Analytical Procedures Transfer Quiz
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Questions and Answers

What is the name of the document that outlines the details of a procedure transfer?

  • Covalidation protocol
  • Validation protocol
  • Transfer protocol (correct)
  • Prequalification protocol

    • What is an example of a 'similar product' for which a transfer of analytical procedures may be waived?

  • A product with the same API but different excipients
  • A product with the same API and excipients but different concentrations. (correct)
  • A product with different API but similar excipients
  • A product with the same API and excipients but different dosage form

    • Which of the following is NOT a potential component of a transfer protocol?

  • Materials: samples, reference standards
  • Training program for the receiving unit personnel (correct)
  • Experimental design: specific characteristics to be evaluated
  • Acceptance criteria
  • Instruments and analytical procedure

    • Which of the following is NOT a way to demonstrate the transfer of analytical procedures, as mentioned in the text?

    <p>Method validation at the receiving unit (B)</p> Signup and view all the answers

    What are the minimum number of batches that should be analyzed at each test site to demonstrate reproducibility for a method transfer?

    <p>2 batches (B)</p> Signup and view all the answers

    How should the concentration of spiked impurities be chosen for demonstrating transfer of analytical procedures?

    <p>At concentrations close to the specification limits (D)</p> Signup and view all the answers

    Which of the following is NOT a factor considered for waiving a transfer of analytical procedures?

    <p>The method used is a newly developed method (E)</p> Signup and view all the answers

    Which of the following are required for a successful method transfer? (Select all that apply)

    <p>Specificity (B), Reproducibility (D)</p> Signup and view all the answers

    What is the purpose of using a blank solution in the context of specificity?

    <p>To show that there is no interference. (B)</p> Signup and view all the answers

    Which method is suggested to check peak purity of a drug substance?

    <p>Photodiode array detector (A)</p> Signup and view all the answers

    For establishing accuracy, what is typically used as the reference substance?

    <p>An RS of known purity (D)</p> Signup and view all the answers

    What range is recommended for spiking the FPP with known quantities of API?

    <p>80% to 120% of label claim (C)</p> Signup and view all the answers

    How should impurities be managed within the accuracy assessment?

    <p>Spike API/FPP with known amounts of impurities. (C)</p> Signup and view all the answers

    Which statement best describes precision in the context of accuracy assessments?

    <p>It indicates the reproducibility of results under unchanged conditions. (C)</p> Signup and view all the answers

    What is the typical mean result range for report recovery in accuracy determination?

    <p>98.0-102.0% (A)</p> Signup and view all the answers

    What does ICH Q2 state regarding accuracy inference?

    <p>Accuracy can be inferred after establishing precision, linearity, and specificity. (C)</p> Signup and view all the answers

    What does LOD stand for in the context of validation?

    <p>Limit of Detection (D)</p> Signup and view all the answers

    What is the signal to noise ratio required for LOD?

    <p>3:1 (B)</p> Signup and view all the answers

    What must an applicant provide for validation?

    <p>Method of determination and limits (B)</p> Signup and view all the answers

    Which of the following is not a factor for assessing robustness in analytical methods?

    <p>Changes in instrument sensitivity (C)</p> Signup and view all the answers

    What is indicated if robustness shows limitations in a method?

    <p>Limitations must be noted in the method (D)</p> Signup and view all the answers

    When is revalidation necessary?

    <p>Changes in the synthesis of the drug substance (D)</p> Signup and view all the answers

    What does the linearity of an analytical procedure indicate?

    <p>Its ability to obtain test results proportional to concentration. (D)</p> Signup and view all the answers

    What is the acceptable range for assay concentration in analytical procedures?

    <p>80-120% (D)</p> Signup and view all the answers

    What is the primary objective of validating an analytical procedure?

    <p>To demonstrate suitability for its intended purpose (A)</p> Signup and view all the answers

    Which of the following is recommended for acceptance criteria in validation?

    <p>Criteria based on normal process experience (A)</p> Signup and view all the answers

    Which correlation coefficient indicates an acceptable level of linearity for assay?

    <p>r ≥ 0.999 (C)</p> Signup and view all the answers

    What does the quantitation limit (LOQ) refer to in an analytical procedure?

    <p>The lowest amount that can be quantitatively determined with precision. (B)</p> Signup and view all the answers

    What should the minimum number of concentrations be to demonstrate the range of an analytical procedure?

    <p>5 concentrations (D)</p> Signup and view all the answers

    Which of the following is NOT a requirement for content uniformity?

    <p>Accuracy of 5% within the test concentration (A)</p> Signup and view all the answers

    Which of the following describes the detection limit (LOD) of an analytical procedure?

    <p>It is the lowest amount of analyte that can be detected but not quantified. (C)</p> Signup and view all the answers

    What is the suggested range for impurities in relation to the quantitation limit?

    <p>LOQ to 120% of the shelf life limit (C)</p> Signup and view all the answers

    What is required for in-house methods during full validation?

    <p>Specificity, linearity, accuracy, and intermediate precision (B)</p> Signup and view all the answers

    What does verification typically pertain to?

    <p>Compendial methods primarily (D)</p> Signup and view all the answers

    Why is verification data needed when adopting compendial methods?

    <p>Because different sources may introduce new impurities (C)</p> Signup and view all the answers

    What is expected for the purity validation of specified impurities not in the monograph for API?

    <p>Full validation with all parameters including LOD/LOQ (B)</p> Signup and view all the answers

    Which aspect is not primarily required for the assay of the API?

    <p>Validation for impurities included in the monograph (B)</p> Signup and view all the answers

    What must be ruled out when conducting the assay for FPP?

    <p>Excipient interference (C)</p> Signup and view all the answers

    For a compendial method to be suitable under actual conditions, what should be verified?

    <p>All conditions of use for specified API or FPP (D)</p> Signup and view all the answers

    Which of the following validates the equivalency of an in-house method?

    <p>Specificity testing when a compendial standard is claimed (C)</p> Signup and view all the answers

    What is required for an in-house purity/assay method to be claimed as compendial standard?

    <p>Full validation and demonstration of equivalency to the compendial method (B)</p> Signup and view all the answers

    What does demonstrable equivalency ensure for an in-house method?

    <p>The in-house method is at least not inferior and satisfies compendial standards if applied (C)</p> Signup and view all the answers

    Which statement best describes the reporting validation process?

    <p>All relevant measures such as specificity, accuracy, precision, linearity, and sensitivity must be reported (A)</p> Signup and view all the answers

    What occurs to a compendial method when adjustments are made outside the allowable adjustments?

    <p>It is considered an in-house method (A)</p> Signup and view all the answers

    What is the primary goal of method transfer in analytical procedures?

    <p>Documenting the qualifications of the receiving unit to perform an external test method (C)</p> Signup and view all the answers

    What should be included in the validation report concerning sensitivity?

    <p>Findings of LOD and LOQ must be clearly stated (A)</p> Signup and view all the answers

    What aspect of validation involves evaluating the precision of a methodology?

    <p>Repeatability and intermediate precision data (A)</p> Signup and view all the answers

    Which of the following is NOT a part of the validation process as outlined?

    <p>Conducting a user survey on method clarity (A)</p> Signup and view all the answers

    Flashcards

    Specificity

    The ability to measure only the analyte without interference.

    Blank solution

    A solution with no analyte, used to show no interference.

    Placebo

    A substance with no active ingredient, demonstrating the absence of interference.

    Spiked samples

    Samples added with known substances to ensure separation in results.

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    Stressed sample

    Sample subjected to degradation to show resolution with analyte.

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    Accuracy in testing

    Closeness of test results to the true or reference value.

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    Assay

    Determining the purity of API against a known standard value.

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    Impurities analysis

    Assessing known impurities in a sample to ensure quality.

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    LOD

    Limit of Detection: the lowest concentration that can be detected but not quantified.

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    LOQ

    Limit of Quantification: the lowest concentration that can be reliably quantified.

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    Signal to Noise Ratio

    A measure comparing the level of a desired signal to the level of background noise.

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    Robustness

    A method's ability to remain unaffected by small variations in parameters.

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    System Suitability Parameters

    Criteria to ensure the method is performing correctly and consistently.

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    Revalidation

    Process of validating an analytical method again due to changes.

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    Validation Characteristics

    Criteria to assess the reliability of an analytical method.

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    Chromatograms

    Visual output representing the separation of components in a mixture.

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    Linearity

    The ability of an analytical procedure to obtain results proportional to analyte concentration within a range.

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    Range

    The interval between the upper and lower concentrations where an analytical method maintains precision and accuracy.

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    Assay Concentration

    The acceptable range for assay test concentrations, typically 80-120% of the target value.

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    Content Uniformity

    Measurement variation that should be between 70-130% of the test concentration.

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    Dissolution Limits

    Dissolution testing limits should be ±20% of specified limits, covering a range for controlled release.

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    LOD (Limit of Detection)

    The lowest amount of analyte that can be detected but not quantified precisely.

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    LOQ (Limit of Quantitation)

    The lowest amount of analyte that can be quantitatively determined with precision and accuracy.

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    Correlation Coefficient (r)

    A statistic indicating the strength of a linear relationship, with r ≥ 0.999 for assay and r ≥ 0.99 for impurities.

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    Transfer Protocol

    A documented procedure detailing method transfers and validations.

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    Analytical Procedure

    Methods used to analyze substances in a sample.

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    Reproducibility

    The ability to obtain consistent results across different tests.

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    Evaluation Outcomes

    The assessment of results obtained from analytical tests.

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    Waiver Possibility

    Conditions under which a formal method transfer may be skipped.

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    Acceptance Criteria

    The minimum requirements that results must meet to be considered acceptable.

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    Impurity Analysis

    Testing to identify and quantify impurities in a material.

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    Verification

    Confirmation that a compendial method works under actual use conditions.

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    Equivalency

    Demonstrating that an in-house method is comparable to a compendial standard.

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    Compendial methods

    Standardized procedures developed for specific APIs or FPPs in official compendia.

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    API

    Active Pharmaceutical Ingredient used in drug formulations.

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    FPP

    Finished Pharmaceutical Product that contains the API along with excipients.

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    LOD/LOQ

    Limit of Detection and Limit of Quantification for measuring impurities.

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    Interference

    When other substances affect the measurement of the analyte in testing.

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    Full validation

    Complete verification of in-house methods for specified impurities.

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    Reporting Validation

    Documentation of method performance metrics including specificity, accuracy, and precision.

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    Method transfer

    Process of qualifying a new lab to use a specific analytical method from another lab.

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    Specificity in validation

    The ability of a method to measure only the target analyte without interference.

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    Intermediate precision

    Variance of test results when performed under different conditions or by different operators.

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    Study Notes

    Validation of Analytical Methods

    • Validation is the demonstration that a method is suitable for its intended purpose, with reliable, accurate, and reproducible results.
    • Validation provides confidence that the method will function correctly under defined conditions.

    Outline of Analytical Method Validation

    • Validation/Verification of the methods
    • Compendial methods versus Non-compendial methods
    • Summary of analytical procedure and validation in QOS
    • Method transfer

    Validation of Analytical Procedures

    • Testing a method to demonstrate its suitability for its intended purpose and the reliability, accuracy, and reproducibility of its results.
    • Provides confidence that a method performs correctly under set conditions.
    • Includes tests for the control of impurities, quantification of active ingredients in samples of drug substances/products, assay, content uniformity, dissolution, and preservative content.

    Validation Characteristics for Analytical Procedures

    • Specificity: The ability to discern the analyte from other components, including impurities, degradants, and matrix. Lack of specificity can be complemented by other procedures.

    • Includes tests like blank solutions and spiked samples to demonstrate no interference. Stressed sample (10-20% degradation) verifies resolution between degradants and the analyte. Using PDA (photodiode array) detectors for peak purity checks for drug substance validation.

    • Accuracy: The closeness of the test results to the true value (trueness), using a conventional or reference value. Accuracy should be determined across the range of the analytical procedure.

    • Assay accuracy using a reference standard (RS) or alternate method (known accuracy), analysis in triplicate.

    • FPP (Placebo/Drug) accuracy testing using known quantities of API, at three levels (80%, 100% and 120%) of labeled claim is recommended. Recovery is reported (mean and RSD) between 98.0% and 102.0%.

    Precision

    • Precision of an analytical procedure is the closeness of agreement between a series of results, obtained with multiple samples and tested under prescribed conditions.

    • Measured by the relative standard deviation (RSD) at three levels: repeatability, intermediate precision, and reproducibility.

    • Repeatability: Same analyst, same equipment, and single batch at test concentration (minimum of 6 determinations) or 3 levels (80%, 100%, and 120%) with 3 replicates for each level. Acceptable RSD is typically ≤ 2.0% for assay, and ≤10% for impurities >0.05%.

    • Intermediate precision: Test on multiple days, analysts, or equipment. RSD should match method precision.

    • Reproducibility (inter-laboratory): Not typically requested for submissions, though considered for method transfer.

    Linearity/Range

    • Linearity describes the direct proportionality between test results and the analyte concentration, within a given range.

    • Range specifies the interval of analyte concentrations where the procedure displays acceptable precision, accuracy, and linearity (minimum of 5 concentrations).

      • The range and values for different test types are as below: Assay (80-120%), Content Uniformity (70-130%), Dissolution ( 20% limit, 0-110% for controlled release) and Impurities (LOQ-150% of shelf life limit).

    • Correlation coefficient (r) for assay should be ≥ 0.999, for impurities ≥ 0.99

    • Y-intercept and slope should be included with the plot of data.

    LOD/LOQ

    • LOD (Limit of Detection): The smallest amount of analyte that can be detected but not usually quantified.
    • LOQ (Limit of Quantitation): The smallest amount of analyte that can be quantified with acceptable precision and accuracy.
      • LOD: visual evaluation, ratio of signal to noise (3:1) or standard deviation of the response and the calibration curve slope at approximately LOD/LOQ levels. LOQ values at 10:1.
    • LOD/LOQ are not typically required for assay/dissolution.

    Robustness

    • The method's ability to remain unaffected by small, but deliberate changes in method parameters.
    • Factors like pH, mobile phase composition, different columns, temperature, and flow rate are evaluated.
    • System suitability parameters should be established indicating the acceptable ranges of deviations.

    Revalidation

    • Revalidation may be necessary when there are changes in the drug substance synthesis, finished product composition, or analytical procedure.

    Compendial versus In-house Standards

    • Validation: In-house methods require full validation (specificity, linearity, accuracy)
    • Verification: Compendial methods require verification.
    • Equivalency: In-house methods claiming equivalence to a compendial method require demonstration of equivalence.

    When Compendial methods are adopted

    • API Assay: Generally, no additional validation is required, but specificity for any specified impurities should be validated.
    • API Purity: Full (re)validation for impurities not in the monograph.
    • FPP Assay: Specificity, accuracy and precision for interference from excipients should be validated.
    • FPP Purity: Full validation for impurities not in the monograph

    Compendial Standard Claimed, but In-house method used

    • Full validation is required for in-house methods.
    • Equivalency is needed between in-house and compendial method (Assay and Related substances evaluation).

    Equivalency

    • Demonstrate the in-house method is not inferior, and the compendial method is attainable
    • Two samples can be sufficient comparisons

    Transfer of Analytical Procedures

    • Method transfer is a process enabling a lab (receiver) to utilize a method developed in another existing site (transfer).
    • Verify receiving lab's method understanding and execution capability in the new lab.
    • Several demonstration approaches like comparative testing on homogeneous lots; covalidation between labs, and/or a pre-approved transfer protocol may be used.

    PQP practice

    • Method transfer must include specificity, reproducibility to be verified, and multiple batches (2 or more) at site-specific tests
    • Impurities should be considered and reviewed

    Reporting Validation

    • For validation reporting: Specificity, Accuracy(Conc., recovery, RSD), Precision (RSD), Linearity (range), and Sensitivity (LOD, LOQ)
    • QOS 3.2 R.2 (example of a validation method that is needed)

    Conclusion

    • Clarify and completely describe the analytical methods
    • Confirm equivalence with compendial methods if compendial standards are being used
    • Review verification/validation/equivalence data to demonstrate suitability of the method of use
    • Review QOS 3.2.R.2 and confirm the data matches the submitted dossier.

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    Test your knowledge on the key aspects of analytical procedures transfer. This quiz covers protocol components, methods to demonstrate reproducibility, and considerations for successful method transfer. Perfect for professionals in pharmaceutical and analytical chemistry.

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