This month sees the close of the consultation on the application of Analytical Quality by Design to pharmacopoeial standards. We sat down with Peter and Stephen, pharmacopoeial scientists for the British Pharmacopoeia, to discuss why this consultation may prove vital to the future of pharmacopoeial standards and why stakeholders should take the opportunity to have their say.
On AQbD and Pharmacopoeial Standards
What is Analytical Quality by Design and why is the MHRA interested in it for Pharmacopoeial Standards?
Analytical Quality by Design (AQbD) takes a structured approach to the development of analytical procedures which are fit for purpose and that consistently deliver results that meet predefined objectives.
It achieves this through a detailed understanding of all aspects of the analytical methods performance ensuring adequate control and an ability to react to changes which can affect the quality of results.
The Agency is committed to safeguarding the quality of medicines for the public in order to ensure they work and are acceptably safe. At the MHRA, the British Pharmacopoeia sets the legal standards by which UK pharmaceuticals are measured. Decisions on whether these products are safe and efficacious are made based on data produced through our methods. It is therefore critical that these methods are suitable for all products throughout their lifecycle and that the results they produce are accurate, in order to ensure the continuous supply of high quality medicines. AQbD has the potential to aid these decisions through the application of the principles detailed in the technical summary published with the ongoing consultation.
This Agency project is unique in that it is a collaboration between all parts of the UK’s regulatory system, combining expertise from Licensing, Inspections and Standards as well as industry and academic partners. It also takes a pragmatic approach, generating real world test data to investigate various principles, supplementing existing theoretical understanding.
Case Study: Assay for Atorvastatin tablets
Why were the Assay for Atorvastatin tablets selected as the case study?
Atorvastatin tablets, a type of statin, were selected as the subject for this project because they are widely prescribed for long term management of high cholesterol and prevention of cardiovascular disease. Diversity in the formulations and manufacturing methods used for the available products also made Atorvastatin tablets an ideal candidate for this study.
Content is a critical quality attribute for any product and therefore Assay is fundamental for pharmacopoeial standards. The gradient based High Performance Liquid Chromatography (HPLC) procedure is also representative of a large number of procedures in the BP, allowing for the learnings of this case study to be further applied throughout the pharmacopoeia.
Impacts of Analytical Quality by Design
Is the goal of Analytical Quality by Design to have a “design space” for pharmacopoeial analytical procedures?
Analytical Quality by Design has many different benefits, it’s not just about a design space. We’ve already found a number of useful advantages which can be tailored to individual needs.
For example, the MHRA’s project has built an understanding of the Atorvastatin Tablet Assay procedures operable region. This region has been assessed to ensure that the method selected sits in a plateau of stability. This could be taken further to understand the edges of failure and implement specific elements of control to ensure robustness in use.
The project report seems to contain a substantial amount of work, could AQbD be too labour or time extensive to implement?
Developing an analytical procedure using Analytical Quality by Design is perceived as having a greater cost when compared to traditional methodologies.
However, an aim of this project is to understand the resource required to implement various AQbD concepts against the benefits each brings.
In addition to producing a more robust method reducing long term costs of revisions, we’ve already identified efficiencies for the BP laboratory by taking a risk-based approach to the marketed products we sample for analysis.
We can also see potential savings using risk analysis techniques to target our analytical assessment to critical areas of a procedure.
The consultation closes on Saturday 31 August 2019.