Development and Validation of Pharmaceutical Analytical Procedures

By January 8, 2022 Pharmaceutical Development
Development and Validation of Pharmaceutical Analytical Procedures

Table of Contents

Method Development and Validation for Pharmaceutical Analytical Methods

In order to protect customers’ health and safety, analytical procedures must be thoroughly tested. Validation of analytical methods on pharmaceutical products is a requirement of current Good Manufacturing Practices (cGMP). Validation of data collection methods for pharmaceutical manufacture and regulatory filing is also required before their use.

Validated analytical procedures aid in drug characterization, quality control, and batch-record keeping. – Method performance may be verified, and results in quality and reliability are ensured thanks to this analytical test method validation procedure, which provides documentation that the test methodology is appropriate for its intended purpose.

Data Quality

There are several steps that go into producing consistent and trustworthy quality data, including test technique validation. Analytical instrument qualification, a collection of documented evidence that the instruments used in the procedure perform effectively for their intended purpose, is the first important component for providing quality data.

Installation, Operational, and Performance Qualifications must be used to certify all hardware, software, and databases before method validation.

An established method and approved equipment ensure that the design will provide accurate results. It is important to conduct System Compatibility Tests to make sure that the various components of the testing system are compatible.

Method Development

The number of new drugs entering the market grows each year. Some of these medications are entirely novel, while others are just minor alterations to already available formulations. Many medications are added to pharmacopeias after some time has passed after they were first introduced. One reason for this is prospective worries about continued and growing usage of medications, reports of new toxicities (resulting in market removal), the emergence of patient resistance, and the introduction of better therapies by competitors. The pharmacopeia may be unable to provide standards and analytical procedures for certain pharmaceuticals due to the current situation. This necessitates the development of new analytical methods for these drugs.

Criteria that must fulfill for creating new drug analysis techniques

  • Any pharmacopeia may reject the analytical technique for a pharmaceutical or medicinal combination.
  • Due to patent constraints, an appropriate analytical technique for the medicine may not be available in the literature.
  • Excipients in a formulation may interfere with analytical methods for the drug in the formulation.
  • Detecting drug levels in bodily fluids is most likely impossible.
  • Analysis techniques may not be accessible when drugs are mixed.
  • Existing analytical procedures may require the use of costly reagents and solvents. Time-consuming operations that are either dependable or unreliable may also be required.

Guidelines and requirements

Method validation is required for all pharma test techniques, although the method validation approach varies greatly depending on the regulatory agencies that control drug research, manufacture, and the method’s purpose. Pharmaceutical companies and contract analytical testing laboratories rely on advice for method validation since government rules do not specify the scientific approach to the validation of methods.

Development and Validation of Pharmaceutical Analytical Procedures

Regulation and government bodies such as the FDA and the International Conference on Harmonization (ICH) make non-binding suggestions for safe pharmaceutical product development consistent with regulatory criteria and industry standards. The following are a few examples of guidance documents available:

  1. Validation of Analytical Procedures: Text and Methodology 
  2. Guidance for Industry: Analytical Procedures and Methods Validation for Drugs and Biologics
  3. Guidance for Industry: Bioanalytical Method Validation
    • Validation of Compendial Procedures
    • Verification of Compendial Procedures
    • Analytical Instrument Qualification.

The method validation process includes specific features or performance parameters in regulatory guidance documents. Assay validation parameters might vary greatly among methods, depending on the essay’s purpose or the chemical of interest; thus, it is important to know what variables will be investigated in the process.

Because of this, validation will demonstrate that the method’s performance characteristics are reliable as well as acceptable for the intended use. Early in the procedure, the acceptability of the analytical results and the breadth of the approach must be verified according to certain criteria.

According to Validation of Analytical Procedures:

  • Accuracy – To be accurate, a technique must yield test findings that areas near to the real value, regarded as a genuine traditional or as a reference value. Accuracy is usually assessed by the use of reference standards or by estimating the percentage of recovery of a known additional quantity of analyte in a sample. In order to ensure that the analytical technique is correct over its predicted range of results, the method should be tested for its accuracy.
  • Precision – the degree of agreement among a set of measurements performed from repeated samples of the same homogenous material under tightly controlled experimental circumstances. It should indicate the method’s repeatability and reproducibility. It must be evaluated over the predicted range of measurements as with determining accuracy.
  • Specificity – The capacity to evaluate the analysis in the presence of components that are expected to exist, such as contaminants, degraded products, and matrix; in the presence of high concentrations of other similar but not identical things, will identify the item in a given method even at low amounts. Again, establishing a procedure’s specificity must be done over the anticipated range of values and under tightly specified circumstances.
  • The detection limits – When assessing how much of a substance is present, the minimal quantity of the substance in a model that can be observed but not necessarily quantitated is the lowest level of the material that can be recognized but not necessarily quantitated. The tested drug with the smallest amount in the sample yields a positive result above the noise.
  • Quantitation limit – The lowest amount of analyte in a model that can quantify with adequate precision and accuracy is the smallest analyte in a sample that can quantify with appropriate precision and accuracy under specified experimental conditions. The quantitation limit set will show the method’s lowest point in its range.
  • Linearity – Linearity refers to an analytical method’s capacity to yield test findings that are proportionate to the analyte concentration in the sample, either directly or via a well-defined mathematical transformation within a certain range. A non-linear model may be employed if linearity is not attainable. Any quantitative approach must demonstrate a clear quantitative link between assay measurement and quantity of substance of interest in the tested sample. The range of an analytical method is the difference between the top and lower analyte values in the model. The analytical method process analytical has been shown to have appropriate precision, accuracy, and linearity.


The capacity of an analytical technique to be unaffected by slight but purposeful alterations in method parameters suggests its dependability under normal settings.


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