FAQ - Cleanroom technology

Cleanroom technology is a field of technology that is dedicated to protecting certain work areas from undesirable external influences. Since the end of the 1950s, cleanroom technology has been pursued as an independent technology over and above internal company developments. The impetus came from space technology with its demands for miniaturization of components while at the same time placing the highest demands on the functional safety of the systems.

Contaminants that can lead to the destruction or unusability of the end product or to the impairment of persons involved in the work process are, in addition to gaseous or vaporous components, solid or liquid particles of different sizes that settle on solid surfaces or penetrate into fluids.

Increasingly stringent industrial requirements are leading to an extraordinary refinement of the technologies and process techniques used in many branches of production. The methods used are becoming ever more precise and effective. However, in order to fulfill the demand to produce top quality while simultaneously mass producing, much more precise boundary conditions of production must be adhered to. The requirement to keep the production facility free of dust and germs is therefore of great importance. This has led to an above-average increase in the use of laminar flow technology and cleanroom technology itself in recent years. For example, the electronics industry is developing miniaturized electronic semiconductor components with high functional capacity (microchips), while precision engineering uses the smallest components with high precision. Manufacturing these parts in uncontrolled air would lead to rejects or impair their function.

Preparations for the prevention and treatment of diseases have reached a level that can hardly be surpassed. They therefore require a high degree of asepsis. Dust and microorganisms in particular reduce the quality of these products or call them into question altogether. The same applies to high-quality foodstuffs, where contamination has a negative impact not only on quality but also on shelf life. In complicated clinical operations, the bacterial content of normal air leads to wound infections that cause post-operative problems.

New technologies are often initially developed in laboratories, tested and brought to production maturity. However, the interfering factors in the air can lead to false conclusions, as they falsify the results. Only the use of modern clean room technology can provide a radical remedy. Its advantage is that it removes almost all airborne foreign particles. It therefore has a wide range of applications, as it removes all suspended particles, i.e. dust and microorganisms. Since the introduction of cleanroom technology in practice, it has quickly become indispensable for many techniques. New areas of application and use are constantly being developed.

Nowadays, cleanrooms are used in many different ways: in research laboratories, in the manufacture of medicines, chemical production and even microchip production. The purpose of cleanrooms is to create a defined area where work can be carried out under "clean conditions". In order to make this "clean workplace" possible, it is not enough to supply the room with clean air; it is also necessary to prevent the resulting contaminants from being deposited in the room. In general, it can be said that no two cleanrooms are the same, as the spatial conditions, the process sequence, the desired cleanroom class and, of course, the investment and operating costs require individual solutions.

>> Der Bau eines Reinraums erfolgt in drei Phasen <<

Phase 1: Planning

Due to different user requirements, local conditions, economic factors, etc., the construction of a cleanroom cannot be coordinated without a specification sheet. The specification serves the customer (user of the cleanroom) to define and thus specify his requirements for the cleanroom. The contractor is obliged to respond in the form of a specification sheet and to document which services his product ("cleanroom") will fulfill. The actual order is only placed once the specifications have been signed by both parties. Then it starts: measuring, studying plans, construction site meetings, clarifications with suppliers, .... For a GMP-compliant system, the entire planning process must also be documented. This is done in the form of design qualification (DQ). This is the documentary evidence that all plant components or systems have been planned in accordance with the currently valid regulations and guidelines (FDA, cGMP, ...). When planning a cleanroom, it is necessary to know the requirements for which the room will be used and how the work process will be defined. How many people will be involved in the work process, what protective clothing will be worn, what heat will be generated, .... All these questions must be discussed with the actual user of the room. Only after these points have been clarified can the flow system (low-turbulence displacement flow, turbulent mixed flow, directional flow, etc.) be selected for the cleanroom. It is also important to consider the condition in which the desired cleanroom class is to be guaranteed: "as build", "at rest" or "in operation".

Phase 2: The construction phase
In the first construction phase, the rough structural work is carried out, e.g: Wall openings for ventilation ducts, gas and power supply, cold and hot water, suspension structures, any dismantling and much more. The air conditioning units are then set up at their destination and the ventilation ducts are installed. Once this work has been completed, the cleanroom walls and doors can be installed. Once these have been completed, the false ceiling construction is installed. The sterile air supply components are then installed in these.

(laminar flow, suspended ceiling outlets, ...), the lighting beams and fire detectors. However, before the suspended ceiling is closed and sealed, the ventilation and electrical systems must be connected. Once this work has been completed, the room must be cleared and cleaned. From then on, the floor layer has the space to lay a cleanroom-compatible plastic floor with coving. The flushing system can then be put into operation and fine cleaning carried out. The final filters (HEPA filters) are only inserted into the systems once all the work in the room has been completed. The ventilation technician now has the task of setting the system to the specified values: Air volume, pressure levels to the adjoining rooms, air speed, temperature, humidity, ....

Phase 3: Acceptance & testing
Acceptance usually takes place in the presence of the planners, users and suppliers involved in the project. The purpose of IQ (Installation Qualification) is to check whether the system components specified during planning (DQ) have been delivered and installed completely, correctly and without damage.

An OQ (Operation Qualification) system inspection can be carried out after the room has been purged for a certain period of time. The OQ is the documentary evidence that all plants or systems can be operated in accordance with their planned specifications and requirements and that the cleanliness zones without activity (personnel and production) meet the defined criteria. As a rule, a seal fit and leak test measurement of the filters used is carried out first, followed by particle measurement and flow visualization. The cleanroom is only approved for production once all these tests have been successfully completed. Achieving a certain cleanroom class in an "empty room" does not require too much effort. The actual requirement for a cleanroom is to guarantee the requirements for air purity even when it is "in operation" (with personnel and production). The documentary evidence that all equipment and systems meet the planned specifications under routine conditions of use in the clean zones is recorded in the form of the PQ (Performance Qualification). Once this final test has been completed, the cleanroom can be released for production.

In order to set up a clean room, 3 areas must be observed:

Cleanroom technology:
It is the responsibility of the cleanroom technician to select the optimum system (flow type) and determine the associated air volume, taking into account the disturbance variables. (recirculated air and fresh air proportion) Furthermore, the cleanroom technician must monitor that all components used comply with the cleanroom class. The reasons for not achieving the required cleanroom class are usually trivial, e.g. missing door locks, gaps in doors, leaking windows, vibrations. The cleanroom technician is subsequently held responsible for all these errors. It is therefore advantageous to commission an experienced cleanroom technician with the controlling.

Air conditioning technology:
The task of the air conditioning technician is to implement the specifications of the cleanroom technician (air volume, air supply, extraction, air routing, temperature differences...) with the desired room conditions (temperature and humidity) using suitable air conditioning units. The following questions typically arise: Installation location of the air conditioning units, noise level, cooling and heating energy, fire protection regulations, room condition tolerances, etc.

Interior decorator:
Of course, for a cleanroom of the higher classes, it is also necessary to create the right enclosures (sheathing). Cleanroom walls and doors must be smooth, seamless, easy to clean, antistatic, light-colored, easy to retrofit, resistant to disinfectants, stable, heat-insulating and usually also sound-insulating (possibly also door locks). Additional requirements are placed on the floor, such as electrically conductive, with coving in the edge areas and resilient. The area of responsibility of the interior designer also includes the suspended ceiling: lighting, air ducting, fire alarm systems and service access. Not forgetting the right choice and position of furnishings such as tables, cupboards, etc. As a rule, a ceiling plan and wall elevations are drawn up by the interior designer and signed off by the cleanroom technician and the user before production.

Cleanroom technology protects products, processes and workers from the harmful effects of contamination.

The actual task of cleanroom technology is to ensure a predetermined air purity in a workspace with regard to airborne particulate air pollutants in order to prevent harmful effects of these air pollutants on processes and people!

This results in the following tasks in a broader sense:

• Keep particles from the ambient air away from the work area
• Air filtration and flow control
• Underpressure and overpressure grading between rooms and room types
• Maintain certain air conditions such as air temperature and humidity
• Feed high-purity media into the process
• Cleanroom-compatible production technology and process control
• Adapted staff behavior and the necessary training and motivation
• Control of the surface cleanliness of products, work surfaces and packaging materials
• remove and dispose of the process exhaust air

One or both of the following protection goals must be achieved:

• the protection of products, objects and/or work processes from contamination-related damage and/or loss of performance:
• the protection of workers from health-threatening process risks

In addition, it may also be necessary to ensure the protection of the population in the operating environment from harmful airborne emissions.

In principle, cleanroom technology is divided into two groups:

Product protection:

• Protection of the active ingredients from cross-contamination by other active substances produced in the same plant;
• the protection of intermediate and end products of pharmaceutical production from contamination by microorganisms and their metabolic products (pyrogens)
• the protection of biotechnology work processes from contamination by microorganisms foreign to the process;
• ensuring the sterility of parenterals

Personal protection:

• Shielding employees from process risks
• Protection against contact with highly active substances
• Protecting the operating environment from hazardous substances

With this range of tasks, cleanroom technology is a key link in the chain of hygiene measures in the manufacture of sterile pharmaceutical forms. However, they also make significant contributions to process safety in chemical and biotechnological synthesis of active ingredients, in the manufacture of solid, semi-solid and liquid pharmaceutical forms of all kinds, in biotechnological research and product development and in the quality testing of intermediate and end products

Cleanroom systems were used wherever cleanroom technology provided essential prerequisites for technological progress:

• in the chemical and pharmaceutical industry in the production of high-purity chemicals
• in microelectronics in the development and production of memories and integrated circuits with ever-increasing information density
• in the mechanical and optical industry when assembling highly sensitive components or testing precision instruments
• in the hospital sector for the asepsis of operating theaters
• in food technology for the processing of products without shelf life additives
• in the field of space research
• and last but not least in areas of basic research that deal with material properties and material structures, for example
  genetic engineering
• Bio-Technology
• Defense technology
• Semiconductor technology
• Laboratories
• Pharmacies

• Personnel
  People are the biggest "particle slingers" in a cleanroom. Despite wearing cleanroom suits, thousands of particles are released into the room through actions such as sneezing, rubbing hands on other parts of the body, etc.
• machine
  Metallic abrasion of system components.
  Flow obstacles
  Work tables, machines, walls can prevent a uniform flow through rooms
• Leak
  A pinhole-sized hole in a supply air filter can cause serious quality losses.
• Heat sources
  Solar radiation or machine heat generate counter currents and lead to turbulence.
• Vibrations
• Electrostatic
• Humidity
• Temperature differences

• Flow form
• Air volume, air speed
• Filter quality
• Room pressure differences
• Surrounding surfaces (walls, ceilings, floors)
• Working persons
• Access points such as doors, windows, locks
• Workplaces
• Sensors, alarms, control
• Light and heat sources
• Process equipment
• Humidity, temperature
• Media supply
• Safety devices
• Static charging of surfaces
• Possible vibrations
• Flow obstacles
• Sound level
• Particle emission sources

• Microorganisms
  Microorganisms are an important subclass of particles: single-celled organisms of microscopic size that can multiply by cell division under suitable conditions.
• CFU
  Colony forming units :: germs capable of reproduction :: bacteria, fungi, yeasts,....
• Particles
  are solid or liquid particles with defined physical boundaries, i.e. with a clearly defined contour.
• Cleanroom technology
  (contamination control) is the chain of all technical and operational measures to prevent the harmful effects of impurities (contamination) in the workplace.
• Clean room
  is defined as a room in which the concentration of airborne particles is controlled and managed. It is operated in such a way that the supply, release and deposition of particles are minimized. Additional cleanliness-relevant variables such as temperature, humidity and pressure must be controlled as necessary.
• cGMP Directive
  current Good Manufacturing Practices - Directive of the European Union for good manufacturing practice
• FDA
  Food and Drug Administration :: American safety authority
• PIC
  International agreement for the mutual recognition of pharmaceutical inspections
• DEHS
  Diethyl hexyl sebacate :: Monodisperse aerosol used for testing air filters.
• DOP
  Dioctyl phthalate :: Formerly used test aerosol, but which has harmful effects.
• MPPS
  Most Penetrating Particle Size :: Particle size with the highest transmittance on a filter.
• SOP
  Standard Operation Procedures :: Standardization of regular procedures
• VMP
  Validation Master Plan
• HEPA
  High Efficiency Particulate Air Filter = HOSCH High Efficiency Particulate Air Filter, H10-H14
• ULPA
  Ultra Low Penetration Air Filter, U15-U