Introduction
In the pharmaceutical, food & beverage, and biotech industries, contamination-free processing is critical. The integrity of the sanitary manufacturing application is essential for full compliance to the validation process.
The potential for contamination increases with the introduction of peripheral components, such as filtration and temperature and pressure measuring instrumentation required to ensure process parameters remain within acceptable limits. As a result, these inline devices must themselves meet standards set by governing agencies to ensure there are no weak links in the sanitary chain.
The most common of these standards include:
3A—3A Sanitary Standards, Inc. (3A SSI) is a non-profit association representing equipment manufacturers, processors, regulatory sanitarians and other public health professionals. 3A Sanitary Standards and 3A Accepted Practices pertain to dairy and food processing equipment, and focus on sanitary design, materials, and surface finish.
USP Class IV—The United States Pharmacopeia (USP) is an independent, science-based public health organization. It sets standards used by more than 130 countries for the quality of pharmaceutical and healthcare products. Their process work pertains to standards for plastic components.
FDA Compliant—The United States Food & Drug Administration (FDA) is a federal agency that regulates all food processing and drug manufacturing in the U.S. It sets and enforces standards and government codes. Its process-related compliance requirements pertain mainly on the quality of stainless steels, gasket materials, and filling liquids.
cGMP—current Good Manufacturing Practices (cGMP) are FDA requirements as set out in the 21 Code of Federal Regulations, Parts 210 and 211, regarding manufacturing, processing, packing, or holding of drugs and finished pharmaceuticals. Their main focus is on the process and facilities.
EHEDG-Certified—The European Hygienic Engineering & Design Group (EHEDG) is a consortium of equipment manufacturers, food industries, research institutes, and public health authorities that provides guidance on the hygienic engineering aspects of the manufacturing of safe and wholesome food. It provides certification of process equipment and focuses mainly on a product’s sanitary design and ease of cleaning.
Process Connections
Sanitary connections must meet USDA or FDA requirements, or meet 3A sanitary standards, for a process system to be eligible for validation. If it is a plastic device used for pharmaceuticals, it must be in compliance with USP Class IV requirements. Available sanitary connections include Tri-Clover® Tri-Clamp®, Cherry-Burrell®, DIN 11851, DIN 32676, ISO 2852, Varivent®, and 4” Tank Spud, among others.
Materials
Austenitic stainless steel is used as the standard material for sanitary applications. 316L stainless steel is the most common. This material provides good welding and corrosion-resistance attributes in addition to having the ability to be polished to a mirror finish.
In special applications where 316L stainless steel is not compatible with the process media, materials such as Hastelloy® and PTFE can be specified for process-wetted surfaces.
Surface Finish
The ease with which the process system can be cleaned—its clean-in-place and steam-in-place (CIP/SIP) designation—is influenced by the quality of the process wetted surfaces. The surface in contact with the process media needs to be passive and free of microscopic faults to avoid buildup of pathogenic organisms and/or the formation of biofilms.
An average surface roughness of Ra < =20 µin is deemed to be sufficient for sanitary processes in most relevant standards. More stringent applications require a surface finish of Ra <=15 µin, for which an electro polished finish should be considered.
Mechanical Gauge Cases
The external case finish on a mechanical gauge must comply with certain requirements to meet the highest sanitary standards. Preferably, the case should be made of stainless steel and should be watertight to protect against cleaning agents.
Mechanical gauge cases used in clean rooms, and/or in the pharmaceutical and biotech industries, are often electro polished to reduce the likelihood of unwanted particles adhering to any external surface.
Electronic Instrument Housings
The housings on electronic pressure instrumentation (transducers, transmitters, switches, etc.) must be capable of withstanding the most severe environment within the application, including the sterilization process. The recommended environmental rating for acceptance within the sanitary industry is NEMA 5 (IP 65) or better. Instrumentation exposed to CIP or SIP should consider an environmental rating of NEMA 4 (IP 67) or better.
Autoclave Sterilization
An autoclave sterilizes materials and instruments by subjecting them to superheated steam under very high pressure (typical: 250ºF for 15 to 30 minutes). Steam sterilization is a time-proven and economical process for killing micro-organisms.
For a sanitary mechanical gauge assembly to be capable of withstanding the autoclave process, the window material must be able to withstand the temperature of the steam. Polysulfone, the most commonly used material in sanitary gauge windows, is well-suited for this.
Autoclavable instruments should also have a drain mechanism for the elimination of unwanted cleaning agents and condensed water. This is achieved by installing weep holes in the bottom of the case to ensure proper drainage.
Diaphragm Seals
Most pressure instruments (gauge, switch, transducer, or transmitter) are designed without sanitary process connections. This can be rectified by using diaphragm seals as adapters. The resulting connection should meet domestic and international sanitary standards.
Diaphragm seals isolate the instrument from the process media through the use of a thin flexible diaphragm welded flush to a housing that is compliant with sanitary requirements. The sanitary design ensures the connection between the instrument and the process media is free of dead space, or that the dead space is dramatically reduced.
Diaphragm seals can be fitted onto instruments measuring pressures as high as 20,000 psi and as low as 10” H2O differential.
Available sanitary diaphragm connections include Tri-Clover® Tri-Clamp®, Cherry-Burrell®, DIN 11851, CPM, Varivent®, 4” Tank Spud, and homogenizer, among others.
Most diaphragm seals are designed to be installed into the process flow by use of a “T” or butt weld fitting. This T type installation allows a diaphragm with a relatively large surface area to be exposed to the process to ensure accurate pressure readings. The flow-through cylindrical diaphragm connector, for example, becomes an integral part of the inline system. It does not produce turbulence or introduce corners or dead space which could obstruct the flow. This type of seal is also self-draining to assist in the cleaning of the piping system.
Diaphragm seals also provide the option of remote mounting, keeping the instrument away from the process for safety concerns or when extreme process temperatures exceed the instrument rating.
The diaphragm seal can be attached to the instrument in three basic configurations:
- Instrument direct-mounted onto the diaphragm seal
- Instrument mounted via cooling element due to extreme process temperatures
- Instrument mounted via flexible capillary in order to remote-mount the instrument due to extreme process temperatures
Advantages of Diaphragm Seals
- Diaphragm seals can be installed on almost any pressure measuring instrument
- Contrary to ceramic principles, use of a diaphragm seal does not require an additional sealing element due to the all-metallic construction, and thus requires less maintenance
- Various materials of construction can be used, and process connections achieved, without changing out the pressure instrumentation
- Ceramic measuring cells are highly sensitive to dynamic loads; use of metallic diaphragm seals on a non-ceramic measuring cell does not hinder the built-in overpressure safety of the instrument
- Accessories can be added to the pressure instrumentation while maintaining sanitary conditions, i.e.:
- Pressure dampening device can be added to slow response time and minimize any fluctuation in the pressure reading
- Two or more measuring devices can be installed on one sanitary diaphragm seal to provide, for example, local and remote readings.
System Fill Fluids
When using a diaphragm seal, the space created behind the thin flexible diaphragm should be completely filled with a system fill fluid that transmits the pressure from the diaphragm to the measuring instrument.
The choice of pressure transmitting fluid is critical since the fluid needs to perform under the most taxing process and system cleaning conditions. Above all, it must be compatible with the process media in case a breach occurs, compromising the seal.
Several FDA-compliant fill fluids are NOT recommended for use in a vacuum or under extreme temperatures (see table below). In fact, the most widely misused system fill fluid is water-based glycerine, which should not be subjected to hard vacuum or high temperature due to the risk of vaporization, which can permanently destroy the diaphragm seal. Additionally, at low temperatures glycerine becomes too thick to produce accurate readings due to extremely slow response time.
Temperature Measurement
You can measure temperature in a sanitary application using a variety of technologies, including bi-metal, resistance, and thermocouple. Each technology has different advantages and disadvantages. Bi-metal thermometers, for example, can only supply local readings, while resistance thermometers and thermocouples are primarily used to obtain an electrical output for remote readings. However, devices exists which combine resistance and bi-metal elements, and provide both local and remote capabilities in one package. This allows the user to tap into the process only once, reducing the potential for contamination.
The same wide varieties of sanitary process connections are available for temperature measurement as pressure measurement. The sanitary fitting can be positioned directly onto the instrument or connected via use of a thermowell.
Most temperature instruments are designed to be installed into the process flow by use of a “T” or butt weld socket. This T type installation allows for a relatively large selection of stem insertion lengths to ensure accurate temperature readings. For example, resistance thermometers are available which connect as an integral part of the inline system. They do not produce turbulence or introduce corners or dead space which would otherwise obstruct the flow.
Advantages of Thermowells
- Measuring instrument can be inserted or removed without impacting (i.e., shutting down) the process
- Eliminate the potential for bending or severing the insertion probe due to the force of a high-viscosity process media
- Available in a wide variety of materials to ensure compatibility with the process media
