Particle Size Analyzer (QC) Validation Overview

Overview of Particle Size Analyzer Validation in QC Laboratories

In the tightly regulated world of GMP pharmaceutical manufacturing, particle size analyzers (PSAs) play a pivotal role within Quality Control (QC) laboratories. PSAs are analytical instruments designed to determine the particle size distribution of raw materials, intermediates, and finished products. Their principal function is to support batch release and stability testing by ensuring products meet critical quality attributes (CQAs) associated with safety, efficacy, and manufacturability. The validation of particle size analyzers is a crucial activity that guarantees reliable and traceable results, compliant with regulatory and industry standards.

Function and Application within QC

A PSA in a QC environment is typically utilized to measure the size range and distribution profile of particles present in pharmaceutical powders, granules, suspensions, or emulsions. The intended use of this equipment generally covers:

• Routine release testing for active pharmaceutical ingredients (APIs) and finished dosage forms.
• Stability sample analysis to monitor changes in particle size over time.
• Comparative studies for formulation and process development.
• Verification of raw material specifications when particle size is a critical quality parameter.

The boundaries of intended use exclude the use of PSAs for real-time or at-line process control, regulatory method development, and applications where the material matrix falls outside validated instrument performance parameters (such as highly opaque or sticky suspensions if not supported by the equipment).

Scope of Validation and Exclusions

The validation scope for a particle size analyzer in a QC context is rooted in its intended use within the quality system. Key elements in scope are:

• Installation Qualification (IQ), to confirm physical and electronic set-up as per manufacturer and facility requirements.
• Operational Qualification (OQ), to verify the PSA performs according to specified functional criteria across its declared working range.
• Performance Qualification (PQ), to demonstrate consistent performance under typical use conditions with relevant matrices and test materials.
• Software validation, if the instrument is fitted with or connected to data acquisition or analysis software affecting data integrity or compliance.
• User requirement specification (URS) development and traceability to GxP needs.
• Data management and integration with laboratory information management systems (LIMS), where applicable.

Out of scope:

• Maintenance/service module validation not affecting analytical performance.
• Post-marketing surveillance or indirect upstream/downstream process changes not related to PSA operation or performance.
• Process scale-up activities outside routine QC laboratory testing.
• Non-GxP uses, including R&D screening unrelated to batch release or clinical sample analyses.

Criticality Assessment

A rigorous assessment of the PSA’s role in the overall product lifecycle is necessary to determine qualification depth and justification. The following areas must be considered:

• Product Impact: Particle size directly relates to bioavailability, blend uniformity, dissolution, stability, and, in some cases, product safety.
• Patient Risk: Failure to detect out-of-specification (OOS) particle size can lead to dose non-uniformity, variable therapeutic outcome, or adverse events.
• Data Integrity Impact: Inaccurate or manipulated data acquisition impacts product release decisions and regulatory submissions; data integrity controls (ALCOA+) are essential.
• Contamination Risk: Ineffective decontamination or incorrect sample handling could lead to cross-contamination or false results, affecting product assessment.
• Environmental, Health, and Safety (EHS) Risk: The instrument may use laser optics or solvents; potential chemical, electrical, or optical hazards require mitigation by design and procedure.

The criticality assessment positions the PSA as a direct product-contact analytical device with significant impact on product quality and patient safety, requiring robust validation controls and justification of all risk acceptances.

Key GMP Expectations for Particle Size Analyzers

Regulatory expectations for particle size analyzer validation focus on several good manufacturing practice principles:

• Data Integrity: Secure, attributable, and tamper-evident data records.
• Traceability: All measurement results traceable to standards, with full audit trails for changes.
• Instrument Suitability: Clearly defined operating ranges, limitations, and periodic verification/calibration schedule.
• Change Control: Any modification to instrument hardware/software or test methods must trigger documented assessment and potential re-qualification.
• System Security: Role-based user access, transaction logs, and validated backup/restore capabilities.
• Documentation: All qualification and validation activities documented, reviewed, and approved per site SOPs.

User Requirement Specification (URS) for a Particle Size Analyzer

A clear URS is the foundation of successful PSA qualification. It should express what the QC laboratory requires from the instrument, not how the requirements should be met technically. The URS must include:

• Intended Use: State the sample types, particle size range, and frequency of use.
• Functional Requirements: Specify technical capacities such as minimum and maximum size detection, accuracy, repeatability, sample volume, and measurement speed.
• Data Management: Define requirements for data capture, storage, integration, backup, and audit trail.
• Compliance & Security: Include needs such as electronic record/e-signature functions, user-level access, and GLP/GMP compatibility.
• Environmental Requirements: Temperature/humidity tolerance, safety features, and decontamination procedures.
• Operator Interface: Language, ease of method creation, report outputs.

Example URS excerpt:

• Measure particle sizes from 0.1 µm to 500 µm with a resolution of ±3% across range.
• Localized user interface in English with secure password login for each analyst.
• System must generate and retain electronic records conforming to 21 CFR Part 11 and EU Annex 11 requirements.
• Able to connect directly with LIMS via standard CSV export protocols.
• Provide automated calibration and system suitability reminders based on defined intervals.

Risk Assessment Foundations in Qualification Planning

Risk management is integral to establishing an appropriate qualification and validation program for PSAs. A failure modes and effects analysis (FMEA) approach is recommended, where each major function or component is reviewed for potential failures, their impact on results, and corresponding mitigations or controls.

For example, in the risk assessment process, measuring a robustly validated sample with known particle size enables rapid detection of drift or system failure. The qualification plan must address the highest risks first, ensuring critical functionalities are challenged and verified under realistic, user-approximated lab conditions.

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

Supplier Controls for Particle Size Analyzers

Effective particle size analyzer validation in QC environments begins with rigorous supplier control. This ensures that the particle size analyzer, whether laser diffraction, dynamic light scattering, or alternative technology, is suitable and compliant for its intended GMP use. The process incorporates structured vendor qualification, comprehensive documentation review, and evaluation of both hardware and software supplied with the instrument.

Vendor Qualification

Before procurement, vendor qualification assesses both the manufacturer’s technical capabilities and their compliance with relevant standards (ISO 9001, ISO/IEC 17025, etc.). General steps include:

• Reviewing quality system certification and audit reports
• Evaluating supplier’s past performance with similar GMP-regulated equipment
• Assessing after-sales technical support, calibration, and spare parts availability
• Confirming vendor’s experience supplying particle size analyzers with validated software and GMP documentation

Supplier Documentation Package

Upon purchase order, the supplier must provide a documented package to support subsequent qualification. The expected content is as follows:

• Equipment Manuals (installation, operation, maintenance, calibration)
• Material Certificates (e.g., 3.1 certificates for contact parts, compliance with USP Class VI or equivalent if required)
• Software validation documentation (if analyzer software is supplied)—user requirements, risk assessment, development and validation summary, release testing, and cybersecurity details
• Factory test certificates (pre-dispatch QC and calibration checks)
• Spare part/consumable lists with recommended intervals
• Drawings: General arrangement, electrical, pneumatic, hydraulic (as applicable); vessel and flow path diagrams for wet dispersion systems
• Declaration of conformity to CE or other relevant directives

Checklist: Supplier Documentation & DQ/IQ Package

Factory Acceptance Testing (FAT) and Site Acceptance Testing (SAT)

FAT is typically executed at the supplier’s premises, demonstrating that the particle size analyzer meets basic performance requirements before shipment. Key focus areas:

• Electrical and mechanical functionality verification
• Software version verification and basic integrity tests
• Standard reference material measurement (NIST-traceable; expected sizing reproducibility)
• Safety features (interlocks, covers, alarms)
• Review of supplied documentation and certificates

SAT is conducted upon delivery at the installation site. It verifies equipment integrity, correct delivery, and basic start-up in the actual QC laboratory context:

• Visual inspection for transport damage
• Power-on and start-up checks
• Instrument and software configuration matches purchase scope
• Performance of key functional tests with standard material
• Environmental (power, humidity, temperature) checks

Witnessing & Deviation Management: While the vendor conducts FAT/SAT activities, representatives from the buyer’s quality, validation, and/or engineering departments should witness and sign off results. All observed deviations and non-conformances must be logged, investigated, and resolved by agreed corrective action prior to proceeding.

Design Qualification (DQ) for Particle Size Analyzers

DQ formalizes the review of system design against User Requirement Specifications (URS) and GMP compliance requirements. For a particle size analyzer in QC, include:

• Evaluation of detector and light source design (e.g., laser safety class, light path configuration)
• Review of materials of construction— sample cells, flow paths, seals—ensuring compatibility with samples, cleaning agents, and GMP hygienic standards
• Assessment of dust/water ingress protection (IP rating), especially if analyzer is used in wet or solvent-based dispersion methods
• Verification of cleaning accessibility and absence of contamination traps
• Software: 21 CFR Part 11/data integrity capability, user authentication, and audit trail functionality
• Reference standards compatibility and traceability
• Review of wiring and grounding for electrical safety; electromagnetic compatibility (EMC) as per regional requirements

The DQ process should be documented with a clear decision trail showing that design choices fulfill all critical quality and regulatory requirements.

Installation Qualification (IQ) of Particle Size Analyzer: Planning and Execution

The primary goal of IQ is to confirm that the analyzer is delivered, installed, and documented in accordance with approved specifications and GMP standards. A robust IQ protocol covers:

• Installation Confirmation: Analyzer sited in correct QC laboratory area, as per layout drawing; mounting/fixation checks; vibration control (if applicable)
• Connection and Utility Checks: Power supply voltage, outlets, harmonics filtering; emergency shutoff; compressed air or vacuum supply (if required)
• Environmental Confirmation: HVAC class (e.g., ISO 8 for typical QC lab, or as defined in URS); ambient temperature and humidity monitoring as required by instrument specification
• Instrument Calibration Status: Verification of on-board and external calibrations against latest certificates (lasers, detectors, temperature probes, flowmeters if present)
• Labeling and Identification: Equipment and major component labeling as per site asset management and GMP traceability practices
• Review of As-Built Dossier: Integration of installation drawings, utility connection details, cable routing, and post-installation “as found” state photographs
• Software Installation & Password Management: Confirmation of correct and secure software version installed on local workstation/server, with initial configuration and user management controls validated
• Verification of Safety Systems: Laser safety (interlocks, warning lights, eyewear), electrical earth continuity, fusing, cover microswitches, fire safety (lab and instrument area)
• Instrument Accessories: Proper installation and referencing of accessories—autosamplers, dispersion units, static/dynamic cell assemblies

Environmental and Utility Dependencies

Acceptable operation and valid results from a QC particle size analyzer demand strictly controlled environmental and utility conditions. These are usually captured in the URS and verified during IQ:

• HVAC (Heating, Ventilation, Air Conditioning): QC labs typically require ISO Class 8 or better. Excess particulate/volatile organic content can compromise sample integrity, especially for low-concentration dispersions or sensitive detectors.
• Compressed Air: If the analyzer uses pneumatic sample delivery or cleaning, supply must be clean, oil- and moisture-free, filtered per ISO 8573-1:2010 Class 1.2.1 or as defined in the URS.
• Water Supply (RO/PUW): For wet dispersion, rinse, or cleaning cycles, water quality must match instrument and method specifications (e.g., conductivity, resistivity, microbial limits).
• Steam: Generally not directly required for most laboratory analyzers but, if used (e.g., for in-line CIP on larger automated systems), steam must be clean and dry, validated per EN 285 or equivalent.
• Power Quality: Analyzer and associated IT equipment require stable supply; voltage, frequency, and total harmonic distortion (THD) should match supplier recommendations. UPS deployment is advised to prevent data loss during power interruptions.
• Ambient Variables: Temperature and humidity must be maintained within the analyzer’s operational limits (e.g., 18–25°C and 40%–60% RH), usually traceable to method validation and instrument specification.

Traceability Matrix: URS to Test to Acceptance Criteria

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

Operational Qualification (OQ) for Particle Size Analyzer: Key Aspects

The Operational Qualification (OQ) phase of particle size analyzer validation ensures that the instrument consistently performs within its specified operational limits under simulated routine conditions. During OQ, the tester verifies that the analyzer’s functions, controls, and alarms work as intended, and that the system is capable of generating accurate and reliable data in compliance with Good Manufacturing Practice (GMP) standards.

Functional Tests and Operating Ranges

Functional testing is at the core of operational qualification for a particle size analyzer. This involves methodically operating the instrument through all anticipated ranges and verifying its performance under each condition. The following activities are typically included:

• Running the analyzer over the full range of manufacturer-specified particle size measurement (e.g., 0.02 – 2000µm).
• Testing the sample introduction system for reproducibility and accuracy.
• Validating sample dispersion (e.g., wet/dry dispersion units).
• Evaluating measurement modes, such as static and dynamic light scattering, as available.
• Verifying response to control inputs such as start, stop, and abort functions.

The operating limits for each critical parameter are derived from the user requirements/specifications and equipment manual. For instance, an acceptance criterion might specify a reproducibility of <3% relative standard deviation (RSD) for repeat particle size measurements under routine conditions (example value). The OQ protocol should include test sequences that fully exercise the menu-driven user interface, lamp stability, background noise, sample recirculation, and adequate sample obscuration according to the manufacturer’s recommendations.

Verification of Alarms, Interlocks, and Setpoints

Particle size analyzers often incorporate built-in alarms and interlocks to safeguard both the instrument and operator. These protections must be challenged systematically during OQ:

• Alarms: Test out-of-specification sample volume warnings, laser lamp failures, and any cover interlock alarms.
• Interlocks: Verify that measurement cannot begin if the sample chamber is not closed or if critical subassemblies are unseated.
• Setpoints: Confirm that setpoints such as sample flow rate, temperature, and obscuration thresholds can be programmed and are respected during operation.

Example: When the sample chamber cover is opened, the system should stop data acquisition and display an interlock warning. Acceptance: Instrument must halt measurements within 2 seconds (dummy specification).

Instrumentation Checks and Calibration Verification

Calibration status of both the particle size analyzer and its key components must be confirmed as part of OQ. Instrumentation checks commonly contain:

• Verification of internal reference standards (e.g., polystyrene microspheres) against certified values.
• Assessment of laser alignment and power output within manufacturer’s tolerances.
• Review of instrument diagnostics/self-test results and error logs for anomalies.
• Verification that all instrument sensors (temperature, flow, pressure, etc.) are within current calibration and function as intended.
• Documentation of calibration labels and certificates for traceability.

Sample acceptance criteria for calibration verification:

• Measured mean particle size of 5µm ± 0.2µm for 5µm reference standard (example value).
• Laser output stability >99% during a 10-minute stability test (example value).

Challenge Tests

Challenge tests are designed to confirm the analyzer’s response to known stresses or abnormal conditions:

• Intentional blockage of sample path to verify stoppage and alert mechanism.
• Measurement of out-of-range sample concentration to confirm triggering of high/low obscuration alarms.
• Testing automated cleaning or purging cycles to ensure full cycle execution upon command.

Challenge tests are critical for establishing reliability and performance consistency, especially for instruments deployed in regulated QC environments.

Data Integrity Controls for Computerized Particle Size Analyzers

Where the particle size analyzer incorporates a computerized system or software-controlled interface, OQ must rigorously test GMP data integrity controls:

• User Roles, Access, and Security: Validate the creation of user accounts with differentiated permissions (e.g., operator, supervisor, administrator).
• Audit Trail Functionality: Confirm that all critical activities (data changes, deletions, parameter changes, etc.) are captured with who/what/when/why details, stored in a secure, non-editable format.
• System Time Synchronization: Test that date and time stamps are accurate and synchronized with the site’s primary time servers.
• Data Backup and Restoration: Simulate scheduled and manual backup, followed by restore processes to ensure data is recoverable and unaltered post-recovery.
• Password and Lockout: Check password strength enforcement, lockout after failed logins, and automatic session timeouts.

Example acceptance criteria: All audit trail entries are time-stamped to within 1 second accuracy and cannot be deleted or altered by any user (dummy value for illustration).

GMP Controls: Supporting Documentation and Traceability

Effective control of the particle size analyzer’s operational environment is vital for regulatory compliance and data integrity. During OQ, the following GMP controls should be demonstrated:

• Line Clearance: All previous samples and reference materials are cleared prior to qualification runs—a documented checklist should be used.
• Status Labeling: Attach clear “UNDER QUALIFICATION” or “IN USE/OUT OF SERVICE” labels throughout OQ and routine operations.
• Logbooks: Maintain equipment logs recording all qualification runs, routine maintenance, and calibration events, signed and dated by responsible personnel.
• Batch Record Integration: Verify workflow for associating analyzer outputs (e.g., reports, raw data) with batch manufacturing or QC records, ensuring traceability.

Acceptance examples:

• Each run is logged with operator identity, date/time, sample ID, and result summary.
• Status labels are visible from operator position and match the current equipment usage state.

Safety and Compliance Features Verification

Safety and environmental compliance features must be checked for operability:

• Guards and Enclosures: Confirm that all moving parts, laser sources, and hazardous zones are appropriately shielded with interlocks where required.
• Pressure Relief: Where applicable (e.g., wet dispersion units under pressure), verify operability and setpoints of relief valves.
• Emergency Stops: Test each “EMERGENCY STOP” for immediate power-down and system lockout.
• Environmental Controls: Validate performance under recommended environmental conditions (e.g., temperature, humidity ranges per manufacturer).

Example acceptance criteria:

• Emergency stop halts system within 1 second (dummy specification).
• No laser emission detected when cover is open, confirmed by built-in laser sensor.

Sample OQ Execution & Data Integrity Checklist for Particle Size Analyzer

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

Performance Qualification (PQ) of Particle Size Analyzers

Performance Qualification (PQ) is the culminating stage of particle size analyzer validation in a GMP Quality Control (QC) environment. PQ assesses whether the particle size analyzer operates consistently and reproducibly under typical and worst-case routine laboratory conditions. This phase demonstrates that the equipment will reliably measure particle size distributions in actual QC workflows, using real or simulated samples representative of the pharmaceutical dosage forms handled onsite.

PQ Execution Strategy

PQ should encompass both routine scenarios (regular product matrices and concentrations) and worst-case challenges—such as samples with borderline particle sizes, highly polydisperse mixtures, or substances prone to agglomeration. The protocol must define:

• Sample types—covering range of materials commonly analyzed (e.g., powders, suspensions)
• Replicate tests for repeatability (intra-assay) and inter-analyst or inter-day runs for reproducibility (inter-assay)
• Challenge samples simulating low/high concentration, viscosity extremes, and interfering excipients
• Full data acquisition, processing, and reporting flows

Sampling Plans and Acceptance Criteria

A statistically justified sampling plan ensures comprehensive PQ coverage. At minimum, PQ should test each key product type, with a sufficient number of replicates to evaluate variability and system suitability. Below is a sample PQ plan outline:

Acceptance criteria should reference validated standards/certified reference materials when possible. Criteria typically include measures such as percent relative standard deviation (%RSD), agreement with expected D10/D50/D90 values, and documentation of absence of significant outliers or instrument errors.

Cleaning and Cross-Contamination Controls

For particle size analyzers with product-contact components (e.g., sample cells, funnels, cuvettes), validated cleaning procedures must mitigate cross-contamination risks. During PQ, cleaning effectiveness can be challenged by running blanks after worst-case samples and analyzing for carryover. Operators should demonstrate:

• Consistent use of validated cleaning SOPs for sample holders/contact parts
• Verification runs using highly potent, sticky, or high-load samples
• Analytical confirmation that blank or placebo runs after cleaning yield results below established thresholds (e.g., baseline/no detectable particles)

PQ integrates with the cleaning validation/verification program. Failures in cleaning steps during PQ indicate the need to re-examine cleaning methods and may postpone system qualification.

Continued Process Verification & Qualification Maintenance

Whereas PQ provides the initial assurance of reliable performance, ongoing qualification (“continued process verification”) assures sustained compliance. Key activities include:

• Periodic reviews of routine QC data for trends, drifts, or out-of-trend results
• Scheduled annual or bi-annual requalification using a subset of PQ tests (e.g., standard material analyzed quarterly)
• Routine system suitability checks—analysis of certified reference materials before/after sample batches
• Documentation and trending of preventive maintenance, calibration, and performance checks within logbooks or electronic systems

Trends indicating decreasing repeatability, instrument drift, or failure to meet system suitability prompt investigation, servicing, or partial/full requalification, as appropriate.

SOPs, Training, Maintenance & Calibration

Robust Standard Operating Procedures (SOPs) are essential for particle size analyzer validation. These should cover:

• Sample preparation and handling
• Instrument operation, software use, and result reporting
• Cleaning and decontamination procedures (as above)
• SOPs for periodic calibration and maintenance actions—e.g., alignment checks, optical/electronic verifications
• Checklists and documentation requirements

Only qualified, trained personnel should operate and maintain particle size analyzers. Routine preventive maintenance and calibration—often defined by the manufacturer—must be included in the site’s equipment management program, alongside identification and stocking of critical spare parts (e.g., lasers, pumps, sample cells).

Change Control, Deviations & CAPA Linkage

All changes to the particle size analyzer, associated software, or validated procedures—such as hardware/firmware upgrades, analytical method changes, or movement to a new location—must be managed through the change control process. Change control assesses the potential impact on validated state and defines requalification needs. Triggers demanding partial or full requalification include:

• Installation of new software or software patches
• Major repairs or replacement of key components (optical detectors, dispersion units)
• Relocation or environmental changes
• Repeated or critical out-of-specification results

Deviations (e.g., PQ failures, cleaning/maintenance lapses) and the subsequent Corrective and Preventive Actions (CAPA) process must be tightly integrated—investigations should document root cause analysis, impact assessment (including data integrity risk), and actions taken (such as revalidation or enhanced training).

Validation Deliverables and Traceability

The validation package for a particle size analyzer typically comprises:

• PQ Protocol: Defined objective, scope of testing, detailed test plan, sample selection, acceptance criteria, and responsibility assignments.
• PQ Report: Summarized test execution details, raw data, results vs. criteria, outlier or deviation documentation, and conclusion of suitability.
• Traceability Matrix: Demonstrates linkage from user requirements/specifications and risk assessments to qualification test items and raw data.
• Summary Report: Executive summary integrating IQ/OQ/PQ outcomes, outstanding issues, and a final validation statement with any restrictions or conditions for use.

All records must be ALCOA+ (Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, and Available), supporting rapid retrieval for audit or regulatory inspection.

FAQ: Particle Size Analyzer Validation

What types of samples should be included in PQ for particle size analyzers?

PQ should evaluate all representative pharmaceutical matrices measured on the analyzer—powders, suspensions, granulates—across concentration and size extremes, as well as challenging substances (e.g., sticky, high-load, or highly polydisperse materials).

Is cleaning validation always required for QC particle size analyzers?

Cleaning validation or verification is required when product-contact components are not single use. Demonstrating effective cleaning prevents cross-contamination; verification (e.g., reusable cuvettes/cells) is often performed during PQ with blanks or low background measurements.

How often should requalification of a validated particle size analyzer occur?

At minimum, an annual performance check using reference standards is best practice. Full or partial requalification is also triggered by major repairs, software updates, or if recurring deviations are detected.

What are the main sources of analytical variability in particle size measurements?

Analytical variability can stem from sample preparation, inconsistent dispersion or dilution, operator differences, environmental factors, and instrument aging or drift. PQ is designed to quantify and control these sources.

How are acceptance criteria established for PQ tests?

Acceptance criteria are based on method validation (particularly precision and accuracy), manufacturer specifications, regulatory guidelines, and previous system suitability data. Using certified reference materials is highly recommended.

What documents must be retained following validation?

Retain all protocols, raw data, completed checklists, deviation/CAPA records, PQ reports, validation summary, and traceability matrices for the system’s lifecycle. These support compliance and data integrity audits.

How does software change impact validation status?

Any software revision, patch, or configuration change should undergo change control review. Significant updates generally necessitate at least partial requalification to confirm continued reliable measurement and data handling.

What is the relationship between PQ and routine system suitability?

PQ provides the baseline; routine system suitability tests (e.g., certified standards before runs) confirm ongoing analyzer performance and are part of continued qualification per GMP expectations.

Conclusion

Particle size analyzer validation is a critical control in pharmaceutical QC, ensuring that particle size determinations—essential for dosage form performance and safety—are accurate, reproducible, and regulatory compliant. Comprehensive PQ, tightly managed cleaning procedures, robust maintenance and calibration, and rigorous change control underpin lifecycle qualification. Proper protocol execution, clear documentation, and alignment with both method and GMP requirements collectively safeguard data integrity and patient safety for every batch analyzed.