Pharmaceutical Technology - November 2018

Pharmaceutical Technology - eBook

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Page 22 of 45

Pharmaceutical Technology LABORATORY BEST PRACTICES 2018 23 • All method validation tests are conducted by following defined protocols. • All prospectively set validation acceptance cri- teria are met. Development of solid, reliable analytical meth- ods is not only important for the measurement of particular product attributes, it also has a signifi- cant impact on defining product specifications. When establishing product specifications, the acceptable range is based on the combination of product variability and variability of the testing methods, as defined by Equation 1. Product Specification = X × √ (σ 2 an + σ 2 pr ) [Eq. 1] Where X ranges between 2 and 3, in most cases σ 2 pr = Lot to lot product variability resulting from manufacturing process variability σ 2 an = Analytical variability σ 2 an = σ 2 rep. + σ 2 int. [Eq. 2] σ 2 rep. = Intra-run variability; σ 2 int. = Inter-run vari- ability Poorly performing ana ly tica l met hods not only increases the risk of method dependent out- of- specification results but will also lead to wider product specifications, due to a disproportionate contribution of analytical variability (Equation 1). A wider specification range heightens the poten- tial for allowing non-conforming product lots to meet specification limits and thus be accepted for release when such lots should be rejected. To summarize, the benefits of using QbD are significant: • Fewer analytical method-related out-of-specifi- cation and failure investigations • Lower failure rates in method transfer • Method changes can occur without re-valida- tion, if continuing to operate within the defined design space • New technologies can be more easily introduced into existing methods when developed through QbD • Ease of adaptability to continuous improvement. It is clear that QbD is the right approach when developing/validating analytical methods for use in testing pharmaceutical/biopharmaceutical products. References 1. ICH, Q8(R2), Pharmaceutical Development (ICH, 2009). 2. ICH, Q9, Quality Risk Management (ICH, 2005). 3. C. Ye, et al., J. Pharmaceut. Biomed. 23, 581-589 (2000). 4. ICH, Q2(R1), Validation of Analytical Procedures: Text and Methodology (ICH, 2005). 5. FDA, Analytical Procedures and Methods Validation for Drugs and Biologics (FDA, 2015). PT More on analytical method development Visit to read the following articles on analytics: • Lot Release Testing Analytics for Small-Molecule Drugs analytics-small-molecule-drugs • Outsourcing Glycan Analysis • Testing Foreign Particulate Matter in Inhaled Products particulate-matter-inhaled-products • Outsourcing Analytical Methods

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