01 Create a Validation Plan

The validation plan, or validation master plan, is the document used to specify the company’s decisions about qualifying every aspect of the facility, equipment, and processes to maintain a GMP compliant environment. The plan should take a risk-based approach, with a rationale based on verifiable data. The plan should focus on where environmentally sensitive products and materials will be stored and whether environmental controls can meet specified storage requirements. The validation master plan should:

• State the validation objectives and identify staff roles, responsibilities, and who will have authority.
• A detailed list of validation activities, processes, and the equipment that will be used.
• What the company’s response will be if temperature, humidity, pressure or CO2 levels breach tolerance.
• The validation schedule.
• Reassessment protocol when conditions or events such as maintenance, construction, or reorganizing result in the need for revalidation, or if the study results indicate the need for adjustment.

02 Identify Areas At Risk

To map a warehouse or storage space, you first must identify areas where product quality may be at risk because of unacceptable variations in temperature and humidity. Many factors affect the control or variability of your space. (Because relative humidity is dependent on temperature, variations in temperature will affect humidity as well.) Considering each of these factors will help you identify risks:

• The volume of space and HVAC demands.
• Temperature gradients from cooler air near the floor and warmer air near the warehouse ceiling.
• Fans, air conditioners, or space heaters may create pockets of warm or cold air.
• High traffic areas, windows, doors, or loading docks.
• The layout of shelving and racks to identify any airflow obstruction.
• Seasonal temperature changes or extreme weather events.

03 Develop Protocol Information

Once you’ve identified areas of risk, develop a protocol for the mapping study that describes the following, with justifications for each decision:

• What parameters will be monitored and at what reading intervals (example relative humidity at 5 minute intervals).
• How many data loggers will be used of each type and the distance between where they will be placed.
• Schematic or diagram of sensor locations.
• The duration of the mapping study (be sure that the duration spans any variety of activities that may impact fluctuations such as weekends versus weekdays or delivery days for example).
• Calibration requirements of the data loggers.
• Acceptable range of variation over time and across the space, which will depend on the product stored.
• Acceptable limits for temperature or relative humidity excursions.

04 Determine Sensor Distribution

How many sensors will you need to map a particular space? Where will you put them? There are no simple answers. Sensor distribution must be adequate to assess temperature uniformity. Good practice means that you use a sufficient number of sensors to understand your environment, especially areas where risk is greatest. You’ll need to place sensors in a uniform pattern in all three dimensions of the space – top to bottom, left to right, and front to back. Add additional sensors where you suspect cool or warm areas exist, as well as near the control sensors and monitoring sensors. Placement of temperature and relative humidity sensors is a function of the risks identified in Step 2.

In mapping, a large warehouse, set sensors as far as 30 meters apart, with additional sensors in vulnerable areas affected by:

• Heat or cold from external walls, solar heating, windows, lighting
• Air circulation or drafts from entries, traffic, or the HVAC system
• Temperature extremes in poorly insulated areas
• Localized effects of space heaters and air conditioners

05 Select Suitable Technology

Use equipment designed for mapping. Software that accompanies the sensors is used to set up the equipment and download data. Software should produce tabular and graphical reports that meet all requirements of 21 CFR Part 11 and comparable international standards, such as European Commission Annex 11, and those contained in European Union GMP Volume 4. When choosing data loggers, look for the following features:

• Minimal potential for data loss or error.
• High accuracy in the measurement range. Vaisala DL2000 data loggers, for example, are accurate to ± 0.1 °C over +20 °C to +30 °C, with humidity accuracy of ± 1 %RH in 10 to 80 %RH.
• Speed of response time and sensitivity of the device (a faster response will provide more specific results to help identify problems).
• Maintenance and calibration frequency required
• Configurable alarm notification options to quickly inform users of any deviations, such as audible, text, and email alerts.
• Clear, comprehensive, and accessible calibration records.

06 Set Up Mapping Equipment

After you’ve identified risk areas and determined sensor distribution, it’s time to set up mapping equipment and conduct a test of the storage space. The purpose of this initial test is to determine where variable conditions exist, and where temperature and humidity are uniform and suitable for product storage. Work through the following checklist and document each step:

• Equipment has been calibrated. Document by whom, when, and the next calibration date.
• Equipment has been validated. Installation qualification and operation qualification (IQ/OQ) is typically provided by the mapping system supplier.
• Ensure mapping software access has been secured and authenticated.
• Ensure the software reads and records hardware and firmware model, version, and serial number.
• Ensure the warehouse area and data logger locations are accurately described.
• Regular sample intervals have been determined.
• Study duration has been determined.
• Data loggers link to an audit trail file for traceability.
• Data loggers are functional and positioned in defined locations.

07 Conduct Test & Review Data

You’ll need to establish the reporting information you’ll use to evaluate the test. When the test is complete, the software will read the secure files from the data loggers, show recorded data, perform calculations, and graph the results selected for a mapping study report.

• Raw data with times and dates.
• Calculated values such as temperature minimum, maximum, and average.
• A graph of all sensors over the test period.
• Instrument settings.
• Calibration information.
• Date and time of the test.
• Space for review and approval signatures on printed reports.

08 Make Modifications as Necessary

Use the results from the initial test to identify locations where the product may be exposed to unacceptable conditions.

• Moving rack locations that are too close to risk factors.
• Adjusting HVAC settings or location of vents (an HVAC expert may be needed to evaluate the system).
• Rearrange shelves or racks to eliminate obstruction of airflow.
• Add fans or increase ventilation in certain areas.
• Address traffic to reduce opening and closing of doors.
• Block sunlight that may be causing a hot zone.
• Each modification made in the system should subsequently be documented in the protocol and approved.

09 Document & Schedule Mapping Study

After you adjust for environmental variability in the warehouse, it’s time to conduct and document a mapping study for approval.

How long should mapping last?
As with your initial mapping test, there’s no fast rule. Your rationale and protocol may support a single long study or a series of shorter studies. Either way, it’s important to measure the environment during a range of different work activities in the warehouse, such as loading, moving products, and periods such as weekends when little activity might occur.

How often should you map a space?
Some protocols call for mapping every three months while others can justify mapping yearly or even less frequently. The validation master plan should anticipate variables that can change storage conditions after the completion of a warehouse qualification.