Factors to Consider When Designing Industrial Heaters for Bio-Pharma Cleanrooms
Current Good Manufacturing Practice (cGMP) requires that the temperature in bio-pharma operations be kept within strict limits, and that the heating systems used are compatible with rigorous cleaning and sterilization regimens and designed to prevent contamination entirely. Any deviation from expected conditions jeopardizes the quality and integrity of manufactured products and is costly to remediate.
High-purity industrial heaters use electric or steam heating rather than combustion processes. Those integrated into HVAC systems must provide the air quality and stability needed, while process heating systems, from those used in bioreactors and purification systems to aseptic fill and finish operations, must deliver precision and regulatory compliance.
A critical design consideration is that heating equipment installed in upstream or downstream operations is not readily upgraded and improved. Rather, the right approach is to consider industrial heater design from the project outset. This demands a detailed understanding of relevant standards (especially ASME BPE), and careful specification and selection of equipment during the cleanroom design phase.
Here’s a look at the most important factors to consider when designing high-purity industrial heaters for your cleanroom:
Surface Finish Requirements
The ASME bioprocessing equipment (BPE) standard imposes stringent limits on the roughness of equipment surfaces; surfaces that are uneven at the microscopic level provide places for dirt and microbes to adhere and are harder to sterilize.
ASME BPE specifies a maximum roughness of 35 μin Ra (0.89 μm) for sterile surfaces. However, in practice, many manufacturers aim for significantly smoother surfaces as this improves ease of cleaning.
Approved methods for achieving the necessary surface finish are machining, mechanical polishing, and electropolishing.
Material Resistance to Cleaning Agents
The materials used for bio-pharma equipment must withstand exposure to isopropyl alcohol, hydrogen peroxide, alkaline cleaners, and other sterilization solutions. They must also not release any particles that would cause contamination.
PTFE coatings are widely used for protection, as this material is highly inert and resists attack by nearly all chemicals. 316 stainless steel is the preferred choice of metal for most bio-pharma equipment, but it is susceptible to attack by chlorine. If chlorine-based cleaners will be used, it’s important to select other metals and/or use robust coatings like PTFE.
Cleanroom Classification
Cleanrooms, such as those used in bio-pharma processing, are classified according to ISO 14644-1. This replaces the older Federal Standard 209E, which used designations like Class 100 for particle density.
Most bio-pharma cleanrooms meet the ISO Class 7 and 8 standards. Some, principally those used for aseptic filling and open product handling, are engineered to the more demanding Class 5 and 6 levels. These dictate not only the maximum particle density per cubic meter by size group, but also the minimum airflow rates.
To give a specific example, ISO Class 5 allows a maximum of 3,520 particles less than 0.5 µm per cubic meter. It also requires up to 480 air changes per hour. (Class 7 needs only 30 to 60 air changes per hour.) Higher air change rates have implications for HVAC system design.
Airflow Pattern
Since some particles are always present, even in an ISO Class 5 cleanroom, it’s also important that the system manages airflow effectively. Two aspects of this addressed by the ISO standard are air movement direction and relative pressurization.
Critical areas should have laminar or unidirectional airflow, minimizing turbulence or, ideally, eliminating it to ensure particles move in a known direction.
Maintenance Accessibility
Heating systems, both for HVAC and processes, should be developed with ease of maintenance and, especially, cleaning in mind. Where needed, surfaces should be removed easily and parts tested and replaced with the minimum of interruption and disruption to normal operations.
It is especially important not to release any particles into the air during cleaning and maintenance, as this will prolong cleanroom downtime and could require extensive remediation.
Heat Distribution
Many cleanrooms require temperatures to be maintained within +/-0.2°C. Any variation across or within a cleanroom can affect the processes being performed. Accordingly, HVAC systems and airflow must be designed to meet this requirement.
How Much Material Will Be Heated At a Given Time
Thermal mass is a critical consideration when designing both HVAC systems and processing equipment for bio-pharma applications because it determines rates of warming or cooling and the ability to dampen fluctuations.
Accordingly, when designing or specifying heating systems for bio-pharma applications, always determine the mass of material to be heated/kept warm, and its thermal properties.
Insulation
While necessary for energy efficiency, to achieve temperature uniformity, and sometimes as protection against burns, insulation can cause contamination within cleanroom environments. Particular concerns include the release of fibrous particles, dust collection, and the potential for moisture capture and retention.
Closed-cell and rigid foams are sometimes used, although outgassing that releases even small levels of chemicals can be a concern. Mineral wool is a popular and effective insulating material, but it can release fibrous particles into the environment.
Encapsulation is generally needed for all types of insulation. Insulation jackets have the advantage of being easily removed for cleaning and equipment maintenance.
Compatibility With Controllers & Sensors
Temperature sensors and heating system controllers are important elements of systems required to maintain temperatures within tight limits. For temperature measurement in bio-pharma applications, RTDs (resistive temperature devices) are generally preferred over thermocouples. They offer higher precision, a more linear response, and are less prone to drift.
Temperature is almost always managed with PID controllers, often in complex configurations such as cascade arrangements, ramp/soak setups, and recipe-based operations, to keep temperatures within narrow limits and avoid overshoots during heating or cooling.
When designing or selecting industrial heaters for cleanroom processes or HVAC systems, temperature control technology should be a primary consideration. Look at both the sensors used and how the equipment will integrate with other hardware in use.
Load Requirements
For HVAC systems, the thermal load usually remains relatively constant. However, in process equipment, especially for drying, sterilization, and WFI preparation, there can be significant variation.
This variation is often addressed through cascade arrangements that separate the management of fast and slow-changing thermal dynamics. Other approaches include increasing thermal mass to dampen fluctuations or using multi-stage or hybrid heating strategies that combine different methods in parallel.
Compliance Requirements
Bio-pharma processing operations are usually expected to conform to cGMP, while equipment should be manufactured in accordance with ASME BPE standards. 3-A is another critical certification that verifies the effectiveness of equipment installations.
Collectively, cGMP, ASME BPE, and 3-A ensure that bio-pharma processing is performed under conditions that assure product quality and safety. When designing heaters for these applications, always review the specific application requirements.
Get Engineering Expertise From Hi-Watt
Hi-Watt is a turnkey provider of industrial heating equipment and partners with leading manufacturers of high-quality heaters, sensors, and process controllers, including Watlow, Chromalox, and Gefran. We use our understanding of heating technologies to help manufacturers improve efficiency, reduce downtime, and meet complex regulatory challenges.
If you’re in the pharmaceutical sector, we can help you configure high-purity industrial heating solutions, whether circulation heaters, tank heaters, PID controllers, or RTD sensors. Contact our experts today to get started.