Introduction of Analyst Validation
Analyst Validation-Reliable laboratory results depend not only on validated analytical methods and qualified instruments, but also on the competence of the analyst performing the test. Even when an approved method is followed, errors in weighing, pipetting, sample preparation, calculations, instrument operation, or interpretation can affect the final result.
Analyst validation is therefore an important quality control activity used to demonstrate that an analyst can perform assigned analytical procedures accurately and consistently before being permitted to perform routine testing independently.
What Is Analyst Validation?
Analyst validation, more appropriately described in many pharmaceutical laboratories as analyst qualification or competency assessment, is a documented exercise used to demonstrate that an analyst has the necessary skills to perform a particular analytical test correctly.
The exercise compares the analyst’s results with established or previously generated results from a trained/qualified analyst. The comparison is performed against predefined acceptance criteria.
The assessment may cover:
- Weighing and pipetting technique
- Assay testing
- Dissolution testing
- Related substances analysis
- Water content determination by Karl Fischer titration
- Physical parameters
- Microbiological analysis
- Other laboratory tests according to the analyst’s assigned responsibilities
Why Analyst Qualification Required?
Analytical testing in pharmaceutical manufacturing directly supports decisions concerning raw materials, packaging materials, in-process materials, finished products, stability samples, and other quality-related activities.
An analyst who has not demonstrated adequate competency may introduce errors that could affect:
- Product quality decisions
- Batch release
- Stability evaluation
- Investigation of atypical or OOS results
- Compliance with laboratory procedures
- Data reliability and traceability
Analyst Validation Importance in Pharmaceutical Quality Control
A pharmaceutical QC laboratory relies on several interconnected elements:
- Approved analytical procedures
- Suitable and qualified instruments
- Appropriate reference standards and reagents
- Trained personnel
- Controlled laboratory conditions
- Accurate calculations and documentation
- Appropriate review and approval
When Should an Analyst Be Qualified or Requalified?
An analyst qualification exercise may be required in situations such as:
New Analyst
A newly appointed analyst should undergo appropriate training followed by competency assessment before being assigned independent routine analytical work.
Change in Job Profile
An existing analyst moving into a different testing area or receiving responsibility for new analytical techniques should be assessed for the applicable tests.
Requalification Following Repeated Analytical Errors
Requalification may be required when repeated errors attributable to the analyst indicate that additional training or competency assessment is necessary.
The in-house procedure provided for this article identifies repeated errors of the same type, including a threshold of six or more incidents in the current year, as a trigger for requalification.
Analyst-Related OOS or Analytical Failure
When an investigation establishes that an OOS or other analytical failure resulted from analyst error, the analyst may require retraining and requalification for the affected test or product before returning to independent routine testing.
Roles and Responsibilities
A clearly defined responsibility structure helps maintain the integrity of the qualification process.
| Function | Typical Responsibility |
| QC Executive/Senior Executive | Provide training and execute the analyst qualification exercise |
| QC Department Head | Ensure implementation of the procedure, review results, and determine suitability for routine analysis |
| QA Department | Review/approve the procedure and maintain appropriate document control |
| Section Head/Designee | Initiate the assessment, select appropriate testing material, and coordinate the exercise |
| Analyst | Perform the assigned test according to the approved analytical procedure and document all results accurately |
Selection of Samples for Analyst Qualification
The sample used for qualification should be appropriate for the analytical activity being assessed.
According to the supplied in-house procedure, the sample is selected by the relevant QC/GLP function and should be an approved batch that has not yet been dispatched.
The selected material should be properly controlled and issued through the established material-issuance process after the required approval.
Analyst Validation Procedure
The exact tests selected should depend on the analyst’s assigned responsibilities. An analyst does not necessarily need to perform every parameter listed below if those tests are outside the individual’s authorized scope.
1. Weighing and Pipetting Assessment
Weighing and pipetting are fundamental laboratory skills because inaccurate liquid transfer or weighing can influence sample preparation and final analytical results.
The supplied procedure assesses pipetting using 1 mL, 5 mL, and 10 mL pipettes with purified water at ambient conditions. Three replicate transfers are performed and the transferred water is weighed using a suitable tared container.
The measured mass can be converted into volume using the density of water applicable to the test conditions.
Important technical note: The formula reproduced in the source SOP appears dimensionally inverted. The normal relationship is:
Actual Volume = Weight of Water ÷ Density of Water
When a density value of 0.99705 g/mL is applicable:
Actual Volume (mL) = Weight of Water (g) ÷ 0.99705 g/mL
The percentage of actual volume can then be calculated as:
% Actual Volume = (Actual Volume ÷ Nominal Pipette Volume) × 100
The supplied procedure specifies the following acceptance criteria:
- Actual volume: 99.0% to 101.0% of the nominal volume
- %RSD of the three replicate results: NMT 1.0%
The laboratory should ensure that the density value used in the calculation is appropriate for the actual temperature and applicable procedure.
2. Assay Testing
The analyst may be assessed using an applicable assay procedure, such as:
- HPLC
- UV-Visible spectrophotometry
- Titration
- Potentiometric titration
The supplied procedure specifies three assay preparations for the analyst qualification exercise.
The average result is compared with the established initial result.
The specified acceptance criterion is:
Percentage variation from the initial result: ±2.0%
The exact comparison should be performed using the approved calculation and documented in the qualification report.
3. Dissolution Testing
Dissolution testing may be included when the analyst’s routine responsibilities involve dissolution analysis.
The supplied procedure describes a single preparation for the qualification exercise and specifies:
Variation from the initial result: NMT ±10.0%
Because dissolution results can depend on several experimental variables, the analyst should demonstrate correct operation of the dissolution apparatus, sampling technique, sample preparation, filtration where applicable, and analytical measurement.
4. Related Substances by HPLC
Related substances testing requires careful control of sample preparation, chromatographic operation, integration, calculations, and result interpretation.
For individual impurities, the supplied procedure gives the following comparison criteria:
| Initial impurity result | Permitted difference from initial result |
| 0.1% to 0.2% | NMT ±25% |
| Above 0.2% | NMT ±20% |
| Below 0.1% | Not considered for comparison when both results are below 0.1% |
These criteria should be applied exactly as defined in the approved site procedure.
Special attention should be given to low-level impurity results because percentage differences can appear disproportionately large when the absolute concentration is very small.
5. Karl Fischer Water Determination
Where Karl Fischer titration forms part of the analyst’s assigned duties, competency may be assessed using disodium tartrate as the specified test material.
Three replicate determinations are performed according to the approved procedure.
The supplied acceptance criterion is:
%RSD: NMT 1.0%
The analyst should demonstrate correct handling of the Karl Fischer instrument, sample introduction, endpoint determination, calculations, and documentation.
6. Physical Parameter Testing
Before an analyst is assigned to instrumental testing, appropriate training and competency assessment may be performed for applicable physical tests.
Examples include:
- Friability
- Disintegration
- Tablet diameter
- Tablet thickness
- Hardness
- Loss on drying
- Specific or related physical parameters defined by the laboratory
The analyst should demonstrate correct operation of the equipment, sample handling, observations, calculations, and recording of results.
7. Microbiological Analysis
For microbiological testing, qualification should be based on the approved microbiological procedure and applicable product/material specification.
The supplied procedure identifies specification compliance as the acceptance basis for microbial analysis rather than assigning a universal numerical variation criterion.
Calculation of Percentage Difference during Analyst Validation
When comparing the analyst’s result with the initial result, the following general calculation can be used:
% Difference = |Analyst Validation Result − Initial Result| ÷ Initial Result × 100
The approved site procedure should define whether absolute difference, signed difference, percentage difference, or another statistical comparison is required for a particular test.
All calculations should be independently checked where required by the laboratory’s documentation and review practices.
Acceptance Criteria – Analyst Validation
The supplied procedure provides the following qualification criteria:
| Test/Parameter | Acceptance Criterion |
| Weighing & pipetting | Actual volume 99.0–101.0%; %RSD NMT 1.0% |
| Karl Fischer water determination | %RSD NMT 1.0% |
| Assay by titration | ±2.0% from initial result |
| Assay by UV | ±2.0% from initial result |
| Assay by HPLC | ±2.0% from initial result |
| Related substances, impurity 0.1–0.2% | NMT ±25% |
| Related substances, impurity >0.2% | NMT ±20% |
| Individual impurity <0.1% | Not considered when both results are <0.1% |
| Dissolution | NMT ±10% |
| Microbial analysis | As per applicable specification |
These are the acceptance criteria contained in the supplied in-house procedure. They should not be treated as universal regulatory limits for analyst qualification. Each pharmaceutical site should establish scientifically justified criteria within its approved procedures.
Practical Workflow for Analyst Qualification
A practical workflow can be organized as follows:
- Identify the analyst and testing scope.
- Review the analyst’s training status.
- Complete the analyst assessment/qualification form.
- Select an appropriate approved sample or test material.
- Assign a unique qualification number.
- Provide any required pre-qualification training.
- Allow the analyst to perform the designated test independently under controlled conditions.
- Record raw data, calculations, chromatograms, observations, and final results.
- Compare results against the approved acceptance criteria.
- Have the qualification package reviewed by the appropriate QC authority.
- Document the final qualification decision.
- Authorize routine testing only after satisfactory qualification.
Comparison With the Initial Result
The analyst’s results should be compared with appropriate initial or reference results generated by a trained and qualified analyst.
The comparison should consider the nature of the analytical method.
For example:
- Assay may be compared using percentage difference.
- Pipetting may be evaluated using actual volume and precision.
- Dissolution may be compared using the specified variation criterion.
- Related substances require impurity-specific evaluation.
- Microbiological testing should be assessed against the applicable specification and procedure.
The comparison should be scientifically meaningful rather than simply based on whether two numbers appear identical.
What Happens if the Analyst Fails in Qualification?
Failure to meet the established acceptance criteria should not automatically be treated as evidence of analyst incompetence without evaluation.
The laboratory should review possible causes, such as:
- Inadequate training
- Incorrect understanding of the procedure
- Pipetting or weighing error
- Incorrect sample preparation
- Instrument operation error
- Calculation mistake
- Incorrect dilution
- Improper integration
- Incorrect use of reference standards
- Equipment or environmental factors
- Documentation error
Where the failure is attributable to the analyst, appropriate retraining should be completed.
The analyst should then undergo requalification before being authorized to perform the affected routine analysis independently.
Requalification Procedure
After an Analyst-Related OOS
If an investigation determines that an OOS result was caused by analyst error, the analyst should be evaluated according to the site’s approved investigation and requalification procedure.
The supplied SOP specifically indicates that the analyst should be revalidated for the same test/product following an analyst-related OOS.
The requalification should be appropriately documented and should demonstrate that the analyst has corrected the identified deficiency.
Repeated Analytical Errors
Repeated errors of the same nature should receive particular attention.
The supplied procedure uses repeated similar analytical errors at or above the defined annual threshold as a requalification trigger.
A trend-based approach is useful because an isolated mistake and a recurring competency problem have different implications.
Trending can help identify:
- Recurrent pipetting errors
- Calculation mistakes
- Incorrect sample preparation
- Instrument-operation errors
- Documentation deficiencies
- Repeated procedural deviations
The laboratory can then determine whether additional training, supervision, procedural clarification, or requalification is necessary.
Documentation and Records
The analyst qualification package should provide sufficient evidence that the assessment was properly planned, executed, reviewed, and concluded.
Depending on the site’s document system, records may include:
- Analyst qualification/assessment form
- Qualification protocol
- Sample identification
- Test method/reference procedure
- Raw data
- Worksheets
- Calculations
- Instrument printouts
- Chromatograms
- Replicate results
- Initial/reference results
- Comparison calculations
- Training records
- Deviation or investigation records, where applicable
- QC review comments
- Final qualification decision
- Analyst qualification certificate, where applicable
All records should be attributable, legible, contemporaneous, original/controlled, accurate, and traceable in accordance with the laboratory’s applicable documentation practices.
Common Problems During Analyst Validation
Several issues can reduce the value of an analyst qualification program.
1. Qualification Without Adequate Training
An analyst should not be expected to demonstrate competency in a procedure that has not been properly explained and demonstrated.
2. Using Unclear Acceptance Criteria
Acceptance criteria should be predefined and understood before the exercise begins.
3. Inadequate Documentation
Missing raw data, calculations, chromatograms, or review comments can make it difficult to demonstrate that the qualification was properly conducted.
4. Comparing Inappropriate Results
The reference result should be suitable for the particular analytical parameter. A simple numerical comparison may not be appropriate for every test.