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).