Pharma companies must address the same group of stakeholders-customers, employees, shareholders-as any other industry, plus one more. Compliance with FDA and other regulatory agencies is not only critical for success, for some life science companies it determines their very survival.
Pharma companies must address the same group of stakeholders-customers, employees, shareholders-as any other industry, plus one more. Compliance with FDA and other regulatory agencies is not only critical for success, for some life science companies it determines their very survival. And yet, although compliance remains a cornerstone of doing business for pharma, clearly, some companies are better at it than others. Those that succeed do so because they expand their scope to include the organizational and process enhancements necessary to ensure that they meet both compliance and operational requirements efficiently and effectively. With that support in place, a company can achieve the systemic discipline required to satisfy FDA regulations. But achieving compliance can mean more than keeping regulators happy. It can also improve the bottom line. This article offers a case study that illustrates the specific tactics employed to achieve regulatory compliance and shows pharma companies how they can focus their efforts to reap the full benefits of compliance.
The demands of compliance are easy to understand, but its practice is complex and requires the coordinated effort of everyone in the company. The reasons for that are threefold. First, compliance permeates every stage of a long process-often more than ten years-from clinical trials to prescribed medicines. Second, functions such as documentation and investigation must be well conceived and practiced by every employee, every day, without exception. Third, total compliance can appear to conflict with business and market needs, creating situations that require integrity and accountability to properly resolve.
In a case that occurred several years ago, FDA sent a global pharmaceutical company a warning letter and several negative 483 notices (FDA inspection reports). Underestimating the amount of remediation required, company executives promised FDA that they would address all the issues in less than a year. They formed several teams to define and implement core compliance components such as validation, documentation, investigation, and corrective and preventive action (CAPA). Another team was charged with addressing the 483 notices.
Progress was slow. Members of the new teams struggled to juggle the new responsibilities on top of their regular workload. Some teams made decisions without consulting their stakeholders, only to have to return to the drawing board when major flaws became apparent. Soon the deadline arrived without concrete improvements. When the company had to ask FDA for more time, management decided to reconsider its approach.
With advisory help, company leaders identified several problems with their original approach. They saw that the lack of interdepartment communication resulted in misunderstandings and poorly conceived methods. Many employees were unaware of the compliance effort. And even those who knew of the effort had no clear direction and had difficulty giving it enough attention and support. Team leaders lacked accountability for results, often citing problems with other departments or teams for their own delays. Lacking common metrics and reporting mechanisms, management also found it difficult to track progress.
To address those problems, company executives and consultants outlined a clear strategy for implementing a quality system. While the initial teams continued to focus on validation, CAPA, documentation, and 483 items, management paid great attention to the people, process, and strategic issues involved in supporting the teams.
People. In company meetings, newsletters, and other communications, management reiterated that implementing a compliance system was the highest priority for all employees. The company also created a quality policy, and top management led interactive sessions with employees to reinforce those values.
Second, management established clear lines of communication by setting up an executive level, cross-functional steering committee to demonstrate support for the compliance effort and to bring visibility and resolution to important issues. The company also instituted a management review process to formalize key flows of communication from the bottom of the organization to the decision makers and back down again. Weekly meetings at the staff and director levels focused on key topics such as validation, documentation, and employee accountability.
The third step was to promote accountability. Management conducted cross-functional awareness and training sessions for directors and those who reported to them. The purpose was to collaboratively develop responsibility and relationship networks that cut across the departments involved in system-level compliance. Those networks educated employees about the comprehensive set of compliance-related activities and raised awareness of the inter-departmental cooperation and coordination required. From those networks, the directors and their staffs were able to clearly define their responsibilities in the context of the entire organization.
Process. At the same time it was motivating its people and culture, the company also evaluated its core processes to minimize roadblocks and systemic breakdowns. First, it dedicated a competent and well-respected project manager to oversee the entire initiative. He kept track of the disparate initiatives through a master project plan, including actions needed. The manager also created a series of key performance metrics to gauge the progress of the implementation project across multiple dimensions and communicated those metrics at weekly meetings.
The company's next move was to establish cross-functional teams to map core processes such as production, packaging, and materials management and to identify both compliance and operational issues that needed improvement. The teams prioritized those issues and opportunities based on customer safety, business impact, and speed and ease of implementation, then aggregated them into action items. Steering committees tracked the completion of each item. From the original "as is" process maps, the teams reconvened to create "should be" or future maps to guide the process improvement effort.
In one case, mapping the documentation process revealed long document approval delays. The team identified the review and approval stages as major bottlenecks and suggested several improvements. It redesigned the "should be" process to convene key stakeholders in a preliminary discussion about the document in question. That preliminary meeting shortened the review process because consensus between stakeholders was achieved before the document entered the system. The team also decreased the number of reviewers and approvers to an essential list, further streamlining the approval process.
Additionally, it encouraged directors and managers to promote a culture of continuous improvement within their groups. One tactic was to establish a policy of rewarding employees for bringing compliance-related problems and solutions to the attention of their supervisors. All employees were trained in root cause analysis and problem solving skills to solidify their ability to participate in the continuous improvement effort.
Strategy. People and process enhancements were not enough. The company also strove to approach compliance more strategically. Managers assessed the compliance risk exposure and determined that the company produced more than ten products at the same facility in varying quantities. They realized that each product had a unique compliance risk, and so they weighed the potential revenue against the compliance risk for each. The analysis revealed that certain older and lower-volume products failed to contribute enough in profits to warrant the compliance risk, so the company discontinued them. That left it with a smaller number of high-volume and high-value products on which to focus its compliance efforts.
The company also minimized overall compliance risk by launching several initiatives to prepare for an FDA inspection. It set up an audit response team and protocols and ran frequent mock audits to flush out areas of risk. Because they were likely to be included in a future audit, the company also ensured that it addressed all 483 issues with objective evidence.
As the case study suggests, addressing compliance issues requires deep involvement in cultural and process issues that may not be initially apparent. There are many examples of unsuccessful implementation of quality systems-often resulting from poor integration and coordination across departments and a lack of executive support.
Elan signed a consent decree with FDA last May after six years of repeated good manufacturing practices (GMP) violations, and Wyeth-Ayerst Labs executives signed a consent decree-allowing FDA much greater scrutiny of its operations-after three warning letters in five years. The problem was not that those companies did not attempt to achieve compliance, but that they did not expand their approach to include the people and processes within all systems across pharma operations.
Initial efforts to achieve compliance are often reactive and superficial because they do not get to the root of the problem. Companies need to approach compliance proactively and systematically to strengthen core elements in support of a long-term commitment to quality and operational excellence.
By focusing on people, processes, and strategy in advance of an upcoming inspection, companies can improve their bottom line through uninterrupted production and the ability to bring new drugs to market more quickly with less waste. Another long-term benefit is the creation of a more flexible organization that is able to react to production problems and market or regulatory changes as they occur. Because of its immediacy and visibility, companies can use compliance as a platform to initiate system-wide change with results that extend well beyond compliance.