable to have several smaller cryo-storage hubs, appropriately distributed globally, than one big master centre.

Stage 4 – Field Validation

This stage of the framework is focused on large-scale validation of the logistics platform with a view to gathering “in-the-field” data.  

Stage 5 – Scaling for commercial operations

This stage of the framework focuses on the scale-out of the logistics platform to cover the full commercial footprint. Exemplars of activities that may be actioned at this point in the development plan include:

• Bringing on board additional warehousing
• Lane mapping to ensure delivery windows are achievable based on clinical availability, manufacturing schedules, etc.
• Implementation of training in key procedures and processes to new market sectors
• Translation of documents into languages for new market sectors not covered in the pivotal clinical trials
• Embedding novel technologies (e.g. controlled thawing devices) at new clinical sites
• Bringing on-line additional manufacturing facilities to meet expected market demand

Stage 6 – Commercial Deployment

This stage of the process involves executing the developed commercial logistics platform, undertaking continual performance monitoring with a view to identifying points of failure (where and why) and where appropriate, implementing further mitigation strategies to correct these in real time. Additionally, once substantial volumes of data are generated, iterative review procedures can be started to identify opportunities to further streamline the logistics platform.

Conclusion

LbD gives therapy developers, for the first time, the tools to identify risks, utilise providers’ expertise, coordinate the solution, and create logistics platforms that connect their therapies to their patients at both clinical and commercial scale.

There may not be easy solutions to the challenges identified but having the knowledge and making data-driven based decisions early in the development lifecycle, will maximise the chance of developing commercially successful logistics platforms.

References

Full white paper reference: Ellison*, McCoy*, Bell, Frend, Ward (*Joint 1st Author), Logistics by Design – A framework for advanced therapy developers to create optimal Logistics Platforms, Cell and Gene Therapy Insights, Dec 2018, 1019 - 1039

For the full list of references, please download the white paper by entering your details in the form below.