Failure to store such items within the specified temperature range may affect their quality and effectiveness. In the case of vaccines, heat may speed up a decline in their potency, and freezing may cause increased reactogenicity and loss of potency.

Failure to monitor and record temperatures accurately can mean that health professionals may be unaware of these potential effects on medicines, and of course their recipients.

In the UK, warehouses for storing pharmaceutical products need to comply with MHRA (Medicines & Healthcare Products Regulatory Agency) regulations concerning temperature control. The regulations require that "medicines are… consistently stored, transported and handled under suitable conditions, as required by the marketing authorisation or product specification."¹ This may well include the monitoring and control of ambient as well as chilled storage.

European Good Distribution Practice (GDP)

Good Distribution Practice Guidelines² came into operation in September 2013. Good Manufacturing Practice (GMP) and GDP relate to quality assurance for medicines in the European Economic Area (EEA). These activities are coordinated by the European Medicines Agency and the principles and Guidelines are mandatory within the EEA.

GDP ensures that the level of quality determined by GMP is maintained throughout the distribution network, so that medicines are distributed without any alteration of their properties. A quality system requires, amongst other standards, that "storage conditions are observed at all times."

The Guidelines require that suitable equipment and procedures are in place to check the environment where medicinal products are stored, taking into consideration factors such as temperature and relative humidity. After an initial temperature mapping exercise, monitoring equipment should be located accordingly, particularly in areas that are shown to experience fluctuations or extremes of temperature. Even for smaller premises which are at room temperature, consideration should be given to potential risks such as heaters, and temperature monitors placed as required.

Alarms should be in place to alert to any deviations from predefined conditions. Equipment used to control or to monitor the environment where the medicinal products are stored should also be calibrated at defined intervals.

GDP also specifies that the correct temperature conditions are maintained during transportation. There should be a means of demonstrating and investigating the conditions medicines have been exposed to, and if requested, information should be available for review to demonstrate that the correct temperature/RH storage conditions have been maintained.

WHO Guidelines

The World Health Organisation (WHO) also has specific guidelines for good storage practice for pharmaceuticals, stating "Where special storage conditions are required on the label (e.g. temperature, relative humidity), these should be provided, checked, monitored and recorded." It recommends that pharmaceuticals stored in ambient conditions in dry, well-ventilated premises, should be kept at temperatures of 15-25°C.

WHO Guidelines also cover transportation, recommending that devices to monitor conditions such as temperature are used where appropriate.³

The WHO goes on to recommend that recorded temperature monitoring data should be available for review and records kept. Like the European GDP Guidelines, it recommends temperature mapping and regular calibration of monitoring equipment.

Vaccines require very specific storage conditions. In general, the WHO stipulates that vaccines should be stored according to the manufacturers' recommended temperature range until the point of administration. This is typically +2 to +8°C, however temperature ranges may vary, and be very specific, for different types of vaccine.

The WHO states that "In all countries, systems of refrigeration, temperature monitoring and record keeping are required to make sure that each vial of vaccine is maintained under appropriate conditions."⁴

Using data loggers for temperature/RH monitoring of pharmaceuticals

Tinytag data loggers can help satisfy the requirements of European GDP to provide suitable temperature and relative humidity monitoring for stored pharmaceuticals and other sensitive medical equipment.

Tinytags are accurate and able to measure small changes in temperature/RH, and loggers with external probes are available to provide monitoring in hard to reach areas or fridges. Loggers can be easily moved to different locations, or more units added over time to build profiles throughout a site, or as premises or the area to be monitored expand.

Tinytag Explorer software presents the recorded results clearly and in detail, and allows data from different logging runs to be combined for comparison and analysis. Data is presented initially in graphs and tables which can easily be printed, copied and pasted, or exported into popular software packages.

Setting up the system

In terms of setting up a data logging system according to European GDP, this will be a two part process.

The first stage will be to temperature map the storage area(s). This mapping enables risk areas to be pinpointed, which will be the places in which ongoing temperature monitoring points (stage two) will be positioned. Mapping should take into account seasonal variations: for most climates this will necessitate both a winter and a summer study. Secondly, mapping should include locations which are likely to have a higher or lower temperature, for example, loading bays, near heaters, doors, windows, the south side of a building (north side in southern hemisphere). The mapping will be carried out before the storage facility is brought online, and any significant changes that are made as a result of analysing mapping data will require the mapping exercise to be repeated.

The best practice for a mapping study duration is two weeks, including a weekend to account for differences in building use and HVAC system programming.

Having identified the warmest and coldest spots from the mapping, the second stage will be to install permanent temperature logging at the risk spots. The number of logging points the installed system has will vary, depending on the amount of risk points identified by the temperature mapping and the general layout and size of the facility. As an indication, big warehouses may require up to 100 monitoring points

Choosing the right data logger

Initial warehouse temperature mapping may require a large number of loggers for a short period of time only. A basic entry level logger, such as the Tinytag Transit 2 for example, is ideal for this. Loggers can be left to record in particular areas then moved as required, and the recorded data used to provide an overall profile of environmental conditions throughout a facility.

For smaller facilities or areas, standalone loggers can also be used for all or part of the permanent monitoring solution. They are robust and reliable, and their battery life means they can be left to record for long periods if required.

Part of a good system (and in order to pass any GDP inspections from the regional Health Authority inspectorate) is to have an appropriate alarm system (and procedures for managing alarms/temperature excursions). Standalone Tinytags provide the necessary alarm warnings if conditions fall outside the pre-defined range. Alarms are indicated by a red flashing LED on the logger, or an audible alarm box which is available for some models. The Tinytag View 2 logger has a digital display which includes an alarm icon.

The Tinytag Radio Data Logging System is well suited to stage two permanent monitoring of pharmaceutical warehouses. It is ideal for larger premises with multiple monitoring points, or those requiring immediate central access to readings, as well as logging over time. Radio loggers gather data automatically and send it using wireless communications via a receiver for viewing on a PC, across a LAN, or remotely across the internet.

Radio loggers can be left to record in inaccessible areas or at height, for example, without having to physically access them to download data. A mains powered option is also available if required. Logger quantities and their positions can easily be changed due to expansion of facilities/re-mapping following other changes. In terms of the requirement for alarm warnings, if conditions fall outside the predefined range, notifications appear in the software. Alarm warnings can also be sent via email or SMS, enabling corrective action to be initiated.

The WHO and European GDP guidelines recommend regular calibration checks for temperature monitoring equipment. Gemini Data Loggers offers a calibration service for Tinytags with certificates traceable to national standards. Calibration can be purchased at the time of order, and loggers can be returned for a service calibration for a standard charge at any time.

References

1. https://www.gov.uk/good-manufacturing-practice-and-good-distribution-practice
2. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000154.jsp&mid=WC0b01ac0580027088
3. http://apps.who.int/prequal/info_general/documents/TRS908/WHO_TRS_908-Annex9.pdf
4. http://whqlibdoc.who.int/hq/2006/WHO_IVB_06.10_eng.pdf