sop for Analytical Method Transfer

Analytical Method Transfer
1.0 PURPOSE
To define a procedure for transfer of analytical methods from one laboratory to other laboratory.

SCOPE
This procedure is applicable to the transfer of analytical method (drug substances and medication items) for assay, related substances, dissolution, preservative/antioxidant content, uniformity content, residual solvents and microbiological test or any other critical test for drug substances

a: Process flow chart for analytical methodtransfer.
b: Pre-requisite checklist for analytical technology transfer from Transferring Laboratory to ReceivingLaboratory
c: Analytical Method TransferProtocol
d: Analytical Method TransferReport
e: Analytical method transfer approvalcertificate.
f: Analytical method transfer trainingcertificate.

DEFINITION &ABBREVIATION(S)
Definitions
TransferringLaboratory:
The laboratory that has conducted the original method development and method evaluation/ technique improvement or the laboratory that has previously acted as receiving laboratory has successfully completed the analytical methodtransfer.
Receiving Laboratory:
The laboratory to which the analytical method is to be transferred.

Abbreviations
API: Active Pharmaceuticals Ingredients
GC: Gas Chromatography
HPLC: High Performance LiquidChromatography.
ppm: Parts PerMillion.
QA: Quality Assurance.
QC: Quality Control.
RSD: Relative Standard Deviation.
RL: ReceivingLaboratory
TL: TransferringLaboratory

RESPONSIBILITY
Corporate QualityAssurance
To prepare theguideline.
To ensure implementation of theguideline.
TransferringLaboratory:
To demonstrate analytical method to receivinglaboratory.
To communicate with Receiving laboratory and resolve the issues of analytical methodtransfer.
To provide analytical method transfer package to receivinglaboratory.
To provide pre-requisite to receivinglaboratory.
To provide analytical method transferprotocol.
To provide proper training to receiving laboratory analysts stepwise during performing technology transfer activities (safety considerations, clear equations, any criticality of sample preparation and calculationsetc.)
To provide only history/ issue trend, ifany.
ReceivingLaboratory:
To perform analysis as per standard test procedure provided by transferringlaboratory.
To prepare standard test procedure, specification as per transferpackage.
To report results and critical observation and preparation of analytical method transferreport.
To communicate results and observation of analytical method transfer with transferringlaboratory.
Head QC or designee- Transferring & Receivinglaboratory
To review and approve the analytical method transferprotocol.

To evaluate impact of the failure (if any) and decide further course ofaction.
To review the critical observation (if any) and take the necessaryaction.
To review and approve the report, training certificate and technology transfercertificate.
Quality AssuranceHead:
To ensure implementation of system as perprocedure.
To approve the protocol, report, training certificate and technology transfercertificate.

Distribution:
I. QualityAssurance
II. QualityControl

PROCEDURE:
General
After successful development and verification of analytical method, the transferring laboratory in consultationwithreceivinglaboratoryshallinitiatetheprocessbyinformingthereceivinglaboratory in advance of the proposed methodtransfer.
Transferring laboratory shall send a pre-requisite checklist of analytical method to receiving laboratory (a particular synthetics, reagents, reference guidelines, instruments, segment needed to accepting lab) as per Attachment-II.
Receiving laboratory shall review and verify the pre-requisite check list of analytical method to be transferred, procure all required reagents and ensure availability of required instruments and inform to transferring lab for methodtransfer.
In-house drug /drug product, analytical method shall be transferred. Compendia method shall not be transferred. Only method verification is required for compendia method. If there is any modification in compendial method then method transfer shall be required.
In the case of multiple strength of the same product for linear and non-linear, decision to be taken for analytical method transfer to be performed on which strength by transferring laboratory based on the criticality of the product and justification for rational shall be provided by the transferringlaboratory.

Analytical methodtransfer

Transferring laboratory shall send the Analytical Method Transfer protocol as per Attachment-III to the receiving laboratory. Receiving laboratory shall review the protocol and shall be approved by Receiving and transferringlaboratory.
Transferring laboratory shall analyze the sample of one batch of evaluation sample which is going to be sent to the receiving laboratory for tests and report the result. If a result of the sample meets the specification then transferring laboratory shall mention the same in the Certificate of Analysis (COA) and send it to receiving laboratory.
Transferring laboratory shall provide the analytical method transfer package to the receiving laboratory and receiving laboratory shall plan for tests for method transfer as mentioned in section6.2.9.
Before execution of the activity for analytical method technology transfer, lab training and familiarization with the method to be transferred, shall be organized by transferringlaboratory.
The analyst at both the laboratory (Transferring and receiving) shall perform analysis on the same batch.
The receiving laboratory shall use instrument that are equivalent to the transferringlaboratory.
The sample shall be tested according to approved analytical method provided by Transferring laboratory.
Method transfer activity shall be recorded in respective analytical method transfer report format (Attachment-IV).
Methodology and Acceptance Criteria: Analytical method transfer activity shall be executed by 2 analysts (one analyst from the transferring laboratory and one analyst from the Receivinglaboratory).

Test	Replicate of Tests	Acceptance Criteria
Identification	2 analyst (one analyst from each site)	The result of both analysis shall meet the requirement as per specification.
Assay	2 Analyst x 6 samples preparation (Prepare samples from same lot/ batch no. and analyse)	The results obtained by individual analyst % RSD forassay Analyst A: NMT 2.0 % Analyst B: NMT 2.0 % Overall RSD or both the Analyst NMT 3.0 %.
Content Uniformity/ Dose Uniformity*	2 Analyst x 10 dosage unit (Prepare samples from same lot/ batch no. and analyse)	Mean RSD of both analyst NMT 5.0 %. Overall RSD of both the analyst NMT 3.0 %.

Test	Replicate of Tests	Acceptance Criteria
* Method transfer for content uniformity to be performed only if the assay method is different from content uniformity method.
Preservative content/ Antioxidant	2 Analyst x 6 samples preparation (Prepare samples from same lot/ batch no. and analyse)	Individual analyst % RSD should be NMT 10.0 % The overall % RSD for results obtained by both the analysts should be NMT 15.0 %.
Dissolution/ % Drug Release	2 Analyst x 6 units (Prepare the dissolution samples on 6 units from same lot/ batch no. and analyse)	Immediate Release- RSD of six units of individual analyst NMT 5.0%. Overall RSD for both the analyst NMT 5.0%.
		Delayed Release- For Acid stage: It should meet the specification for both the analyst. For buffer stage: RSD of six units of individual analyst NMT 5.0%. Overall RSD for both the analyst NMT 5.0%.
		Modified Release- Mean result obtained of both analyst NMT 10.0% at each specified time point.
Related Substance/ compounds/ chromatography purity	2 Analyst x 6 samples preparation (Prepare samples from same lot/ batch no. and analyse)	Case-1: If the specification limit of impurities is less than and equal to 0.20%. The % RSD obtained by individual analyst and the overall % RSD for result obtained by both the analysts should be NMT 15.0. Case-2: If the specification limit of impurities is t more than 0.20%. The % RSD obtained by individual analyst should be NMT 10.0. The overall % RSD for result obtained by both the analysts should be NMT15.0. Case-3: If the specification limit of impurities is less than and equal to 0.10%. The % RSD obtained by individual analyst should be NMT 25.0. The overall % RSD for result obtained by both the analysts should be NMT 25.0.
NOTE: Any unknown impurities below 0.05% and known impurities below LOQ shall not be compared.

Test	Replicate of Tests	Acceptance Criteria
Residual Solvents	2 Analyst x 6 samples preparation (Prepare samples from same lot/ batch no. and analyse)	If solvent content is more than 50 ppm and 50.0%, the difference of the means of each solvent result by 2 analysts should be NMT20.0%. If solvent content is less than or equal to 50 ppm, the RSD of each results of residual solvents obtained by each analyst for each solvent shall NMT 15.0%.
Microbiological testing (Qualitative and Quantitative Limit tests)	Execute common on-site validation.	Demonstrate recovery of microorganism and recoverylevelwithinacceptancelimitsspecifiedin protocol or in Standard testing procedure.
Any other critical test	As per the protocol	As per the Specification

Method Transfer waiver: Subsequent to this transfer activity, if new strengths are added it shall be considered for a waiver/further transfer. The transfer waiver

shall be taken in followingcases:
If the newly added strength lies between lower and higher strengths of the transferred product, waiver shall be taken without any furtherjustification.
However, if the proposed strength does not lie in between lower and higher strengths, it shall also be considered for waiver based upon the

familiarity/ expertise of the method at the receiving laboratory. If any of the method are found critical based on the strength, same shall be considered for

method transfer activity.
The new product composition is comparable to that of an existing product and/ or the concentration of the active ingredient is similar to that of an existing

product and is analyzed by procedure with which the receiving laboratory already hasexperience.
The analytical procedure transferred is same as or very similar to a procedure already inuse.
If eligible for method transfer product, the transferring laboratory shall provide document with appropriatejustification.

Documentation:
Method transfer of all original documents pertaining to method transfer shall be achieved at Receiving Laboratory and TransferringLaboratory.

Assay

Six replicate assay shall be performed by both analysts from both the laboratories on the same sample at receiving laboratory.
Acceptance criteria for drug substance/ drugproduct
All the system suitability criteria shall comply as per the respective standard testprocedure.
All the assay results shall comply as per the respectivespecification.
RSD of assay results obtained by each analyst shall be compared as mentioned in the abovetable.
Overall RSD obtained by each analyst shall also be compared as mentioned in the abovetable.

Content uniformity/DoseUniformity
Test shall be performed on 10 dosage units sample preparation from same sample by both analysts at receiving laboratories (Total 20analysis).
If the analytical method for the content uniformity test is equivalent to the assay method, i.e. standard and sample are prepared at equivalent

concentrations, chromatographic system and system suitability criteria are the same, a method transfer for content uniformity need not be carriedout.
Acceptance criteria for content uniformity/doseUniformity
All the system suitability criteria shall comply as per the respective standard testprocedure.
All the content uniformity results shall comply as per the respectivespecification.
RSD of content uniformity results of 10 dosage units obtained by each analyst shall not be more than 5.0 %.
Overall RSD for each analyst shall not be more than 3.0%.

Related substances /Related Compound/ ChromatographyPurity
Test shall be performed on six sample preparation from same samplebyboth analysts at receiving laboratories (Total 12analysis).
Acceptance criteria for related substances /related compound/ ChromatographyPurity
RSD of individual impurity and total impurities results of six preparations obtained by each analyst shall be compared as mentioned in the abovetable.
Overall RSD of individual impurity and total impurities results of 12 preparations obtained by both analysts shall also be compared as mentioned in the abovetable.

NOTE:
For any unknown impurities below 0.05% and known impurities below LOQ shall not be compared.

Residual solvent
Test shall be performed on six sample preparation for same sample by both analysts at the receiving laboratories (Total 12analysis).
Acceptance criteria for residualsolvent
All the system suitability criteria shall comply as per the respective standard testprocedure.
All the results of residual solvent shall comply as per the respectivespecification.
RSD of the results of residual solvents obtained by each analyst for each solvent shall be compared as mentioned in the abovetable.
The difference of the means of each solvent determined by the two analyst of each laboratory (inter– laboratory) shall be compared as mentioned in the abovetable.

Preservative / Antioxidantcontent
Analyst of both laboratory shall test six sample preparationseach.
Acceptance criteria for Preservative / Antioxidantcontent
All the system suitability criteria shall comply as per the respective standard testprocedure.
All the results of preservative content shall comply as per the respectivespecification.
RSD of the six results of each analyst shall not be more than 10.0%.
Overall RSD of the results of each analyst shall not differ by more than 15.0%.

Dissolution / ReleaseRate
The dissolution test shall be carried out by both the analyst at receiving laboratory on six units of the sample of eachlot.
Acceptance criteria for Immediaterelease
The RSD of six results obtained in each laboratory shall be compared as mentioned in the abovetable.
Overall RSD of the results obtained in each laboratory shall also be compared as mentioned in the abovetable.
Acceptance criteria for Delayedrelease
The release at acid stage for delayed release dosage forms shall comply with the specifications at receiving laboratory by bothanalysts.
For the release at buffer stage for delayed release dosage forms, result obtained at each laboratory shall be compared as mentioned in the abovetable.
Overall RSD of both the analysts shall also be compared as mentioned in the abovetable.

Acceptance criteria for Extended /Modifiedrelease
The absolute difference in mean result of both the analysts obtained at receiving laboratory at final time point shall be compared as mentioned in the abovetable.

Identification
One analyst in each laboratory shall carry out the tests on same sample at receivinglaboratory.
Where the identification test is based on the results of another test, the transfer shall be deemed complete with the transfer of that test e.g.

Identification based on retention time in HPLC/ GCetc.
Acceptancecriteria
The results of both analysts shall meet with the requirements stated in the productspecifications.

Microbiological Testing (qualitative and quantitative limittests)
Execute common on-site validation protocol in triplicate by the transferring laboratory and receiving laboratory. Use different lots for each validationexercise.
Acceptancecriteria
Demonstrate recovery of microorganisms, recovery level should be with in acceptance limit specified in protocol or in specification by either the laboratory oranalysts.
Drug substances and dosage form test shall be transferred as per belowtable.

Dosage Form
Tests	Drug Substance	Solid	Parenteral	Semisolid	Liquid	Oral	Dry	Ophthalmic	Inhalation
Assay	√	√	√	√	√	√	√	√	√
Content uniformity	NA	√	√	√	√	√	√	√	√
Related substance/ Impurity/ Degradants	√	√	√	√	√	√	√	√	√
Residual solvent	√	√	NA	√	NA	√	NA	NA	√
Dissolution	NA	√	NA	NA	NA	√	√	NA	NA
Identification	√	√	√	√	√	√	√	√	√
Preservative Assay	NA	NA	√	√	√	NA	NA	√	NA
Microbiological (MLT)	√	√	√	√	√	√	√	√	√

Concerned Head or designee of receiving laboratory shall instruct the analyst to perform method transfer fortest.
Analyst of receiving and transferring laboratory shall perform testing as per approved STP and analytical method protocol given by transferringlaboratory.
Analytical method transfer shall be completed within 15 days from the day it was started by both the laboratory of the same batch/ lot ofsample.
Analyst shall compile the data and compare the result with certificate of analysis received from transferring laboratory or generate at the site as per acceptancecriteria.
Analyst shall communicate any observations / discrepancies observed during method transfer to Head QC or designee and shall be mentioned in method transferreport.
Concerned Head or designee of receiving laboratory shall ensure the performance and correctness of result of methodtransfer.
Head or designee of receiving laboratory shall communicate the observations/discrepancies observed during method transfer with transferring laboratory vice

versa and can make amendment after confirming with transferring laboratory or receiving laboratory in the method but not limited to following.
• Step up / step down in sample or standard preparation or mobile phasepreparation.
• Addition of identificationsolutions.
• Filtercompatibility

• Sonication time /temperature
• Centrifuge time and / orspeed.
• Stability ofsolution
Based on observation / discrepancies, receiving laboratory shall revise the method and send the revised copy of method and justification if necessary to transferringlaboratory.
If results of method transfer complies as per acceptance criteria then method transfer shall be considered ascomplete.
Receiving laboratory and transferring laboratory shall prepare a comparative summary method transfer report as per Attachment-IV which shall be approved by Receiving and transferringlaboratory.
In case of non –compliance of acceptance criteria the analysis at both the end shall be investigated and concluded in the method transferreport.
In case of any failure, head or designee of receiving laboratory shall evaluate and decide further course of action and same shall be communicated to transferringlaboratory.

Test Results andReports
All analytical results shall be recorded on respective substance/ product data sheet/ protocoltemplate.
Each Transferring and receiving laboratory shall compile the results obtained at the receiving laboratories.
Head QC and Head QA shall review the reported data and shall be approved by both thelaboratories.
If the results do not meet the acceptance criteria, both the laboratories shall investigate reasons for the same and recommendations shall bemade.
The actions and recommendations shall be implemented and the report shall be resubmitted for approval.

Analytical Method TransferCertificate:
If the results of both the laboratories meet the stated acceptance criteria, the Transferring laboratory shall prepare analytical method Transfer certificate (Attachment -V) and release afterapproval.
The Transferring laboratory shall initiate analytical Method Transfer Certificate and the same shall be reviewed and approved by receiving laboratory Head QA and HeadQC.

Analytical Method Transfer training Report

Analytical Method transfer training Certificate shall be prepared by Transferring laboratory analyst and approved by receiving laboratory Head QA and QC

once analytical method is successfully transferred

REVISIONHISTORY