With the dawn of the 21st century came the realization that changes must be made by both the pharmaceutical industry and regulatory authorities across
the globe. These changes are necessitated by a plethora of issues that are faced by companies and the regulatory agencies
alike. The number of blockbuster drugs launched each year has remained relatively constant at 6.5 per year (1). The nearly
threefold increase in R&D spending over the past decade has resulted in an increase in the number of drug candidates entering
Phase I trials. However, this increase has been almost completely neutralized by an increase in attrition, with the probability
that a candidate entering Phase I will become a successful product decreasing from 10% in 2002 to 5% towards the end of the
decade (1). This decline in success rate, along with the increasing scrutiny of healthcare costs in developed economies, has
resulted in unrelenting pressure on the pharmaceutical companies to control drug-development costs.
Anurag S. Rathore, PhD
On the other hand, regulatory authorities are also grappling with the increasing complexity of pharmaceutical manufacturing.
Most pharmaceutical products sold in the US are manufactured outside the US. Even for those drugs that are manufactured in
the US, a significant portion of the raw materials and process intermediates is imported from manufacturers outside the US.
It's no wonder that "Supply Chain Management," "Accountability in a Global Environment," "Foreign Inspections," and "International
Compliance" were some of the key sessions at the 2011 PDA/ FDA Joint Regulatory Conference. Implementation of quality by design
(QbD) in this environment has further contributed to the need to clarify what information needs to be included in a regulatory
filing and how it should be presented. FDA has addressed this gap to some extent through its ongoing QbD pilot program, but
more guidance is needed from the regulatory authorities to ensure widespread successful implementation of QbD (2).
Overall, the regulatory authorities must make changes to address the drug safety dangers that the global environment poses
as well as make changes to the drug review and approval processes to encourage regulatory and pharmaceutical innovation and
faster product availability to patients. Regulators also must offer more flexibility regarding manufacturing changes and application
supplements based on science and risk assessment, so that limited resources on both the industry and regulatory sides will
be available for drug development and innovation.
In this 28th article in the Elements of Biopharmaceutical Production series, the authors focus on the regulatory challenges that arise
in the QbD paradigm, in particular on how review and inspection practices have been and are evolving.