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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
This SOP describes the process and requirements for the transfer of analytical test methods from Transferring Unit to a Receiving Unit.

Scope
This SOP is applicable to all the method transfers made by Transferring Unit to Receiving unit.

Responsibility
All intended users.

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), 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

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.


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

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 Transferring unit, shall be included in Method Transfer program.
  • Head, QA/QC and Head, 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 criticality of the method, as agreed by Head, QA/QC Head R&D – Analytical.

Types of Method Transfers:

Comparative Testing:

A.  Indirect transfer/collaborative:
  • In this type of method transfer, Transferring unit and Receiving unit shall analyze same batch of sample at their respective locations and the results obtained shall be compared.
  • 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 transferring unit. The Chemist/analyst, receiving unit (QC/other laboratory) shall perform the analysis in triplicate and provide the results to transferring unit.

B.  Direct Transfer:
  • This type of method transfer shall include the physical demonstration and joint analysis of sample by Transferring unit, and the Receiving unit
  • Transferring unit visits the receiving unit and demonstrates the method by analyzing the sample as per the protocol. After 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 transfer the transferring unit shall include receiving unit in inter laboratory co–validation including them as a part of the validation team at the transferring unit or receiving unit and thereby obtaining data for the assessment of reproducibility. 
  • The assessment is made using preapproved transfer or validation protocol providing the details of 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 which 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 composition of 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. 
  • Following are circumstances that may justify 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.


  • Analytical parameters like precision by both 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 experiment (Placebo interference) shall be carried out by the Receiving Unit in specified range as per the protocol.
  • Head QA/QC and Head R&D analytical mutually decide on additional parameter based on the complexity of the method. In case of 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 QC laboratory at the manufacturing location well in advance of the proposed exhibit batch/production batch.
  • Before carrying out the method transfer, Head, QA/QC and Head, R&D – Analytical shall set in place an approved protocol. The protocol shall either be prepared on the basis of type of transfer as mutually decided by Head, R&D – Analytical and Head, QA/QC.
  • R&D – Analytical shall inform/provide plant, a list of special chemicals, reagents, working standards, GC/HPLC columns required to QC laboratory.
  • Protocol shall be initiated by the scientist, R&D – Analytical.

Preparation of Protocol:
  • Protocol shall be specific to the product and method. Protocol shall contain the
  1. Objective
  2. Scope
  3. Responsibility of 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 market, 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 increase in ascending order.

  • For 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 increase in ascending order.

  • Protocol shall be prepared by the R&D – Analytical and independently reviewed by another designee. The same shall be approved by Head, R&D – Analytical or designee and forwarded it for the approval of 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 trainings to the Chemist/analyst, QC to make him understand the method complexity and provide him for 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 note book issued at R&D. Details of instrument usage shall be written in the instrument logbook of respective location.
  • The results of chemist/analyst-QC shall be reviewed by the scientist or designee, R&D – Analytical for accuracy. Similarly the results of Scientist or designee, R&D – Analytical shall reviewed by the Chemist/analyst-QC.
  • All the data of method transfer shall be reviewed by Head QC and approved by Head Quality.
  • All the original raw data, 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 Head 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, method transfer certificate shall be signed by Head QA.
  • If the acceptance criteria 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 observed, method can then be transferred with proper justification. If no such ambiguity is found, perform the reanalysis of analytical method transfer at receiving unit.
  • For failure in case of direct method transfer, a fresh batch/ aliquot of sample shall be taken for reanalysis. Repeat analysis shall be performed in duplicate and 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, R&D – Analytical.
  • Investigation report shall be filled along with the transfer certificate.

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.

Revision History
Nil

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