Quality by Design for generic products: opportunities and challenges
The first part of an in-depth article on Quality by Design (QbD), published in European Pharmaceutical Review in December 2016, focused on designing quality in to a pharmaceutical drug product by considering dosage form design, and understanding the importance of active pharmaceutical ingredients’ (APIs’) and excipients’ properties.
In the second instalment of this two-part series, the possibilities for implementing manufacturing efficiencies, particularly those concerned with process monitoring and control, will be explored, thus providing the reader with the rest of the picture on how generics manufacturers might take advantage of QbD concepts in order to gain competitive edge.
Solid dosage form manufacture Yu et al provide a comprehensive listing of material and quality attributes, as well as processing parameters, that are relevant to operations for the manufacture of tablets (or capsules) and that merit programmes to characterise behaviour from a QbD perspective1. The following commonly used operations are considered here:
- Size reduction (drug and/or granulated material)
- Granulation (size enlargement) or densification
- Drying (removal of water or other solvent)
- Compaction/compression (tablet or compact formation)
- Coating tablets or granules.
Such operations have historically been controlled by defining the equipment type, operating conditions and time of operation. However, variations in input materials (drug, excipients and process intermediates), scale of operation, environmental conditions and other factors, such as ‘wear and tear’ of equipment, could cause excessive (‘over’) or ‘under’-processing, thus compromising the attributes of output materials. Novel process analytical technologies (PAT) now promise to change processing paradigms by using online process monitoring capability with automatic termination of the process or sub- process when the requisite material attributes are attained. Possibilities associated with common process operations, or their subsets, are presented here as examples. They do not reflect the totality of emerging opportunities in a rapidly changing environment, particularly with respect to instrumentation for online monitoring. For instance, process analysers are mainly spectroscopic at present, but chromatography-based systems are also emerging. The potential for at-line, in-line or on-line measurements to monitor and assure quality can contribute to flexible and more reliable manufacturing operations and reduced energy consumption, as well as decreasing the need for end-product testing2.