Manufacturing Must be Described Whether QbD or Not, say EMA and FDA

The two regulatory bodies launched a pilot programme in March 2011 to assess the chemistry, manufacturing and control elements of drugs made using production processes developed using quality-by-design (QbD) principles.

According to first conclusions from the pilot​ published this week, the agencies require the same level of detail in the manufacturing process description irrespective of the development approach.

This includes the necessity for process descriptions to “be comprehensive and describe process steps in a sequential manner including batch size(s) and equipment type.”​

On top of this, the agencies have said critical steps and points in manufacturing need to be identified, and all process parameters that have been demonstrated during development as needing to be controlled or monitored to ensure quality must be described.

However, though the pilot has seen the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) working together and harmonizing elements of market approval, there are still differences between the agencies requirements.

For example, the EMA requires a full description of the manufacturing process in all cases, whereas the FDA will accept a comparably detailed process description submission in place of a Master Production Record for branded drug product manufacturing.

Other Conclusions and Response​

Other conclusions reached by the two regulators include the expectations that applicants will: provide Quality Target Product Profile (QTPP) for the finished product, preferably in a table, and provide a list of Critical Quality Attributes (CQAs) for drug substance, finished product, and excipients along with a discussion of how the drug and excipient CQAs relate to the finished product CQAs.

This first assessment was observed by experts from the Pharmaceuticals and Medical Devices Agency (PMDA), Japan’s regulators.

The programme initially sought four applicants by March 2014 and, as of June 2013, it had received one NDA (new drug application) and two INDs (investigational new drug applications), Dr. Elaine Morefield of the FDA’s office of new drug quality assessment told this publication​.

The first drug to be approved under the scheme was Pfizer’s rheumatoid arthritis drug, Xeljanz, which the company said had been subjected to around 35 questions from the FDA, and 100 from the EMA, 19 of which being the same. Though the firm said there were some missed opportunities with the application, it said it would go through the process again willingly.