By Ted Fuhr and Katy George, McKinsey & Co.
As we are constantly reminded, Quality by Design (QbD) has come relatively late to the pharma sector. While other manufacturing industries have routinely focused their quality efforts upstream since the mid 20th Century, many drugmakers stuck firmly to an approach that relies on downstream inspection and control processes to keep sub-standard product out of the supply chain.
In our work with pharma companies, we have seen a fundamental shift in attitudes to QbD over the past five years. At the beginning of that period, most companies were familiar with the term “QbD,” but more often than not they worried that the process would be too technically challenging to implement in their own lines, that inconsistent regulatory frameworks would make it difficult to gain approval for the approach, or that QbD would simply cost too much to be worthwhile. As a result, few had experimented with the concept.
Today, many companies have a much better idea about what QbD actually means for them. There is common and widely published industry understanding of the technical aspects and tools that underpin QbD and most companies have at least attempted to introduce QbD principles into their own processes on a pilot basis. During 2008 and 2009, the FDA’s Office of Pharmaceutical Sciences received 99 initial applications that it considers “QbD related,” around 10 percent of the 980 total applications across new drugs, biologics and generics.
Barriers and Challenges
Significant barriers remain, however, to the widespread adoption of QbD. Some of these relate to regulation, and there is no doubt that the FDA, and other regulators across the world, have work to do in order to improve the guidance they offer to companies embarking on QbD efforts, and the efficiency and consistency with which they handle QbD applications.
Other challenges, however, are firmly rooted in internal company issues. It is here that we believe many pharma companies could make significant strides. Indeed, the companies we speak to that have made the most progress in QbD implementation consistently tell us that, although greater regulatory support would be welcome, they would continue with the effort regardless.
Let’s look at the three most important internal challenges in turn. First, there is still skepticism in some quarters about the business case, with some executives dubious that QbD efforts will pay back, either in terms of improved product quality and risk mitigation or reductions in production cost.
Second, executives often complain about a lack of internal alignment. Delivering the value of QbD efforts requires support right across the organization, from R&D to regulatory affairs to manufacturing, but each function must be committed to making the changes required in its operating model—including changes to the way site manufacturing and quality functions operate.
Third, some companies, particularly smaller ones, are concerned that they simply don’t have the capacity to perform the technical work required to deliver the QbD approach.
Reinforcing the Business Case
When we interviewed over 20 pharma companies about their attitudes and approaches to QbD last year, just over half of them said they saw a solid business case for the approach. Their comments also did much to address the concerns of the large minority that were not yet convinced.
In particular, enthusiasts were quick to debunk the two most common challenges laid at the door of QbD: that is it expensive and that it delays drug launch programs. In fact, our research revealed the additional marginal cost of starting a QbD program to be less than $1 million, while most participants even expected their QbD efforts to drive development costs down in the long run.
On timing, the research showed that, among companies with successful QbD programs, additional effort required during the initial clinical phase of drug development was negligible, amounting to around 6 person-days of effort. Importantly, this extra effort did not affect the critical path of the development program, and even helped to reduce the time spent in the technology transfer and scale-up phases.
Overall, we estimate that the combined advantages of QbD—reduced costs, improved productivity in the technical development phase, reduced quality risks and increased sales from faster, smoother product launches—could deliver a 10 to 20 percent reduction in cost of goods sold to the pharma industry. (Read more on these projections here.)
Compelling as it can be, simply reiterating the business case is not sufficient to get an organization aligned around a QbD effort. To that, companies must embark on a wide-ranging and sustained change management effort. Such efforts can take different forms, but the most mature QbD organizations we have seen tend to share some common characteristics. These include strong support for the program from senior leadership, rigorous, standardized development tools and processes, and close cooperation between R&D and operations, with common incentives and a common culture of continuous improvement.
At least one leading firm now considers product development to be part of its manufacturing function from the phase II clinical trial stage onwards. Other companies have introduced formal partnering processes between R&D and operations from the same stage. Finally, successful organizations typically make a concerted effort to acquire or develop the new talent and capabilities they need to support their QbD efforts.
The best way to overcome concerns about the technical challenges of QbD is to try the approach in a controlled, small-scale trial. Our research found that executing development under a QbD paradigm is at worst neutral versus traditional development, but most companies say that they have reduced overall development cost under the paradigm. In fact, getting a QbD program started requires little actual out-of-pocket cost. Many have said that they got started with less than $200,000 (mostly spent on analytical equipment).
The actual tools of QbD are free and available through multiple industry groups. The only true “cost” to get a program going is management time and thought to install new techniques and thinking into the development process. Getting started is the key. We have been told that once the new, company tailored processes are in place they just make sense to the frontline. “We should have been doing this all along” is a sentiment that we have heard many times. This creates passion within the organization around the program, which is a key first step in making it happen.
Building the tools, systems and culture needed to support the successful introduction of Quality by Design is not simple, but it does not require anything that is beyond they reach of any pharma company we have ever spoken to. Nor is success in QbD dependent the actions of regulators. We have little doubt that the regulatory framework for QbD will become much more straightforward over the coming years. When it does, it will be the companies that already have the foundations in place that will be best positioned to benefit from this revolution on product development and manufacture.
photo courtesy of nasaimages.org
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