USP endorses the concept of mechanical calibration (grounded in metrology), conducted at periodic intervals, to ensure that
the mechanical components meet specifications and are in a state of control. These mechanical checks, however, are necessary
but not sufficient because they ignore the chemical and kinetic aspects of the dissolution procedure, an oversight that is
common in most chemical tests. For example, even the best-calibrated high-performance liquid chromatography equipment still
needs systems suitability standards to ensure proper performance within and across laboratories. In one of the most common
chemical measurement tests performed, pH, it is not sufficient to ensure only that the electronics of the meter (essentially
a voltmeter) are functioning. Rather, there must be assurance that the entire system (the meter, the glass electrode, the
counter electrode, and the analyst) is performing adequately through the use of pH buffer standard solutions. Traceability,
accuracy, and comparability can then be ensured. USP reference standard tablets used in PVT help ensure that the complex character
of a dissolution assembly, coupled with an analyst and analytical procedure, act in concert to yield results within and among
laboratories with acceptable accuracy and precision.
USP has established that mechanical calibration of a dissolution assembly does not address adequately all factors (e.g., vessel
symmetry) that influence dissolution results (9, 13). Recent USP research also leads to the conclusion that the current tolerances
and specifications set for mechanical calibration are inadequate and must be tightened (e.g., 7, 9). Even if mechanical calibration
could be brought to complete realization (i.e., control of all possible impacting factors through conformance to specified
tolerances), a PVT would still be needed to test the system as a whole and in actual use. Control of each factor individually
might be possible, but that would not mean that all elements working in concert would yield reproducible and comparable results.
. In the terminology of the International Organization for Standardization (ISO), USP's chemical reference standard tablets
used in PVT are elements of a proficiency test whereby a laboratory may compare its results to those from other laboratories
(18). USP emphasizes the value of these publicly available reference standards that allow PVT within and among laboratories
to ensure that all laboratories achieve similar results in the interests of setting a metrologically sound and publicly derived
USP performance test in the drug product specification.
Ensuring the quality of data generated by analytical equipment includes an overall approach to equipment quality. Pharmaceutical
scientists have long accepted that equipment qualification—installation qualification (IQ), operational qualification (OQ),
and performance qualification (PQ)—under good manufacturing practices (GMPs) should be executed to verify acceptable quality
of output from multicomponent analytical instrumentation. Although practitioners may debate where in the IQ, OQ, and PQ process
individual qualification activities should take place, the fundamental principles are indisputable. Each component of the
verification process contributes to overall quality of data generated from multicomponent analytical instrumentation, and
omission of any component will compromise the quality assurance of data (19). On the basis of its research, USP concludes
that mechanical calibration must be coupled with PVT to satisfy GMP requirements for OQ and PQ, respectively.