US and EU regulators have announced the release of a new joint question and answer document meant to provide insight into the first-ever parallel assessment of a marketing authorization application by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Background

The pilot program was first launched in March 2011 as a means by which both agencies could communicate review findings with respect to quality-by-design (QbD) elements of applications chosen for review.

QbD refers to purposeful pharmaceutical development in which quality is designed, rather than tested, into the end product. For example, a company with proper QbD systems would have reasonable assurance that all final products were of proper quality, while one without a QbD system would presumably need to test all final products to ensure they met quality standards.

Those QbD standards are primarily contained within the International Conference on Harmonization's (ICH) Q8, 9, 10 and 11 guidelines, which FDA, EMA and Japan's Ministry of Health, Labour and Welfare (MHLW) all recognize.

As most products now seek international market penetration, most notably in the US and EU, this now requires separate application reviews by both FDA and EMA. However, the pilot program is meant to advance a new model, one that allows for simultaneous review of certain aspects of the application-in this case, QbD elements-allowing for an expedited and more thorough review process.

Under the program, applications "are submitted to either both agencies at the same time resulting in a parallel evaluation, or either to EMA or FDA in which case the agency doing the evaluation obtains consultative advice from the other agency," EMA wrote in its Q&A document.

"This parallel assessment aids sharing of regulatory decisions and facilitates the availability of consistent quality pharmaceutical products throughout the US and EU," FDA wrote in a statement.

Initial Takeaways

With the initial assessment process now over, both regulators weighed in with preliminary conclusions. FDA said it found the process "useful," adding that it and EMA had "reached agreement on a wide range of QbD aspects." EMA mirrored FDA's assessment, saying that it was "extremely useful to share knowledge, facilitate a consistent implementation of the ICH guidelines and to harmonise regulatory decisions to the greatest extent possible."

While the question-and-answer section of the document is relatively short at just two pages, it includes advice for:

• submissions of Quality Target Product Profiles (QTPPs) and Critical Quality Attributes (CQAs) (both should be provided)
• the use of Key Process Parameters (not supported by ICH or FDA/EMA)
• expectations for manufacturing process descriptions (same comprehensive level of detail should be provided to regulators regardless of the approach used)
• the use of analytical target profiles (ATPs) for analytical methods (acceptable, though with certain qualifications)

Further conclusions are set to be published on "other QbD-related topics" as the pilot project continues with new batches of parallel assessments, FDA said, including design space verification, Design Space and risk assessment level of detail in submissions, continuous process verification and continuous manufacturing.

Improvements in the parallel assessment process have already been made, EMA added.

Q&A Document

FDA Statement

EMA Statement