SOP for Transfer of Analytical Procedure

The transfer of analytical procedures (TAP), also referred to as method transfer, is the documented process that qualifies the receiving unit to use an analytical test procedure that originated in the transferring unit, thus ensuring that the receiving unit has the procedural knowledge and ability to perform the transferred analytical procedure as intended.

Purpose

The purpose of this procedure is to provide guidelines for the studies required and propose minimum requirements and acceptance criteria for the transfer of analytical methods.

Guidelines are also provided for the design, approval, and execution of analytical method transfer protocols.

Scope

This procedure applies to analytical methods transferred from any originating laboratory to any receiving laboratory, either internal or external to PharmaInfo Pvt Ltd.

This procedure outlines the minimum studies required for the transfer of analytical methods. Additional or different transfer approaches may be considered and documented in the method transfer protocol with scientific justification.

This procedure applies to chemical analytical methods for testing API, excipients, applicable commodities, packaging components, cleaning samples, in-process samples, and finished pharmaceutical products.

This procedure does not apply to microbiological methods or device test methods.

Responsibility

Originating Laboratory

• Provides a copy of the completed test methods, validation reports Validation Change Requests (VCR), and specifications, if available.
• Prepares the transfer Protocol. The protocol will address all testing required for the  product or material and the rationale to justify the requirements for method transfer or
• the waiver of transfer for a specific test method.
• Provides the Receiving Laboratory with sufficient samples to complete the method transfer activities.
• Supplies a reference standard and any specialty chemicals or columns if necessary. Executes the Originating Laboratory portion of the Protocol, if applicable.
• Provides documented consultation or method-specific training to the Receiving laboratory to assist in the execution of the protocol as needed.
• Approves the Protocol along with the Receiving Laboratory.
• Authors, approves, and obtains approvals for the final method transfer report and makes final determination on the success of the transfer.
• Provides safety precautions related to the handling of the materials, appropriate personal protective equipment, and material safety data sheet (MSDS).

NOTE: Based on business needs the responsibilities for transfer protocol and report preparation may be subject to modification. Only qualified personnel can perform the tasks without deviation from the established approval process.

Receiving Laboratory

• Review the methods, validation reports, and other documentation provided to ensure that the method is suitable for transfer.
• As deemed necessary, conduct feasibility runs for identification of possible issues that may need to be resolved prior to finalization of the transfer protocol.
• Reports any problems experienced and make applicable suggestions to the originating laboratory.
• Review and approve the Validation Change Request (VCR) and Transfer Protocol along with the Originating Laboratory.
• Reviews and approves method validation protocol along with the Originating Laboratory in the event of a co-validation.
• Executes the Receiving Laboratory portion of the Transfer Protocol and provides written summary results of analyses and copies of raw and/or processed data, representative chromatograms, charts, etc. to the Originating Laboratory.
• Evaluate the results for compliance with the Transfer Protocol’s acceptance criteria.
• Collaborates with the originating Laboratory in resolving issues that may arise during the execution of the protocol.
• Approves the final method transfer report along with the originating Laboratory

NOTE: Based on business needs the responsibilities for transfer protocol and report preparation may be subject to modification. Only qualified personnel can perform the tasks without deviation from the established approval process.

Accountability

Head, Research and Development – Analytical.

Reference

USP general chapter <1224> Transfer of analytical procedures.

WHO guidelines on transfer of Technology in pharmaceutical manufacturing

Definition

Transferring Unit (TU):

A laboratory (Batch Release Site/QC Laboratory at Manufacturing Site/Contract Laboratory/AR Laboratory etc. as applicable), that is transferring a method to another laboratory (Batch Release Site/QC Laboratory at Manufacturing Site/Contract laboratory/AR Laboratory, etc, as applicable is called a Transferring Unit (TU)

Analytical Test Method

The procedure for performing a test or measurement that describes, in detail, the steps necessary to perform each test. This may include  but is not limited to sample preparation, reference standard and reagents preparations, use of the apparatus, generation of the calibration curve, and use of formulae for calculations.

Change Control

A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status. The intent is to determine the need for action that would ensure and document that the system is maintained in a validated state.

Co-Validation

When a Receiving Laboratory participates in the method validation study. This is typically intermediate precision.

Deviation

Any excursion outside the scope of acceptance criteria specified in the protocol that occurs during the execution of the protocol.

Method Transfer

The systematic process that qualifies a receiving laboratory to perform an analytical procedure previously not performed. This process is coordinated between the originating laboratory and the receiving laboratory.

Method Transfer Protocol

A document containing minimally the purpose, experimental design, and acceptance criteria for the transfer of the analytical method to be transferred, and the responsibilities of the originating and the Receiving Laboratories.

Originating Laboratory

Laboratory from which the analytical method is transferred. The originating laboratory is where the validation of the analytical procedure is conducted.

Receiving Laboratory

The laboratory to which the analytical method is transferred.

Receiving Unit

A laboratory (Batch Release Site/QC Laboratory at Manufacturing Site/Contract Laboratory/AR Laboratory, etc., as applicable) that is receiving a method from another laboratory (Batch Release Site/QC Laboratory at Manufacturing Site/Contract Laboratory/AR Laboratory, etc., as applicable) for routine use is called a Receiving Unit (RU).

ALSO READ: SOP for Concurrent Process Validation

Collaborate or Indirect Type of Method Transfer

An approach to Analytical Method Transfer that involves analysis of the same batches by both Transferring and Receiving Units at respective locations.

Comparative Testing

An approach to Method Transfer that involves two or more laboratories or sites executing a pre-approved Protocol for analysis of a predetermined number of samples of the same lots.

The Protocol details the criteria by which the RU is deemed to be qualified to use the method(s) being transferred.

Co-validation Between laboratories

The Transferring Unit can involve the Receiving Unit in an inter-laboratory co-validation, including them as part of the validation team at the Transferring Unit and, thereby, obtaining data for the assessment of reproducibility per USP Chapter

Direct Type of Method Transfer

An approach to transfer of analytical methods in which an Analyst of the Transferring Unit demonstrates the method to an Analyst of the Receiving Unit laboratory.

Simple Method

Routine tests (pH, LOD, ROI, Karl Fischer, Heavy Metals, ID-IR, ID-UV) which can be executed by any trained, qualified analyst.

Specifications

A list of tests, methods, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the tests described. It establishes the set of criteria to which the material should conform to be considered acceptable for its intended use.

Intermediate

A material produced during steps of the manufacturing of an API that undergoes further molecular change or purification before it becomes an API. Intermediates may or may not be isolated.

Linearity

The linearity of an analytical procedure is its ability to obtain test results that are directly proportional to the concentration of analyte in the sample.

LOD: Limit of Detection

The lowest amount of analyte in a sample can be detected, but not necessarily quantified as an exact value.

LOQ: Limit of Quantitation

The lowest amount of analyte in a sample can be quantitatively determined with suitable precision.

Method Qualification/Method Verification

An approach whereby an analytical method is qualified /verified under reduced validation parameter

Method Transfer Certificate

A certificate was issued with the signatures of relevant stakeholders from TU and RU stating the completion and outcome of the Method Transfer activity.

Method Transfer Initiation Form

A Form sent by TU to RU intimating the plan for Method Transfer along with details of requirements for the Analytical Method Transfer activity, etc.

Precision

The precision of the analytical procedure expresses the closeness of agreement between a series of measurements obtained from multiple samples of the same homogeneous sample under Prescribed conditions.

Specificity

The ability to assess unequivocally the analyte in the presence of extraneous components, which may be expected to be present.

Validation

Documented objective evidence that provides a high degree of assurance that a specific process will consistently produce a product, meeting its predetermined specifications and quality attributes.

Transfer Package

A compilation of supporting documents required for Method Transfer which is sent by TU to RU before the Method Transfer is initiated.

Transfer Waiver

An approach where conventional Analytical Method Transfer may be omitted under certain circumstances based on justifiable reasons as per relevant regulatory/procedural requirements.

A certificate issued with signatures of relevant stakeholders from TU and RU which approves the waiver of a Method Transfer activity at an RU based on justifiable reasons as per relevant regulatory/procedural requirements.

Validation Approach to Method Transfer

An approach where complete or partial analytical method validation is carried out at RU.

Acceptance criteria

Numerical limits, ranges, or other suitable measures for acceptance of results of analytical procedures.

RF value

The ratio of the distance moved by a particular solute to that moved by the solvent's front.

Spiking

The addition of a known amount of a compound to a standard, sample, or placebo, typically to confirm the performance of an analytical procedure.

ALSO READ: Checklist of Technology Transfer for Sending Unit

Procedure:

This SOP Presents the components necessary to complete a successful method transfer by using various types of method transfer.

General considerations

The purposes of performing method transfer studies are:

• To demonstrate that the suitability of all testing methods used shall be verified under actual conditions of use.
• To verify that the method will perform in the Receiving Laboratory as it did during the validation studies.
• The transfer of methods, when necessary, may involve sending the appropriate subject matter expert (SME) to train the lab analysts in the receiving lab priorto a formal transfer  1study. The completion of the training will be documented in a notebook by the Receiving Laboratory.
• The Method Transfer Protocol consists of studies that will demonstrate that the Receiving Laboratory can successfully perform the method as written in the test  procedure without any additional information. If additional information is required to successfully execute the method, this information must be documented in the analyst’s notebook and included in the final test method.
• The intended use of the method as well as the method’s difficulty to execute (complexity) will dictate the needed steps in the transfer process. Chromatographic methods (TLC, HPLC, GC) are classified as moderately complex to complex and require
• formal method transfer. The acceptance criteria presented in this procedure may be modified or adjusted based on actual needs and method / equipment capabilities. Justification for all modifications from the approach presented in this procedure must be included in the individual method transfer protocol.
• Methods transferred from one laboratory to another require an approved Method Transfer protocol and a Method Transfer report. The Method Transfer protocol and report must be approved by the appropriate signatories as specified in the Approvals Section before beginning any transfer activities.
• The test method shall include but not be limited to the following solution preparation elements:

1. System Suitability
2. Solution Preparation
3. Reference Standards
4. Stability of Solutions (if available)
5. Description of Equipment
6. Special Handling Instructions (i.e. protect from light, refrigeration needed, special glassware…etc.)
7. Calculations
8. How to Report Data

All equipment involved in the method transfer must be qualified and calibrated in the operating range established in the method before use.

Analytical Tests: 

• Analytical methods like but not limited to Assay, Related Substances, Dissolution / Drug Release, Residual Solvents, etc., for which Analytical Method Validations have been carried out at the Transferring unit, shall be included in the Method Transfer program.
• Head, of QA/QC, and the Head, of R&D- Analytical shall have the rationale for any methods not included (transfer waiver). Additional pharmacopoeial tests like identification, moisture content/LOD, pH and optical rotation/specific optical rotation, and any other test as applicable in individual monograph/specification shall be considered during the method transfer.
• Method transfer for analytical methods for raw materials shall be carried out based on the criticality of the method, as agreed by the Head, QA/QC Head R&D – Analytical.

Types of Method Transfers:

Comparative Testing:

A.  Indirect transfer/collaborative:

• In this type of method of transfer, the Transferring unit and Receiving unit shall analyze the same batch of samples at their respective locations and the results obtained shall be compared.
• The transferring unit shall provide the Receiving unit with the best procedures, method validation reports, stepwise direction for critical parameters, and certificate of one sample previously analyzed at the transferring unit. The Chemist/analyst, receiving unit (QC/another laboratory) shall perform the analysis in triplicate and provide the results to the transferring unit.

B.  Direct Transfer:

• This type of method of transfer shall include the physical demonstration and joint analysis of the sample by the Transferring unit and the Receiving unit. 
• The transferring unit visits the receiving unit and demonstrates the method by analyzing the sample as per the protocol. After a demonstration by the transferring unit, the Receiving unit shall perform the analysis independently.

Co-Validation Between Two Laboratories or sites

• In this type of method of transfer, the transferring unit shall include the receiving unit in inter-laboratory co-validation including them as a part of the validation team at the transferring unit or receiving unit thereby obtaining data for the assessment of reproducibility. 
• The assessment is made using a preapproved transfer or validation protocol providing the details of the procedure, the samples to be used, and the predetermined acceptance criteria.

Complete or Partial Method Validation or Revalidation

• Revalidation or partial revalidation is another acceptable type of method transfer wherein those characteristics that are anticipated to be affected by transfer are addressed.
• Following are the characteristics addressed in Revalidation or partial validation:

1. Submission to the regulatory agencies of a revised analytical procedure.
2. Use of an established general procedure with a new product or raw material.
3. Changes in the composition of the drug product.
4. Changes in analytical procedures.
5. Omission of Formal Transfer, Transfer Wavier

• In this type of method transfer under certain circumstances, the receiving unit is considered to be qualified to use the analytical test procedures without comparison and generation of inter-laboratory comparative data.

• The following are circumstances that may justify a transfer wavier:

1. The new product composition is comparable to that of an existing product and/or the concentration of active ingredient is similar to that of an existing product and is analyzed by procedures with which the receiving unit already has experience.
2. The analytical procedure being transferred is described in the Pharmacopoeia and is unchanged. Verification should be applied in this case.
3. The analytical procedure transferred is the same as or very similar to a procedure already in use.
4. The personnel in charge of the development, validation or routine analysis of the product at the transferring unit are moved to the receiving unit.

Note: If eligible for transfer waiver, the receiving unit should document it with appropriate justification.

ALSO READ: Checklist for Analytical Method Validation

• Analytical parameters like precision by both the Transfer Unit and Receiving Unit experiment shall be carried out during the analytical method transfer. For assay analysis, one set of linearity (from 80% to 120%) and specificity experiments (Placebo interference) shall be carried out by the Receiving Unit in a specified range as per the protocol.
• Head QA/QC and Head R&D Analytical mutually decide on additional parameters based on the complexity of the method. In the case of the Related Substance test, the available impurities shall be spiked to show the specificity.
• R&D – Analytical in consultation with R&D – Pharma shall initiate the process by informing the QC laboratory at the manufacturing location well in advance of the proposed exhibit batch/production batch.
• Before carrying out the method transfer, the Head, of QA/QC and Head, of R&D – Analytical shall set in place an approved protocol. The protocol shall either be prepared based on the type of transfer as mutually decided by the Head, of R&D – Analytical and the Head, of QA/QC.

• R&D – Analytical shall inform/provide the plant, with a list of special chemicals, reagents, working standards, and GC/HPLC columns required for the QC laboratory.
• The protocol shall be initiated by the scientist, R&D – Analytical.

Preparation of Protocol:

• The protocol shall be specific to the product and method. The protocol shall contain the

1. Objective
2. Scope
3. Responsibility for transferring and receiving unit
4. Product name,
5. Method reference
6. Transferring location name
7. Transfer type
8. Working standard
9. Chemicals details
10. Column details
11. Sample batch no. and precautions to be taken during the analysis/handling.

• For regulated markets, the protocol for analytical method transfer (AMT) shall be numbered as AMT/YY/DNNN/RR

Where,

AMT: Analytical Method Transfer for regulated market; this is common for all AMT protocols, 

YY: year

DNNN: D - Dosage Form, NNN – Product Serial Number

RR: Revision number. For AMT prepared first time RR is 00, on revision it increases in ascending order.

• For the domestic market, the protocol for Analytical Method Transfer (AMT) shall be numbered as DMT/YY/DNNN/RR

Where,

DMT: Analytical Method Transfer for Domestic market; this is common for all AMT protocols, 

YY: year

DNNN: D - Dosage Form, NNN – Product Serial Number

RR: Revision number. For AMT prepared first time RR is 00, on revision it increases in ascending order.

• The protocol shall be prepared by the R&D – Analytical and independently reviewed by another designee. The same shall be approved by the Head, R&D – Analytical or designee and forwarded it for the approval of the Head, QA/QC, or designee.
• After approval of the protocol, the method transfer activity shall be initiated.
• Training during method transfer: R&D – Analytical shall provide necessary training to the Chemist/analyst, QC to make him understand the method's complexity and provide him with the practical tips necessary for the analysis by the method. This shall be documented.
• During the method transfer all the details of analysis shall be written in the laboratory notebook issued at R&D. Details of instrument usage shall be written in the instrument logbook of respective locations.
• The results of chemist/analyst-QC shall be reviewed by the scientist or designee, R&D – Analytical for accuracy. Similarly the results of the Scientist or designee, R&D – Analytical shall reviewed by the Chemist/analyst-QC.
• All the data of method transfer shall be reviewed by the Head QC and approved by the Head of Quality.
• All the original raw data and chromatograms shall be retained at the QC. However, a copy of the method transfer report shall be maintained at the R&D – Analytical.
• Reporting of method transfer results shall be as per format.
• The data shall be authorized by the Head of Quality or the person designated by them. The data shall be screened to note outliers and then subjected to collaborative evaluation.
• After meeting the acceptance criteria of method transfer, the method transfer certificate shall be signed by the Head QA.
• If the acceptance criteria are not met, R&D – Analytical shall analyze the data to look for any ambiguity (e.g. failure in dissolution due to filled content variation/weight variation). If any ambiguity is observed, the method can then be transferred with proper justification. If no such ambiguity is found, perform the reanalysis of the analytical method transfer at the receiving unit.
• For failure in the case of direct method transfer, a fresh batch/ aliquot of the sample shall be taken for reanalysis. Repeat analysis shall be performed in duplicate and the average of the two results shall be reported.
• If the method does not meet the acceptance criteria even after the repeat analysis, the data shall be submitted. The follow-up action shall be decided by the Head, of R&D – Analytical.
• The investigation report shall be filled along with the transfer certificate.

Method Transfer Report

Method Transfer Reports shall contain the following but is not limited to:

• The purpose and scope of the method and its capabilities.
• The name and location of both the Originating and Receiving Laboratories.
• The document number and name of the method being transferred.
• A copy of the final analytical method was transferred.
• Data from the transfer studies performed.
• A summary of the experimental approach for each study and the results obtained, including chromatograms and graphs as applicable.
• The acceptance criteria for each experiment.
• Listing and summary of any deviations.
• Statement as to whether or not the method was successfully transferred.
• Appropriate Protocol Approval Signatures (Approvals Section).

Documentation and Approval

Method Transfer Documents are approved by the following personnel:

• Protocol Author.
• Originating Laboratory Management.
• Receiving Laboratory Management.
• Originating Laboratory and Receiving Laboratory Quality.

Acceptance Criteria Non- Non-Conformance Incidents and Deviations 

Any acceptance criteria non-conformance events (data not meeting the predetermined acceptance criteria established in the approved method transfer protocol) must be investigated.

If the investigation determines that the method, as written, does not contain adequate information and/or instruction to execute the procedure as intended,the method must be revised to include all pertinent information to ensure consistent application of the method.

If the decision is to amend the transfer protocol or to proceed without additional change the rationale and justification for that decision must be documented and approved. Any deviations to the transfer protocol made during the transfer execution must be documented and approved and justified in the final method transfer.

Document Storage

The original documents for transfer protocol and the report will be stored in the QA documents center.

Document Information

Update the “Roles and Responsibilities section of Originating Laboratory and Receiving Laboratory. Add the following note in each section;

NOTE: Based on business needs the responsibilities for transfer protocol and report preparation may be subject to modification. Only qualified personnel can perform the tasks without deviation from the established approval process.

Abbreviations:

AMT: Analytical Method Transfer

API: Active Pharmaceutical Ingredient

AAS: Atomic absorption Spectroscopy.

CE: Capillary Electrophoresis.

COA: Certificate of analysis

DSC: Differential scanning calorimetry.

GC: Gas Chromatography

HOD: Head of Department.

SOP: Standard Operating Procedure

No. : Number

R & D: Research and Development

HPLC: High-pressure liquid chromatography

GC: Gas Chromatography

QC: Quality Control

QA: Quality Assurance

KRM: Key raw Material.

LOD: Limit of Detection.

LOQ : Limit of Quantification.

RF: Retardation factor

RRT: Relative retention time

RU: Receiving Unit.

TLC: Thin Layer Chromatography.

TU: Transferring Unit.

UV: Ultra-Violet

XRD: X-Ray Diffraction

Annexure

Nil

Revision History

Nil

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