GC System Validation Overview

GC System Validation Overview in QC Laboratories

Gas Chromatography (GC) systems are fundamental analytical instruments employed in Quality Control (QC) laboratories within pharmaceutical manufacturing environments. GC systems are used to separate, identify, and quantify volatile compounds—ranging from active ingredients, impurities, residual solvents, to degradation products—in raw materials, intermediates, and finished pharmaceutical dosage forms. Robust gc system validation ensures both data integrity and reliable results, while maintaining regulatory compliance across the product lifecycle.

Role and Boundaries of a GC System in Pharmaceutical QC

GC systems in the pharmaceutical sector serve as a critical release and stability testing tool. These instruments ensure product safety, quality, and efficacy by detecting trace contaminants or verifying content uniformity. A typical GC setup used in QC labs comprises a sample injector, carrier gas supply, chromatographic column, detector (commonly FID or ECD), hardware PCs, and chromatography data system (CDS) software.

Intended Use Boundaries:

• Applicable only to the analysis of volatile and semi-volatile substances.
• Intended for quantitation, identification, and impurity profiling tasks as defined by analytical procedures.
• Not suitable for non-volatile, thermally labile, or ionic analytes.
• Not designed or validated for preparative-scale separations or direct clinical diagnostics.
• Use aligned with regulatory and pharmacopoeial methods within the scope of site procedures and specifications.

Scope of GC System Validation/Qualification

System validation encompasses the demonstration and documentation that a GC instrument, including all integral subsystems (injector, oven, columns, detector, CDS integration), is fit for its intended analytical purpose, consistently produces accurate and reliable data within specified parameters, and maintains ongoing control throughout its lifecycle.

• Within Scope:
  • Qualification (DQ, IQ, OQ, PQ) of primary hardware components and manufacturer-supplied software.
  • Network and electronic data flow between GC, CDS software, and local/server storage relevant to regulated data.
  • Testing safety interlocks, alarms, and environmental operating limits (e.g., temperature/humidity).
  • Verification and calibration of detectors, injectors, and critical measurable/controllable parameters.
  • Integration and functioning of autoinjectors/sample handlers where present.
• Out of Scope:
  • Routine maintenance beyond the initial qualification activities.
  • IT infrastructure outside the CDS system (e.g., backup servers, unrelated network hardware).
  • Analytical method validation, except where directly linked to PQ exercises.
  • Consumables qualification (unless impacting system suitability or data integrity).
  • Standalone laboratory utilities (e.g., gas generators, unless directly integrated and supplying GC system).

Criticality Assessment

GC systems bear a pronounced impact on drug product quality. A thorough criticality assessment, guided by the equipment’s role in decision-making and product safety, drives the risk ranking used in planning the extent of qualification:

• Product Impact: Direct; failure may result in undetected impurities or incorrect assay, endangering product quality.
• Patient Risk: High; undetected or misquantified toxic substances may pose acute or chronic health hazards.
• Data Integrity Impact: High; manipulated or compromised data can lead to false product release or recalls.
• Contamination Risk: Moderate; carryover or leaks may cause false positives, though less than with some liquid handling systems.
• EHS (Environmental, Health, Safety) Risk: Moderate; hazards primarily from carrier gases, heated components, and solvent use.

Key GMP Expectations for GC Validation

Regulatory expectations for GC system validation are founded on principles common to computerized laboratory instruments and critical QC equipment:

• Full documented evidence of equipment installation, operation, and performance.
• Audit-trail-enabled software to ensure tamper-evident, attributable, and reviewable electronic records.
• Access controls, user management, and permissions aligned with data integrity practices.
• Calibration and preventive maintenance per manufacturer and internal SOPs, with traceability.
• Verification of critical safety features and fail-safes (e.g., oven shutoff, gas pressure alarms).
• Definition and implementation of change control and requalification triggers.
• Procedures for error handling, incident logging, and deviation management specific to GC operation.

User Requirement Specification (URS) for GC Systems

The User Requirement Specification (URS) is the foundation of the qualification lifecycle—translating intended use into clear, testable requirements. An effective URS for GC systems captures regulatory, business, and technical needs. Sections usually include:

• Instrument capacity (e.g., number of channels, detectors)
• Performance range (e.g., oven temperature limits, detector linearity)
• Software/data requirements (audit trails, electronic signatures, user roles)
• Sample throughput/autosampler capability
• Communication/network requirements (e.g., LIMS integration, remote access)
• Compliance attributes (21 CFR Part 11, EU Annex 11, ALCOA+ principles)
• Safety and ergonomics (e.g., emergency shutdown, gas leak detection)

Example URS excerpt for GC System:

• Oven temperature range: 20°C to 450°C, accuracy ±1°C
• Capability to support FID and ECD detectors, switchable within 5 minutes
• Autosampler for minimum 100 sample vials, with barcoding
• Chromatography data system must provide secure, time-stamped audit trails and restrict unauthorized data modification
• System must enable electronic signature per 21 CFR Part 11 compliance
• Emergency gas shutoff actuated by leak detection sensor

Risk Assessment Drivers for GC System Qualification

GC qualification is best guided by modern quality risk management, applying methods such as Failure Mode and Effects Analysis (FMEA) tailored to pharmaceutical QC environments. The goal is to identify critical system features and potential failure modes, assess the likelihood and severity of impact on data integrity or product quality, and design controls and qualification tests that mitigate those risks.

Typical risk assessment considerations for GC system qualification include:

• Detector calibration and sensitivity (impact: false negatives/positives)
• Autosampler reliability (impact: cross-contamination or sample mislabeling)
• CDS software validation and data security (impact: data loss or manipulation)
• Carrier gas purity and supply integrity (impact: baseline noise, retention shifts)
• Temperature uniformity and stability (impact: retention time reproducibility)
• Power supply and network interruptions (impact: resilience and data preservation)

The next sections continue the qualification storyline with practical tests, evidence expectations, and lifecycle controls appropriate for this equipment.

Supplier Controls for GC System Validation

Robust supplier qualification forms the foundation of GC system validation in any GMP-regulated Quality Control (QC) laboratory. Ensuring the reliability of a gas chromatograph starts long before installation or operation; it begins with the vendor selection process and extends through comprehensive quality assurance of delivered documentation and components.

Vendor Qualification

Selecting a suitable vendor for GC systems involves thorough due diligence. Audits may be conducted to assess the manufacturer’s quality management systems, regulatory track record, and service capabilities. Criteria typically include:

• ISO 9001 or relevant QMS certification.
• Demonstrated expertise in regulatory-compliant system design and documentation.
• Proven track record of successful installations in GMP environments.
• Availability of support for installation, validation, and maintenance (including remote and local support).

Document Package Requirements

A comprehensive document package from the supplier is essential for regulatory acceptability and seamless validation. The typical document package for GC system validation should include:

• Material Certificates:
  • Certificate of Compliance for system chassis, columns, sample trays, injector parts, and wetted surfaces where any contact with sample or carrier gas may occur.
  • Traceability for materials (such as stainless steels or polymers) to relevant standards (e.g., ASTM, EN, or equivalent).
• Calibration and Test Certificates:
  • Calibration data and traceability for critical components (detectors, flow controllers, thermal sensors).
  • Factory acceptance test records.
• Software Documentation:
  • Software version history, release notes, and validation package.
  • IQ/OQ scripts if provided, and electronic records compliance statement (e.g., 21 CFR Part 11 compatibility).
  • User and system administration manuals, including audit trail and backup procedures.
• As-Built Drawings and Schematics:
  • Detailed P&ID (Process and Instrumentation Diagrams), wiring diagrams, layouts, and mechanical drawings for ease of installation and preventive maintenance scheduling.
• Spare Parts and Maintenance Lists:
  • Complete spare part list, with recommended stocking levels and change frequency.

Supplier Package and DQ/IQ Documentation Checklist

FAT/SAT Strategy for GC System Validation

Factory Acceptance Testing (FAT) and Site Acceptance Testing (SAT) are vital milestones in the qualification of GC systems, ensuring the equipment’s functionality meets both contractual and regulatory requirements before and after delivery.

FAT (Factory Acceptance Test) Approach

The FAT is generally performed at the supplier’s facility to verify that the GC system conforms to the agreed specifications and performs as expected before shipment.

• Test Scope:
  • Verification of software installation and basic communication with LIS/LIMS interfaces.
  • Detector response baseline and calibration check with standard test mixtures.
  • Oven temperature cycling and leakage testing of gas lines.
  • Operation of autosamplers, valves, and auxiliary modules.
• Witnessing:
  • Typically attended by the supplier’s QA, project engineer, and customer representatives (QC, QA, engineering).
• Deviation Recording:
  • Deviations from agreed specifications or test outcomes are recorded with root cause assessment, proposed corrections, and documented impact assessment.

SAT (Site Acceptance Test) Approach

The SAT is executed after the GC system’s delivery and installation at the QC lab. Its focus is on confirming successful installation, environmental compatibility, and reproducibility of key functions under site conditions.

• Test Scope:
  • Electrical safety checks and power quality verification.
  • Gas supply pressure, purity, and leakage assessments.
  • Network and software integration with laboratory IT systems.
  • Verification of system calibration and baseline noise under actual environmental conditions.
• Witnessing:
  • Customer’s QC validation team, QA, and sometimes external validation specialists participate.
• Deviation Recording:
  • All discrepancies are meticulously documented, with corrective actions tracked and formally closed before qualification progresses.

Design Qualification (DQ) for GC Systems

DQ begins with systematic reviews of the supplier’s design output against the laboratory’s User Requirement Specification (URS). Critical elements include:

• System Architecture Review: Ensuring overall hardware and software configuration supports analytical methods, sample throughput, and is scalable for future needs.
• Drawings Review: Mechanical layouts, electrical schematics, and flow diagrams are checked for accuracy, accessibility for maintenance, and compliance with GMP standards.
• Materials of Construction: All hardware in contact with carrier gases, solvents, or samples must be chemically compatible, non-reactive, and ideally traceable to their batch origins.
• Hygienic Design (Where Applicable): While full hygienic design like that used for direct-contact drug product equipment may not be necessary, the system must prevent cross-contamination, allow easy cleaning (e.g., inert sample paths), and ensure no dead legs remain in tubing.
• Safety Features: Interlocks for oven over-temperature, gas leak sensors, and electrical safety compliance (CE/UL marking as per market and site standards).
• Audit Trails and Data Integrity: For computerized GC systems, provision of robust software controls for user authentication, data traceability, and record retention as per ALCOA+ principles and 21 CFR Part 11 (if electronic records are used).

Installation Qualification (IQ) of GC Equipment

IQ verifies and documents the correct installation of the GC system. The following checks and activities are typically performed and recorded:

• Physical Installation Checks:
  • Proper placement in designated lab area per approved floor plans and ergonomic/laminar flow guidelines.
  • Anchoring, vibration damping, and anti-static measures as per specification.
• Utilities Verification:
  • Electrical supply meets required voltage, current, and power stability (including UPS/generator backup for critical systems).
  • Carrier and auxiliary gas connections (grade, pressure regulation, and leak tightness).
  • Data connections, groundings, network and printer interface verification.
• Instrumentation and Calibration Status:
  • Verification of installation date/status labels—calibration, maintenance, and next due.
  • Confirmation that detectors, injectors, and oven sensors have current calibration certificates traceable to recognized standards.
• Identification and Labelling:
  • Clear equipment tags/ID plates matching documentation and asset register entries.
  • Safety signage (high temperature, laser warning if applicable, compressed gases).
• As-Built Dossier Compilation:
  • Archived set of as-built mechanical/electrical drawings, part lists, and network configuration screen shots.
• Safety Compliance Checks:
  • Ground continuity, insulation resistance, and ESD checks supported by test records.
  • Verification of accessible emergency shutdown controls and fire detection devices in the GC area.

Environmental and Utility Dependencies in GC System Validation

Reliable operation of the GC system in a QC setting depends heavily on supporting utilities and environmental controls. These dependencies are established upfront in the DQ and must be verified during IQ. Examples include:

• HVAC Class: The GC should be installed in controlled laboratory environments, typically ISO 8 or better, maintaining specified temperature and humidity limits for sensitive analytical balances and electronics (e.g., 20–25°C, 40–60% RH).
• Compressed Air: If autosampler or valve actuators are pneumatic, compressed air should meet oil- and particle-free criteria, ISO 8573-1:2010 Class 1.2.1 or better.
• Water Quality: While generally not a direct GC utility, any humidification or cooling system must use RO/PUW to prevent deposition or spotting on sensitive components.
• Steam: Rare for routine GC, but if present for valve sterilization, must meet local quality and pressure requirements with full documentation.
• Electrical Power Quality: Voltage and frequency deviations must be within ±5% of nominal; harmonics kept within IEC 61000-2-2 levels to avoid data corruption or control system errors.

Deviations from these requirements can lead to out-of-spec results, equipment downtime, or data integrity issues, and hence are included in acceptance criteria during qualification.

GC System Validation Traceability Table

The next sections continue the qualification storyline with practical tests, evidence expectations, and lifecycle controls appropriate for this equipment.

Operational Qualification (OQ) for GC System Validation

Operational Qualification (OQ) is a cornerstone of GC system validation within GMP environments. This critical phase demonstrates that the installed gas chromatograph operates within specified limits throughout all anticipated ranges, as required for its intended analytical applications. GMP-compliant OQ not only verifies equipment performance but also integrates robust data integrity and safety controls, ensuring the reliability and security of QC results.

Key Elements of GC System Operational Qualification

• Functional Tests: Each system module—including injector(s), column oven, detector(s), autosampler, and electronic gas control—must demonstrate correct and reliable function under actual operating conditions. Testing must capture instrument response at both minimum and maximum workload scenarios (e.g., lowest/highest temperatures, flows).
• Operating Ranges: The GC must perform accurately across its stated specification range. This includes verification of oven temperature programming, injector/detector temperature, gas flows/pressures, and voltage/current where applicable.
• Alarm and Interlock Verification: Alarms and interlocks designed to prevent unsafe or erroneous operation (e.g., over-temperature, gas supply failure, leak detection) are challenged to demonstrate response in simulated fault conditions.
• Setpoint Verification: Setpoints for process parameters (e.g., temperature, flow) are challenged, with readings compared against calibrated reference standards or the instrument’s own performance envelope.
• System Challenge Tests: Additional challenges, such as specified sample injections, leak testing, and rapid cycling of oven temperatures, are executed to probe system limits and demonstrate robustness under actual and worst-case usage.

Instrumentation Checks and Calibration Verification

Instrumentation and sensors critical to chromatographic performance must be checked and calibrated per SOPs:

• Temperature Probes/Sensors: Oven, injector, and detector temperature sensors are calibrated with external certified thermometers (e.g., acceptable tolerance: ±2.0°C).
• Gas Flow Controllers: Split/splitless flow, carrier gas flow, and auxiliary flow rates are measured with calibrated bubble meters or flow analyzers (e.g., target: ±5% of setpoint).
• Pressure Sensors: Gas inlet and outlet pressures verified with calibrated manometers.
• Syringe/Autosampler Precision: Injection volume precision validated by serial injections (e.g., RSD ≤ 1% for 1 µL volume).
• Data Acquisition/Analog Output: Detector response (e.g., FID voltage) confirmed using certified electronic simulators.

Calibration records must be readily available, and all relevant verification data captured within the OQ protocol.

Computerized System and Data Integrity Verification

If the GC system includes built-in or integrated computerized components (such as chromatography data systems, CDS), the following controls must be established and tested during OQ to comply with ALCOA+ principles:

• User Account and Role-Based Access: Verification that only authorized, uniquely identified users can access, operate, and configure the system according to their designated roles.
• Audit Trail Functionality: Every critical event (configuration change, calibration adjustment, data acquisition start/stop, result modification) is automatically and securely timestamped and traceable.
• System Time Synchronization: All system components (including networked instruments and data servers) must maintain the correct, synchronized date/time, as proven by comparison against a certified standard, to ensure trustworthy time stamps on sample data.
• Backup and Restore Operations: Procedures for scheduled and manual data backup and secure restoration are executed and verified, simulating potential data loss scenarios.
• Electronic Signatures: If enabled, the functionality of electronic signatures for approval/release steps must be tested per FDA 21 CFR 11 or equivalent requirements.

Documentation of these tests is essential for demonstrating compliance with regulatory expectations regarding data integrity and electronic records.

GMP-Compliant Controls and Documentation

To ensure full traceability and GMP alignment, operational GC system use is governed by several routine procedures:

• Line Clearance: Before each batch run or analytical campaign, the GC and the immediate environment are verified as clear of unauthorized samples, chemicals, and data files. Results are documented as part of the logbook entry.
• Status Labeling: Physical or electronic status tags indicate whether the GC system is in a qualified, in-use, maintenance, or out-of-service state. Transitions, especially during OQ, are fully documented.
• Equipment Logbooks: Chronological detailing of operations, performance checks, interventions, calibration/maintenance, and deviations.
• Batch Record Integration: Output chromatograms and system usage records are referenced directly in batch records for each analyzed lot, ensuring traceability of data to instrument performance at time of use.

Verification of Safety and Compliance Features

Environmental Health and Safety (EHS) and compliance features, both mandatory and manufacturer-specific, are reviewed and tested during OQ:

• Guarding and Cover Interlocks: All electrical and heated components must have secure covers, with interlocks engaging shutdown upon unauthorized access.
• Gas Leak Detection: System and external detectors/protocols are challenged by applying a calibrated leak to ensure alarms trigger and auto-shutdowns perform as designed.
• Pressure Relief Valves: Tested against manufacturer/set operational limits to ensure safe venting in case of over-pressure events.
• Emergency Stop Buttons: Each E-stop is activated during OQ to confirm total isolation of power and gas supplies, and that restart procedures are effective according to SOP.
• Audit of Exhaust/Ventilation: Verification that system exhausts, including hydrogen or solvent vapors, are vented according to local regulations prior to OQ completion.

Sample OQ Execution and Data Integrity Checklist

Best Practices for OQ Documentation

All OQ test results and supporting calibration records must be documented in detail, with reference to unique test numbers, acceptance criteria, actual measurement data, and pass/fail status. Any deviations from acceptance are investigated per GMP deviation protocols, and change control applied if modifications occur. Where computerized records are utilized, adherence to data integrity principles and retention schedules is mandatory, with review and approval by authorized personnel recorded via electronic or wet signature.

The next sections continue the qualification storyline with practical tests, evidence expectations, and lifecycle controls appropriate for this equipment.

Performance Qualification (PQ) for GC System Validation

Performance Qualification (PQ) is the definitive phase where the validated Gas Chromatography (GC) system, as used in a QC (Quality Control) environment, is shown to consistently perform its intended analytical applications under routine conditions. For GC system validation, PQ explores parameters critical for regulated environments, including suitability for intended products, method-specific performance, and system robustness.

Routine and Worst-case Strategies

PQ for GC systems generally encompasses both routine and worst-case scenarios, simulating operational variances the instrument may face while analyzing a variety of sample matrices. Routine PQ uses representative product samples analyzed under standard testing schedules, whereas worst-case PQ may introduce challenging matrices, low analyte concentrations, or maximum allowed injection numbers to stress the system. This dual approach assures that the GC performance is robust in both daily and exceptional laboratory situations.

PQ Sampling Plans, Repeatability, and Reproducibility

Defining a sound sampling plan is essential. For PQ purposes, replicate analyses are performed using qualified standards and authentic samples. At minimum, 6–9 injections of a standard solution and multiple real or placebo samples are typically required, in line with ICH guidelines for assay validation.

Repeatability refers to intra-assay precision: the GC’s ability to generate consistent responses from multiple injections of the same solution under identical conditions. Reproducibility may be assessed across different days, analysts, or GC channels, reinforcing instrument stability over time and between users.

Example Performance Qualification Table

Cleaning and Cross-contamination Controls

For most GC systems, the user-involved sample introduction (e.g., autosampler vials, syringes, liners) and column flow path constitute product-contact surfaces. PQ should be linked with cleaning studies, especially for labs processing active pharmaceutical ingredients or multiple products/sequences. Demonstrating the absence of carryover (evaluated in PQ by analyzing solvent blanks after high-concentration standards or samples) directly verifies cleaning effectiveness and cross-contamination controls.

If cleaning validation/verification is required, the PQ phase can serve as a platform to collect empirical data on GC system ‘memory effect’ and sample path cleanliness. Acceptance criteria are based on regulatory limits, typically defined as NMT (not more than) 0.1% carryover or below the established threshold for the analyte.

Continued Process Verification and Ongoing Qualification

Continued process verification (CPV) and periodic requalification ensure the GC system remains in a state of control throughout its lifecycle. Key measures include:

• Routine system suitability checks (prior to each analytical run) monitoring PQ parameters (e.g., precision, resolution, retention time stability).
• Trend analysis of system suitability and calibration data to promptly detect performance drift.
• Periodic requalification schedules (e.g., annual, post-maintenance) to replicate PQ tests and affirm ongoing compliance.

This approach is reinforced by defined acceptance criteria and documented procedures for handling deviations.

SOPs, Training, Preventive Maintenance, Calibration, and Spares

Robust SOPs must govern all aspects of GC use, including operation, calibration, maintenance, cleaning, troubleshooting, and PQ execution. Training programs must assure all operators are proficient with the specific model(s) and methods.

Preventive maintenance calendars should be established per the manufacturer’s recommendations, and a calibration program should be implemented for hardware such as injectors, detectors, and pneumatics. Inventories of critical and quick-wear spares (liners, septa, columns) minimize downtime risks.

Change Control, Deviations, CAPA, and Requalification

Every change—hardware, software, method, or even firmware upgrades—must pass through established change control procedures. Impact assessments determine if requalification or partial validation is necessary. Deviations from PQ, system suitability, or routine operation are logged, investigated per root cause analysis, and lead to corrective and preventive actions (CAPA) where appropriate.

Triggers for GC system requalification include:

• Major repairs or component replacements (e.g., detector, injector, column oven changes).
• Software upgrades affecting data acquisition or processing.
• Prolonged inactivity or suspected out-of-control conditions.

All such activities must be fully documented and linked to the validation master plan and equipment history file.

Validation Deliverables: Protocols, Reports, and Traceability

GC system validation deliverables must be comprehensive, compliant, and traceable. The major documents include:

• PQ Protocol: Defines objectives, rationale, test methodology, sampling, acceptance criteria, data capture templates, and deviation management.
• PQ Report: Summarizes execution, raw data, observed results, deviations, and outcomes versus predefined criteria.
• Summary or Final Validation Report: Integrates IQ, OQ, and PQ findings, outlines compliance status, unresolved issues, and recommendations for continuous monitoring.

Traceability is ensured via unique identifiers for all test runs, clear cross-referencing between requirements and evidence, and adherence to data integrity principles (ALCOA+). All raw data, electronic records, and certificates must be archived as per applicable regulatory policies.

Frequently Asked Questions (FAQ) – GC System Validation

How often should PQ be repeated on a validated GC system?

PQ should be periodically repeated according to GMP guidelines, typically every 1–3 years or after significant maintenance, modifications, or a critical deviation investigation.

What is the most common cause of PQ failure in GC validation?

The main causes are usually injector fouling, column aging, or improper maintenance, leading to poor precision, peak shape issues, or resolution failures.

Which GC parts are considered product-contact and must be addressed in cleaning validation?

Autosampler syringes, sample loops, injection port liners, and the column flow path are considered product-contact. Cleaning validation should address these components, especially if multi-product usage is planned.

What kind of deviations typically occur during GC PQ, and how should they be handled?

Common deviations include system suitability failures or sample sequence interruptions. Each deviation must be documented, root cause analyzed, and corrective/preventive actions defined before continuing validation.

How are PQ protocols for GC linked to analytical method validation?

PQ protocols assess system-level performance, but are designed to support or leverage data from method validation, especially in demonstrating precision, accuracy, and robustness in the context of real sample analysis.

What documents are required for a complete GC validation package?

The package typically comprises: URS, DQ, IQ, OQ, PQ protocols and reports, summary validation report, change/maintenance records, calibration certificates, and relevant SOPs/training evidence.

Does software or firmware change in the GC require full revalidation?

Not always. A change impact assessment is needed. For changes affecting data handling or compliance aspects, partial or full requalification is required in accordance with GMP change control.

Are electronic data integrity controls part of GC system validation?

Yes. Audit trails, user management, data backup and restore procedures, and e-record retention policies must be included per regulations such as 21 CFR Part 11 and Annex 11.

Conclusion

GC system validation within a GMP-regulated QC environment is a systematic, risk-based exercise. Performance Qualification confirms the GC’s fitness for use under both routine and worst-case conditions, including critical aspects of sample carryover and instrument robustness. By integrating thorough cleaning strategies, meticulously followed SOPs, ongoing training, robust maintenance, and proactive change control, organizations sustain GMP compliance and data integrity for their chromatographic analyses. An end-to-end traceability approach across protocols, reports, and records completes the validation lifecycle, ensuring that every test and result supports confidence in both analytical quality and regulatory assurance.