In pharmaceutical analysis, USP-NF methods are widely used because they offer a validated framework for drug testing—provided system suitability requirements are met. These methods do not require re-validation if implemented correctly and shown to meet specific performance criteria.
Key System Suitability Requirements
To ensure the method is suitable for use, USP outlines several critical parameters:
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Resolution: A minimum resolution between the active ingredient and any related compound or impurity must be demonstrated.
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Precision: The Relative Standard Deviation (RSD) for peak areas of replicate injections of the active compound must be less than 2%.
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Tailing Factor: The USP Tailing Factor (TF) should be less than 2, indicating acceptable peak symmetry.
These criteria confirm that the chromatographic system is performing adequately and that the method can produce reliable results.
Flexibility in Method Adjustments – USP <621>
USP Chapter <621> provides guidance on permissible adjustments to existing methods without requiring full re-validation, as long as system suitability still passes. For example, changes such as increasing column length by up to 50% are allowed. This flexibility supports method adaptation while maintaining compliance.
The USP <1058> Quality Triangle [2]
To ensure overall data integrity, USP <1058> introduces the Data Quality Triangle, a tiered framework consisting of:
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Analytical Instrument Qualification (AIQ)
AIQ ensures that instruments are fit for purpose, independent of the analytical method. It relies on calibrated, traceable standards and supports technology transfer by demonstrating instrument equivalence.
Our Qualification Kits simplify this process, making AIQ a practical, do-it-yourself solution. -
Analytical Procedure Validation
Once instruments are qualified, the analytical procedure must be validated. This includes defining parameters for data acquisition, processing (especially peak integration), calculation, and reporting. System suitability criteria are established and documented during this phase. -
System Suitability Tests (SSTs)
SSTs verify that the entire analytical system—including instrument, column, mobile phase, and software—is functioning properly on the day of analysis. SSTs are method-specific and are not a substitute for instrument qualification.
NOTE: According to FDA guidance, if SST results fall outside acceptance criteria, the run may be invalidated. Misuse of SSTs to dismiss out-of-specification (OOS) results can lead to regulatory scrutiny.
Important Clarification
As noted by Smith and McDowall
[2]
, SSTs are not instrument qualification tests. They are designed to confirm the performance of the complete analytical system for a specific method, not to assess the instrument itself.
AIQ, on the other hand, uses certified columns and standards to evaluate instrument components against traceable benchmarks.
NOTE: It is highly recommended before you make any adjustments to your current method, you obtain approvals from your Regulatory Affairs department or Laboratory Management.
References
- United States Pharmacopeia 34–National Formulary 29 (USP Convention, Rockville, MD, 2011)
- Smith, P. & McDowall, R.D. Are You Sure You Understand USP <621>?, LCGC International, Vol. 1, Issue 8, Sept 2024, pp. 22–30