GxP Compliance in Monitoring Systems

The ELPRO Cloud is an intuitive and efficient reporting tool that visualizes the activities of your sensors and provides you with  everything you need to set up a professional GxP-compliant temperature monitoring solution.

• Somebody has forgotten to equip the pallet with a sensor
• The sensor was started early or stopped late
• The raw data file from the USB data logger was not uploaded
• The real-time logger lost connection and data never arrived

Intact Data – Although the risk for accidental or intentional modification is minimal, the integrity of data in a measurement chain can only be achieved by encrypting the data all the way from the measuring wireless sensor through the communication bridge (LPWAN network or email) to the cloud. Once the data has arrived in the software it is important that no raw data can be deleted or modified. No user should not be able to change the raw data, however it is possible to add certain types of additional information. For example, in order to add an interpretation of the data, certain comments or acknowledgements about the raw data can be added to the system. Furthermore, in order to create selective views on the raw data, reports can be created and exported.

Maintaining Electronic Data in its Original Context – Keeping the data in one single source on a central cloud infrastructure ensures that it is kept in its original recorded context and the risk of misinterpretation is therefore eliminated. Warnings, alarms, and reports should always refer to the unique sensor name, event number, and time stamp.

The Audit Trail: 
Compliance in User Management and Authentication

There are many rules to follow when it comes to compliance in user management. Every user with access to the solution must be identified by a unique username and password and must have a clear role and rights. Additionally, every action taken by the user in the system must be identified and tracked. When conducting critical operations, such as the acknowledgement of an alarm, the user even needs to confirm his action by inserting his password a second time. In order to avoid unauthorized access it is important to implement a time-out mechanism in case the user is not taking action for a longer time period.

The result tracking functionalities mentioned above is a complete audit trail aligned with compliance. It answers the questions: who has done what and why? Technically, the audit trail keeps track of every single automated event the system is generating and every single manual task a user is performing. So, regardless from which perspective one takes a look into the system, a full audit trail could be:

• Sensors: Timeline of all events on a sensor like measurement values, status, setting changes, warnings, alarms, and acknowledgments
• Warnings and alarms: Time stamps, statistics, who has commented on what, who has acknowledged something, and when
• Reports: Sensor names, timeline, and the user that created the report

In a Cold Chain database the question of audit trail is much more complex than for a solution monitoring rooms and equipment. Why? Because there are many more participants included.

• High battery consumption resulting in bulky devices and short battery life
• Lack of standardization in roaming and SIM-card handling
• Lack of an international standard for airline approvals

As a result, those devices were dedicated to a local trucking market or to the maritime market transmitting values from ocean containers to proprietary antennas on ships. One of the first companies to launch a true international real-time temperature and position logger was a freight express company operating a fleet of aircrafts. The price for one device was higher than 1000 USD per device – not including the connectivity and roaming.

Later devices used the 3G/4G network, which meant a significant reduction of battery consumption. Powered by lithium batteries, they achieved a battery life of 30 or more days. To get airline approval, they had to be multi-sensor devices monitoring all kinds of parameters like pressure, acceleration and light. Using lithium batteries (other than button cells) however resulted in a new problem. In 2017, IATA released a new regulation limiting the number of lithium cells per handling unit and also requested declaration of each data logger sensor used in a shipment. This was a draw back again and one of the reasons why real-time temperature loggers did not break through so far.

How to Qualify a Data Logger and Database

GMP and GDP clearly require qualifying all equipment used to produce, store, and transport temperature sensitive pharmaceuticals. This obviously includes data loggers. As a pharmaceutical company using a data logger and/or a cold chain database, you need to proof that it fulfills the intended purpose.

Qualification is the documented proof by the Market Authorization Holder (MAH), that the Cold Chain monitoring solution fulfills its intended purpose: documenting a release decision.

The company using the Cold Chain monitoring solution must perform the qualification job itself and individually on the specific process. The qualification documentation of the Cold Chain monitoring company is a popular target during FDA audits. Qualification of a Cold Chain monitoring solution in a specific situation can be kept simple, if the supplier qualifies all elements of the solution (i.e. hardware, software, services) beforehand, and provides profound documentation to support it. Although qualification is the better term, this activity is often called “component validation.”

Each component used in a Cold Chain monitoring solution must be validated/qualified by the supplier. They must provide documented proof that each component fulfills its intended purpose. 

Comprehensive qualification support packages provided by data logger vendors include:

• URS template describing all functionalities
• High level risk analysis rating the risk (probability, severity and detectability) and mitigation measures
• Validation plan and validation report summarizing referring versions and documents
• Qualification template for an OQ

The supplier typically provides guidance during the qualification and is open for audits. During audits, the detailed V-Model documents can be inspected.

How to Automate GxP Refrigerator and Storage Monitoring

To automate refrigerator and storage monitoring in a GxP environment, replace manual temperature checks with calibrated sensors that record conditions continuously and send the data to a validated monitoring system. The system compares every reading to defined limits, alerts the right people when conditions drift, and records every action in a secure audit trail that supports 21 CFR Part 11 and EU GMP Annex 11.

The sections above explain what regulators expect from a compliant monitoring system. This section shows how pharmaceutical and laboratory quality teams put those requirements into practice for pharmaceutical storage: refrigerators, freezers, ultra-low temperature (ULT) freezers, cold rooms and warehouses.

Why Manual Refrigerator Checks Fall Short in GxP Environments

Many sites still read a min/max thermometer once or twice a day and record the values on paper. The method is simple, but it leaves gaps that are hard to defend during an inspection:

• Blind spots between readings. A refrigerator can drift out of range overnight or over a weekend and recover before the next check, leaving no record of how long product was exposed.
• No real-time response. If nobody is on site, a failed compressor or an open door can go unnoticed until product is already affected.
• Data integrity risk. Handwritten logs are prone to transcription errors, missed entries and late entries, which makes it harder to show that records meet ALCOA+ principles.
• Heavy review workload. QA teams spend time checking, signing and filing logs instead of investigating real deviations.

Automated storage condition tracking closes these gaps by recording at fixed intervals around the clock and flagging deviations as they happen.

What Automated Monitoring in GxP Environments Includes

A GxP-ready temperature monitoring system is more than a sensor with an alarm. Look for these core capabilities:

• Continuous data capture. Calibrated sensors record temperature (and humidity or other parameters where needed) at a set interval, 24/7 and buffer data locally if the connection drops. The result is a complete, gap-free record of storage conditions.
• Automated alerts. Every reading is checked against warning and alarm limits. Notifications go out by email, SMS or on screen, with escalation if no one responds, so teams can act before product quality is affected.
• Audit trail. The system records who did what, when and why, including setting changes, alarm acknowledgments and comments. This supports data integrity requirements under 21 CFR Part 11 and EU GMP Annex 11.
• Electronic records and signatures. Unique user accounts, role-based permissions and password re-entry for critical actions make electronic records trustworthy and equivalent to paper records.
• Dashboards and reports. A dashboard shows the current status of every monitored unit and periodic and excursion reports are generated automatically. QA gets a quick status check and inspection-ready documentation.
• Calibration and qualification support. Calibrated sensors with certificates, plus validation documentation for hardware and software, demonstrate that the system is fit for its intended use.

For more on audit trail requirements, see "The Audit Trail: Compliance in User Management and Authentication" above.

Step by Step: How to Automate GxP Refrigerator Monitoring

• Define scope and requirements. List every refrigerator, freezer, ULT freezer, incubator, cold room and storage area that holds GxP-relevant product or samples. Record the required range for each (for example, 2 °C to 8 °C), what is stored there, and the risk if conditions are lost. Capture this in a user requirements specification (URS).
• Map storage units and choose sensor locations. Temperature mapping identifies hot and cold spots and shows where a monitoring sensor best represents product conditions. Larger spaces such as cold rooms and warehouses usually need several monitoring points. According to ELPRO GxP expert Stephanie Punter, "A sensor tells you what’s happening where that sensor is. That’s why temperature mapping is critical.”
• Select sensors and connectivity. Match the sensor to the application: internal probes for standard refrigerators and rooms, external probes for freezers, ULT freezers and cryogenic storage. Choose a connection that suits your site, such as a wireless radio network, LAN or LPWAN. Confirm that sensors store data locally during interruptions and that each one comes with a traceable calibration certificate.
• Configure alarm limits and escalation. Set warning and alarm limits based on product requirements and mapping results, add alarm delays where appropriate and define who is notified, how and in what order. See the alarm design guidance below.
• Set up user management and the audit trail. Create individual user accounts, assign roles based on what each person needs to do, and require password confirmation for critical actions such as acknowledging an alarm.
• Qualify and validate the system. Document installation, operational and performance qualification (IQ, OQ, PQ) using a risk-based approach such as GAMP 5. Ask your supplier for validation support documents to reduce the effort. See "How to Qualify a Data Logger and Database" above.
• Write SOPs and train your team. Define how alarms are acknowledged, who investigates, how excursions are documented, and when product is quarantined or released. See "How to Deal with Temperature Excursions?" below.
• Review, report and maintain. Schedule periodic reports, review alarm history for trends, test alarms regularly, recalibrate sensors on a defined schedule, and include the system in your periodic review program.
  
  

Automated Alerts for Storage: Designing Alarms Teams Act On

Automated alerts only protect product if the right person sees them and responds. Too few alerts put product at risk. Too many lead to alarm fatigue, where staff start to ignore notifications.

“Collecting the data is usually the easy part. Knowing what to do with it is where companies can struggle."

Stephanie Punter, GxP Team Lead and Deputy Quality for the Americas at ELPRO

Effective alarm design includes:

• Two-level limits. A warning limit signals that conditions are drifting so staff can act early. An alarm limit signals a deviation that requires documented action. For example, a 2 °C to 8 °C refrigerator might have warnings at 3 °C and 7 °C and alarms at 2 °C and 8 °C.
• Alarm delays. A short delay prevents nuisance alarms from routine door openings while still catching sustained deviations. Base the delay on how quickly the unit and its contents warm or cool.
• Technical alarms. Alert on sensor disconnection, low battery and lost communication as well as temperature, so a silent sensor is never mistaken for a stable one.
• Escalation chains. If the first contact does not acknowledge an alarm within a set time, notify the next person. Plan coverage for nights, weekends and holidays.
• Documented acknowledgment. Each acknowledgment should capture the user, the time and a comment explaining the cause and the action taken.
• Regular alarm testing. Test notifications periodically to confirm that contact details are current and messages arrive.

Scaling from a Few Refrigerators to a Multi-Site Storage Network

Many organizations start with a few units in a lab or pharmacy, then expand to cold rooms, warehouses and additional sites. Planning for scalable deployment early prevents rework later:

• Standardize configurations. Use templates for alarm limits, measurement intervals, and notification groups so every site follows the same rules.
• Use a consistent naming structure. Organize sensors by site, building, room and unit so reports and audit trails are easy to follow.
• Centralize visibility, localize response. QA can review status across all sites in one system, while local teams receive the alarms they are responsible for.
• Choose a platform that can grow. Cloud-based systems make it easier to add sensors and sites without new on-site servers. On-premises systems may better suit organizations with strict IT requirements.
• Plan for integration. An API connection lets monitoring data flow into other quality or enterprise systems.
• Keep validation manageable. Use change control and a risk-based approach so adding units or sites does not mean revalidating the entire system.
  
  

Common Mistakes to Avoid

• Placing sensors without mapping data, which can miss hot or cold spots.
• Setting alarm limits equal to product limits with no warning level, which leaves no time to react.
• Sending every alarm to a shared inbox that nobody owns.
• Ignoring technical alarms such as low battery or lost connection.
• Letting calibration certificates lapse.
• Treating validation as a one-time project instead of maintaining it through change control.
  
  

How ELPRO Supports Automated GxP Storage Monitoring

ELPRO combines calibrated ECOLOG-PRO sensors for rooms, refrigerators, freezers, ULT freezers and cryogenic storage with elproMONITOR Cloud software for continuous data capture, automated alerts, audit trails and reporting. ELPRO's GxP services team also supports temperature mapping, calibration and qualification, so quality teams can plan, validate and expand their monitoring with one partner.

Planning to automate monitoring for your refrigerators, freezers, or storage areas? Talk with an ELPRO specialist about sensor placement, alarm design and qualification for your site.