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Volume I - 5.4 Test Methods and Method Validation

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ORA Laboratory Policies

Food and Drug Administration

DOCUMENT NO.:
ORA-LAB.QM

VERSION NO.:1.9

ORA Laboratory Manual of Quality Policies

EFFECTIVE DATE:
10-01-03
REVISED:
01-22-13

5.4.1 General

The scope of test technologies and associated method source routinely used are identified in the laboratory’s accreditation program documentation.

The estimation of the uncertainty of measurement is addressed in Volume I, subsection 5.4.6. and Volume I, Section 5.9 Assuring the Quality of Test Results of this manual describes the quality control processes, including the application of statistical techniques, for supporting test and calibration data.

The laboratory instructions for the use and operation of equipment called for by the laboratory methods is either a laboratory procedure identified on the master list or as equipment manuals. Procedures for the handling of items for testing are addressed in Volume 1, Section 5.8 Handling of Samples. Equipment manuals and standards for the laboratory’s scope of testing technologies are controlled as external documents according to Volume I, Section 4.3 Document Control. Deviations from test methods are documented, technically justified, authorized, and where circumstances call for it, accepted by the customer according to Volume II, Section 2, ORA-LAB.5.10 Reporting Laboratory Data, 6.D.

5.4.2 Selection of Methods

Standard methods are those published by international, regional or national standards-writing bodies; by reputable technical organizations; in legal references; and FDA published methods. FDA “official” methods are those in compendia specified in the FD&C Act and prescribed in the CFR and methods in applications and petitions that have official status are included. These methods include those in the United States Pharmacopeia, National Formulary, Homeopathic Pharmacopeia of the United States, Official Methods of Analysis of the Association of Official Analytical Chemists (AOAC) International or any supplement of any of them, American Public Health Association (APHA) Compendium of Methods for the Microbiological Examination of Foods, FDA compliance programs, the Pesticide Analytical Manual (PAM), the Food Additives Analytical Manual, the Food Chemicals Codex, FDA Bacteriological Analytical Manual (BAM), FDA Macroanalytical Procedures Manual (MPM), and ORA Laboratory Information Bulletins (LIBs) that are included in compliance programs and special assignments. Standard methods are preferred for use and are verified for use in the laboratory. A standard method may be supplemented with additional details in the form of a laboratory procedure to ensure consistent application. Those methods specified by the manufacturer of the equipment are considered as standard methods. Standard methods are verified according to the procedure, Volume II, Section 2, ORA-LAB.5.4.5 Methods, Method Verification and Validation.

Laboratory methods are selected to meet the customer’s need as addressed in Volume I, Section 4.4 Review of Requests, Tenders and Contracts. The laboratory methods are controlled as external documents according to Volume I, Section 4.3 Document Control.

When the customer does not specify the method to be used, a standard method is preferred for use. If a standard method is not found, the laboratory may use either a non-standard method or modify a method for use with the concurrence of the customer. The non-standard or modified method is validated according to Volume I, subsection 5.4.5 Validation of Methods.  

The laboratory informs the customer when the method proposed by the customer is considered to be the incorrect choice or the incorrect revision for the intended purpose. This is done as part of contract review addressed in Volume I, Section 4.4 Review of Requests, Tenders and Contracts.

5.4.3 Laboratory Developed Methods

If a laboratory develops methods for its own use, the laboratory has its own procedure for its introduction. This procedure provides the planned activities, identification of qualified personnel, and resources. Plans are revised as method development proceeds and effective communication amongst all personnel involved is strongly encouraged. Laboratory developed methods adopted by the laboratory are used if they are validated according to Volume I, subsection 5.4.5 Validation of Methods.

5.4.4 Non-standard Methods

Non-standard methods are those methods not taken from authoritative, validated sources. A non-standard method has not undergone validation, such as a collaborative study or process to evaluate the method’s performance capabilities.

Non-standard methods are selected for use when a customer request cannot be addressed with the use of a standard method. Such methods are subject to agreement with the customer and a clear specification of the customer's work requests, including the purpose of the test, is made. This process is described for contract amendments in Volume I, subsection 4.4.5 Amendments to Contracts with laboratory management concurrence. Non-standard methods are validated according to Volume I, subsection 5.4.5 Validation of Methods.

5.4.5 Validation of Methods

5.4.5.1 Definition

Validation is the confirmation by examination and the provision of objective evidence that the particular specifications for an intended use are fulfilled.

5.4.5.2 Methods Requiring Validation

The laboratory validates non-standard methods, laboratory developed methods, and modified standard methods including use outside the intended scope and applications. Validation is conducted to confirm that the methods are fit for the intended use. The validation is documented.

5.4.5.3 Process

The validation process addresses the needs of the given application or field of application. The laboratory analyst records the results obtained according to the procedure, Volume II, Section 2, ORA-LAB.5.4.5 Methods, Method Verification and Validation. The validation results include a statement as to whether the method is fit for the intended use. The needs of the customer define the intended use of the method. The attributes and data quality objectives include but are not limited to:

  • accuracy,
  • precision,
  • specificity,
  • detection limit,
  • limit of quantitation,
  • linearity,
  • range, and
  • ruggedness or robustness.

If all the data quality objectives are met as indicated by the data collected, the method is considered as validated.

5.4.6 Estimation of Uncertainty of Measurement

5.4.6.1 Procedure for Calibration Activities

ORA laboratories do not perform calibration activities. At such time that calibration activities are performed, the ORA laboratories are to address the requirements of ISO/IEC 17025, 5.4.6.1.

5.4.6.2 Procedure for Testing Activities

The laboratory has a procedure, Volume II, Section 2, ORA-LAB.5.4.6, Estimation of Uncertainty of Measurement, to estimate the uncertainty of measurement for testing activities. 

The application of details in cases where the nature of the test method may preclude rigorous, metrologically and statistically valid, calculation of uncertainty of measurement is addressed in the procedure.

An attempt is made to identify all the components of uncertainty and make a reasonable estimation of the measurement uncertainty. This estimation is based on knowledge, experience, and validation data of the performance of the method and on the measurement scope. If needed as a part of the laboratory data, the uncertainty estimation is reported according to the procedure, Volume II, Section 2, ORA-LAB.5.4.6 Estimation of Uncertainty of Measurement.

5.4.6.3 Uncertainty Components

When estimating the uncertainty of measurement, all important uncertainty components are recorded in the uncertainty records for each determination and test technology as addressed in the procedure Volume II, Section 2, ORA-LAB.5.4.6, Estimation of Uncertainty of Measurement.

5.4.7 Control of Data

5.4.7.1 Data Transfers

Calculations and data transfers are reviewed before the data is reported.  All changes are identified and verified where they occur.  This process is detailed in the procedure for laboratory quality control identified in Volume I, Section 5.9 Assuring the Quality of Test Results.

5.4.7.2 Computer Use

When computers or automated equipment are used for the acquisition, processing, recording, reporting, storage or retrieval of test data, the laboratory follows the process in the laboratory’s data protection procedure.

  1. If computer software is developed by the user, its development is documented in detail and algorithms are validated. 
  2. The laboratory’s data protection procedure addresses the protection of the data to include, but not limited to data integrity, data confidentiality during entry, collection, storage, transmission and processing.
  3. Computers and automated equipment are maintained to ensure proper functioning and are provided with the environmental and operating conditions to maintain the integrity of test and data.

Related Procedures