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Analytical Method Transfer – Acceptance Criteria

This SOP describes the process and requirements for the transfer of analytical test method from an originating laboratory (Transferring Unit) to a receiving laboratory (Receiving Unit). This SOP provides the requirements for the transfer of validated analytical methods. It defines a process for preparing for transfer, executing transfer testing and preparing final reports.

Analytical Method Transfer

1.0   PURPOSE:

    • This SOP describes the process and requirements for the transfer of analytical test methods from an originating laboratory (Transferring Unit) to a receiving laboratory (Receiving Unit).
    • This Standard provides the requirements for the transfer of validated analytical method.
    • It defines a process for preparing for transfer, executing transfer testing and preparing final reports.

2.0   SCOPE:

    • This SOP is applicable to analytical method transfer from  originating laboratory (Transforming unit) to  Receiving laboratory (Receiving unit) at Drug product manufacturing locations.

3.0   REFERENCES – ANALYTICAL METHOD TRANSFER:

    • In House
    • ISPE -Good practice Guide -Technology Transfer.
    • USP general chapter <1224> Transfer of analytical procedures.
    • WHO guidelines on transfer of Technology in pharmaceutical manufacturing (TRS No.: 961,2011-Annexure

4.0   RESPONSIBILITY – ANALYTICAL METHOD TRANSFER:

    • Analyst of Transferring laboratory/Transferring Unit shall be responsible for:

    • Compilation of Analytical Method Transfer (AMT) package to be sent to Receiving Unit (RU).
    • Preparation and sign-off of method transfer initiation form, Analytical Method Transfer Protocol and transfer waiver certificate as applicable.
    • Execution of Analytical Method Transfer Protocol, as required.
    • Analytical Method Transfer data compilation and evaluation in conjunction with Analyst – RU, preparation and sign-off of Analytical Method Transfer Report.
    • Providing method-specific training to relevant persons in RU, as required.
    • Analyst –Receiving Unit(RU) shall be responsible for:
    • Ensuring that necessary equipment / instrument and materials as intimated through the Method Transfer Initiation Form are available at RU and are qualified /calibrated before start of Method Transfer.
    • Execution of Analytical Method Transfer Protocol, as required.
    • Analytical Method Transfer data compilation and evaluation, preparation and sign-off of AMT Report in conjunction with Analyst – TU.
    • Preparing and sign-off of Validation Protocol, execution of validation, data compilation and evaluation, preparation and sign-off of Validation Report in case ‘validation’ approach is opted for Method Transfer.
    • Quality assurance–Transferring unit (TU) shall be responsible for:

    • Reviewing and approving deviations related to Analytical Method Transfer arising prior to or during the Analytical Method Transfer activity at TU (if any).
    • Performing investigation jointly with QA – RU in case of any failure during Method Transfer at RU, wherever needed.
    • Reviewing and approving Analytical Method Transfer Protocol or Transfer Waiver.
    • Reviewing of data generated at TU.
    • Quality Control–Receiving Unit (RU) shall be responsible for:

    • Reviewing and approving Analytical Method Transfer Protocol or Transfer Waiver.
    • Reviewing of data generated at RU during Method Transfer and approval of the same.
    • Approving and Reviewing  the Method Transfer Report/Certificate.
    • Performing investigation jointly with QA – TU in case of failure during Method Transfer.
    • Reviewing and approving Validation Protocol and Report in case ‘validation’ approach is opted for Method Transfer.
    • Reviewing and approving deviations related to Analytical Method Transfer arising prior to or during the Analytical Method Transfer activity at RU (if any).
    • Head of Department /Designee-Transferring Unit (TU) shall be responsible for:
    • Providing the analytical procedure, the reference standards, and the validation reports, as well as providing for the necessary training and assistance to the Receiving Laboratory as needed during the transfer.
    • Approving the ‘Method Transfer Initiation’ Form and Method Transfer certificate.
    • Reviewing and approving Analytical Method Transfer Protocol and Report.
    • Reviewing and approving deviations related to Analytical Method Transfer arising prior to or during the AMT activity at TU/RU (if any).
    • Approving Validation Protocol and Report in case ‘validation’ approach is opted for Method Transfer.
    • Head of Department/Designee-Receiving Unit(RU) shall be responsible for:

    • Providing qualified staff, ensuring that the facilities and instrumentation are properly calibrated and qualified as needed, and verifying that the laboratory systems are in compliance.
    • Consenting for initiating Method Transfer at RU based on readiness of RU.
    • Ensuring that all requirements as per Method Transfer Initiation Form are in place before start of Analytical Method Transfer activities at RU.
    • Reviewing and approving Analytical Method Transfer Protocol.
    • Reviewing and approving Method Transfer Report/Certificate.
    • Approving deviations related to Analytical Method Transfer arising prior to or during the AMT activity at RU (if any).
    • Reviewing and approving Validation Protocol and Report In case ‘validation’ approach is opted for Method Transfer.

5.0   ABBREVIATIONS & DEFINITIONS:

    • 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.
    • KRM : Key raw Material.
    • LOD : Limit of Detection.
    • LOQ : Limit of Quantification.
    • R&D : Research and Development
    • RF : Retardation factor
    • RRT : Relative retention time
    • RU : Receiving Unit.
    • TLC : Thin Layer Chromatography.
    • TU : Transferring Unit.
    • UV : Ultra-Violet
    • XRD : X-Ray Diffraction.
  • DEFINITION:
    • Transferring Unit (TU):

    • A laboratory (Batch Release Site/QC Laboratory at Manufacturing Site/Contract Laboratory/AR Laboratory etc .as applicable),which 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)
    • Receiving Unit:

    • A laboratory (Batch Release Site/QC Laboratory at Manufacturing Site/Contract Laboratory/AR Laboratory, etc., as applicable) which 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).
    • Collaborate or Indirect Type of Method Transfer:

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

    • An approach to Method Transfer which 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 <1224>
    • 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.
    • 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 which are directly proportional to the concentration of analyte in the sample.
    • LOD: Limit of Detection:

    • The lowest amount of analyte in a sample that can be detected, but not necessarily quantified as an exact value.
    • LOQ: Limit of Quantitation:

    • The lowest amount of analyte in a sample that 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 issued with signatures of relevant stakeholders from TU and RU stating the completion and outcome of 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:

    • Precision of analytical procedure expresses the closeness of agreement between a series of measurements obtained from multiple sampling 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.
    • Transfer Package:

    • A compilation of supporting documents required for Method Transfer which is sent by TU to RU before 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.
    • Transfer Waiver Certificate:

    • 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 solvents front.
    • Spiking:

    • The addition of a known amount of a compound to a standard, sample or placebo, typically for the purpose of confirming the performance of analytical procedure.

6.0   Procedure & Process Flow for Analytical Method Transfer :

  • Click hear for Complete Guideline & SOP – Method Transfer Protocol

Analytical Method Transfer (USP 1224) Guideline

7.0    Acceptance Criteria for Analytical Method Transfer (AMT)

TABLE 1-Assay

Transfer Type Parameter Acceptance Criteria for Analyte concentration in Matrix(% w/w) HPLC/UV/GC/CE/AAS/IC/Titrimetric
Analyte concentration in matrix(10-100%) Analyte concentration in matrix(1-10%)

(i.e. below 10%)

Analyte concentration in matrix (Less than 1%)
Collaborative/ Direct System Suitability Should comply with STP Comply with STP Should comply with STP
Collaborative Replicate analysis of sample RSD

Inter-lab testing data overall RSD Difference##

NMT 2.0%(N=6)

N.M.T. 2.0% (N=12)

N.M.T. 2.0%

N.M.T. 3.0%(N=6)

3.0% (N=12)

5.0%

NMT 5.0%(N=6)

N.M.T. 5.0% (N=12)

N.M.T. 15.0%

Direct (2-way approach)

Inter-analyst testing data overall RSD Difference##

NMT 2.0%(N=6)*

N.M.T. 2.0%

N.M.T. 3.0%(N=6)*

–   5.0%

NMT 5.0%(N=6)*

N.M.T. 15.0%

(3-way approach)

Inter-analyst testing data overall RSD Difference##

NMT 2.0%(N=6)*

N.M.T. 2.0%

N.M.T. 3.0%(N=6)*

NMT 5.0%

N.M.T. 5.0%(N=6)*

N.M.T. 15.0%

Note:

  1. ##Mean of RU analysis should be within specified acceptance criteria of TU analysis. In case of 3 way approach mean of TU analysis=mean of analysis done by TU Analyst at TU; mean of RU analysis=mean of analysis done by RU analyst at RU.

(Mean of Analysis done by TU Analyst-mean of analysis done by RU Analyst)

% Difference =——————————————————————————————–x100

Mean of Analysis done by TU Analyst

  1. If result are not complying with theses acceptance criteria, accuracy shall be demonstrated in triplicate on one batch at specification level RU by both TU Analyst and RU Analyst in case of direct Analytical Method Transfer and at respective location in case of collaborative AMT ,also precision shall be demonstrated as overall% RSD of all the accuracy values obtained by both the analysts.
  2. The acceptance criteria for accuracy/ precision shall be derived from data generated during method validation/qualification/verification.
  3. If accuracy/precision does not meet required acceptance criteria then investigation shall be initiated.
  4. # Overall RSD of 6 values obtained by TU and RU.
  5. N-Number of samples

TABLE 2-CU*

Transfer Type Parameter Acceptance Criteria
Collaborative/Direct System Suitability Result should comply with STP
Collaborative/Direct Inter-analyst testing data 1. Mean of RU analysis should be within +/- 3% of mean on TU analysis.

In case of 3 way approach, mean of TU analysis=mean of analysis done by TU analyst at TU; mean of RU analysis includes mean of tests done by TU analyst and RU analyst at RU.

2.AV value of 10 units of each analyst should comply with Pharmacopoeia.

*If CU method is equivalent to Assay method then separate Method Transfer is not required.

TABLE 3-Dissolution

Transfer Type Parameter Acceptance Criteria
Collaborative/Direct System Suitability Should comply with STP
Collaborative/Direct Replicate Analysis of Sample RSD

Inter-lab testing data

NMT 10.0%(X=6)

The difference in the mean value between the dissolution results using the same strength does not exceed an absoute10% at time points with less than 85% dissolved and does not exceed an absolute 5% for time points above 85%(X=12)

Direct

(2-ways approach)

Inter-Analyst testing data Overall RSD

Difference##

NMT 10.0%(X=6)

The difference in the mean value between the dissolution results using the same strength does not exceed an absoute10% at time points with less than 85% dissolved and does not exceed an absolute 5% for time points above 85%(X=12)

(2-ways approach)

Inter-Analyst testing data Overall RSD

Difference##

NMT 10.0%(X=6)

The difference in the mean value between the dissolution results using the same strength does not exceed an absoute10% at time points with less than 85% dissolved and does not exceed an absolute 5% for time points above 85%(X=12)

  1. ##Mean of RU analysis should be within specified acceptance criteria of TU analysis. In case of 3 way approach mean of TU analysis=mean of analysis done by TU Analyst at TU; mean of RU analysis=mean of analysis done by RU analyst at RU.
  2. If result are not complying with theses acceptance criteria, accuracy shall be demonstrated in triplicate on one batch at specification level RU by both TU Analyst and RU Analyst in case of direct Analytical Method Transfer and at respective location in case of collaborative Analytical Method Transfer, also precision shall be demonstrated as overall% RSD of all the accuracy values obtained by both the analysts.
  3. The acceptance criteria for accuracy/ precision shall be derived from data generated during method validation/qualification/verification.
  4. If accuracy/precision does not meet required acceptance criteria then investigation shall be initiated.
  5. X-Number of Units.

  6. For extended release/sustained release/Gastro resistant/delayed release formulations, specification shall be met at all-time points for both the analysis and data comparison shall be established at final time point.

TABLE 4-Preservative/Antioxidant/Other additives in drug product

Analyte Transfer Type Parameter Acceptance Criteria
Collaborative/Direct System Suitability Should comply with STP
Preservative/Antioxidant/Other additives in drug product

 

 

 

Collaborative

Replicate Analysis of Sample RSD

Inter-lab testing data

Difference##

NMT 10.0%(X=6)

±25.0%(N=12)

Direct (2-ways approach)

Inter-Analyst testing data Overall RSD*

Difference##

NMT 10.0%(X=6)

±25.0%(N=6)

(2-ways approach)

Inter-Analyst testing data Overall RSD*

Difference##

NMT 10.0%(X=6)

±25.0%(N=4)

Note:

  1. ##Mean of RU analysis should be within specified acceptance criteria of TU analysis. In case of 3 way approach mean of TU analysis=mean of analysis done by TU Analyst at TU; mean of RU analysis=mean of analysis done by RU analyst at RU.

(Mean of Analysis done by TU Analyst-mean of analysis done by RU Analyst)

% Difference =——————————————————————————————–x100

Mean of Analysis done by TU Analyst

  1. N-Number
  2. If result are not complying with theses acceptance criteria, accuracy shall be demonstrated in triplicate on one batch at specification level RU by both TU Analyst and RU Analyst in case of direct Analytical Method Transfer and at respective location in case of collaborative AMT, also precision shall be demonstrated as overall% RSD of all the accuracy values obtained by both the analysts.
  3. The acceptance criteria for accuracy/ precision shall be derived from data generated during method validation/qualification/verification.
  4. If accuracy/precision does not meet required acceptance criteria then investigation shall be initiated.
  1. *Overall RSD of 6 Values obtained by TU and RU.

TABLE 5 :Related Substances/Elemental Impurities, Residual Solvent & Trace Metal Estimation

Analyte Transfer Type Parameter Acceptance Criteria
HPLC/Titrimetric/GC/CE/AAS/IC
Related Substances/Elemental Impurities/Residual Solvent / Trace Metal Estimation

 

 

Collaborative/Direct System Suitability Should comply with STP
Collaborative Replicate Analysis of Sample RSD

Inter-lab testing data

Difference##

NMT 10.0%(X=6)

*(N=12)

Direct (2-ways approach)

Inter-Analyst testing data Overall RSD**

Difference##

NMT 10.0%(X=6)

*(N=6)

(3-ways approach)

Inter-Analyst testing data Overall RSD**

Difference##

NMT 10.0%(X=6)

*(N=4)

*For related substances

                        Analyte Level                                                 Acceptance Criteria

≥0.10% and <0.25%                                              ±25%

≥0.25% and <0.50%                                               ±20%

≥0.50%                                                                   ±15%

For Elemental impurities and Trace Metals

          Analyte Level                                                 Acceptance Criteria

50 ppm                                                                      ±25%

>50ppm                                                                     ±20%

For Residual solvents

Analyte Level                                                     Acceptance Criteria

>50 ppm                                                           % difference is not applicable

50 ppm and <100 ppm                                                  ±25%

 ≤100 ppm                                                                         ±20%

For Related Substances and Elemental Impurities

    • Data analysis shall not be applicable to Related Substances (known nad unknown) which are less than 0.10%(w/w or Area) provided all the analysis report values less 0.10% (w/w or area).
    • Data analysis shall not be applicable to Related Substances that are less than LOQ Level provided the value is less than LOQ on the reports of any one of the analyst.
    • Acceptance criteria shall be applicable only if impurity level is >0.10% LOQ whichever is higher .
    • If Impurity is above 0.10 % or LOQ in one or more batches and impurity level is below 0.10% or LOQ in other batches, then method transfer shall be concluded based on comparison of data of the batches having impurity level grater than 0.10% or LOQ whichever is higher.
    • If result are not complying with the acceptance criteria given in tablets 5 or in the conditions mentioned in (i),(ii),(iii) accuracy shall be demonstrated in triplicate  on one batch at specification level at RU by both TU analyst and RU analyst in case of direct Analytical Method Transfer and at respective location in case of collaborative AMT.
    • Spiking shall be done with at least one impurity for accuracy.

    • Also, precision shall be demonstrated as overall % RSD of all the accuracy values obtained by both the analyst.
    • Quantification shall be done against the respective impurity standard(concentration prepared at specification level)injected in duplicate.
    • The acceptance criteria for accuracy/precision shall be derived from data generated during method validation /Qualification/verification.
    • If accuracy/precision does not meet required acceptance criteria then investigation shall be initiated.
    • For total impurities, known impurities observed below LOQ shall not be added for calculation of total impurities.

For Residual Solvent:

    • Data analysis shall not be applicable to residual solvents which are less than 50 ppm provided the values of all the analyst are less than 50 ppm.
    • Data analysis shall not be applicable to residual solvents which are less than the limit of quantification (LOQ) level provided the value is reported less than LOQ by any one of the
    • In all such cases where analytical data cannot be compared as mentioned in (i),(ii)accuracy study shall be done in triplicate on one batch at RU by both TU Analyst in case of direct Analytical Method Transfer and at respective location in case of collaborative AMT by spiking the sample with ay least one residual one residual solvent (at 50% of specification level given in current specifications at the time of method transfer)
    • .Also, precision shall be demonstrated as overall % RSD of all the accuracy values obtained by both the analyst.
    • Qualification shall be done against the respective residual solvent standard(concentration prepared at 50% of specification level)injected in duplicate.
    • The acceptance criteria for precision/accuracy shall be derived from data generated during method validation/Qualification/verification.
    • If accuracy/precision does not meet required acceptance criteria then investigation shall be initiated.

Note: The observed chromatograms shall be similar in appearance between the TU and RU laboratories for impurities above 0.05%/disregards limit whichever is less (with respect to elution pattern).

** Overall RSD of 6 values obtained by TU and RU.

TABLE 6-Limit Test

Analyte Transfer Type Parameter Acceptance Criteria
Elemental Impurities,Genotoxic Impurities,etc. Collaborative /Direct Inter-analyst data Single analysis-result should comply with specifications

##

  1. Limit tests where content is determined and calculated using standard, accuracy shall be demonstrated in triplicate on one batch at specification level at RU by both TU Analyst in case of direct Analytical Method Transfer and at respective location in case of collaborative AMT.
  2. The acceptance criteria for accuracy shall be derived from data generated during method validation/qualification/verification.
  3. If accuracy does not meet  required acceptance criteria then investigation shall be initiated.
  4. Limit tests where content is not determined and not calculated using standard and in case of chemical tests (as application).

TABLE 7-Particle Size

Parameter Experiment Acceptance Criteria**
Particle Size

( By Laser Diffraction technique)

Analysis of sample in triplicate:

(i)By the TU Analyst in its Lab#.

(ii)By the TU Analyst in RU*.

(iii) By RU Analyst in RU.

Overall RSD between (i),(ii) and (iii) for D(v.0.1) should be less than 15%

Total RSD between (i),(ii) and for D(v.0.5)Should be less than 10%

Overall RSD between (i),(ii) and (iii) for D(v.0.9) should be less than 15%

Note: For particle size below 10µm,limits for acceptance criteria shall be double the stated Values.

*    Not applicable in case of collaborative study.

**  For Collaborative study ,the overall RSD is applicable between (i) & (iii) only.

#   Not Applicable  in case of 2-way approach, for 2-way approach, overall RSD is applicable      between (ii) & (iii).

TABLE 8-Microbiological Assay

Parameter Transfer Type Experiment Acceptance Criteria
Microbiological Assay Collaborative Sample to be analysed six times(N=6) at each laboratory RSD (N=6) & overall RSD (N=12)

Shall not be more than 7.5%.

Microbiological Assay (3 way Approach) Direct Sample to be analysed in duplicate (N=2) Overall RSD (N=6) shall not more than 7.5%
Microbiological Assay(2 way Approach) Direct Sample to be analysed in duplicate (N=3) Overall RSD (N=6) shall not more than 7.5%
N-Number of Replicates

 

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