One of my first tasks this year was to put the finishing touches to a new paper which discusses a subject that I’m pretty sure will resonate with many of you in the pharmaceutical industry – the challenge of setting effective product and processing specifications. And I know it can be a challenge – too tight a spec and manufacturing becomes more difficult than it needs to be, too loose and you risk product inconsistencies that affect performance. Setting appropriate specifications is fundamental to Quality by Design (QbD), as described in ICH Pharmaceutical Development guidice Q8,  and is therefore a key part of the current shift towards a risk-based approach to pharmaceutical production. And since particle size is often a Critical to Quality Attribute, controlled by and during the manufacturing process, getting that specification right is extremely important.

Why we need to set specifications

According to FDA guidance specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities as conditions of approval. Such specifications define product acceptability so the need for them is based on there being a link between a variable and some aspect of performance. For solid dosage forms and liquids, if particle size is critical to any of the following, a specification must be set:

  • Dissolution, solubility, bioavailability
  • Processability
  • Stability
  • Product content uniformity

What we need to know to be able to set specifications

Having defined when and why we need to set particle size specifications, in order to do so effectively it is necessary to consider a number of different issues. These include how to measure particle size, how to represent the size distribution, defining the particle size of interest, selecting an appropriate parameter, and setting tolerances. Recognising the parameters that different particle sizing techniques deliver, and the relevance of alternative size descriptors, is crucial.

Laser diffraction detail

Laser diffraction is probably the most widely used particle sizing technique within the pharmaceutical industry and in future blogs I’ll be homing in some of the detail of setting specifications and how the latest particle size analyzers support you in this process. Meanwhile, Malvern’s laser diffraction Masterclass series of presentations provides a useful introduction to the process of setting realistic and meaningful prroduct specifications. And there’s a whole team here who can help you further– just contact our Helpdesk for details.