Method Qualification / Validation Report

A report on method development / qualifications/ validation shall provide all the information in a structured format for review and understanding. It shall contain experiment/parameter wise result discussion and summary. The report shall end into a proposed test method used for quality control analysis. Following are the contents (but not limited to) of the report:

1             OBJECTIVE:

(Objective of development studies as defined in protocol shall be provided).

2             INTRODUCTION

(Introduction shall include test method principle, application and scope of the test method, rationale for selecting the test method for specified sample analysis).

3             METHOD DEVELOPMENT/QUALIFICATION/VALIDATION SUMMARY

(This shall contain the overall strategy and the flow of the method development. Provide the basis on which initial method was defined. Also provide the rationale of the method and the flow of method developmental activity. Provide the summarized information of all the development and finalized parameters. Wherever required tabulated representation of parameters explored. Also mention the recommendation (if any))

4             DEFINITIONS & ABBREVIATIONS

(Provide definitions and abbreviations applicable to the report).

5             EXPERIMENTAL DETAILS

(Provide the details as below:

·         Material,

·         Equipment’s & Instruments,

·         Reagent and Solutions (Identified as critical reagents),

·         Sample Details,

·         Standard Details

·         Initial Method/Method Reference, Provide the source from where the method was taken or provide method reference.).

6             RESULTS & DISCUSSION

(Describe the method and mention the parameters which were taken up for development/qualification/validation with protocol reference wherever applicable).

6.1          Parameter 1

6.1.1      Experimental details/Test Procedure

(Mention the brief of the parameters selected and the procedure of the experiment).

6.1.2      Observation & Interpretation

(Provide details of observation, results and interpretation of results for parameter studied).

6.1.3      Conclusion & Statistical Analysis

(Conclusion and recommendation for each parameter studied).

6.1.4      Acceptance Criteria

(Wherever applicable)

6.1.5      Documentation

(Source data record and archival)

6.2          Parameter 2

and so on…….

7             DEVIATIONS & CORRECTIVE ACTIONS

(Wherever applicable)

8             CONCLUSION:

(Provide overall conclusion of the entire experimentation performed)

9             TEST METHOD

(Provide the details of the proposed test method with controls).

10          REVALIDATION CRITERIA:

(Wherever applicable)

11          REFERENCES

(List of references consulted during the experimental studies)

12          Enclosures

(Provide list of annexure and attachments of the report, this may include Protocol working copy (wherever applicable), Data Record (solution preparation and test & Analysis), calculation sheets and raw data)

Method Qualification / Validation Protocol

A defined master template of a document ensures uniformity in knowledge management and compliance. Importance of capturing correct information during development studies can never be overemphasized.

Component of Method Qualification/Validation protocol are listed below to ensure consistency in document format and information capturing during the study. A protocol shall:

·         be identified with a number and date,

·         study title

·         contain name and titles of the investigators and personnel supervising the study along with address,

·         contains names and titles of authorized personnel who approve the study design,

·         protocol effective date.

The contents of protocol shall include (but not limited to) the following:

1             OBJECTIVE

(Specific objectives providing statement of research question(s) shall be provided under this section. The objectives shall be stated in advance and shall not be depended upon research outcome. Like other objectives, the objectives of qualification/validation study shall be SMART (Specific, Measurable, Achievable, Relevant and Time Bound).  After statement of the primary objective, secondary objectives may be mentioned.).

2             SCOPE

(Scope is defined as the extent of the area or subject matter that something deals with or to which it is relevant. The scope of protocol shall indicate "when" the study needs to be performed and "where" it applies.)

3             INTENDED USE OF METHOD

(This section shall define "why" the protocol is being written, study designed and where the final method will be used. Based on objective and scope, details of intended use of method with respect to samples (at different stages of process) shall be provided.).

4             RESPONSIBILITY

(Provide details of “who” performs the procedure and who is responsible to see it is performed correctly. Responsibilities for each critical stage such as sample provisions, sample storage, preparations of reagents and solutions, testing, data recording, data review, data archival, study approvals etc., shall be provided. Tabulated representation is preferred).

5             DEFINITIONS & ABBREVIATIONS

(Provide definitions with respect to study and internal systems with will clarify the strategy and study plan. List of abbreviations used shall be provided).

6             SAFETY CONSIDERATIONS

(Provide safety considerations and precautions for work with respect to physical, instruments, equipment, chemicals, bio-hazard, sample, reagents/solutions, disposal and spill control with available person safety tool requirements etc.)

7             INTRODUCTION

(This is where the protocol differs from SOP. An introduction shall provide background of test method/equipment and instrument principle, source of selected test method, application and scope of the test method, rationale for selecting the test method for specified sample analysis. Relevant references shall be provided).

8             MATERIALS

(This section along with section 9, 10, 11 & 12 defines “what” is needed to perform the test. The list should be complete and specific Details of material used in study with respect to material description, make, catalogue number/part number, quantity. This should include chemicals, reagents, consumables, etc. Tabulated representation is preferred).

9             EQUIPMENT AND INSTRUMENTS

(Details of equipment’s and instruments used in the study with make, model, ID No, Reference SOP, calibration and qualification requirements etc. shall be provided under this section).

10          REAGENTS AND SOLUTIONS

(Details of reagents and solutions to be used in study shall be provided. Ready to use solutions and reagents shall be listed first with details such as solutions/reagent description, make, catalogue number/part number and storage details in any. Subsequently the description of reagents and solution to be prepared shall be provided with standard formulae and step wise preparation procedure followed by storage conditions and use before date. It is preferable to identify the critical reagents used in the study).

11          SAMPLE DETAILS

(Details of sample with respect to sample description, sample source, process stage, matrix details, storage conditions, handling instructions if any shall be provided. Wherever sample preparation is required before analysis, relevant details shall be provided.)

12          STANDARD DETAILS

(Details of standard with respect to standard description, sample source/make, catalogue number, matrix details, storage conditions, handling instructions if any shall be provided. Wherever standard preparation is required before analysis, relevant details shall be provided.)

13          METHOD DESCRIPTION/ METHOD REFERENCE

(Clear concise, step by step instructions on "how" to perform the test. This should be written as instructions for the operator to follow, without a lot of theoretical background. A section on fundamental principles can be included if necessary. Wherever, applicable a method reference shall suffice.).

14          STUDY PLAN/ DESIGN/PARAMETERS TO BE STUDIED

Clear concise, step by step instructions on how study will be performed. Provide details of each parameter to be studied, with justification/selection criteria.

Each parameter shall be elaborated in following sub headings:

·         Parameter Name/Description:

·         Test Procedure

·         Calculations and Statistical analysis        

·         Acceptance Criteria

·         Documentation (record of data during analysis)

Following parameters are usually studied during method qualification / validation (depend upon the strategy adopted):

·         Specificity

·         Linearity and Range

·         Precision

o   Method precision (Repeatability)

o   Intermediate precision (Ruggedness)

·         Accuracy

·         Limit of Detection (LOD)

·         Limit of Quantification (LOQ)

·         Robustness

·         Solution/Reagent stability

·         Forced Degradation study

·         System Suitability

15          STUDY PLAN SUMMARY

Summary of Study Plan with samples, number of replicates, number of repeats and, day of analysis shall be provided, preferably in tabulated form.

Replicates and repeats are distinguished as below:

Replicates (Measurement Replicates): These are repeated measurement of same item, i.e., single sample is measured more than once in same experimental run.

Repeats: Here implies to repeated experiment from sample preparation to measurement, an independently repeated data.

Wherever, data from one parameter is used in analysis of the other parameter, details of such strategy shall be provided.

16          DOCUMENTATION AND DATA RECORDING

This section details “What Next”

a) Indicate where the results should be recorded.

b) Explain what to do if there are problems during the test.

c) Indicate that deviations to the procedure must be approved and recorded.

d) Identify the person to whom the final results should be reported.

Details of documentation and data recording strategy adopted to ensure complete, consistent, accurate data which shall be contemporaneously recorded).

17          REVALIDATION/REQUALIFICATION CRITERIA

         (Wherever applicable, revalidation/qualification criteria shall be mentioned).

18          REFERENCES

         (List of references consulted during the experimental studies)

19          ENCLOSURES

         (Provide list of enclosures to protocol, this may include flow charts, tabulated strategy with                    acceptance criteria etc.)

Wherever contemporaneous record of the experiments need to recorded, a record forms shall be annexed with the Protocol.)

20          HISTORY

         (Provide details of document history in below table).

Study Protocol: Central Elements

Protocol is an established code of procedures.

A protocol defines a set of operational procedures to ensure that there is a well- defined way of doing a particular task or range of tasks (often informed by past experience). Protocol is a “road map” for the research project/work.

It is a predefined written procedural method in the design and implementation of experiments. It is an exploratory document with a defined plan and shall clearly spells out why you are doing the research, what the research question and data needed to answer the question are, and how to gather and analyze the data.

In most cases it is a formal agreement and commitment between two or more parties on a common response to specified issues, events or circumstances e.g. information sharing.

Protocol should stand on its own, and refrain from referring to multiple documents for execution of the activity. Protocols are written whenever it is desirable to standardize a laboratory method to ensure successful replication (reproducibility) of results by others in the same laboratory or by other laboratories. Detailed protocols also facilitate the assessment of results through peer review. Protocols are employed in a wide range of experimental fields.

The central elements of protocol include:

·         Study rationale with background

·         Study objective(s)

·         Study Design (organization of experiment) and methodology

·         Required equipment and instruments

·         Safety precautions

·         Detailed procedures/methods

·         Study population/samples

·         Study time frame (Duration)

·         Calculation of results and reporting standards

·         Statistical considerations

·         Rules for predefining and documenting excluded data to avoid bias.

·         Accepted outcome/acceptance criteria

Protocol differ from SOP in being more elaborate; provide background & rationale for exploratory study with objectives and at times acts as an agreement between two or more parties/stakeholders (multi center studies). Protocol is often employed for a one time study. On the other hand the SOP provides a set of systematically written instructions to ensure that a task is performed same way each time.