Preventing Cross-Contamination in Cleanrooms
Preventing errors, contamination, and cross-contamination is a core aspect of GMP (Good Manufacturing Practice). Cross-contamination refers to the mixing of components from different types of pharmaceuticals through personnel movement, tool transport, material transfer, airflow, equipment cleaning and disinfection, and work area cleaning, leading to contamination. It can also occur due to improper flow of personnel, tools, materials, or air, allowing contaminants from lower-cleanliness areas to enter higher-cleanliness areas. So, how can cross-contamination in cleanrooms be prevented? The "Cleanroom Design Code," implemented in 2002, clearly states that the "process layout of cleanrooms should be reasonable and compact. Only necessary process equipment and processes and work areas with air cleanliness requirements should be arranged within the cleanroom or clean area."
A reasonable layout of space is crucial. First, the process flow must be streamlined to avoid detours. The floor plan of the work area should be reasonable, facilitating both operation and maintenance, and should not reserve idle space. A reasonable space and area also facilitate proper zoning, preventing accidents caused by mixing of different components.
It is important to note that larger cleanrooms are not necessarily better. The size of the area directly affects the airflow, thus determining air conditioning energy consumption and impacting project investment. However, the cleanroom space should not be too small either, as this may hinder operation and maintenance. Therefore, a well-designed space should consider the needs of equipment operation and maintenance. Production and storage areas should have sufficient space to accommodate equipment and materials, facilitating operation and maintenance. Generally, the height of a cleanroom is controlled at 2.60 meters. For individual taller equipment, local increases are possible, but it is not advisable to raise the overall height of the cleanroom area. The workshop should have an intermediate material storage station with sufficient area to store materials, intermediate products, inspection items, and finished products, and clear zoning to minimize errors and cross-contamination.
Improving Equipment Quality: The materials, processing precision, airtightness, and management systems of equipment all relate to cross-contamination. Therefore, in addition to a reasonable layout, improving the automation level of equipment and forming interconnected production lines to reduce operators and lower personnel activity frequency are necessary measures to prevent cross-contamination.
Solid dosage form workshops generate a large amount of dust. How can cross-contamination be prevented in solid dosage form workshops? First, the selected equipment should have protective covers and be equipped with dust removal devices. Second, isolation measures should be taken, dividing it into an operating room and an anteroom, or an operating room and an auxiliary equipment room. The anteroom is generally arranged as a single room for each machine, while the auxiliary equipment room can be located in a non-clean area, with the access door on one side of the corridor. This separation method can be used for equipment such as tableting, automatic coating, and capsule filling machines. For some single machines that do not have dust removal auxiliary equipment and are not sealed, such as pulverizers, powder or granule packaging machines, the exhaust air in the isolation area can be filtered and then returned to the isolation area, forming a self-circulating system.
During the production process, some pharmaceuticals are highly hygroscopic. When the required relative humidity is below 50% or even 45%, refrigeration dehumidification is difficult to achieve. Among many dehumidification methods, lithium chloride rotary dehumidifiers are more suitable. Dehumidifiers can be installed in clean rooms with special dehumidification requirements, using purified air as protective low-humidity air for that work area, forming a self-circulating system.
Separate Air Conditioning and Purification Systems: Cleanrooms should have separate air conditioning and purification systems based on different cleanliness levels. For work areas handling β-lactams, contraceptives, hormones, highly toxic microorganisms, antitumor drugs, and radioactive drugs, separate air conditioning and purification systems should be installed, with high-efficiency filters installed at the exhaust vents to minimize contamination from these drugs. For cleanrooms of different cleanliness levels, cleanrooms that generate dust and harmful gases, and work areas where the discharged media is highly toxic or contains flammable or explosive gases, separate local exhaust systems should be provided. Cleanroom exhaust vents should have backflow prevention devices. The opening and closing of supply air, return air, and exhaust air should be interlocked.
Strict Control of Personnel and Material Flow: Cleanrooms should have dedicated personnel and material flow channels. Personnel should enter according to the prescribed purification procedures, and the number of personnel should be strictly controlled. Materials can be removed from their outer packaging after removing floating dust and then sent in through buffer rooms or pass-through cabinets. Items from clean areas of different cleanliness levels should be transferred through pass-through windows. Intermediate stations should preferably be located in the center to shorten transportation distances. No pipes unrelated to the work area should be installed within the clean area. Make full use of the technical interlayer above, below, or around the room; all utility and process main pipes should be installed in the technical interlayer. Pipes crossing the floor or partition walls should be laid as close as possible to the point of use and with sleeves. There should be no welds on the pipes inside the sleeves, and there should be a fork-proof seal between the pipes and the sleeves. Pipes entering the cleanroom should be made of stainless steel.