It was Dr. Janet Woodcock who introduced the concept of risk management to the FDA’s analysis of drug safety. She was first to envision the Life Science Manufacturing Sector which was reliant on the rationalised decision-making process, rather than an artistic decision-making process.
In 2004, US FDA’s Quality journey began with a report on “Pharmaceutical cGMPs for the 21st Century- A Risk-Based Approach”. The vision in this approach was then adopted in several ICH guidelines Q8(R2), Q9, and Q10 in later years. The term ‘Quality by Design (QbD)’ and its principles were first introduced in ICH guideline Q8(R2). As per this guideline, ‘QbD’ is, ‘a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management’. The guidelines related to QbD contain information on identifying QbD elements such as Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs) and Critical Material Attributes (CMAs). The QTPP and the CQAs can be together termed the key performance indicators (KPIs) which can be used to assess the efficacy and safety of the drug product inside the patient’s body. Since QbD is a risk-based approach, the FDA expects manufacturers to assess the root cause for every possible event of deviation from these (KPIs) and to identify the CPPs or the CMAs which cause this deviation. The manufacturers are expected to build a knowledge space around how these QTPP, CQAs, CMAs, and CPPs are inter-related. This knowledge space can be built using literature, know-how in similar products, empirical experiments, Design of Experiments, or any other statistical modeling approaches.
Soon after these guidelines were released, quality practitioners started evaluating this approach against existing quality management philosophies including Motorola’s ‘Six Sigma’. This was probably because of the recommendation to use statistical modeling approaches for product development as well. The Six Sigma heavily relies on statistical approaches for measuring and producing quality products too. In this article, we are going to compare Six Sigma and QbD to find out their similarities as well as differences.
Before we begin, let us also try to understand Motorola’s Six Sigma. The Six Sigma approach focuses on driving improvement projects by standardizing the defect measurement process. Six Sigma is a performance metric that corresponds to 3.4 defects per million units or opportunities. In addition to this Six Sigma also comprises of a management strategy for the organization-wide deployment of the improvement projects. The project selection process is based on the commercial potential of the proposed improvement project. For example, the management may want to take up only those improvement projects which can potentially save $1,000,000 Billion.
The task of project selection is assigned to sponsor or a Master Black Belt who generally leads the business unit. The sponsor is responsible for creating a team that comprises all the cross-functional stakeholders and a Six Sigma Black Belt who are together responsible for executing the project. The job of the Six Sigma Black Belt team member is to facilitate the implementation of Six Sigma philosophy in the improvement projects while that of the cross-functional team members is to provide their core expertise. All in all, the ultimate goal of a Six Sigma project is to improve the quality of a product, process or service and thereby save the cost of poor quality but it additionally provides for management principles to accomplish the goal. Below is an example of work structure in Six Sigma where Yellow Belts are cross-functional team members who are aware of Six Sigma methodology but not necessarily skilled in Six Sigma tools.
Based on the above description, we may conclude that the ultimate goal of a Six Sigma project is slightly different than the ultimate goal of the QbD project where the therapeutic efficacy of the product as well as patient safety are more important than the commercial success. However, following the QbD strategy will enable manufacturers to produce sustainable products as they would get lesser product recalls or import alerts. Therefore, although the QbD strategy was first envisioned for the benefit of the patients, it indirectly helps the manufacturers to make robust products that are less likely to be rejected, recalled, or fail. In fact, if QbD is implemented using the DMAIC (Define-Measure-Analyse-Improve-Control) philosophy of ‘Six Sigma’ then manufacturers can benefit from the best of both worlds. This can be done by using the following approach:
In conclusion, ‘QbD’ and ‘Six Sigma’ are the same concepts with slightly different end objectives. The Six Sigma approach focuses more aggressively on saving costs by reducing the cost of poor quality while the QbD approach being an FDA proposed quality management approach focuses on delivering the best quality product to the patient irrespective of cost-benefit to the manufacturer. In any case, if the manufacturers use Six Sigma philosophy to get the cost-benefit and structured approach for organization-wide governance of QbD principles, then they create a win-win situation for the patients as well as themselves.