At a time when regulations are becoming stringent and with quality assurance people are having greater knowledge and awareness of science, it is a big relief that Quality by Design (QbD)- met products are easy for getting approval from regulators.
In QbD, products are scientifically designed to meet patients and performance requirements. All Critical Quality Attributes (CQA)are defined and Critical process Parameters(CPP) identified and controlled . Impact variables such as raw materials, process equipment, personnel are identified and understood & controlled to meet CQAs. Some of the tools to enable QbD are Quality Risk Management, PAT ( Process Analytical Technology) and DOE (Design Of Experiments)
Heparin was a wake up call. It is an anticoagulant, up to 30 per cent contamination of finished product. This product was present in many countries and undetected by acceptance and release testing , thus brought home the need for vigilance throughout supply chain and in all global settings.
What should be the aim of QbD ? It should impact and process development and manufacturing and help in FDA's draft validation guidance. Firstly pharmaceutical companies look at the pressure on cost, time and innovation. ICH Q8R (2) defines QbD as " a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management".
QbD is a holistic approach firstly product design , then process design and then manufacturing and finally process monitoring /continuous verification these touches ICH Q8/Q* ® which is on pharmaceutical development, ICH Q11 - API development (to come) PAT Guidance , ICH Q9- Quality Risk Management, ICH Q10- Pharmaceutical Quality Systems and finally process validation.
QbD projects is firstly a cross functional and requires different skills from QA, statistician, process engineer, analytical scientist, project manager, pharmacist and so on. What will the out CME of Qbd? Experience the science, risk management, design of experiment, process analytical technology, clinical knowledge, multivariate data analysis, process design,manufacturing, packaging , technology transfer, QC and so on.
PAT and design space are complimentary to each other. The design space is defined by the key and critical operational parameters identified from process characterization studies and their acceptable ranges. These parameters are the primary focus for on or at line PAT applications. In principle "real time " PAT assessments could provide the basis for continuous feed back that results in improved process robustness. For e.g process adjustments could be implemented to mitigate a reasonable amount of variability in raw materials and other aspects of the manufacturing process. Benefits from PAT is better understanding the process, introduction of real time release , reduction of cycle times, less batch failure, better management of change controls, finally regulatory relief.
As many CQA , formulations heads are interested in DOE basics, I have certain suggestions on the the approaches to experimentation. Firstly build test fix, secondly one factor at a time ( the classical approach) and finally designed experiments (DOE).Your test fix should be pound to fit and paint to match. Plan in such a way when it works stop, think on rework also, finally continual fire fighting .
DOE is a planned approach to determine cause and effect relationship. It was originally used for agriculture in world war II. Now it is a tool for quality improvement. It is always said assumptions and collective study is not for record and this is widely looked for references and DOE will show the standard deviations and areas of corrective actions for making QbD accept.
The QbD approach brings all the critical quality attributes , critical process parameter and control strategy bringing in SOP and PAT address each area, thus bringing in DOE ( Design of Experiments addressing the critical areas. Reporting the results will enable a quick and easy implementation of QbD in a small way but giving confidence to all in a big way.
The author is Conference Director , International Business Conferences (IBC)