Guideline For Submission Of Analytical Method Validation
The requirements for the submission of the analytical method validation data and documents by the industry to the Drug Analysis Division, National Pharmaceutical Control Bureau (NPCB) are presented in this guide.
All the analytical validation done by the industry should be in accordance to ASEAN and ICH Technical Requirements Guidance Documents specifically:-
Q2A: Text on validation of analytical procedures, 1994
Q2B: Validation of analytical procedure: methodology, 1996
The industry is required to submit the following documents for evaluation by NPCB:-
a. Analytical method protocol for the testing of the raw materials (only the active pharmaceutical ingredients (API) and preservatives if any). This should include the specifications and certificate of analysis. All analytical test procedures where possible should be in accordance with the official monograph of that ingredient in the latest edition of the official pharmacopoeia such as British Pharmacopoeia, United States Pharmacopoeia and WHO.
b. Analytical method validation protocol for the finished product. The protocol of analysis should be in accordance with NPCB’s guidelines for the submission of protocol of analysis.
c. Protocol for the analytical method validation procedure carried out on the finished product. This procedure should include all details about the validation process including preparation of all solutions used – standards, samples, placebo etc, detection methods, test conditions, equipment used, statistical analysis & evaluation, calculations etc.
Types of analytical procedures to be validated includes:-
i. Identification tests
ii. Quantitative tests for impurities' content
iii. Limit tests for control of impurities
iv. Quantitative tests of the active ingredient in the sample
v. Pyrogen / Bacterial endotoxin test
vi. Sterility test
A brief description of the type of tests considered in this document is provided below:-
Identification tests are intended to ensure the identity of an active ingredient in the sample. This is normally achieved by comparison of a property of the sample e.g. spectrum, chromatographic behavior, chemical reactivity, etc) to that of a reference standard.
Testing for impurities can be either a quantitative test or a limit test for the impurity in the sample. Either test is intended to accurately reflect the purity characteristics of the sample. Different validation characteristics are required for a quantitative test than for a limit test.
Assay procedures are intended to measure the content of active pharmaceutical ingredient present in a given sample. The analytical data submitted must be able to support the claim that the analytical method employed has been validated.
Pyrogen Test and Limulus Amebocyte Lysate Test -
Relevant validation data for pyrogen test and Limulus Amebocyte Lysate Test include product independent data such as equipment validation, validation of temperature system, lysate sensitivity and product dependent validation data such as inhibition / enhancement studies and validation for routine LAL tests according to the type of LAL test method employed eg. Gel Clot method, quantitative end point method or quantitative kinetic method.
Sterility testing applied to products that are required to be sterile. A satisfactory result indicates that no contaminating microorganism has been found in the sample examined in the condition of the test. For sterility testing it is imperative that the testing procedure adopted by the manufacturers include all aspects of validation of the testing method including the precautions against microbial contamination.
d. Complete set of data obtained from the validation process. These include all raw data such as weights used, chromatograms, tabulated sets of value as well as graphs, statistical analysis & evaluation, calculations & formulae etc. Summary of data will not be accepted. Acceptance criteria for each characteristic/ parameter should also be submitted. For products tested using analytical methods described in official pharmacopeias, users are not required to validate accuracy and reliability of these methods, but must submit data verifying their suitability under actual conditions of use.
e. Certificate of analysis of three (3) recent batches of the finished product.
f. Certificate of analysis for one batch of API used in the product.
g. Summary on the validation process together with conclusion reached.