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
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analytics-small-molecule-drugs
• Outsourcing Glycan Analysis
www.pharmtech.com/outsourcing-glycan-analysis
• Testing Foreign Particulate Matter in Inhaled Products
www.pharmtech.com/testing-foreign-
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• Outsourcing Analytical Methods
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