Improving the quality of clinical trials has emerged as a major strategic activity for Big Pharma, one where efficient management of a demanding set of regulatory requirements—not to mention mounting clinical and patient expectations—can have a positive impact on the bottom line. In the following "leading practices" feature, Pfizer outlines how it has employed a management tool first introduced in the automotive sector to enhance its ability to process reams of data from clinical trials to raise the quality of trial submissions, improve regulatory compliance, and avoid costly rework that ultimately impacts speed to market performance for new drugs.
Pharmaceutical companies are facing growing quality and compliance concerns because of the increasing complexity of clinical trials and substantial changes in the regulatory environment. To protect patient safety and improve the quality of drugs coming to market, Health Authorities are imposing more stringent requirements and higher levels of scrutiny on companies' compliance with rules and regulations. In 2011, the FDA issued more than twice the number of company warning letters compared to 2005. As a result of greater regulatory hurdles for drug approvals and the need to demonstrate medical differentiation from existing therapies, companies are executing more complex clinical trials in an increasingly cost constrained environment. These challenges have generated an industry-wide imperative to overhaul clinical trial processes in order to improve quality and operational efficiency.
Pfizer experienced the effects of these pressures as keenly as any other company. These challenges were compounded by changes in the company's operating model. These factors created an impetus to change the way it managed clinical trial processes and the approach to quality and risk management. As such, the company embarked on an organization-wide initiative to improve the overall quality of its clinical trials with the ultimate goal of protecting patient safety, adherence to protocols, and ensuring the integrity of clinical data.
One of the key tenets of this initiative is the application of a QbD approach to its clinical trial processes. The concept of QbD was initially developed by the management expert Joseph Juran in the 1970s and later applied to the automotive manufacturing industry. Juran believed that quality could be transformed into a process and that most quality issues can be directly attributable to the way in which quality of the final product was planned. In 2002, the FDA adopted the QbD approach to address quality concerns in the pharmaceutical drug manufacturing process and launched a new initiative called "Pharmaceutical CGMPs for the 21st Century: A Risk Based Approach." As stated in a recent guidance from the FDA, "Quality by design means designing and developing manufacturing processes during the product development stage to consistently ensure a predefined quality at the end of the manufacturing process," (FDA guidance "Q10 Quality Systems Approach to Pharmaceutical GMP Regulations). Pfizer has recently taken the innovative approach of applying QbD principles to its clinical trial processes.
QbD's foundational principle is based on a deep understanding of the process and knowledge of the risks involved. QbD leverages an integrated set of leading edge techniques to build quality into the process by determining critical-to-quality (CTQ) requirements and proactively managing potential risks that are common to the process. The QbD approach focuses on removing waste and reducing variability while driving higher levels of process predictability, excellence, quality, and compliance. This approach enables pharmaceutical companies to achieve sustainable bottom-line benefits, which include avoidance of costly and time consuming rework that can slow down submissions and impact pre-approval inspections. With this in mind, Pfizer is embarking on a broad initiative to apply these same principles to improve the quality of its clinical development processes, starting with the trial master file (TMF).
The redesigned global TMF process.