Increased globalization of clinical trials has made effective management of the supply chain for clinical trial materials (CTM) an evermore crucial component of the drug-development process. The greater complexity inherent with increased globalization, combined with higher levels of outsourcing, has raised the bar in organizational and operational performance for CTM supply for both sponsor companies and contract manufacturers supplying CTM.
“The level of outsourcing in CTM supply is increasing due to a variety of factors,” says Robert Handfield, PhD, Bank of America University Distinguished Professor of Supply Chain Management at North Carolina State University, and director of the Supply Chain Resource Cooperative at North Carolina State University, Jenkins College of Management. Handfield will be speaking at the “Second Vetter Drug Management Leadership Conference: New Pathways in the Pharma Landscape,” which will be held in Lindau on Lake Constance, Germany, Sept. 23–24, 2009. “Pharmaceutical and biopharmaceutical companies are reluctant to increase internal headcounts and see increased outsourcing as means to reduce and manage costs,” he says. “In the face of increased numbers of clinical programs over the next two years, it is important for companies to evaluate and address problems in both clinical operations and the supply chain to avoid delays in the drug-development process.”
Handfield recently completed a clinical supply-chain maturity assessment to examine the current challenges and critical success factors in CTM supply. The study was based on a supply-chain maturity model. “Proper planning between clinical operations and supply-chain managers is critical,” says Handfield. The assessment analyzed input from clinical operations and supply-chain managers to understand the factors from each area that contribute to problems in CTM supply and the resulting delays in the drug-development process.Supply-chain managers point to several problems in clinical operations. These include: failure by clinical operations to provide accurate patient-enrollment forecasts; a lack of resources and capacity in clinical operations and distribution; a lack of processes and distribution lanes for new country distribution; and poor clinical visibility and interactive-voice-response-system (IVRS) performance.
In turn, clinical operations personnel point to several supply-chain weaknesses. A key problem relates to the increased globalization of clinical trials and the resulting problems in rest-of-world distribution management that cause delays in receiving CTM on time. These problems involve delays in the customs-clearance processes, a lack of distribution capacity, and poorly established distribution lanes. Other concerns in the supply-chain include poor planning processes in clinical contract manufacturing that can cause delays as well as long lead times for comparator sourcing.
Managers in clinical operations and supply-chain activities also point to some common problems. These involve the necessity of having to re-order production quantities of active pharmaceutical ingredients (APIs), leading to delays of trials; inherited small-molecule programs that are not well-developed that result in delays in trials; and difficulties in controlling shipping-temperature excursions. Effective cold-chain management is of growing importance as the level of biopharmaceuticals in clinical development increases.
“The poor handoff between clinical research, clinical logistics, and supply-chain managers is a reason for delays,” says Handfield. “Effectively managing the interface between clinical operations and supply-chain managers, whether it is done internally or through third-party suppliers in an outsourced relationship, is key.” To avoid these problems, Handfield recommends that regularly scheduled tactical forecasting and planning meetings be held to update clinical trials information and to ensure alignment between planning, contract manufacturing, and logistics. “Planning is a critical lynchpin in the clinical supply chain and relies on effective forecasting, communication, and capacity analysis,” he says. Using tools such as country-risk analysis to prioritize planning requirements and lead times in clinical trials and more importantly, establishing defined roles and responsibilities for staffing in pharmaceutical operations and technology and clinical operations is crucial. “There needs to be a discipline that is driven by metrics and changes in behaviors, with consequences for a lack of compliance to the planning process,” says Handfield.
Another cause for delay in CTM supply relates to securing internal approvals for sourcing and contract-manufacturing arrangements. “A lack of a framework and direction on approval rules and policies can cause undue delays,” says Handfield. To address these problems, Handfield recommends defining more clearly and streamlining the approval process through improved documentation, the use of contract-manufacturing and sourcing approval coordinators, and automation of the approval process.
Tools for improving the planning and implementation of clinical logistics are also valuable. “A common problem relates to missed deliveries to a clinical trial site,” says Handfield. “Time is spent in trying to determine what went wrong with a shipment, locating a shipment, and then trying to get the material delivered.” Limited use of capabilities of IVRS inventory and order tracking, poor coordination in notifying logistics of changes in schedules or trial locations, a lack of performance metrics for logistics, and inadequate resources for staffing and training in logistics are some common problems encountered in clinical logistics. Designing and building a logistics tracking and planning system that effectively uses IVRS capabilities for inventory control and replenishment is critical, says Handfield. Another important strategy is to establish local-country logistics-planning coordinators that can monitor market and government developments, manage local depots and supplier relationships, troubleshoot shipments, and supervise depots.
Vendor selection and metrics
As in outsourcing any function, the selection of a contract-service provider in CTM supply is a decision that involves proper due diligence based on financial, geographic, and performance criteria. Once a vendor has been selected, ongoing performance evaluations are essential. To evaluate CTM supply, a metric of increasing importance is that of the “perfect order,” which includes various criteria to measure customer satisfaction. “Perfect order means getting the right dose in the right quantity at the right temperature to the clinical trial site,” explains Handfield. Good planning and execution in a collaborative relationship among clinical research, clinical operations, and contract manufacturers or internal supply-chain staff are needed to reach that metric. It also is important to evaluate performance using a scorecard to provide a quantitative assessment of other factors such as quality, level of responsiveness, and service criteria.
In sum, proper planning, execution, performance evaluation, and review are essential elements in achieving the continuous improvement required to managing the changing CTM supply chain.