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IMPURITIES ABOVE 0.1%
The
studies (e.g., NMR, IR, and MS) conducted to characterize the
structure of actual impurities present in the drug substance at or
above an apparent level of 0.1 percent (e.g., calculated using the
response factor of the drug substance) should be described. All
recurring impurities at or above an apparent level of 0.1 percent (see
section IV) in batches manufactured by the proposed commercial process
should be identified.
The DMF holder or the
ANDA applicant should summarize those actual and potential impurities
most likely to arise during the synthesis, purification, and storage
of the drug substance. This summary should be based on sound
scientific appraisal of the chemical reactions involved in the
synthesis, impurities associated with raw materials that could
contribute to the impurity profile of the drug substance, and possible
degradation products.
IMPURITIES BELOW 0.1%
Identification of impurities below apparent levels of 0.1 percent is
generally not considered necessary. However, identification should be
attempted for those potential impurities that are expected to be
unusually potent, producing toxic or pharmacologic effects at a level
lower than 0.1 percent. In all cases, impurities should be qualified
as described later in this guidance. Although it is common practice to
round analytical results of between 0.05 and 0.09 percent to the
nearest number (i.e., 0.1 percent), for the |
