Quality manual

5.5 Examination Procedures

1. 
   Selection, Verification and Validation of Examination Procedures
   

1. 
   General
   

The Department of Pathology uses examination (testing) procedures, including those for selecting/taking sample portions, which meet the needs of the users and are appropriate for the examinations. The Department of Pathology uses procedures that have been published in established/authoritative textbooks, peer-reviewed texts or journals, or in international, national or regional guidelines.

5.5.1.2 Verification of Examination Procedures
The Department of Pathology validates all testing procedures before being introduced into routine use as per the requirements of the VMP-GEN-0001 Validation Master Plan for the Pathology Laboratory. Retrospective validation is performed on existing procedures. Approved Validation Plans are used to confirm that the testing procedures are suitable for their intended use. Testing is performed as indicated in the Validation Plan. Results of all validation testing are recorded and assessed against the acceptance criteria specified in the Validation Plan. A Validation File is maintained for each test method or group of parameters that constitute the method/test examination. The identity of persons performing activities in examination processes is recorded.
Validation examination procedures used without modification are subject to independent verification by the laboratory before being introduced into routine use.
The laboratory obtains information from the manufacturer/method developer for confirming the performance characteristics of the procedure.
The independent verification by the laboratory confirms through obtaining objective evidence (in the form of performance characteristics) that the performance claims for the examination procedures have been met. The performance claims for the examination procedure confirmed during the verification process are those relevant to the intended use of the examination results.

The laboratory documents the procedure used for the verification and records the results obtained. Staff with the appropriate authority reviews the verification results and record the review.

5.5.1.3 Validation of Examination Procedures
Validation is completed on

2. 
   Non-standard methods
   
3. 
   Laboratory designed and developed methods
   
4. 
   Standard methods used outside their intended scope
   
5. 
   Validated methods subsequently modified
   

The Department of Pathology validates examination procedures derived from Laboratory designed or developed methods as per VMP-GEN-0001 Validation Master Plan for the Pathology Laboratory.

The validation is as extensive as is necessary and confirms, through the provision of objective evidence (in the form of performance characteristics), that the specific requirements for the intended use of the examination have been fulfilled.
Performance characteristics of the examination procedure include consideration of: measurement trueness, measurement accuracy, measurement precision including measurement repeatability and measurement intermediate precision, measurement uncertainty, analytical specificity, including interfering substances, analytical sensitivity, detection limit and quantitation limit, measuring interval, diagnostic specificity and diagnostic sensitivity.
The laboratory documents the procedure used for the validation and record the results obtained. Staff with the authority reviews the validation results and record the review.
When changes are made to a validated examination procedure, the influence of such changes is documented and, where appropriate, a new validation is carried out.

4. 
   Measurement Uncertainty of Measured Quantity Values
   

The Department of Pathology determines the uncertainty of results, in the examination phase used to report measured quantity values on patients’ samples. The laboratory defines performance requirements for the measurement of uncertainty of each measurement procedure and regularly reviews estimates of measurement uncertainty in accordance with LP-GEN-0010 Uncertainty of Measurement.

The relevant uncertainty components are those associated with the actual measurement process, commencing with the presentation of the sample to the measurement procedure and ending with the output of the measured value.
It is the policy of the Department of Pathology to focus on the elimination or reduction of errors in the following critical areas of activity:

• 
  Sampling
  
• 
  Sample preparation
  
• 
  Sample portion selection
  
• 
  Calibrators
  
• 
  Reference materials
  
• 
  Input quantities
  
• 
  Equipment used
  
• 
  Environmental conditions
  

Examples of areas of uncertainty of measurement are:

• 
  Procedure is not defined or ambiguous
  
• 
  Environmental conditions are inaccurate for storage or testing
  
• 
  Incorrect sample type received
  
• 
  Inaccurate dilutions
  
• 
  Incorrect use of reagents
  
• 
  Inadequate training of staff
  
• 
  Scientific misinterpretation by staff
  
• 
  Transcription errors
  
• 
  Equipment systematic or random errors
  
• 
  Inadequate preventative maintenance
  

This list is not exhaustive

5.5.2 Biological Reference Intervals or Clinical Decision Values

The laboratory defines the biological reference intervals or clinical decision values, documents the basis for the reference intervals or decision values and communicates this information to users via the report form.

When a particular biological reference interval or decision value is no longer relevant for the population served, appropriate changes are made and communicated to the users.
When the laboratory changes an examination procedure or pre-examination procedure, the laboratory reviews associated reference intervals and clinical decision values, as applicable.
Biological reference intervals are periodically reviewed at quality meetings for their appropriateness. A review of biological reference intervals also takes place when there is a change in any pre-examination or examination procedure. All changes are managed using MP-GEN-0019 Management of Change Control.
5.5.3 Documentation of Examination Procedures
Examination procedures, in the form of Standard Operating Procedures (SOPs) are available at the work station where the test and examination procedures are performed.
The testing procedures are based on instructions for use from the manufacturer. All additional information required to perform the test is documented in the technical procedure for the test method(s).
Performance specifications for each procedure used in an examination relate to the intended use of that procedure. This is implemented through the relevant technical procedure.
Where summaries of information are available at a workbench for quick reference (e.g. test codes), these correspond to, and are referred to in, the relevant technical procedure. Such summaries are controlled under MP-GEN-0002 Management of Documentation Preparation and Control.
All test procedures are reviewed every 2 years or before that if a major amendment is required. These reviews are documented.
All test/ examination procedures are prepared as per QP-GEN-0010 Writing a Standard Operating Procedure and as per MP-GEN-0002 Management of Documentation Preparation and Control and are subject to document control. In addition to document control identifiers, documentation includes, where applicable to the examination procedure, the following:
a) Purpose of the examination

2. 
   Principle and method of the procedure used for examinations
   

c) Performance specifications (e.g. linearity, precision, accuracy expressed as uncertainty of measurement, detection limit, measuring interval, trueness of measurement, analytical sensitivity and analytical specificity)

d) Type of sample (e.g. plasma, serum,)
e) Patient preparation
f) Type of container and additives

7. 
   Required equipment and reagents
   

8. 
   Environmental and safety controls
   

i) Calibration procedures (metrological traceability)

j) Procedural steps
k) Quality control procedures
l) Interferences (e.g. lipaemia, haemolysis, bilirubinemia, drugs) and cross reactions
m) Principle of procedure for calculating results, including, where relevant, the measurement uncertainty of measured quantity values
n) Biological reference intervals or clinical decision values
o) Reportable interval of examination results
p) Instructions for determining quantitative results when a result is not within the measurement interval
q) Alert/critical values, where appropriate
r) Laboratory clinical interpretation
s) Potential sources of variability
t) References
The Acting Chief Medical Scientist is responsible for ensuring that the contents of examination procedures are complete, current and reviewed by the Consultant.
Where a change is made in the manufacturer’s instructions, the reagent is checked for performance and continued suitability for intended use. This is carried out and changes to technical procedures are made as described in MP-GEN-0019 Management of Change Control.
All changes to test/ examination procedures are processed through the MP-GEN-0019 Management of Change Control and the MP-GEN-0002 Management of Documentation Preparation and Control.
Additional validation testing performed as required.
It is policy of the Department of Pathology to inform users in advance of change to an examination procedure such that results or their interpretations could be significantly different. The implications are explained to users by memo prior to the introduction of the change. This is implemented through the MP-GEN-0019 Management of Change Control.
The Department of Pathology provides users of the service with a list of current examination procedures, including primary sample requirements and relevant performance specifications and requirements, on request. This is implemented through the LP-GEN-0007 User Manual.

Reagent Logs in the Department of Pathology list all reagents in use, the revision number of the package insert of the batch in current use. Current product inserts for each reagent are retained. On receipt of reagents, the revision number of product inserts is checked to be current as part of the incoming inspection process, as described in LP-BT-0002 Monitoring of Materials in Blood Transfusion, LP-HAEM-0012 Batch Acceptance of Reagents in Haematology, LP-BIO-0007 Batch Acceptance of Reagents, Calibrators, Q.C. and Consumables and LP-MIC-0065 Batch Acceptance in Microbiology.