SOP for Analytical Method Verification

The verification process for compendial test procedures is the assessment of whether the procedure can be used for its intended purpose, under the actual conditions of use for a specified drug substance and/or drug product matrix.

Verification requirements should be based on an assessment of the complexity of both the procedure and the material to which the procedure is applied. Although complete revalidation of a compendial method is not required to verify the suitability of a procedure under actual conditions of use, some of the analytical performance characteristics

Verification should assess whether the compendial procedure is suitable for the drug substance and/or the drug product matrix, taking into account the drug substance’s synthetic route, the method of manufacture for the drug product, or both, if applicable. 

Verification should include an assessment of elements such as the effect of the matrix on the recovery of impurities and drug substances from the drug product matrix, as well as the suitability of chromato-graphic conditions and column, the appropriateness of detector signal response, etc.

‘Verification is not required for basic compendial test procedures that are routinely performed unless there is an indication that the compendial procedure is not appropriate for the article under test. Examples of basic compendial procedures include, but are not limited to, loss on drying, residue on ignition, various wet chemical procedures such as acid value, and simple instrumental determinations such as pH measurements.’

Objective 

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

Scope

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

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These are:

1. Method Verification for Pharmacopoeial/Compendia Methods
2. Analytical Method verification for already validated method
3. Method verification for outsourced drug substance received from DMF source or CEP source
4. Method verification activity for contract laboratory for outsourced sample testing.

Procedure

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

Method validation

1. Method validations are performed for new methods that have just been developed or instituted, and that require revisions because they have been significantly changed.
2. 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

1. 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.
2. It’s a validated method but there is a need to ensure that the lab is capable of performing that method.
3. 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 shows and proves that a given lab is capable of performing that particular test reliably and precisely.
• In this SOP the emphasis is given to method verification activity to be performed at a 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

1. Loss on drying
2. Water by Karl Fisher
3. Residue in ignition
4. Microbial tests
5. Heavy metal
6. Arsenic
7. Chloride
8. pH measurements
9. Specific Optical Rotation
10. Melting point etc.

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• Drug substances from different suppliers may have different impurity profiles that are not addressed by the compendial test procedure such methods shall be verified.
• Different excipients, antioxidants, buffers, Colorants or container extractives in a drug product can vary widely among manufacturers 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 the specificity parameter for verification of the analytical procedure of the drug product.
• Product which is considered under the scope of Method transfer SOP, shall not be considered for verification.
• Method verification of analytical procedure shall be executed before the commencement of 1-time testing of drug substance/ drug product at the site.

Preparation, Review and Approval of Documents

Analytical method verification activity shall include the test parameters like-

1. Assay
2. Organic impurities (Related substances or compounds)
3. Dissolution
4. Content Uniformity
5. Enantiomeric purity (Chiral Purity)
6. Residual solvents (but not limited to) for Drug Products and Assay
7. Organic impurities (Related substances or compounds)

Compendial Method

Case I: Applicable to drug substance/product

The procedure is applicable for 1st-time adoption of the Compendial method at the site.

• Complete validation is not required to verify the suitability of the method.
• Assessment of specificity needs to demonstrate the suitability of the method for the particular drug substance or product.
• Other analytical performance characteristics such as an assessment of the Precision of test procedure may be useful to demonstrate the suitability of the Compendial method under actual conditions of use wherever required as given below table:

Case II: Vendor’s drug substances or product

1st-time adoption of Compendial method at the site, wherein the same method is already verified at another site (Transfer site)

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

Note: Complete raw data shall be shared with the receiving site from the 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 needs to be demonstrated with other parameters as suggested in the below table.

In case of verification at Contract Laboratory:

Parameter to be done

1. Specificity
2. Precision at LOQ
3. Linearity
4. Precision
5. Accuracy
6. Robustness
7. Filter Compatibility.

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 the intended purpose of verification and the requirement of the respective test.
• For detailed requirements and acceptance criteria for verification shall be in-line with the analytical procedure validation SOP.

The content of the Verification Protocol shall have the below heading

1. Protocol approval
2. Objective
3. Scope
4. Responsibility of the validation team
5. Product Profile
6. Material, Chemical, Reagents and Instrument
7. Methodology
8. Incident/ Deviation
9. Summary/ Recommendation
10. Revision history

• For each verification activity, the QC analyst shall prepare the report and review by the concerned QC Head.
• Forward the same compiled report along with raw data and chromatograms to the QA department for review.
• Incorporate the necessary corrections/suggestions received from the QA department and the final corrected report shall get approved by the QA Department (Head/In-Charge).

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