APR September/October 2020 - 78

MANUFACTURING

This program will evaluate each change that could impact the method
validity, discuss deviations, track the corrective and preventive actions,
and evaluate the method performance. Risk assessment should
be integrated into the revalidation for the selection of validation
parameters to ensure the intended use of the method is met. Whether
the activity is validation, revalidation, or verification, the activities
should be performed under an approved protocol with appropriate
acceptance criteria to assure that the analytical method is fit-forpurpose and stays in compliance.16
If the evaluation determines that the change is within the scope of
the method, no additional validation is needed. This evaluation and
its conclusion should be documented. The system suitability test
parameters should also be reviewed and redefined, if necessary.

Verification of
Compendial Monographs
For standard methods recognized by organizations such as The
American Society for Testing and Materials (ASTM), International
Standard Organization (ISO), United States Pharmacopeia (USP), which
has already been validated by the method's sponsor, validation is not
necessary by the second user. However, verification is necessary, and
the validation parameters should be evaluated to determine which
additional experiments are necessary to ensure that the compendial
method is suitable for the test sample. USP General Chapter <1226>
contains recommendations to be used for different types of methods.6
In most cases, the manufacturer should evaluate the analytical
method to ensure that the method can be used for their material,
and the system suitability requirements should be verified under the
actual conditions of use. The most critical parameter is the specificity
to assure that the method is specific for the material tested, and all
impurities/degradation products are accounted for. In many cases,
the compendial method may need to be adjusted for use in a routine
analytical laboratory. While method validation is the qualification of
an analytical method using a well-qualified sample lot, verification is
a qualification of a material of interest using a well-qualified standard
method. The verification plan should be done under a protocol, and a
report will be assembled to document the verification data generated.

Method Lifecycle Management
Analytical data are used to determine the quality of the drug
substance and drug products; for that reason, method performance
should be reviewed and trended every time that the procedure is
used. Therefore, method validation is an ongoing process. Figure 3
illustrates the method lifecycle. The analytical procedure is developed,
qualified, and validated according to the intended use of the method.
Once the method is implemented, it should be reviewed periodically
and optimized to assure that it is sufficiently robust for routine use
over a long period.

78 |

APR_SeptOct2020.indd 78

Figure 3. Method Validation Lifecycle

To support the product testing, validation must be studied carefully to
understand the critical parameters. The performance of the method
must be tracked, and trend analysis should be done at regular intervals
to proactively prevent unintended changes to the method that could
impact the monitoring of the drug product. Table 3 gives a template to
plan for the validation activities of an analytical procedure.
While most of the ICH guidelines focus mainly on early phases
of development and prepare for registration, ICH Q12 provides
regulatory and technical considerations to manage the lifecycle
of pharmaceutical products using a risk-based and science-based
concept.17 In essence, this guideline provides the framework to allow
flexible regulatory approaches to post-approval changes to the
pharmaceutical product using the information collected through
product development. The product lifecycle consists of three stages:
Table 3. Planning for a method validation
Validation Parameters

Procedure

Principle/Scope

What is the scope? Principle of the procedure?

Apparatus/Equipment

Which apparatus is used?

Operating Parameters

Operating parameters to be studied?

Reagents/Standards

List of reagents, sources, availability?

Sample preparation

How is a sample prepared?

Standards control

What is the reference standard used?

Solution preparation

How is the solution prepared? Which volume?

Procedure

Step-by-step procedure

System Suitability

Acceptance criteria for system suitability test?

Calculations

All different calculations including the units

Data Reporting

How data are reported officially

| September/October 2020

10/2/20 11:45 AM

APR September/October 2020

Table of Contents for the Digital Edition of APR September/October 2020