Method Development and Method Validation

Method Development and Method Validation

The development and validation of methods of analysis for quality control

For new products, it is essential to develop suitable analysis methods for release or for stability testing. As a GMP-accredited and FDA-approved contract laboratory in Switzerland, we can draw on an enormous wealth of knowledge and can contribute to your achieving the desired result quickly with targeted literature research and feasibility studies.

The validation of analytical methods is demanded in the GMP regulations. The methods of analysis for a product must be validated at the latest before the start of clinical trials. Fully comprehensive validation in accordance with the ICH and FDA guidelines up until approval is absolutely necessary. Validation of an analytical method provides evidence that the selected method is both suitable and applicable for the analysis purposes intended.

The scope of the validation will be determined together with you in a validation protocol. The experimental work will be carried out by qualified and trained personnel and the results will be summarised in a comprehensive validation report.

Do you require support in method development, or would you like to know whether product-specific validation is necessary?

 

We will be happy to advise you.

Read on here for more information or contact us.


The validation of analytical methods according to the type of analysis

Distinctions are made between the following different types of analysis:

  • Identification testing
  • Quantitative determination of the level of impurities
  • Limit tests for the monitoring of impurities.
  • Quantitative determination of the active substance content

The identity of an analyte is confirmed by means of an identification. This is generally performed by comparing a sample with a reference standard using chromatographic or spectroscopic methods.

The test for contamination can be performed either by using a limit test or by quantitative determinations. Different validation parameters are required according to the type of the test.

Content determinations enable the quantitative determination of the analyte in a sample. Chromatographic methods are mainly used and validated in content determinations.

Additional methods for release reactions of the active ingredient in combination with HPLC and UV are validated for the finished product.

Procedure for validations

The procedure parameters to be determined are dependent on the type of analysis and are described in the ICH guideline Q2(R1). The “Validation of Analytical Methods” table gives an overview of this.

Validation of analytical methods

Type of analytical procedure

IDENTIFICATION

TESTING FOR IMPURITIES ASSAY - dissolution

(measurement only) - content/potency

characteristics   quantitative

limit

 
Accuracy

-

+

-

+

Precision Repeatability
Interm.Precision

-
-

+
+ (1)

-
-

+
+ (1)

Specificity (2)

+

+

+

+

Detection Limit

-

- (3)

+

-

Quantitation Limit

-

+

-

-

Linearity

-

+

-

+

Range

-

+

-

+

 

- signifies that this characteristic is not normally evaluated

+ signifies that this characteristic is normally evaluated

(1) in cases where reproducibility (see glossary) has been performed, intermediate precision is not needed

(2) lack of specificity of one analytical procedure could be compensated by other supporting analytical procedure(s)

(3) may be needed in some cases

Further FDA requirements regarding validation

The FDA guidelines give further validation requirements in addition to the ICH guidelines. Particular value is placed on the robustness of a method. Evidence that small variations, such as in buffer composition, HPLC flow or temperature etc., do not influence the validity of the method is required.

Stability indicating

As part of a stability study, in the case of a method to determine contents and degradation products (nowadays typically the HPLC methods), it must also be demonstrated that the method is “stability indicating”. This is done by performing forced degradation studies, forced degradation is obtained by using severe chemical and physical influences and evidence is gained that the degradation products and the active ingredient in the chromatogram can be separated with the analytical method selected.


Our services in detail:

HPLC analysis: Method Development and Method Validation
HPLC analysis: Method Development and Method Validation
  • Consultation and literature research for method development
  • Method development
  • Creation of an SOP for the analytical method
  • Consultation on the scope of the validation and creation of a validation protocol (validation plan)
  • Method validation and validation report
  • Additional services are according to the directory of services or upon request