FOOD AND DRUG ADMINISTRATION
OFFICE OF REGULATORY AFFAIRS
Quality
Document Number:
MAN-000037
Revision #: 03
Revised:
31 Oct 2023
Title:
ORA Lab Manual Vol. II - Methods, Method Verification and Validation (ORA-
LAB.5.4.5)
Page 32 of 34
For the most current and official copy, check QMiS.
the analysis and the requirements of the customer considered. The
specified acceptance criteria can then be modified, if sufficiently justified.
b. For most purposes, the quantitative or qualitative range of a method will be
appropriately established through determination of linearity, accuracy, and
LOD/LOQ, as described above.
c. The validation parameter “Robustness” is frequently discussed. When the
method being validated is for single occurrence use or internal use, this
determination may not be necessary. For a more complete validation, as
in cases where the method is intended for publication or establishment as a
future “Standard Method”, robustness should be assessed through
variations in the analytical procedure (e.g., change in flow rate, use of
differing equipment, different column lots, etc.) Consult with the lab
manager for specifics on test requirements.
d. ICH and other guidelines recommend, for Accuracy determination, an
assessment using a minimum of 3 replicates at each of 3 concentrations,
thereby equating to a minimum of 9 determinations. This should be done
when the method is intended for publication or establishment as a future
“Standard Method.” For routine regulatory analytical purposes,
ISO17025:2017 requirements will be considered met if each of the three
single preparations evaluated under “Accuracy” meet the Acceptance
Criteria. If one or more preparations fails to meet these criteria, the
laboratory should conduct a failure investigation, to include an examination
of possible causes for this failure.
e. For certain types of methods, e.g., Atomic Emission Spectroscopy, a non-
linear standard curve may be expected, and can be used. Linear
Regression analysis would not apply to such situations.
D. Categories of Methods; Validation Parameter Requirements
1. Category I: Quantitative Assessment of Major Components: (i.e.
Assay, Content Uniformity, determinative step for Dissolution/Release
Rate). Required parameters: Accuracy, Precision, Linearity, Specificity
2. Category IIa: Quantitative Assessment of Minor Components: (i.e.
Impurity and Degradant quantitative determinations). Required
parameters: Accuracy, Precision, Linearity, Specificity, Limit of
Quantitation
3. Category IIb: Qualitative Assessment of Minor Components: (i.e.
Impurity and Degradant Limit Tests). Required parameters: Specificity,
Limit of Detection