Blog

Standard Operating Procedure for performing analytical method verification of compendial procedure/ validated analytical methods in quality control department. Describes characteristics for analytical method verification to be carried out for drug substances and drug products.

Analytical Method Verification

1.0   Objective :

• • To lay down the procedure for performance of analytical method verification of compendial procedure/validated analytical methods in quality control department.

2.0   Scope – Analytical Method Verification:

• • This SOP is applicable for performing analytical method verification of compendial procedure/validated analytical methods in quality control department.

• • It describes characteristics for analytical method verification to be carried out for drug substances and drug products to confirm the suitability of analytical procedure.

• • These are:-

• • • Method Verification for Pharmacopoeial/compendia methods

• • • Analytical Method verification for already validated method

• • • Method verification for out sourced drug substance received from DMF source or CEP source

• • • Method verification activity for contract laboratory for outsourced sample testing.

3.0   Procedure:

• • The suitability of analytical method in the laboratory shall be determined by analytical method validation, method transfer and method verification which is describe as follows:

• • Method validation:

• • Method validations are performed for new methods that have just been developed or instituted, and that require revisions because they have been significantly changed.

• • So oftentimes its “re-validation” that is really required in the wake of making significant changes to a method, equipment, or conditions of the analysis. Example: changes in the formulation etc.

• • Analytical Method Transfer:

  • Method transfers are performed for validated methods, where methods have already been validated and it’s transferred to a new laboratory or a new facility.

• • It’s a validated method but there is a need to ensure that the lab is capable of performing that method.

• • There is a process that needs to be followed and in place, to ensure that the transferring lab can perform that test reliably and accurately.

• • Analytical Method Verification:

• • Method verification is materially different and a little more limited, and not as robust or rigorous as method validation.

• • Regardless, verification is needed in order to verify that a lab is capable of performing an analytical method reliably and precisely for its intended use.

• • Method verifications are really performed for compendial methods, where there is already an existing method in compendia, like USP, NF, BP and EP.

• • It is showing and proving that a given lab is capable of performing that particular test reliably and precisely.

• • In this SOP the emphasis is given in method verification activity to be performed at site along with elaboration and detail requirements.

• • Verification is not required for basic compendial test procedure that is routinely performed unless there is an indication that the compendial procedure is not appropriate for the material under test.

• • For example –

• • • Loss on drying,

• • • Water by Karl fisher,

• • • Residue in ignition,

• • • Microbial tests,

• • • Heavy metal,

• • • Arsenic,

• • • Chloride,

• • • pH measurements,

• • • Specific Optical Rotation,

• • • Melting point etc.

• • Drug substances from different suppliers may have different impurity profiles that are not addressed by the compendial test procedure such methods shall be verify.

• • Different excipients, antioxidants, buffers, Colorants or container extractives in a drug product can vary widely among manufactures and may have the potential to directly interfere with the procedure or cause the formulation of impurities that are not addressed by the compendia procedure.

• • All such excipients shall be considered during specificity parameter for verification of analytical procedure of drug product.

• • Product which is considered under the scope of Method transfer SOP, shall not consider for verification.

• • Method verification of analytical procedure shall be executed before commencement of 1^st time testing of drug substance/ drug product at site.

• • Preparation, Review and Approval of Documents

• • Analytical method verification activity shall include the test parameters like-

• • • Assay,

• • • Organic impurities (Related substances or compounds),

• • • Dissolution,

• • • Content Uniformity,

• • • Enantiomeric purity (Chiral Purity),

• • • Residual solvents(but not limited to) for Drug Product and Assay,

• • • Organic impurities (Related substances or compounds),

• • • Enantiomeric purity (Chiral purity),

• • • Residual solvents (but not limited to) for Drug substance (Where ever applicable).

• Compendial Method:

  • Case I:  Applicable to drug substance / product.

• • Below Procedure is applicable for 1^st time adoption of Compendial method at site.

• • Complete validation is not required to verify the suitability of the method.

• • Assessment of specificity need to demonstrate suitability of the method for the particular drug substance or product.

• • Other analytical performance characteristics such as an assessment of the Precision for test procedure may be useful to demonstrate the suitability of the Compendial method under actual conditions of use wherever require as given below table:-

Table I

• • Case II:-

  • Vendor’s drug substances or product.

• • 1^st time adoption of Compendial method at site, wherein same method is already verified at other site (Transfer site)

• • Complete Validation is not required to verify the suitability of the method if complete validation is executed (at vendor end or any site of company) and documents are available with site.

                                                                        Table II

Note: Complete raw data shall be shared to receiving site from transferring site for such cases.

• Non-Compendial method:

  • Complete validation is not required to verify the suitability of the method if complete validation is available.

• • Specificity need to demonstrate with other parameters as suggested in below table.

Table III

• • In case of verification at Contract Laboratory:-

# Parameter to be requested as per requirements with scientific justification.

• • Prepare protocol and report as per respective laboratory policies.

• • The approval authority for protocol and report shall be made by site representative.

Note: Incorporate the verification characteristics as per requirement regulatory/customer.

• Verification procedure and acceptance criteria:-

• • Design the Protocol as per intended purpose of verification and requirement of respective test.

• • For detailed requirement and acceptance criteria for verification shall be in-line with analytical procedure validation SOP.

• • The content of Verification Protocol shall have below heading as per requirement of study.

• • • Protocol approval

• • • Objective

• • • Scope

• • • Responsibility of validation team

• • • Product profile

• • • Material, Chemical, Reagents and Instrument

• • • Methodology

• • • Incident/ Deviation

• • • Summary/ Recommendation

• • • Revision history

• • For each verification activity, QC analyst shall prepare the report and reviewed by concerned QC Head.

• • Forward the same compiled report along with raw data and chromatograms to QA department for review.

• • Incorporate the necessary corrections/suggestions received from QA department and final corrected report shall get approved by QA Department (Head/In-Charge).

• • Archival Procedure:-

• • QC Documentation cell (where verification is performed) will be responsible for proper archival and storage of verification report along with raw data and protocol.