Chemistry Reference
In-Depth Information
6.4 unIversAl tests/crIterIA
There are some tests that are considered universal for setting specifications for
new drug substances and products. These universal tests include Description,
Identification, Assay, and Impurities. Implementation of tests in this category should
also take into account general method validation guidelines found in other USP and
ICH documents [3,4]. A
Description
constitutes a qualitative statement about the
state and color of the new drug substance.
Identification testing
should be able to dis-
criminate between compounds of closely related structure that might be present, and
should be specific for the new drug substance. Chromatographic retention time, for
example, is not specific; however, the addition of an advanced detection technique
such as photodiode array (PDA) or mass spectrometry (MS) is generally acceptable.
An
Assay
to determine the new drug substance content should be specific, and sta-
bility indicating. Impurities (organic and inorganic impurities and residual solvents)
are governed by additional ICH guidelines; organic impurities that are degradants of
the new drug substance, and process-related impurities from the new drug product
should be monitored, with acceptance limits (5-10).
For many of these tests, reference standards are used that in most cases are more
stringently characterized than the substance being regulated. Reference standards
should be accompanied by a certificate of analysis from a reputable source and have
a quality appropriate for their intended use, including control of impurities, often by
procedures not routinely applied in routine testing.
6.5 specIFIc tests/crIterIA: neW drug substAnces
In addition to the foregoing general tests, the following specific tests may be consid-
ered for new drug substances.
6.5.1 P
hySIcochemIcAl
P
roPertIeS
Used to measure properties such as pH, melting point/range, and refractive index,
these tests are determined by the physical nature of the drug substance and its
intended use.
6.5.2 P
ArtIcle
S
Ize
For many formulations, particle size can have a significant effect on dissolution rates,
bioavailability, and stability. Testing should be carried out using an appropriate pro-
cedure, and acceptance criteria should be provided.
6.5.3 P
olymorPhIc
f
ormS
Differences in polymorphic forms can, in some cases, affect quality or performance
of the product, as different crystalline forms can alter physical properties. In the
cases where differences are known to exist, the appropriate solid state should be
specified. Physicochemical techniques such as melting point (including hot-stage
microscopy), solid-state IR, x-ray powder diffraction, thermal analysis (procedures
