Published on 07/12/2025
Comprehensive Guide to Calibrating Temperature, Pressure, and Humidity Devices in Pharma
Introduction
Temperature, pressure, and humidity measuring devices are critical to GMP-compliant pharmaceutical manufacturing. Whether they monitor cleanroom environments, equipment conditions, or stability chambers, their accuracy directly affects product quality. Regulatory agencies such as the FDA, EMA, and WHO require routine calibration of these instruments with traceable standards and well-documented protocols.
This article provides a step-by-step approach to calibrating temperature sensors, pressure gauges, and humidity probes, including protocol elements, acceptance criteria, documentation, and compliance requirements.
Regulatory Requirements
Calibration of instruments is mandated under various global GMP standards:
- 21 CFR 211.68(b): “Automatic, mechanical, or electronic equipment… shall be routinely calibrated, inspected, or checked according to a written program.”
- EU GMP Chapter 3: “Measuring instruments shall be calibrated and checked at defined intervals.”
- WHO TRS 1019 Annex 9: “All equipment used in manufacturing and control must be calibrated with reference standards traceable to national or international standards.”
Failure to calibrate accurately can result in FDA 483s or EU Annex 15 non-compliance findings. Therefore, every critical device must follow an approved calibration schedule.
Device Categories and Calibration Frequency
Temperature, pressure, and humidity instruments typically requiring calibration include:
- Digital and analog
Recommended calibration frequencies:
| Device Type | Calibration Frequency | Standard Used |
|---|---|---|
| Digital Temperature Sensor | 6 Months | NIST Certified Dry Block |
| Analog Pressure Gauge | 12 Months | Dead Weight Tester |
| RH Sensor | 6 Months | Salt Chamber Calibrator |
| Data Logger | Before Each Validation | Temperature Bath/Controller |
Calibration Protocol Components
Each calibration must be performed under a written, approved protocol. Essential sections include:
- Objective: Define the goal (e.g., “To calibrate pressure gauge PG-203 in AHU-7 zone”).
- Scope: Mention device make, model, ID, and location.
- Reference Standards: Include certificate numbers, traceability chain (e.g., to NIST or NABL), and expiry dates.
- Calibration Method: Step-by-step procedure for each point.
- Acceptance Criteria: Define permissible tolerance limits (e.g., ±0.5°C for temperature; ±2% for RH sensors).
- Environmental Conditions: Room temperature, humidity, power supply — must be within acceptable range during calibration.
- Results Table: Format to record reading vs. standard.
- Deviation Handling: Procedure for failed calibration or OOT.
Sample Calibration Table
Below is an example calibration results table for a digital temperature probe:
| Setpoint (°C) | Standard Reading (°C) | Device Reading (°C) | Deviation (°C) | Status |
|---|---|---|---|---|
| 0 | 0.02 | 0.30 | +0.28 | Pass |
| 25 | 25.01 | 24.92 | -0.09 | Pass |
| 50 | 49.98 | 50.25 | +0.27 | Pass |
| 100 | 99.95 | 100.40 | +0.45 | Pass |
Always ensure that each reading is within the pre-defined acceptance range. Deviations must be documented and evaluated for impact on previously recorded data.
Use of Certified Reference Standards
Reference standards used in calibration must be:
- Calibrated by ISO/IEC 17025 accredited laboratories
- Traceable to international bodies like NIST, NABL, or DKD
- Within validity period (typically 1 year)
- Accompanied by calibration certificates with uncertainty levels
Example: For RH sensor calibration, use saturated salt solutions (e.g., MgCl2 for 33% RH) certified with ≤2% uncertainty.
Out-of-Tolerance (OOT) Results Handling
If a device fails to meet the acceptance criteria during calibration, it is classified as Out-of-Tolerance (OOT). Immediate actions must be taken:
- Isolate the instrument: Remove from service and label as “OOT – Do Not Use.”
- Initiate deviation: Log incident in deviation management system for impact assessment.
- Impact Assessment: Review all critical data logged since the last valid calibration. For example, review temperature records of product batches stored in a chamber controlled by the OOT device.
- Corrective Action: Repair and recalibrate the device. Update the calibration log.
- Preventive Action: Investigate root cause (e.g., drift, shock, expired sensor).
OOT events must be logged in audit trails. Refer to pharmaregulatory.in for deviation and CAPA SOPs.
Calibration Tags and Status Labeling
All calibrated devices must carry a visible status label. Elements include:
- Instrument ID
- Calibration Date
- Due Date
- Calibrated By
- Status (PASS/FAIL)
Example:
ID: TEMP-007 | Calibrated: 15-JUN-2025 | Due: 15-DEC-2025 | By: QA-CAL | Status: PASS
Fail tags must be RED and should clearly indicate “Not for Use” until recalibrated or replaced.
Calibration Documentation & Audit Trail
Every calibration must be documented with:
- Calibration Protocol (approved)
- Raw Data Sheets
- Calibration Certificate (signed, dated, traceable)
- Results Summary Table
- OOT Investigation Report (if applicable)
- Recalibration Certificate (if applicable)
- Updated Calibration Register / Equipment Logbook
Electronic calibration systems must ensure ALCOA+ principles are met. For LMS integrations, explore solutions on PharmaGMP.in.
Calibration Master Plan (CMP)
The CMP defines the overall calibration strategy, frequency, responsibilities, and acceptable tolerances for all equipment in the facility. Elements include:
- Scope and equipment classification
- Master list of instruments and calibration frequency
- Reference standards to be used
- Format and approval flow for calibration protocols
- System for tracking due dates and overdue devices
- Audit and review mechanism
The CMP should be reviewed annually and revised if there are changes to equipment, product, or regulatory expectations.
Digital Tools for Calibration Management
Modern pharma facilities use digital calibration management software to reduce manual errors and ensure audit readiness. Features include:
- Auto alerts for upcoming due dates
- Integration with QMS modules
- Automatic report generation
- Trend analysis on drift and failure rates
Platforms such as StabilityStudies.in and ClinicalStudies.in offer calibration and equipment lifecycle modules.
Training & Competency Requirements
Personnel performing calibrations must be trained in:
- Use of reference standards and calibrators
- Understanding uncertainty and tolerances
- Deviation documentation and response
- Reading calibration certificates and logs
Training must be documented, with practical assessments conducted annually. Retraining should be triggered by any calibration failure linked to operator error.
Conclusion
Calibration of temperature, pressure, and humidity devices is a critical control point in pharmaceutical operations. Proper calibration ensures data integrity, product quality, and regulatory compliance. A robust program includes scheduled calibration, deviation handling, traceability to standards, and a strong documentation system.
Explore SOP templates, master plan formats, and validation tools at PharmaSOP.in and stay ahead of compliance challenges.