Temperat emperature ure Mapping and Monitoring: Quality-Contro Quality -Controll Tools Tools for Pharmaceutical and Medical Device Warehousing By Gregory Brian Weddle Global Manager Critical Environments Raymond L. Benton Critical Environments Solutions Consultant
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t is said that if you stand with one foot in scalding water and the other in a block of ice, on average you are comfortable.
That adage applies to large warehousing spaces regulated solely by thermostats. A space measuring tens or hundreds of thousands of square feet, reaching 40 to 80 feet high, divided by floor-to-ceiling racks, and without a sophisticated climate-control system, is likely to exhibit zones of different temperatures, even when wall thermostats say conditions are in the desired range. While that may be of little consequence for storage of office supplies, canned goods, hardware, toys, books and other non-perishables, it raises concerns in the storage of temperature- and humidity-sensitive product. Makers of pharmaceuticals and medical devices, deeply concerned about consumer safety, product quality, and FDA compliance, are starting to take notice. Today, simple technology enables such companies to monitor conditions in three dimensions within raw-material or finished product storage areas. This technology, using digital sensors from which temperature and humidity data can be downloaded to a computer and analyzed by simple software, can cost-effectively provide a complete profile of storage-space conditions, either as a snapshot in time (temperature mapping) or continuously (temperature monitoring). In either case, the warehouse owner or operator receives hard data documenting that product is being stored at its specified conditions, or pointing out potential problem areas that should be addressed. Mapping and monitoring can be valuable quality assurance tools for spaces that store bulk and final pharmaceutical, biomedical products, ingredients, medical devices, and other sensitive materials.
The state of storage Pharmaceutical and biomedical companies face exacting FDA standards affecting production. Space temperature and humidity, air quality, equipment sanitation, and many other conditions must be strictly controlled and validated. Those stringent requirements thus far do not extend to warehousing. Manufacturers are simply required to store perishable product in the temperature, humidity and light conditions
they have found necessary to sustain product safety and efficacy, based on stability testing. Most product warehouses have limited environmental control. Packaging obviously protects products against contamination and degradation from light, but the contents remain vulnerable to temperature and, in some cases, humidity. Warehouses typically do not have air conditioning– the majority rely on ventilation alone or, in colder cli mates, ventilation and heating. The warehouse environment is typically regulated by simple line-voltage thermostats that activate heaters or ventilators when temperatures rise above a setpoint. The building may have ceiling fans to circulate the air. Facility personnel may crudely regulate temperature by keeping loading dock doors open or closed during extremely hot or cold days. Historically, pharmaceutical and medical device producers have not owned the warehouses, instead leasing the space from development companies, which may also manage and operate the buildings. Warehouses in these sectors tend to experience high throughput; spaces are reconfigured often as new products come in and as demand patterns change. Underlying assumptions seem to be that 1) the product stays in the warehouse for only a week or a few days, so variation in environmental conditions during that time will not degrade the product significantly, or 2) building conditions veer out of control only in extremely hot or extremely cold weather, which occurs on just a few days out of the year, with little likelihood of product degradation during those days.
Emerging concerns In recent years, as FDA scrutiny grows stricter, and as consumers and the healthcare industry raise their expectations for product effectiveness and safety, manufacturers are focusing more attention on product storage. For example, the Society for Life Sciences Professionals (ISPE) is developing a new volume in its series of Baseline ® Pharmaceutical Engineering Guides devoted specifically to packaging, labeling and warehousing operations (planned for release in mid-2004). The warehousing section will cover topics including incoming materials, in-process materials, shipment of goods, facility planning, flow of materials, utilities, environment, and equipment operations.
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Meanwhile, temperature and humidity sensing technology has advanced, making measurement and monitoring easier, more accurate and less costly. In addition, experiences in other industries provide lessons on the importance of environmental control. For example, computers and servers operated by Internet service providers, financial service firms, telecommunication companies and online merchants have proven highly vulnerable to temperature and humidity outside equipment makers’ specifications. Companies that inadequately control their computer room environments have faced premature equipment failure and the threat of critical network outages potentially affecting millions of customers – not just when overall room temperature and humidity slip out of prescribed ranges but when “hot spots” and “cold spots” exist within rooms. Detailed temperature mapping and monitoring have helped many of these companies to identify environmental problems and take measures to bring their computer rooms back into control. Certainly, out-of-spec conditions in a drug warehouse will not cause anything as sudden or dramatic as the failure of a cellular telephone network or the crash of a popular e-commerce web site. Still, no pharmaceutical or medical device manufacturer wants to face the prospect of a consumer safety concern involving its product that could be traced back to questionable or poorly documented storage practices. Against such events, temperature mapping and monitoring can provide cost-effective insurance.
Taking the temperature Large, open spaces with high ceilings are vulnerable to temperature and humidity variation, especially if they have only rudimentary heating, ventilating and air conditioning (HVAC) systems. For example: • Areas near the ceiling or exterior walls may stay warmer or cooler in response to temperatures outside. • Temperatures may stratify simply because warmer air rises. • Temperatures will be higher near heaters, especially if fans are undersized or improperly placed and so incapable of mixing the heated air effectively.
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• Racking and shelving configurations may contribute to “hot spots” by obstructing air circulation. • Doors left open to regulate overall temperature will affect conditions around nearby racks. These and other factors may create substantial temperature differences from floor to ceiling and within building zones. In fact, variations of several degrees C are common in large storage facilities. In such facilities, temperature mapping is a simple procedure. The basic measurement tools are small, batteryoperated sensors that measure temperature, or both temperature and humidity, automatically at prescribed intervals. At the end of the measurement period, sensor data is downloaded to a computer and analyzed. This technology enables detailed mapping studies with the bare minimum of labor and so at affordable cost. Sensors are placed in a grid pattern at regular intervals around the warehouse, typically at three l evels: near the floor, near the ceiling, and at a midpoint. The sensors attach to the racks by way of simple plastic tie wraps. A map of the facility is created and the coordinates of all sensors recorded. Each sensor bears a serial number that is matched with its coordinates. Typically, sensors operate for one to or two weeks, taking measurements every 10 minutes. This enables the building owner to track accurately how conditions change during a typical working day, overnight, and through weekends. Ideally, mapping studies should be performed twice – during midsummer and mid-winter – to account for seasonal effects. When the measurements are complete, data is downloaded, and the mean kinetic temperature (MKT) is calculated for all the data points to determine whether conditions are within prescribed limits. Software generates multiple twodimensional and three-dimensional color-coded charts and graphs that visually show temperature profiles and make it easy to identify specific problem areas (see accompanying examples). In cases where significant temperature anomalies are documented, control specialists visit the facility to look for the probable causes.
Summary of Minimum Temperature Data Points Collected Summer 2002 Ⅵ 25.00-25.50 Ⅵ 24.50-25.00 Ⅵ 24.00-24.50 Ⅵ 23.50-24.00 Ⅵ 23.00-23.50 Ⅵ 22.50-23.00 Ⅵ 22.00-22.50 Ⅵ 21.50-22.00 Ⅵ 21.00-21.50
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Summary of Maximum Temperature Data Points Collected Summer 2002
• Repositioning racks or shelving to improve air circulation. • Changing the location of heating devices. • Adding air conditioning. • Improving ventilation. • Installing more or larger-capacity fans. • Adding humidification or dehumidification. • Installing an HVAC control system.
Taking the next step A temperature mapping study provides a one-time view of storage conditions. Because facility configurations and product mixes can change frequently, long-term temperature and humidity monitoring can be advantageous. A monitoring system uses a matrix of permanent sensors that record the same basic data collected in mapping studies. The sensors can be easily moved as the storage scheme or product mix changes.
Putting data to work
An attractive option is to install sensors that communicate continuously with a Part 11 compliant building automation system (BAS). The BAS can be programmed with alarm setpoints so that personnel on duty around the clock can alert service technicians by e-mail, page or telephone to adverse changes in space conditions.
The graphs and charts and on-site observations become part of a complete report that notes any undesirable temperature or humidity patterns and recommends potential remedies. The report contains copies of all sensor calibration certificates, questionnaires, and other information used to complete the study. If the mapping study indicates undesirable conditions, facility owners can take a wide range of measures, depending on the problems’ severity. They include:
Monitoring provides added assurance that space conditions match product storage specifications. A continuous record also can be valuable in case of an FDA inquiry or audit – especially if the monitoring information is combined with the detailed inventory data pharmaceutical and biomedical companies already keep. With both kinds of data in hand, a company could document the location in which a given container of medicine was stored and the temperature and humidity conditions that existed while it was there.
Row Number Ⅵ 31.00-31.50
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28.50-29.00
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28.00-28.50
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• Removing product from problem areas (such as hot spots near ceilings). • Changing work practices (such as keeping doors open or closed). • Changing racking or shelving configurations.
Toward strategic planning Temperature mapping is a key first step to understanding environmental conditions in critical storage facilities. When combined with ongoing temperature monitoring, a long-term
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storage facility environmental control strategy can be implemented. Such a strategy has four essential parts: • Analyze: Determine the space conditions that must be maintained. • Act: Put equipment, operating practices and data reporting in place to enable those conditions to be met. • Audit: Track space temperatures continuously and evaluate conditions as needed. • Adapt: Change the environmental control system as necessary; commit to continuous improvement.
Conclusion Temperature mapping and monitoring, when conducted by a qualified provider, are high-value quality-assurance tools with the potential to aid in regulatory compliance. Companies in need of mapping and monitoring services should consult a provider not only with experience in facility environmental control but well versed i n the pharmaceutical and biomedical industries and with a comprehensive knowledge of FDA validation requirements.
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About the Authors
Mr. Weddle is the Global Manager of Critical Environments for Johnson Controls, Inc. He is responsible for the direction and leadership of the Global Validation Services Business Unit. Mr. Weddle provides validation pro- gram development, solutions development, direct business unit sales and area technical support. In his 19 years with Johnson Controls, Mr. Weddle has held numerous positions in application engineering, project management, and quality assurance. He has also been Bio-Pharm team leader and instructor. He holds a Bachelor of Science degree in Mechanical Engineering from Purdue University and is a licensed HPAC contractor. Mr. Benton is currently a Critical Environments Solutions Consultant in the Johnson Controls Validation Support Services group. He holds a Bachelor of Science degree in Mechanical Engineering from Purdue University. During his ten years with Johnson Controls, Mr. Benton has been con- tinuously involved with all aspects of delivering solutions to the Life Sciences Market. In 1998, Mr. Benton accepted a position with the Validation Support Services group. That group developed and maintains a set of validation standards that are deployed throughout the corporation and provides consulting services to both internal and external customers. Recently, Mr. Benton has focused on delivering solutions to the Life Sciences Marketplace that address the FDA’s 21 CFR Part 11 regulations concerning Electronic Records and Electronic Signatures.
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