LAB-QM-ANA-003 — Method Validation Policy

1.0 Purpose

The purpose of this policy is to establish defined protocols for verifying and validating examination methods before they are introduced into routine diagnostic service at Tarangnan Community Hospital Clinical Laboratory. This ensures that analytical methods achieve acceptable accuracy, precision, reportable range, and measurement uncertainty to support clinical decision-making.

2.0 Scope

This policy applies to all existing, new, modified, or relocated examination methods, analytical instruments, and test kits utilized across the Clinical Laboratory, and governs the verification responsibilities of all Medical Technologists and technical personnel.

3.0 Definitions

• Method Verification — confirmation through objective evidence that an unmodified, commercially established examination method meets manufacturer-specified performance claims under local laboratory conditions.
• Method Validation — confirmation through objective evidence that an in-house developed, modified, or off-label examination method satisfies specific intended clinical requirements.
• Accuracy (Trueness) — the closeness of agreement between the mean of a vast series of replicated test results and the true reference value.
• Precision — the closeness of agreement between repeated independent test results obtained under specified conditions (within-run repeatability and between-day reproducibility).
• Limit of Detection (LoD) — the lowest analyte concentration in a sample that can be reliably distinguished from zero background.
• Measurement Uncertainty (MU) — a non-negative parameter characterizing the dispersion of values that could reasonably be attributed to the measurand.

4.0 Responsibility

4.1 Hospital Director

• Authorizes capital equipment acquisitions and ensures adequate resources for validation consumables and reference standards.
• Exercises executive oversight per Organization and Governance.

4.2 Pathologist

• Reviews and grants final clinical approval for all method verification and validation study summaries prior to reporting patient results.
• Authorizes clinically acceptable Total Allowable Error (TAE) goals and reference interval adaptations per Organization and Governance.

4.3 Chief Medical Technologist / Laboratory Quality Manager

• Designs verification protocols, coordinates study sample acquisition, and supervises statistical calculations.
• Evaluates precision, accuracy, linearity, and measurement uncertainty data, ensuring full regulatory compliance with DOH and ISO 15189:2022 standards.
• Prepares validation summary dossiers for Pathologist review and sign-off.

4.4 Medical Technologists

• Execute verification protocols, perform precision runs, analyze comparison samples, and record raw test data.
• Maintain instruments in calibrated condition throughout study execution and assist in statistical data entry.

4.5 Laboratory Aides

• Assist in specimen archiving, retrieval, and inventory handling under Medical Technologist direction.
• Shall never perform analytical verification procedures, calculate statistics, or authorize method validation records.

5.0 Policy / Procedure

5.1 Policy Statement

Prior to releasing patient results from any new, modified, or relocated test method, the laboratory shall complete documented performance verification studies. For standardized, commercial in vitro diagnostic systems used without modification, method verification shall confirm that manufacturer performance claims (precision, trueness, linearity, reportable range, and reference intervals) are successfully reproduced in the TCH laboratory environment.

Any non-standard or modified method shall undergo validation (see Figure 1).

Figure 1 — Method verification study execution and Pathologist approval flow

5.2 Precision Verification

• Within-run precision (repeatability) shall be evaluated by testing at least 2 control levels or patient pools in 20 replicates within a single analytical run.
• Between-day precision (reproducibility) shall be evaluated by testing 2 control levels in duplicate across 10 to 20 testing days.
• Observed coefficient of variation (CV%) shall not exceed the manufacturer's stated precision specifications or established clinical quality requirements.

5.3 Accuracy and Trueness Verification

• Accuracy shall be verified by analyzing at least 20 patient specimens in parallel against a validated comparative method or accredited referral laboratory (e.g., Samar Provincial Hospital).
• Alternatively, accuracy may be verified using certified reference materials, proficiency testing materials with assigned peer values, or commercial calibrators with verified target values.
• The observed mean bias shall fall within predefined acceptable allowable bias criteria.

5.4 Analytical Measurement Range and Linearity

• Linearity shall be verified across the manufacturer's stated analytical measurement range (AMR) using serial dilutions of high-concentration patient pools or commercial linearity verification sets.
• The reportable range shall span clinically relevant low, normal, and high diagnostic intervals. Results exceeding the validated upper limit shall be diluted in accordance with validated SOP instructions.

5.5 Analytical Sensitivity and Specificity

• Limit of Detection (LoD) and analytical cut-off values shall be verified for qualitative and semi-quantitative rapid test kits using known negative and weak-positive reference samples.
• Potential common analytical interferences (hemolysis, icterus, lipemia) shall be identified in accordance with manufacturer package inserts and documented in technical SOPs.

5.6 Carryover Assessment

For automated analyzers (e.g., Horiba Pentra XLR), potential sample-to-sample carryover shall be evaluated by alternating high-concentration and low-concentration specimens in sequence (High-High-High followed by Low-Low-Low) to verify that carryover is clinically insignificant.

5.7 Reference Interval Verification

• The laboratory shall verify manufacturer-provided reference intervals (normal ranges) before adoption for clinical reporting.
• Verification shall be conducted by analyzing at least 20 reference specimens from local healthy individuals. If no more than 10% (2 of 20) fall outside the proposed interval, the manufacturer reference range is verified and clinically adopted.
• If more than 2 specimens fall outside, the interval shall be investigated with additional specimens or adjusted under Pathologist authorization.

5.8 Instrument and Method Comparability

• When an examination is performed on more than one instrument or method within the facility, comparability of patient results shall be evaluated at least semi-annually.
• Split-sample testing shall confirm that results across different systems correlate within defined clinically acceptable limits.

5.9 Measurement Uncertainty Evaluation

• Measurement uncertainty (MU) shall be determined for all quantitative examination procedures reported by the laboratory.
• Long-term internal quality control reproducibility data (intermediate imprecision SD and CV%) shall serve as the primary basis for estimating measurement uncertainty.
• Measurement uncertainty estimates shall be reviewed annually and made available to clinical users upon request.

5.10 Approval and Archiving

• A Method Verification and Validation Report shall be compiled summarizing all study data, calibration records, precision statistics, accuracy bias, and conclusions.
• Patient testing shall not commence until the Pathologist signs the formal approval report.
• All verification dossiers and raw study data shall be retained in accordance with Laboratory Retention Schedule Policy.

6.0 Records

The following controlled records are maintained under this policy:

These records are maintained electronically in analyzer memory, the LIS, and dedicated electronic workbooks registered under F-QM-002-B-V0 (Decision D5); no separate paper form is maintained for them.

7.0 References

• DOH QMS Tool, Section 4 (Monitoring Performance — Internal Quality Control)
• DOH Administrative Order No. 2021-0037, Annex B1 (Technical Standards for Clinical Laboratories)
• ISO 15189:2022, Clause 7.3.2 (Verification of examination methods), Clause 7.3.3 (Validation of examination methods), Clause 7.3.4 (Evaluation of measurement uncertainty)
• WHO LQMS Handbook, Chapter 7 (Process control — QC for quantitative tests)
• CLSI EP15-A2, User Verification of Precision and Estimation of Bias

Companion policies:

• Quality Control Policy — Ongoing internal quality control and analytical performance monitoring
• Proficiency Testing Policy — External quality assessment and alternative proficiency assessment
• Laboratory Retention Schedule Policy — Retention schedules for validation studies and equipment files

Controlled visual annex:

• IG-26 — Method Verification — one-page visual annex to this policy, controlled under Document Control Policy Section 5.2.6 and registered in F-QM-002-B-V0. Master files: infographics/IG-26-Method-Verification-LAB-QM-ANA-003.png (PNG, print PDF, and editable HTML).