Temperature and Humidity Monitoring in Pharma Plants and Stores

In short: GMP requires temperature and humidity in production areas and stores to suit the materials and products, and to be checked and monitored where special conditions apply. This page explains the regulatory basis, how to set limits, map, monitor, alarm and calibrate, and how to design humidity control without creating a contamination risk. It is for QA, engineering and warehouse staff.

Why it matters

Heat and moisture speed up degradation of many materials. Moisture can cause hydrolysis, caking, softening of coatings and microbial growth; heat can cause oxidation and loss of potency. Biological products are especially sensitive. Temperature and humidity also affect how equipment works and how comfortable operators are in cleanroom gowning. For these reasons, conditions must be controlled, monitored and recorded wherever they matter to the material, the product or the process.

What the regulations say

Source	What it says (paraphrased)
EU GMP Part I, Chapter 3 (Premises and Equipment), 3.3	Lighting, temperature, humidity and ventilation should be appropriate so they do not harm medicinal products during manufacture and storage, or the accurate working of equipment.
EU GMP Chapter 3, 3.12	Production areas should be effectively ventilated, with air control (temperature, and humidity and filtration where needed) suited to the products, the operations and the outside environment.
EU GMP Chapter 3, 3.19	Storage areas should be clean, dry and kept within acceptable temperature limits. Where special conditions such as temperature or humidity are needed, they should be provided, checked and monitored.
21 CFR 211.142(b)	Written warehousing procedures must cover storage of drug products under appropriate conditions of temperature, humidity and light so identity, strength, quality and purity are not affected.
WHO TRS 961 (2011), Annex 9, sections 4.5 to 4.10	Model guidance on control, monitoring, alarms, qualification and calibration for temperature-controlled stores of time- and temperature-sensitive pharmaceutical products.

The WHO Annex 9 text is written for time- and temperature-sensitive products (cold chain and controlled room temperature), but its approach is widely used for any controlled store.

Do not confuse storage-area limits with stability conditions. The ICH Q1A(R2) conditions (for example 25 °C/60 % RH or 30 °C/65 % RH) are the conditions used in stability studies to support shelf life and labelled storage statements. They are not set as warehouse or production-room limits. A warehouse limit comes from the product label and the stability data behind it, for example “do not store above 25 °C”, and from your own risk assessment.

Setting limits

Start from the label storage statement of the product (or the supplier’s statement for materials).
State humidity together with temperature. A relative humidity figure means nothing without the temperature at which it applies.
Do not set the band so tight that normal fluctuation causes constant alarms, nor so wide that it no longer protects the product.
For operator comfort in cleanrooms, remember that gowning raises body heat, so the room temperature may need to be lower than in offices.

Example in-house criteria (adapt to your own products and risk assessment): general store 15–25 °C or 15–30 °C as per label, relative humidity not more than 60 % for moisture-sensitive materials, cold room 2–8 °C. These are examples, not regulatory limits.

Mapping (qualification) of stores

WHO Annex 9 (4.7) says to qualify new temperature-controlled stores and refrigeration equipment before use. The exercise should show the air temperature profile in the empty and normally loaded store, identify zones that should not be used for storage (for example close to cooling coils, cold air streams or heat sources), and show how long temperatures take to exceed limits after a power failure. Repeat the study when changes could affect loading or air circulation, and consider it again when monitoring shows unexplained variability.

Example in-house criteria for the practical side of mapping:

Place calibrated data loggers at corners, centre, near doors, near the HVAC supply and return, and at different heights.
Run for a defined period that covers a typical load and weather range (for example 3 to 7 days; for a seasonal study, a hot-weather and a cool-weather run).
Repeat after major layout, HVAC or load changes, and review at a periodic interval set by risk (for example every 1 to 3 years).

Monitoring

Per WHO Annex 9 (4.5.2 and 4.5.4):

Sensors should be placed where the greatest variation (worst case) is expected within the qualified space, and positioned so door openings affect them as little as possible.
Electronic temperature sensors accurate to ±0.5 °C or better; humidity sensors accurate to ±5 % RH.
A recording frequency of at least six readings per hour for each sensor position, with records that can be stored and retrieved.
Monitoring should keep working independently in a power failure.
Where a person checks the devices or traces, check at least twice a day (morning and evening), seven days a week, including public holidays.

For compliance with data integrity expectations, protect electronic records (user access, audit trail, backup) and review them at a defined interval. Example in-house review: supervisor daily, QA weekly, with trend review in the periodic report.

Keep monitoring records, mapping reports and excursion investigations at least 1 year after the expiry date of the respective product batch (EU GMP Part I, Chapter 4, 4.11; 21 CFR 211.180(a)), longer if local law or the marketing authorisation requires.

Alarms

WHO Annex 9 (4.6) expects high and low alarm set points to trigger a visual alarm in a suitable location, preferably also an audible alarm, and preferably an automatic dial-up or SMS alert to on-call staff outside working hours. Alarm sensors should be accurate to ±0.5 °C, and positioned at worst-case locations (close to the monitoring sensors if the alarm is not part of the monitoring system). Check that alarms work at their set points at least every six months and keep records (4.10.3).

Example in-house practice: set an alert level inside the acceptable range and an action level at the limit, with a time delay to avoid false alarms from door openings.

Calibration

WHO Annex 9 (4.10.1 and 4.10.2) says to calibrate temperature and humidity devices against a certified, traceable reference standard at least once a year unless otherwise justified. For temperature devices, calibration should show accuracy across the whole range over which the device is used. Single-use devices supplied with a manufacturer’s calibration certificate need not be recalibrated. See the example SOP for Calibration.

Handling an excursion

Record the time, duration, location and the highest or lowest reading.
Quarantine affected stock until QA assesses it.
Assess impact using the label statement, stability data and any supplier or manufacturer data on temperature excursions.
Investigate the cause (equipment, door left open, power, HVAC) under your deviation procedure, and fix it.
Decide disposition and document it.

Humidity control in production areas

The following points are good practice for HVAC design in areas that need low or controlled humidity. They follow the WHO HVAC guidance for non-sterile products (TRS 1010 Annex 8, 2018, sections 8.3 and 8.4, and its interpretation document TRS 1019 Annex 2, 2019, section 8).

Rooms that need low humidity should have well-sealed walls and ceilings, and be separated from higher-humidity areas by suitable airlocks. Prevent moisture moving between areas, which adds load to the HVAC system.
Dehumidify using refrigerated or chemical (desiccant) dehumidifiers; chemical driers such as silica gel or lithium chloride are acceptable if they do not become a source of contamination. Cooling coils can use low-temperature chilled water, glycol mixture or refrigerant.
Avoid humidifiers where you can, because they can grow microbes. Where humidification is needed, steam injection into the air stream is preferred, and a product contamination assessment should decide whether pure or clean steam is needed.
Do not add corrosion inhibitors or chelating agents that could harm the product to boiler water used for steam humidification.
Avoid evaporative systems, atomisers and water-mist sprays because of the microbial risk.
Humidification systems should drain well, so that condensate does not collect in the air handling system. Do not install air filters immediately downstream of a humidifier, and keep duct material near the humidifier from adding contaminants to air that is not filtered afterwards.
Insulate cold surfaces to prevent condensation in the clean area or on air-handling parts.

Frequently asked questions

Can I use ICH 25 °C/60 % RH as my warehouse limit?

Not automatically. Those are stability study conditions. Use the label statement and your own risk assessment.

How often should temperature and humidity be recorded?

WHO Annex 9 (4.5.2, 4.5.4) gives at least six readings per hour for each sensor position in temperature-controlled stores, and manual checks at least twice daily.

How often should sensors be calibrated?

At least yearly against a certified traceable standard, unless justified otherwise (WHO Annex 9, 4.10).

Is temperature mapping required for every warehouse?

EU GMP expects special storage conditions to be provided, checked and monitored (Chapter 3, 3.19). Mapping is the usual way to show where to place sensors, and WHO Annex 9 expects qualification of temperature-controlled stores.

References

European Commission, EudraLex Volume 4, Part I, Chapter 3: Premises and Equipment, paragraphs 3.3, 3.12 and 3.19.
European Commission, EudraLex Volume 4, Part I, Chapter 4: Documentation, 4.11 (retention).
US FDA, 21 CFR 211.142 (warehousing procedures) and 211.180(a) (retention of records).
WHO Technical Report Series No. 961 (2011), Annex 9: Model guidance for the storage and transport of time- and temperature-sensitive pharmaceutical products.
ICH Q1A(R2): Stability testing of new drug substances and products (Step 4, February 2003; for stability conditions only).
WHO Technical Report Series No. 1010 (2018), Annex 8: Guidelines on heating, ventilation and air-conditioning systems for non-sterile pharmaceutical products (Part 1), sections 8.1 to 8.4; and WHO TRS No. 1019 (2019), Annex 2: Part 2, interpretation of guidelines, section 8 (these revise TRS 961 Annex 5, 2011).