A review of the Drug Safety process from a Lean Perspective
Drug Safety Departments
By Robert Burke & Patrick Lucansky of the VIPGroup
Drug Safety (Pharmacovigilance) is the practice of receiving, reviewing, assessing and reporting adverse events from drugs produced and administer during the different phases of clinical trails and post-marketed studies. The main objective of Pharmacovigilance is two-fold; (1) Legislative Compliance, Periodic Safety Updates, Registration, SERM, Product Safety Updates, CIOMS and Medwatch and (2) Protect the patient and the company. The Center for Drug Evaluation and Research (CDER) in the United States is responsible for evaluating the safety profiles of drugs available to American consumers throughout the life cycle of these drugs.
They maintain a system of post-marketing surveillance and risk assessment programs to identify adverse events that did not appear during the drug development process while using this information to identify drug safety concerns and recommend actions to improve product safety and protect the public health. Activities include updating drug labeling, providing more information to the community, implementing or revising a risk management program, and, on rare occasions, reevaluating approval or marketing decisions.
The Drug Safety department of a major pharmaceutical company came under an external regulatory audit for compliance of adverse events and periodic reports. Adverse events had doubled during the last two years while staffing levels remained unchanged. The audit findings conclude the department was delinquent on better than 75% of 15 day reportable adverse event submissions, data collection and integrity was weak, databases not validated, training systems were inadequate and periodic reports were incomplete and late.
Further, the audit pointed to a clear lack of quality checks in the process, a deficient SOP process, poor adherence to existing SOP’s, a non-existent signal process and an overburdened staff. The regulators issued a 483 warning letter requiring a 90 day period to correct the violations.
The Typical Response
Most companies at this point huddle with key executives to map out their response strategy which often includes many of the following actions:
As the pendulum swings from minimal compliance to SOP’s to extreme compliance with very limiting rules and regulations governing operations, department staffing often grows in size from 20-30 to well over 200 resulting in increased costs of labor, materials and time. Increased outlays of capital are expended for the additional labor, training, and the new adverse events database. The new database is generally seen as a “silver-bullet” towards improved reporting compliance. A global presence can further exacerbating these issues by compounding the expenditures 2 and 3 fold. Interestingly, lead-times for the 15 day AE reportables often get longer as a result of the increased number of quality reviews and hand offs.
Seem unrealistic? We have witnessed many of these responses and results from some of the most prominent pharmaceutical companies around the world. It becomes compliance at any cost or at least a very high cost. From an analysis of 20 major pharmaceutical firms, other issues which complicated the matter are:
The number of process steps necessary to complete a report can grow from 20-30 to 200500. Quality is not markedly improved and often times becomes worse. Lead-times, while improved at first, can grow and exceed pre-audit times thus making compliance worse. Stress and workloads increase dramatically while efficiencies drop.
The best method to resolve these issues is to apply the Lean tools and techniques prior to hiring more staff and purchasing expensive databases. However, many times the need for change is so urgent, companies will respond first with costly fixes and hope to reign in the process later. Either way, lean techniques can certainly provide the Drug Safety department with the necessary tools and applications to maintain compliance achieve high levels of quality and ensure trained staff members without the major capital expenditures we typically see with first responses.
Having a vision of Lean Pharmacovigilance is an essential first step in the transformation process (see Figure 2). In order for a company to deploy a Lean approach to Pharmacovigilance, we must first understand Lean concepts. We define Lean to be “delighting the customer through a continuous stream of value adding activities,” …where an organization “adheres to the highest standards of business performance as measured by the customer. In other words, value is always defined from the customer’s perspective.
Understanding your customer’s needs (in this case, the customer is also comprised of regulators) is a prerequisite for driving Lean principles and methodologies. From the time a customer need is recognized until it is satisfied, the process and all its elements must add value for the “value stream” to be meaningful (see figure 3).
The basic component of this Lean system is waste elimination through the application of a four step process:
Analyzing the process and systems – where root cause analysis is preformed,
Root Cause Analysis
Identifying the root cause of a problem is a difficult and often painful exercise. As a result, we often treat the symptom rather than address the real issue. Needless to say, in providing health care, we may not always know the cause or the cure, but when dealing with processes, we can always get to the root cause and find an optimal solution.
The main reasons organization’s fail to achieve root cause identification is the time required to perform an analysis, lack of internal resources, lack of understanding of value-add versus non-value add and finally, the need to react and implement an adjustment to answer the regulator's concerns. This becomes a self-fulfilling prophecy as the FDA often times is satisfied to see traditional solutions applied.
Value stream mapping (VSM) is an essential tool to understanding the situation at hand and to identify the complicating factors. VSM (See Figure 3) provides a visual picture of the processes, with accompanying metrics, staffing levels, bottlenecks, cycle times, volumes, customer demands and input variations. These maps are the essential ingredient in moving towards a process cure and an organizational understanding of “where the organization is today”.
With the root cause analysis complete through value stream mapping, a three step process is deployed to resolve non-compliance and simplify the process. First, the process is analyzed for critical path cycle times. Comparisons are made between current actual times and required times. A word of caution, required times are those times as specified by the customer (regulatory bodies) not your internal interpretation of the regulator's needs. This is a key issue to understanding the magnitude of change required in the processes. Second, a value added analysis is performed by identifying process steps as value added, non value added or sustaining.
Once an understanding of which activities do not add value or meet regulatory requirements, but are in the critical path of compliance, can you then eliminate them, leaving only value added and sustaining activities. The third step is to reduce, improve, and/or eliminate the sustaining steps through experience or technology, leaving a final “To-Be” process of optimal activities designed to deliver compliance, quality and customer service. With the new process designed, investigate and address any affects the new process may have with other processes or departments or organizations.
The purpose of integration is to ensure the new process does not adversely affect other processes or departments, thereby reducing the organization’s ability to be compliant and Lean. For example, if the new process requires that the regulatory department must install a special sub-process with additional staffing, then you have not been diligent in the redesigned process. Spend all the time necessary talking and communicating with personnel about Lean compliance and the new process, and spend no time discussing returning to the old process. Be aware, departments or groups who have been removed from the critical path may attempt to move the process back to the original format.
This should be the last step in the process. Often, companies move toward this stage first, before the root cause and value added analysis have been completed. By simplifying and integrating the process first, automation may not be needed. If automation provides an enhanced solution, the results will be longer lasting and more business effective.
All the bells and whistles associated with an off-the-shelf solution may not be needed; in fact, many companies find that spreadsheets often suffice saving millions of dollars in capital expenditures and countless hours of human capital. A word of caution, if a process is automated to a 'predetermined solution', or an 'off the shelf package', the solution should not force any change in the new process, in order to match the solution. This would undue all of the great progress achieved and may cause additional compliance concerns.
Combining Lean thinking with Pharmacovigilance can provide organizations with many positive results that are both financial and operational. Typical improvements realized are:
The Transformation requires a ‘Paradigm Shift’
Lean Pharmacovigilance occurs when an organization delivers performance excellence within its’ regulated environments, where effective processes are both compliant and cost efficient. Service, responsiveness, efficiency, information capture and compliance performance can be improved together through the application of Lean techniques.
The result is a perfect balance between improved service levels, quality and cost performance in parallel with improved compliance performance. Lean Pharmacovigilance builds on the principles of Lean thinking to realize the benefits of aligned and effective processes. Creating efficient cost effective processes adds value to the organization, resulting in rapid response to marketplace and regulatory requirements.
For question or comments relating to the article or Lean tools and techniques, please email authors.
VIP is an operations improvement consulting firm specializing in the delivery of value through implementation of Lean Manufacturing and Supply Chain Management tools and techniques in a variety of industries from discrete parts to continuous flow, from distribution to assembly, from aerospace to pharmaceuticals. We have enjoyed equal success deploying these tools and techniques in non-traditional settings like offices, regulated environments and retail settings.