Chemistry Reference
In-Depth Information
The protocol must be prepared and approved before the official validation process
begins. In addition, the validation protocol typically contains the following:
• Protocol title
• Purpose of the analytical method to be validated
• Description of the test and reference substances
• Summary of the analytical method to be validated, including the equip-
ment, specified range, and description of the test and reference substances
(may be referenced or appended to the protocol)
• Validation parameters to be demonstrated
• Establishment and justiication of the acceptance criteria for the selected
validation parameters
• Dated signature of approval of a designated person and the quality unit
The
protocol title
is a brief description of the work or study to be performed: for exam-
ple, “Validation of the Test Method for the HPLC Assay of Drug Substance X in Drug
Product B.” The
purpose
should specify the scope and applicability of the method. The
summary
is the actual written method or procedure, with enough detail to be easily
reproduced by a qualified individual. To reduce repetition, the method may be included
by reference or as an appendix to the protocol. The specific
validation parameters
to be evaluated are also included in the protocol, because the validation parameters
are dependent on the type of analytical method (Section 4.4).
Acceptance criteria
for
method validation often are established during the final phase of method development,
such as during experiments to show that the method is capable of being validated
(sometimes referred to as “prevalidation” experiments). The
designated Quality Unit
representative
reviews and approves the protocol to ensure that the proper regulatory
regulations will be met and that the proposed work will satisfy its intended purpose.
Experimental work outlined in the validation protocol can be designed such that
several appropriate validation parameters are measured simultaneously. For exam-
ple, linearity uses the accuracy and precision sample preparations and data; LOD
and LOQ are determined from the range and linearity data; sample and standard
solution stability use the same preparations from accuracy and precision. Executed
in this manner, the experimental design makes the most efficient use of time and
materials. An example validation protocol can be seen in Appendix A.
4.5.2 t
eSt
m
ethod
The test method is the formal document that contains all the necessary detail to
implement the analytical procedure on a routine basis. The test method is a con-
trolled document with revision control (the requirement that any document changes
are authorized and that all revisions are available for later comparison), approvals at
the appropriate levels (including the quality unit), and written with enough detail to
warrant only one possible interpretation for any and all instructions. A typical test
method will include the following:
• Descriptive method title
• Brief method description or summary
