A Complete Guide To Effective Method Development In Bioanalytics

Bioanalytics is a science in its own right, with its roots in the project that completed the sequencing of human genomes between 1995 and 2004. It is really a type of systems biology integrated with biotechnology, cell biology, informatics, and systems theory. 

Bioanalytics in Drug Discovery and Development

Bioanalytics in the pharmaceutical industry relates to the application of bioanalysis in the process of drug discovery and development. The main aim of bioanalysis in this process is to determine the concentration levels of therapeutic agents and their metabolites. 

It also facilitates the determination of pharmacodynamic biomarkers in biological fluids. Bioanalysis typically applies validated methods to quantify analytes and metabolites in typical biological matrices like cerebrospinal fluid (CSF), plasma, serum, urine, etc.

Bioanalytical method validation to quantitatively demonstrate the accuracy, specificity, selectivity and stability levels of sample analysis is critical in the process. That constitutes the basis of drug approval. 

Compliance with the regulatory standards stipulated by the respective authorities, such as the Food and Drug Administration (FDA) in the U.S. is also vital for the drug approval process. 

What It Needs For Effective Method Development In Bioanalytics 

One of the major contributions of bioanalytics to the pharmaceutical industry has been to add an unprecedented degree of dynamism in the sphere of method development. Bioanalytics has made it possible to enable an interplay of methods. 

That allows new synergized solutions to emerging, which transcend the limitations of individual methods. Hyphenated techniques with faster and accurate analysis have evolved as a result.

Methods for the quantification of low molecule drugs, for instance, have shifted sharply towards mass spectrometry-based hyphenated methods such as GC-MS, LC-MS, and LC-MS/MS. These methods also allow higher sample throughput, a higher degree of automation, and improved reproducibility. 

Bioanalytical Method Development Parameters

The latest FDA document for industry guidance lists nine parameters for method development, in the order listed below.

  1. Reference standards: Should be identical to the analyte. When that is not possible, an established chemical form of known purity needs to be used. 
  2. Critical reagents: Include antibiotics, labelled analytes, and matrices. Needs proper characterization and documentation for identity, purity, and stability.
  3. Calibration curve: The concentration range expected in a study should guide the quantitation range and the calibration standards of the assay. 
  4. Quality control (QC) samples: QCs need to be prepared in the same matrix as the study samples.
  5. Selectivity and specificity: The selected bioanalytical method must be able to differentiate and measure the analyte while other components such as degradants, impurities, matrix, metabolites, etc.are present.
  6. Sensitivity: Needs to be measured using LLOQ (lower limit of quantitation).
  7. Accuracy and Precision (A&P): The performance of replicate QCs across LLOQ, mid, and high levels needs to be evaluated. The FDA recommends the use of freshly prepared QCs in all the A&P runs. 
  8. Recovery: Recovery of the analyte needs to be optimized for the extraction to be efficient and reproducible.
  9. Analyte stability in the matrix: The FDA recommends the use of the matrix that the study intends to use. Only a rare matrix may be replaced by a surrogate matrix. 

Full details of the FDA’s recommendations on each of the parameters are available on pages 20-27 of the FDA guidelines (link below).

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