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karl2100(金币+1,VIP+0):多谢提供！
除了楼上的， 我想补充一些内容，因为我们还应该考虑ICH的相关指南（完整的见附件2，From: http://www.emea.europa.eu/pdfs/human/ich/038195en.pdf），因为FDA的指南（稍完整文件的见附件1， 出处http://www.fda.gov/CDER/GUIDANCE/cmc3.pdf）并不详细。
FDA的指南（见附件1）给出了关于RECOVERY的以下内容：
F. Recovery
Recovery is expressed as the amount/weight of the compound of interest
analyzed as a percentage to the theoretical amount present in the
medium.
Full recovery should be obtained for the compound(s) of interest. During
the sample preparation procedure, the compound of interest is recovered
from excipients in the formulation matrix ranging from a simple aqueous
solution to complex cream formulation, and from potential adhesion to
container/closure components, e.g., glass vial, metered valve. In
general, a simpler sample preparation procedure will result in a lower
variation of recovery. Data collection for recovery are discussed in
section IV.A under Accuracy.
IV. PARAMETERS FOR VALIDATION OF HPL CHROMATOGRAPHIC
METHODS FOR DRUG SUBSTANCE AND DRUG PRODUCT
Though many types of HPL chromatographic techniques are available, the most
commonly submitted method, the reversed-phase HPLC with UV detection, is selected
to illustrate the parameters for validation. The criteria for the validation of this
technique can be extrapolated to other detection methods and chromatographic
techniques. For acceptance, release or stability testing, accuracy should be optimized
since the need to show deviation from the actual or true value is of the greatest
concern.
A. Accuracy
Accuracy is the measure of how close the experimental value is to the
true value.
Accuracy studies for drug substance and drug product are recommended
to be performed at the 80, 100 and 120% levels of label claim as stated in
the Guideline for Submitting Samples and Analytical Data for Methods
Validation.
For the drug product, this is performed frequently by the addition of
known amounts of drug by weight or volume (dissolved in diluent) to the
placebo formulation working in the linear range of detection of the
analyte. This would be a true recovery for liquid formulations. For
formulations such as tablet, suppository, transdermal patch, this could
mean evaluating potential interaction of the active drug with the
excipients in the diluent. From a practical standpoint, it is difficult to
manufacture a single unit with known amount of active drug to evaluate
recovery. This test evaluates the specificity of the method in the
presence of the excipients under the chromatographic conditions used for
the analysis of the drug product. It will pick up recovery problems that
could be encountered during the sample preparation and the
chromatographic procedures. However, it does not count the effect of the
manufacturing process.
At each recommended level studied, replicate samples are evaluated.
The RSD of the replicates will provide the analysis variation or how
precise the test method is. The mean of the replicates, expressed as %
label claim, indicates how accurate the test method is.
Recommendations:
Recovery data, at least in triplicate, at each level (80, 100 and 120% of
label claim) is recommended. The mean is an estimate of accuracy and
the RSD is an estimate of sample analysis precision.
但是ICH的相关指南（完整的文件见附件2）给出了更为详细的指导原则， 请注意测定CU时，
应该考虑70％， 100％，130％范围；测定溶出度或杂质时的规定又不一样了。
3. RANGE
The specified range is normally derived from linearity studies and depends on the intended
application of the procedure. It is established by confirming that the analytical procedure
provides an acceptable degree of linearity, accuracy and precision when applied to samples
containing amounts of analyte within or at the extremes of the specified range of the
analytical procedure.
The following minimum specified ranges should be considered:
• for the assay of an active substance or a finished product: normally from 80 to 120
percent of the test concentration;
• for content uniformity, covering a minimum of 70 to 130 percent of the test
concentration, unless a wider more appropriate range, based on the nature of the
dosage form (e.g., metered dose inhalers), is justified;
• for dissolution testing: +/-20 % over the specified range; e.g., if the specifications for a
controlled released product cover a region from 20%, after 1 hour, up to 90%, after 24
hours, the validated range would be 0-110% of the label claim.
• for the determination of an impurity: from the reporting level of an impurity （Please refer:
chapters Reporting Impurity Content of Batches of the corresponding
ICH-Guidelines: Impurities in New Drug Substances and Impurities in New Drug Products）
to 120% of the specification; for impurities known to be unusually potent or to produce toxic or
unexpected pharmacological effects, the detection/ quantitation limit should be
commensurate with the level at which the impurities must be controlled.
Note: for validation of impurity test procedures carried out during development, it may
be necessary to consider the range around a suggested (probable) limit;
1
• if assay and purity are performed together as one test and only a 100% standard is
used, linearity should cover the range from the reporting level of the impurities to
120% of the assay specification. |
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