A Guide to Analytical Method Development: Part 1

Early Step by Step Questions to Ask

  • Step I: What type of product/analyte is being tested?
  • Step II: What is the intended purpose of the method?
  • Step III: What type of method should I use?
  • Step IV: What components will effect my method?

Development Phase

Step I: Product/Analyte

What type of product/analyte is being tested?

  • Small or large molecules (proteins/peptides).
  • Raw materials.
  • Intermediates/in-process or finished products.

What is the sample composition?

  • Sample matrix.
  • Target concentration.

Step II: Method Propose

What is the intended purpose of the method? 

  • Quantitate, detect, identify, purify, characterize.

Will the method be used for:

  • Intermediate/release/stability testing.
  • Characterization, formulation, or degradation studies.
  • Reference standard qualification.
  • Potency, excipient, or impurity testing.

Step III: Method Selection

What type of method should I use? 

  • Compendial: Standardized Methods (United States Pharmacopeia/National Formulary) or FDA recognized procedures. Requires verification.
  • Non-compendial: Method which requires full development and validaiton.
  • Literature research

Step IV: Method Components

What components will effect my method?

  • Instrumentation selection.
  • Reagent/solution/diluent selection.
  • Reference standard and control selection.
  • Instrument and operation parameter set-up.
  • System suitability.
  • Test sample used.

Establishing conditions, setting operations parameters, and challenging method performance properties must be measured. This is the QUALIFICATION PHASE!

You may be interested in the following article:

A Comparative Framework Between New Product and Legacy Product Process Validation

This paper is a comparative analysis between the application of the FDA Process Validation Guidance (2011) to new products and legacy products.