Analytical Method Development for Impurity Detection

In general, analytical method for impurity detection is developed based on adequate analysis of impurity in the generic drugs. In the consistency evaluation, the FDA requires generic manufacturers to establish impurity analysis methods with reference to existing standards such as pharmacopoeia standards and the Reference Listed Drugs (RLDs) detection methods. Alfa Chemistry provides comprehensive services of analytical method for impurity detection to meet the requirements of method applicability.

Figure 1. Considerations for initiating method development. (Steve, A. 2016)

Our Services

Establishment of Analytical Method

When the analytical method is different from the existing standard method, we provide comparative data on the detection results in terms of system applicability and detection sensitivity, to prove the detection ability of the established method is not less than the existing standard method.

1. Analysis of structure and physical & chemical properties of impurity

Determination of separation mode, liquid phase method (chromatographic column, mobile phase)

2. System suitability testing (TST) of analytical method

The system suitability reflects the separation degree of the sample. For analytical methods with low sensitivity, we provide an additional precision test to ensure that the sensitivity of each sample detection can meet the requirements.

3. Determination of the detection system for the analytical method

Determination of detection wavelength by comprehensively considering the maximum absorption of principal components and most known impurities. For individual impurities with large differences in UV absorption from the main component, the external standard method or the main component self-control method using correction factor is used for the calculation.

Figure 2. Method development of impurity assay. (Clarke, A. M.; Riley, C. M. 2020)

Optimization of Analytical Method

We correct and improve the analytical method to confirm the effectiveness. Forced degradation test is performed to confirm the robust of the established chromatographic conditions and the stability of the product.

Validation of Analytical Method

We provide analytical method validation services to prove that the established method can meet the requirements of applicability, sensitivity and accuracy of impurity detection.

Determination of the Impurity Limits

Before the determination of impurity limits, we conduct research on the known impurity of the RLDs, including chemical names and structural formulas, to preliminary determine the process impurities and degradation impurities that may be produced by generic drug products.

• Determination of limits of known impurities: Reference to the requirements in the FDA guidance
• Determination of limit of unknown impurities that present at an apparent level of more than (≥) the identification threshold: Analyze the source of the impurity and conduct qualitative analysis, safety assessment, and determine its limit in combination with the production process
• Determination of limits of unknown impurities that present at an apparent level of not more than (≤) the identification threshold: Reference to the limits of any individual impurity in FDA guidance
• Determination of limit of total impurities: Reference to the requirements in the FDA guidance