Terra manufactures five distinct cleanroom designs. Each design is ideal for different user requirements, based on ISO rating and environmental controls, for medical device, semiconductor, defense, pharmaceutical, biotechnology, and aerospace applications. As a pioneer in the critical environment industry, Terra Universal has developed and manufactured innovative solutions for over 45 years. Combining high-throughput, automated fabrication equipment with a robust, active stock of raw material, Terra is capable of producing cleanrooms of any design, size, scope and complexity at industry-leading build times. In the past 6 years, we have installed 2,132 cleanrooms, based on Terra’s scope, in active operation across the globe.

GMP Cleanrooms for Manufacturing Pharmaceuticals, Biologics and Medical Devices

Cleanrooms designed to house manufacturing operations for pharmaceuticals, biologics and medical devices fall under the auspice of the FDA’s Good Manufacturing Practices, or GMP.  Good Manufacturing Practices (GMPs) are a set of regulations that are used to ensure that products are consistently produced and controlled to meet quality standards. GMP classifications are used to categorize pharmaceutical, biological and medical products based on their level of risk and complexity, and the level of regulatory oversight required to ensure their safety and efficacy. 

The four main GMP classifications are as follows.

1. General GMPs: Apply to all pharmaceutical products and manufacturing processes, and are aimed at ensuring that all products are manufactured to a consistent level of quality.  General GMPs cover aspects such as personnel training, documentation, process validation, and equipment calibration.  Cleanroom grades C and D apply to this GMP classification.
2. Sterile GMPs: Additional requirements that apply to products that are intended for injection or implantation and must be free from microorganisms.  Sterile GMPs cover aspects such as air quality, personnel gowning, sterilization procedures, and container/closure systems.  Cleanroom grades A and B apply to this GMP classification.
3. Biologic GMPs: Supplementary requirements that apply to products derived from living organisms, such as vaccines, blood products, and gene therapies.  Biologic GMPs cover aspects such as raw material sourcing, cell bank testing, and the use of validated manufacturing processes.  Cleanroom grades A and B apply this GMP classification and biologic samples must be handled in RABS glove box systems designed to protect the samples from contamination and the operators from exposure.
4. Radiopharmaceutical GMPs: Added requirements that apply to products that contain radioactive materials, such as imaging agents and cancer treatments.  Radiopharmaceutical GMPs cover aspects such as radiation protection, product labeling, and the handling and disposal of radioactive materials.  Cleanroom grades A and B apply to this GMP classification, but additional safeguards are required to prevent radiation exposure, such as lead-lined isolators and pass through chambers.

In addition to the four main GMP classifications, specialized GMPs are formalized for manufacturing of specific products, such as oral dosage forms, topical drugs, non-invasive medical devices, and active pharmaceutical ingredients (APIs). 

GMP cleanrooms must adhere to the criteria of the following grades (A, B, C or D) depending upon the level of cleanliness required to ensure product quality, worker safety, protection from cross contamination and environmental hazards.  For GMP spaces housing work with biologics or radiopharmaceuticals, additional secondary engineering controls, such as RABS systems and lead-lined isolators, are required to enclose all sample-processing operations.

1. Grade A (ISO Class 5): The cleanest classification is used for high risk operations, including vial filling, ampoule capping, and aseptic testing.  The maximum particle count in this type of cleanroom, at rest and in operation, is 100 particles per cubic foot (or approximately 3,520 particles per cubic meter) of air that are 0.5 microns in size or larger.  Sinks and drains are prohibited in Grade A areas.
2. Grade B (ISO Class 7): This classification is used for less critical manufacturing areas, such as aseptic preparation and batch filling, where a lower level of cleanliness is required. The maximum particle count in this type of cleanroom, during operation, is 10,000 particles per cubic foot (or approximately 352,000 particles per cubic meter) of air that are 0.5 microns in size or larger.  However, Grade B spaces must maintain ISO 5 conditions while at rest.  Grade B areas must be equipped with particle monitoring systems with audible alarms if limits are exceeded.
3. Grade C (ISO Class 8): This classification is used for non-critical manufacturing areas where a relatively low level of cleanliness is required, such as solution preparation, powder weighing, and product filling for terminal sterilization. The maximum particle count in this type of cleanroom, during operation, is 100,000 particles per cubic foot (or approximately 3,520,000 particles per cubic meter) of air that are 0.5 microns in size or larger.  However, Grade C spaces must maintain ISO 7 conditions while at rest.
4. Grade D (unrated): This classification defines a Clean Non-Classified (CNC), which acts as a background zone for processes such as equipment cleaning, component assembly and handling of closed, sterilized aseptic containers.  As an unrated space, Grade D rooms are not expected to maintain a defined particle count during operation.  However, they must maintain ISO 8 conditions while at rest.

The features of GMP cleanrooms may vary depending on the specific needs of the manufacturer and the regulatory requirements governing the production of the product. However, some common features of pharmaceutical cleanrooms include:

1. HEPA or ULPA Filters: Micro filters used to remove particles from the air to prevent circulation throughout the cleanroom.  HEPA filters are 99.99% effective in capturing particles as small as 0.3 microns in size, while ULPA filters are 99.9999% effective in capturing particles down to 0.12 microns in size.  While limited particle counts are of primary importance, air flow laminarity is less of a concern, given the secondary controls in place to prevent contamination influx.  So, many GMP cleanrooms feature ducted filter modules connected to a central air handling system, rather than individual filter fan units.
2. Controlled temperature and humidity: GMP cleanrooms are maintained at specific temperature and humidity levels, with very tight tolerances, to ensure the stability of products during manufacturing, testing and storage.  These precise environmental set points are maintained through building HVAC integration, rather than modular air conditioning systems.
3. Sterilization Procedures: Equipment, tools, and surfaces within the cleanroom must be regularly sterilized to prevent contamination.  Rigorous sterilization methods, such as UV-C (Germicidal Ultra-Violet Light) and VHP (Vaporized Hydrogen Peroxide), are used to daily disinfect surfaces and equipment, while tools are commonly sterilized inside an autoclave.
4. Controlled Access: Access to the cleanroom is often limited to authorized personnel and may require security measures, such as keycard entry or biometric authentication, on all points of entry, including interlocking, automatic hands-free doors, personnel air locks, air showers, and pass through chambers.
5. Integral Flooring: GMP cleanrooms must include epoxy-coated or GMP-grade vinyl flooring coved at the floor-to-wall transition for easy cleaning.
6. Monitoring Systems: GMP cleanrooms are equipped with monitoring systems to track temperature, humidity, and particle counts to ensure that the environment is maintained within the required parameters.  The monitoring systems include audible and visual alarms, remote access through a mobile app, and building management system integration to ensure that appropriate personnel are quickly informed when the cleanroom is operating outside of set point.

Terra’s GMP Design: BioSafe Modular Hybrid Cleanrooms

The BioSafe Modular Hybrid system meets all GMP cleanroom requirements for Grade A, B, C or D spaces.  The BioSafe Hybrid wall panels utilize joint connectors to maintain a flush finish; all gaps are filled by an FDA-grade sealant to ensure a leak-tight system without cavities where microbes colonize.  The cleanroom walls, composed of a steel substrate with a selection of different finishes, feature a plenum space to house utility and filling lines, providing the end user with convenient access to gas, vacuum and water connections along with duplex outlets, control panels, and phone jacks.  Terra’s BioSafe Hybrid wall system features pre-fabricated coving panels to accommodate wall-to-floor and wall-to-ceiling conversions, ensuring a smooth transition free of cracks, crevices and gaps.  The cleanrooms feature hard ceilings composed of robust, rugged components capable of handling daily spray-down cycles or VHP sterilization.  Terra’s BioSafe Hybrid rooms are constructed from rugged, durable, GMP-rated materials resistant to scratches, corrosion, and common disinfectants, such as Spor-Klenz, quaternary and phenolic cleaners.  All materials are pre-cut and precisely engineered to reduce fabrication and assembly times.

Learn More: BioSafe Modular Hybrid Cleanrooms

Terra’s Manufacturing Capabilities

Terra builds and installs over 500 cleanrooms per year, on average. All cleanroom components are pre-engineered, quality control tested, and stocked for quick integration and assembly. In addition to product manufacturing, Terra offers a wide range of value-add services, including white glove delivery, cleanroom installation, structural seismic analysis, expedited production, qualification documentation and extended warranties. Order-specific certificates of compliance, listing each product’s adherence to ISO, UL, OSHA and seismic standards, are supplied with every qualifying sale. The leader in critical environment solutions, Terra also manufactures laminar flow hoods, desiccator cabinets, glove box isolators, pass through chambers, and a broad array of cleanroom-compliant furniture, storage and gowning equipment. To determine the appropriate ISO rating, room design and configuration for your project; please call 714-578-6100 to consult with a Terra cleanroom professional.