Temperature Mapping (Thermal Mapping) — Detailed Protocol & Guidance

Purpose

To demonstrate that temperature (and where applicable RH) across storage areas, cold rooms, chambers, incubators, refrigerators, freezers, and transport shippers remains within qualified limits under normal operating and worst-case conditions. Mapping verifies uniformity, hot/cold spots, and equipment performance for storage, stability, and transport qualification.

Scope

Applies to:

• Warehouses, cold rooms, freezer rooms (2–8 °C, -20 °C, -80 °C)
• Stability chambers, stability rooms, incubators, ovens
• Refrigerators, clinical shippers, active containers, controlled transport boxes
• Point-of-use storage (e.g., clinical trial lockers)
• Any temperature-controlled GMP area requiring qualification or requalification

References / Standards

• WHO TRS / Good Distribution Practices
• EU GDP / Annex 1 (where applicable)
• ISO 14644 (environmental context)
• Local pharmacopeial / regulatory expectations
• Manufacturer recommendations for equipment

Acceptance Criteria (examples — define in URS/Protocol)

• Rooms/areas: Temperature must remain within defined setpoint ± allowable tolerance (e.g., 2–8°C ±2°C) for the entire mapping period.
• Refrigerators/freezers: all mapped points must be within defined limit (e.g., −20 °C ±5 °C).
• Stability chambers: meet specified setpoint with allowed drift per stability protocol.
• Point-of-use: no more than X% points outside limits (preferably zero).
• Maximum permitted excursion duration should be defined (e.g., excursions >30 minutes require investigation).
  Acceptance criteria must be defined in the mapping protocol as per product stability or storage URS.

Instruments & Calibration

• Temperature data loggers (multi-channel or individual) — calibrated, NIST-traceable, with certificate.
• Reference calibrated thermometer(s) for spot checks.
• RH loggers where RH is critical — calibrated.
• Thermal couples or PT100 probes for chambers/ovens.
• Software for logger download, timestamp alignment, and plotting.
• Calibration certificates must be current and traceable at time of mapping.

Calibration scope: logger accuracy, resolution, and calibration date; if using thermocouples/PT100s, include thermocouple mapping and cross-verification.

Pre-Mapping Activities

1. URS / Protocol Preparation: Define areas, setpoints, acceptance criteria, mapping duration, worst-case scenarios, and number of sensors.
2. Risk Assessment: Identify worst-case zones (near doors, corners, ceilings, under pallets, next to HVAC diffusers or returning air).
3. Number & Placement of Sensors: Based on volume and complexity — typical guidelines below.
4. Environmental Set-up: Ensure equipment is at normal working temperature, load condition (empty vs loaded) as per URS. If assessing loaded conditions, prepare representative load (pallets/boxes).
5. Instrument Check: Calibrate loggers and verify battery life and memory capacity. Synchronize clocks.
6. Notification & Safety: Notify operations to avoid door openings other than defined test occurrences; define staff movement rules.

Sensor Count & Placement Guidance (examples)

• Small refrigerator (1–2 m³): 6–12 sensors — corners, center, near door, top and bottom shelves.
• Walk-in cold room: 12–30 sensors depending on size — each corner, ceiling, floor, door zone, multiple rack positions, return air near AHU, supply air plenum, mid-plane.
• Trailer/Reefer: 8–20 sensors — head, middle, tail, both sides, top/mid/bottom levels, underside of pallets.
• Stability chamber: one sensor per shelf + 3–5 extra for corners and door side.
• Shippers/Insulated boxes: 4–8 sensors — center, near walls, near coolant, near top/bottom.
  Sensor spacing should give full 3-D coverage; use more sensors for complex airflows.

Mapping Scenarios & Duration

• At-rest mapping: System running, no personnel movement. Duration typically 24–72 hours depending on equipment and URS.
• Operational mapping: With normal activity (doors opening, personnel, forklift) to capture disturbances — 24–72 hours.
• Empty vs Loaded mapping: If process load affects temperature, perform loaded mapping to represent worst case.
• Seasonal mapping: For vehicles/long routes consider summer/winter trials.
• Transport mapping: Full route PQ trials including transit, handling, door open events, and simulated delays.

Mapping duration must reflect the system qualification needs (e.g., refrigerators 24–48 h; cold rooms 48–72 h; stability chambers according to stability protocol).

Execution Steps

1. Place loggers at pre-defined locations and secure them (label each sensor, note exact position). Photograph placement and tag IDs.
2. Log pre-start conditions: traceability list, logger IDs, calibration certificates, start time, ambient conditions.
3. Start loggers simultaneously; record start time and operator.
4. During mapping, record any planned interventions (door openings, loading/unloading) with timestamps. For uncontrolled events, log incidents.
5. At end of run, stop loggers, download raw data, and archive original files.
6. Cross-check logger readings against reference thermometer at start and end.
7. For transport trials, recover loggers and download immediately; correlate GPS/time if used.

Data Analysis & Reporting

• Plot time–temperature profiles for each sensor (overlay setpoint and acceptance band).
• Determine min, max, average, and standard deviation for each point.
• Identify excursions (points outside limits) and total excursion durations.
• Create a spatial map (plan view & elevation) showing hot/cold spots annotated with min/max values.
• Correlate events (door openings) with excursions.
• Perform statistical analysis for stability chambers (uniformity, drift).
• For transport, provide Tt graph (time-temperature) and excursion table.

Report Contents:

• Executive summary & conclusion (pass/fail)
• Test objective, scope, and acceptance criteria
• Area drawings with sensor locations (plan & elevation)
• Calibration certificates & logger list
• Raw and processed data plots (per sensor)
• Summary tables (min/max/mean/std/excursions)
• Photographs of sensor placement & test conditions
• Root cause analysis for any excursions and CAPA recommendations
• Signatures and approval

Acceptance & CAPA

• If mapping meets criteria → issue Certificate of Conformance and update URS/qualification pack.
• If excursions occur → investigate root cause (equipment, loading, user behavior, door seals), implement CAPAs (balancing, additional racks, relocation of sensors, SOP changes), re-map after corrective actions.
• For transport excursions, evaluate packaging/shipper changes or different carriers.

Common Findings & Mitigations

• Hot/cold spots near doors: Add vestibules, reduce door openings, install strip curtains, reposition racks.
• Stratification in large rooms: Increase ACPH, install destratification fans or recirculation.
• Poor pallet loading patterns: Change loading patterns to allow airflow, use gaps between pallets.
• Sensor drift/outliers: Replace/calibrate sensors and repeat mapping.
• Freezer thawing during door opening: Minimize door cycles or add pre-chill staging area.

Good Documentation Practices

• Use tamper-evident labels & unique IDs for loggers.
• Keep an audit trail of data files; store raw files in read-only format.
• Timestamp all manual logs and correlate precisely with logger times.
• Use approved electronic systems or validated software for data handling if required by Part 11.

Example Appendix: Minimal Mapping Matrix (sample)

• Area: Cold Room A (2–8 °C)
• Duration: 72 hours (24 h at-rest + 48 h operational)
• Sensors: 18 (list IDs + locations)
• Frequency: 5-minute logging interval
• Acceptance: 2–8 °C ±2 °C; zero excursions >30 minutes
• Deliverables: Protocol, Raw data, Plots, Report, CAPA (if any)

Template Items I Can Provide Next (if you want)

• Full Temperature Mapping Protocol template (editable)
• Sensor placement drawing sample (plan & elevation SVG)
• Excel template for analysis (min/max/mean/std + plots)
• Report template with sections and figure placeholders
• Short 15-word card copy for the website