In a pharmaceutical production workshop, how should the clean pass box be arranged?

In the pharmaceutical production workshop, the layout of clean transfer Windows must strictly follow the requirements of GMP (Good Manufacturing Practice for Pharmaceuticals). The core objective is to reduce cross-contamination among areas of different clean levels, ensure the safety of material/item transfer, and at the same time, take into account the efficiency of the production process. The following is a detailed explanation of aspects such as layout principles, specific locations, and installation details:
I. Core Layout Principles
Prioritize isolation to avoid cross-contamination
The transfer window must be set at the junctions of different cleanroom levels (such as between the clean area and the non-clean area, or between the high cleanroom level and the low cleanroom level), and the direct air circulation between the two areas should be blocked through the double-door interlocking function.
Transfer Windows must be set up between the clean area (Class C) and the general production area, as well as between the sterile area (Class A/B) and the clean area (Class C). Direct crossing is strictly prohibited.
It conforms to the process flow and reduces the round-trip path
The transfer window should be close to the usage point or temporary storage area of the materials/items to avoid long-distance handling within the clean area during the transfer process (increasing the risk of contamination).
Transfer Windows should be set up nearby between the raw material temporary storage room and the mixing room, as well as between the inner packaging material sterilization room and the filling room.
Avoid becoming a gathering place for pollution sources
Sufficient operating space should be reserved around the transfer window (it is recommended to be ≥80cm) to facilitate cleaning and disinfection. It is prohibited to be near pollution sources such as floor drains, sewage outlets, and waste channels (with a distance of no less than 1 meter).
Coordinate with the air flow organization in the clean room
The position of the transfer window should not disrupt the original airflow direction of the clean room (such as unidirectional flow), to avoid the disorder of the clean airflow caused by opening the door. It is recommended to stay away from the core area of the return air outlet or supply air outlet.
Ii. Layout positions classified by cleanliness levels
The cleanliness levels of A pharmaceutical production workshop are typically classified as Class A (high-risk operation area), Class B (Class A background area), Class C, Class D, and non-clean areas. Transfer Windows should be arranged according to the "level gradient."
Non-clean area ↔ Class D clean area
Location: Usually located beside the "General Area → Clean Area" buffer room at the workshop entrance, it is used for transferring raw materials, tools, etc., after their outer packaging has been cleaned.
The transfer window should be equipped with basic double-door interlocking. The outer door (the non-clean area side) can be made of ordinary materials, while the inner door (the D-class side) should be smooth and easy to clean. The cavity can be wiped regularly with 75% alcohol.
Class D clean Area ↔ Class C clean area
Location: It is set at the partition wall between the two areas, close to the material transfer route (such as between the weighing room and the granulation room).
The material of the transfer window should be 304 stainless steel (corrosion-resistant and easy to disinfect). Ultraviolet lamps can be installed in the cavity (to assist in sterilization) to prevent particles from the low-level area from being brought into the C-level area.
Class C clean area ↔ Class B/B/ B/Class A clean area
Location: It should be adjacent to the aseptic operation area (such as the filling room, next to the freeze dryer), and be used for transferring sterilized inner packaging materials, aseptic raw materials, aseptic tools, etc.
Requirements: A clean transfer window with a high-efficiency filter (HEPA) must be used (or directly upgraded to a laminar flow transfer window). The cleanliness inside the cavity must reach Class C or above. Before transfer, the surface of the items must be disinfected (such as VHP vaporized hydrogen peroxide), and the door opening operation must be carried out under Class A laminar flow protection.
Iii. Layout Requirements for Special Scenarios
Sterile preparation workshop (such as injection, freeze-dried powder injection)
The A-level operation area (such as filling needle and rubber stopper transfer) should use laminar flow transfer Windows, and the inner side door of the transfer window should be embedded in the enclosure structure of the A-level area to ensure that the unidirectional flow in the A-level area is not disrupted when the door is opened.
The transfer window needs to be linked with sterilization equipment (such as wet heat sterilizers and dry heat sterilizers), and the sterilized items directly enter the sterile area through the transfer window to reduce contamination in the intermediate links.
Oral solid dosage form workshop
The raw material transfer window should be close to the weighing room to avoid multiple transfers of raw materials within the clean area.
The inner packaging material transfer window should be adjacent to the packaging material disinfection room to ensure that the disinfected packaging materials directly enter the inner packaging area.
Biological products workshop (such as vaccines, blood products)
The transfer window should have biological airtightness (such as enhanced sealing with silicone sealing strips) to prevent the leakage of live viruses and bacteria.
When necessary, set up "double-door transfer Windows" (for more thorough physical isolation between the two side doors) or install disinfection devices (such as ozone or hydrogen peroxide atomization).
Iv. Installation and Operation Details
Structure and Material
The box body of the transfer window should be flush with the wall of the clean room, and the gap should be sealed with sealant to prevent dust accumulation.
The inner wall and door frame should have no dead corners or depressions. The material should be 304/316 stainless steel, which is convenient for steam or chemical disinfection.
Interlocking and monitoring
The double-door interlock should adopt both mechanical and electronic interlocks to prevent faults from causing both doors to open simultaneously.
The transfer Windows in key areas (such as from Level B to Level A) need to be equipped with door opening record sensors and ultraviolet lamp operation timers, ensuring data traceability.
Cleaning and disinfection
The interior of the transfer window should be included in the daily cleaning SOP of the clean area (such as wiping with purified water every shift and disinfecting with disinfectant every week).
The transfer window in the sterile area needs to be regularly verified for its airtightness and cleanliness (such as dust particle detection and microbial challenge tests).
Summary
In the pharmaceutical production workshop, the layout of clean transfer Windows should revolve around the four core aspects of "hierarchical isolation, process efficiency, cleanliness, and compliance". The specific location should be comprehensively designed in combination with the product dosage form (sterile/non-sterile), cleanliness level gradient, and production process path, while meeting the GMP requirements for cross-contamination prevention and control and data traceability. When necessary, the rationality of the layout should be verified through simulation tests (such as air flow visualization tests) to ensure that the transfer process does not hurt the clean environment.