Christophe Golenvaux

The current global economical and regulatory environment has led the biopharmaceutical industry to transform the clinical supply from oversight of a domestic, linear process into management of a complex network of global demand and supply lines, addressing additional challenges. New adaptive study designs, new target diseases, and global studies require on-demand packaging and labeling methods in order to keep operating costs under control. 

These challenges create significant opportunities for clinical supply chain to drive efficiency, lower costs, and reduce lead times for drug launches. There is an urgent need to set up and deploy integrated management solutions from investigative center opening to study closeout in order to streamline the entire clinical supply chain.  

Electronic good supply practices (eGSP) ensure that the supply chain, supported by integrated e-platforms, is safe and meets its intended use while guaranteeing full traceability and accountability. This article aims at simplifying some critical steps of parallel logistics processes to optimize operational challenges faced by clinical trial stakeholders and to achieve significant savings through process rationalization and data integration. 

Clinical research logistics have not evolved to keep pace with the outsourcing of activities to contract manufacturing organizations (CMOs), contract research organizations (CROs), central laboratories, centralized ECG, and bio-imaging providers. Even though the logistics processes for clinical trial materials do not vary significantly from study to study, the supply chain remains fragmented among various subcontractors and suppliers. This results in increased complexity, redundancy, higher costs,

  and even confusion at investigator sites. 

Despite the success of interactive voice/web response services (IXRS) facilitating the logistical issues surrounding the conduct of clinical trials, no efforts have been made to integrate the supply chain of investigational medicinal products (IMPs), sampling kits, and ancillary supplies. The eGSP approach is the turnkey to streamline the clinical trial supply chain and to provide all stakeholders with the required tools to manage a specific part of the supply chain or to give the complete overview and status of all aspects of the study. 

Beyond the business process and complexity issues, a lack of software integration and functionality/gaps also causes difficulties. Packaging operations are managed through an independent control system. The IXRS systems generating orders for clinical trial kits are not usually integrated with the planning processes, which are distinct from the systems used to manage internal and third-party production and distribution operations. 

New technologies are emerging to help pharmaceutical companies distribute medicines. E-platforms help share data securely and economically with suppliers around the world, analyze the data very rapidly, and respond to sudden changes in supply and demand, while advanced tracking technologies enable them to monitor products from the factory gate to the patient.

While several solutions are available, such as clinical trial management systems (CTMS), clinical data management systems (CDMS), enterprise resource planning (ERP), laboratory information management systems (LIMS), manufacturing execution systems, business intelligence, IXRS, and SAS business analytics software applications used in clinical development, most of these are isolated applications that do not share data, resulting in delay and poor data accuracy and data availability. 

Forecasting and inventory visibility challenges can also be attributed to the fact that the CRO—to which most of the trials are outsourced—usually does not share the same platform of applications and depends more on the IXRS to provide dynamic forecasts. Thirty-five percent of businesses recently surveyed by Gartner Inc. identified the inability to synchronize end-to-end business processes as an issue, which will increase demand for supply chain management application convergence.

  In the clinical research supply chain, we struggle with functional and application silos of each stakeholder, that make orchestrating and synchronizing business processes across the stakeholders nearly impossible. 

The key success factor to streamline the collection and exchange of data is the development of secure e-platforms for capturing, gathering, consulting, sharing, and tracking all study data. The real added value, therefore, comes from the development of the e-platform best suited to support each trial. eGSP incorporates the good practices of integrating electronically all information systems related to the supply chain in clinical trials. 

A range of internal stakeholders, including clinical operations, regulatory affairs, clinical quality, manufacturing and supply, and the qualified person (QP) are all involved in various aspects of ensuring adequate supply. Involvement of the right people who know the business is critical in the setup of an eGSP approach. Those from clinical operations, clinical supply chain, regulatory, and workers in the plants should be involved in the early stage of  trial development to review process maps and gather feedback on how the new system would operate. Typical stakeholders who should be involved in eGSP implementation are: 							

Project manager of each involved party (sponsor, CRO, CMO, central lab, core lab): coordinating study setup phases and seeking optimization of stakeholders' involvement

Production specialist: considers all aspects bound to production

Packaging specialist: focusing on packaging issues

Regulatory expert: ensuring all regulatory requirements are met

Warehouse manager: guaranteeing operational feasibility of deployment steps involving the warehouse

Distribution specialist: safeguarding distribution from a logistical perspective

Investigative site expert (e.g., head of CRAs): mastering all practical aspects bound to site staff involvement

Such stakeholders must have a clear operational view on their own business as well as a proven experience in the collaboration with other involved departments/vendors/CROs. 

The design of the clinical study protocol is a mandatory first step in the application submission and approval process of a clinical trial. It is the starting point and reference document throughout the entire duration of the study and details the background of the study, the objectives, the clinical design, Inclusion/exclusion criteria, treatment of subjects, reporting, data collection, and many other topics. Surprisingly, none of the topics from the protocol describe logistics, although one can consider the development of the study as a huge logistical process. While logistics operations might be out of sight, logistics is under significant pressure to deliver near-perfect performance under more complex, risky, and difficult business conditions. Many reconsiderations based on previous experiences demonstrate the importance of defining the logistics design sooner, if not already during the development of the clinical study protocol. This path becomes increasingly critical with the adoption of new study designs such as adaptive trials. 

When considering the percentage of logistics in the total cost of a project and knowing the current financial pressure on the pharmaceutical industry to reduce costs, it is urgent that all parties involved in the practical implementation of a study join their efforts in achieving the most cost efficient and seamless clinical supply chain. The eGSP is the best approach in this strategy, but how can it be ensured that this e-platform is set up in such a way that it allows for each specific clinical trial to collect and centralize the appropriate information at the right moment and in the most appropriate way? There is need to outline the supply chain processes of all materials (i.e., IMPs, sampling kits, biological specimens, ECG, bio-images, ancillary supplies) and to determine the roles and responsibilities of all parties involved in the "clinical supply protocol." The clinical study protocol brings together the clinical expertise and the logistics expertise and will allow the design of the optimal supply process for a study, ensuring operational and financial efficiency. 

For every item in the clinical study protocol, the supply chain implications are identified and fully described. This process should not be unilateral or separate, but should ideally be done in parallel with the clinical study protocol. Supply chain aspects could also influence some aspects from the protocol. 

The structure of the clinical supply protocol should be clear and practical: 							

Product stability, including packaging, storage, transport requirements

Product-related regulatory requirements (may influence the choice of participating countries)

Data format requirements (will determine barcode type, RFID)

Specimen types (can influence the choice of collection devices, storage, transport, and lab processes)

Reporting format (has an impact on the choice of reporting tools, definition of KPI's) and required ancillary supplies (can impact several site-related activities)

Data to be used by different parties throughout the logistics processes should be outlined in the clinical supply protocol. Typical supply chain aspects consist of production, warehousing, distribution/transport, and returns. For all these activities, specific quantifiable information (volumes, timelines, etc.) should be collected. Specific software tools used by the different subcontractors should be listed and their interface requirements with the e-platform identified. Finally, the roles and responsibilities of all stakeholders involved in the protocol supply chain should clearly be assigned and validated by each party. 

Based on such information summarized in a well-elaborated clinical supply protocol, the set-up of the project in the integrated e-platform will be an easy and smooth process. The framework of the clinical supply protocol provides a single, integrated landscape to manage the complete clinical supply chain by addressing all challenges faced by the different logistics stakeholders. 

Study conduct: From site opening to site close-out 

In an eGSP approach, upon availability of the clinical supply protocol, operational processes must be delineated step-by-step in order to ensure appropriate interaction between the following stakeholders involved: 							

The vendor(s) for data collection and patient randomization services (eCRF and IxRS)

The supply chain stakeholders (CMO, central lab, core lab)

The investigating center (investigator, study nurse, pharmacist)

There are three essential processes that are supported by integrated e-platforms to allow these stakeholders to best interact with an innovative eGSP approach: 					

The clinical supplies process supported by an e-platform is very comprehensive. According to their access rights, the e-platform will involve the related stakeholder to ensure clinical supplies, but also sampling kits and ancillary supplies are available on-site. The supply process starts with the involvement of the project manager (from the CRO or sponsor) to give a "green light" through the e-platform in order to release shipping orders.  

Once green light is given for an investigator site, a shipping order (built in a suitable format and according to a predefined structure) is sent to the CMO for automated integration into its system. A shipment date is associated with each shipping order and the site is immediately notified when the shipment will be performed. Just-in-time packaging and labeling is then carried out as well as the connote (air waybill) preparation. Shipment information (content and connote number) is confirmed in the e-platform that will promptly notify involved parties (sponsor/CRO and site). Shipment confirmation will also trigger a notification to the parties as well as the proof-of-delivery confirmation. The person on site responsible for receiving the shipment will be prompted to confirm shipment content and integrity (received in good state or damaged, correct quantities, etc.) by accessing the e-platform and completing the necessary online form. This will allow the CMO and project manager to be notified accordingly. Should some actions be required following the confirmation performed by site (e.g., goods received damaged), the e-platform will trigger appropriate notifications to the CMO and project manager, allowing a timely follow-up with the sites.  

Articles

eGSP-driven approach focuses on overcoming operational challenges through data integration.

Optimizing Trial Supplies Via Integrated e-Platforms

 The current global economical and regulatory environment has led the biopharmaceutical industry to transform the clinical supply from oversight of a domestic, linear process into management of a complex network of global demand and supply lines, addressing additional challenges. New adaptive study designs, new target diseases, and global studies require on-demand packaging and labeling methods in order to keep operating costs under control.

These challenges create significant opportunities for clinical supply chain to drive efficiency, lower costs, and reduce lead times for drug launches. There is an urgent need to set up and deploy integrated management solutions from investigative center opening to study closeout in order to streamline the entire clinical supply chain.

Electronic good supply practices (eGSP) ensure that the supply chain, supported by integrated e-platforms, is safe and meets its intended use while guaranteeing full traceability and accountability. This article aims at simplifying some critical steps of parallel logistics processes to optimize operational challenges faced by clinical trial stakeholders and to achieve significant savings through process rationalization and data integration.

 and even confusion at investigator sites.

Despite the success of interactive voice/web response services (IXRS) facilitating the logistical issues surrounding the conduct of clinical trials, no efforts have been made to integrate the supply chain of investigational medicinal products (IMPs), sampling kits, and ancillary supplies.

The eGSP approach is the turnkey to streamline the clinical trial supply chain and to provide all stakeholders with the required tools at their fingertips to manage a specific part of the supply chain or to give the complete overview and status of all aspects of the study.

Beyond the business process and complexity issues, a lack of software integration and functionality/gaps also causes difficulties. Packaging operations are managed through an independent control system. The IXRS systems generating orders for clinical trial kits are not usually integrated with the planning processes, which are distinct from the systems used to manage internal and third-party production and distribution operations.

Forecasting and inventory visibility challenges can also be attributed to the fact that the CRO—to which most of the trials are outsourced—usually does not share the same platform of applications and depends more on the IXRS to provide dynamic forecasts.

Thirty-five percent of businesses recently surveyed by Gartner Inc. identified the inability to synchronize end-to-end business processes as an issue, which will increase demand for supply chain management application convergence.

 In the clinical research supply chain, we struggle with functional and application silos of each stakeholder, that make orchestrating and synchronizing business processes across the stakeholders nearly impossible.

The key success factor to streamline the collection and exchange of data is the development of secure e-platforms for capturing, gathering, consulting, sharing, and tracking all study data. The real added value, therefore, comes from the development of the e-platform best suited to support each clinical trial. eGSP incorporates the good practices of integrating electronically all information systems related to the supply chain in clinical trials.

A range of internal stakeholders, including clinical operations, regulatory affairs, clinical quality, manufacturing and supply, and the qualified person (QP) are all involved in various aspects of ensuring adequate supply. 

Involvement of the right people who know the business is critical in the setup of an eGSP approach. Representatives from clinical operations, clinical supply chain, regulatory, and workers in the plants should be involved in the early stage of clinical trial development to review process maps and gather feedback on how the new system would operate.

Typical stakeholders who should be involved in eGSP implementation are:

Project Manager of each involved party (sponsor, CRO, CMO, central lab, core lab): coordinating study setup phases and seeking optimization of stakeholders’ involvement

Production Specialist: considering all aspects bound to production

Packaging Specialist: focusing on packaging issues 

Regulatory Expert: ensuring all regulatory requirements are met

Warehouse Manager: guaranteeing operational feasibility of deployment steps involving the warehouse

Distribution Specialist: safeguarding distribution from a logistical perspective

Investigative Site Expert (e.g., head of CRAs): mastering all practical aspects bound to site staff involvement 

Such stakeholders must have a clear operational view on their own business as well as a proven experience in the collaboration with other involved departments/vendors/CROs.

The design of the clinical study protocol is a mandatory first step in the application submission and approval process of a clinical trial. It is the starting point and reference document throughout the entire duration of the study and details the background of the study, the objectives, the clinical design, Inclusion/exclusion criteria, treatment of subjects, reporting, data collection, and many other topics. Surprisingly, none of the topics from the protocol describe logistics, although one can consider the development of the study as a huge logistical process. While logistics operations might be out of sight, logistics is under significant pressure to deliver near-perfect performance under more complex, risky, and difficult business conditions.

One would think that involving the supply chain so late in the picture of designing a trial is barely believable. Many reconsiderations based on previous experiences demonstrate the importance of defining the logistics design sooner, if not already during the development of the clinical study protocol. This path becomes increasingly critical with the adoption of new study designs such as adaptive trials.

When considering the percentage of logistics in the total cost of a project and knowing the current financial pressure on the pharmaceutical industry to reduce costs, it is urgent that all parties involved in the practical implementation of a study join their efforts in achieving the most cost efficient and seamless clinical supply chain. The eGSP is the best approach in this strategy, but how can it be ensured that this e-platform is set up in such a way that it allows for each specific clinical trial to collect and centralize the appropriate information at the right moment and in the most appropriate way? There is need to outline the supply chain processes of all materials (i.e., IMPs, sampling kits, biological specimens, ECG, bio-images, ancillary supplies) and to determine the roles and responsibilities of all parties involved in the “clinical supply protocol.” The clinical study protocol brings together the clinical expertise and the logistics expertise and will allow the design of the optimal supply process for a study, ensuring operational and financial efficiency.

The structure of the clinical supply protocol should be clear and practical: 

Product stability, including packaging, storage, transport requirements 

Product-related regulatory requirements (may influence the choice of participating countries) 

Data format requirements (will determine barcode type, RFID) 

Specimen types (can influence the choice of collection devices, storage, transport, and lab processes) 

Reporting format (has an impact on the choice of reporting tools, definition of KPI’s) and required ancillary supplies (can impact several site-related activities)

Based on such information summarized in a well-elaborated clinical supply protocol, the set-up of the project in the integrated e-Platform will be an easy and smooth process. The framework of the clinical supply protocol provides a single, integrated landscape to manage the complete clinical supply chain by addressing all challenges faced by the different logistics stakeholders.

Study conduct: From site opening to site close-out

In an eGSP approach, upon availability of the clinical supply protocol, operational processes must be delineated step-by-step in order to ensure appropriate interaction between the following stakeholders involved: 

Diagrams below illustrate three essential processes that are supported by integrated e-platforms to allow these stakeholders to best interact with an innovative eGSP approach:

The e-platform to be built and deployed will become the single point-of-access for all stakeholders involved in the study and should, therefore, not only integrate data from different systems but also work in a very proactive way, allowing prompt reaction in due time by the relevant party.

 shows the comprehensive clinical supplies process supported by an e-platform. According to their access rights, the e-platform will involve the related stakeholder to ensure clinical supplies, but also sampling kits and ancillary supplies are available on-site. The supply process starts with the involvement of the project manager (from the CRO or sponsor) to give a “green light” through the e-platform in order to release shipping orders.
    
    Once green light is given for an investigator site, a shipping order (built in a suitable format and according to a predefined structure) is sent to the CMO for automated integration into its system. A shipment date is associated with each shipping order and the site is immediately notified when the shipment will be performed. Just-in-time packaging and labeling is then carried out as well as the connote (air waybill) preparation. Shipment information (content and connote number) is confirmed in the e-platform that will promptly notify involved parties (sponsor/CRO and site). Shipment confirmation will also trigger a notification to the parties as well as the proof of delivery confirmation. The person on site responsible for receiving the shipment will be prompted to confirm shipment content and integrity (received in good state or damaged, correct quantities, etc.) by accessing the e-platform and completing the necessary online form. This will allow both the CMO and project manager to be notified accordingly. Should some actions be required following the confirmation performed by site (e.g., goods received damaged), the e-platform will trigger appropriate notifications to the CMO and project manager, allowing a timely follow-up with the sites.    
    
    The aforementioned process will only be enabled if all e-systems are fully used and integrated and if all steps are first thoroughly identified to ensure smooth and efficient implementation in the custom-made e-platform; this is the essence of an eGSP solution.

 depicts another critical step in eGSP implementation: patient material/ record collection. Building an e-platform should not be restricted to the management of IMPs; sampling kits, ancillary supplies, and any other material deemed necessary to conduct a clinical trial should also be considered when building the e-platform. As demonstrated in the diagram, a direct link between investigating staff and the whole supply chain is enabled. After linking the patient material/record with the patient demographics collected in the eCRF, the e-platform will generate a consistent e-requisition form to each supply chain vendor. In addition, the e-platform will automate stock level checks on-site and generate, when needed, re-supply orders. After processing of collected material by the central lab and core lab, their outputs (e.g., lab results) are integrated into the e-platform (e.g., after upload), so that both project manager and site staff are notified about the results.

 shows the IMP prescription (and re-supply) process and its tight link with the clinical supplies process. This process is involved at critical study phases: patient randomization and follow-up. 

Depending on the study conduct phase, one of the processes described above will be involved. The typical study conduct phases are:

 consists in granting access to the sponsor or CRO project manager to give the site regulatory green light through the e-platform. Once confirmed, the site will be virtually opened and all study stakeholders will be notified accordingly. Site opening will then automatically trigger the clinical supply process (see Diagram 1).

 is performed by investigational staff through the eCRF section of the e-platform, triggering notifications to the project manager and allowing a tight link with the patient material / record collection process. (see Diagram 2)

 is a critical phase allowing site staff to allocate a patient to the right treatment arm. For an enhanced interactive eGSP approach, the use of an eCRF with embedded IWR system will be preferred. Once the patient has been randomized successfully, automatic notifications to the project manager and to the supply chain as well as a seamless link with IMP prescription and patient material/record collection processes will be enabled.

New adaptive study designs, new target diseases, and global studies require on-demand packaging and labeling methods in order to keep operating costs under control.

Christophe Golenvaux

Articles

Optimizing Trial Supplies Via Integrated e-Platforms

eGSP: Operational Approach for Optimization of Clinical Trial Supplies Through Integrated e-Platforms