Supporting Documents

• Phase specific validation for raw materials, API

Guidances

• ICH Q2(R1) Validation of Analytical Procedures (previously Q2A,Q2B

• FDA Draft Guidance- Analytical Procedures for Method Validations CMC Documentation (and references therein)

• FDA Reviewer Guidance Validation of Chromatography Methods

• FDA Guidance- Out of Specification (OOS) Investigations

See also relevant sections in:

• Guidance cGMP for Phase 1 Investigational Drugs Final July 2008

• Guidance for Industry cGMPs for Phase 2 and Phase 3

• Q1C Stability Testing of New Formulations of Existing Products

Forced Degradation

• Guidances (Drugs) Forced Degradation Questions and Answers on Current Good Manufacturing Practice

USP 

• See USP Guideline- Testing small molecules and well characterized biotechnology products

GLP 

• Analytical Validation GLP Studies

See also following Link

Acceptance Criteria: Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical procedures.

Active moiety: The molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance (21 CFR 314.108(a)). The active moiety is the entire molecule or ion, not the active site.

Detection Limit: The detection limit of an individual analytical procedure is the lowest amount of analyte in a sample that can be detected, but not necessarily quantitated as an exact value.

Drug Product: A finished dosage form, for example, a tablet, capsule, or solution that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients (21 CFR 314.3(b)).

Drug Substance/Active Ingredient: An active ingredient that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the human body. The active ingredient does not include  intermediates used in the synthesis of such ingredient. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect (21 CFR 210.3(b)(7) and 314.3(b)).

Placebo (or Blank): A dosage form that is identical to the drug product except that the drug substance is absent or replaced by an inert ingredient or a mixture of the drug product excipients quantitatively equivalent to those found in the drug product dosage form.

Quantitation Limit: The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample that can be quantitatively determined with suitable precision and accuracy. The quantitation limit is a parameter of quantitative assays for low levels of compounds in sample matrices, and is used particularly for the determination of impurities and/or degradation products.

Reagent: For analytical procedures, any substance used in a reaction for the purpose of detecting,measuring, examining, or analyzing other substances.

Specification: The quality standards (i.e., tests, analytical procedures, and acceptance criteria) provided in an approved application to confirm the quality of the drug substances, drug products, intermediates, raw materials, reagents, and other components including container closure systems, and in-process materials.

Spiking: The addition of a small known amount of a known compound to a standard, sample, or placebo, typically for the purpose of confirming the performance of an analytical procedure or the

Stability-Indicating Assay: A validated quantitative analytical procedure that can detect the changes with time in the pertinent properties (e.g., active ingredient, preservative level) of the drug substance and drug product. A stability-indicating assay accurately measures the active ingredients without interference from degradation products, process impurities, excipients, or other potential impurities.

Working Standard: A standard that is qualified against and used instead of the reference standard (also known as in-house or secondary standard).