By Alícia Tébar Pérez and Antoni Ruiz Puigdomènech, dTC Consulting

The new vision of quality driven by ICH — embodied by the concept of Quality by Design or QbD — is changing many things in the pharmaceutical world. This change can be illustrated by the way that companies plan and perform development and marketing of their products.

ICH guidelines Q8, Q9 and Q10 have tried to define a new regulatory framework for companies adopting QbD strategies. But we have to take into account that the QbD initiative was born in the U.S. The fundamentals of QbD were outlined in 2002, when FDA issued its Pharmaceutical GMP´s for the 21st Century document. And while ICH guidelines are intended to have a global impact, they are still subject to local regulations and interpretations.

Therefore, while the regulatory framework to allow manufacturers to develop or improve their processes with QbD is fully defined within the U.S., E.U. and Japan, practical implementation is much different within each. From the European perspective, the implementation of QbD is lengthy and troublesome.

I don’t believe that this perception is shared by American manufacturers. To find out, we are currently conducting a survey to collect more information from companies on both sides of the Atlantic about their positive or negative experiences in QbD implementation. Some of the initial data from E.U.-based manufacturers is below, and we hope to share data from manufacturers around the globe with Pharmaceutical Manufacturing readers in the coming months.

One of the main differences between the U.S. and E.U. in terms of QbD may be that, in the former, FDA is very proactive in promoting QbD approaches with industry partners. In addition, FDA has been training its staff in the scientific disciplines necessary to evaluate and inspect activities in a QbD environment.

EMEA has been promoting QbD initiatives as well, and encourages European manufacturers interested to contact the Agency to establish the appropriate mechanisms of support and surveillance.

In spite of these efforts, in Europe we are far behind the U.S. in some aspects of QbD. There are companies that are still experiencing problems in applications to replace, for instance, a traditional HPLC-based control method with one based on NIR with multivariable processing.

On the other hand, EMEA has made a quick adoption of ICH Q9 and ICH Q10 to regional GMP regulations. Risk management nowadays is a GMP requirement, and there is a provision to change Chapter 1 of the EU GMP Guide in the coming months to include principal elements and concepts from Q10 into the GMP quality system definitions and requirements.

On the whole, however, it is apparent that any European company has sufficient elements to embrace QbD, but in practice continuous improvement is the “twilight zone”. Only a few companies have performed an ROI study to know the economic reward of redesigning a non-robust, low-capacity process that is generating many deviations and therefore many non-quality costs.

The preliminary results of the survey, from a sampling of approximately 25 E.U.-based manufacturers, seem to confirm these trends:

• 75% of respondents have a Quality Risk Management (QRM) process in place (ICH Q9)
• 60% have a Q10-like Quality System model in place
• 50% apply Design of Experiments (DoE) during development
• 25% are working on a Design Space
• 25% of respondents are deploying some form of Process Analytical Technologies (PAT).

The high scores in Q9 and Q10 indicate that quality systems are being adapted rapidly and that European companies have introduced a risk-based view in their activities without difficulty.

But the much lower scores in Q8 elements imply that the core of QbD is not being introduced as easily in development. Thus, the premise of “building quality into the design” is not being accomplished, as principal tools and concepts such as DoE, Design Space and PAT are being used by just a small percentage of companies. (And we have to consider that respondents to the survey are most likely people promoting QbD activities in their companies. In this sense, the survey may be “positive”-biased.)

As an initial conclusion, we could say that European QbD has a nice wrapping but a small gift inside. We hope to have more input from American companies in the coming months to test these first impressions and derive more significant results.

Editor’s Note: To participate in the dTC consulting survey on QbD, visit the dTC Quality by Design blog at http://www.qbd-dtc.com/.

About the Author

Alícia Tébar Pérez and Antoni Ruiz Puigdomènech are senior consultants with Development Team Consulting (dTC), based in Barcelona.