Insight | White Paper
Driving faster,
more effective
clinical trials
In this white paper
A critical step of the development chain: Clinical trial supply 3
Clinical trial supply challenges 3
How technology can help 5
Systems alone are not the solution 6
Life Sciences
| Clinical Trial Supply Management
Streamlining clinical trial
supply management
One of the most important factors in
successfully conducting clinical studies
is the efficient management of clinical
study supplies.
Insight | White Paper 3
Within the process of bringing a new drug to market, clinical development represents the longest and most cumbersome aspect of product development. Solutions that support collaboration and compliance in the manufacture and management of clinical trial supplies are key to the future growth of pharmaceutical and biopharmaceutical companies.
A critical step of the
development chain:
Clinical trial supply
Within the process of bringing a new drug to market, clinical development represents the longest and most cumbersome aspect of product development. Always time-consuming, clinical development is becoming more difficult due to an upsurge in the number of regulatory requirements (including a dramatic increase in the number of required patients), the advent of new technologies, and a growth in the overall complexity of most studies. In addition, because clinical develop-ment generally requires an average six to eight years to complete, its proc-ess alone can absorb up to two-thirds of a drug’s development budget. One of the most important factors in successfully conducting clinical studies is the efficient management of clinical study supplies (Figure 1). Not only does supply management require detailed monitoring, it requires precise planning and coordination of the activities of
many players, both within and outside a pharmaceutical company. Solutions that facilitate collaboration and compliance in the manufacture and management of clinical trial supplies are key to the future growth of pharmaceutical and biopharmaceutical companies. In this white paper, we will examine the key challenges surrounding clinical trial supply management and evaluate potential solutions available to pharmaceutical and biotechnology development organizations.
Clinical trial
supply challenges
At the outset of any clinical trial, the enterprise uses a standard formula— the number of participating patients at each site, multiplied by the number of doses administered daily, multiplied by the length of time of the trial—to calculate how much of the drug and placebo/comparator to make available to accommodate all patients for the length of the trial.
Figure 1. Clinical materials flow for clinical trials Life Sciences | Clinical Trial Supply Management
Study definition and design Patients and treatments Patients and treatments Patients and treatments Study site Study site Study site Clinical study local depot Clinical study local depot Clinical supply central depot Manufacturing and labeling Patient recruitment and enrollment
Number of patients, sites,
treatments/dosages Supplies forecast
En ro llm en t r eq u es ts Restock requests Restock requests Re st oc k r eq u es ts
Life Sciences | Clinical Trial Supply Management
“ Most states have every type of server
known to mankind. Most have multiple
e-mail systems and communications
systems. Those are issues that you have
to deal with as they impact a central
organization that provides network
support to all of them.”
Jim Dillon, CIO, New York State
If everything worked beautifully, that would be the end of the story as far as planning goes. But things generally aren’t that simple. Let us take a closer look at the three key challenges in clinical trial supply management: planning, manufacturing and distribution (Figure 2).
Planning
Effective clinical trials depend heavily on providing study supplies to various sites so that prescribed drugs are adminis-tered at the correct times throughout the study. If supplies run out (known as a “supply stock-out”), patients using the drug may be disqualified and the entire clinical study could be jeopardized. Forecasting supply stock-outs is difficult for a variety of reasons.
Patient recruitment can proceed at different speeds in the different study sites, resulting in “staggered” enroll-ment, with a fraction of the planned participants entering the study one week, additional patients coming on board during subsequent weeks, and patients being added or the study being extended over a longer period of time. Additionally, participants often drop out before the treatment is complete. As a result, some sites may enroll significantly more participants than others. How-ever, regulatory restrictions sometimes prohibit shifting delivered product from one test site to another.
Expiration dating also has an impact on supply management. Often, clinical supplies must be manufactured prior to the availability of medium- to long-term stability data. Clinical supplies may be produced and packaged with a “short date” and may subsequently need to be relabeled or discarded, requiring the manufacture of replacement materials. Delays or extensions in the clinical study may also result in expired supplies—again resulting in relabeling or additional manufacturing campaigns.
Manufacturing
The production of clinical supplies in most ways mirrors the production of commercial drug products. All operations and processes must be fully compliant with current Good Manufacturing Practices (cGMPs) and are subject to audit by regulatory agencies such as the Food and Drug Administration (FDA). Clinical supply manufacture faces a number of additional challenges that do not impact commercial drug supply chain operations to the same degree. These challenges include:
• The lack of adequate supply of the active pharmaceutical ingredient (API). • The necessity to manufacture
numerous small lots of the drug product.
• The reduced expiry dating due to lack of medium- or long-term stability data. • The manufacture of numerous dosage strengths, placebos and comparator products that all need to look alike but must be controlled as unique entities throughout the supply chain. This includes handling labeled and unlabeled materials that are “blinded” to the clinical site and patient. • An enhanced complexity in primary
and secondary packaging.
• The coordination of manufacturing, which may occur in a pilot plant or development laboratory, contract manufacturer site, and/or the commercial manufacturing site.
Figure 2. Clinical trial management process
Clinical study definition and design Patient recruitment and enrollment Forecast supply requirement Devise manufacturing campaign Order raw materials and packaging Receive/stage materials and packaging Label packaged product Inventory packaged product Package bulk product Manufacture drug product and placebo Inventory bulk product Dispense
to patient Inventory product at clinical site Inventory product at distribution center Inventory labeled product Ship product
Resupply requests Resupply requests
Planning
Manufacturing
Insight | White Paper 5
Distribution
Compliant shipment of the drug to many trial sites, which are often scattered in different countries, may seem simple, but it is difficult to achieve because there is the requirement to comply with Good Clinical Practices (GCP) and cGMP regulations.
Another challenge is tracking the drug throughout the value chain. In fact, it is essential to have a reliable and efficient accountability process in place so that unused drugs may be reconciled, returned and destroyed.
How technology can help
Technology may significantly streamline and improve the forecasting, manufac-turing and distribution of clinical trial supplies. Clinical trial demand is defined as the number of doses of the trial drug and placebo required for each planning period multiplied by the number of trial participants at that testing site. Demand should be placed at the testing sites, in defined time periods, and this demand is then aggregated to a regional distri-bution point. The aggregated demand forecast should be developed at this distribution point, rather than at the test site or the point of manufacture. By using this approach, the manufacturer can allow for distribution flexibility to meet requirement changes and also help commit materials to testing sites in the appropriate amounts on the neces-sary dates. The commitment of planned manufacturing orders and planned distribution must take place in time to meet the most recent demand placed at the distribution point. This commit-ment to planned demand supports just-in-time (JIT) packaging and labeling of bulk product to add flexibility in the supply chain.
Demand-planning applications aid greatly in the initial forecasting as well as subsequent adjustments and distribu-tion planning. Once created, the forecast is passed to a component application for supply chain planning that lays out the clinical trial requirements and corresponding distribution plan.
Supply chain planning applications evaluate demand requirements, taking into account the on-hand inventory, and create planned orders to cover the net clinical trial requirement. The output will be planned orders for manufacturing, purchase requisitions for to-be-purchased items, and a distribution plan for JIT distribution of the clinical trial materials to the various distribution points. Sourcing of clinical trial materials can be either fixed, using a single source, or dynamic using multiple sources. The use of dynamic sourcing will select a feasible sourcing plan that includes, when possible, material redistribution to the appropriate regional distribu-tion point to accommodate changes in demand due to fluctuations in patient participation at the testing sites. The advanced planning systems may also be used to perform safety-stock planning to ensure reasonable levels of availability. Any last-minute demand changes are updated in the planning process and resolved using interactive planning to create a new demand-supply scenario. Rough-cut capacity planning helps establish and maintain manufacturing capacity and create supply chain alerts to warn proactively of date and material shortfalls. At the end of the planning cycle, the clinical trial planned orders and requisitions are committed to an enterprise resource planning (ERP) system for execution.
Manufacturing execution systems (MES) may be effectively used to manage the manufacturing, packaging, labeling and shipping activities to help maintain both product integrity and traceability.
Applications available to manage clinical trial forecasting, study management, manufacturing and distribution may be grouped into three major categories: • Advanced planning and scheduling
(APS) systems that perform forecast- ing and supply chain planning. • ERP systems that manage the
manufacturing and distribution of the clinical trial materials. • Clinical trial management systems
that perform these specific business processes: – Study management.
– Site management and collaboration. – Packaging and labeling.
– Batch records management. – Interactive voice recognition
systems (IVRS).
Some functionality, such as forecasting, may be performed by some or all three application categories. APS and ERP, for example, perform batch control and tracking. Other functionality is unique to clinical trial study management and has been developed by these vendors to perform very specific tasks.
It is clear that no single technology solution can manage clinical trial processes completely and effectively by itself. More advantageous than a single-vendor solution would be a combination of planning systems fully integrated into an ERP system and an MES application designed specifically for clinical trial product management.
Demand-planning applications aid greatly in the initial
forecasting as well as subsequent adjustments and
distribution planning.
Life Sciences | Clinical Trial Supply Management
Systems alone are
not the solution
Systems are merely tools to facilitate the clinical trial operation. The underlying business processes must be evaluated, improved and aligned. For example, if a company accurately forecasts its clinical supplies need for a three- to five-month time horizon, but the manufacturing lead time is 12 to 18 months, no soft-ware tool is gong to fix the underlying problem. By evaluating the underlying issues and redesigning the clinical supplies processes, the business can then use automated tools and systems to further streamline its operations. Leading practices for clinical trial management have shown that forward-thinking organizations seek first to: • Clarify the goals of clinical
trial management.
• Determine the core business processes required to reach these goals. Based on the business requirements of the processes, enterprise business management may evaluate applica-tions and systems and decide which technology would best support—and enhance—the processes.
Merely defining processes is not enough. Processes must be formalized as written procedures with clear roles and responsibilities for each person and group involved in the clinical trial supply processes and with clear time frames and metrics to verify that the procedures are followed. Additionally, the staff must be informed and trained on the new procedures. Finally, performance measures must be established to keep the organization on a path of continuous improvement.
The current road map for clinical trials contains numerous time-consuming regulatory requirements and over time, we expect additional regulations will make the process even more complex. BearingPoint believes that by crafting a sound strategy for sharpening internal processes and combining it with leading technologies and technology integration, the pharmaceutical enterprise can be prepared to deliver breakthrough drugs more efficiently and cost-effectively.
About the authors
Adriana Salvatore is a senior man- ager in the Life Science practice of BearingPoint Switzerland. She has more than 15 years of experience in the health care arena, gained both in the pharmaceutical industry and in consulting firms. She has a degree in chemistry and pharmaceutical technology and a degree in pharmacy from University of Rome-Italy, and an MBA from Henley Management College in the United Kingdom.
The current road map for clinical trials contains numerous
time-consuming regulatory requirements and over time,
we expect additional regulations will make the process
even more complex.
Don Parriott is a manager in the Life Sciences group at BearingPoint. He has more than 20 years of experience in the pharmaceutical industry, having worked in both the prescription and consumer health care business sectors and in positions within manufacturing and research and development. He has managed pilot plant and clinical supplies manufacturing operations, quality assurance organizations, and analytical research organizations. His B.S. degree in biochemistry is from Manhattan College, and he earned an M.S. in chemistry with a minor in business from Seton Hall University.
Mark Parry is a senior consultant in the Life Sciences group at BearingPoint. He has more than 30 years of experience in supply chain management, having worked in both the pharmaceutical and consumer products business sectors and in positions within manufacturing and distribution. He earned a B.S. degree in industrial management from Purdue University Krannert School of industrial management and an MBA from Indiana University.
BearingPoint believes that by crafting a
sound strategy for sharpening internal
processes and combining it with leading
technologies and technology integration,
the pharmaceutical enterprise can be
prepared to deliver breakthrough drugs
more efficiently and cost-effectively.
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