The safe transfer of materials is crucial to maintaining the integrity of cleanrooms, whose primary purpose is to isolate operations and processes from the uncontrolled and highly contaminating outside environment. Both airlocks and SAS (Safety Access Systems) are commonly accepted systems for this transfer.
Design of SAS and Airlocks according to GMP Standards
- An airlock is defined as an enclosed space with two or more doors, interposed between two or more rooms of different cleanliness level, to control air circulation between them during passage. They are designed for use by both people and objects.
- A SAS (also known as a Pass Thru, Pass Box or Material Pass-through) is considered a smaller “box” interposed in the separation wall between two areas of different classification. Ovens, double door autoclaves and sterilization tunnels can be considered special cases of transfer systems.
- GMP regulations generally avoid indicating specific technical solutions, basing the design and technical measures on a risk analysis.
- A fundamental design principle is that the gates of an airlock or SAS should not be able to open simultaneously, which is achieved by means of mechanical or magnetic interlocks, indicator lights and/or audible alarms.
- Generally, a pressure gradient from the cleanest zone to the least clean zone is assumed. The American cGMP regulation establishes pressure gradients between 10 and 15 Pa, with a minimum of 12.5 Pa between a Sterile Zone and an Unclassified zone.
- The grade of a SAS or airlock must correspond to that of the adjacent area of higher grade, according to WHO. Some regulations even specify that the final phase of the material airlock must have, at rest, the same grade as the area to which it leads.
- Personnel airlocks may have several successive steps for the physical separation of the different phases of change of clothing, and the final phase must have, at rest, the same grade as the zone to which it leads. In contrast, material airlocks usually have only one step.
Ventilation in SAS and Airlocks
- Large airlocks are typically ventilated and classified by the overall cleanroom HVAC system. It is desirable to ensure that the interior regains the specified classification grade before opening the clean side door, which can be achieved with timing or HEPA recirculation systems.
- Single pass-through SASs do not have indoor air control. However, to control particulate contamination or when the same grade as the room it accesses is required, SAS must be fitted with a swept interior system with ultrafiltered air (HEPA).
- There are several types of HEPA ventilation systems for SAS: closed loop recirculation, open loop recirculation, closed loop recirculation with air intake, and stand-alone ventilation without recirculation. Stand-alone ventilation with HEPA supply and exhaust allows pressure control and can be stopped when the SAS is not in use.
Implementation and Validation of VHP Decontamination Technologies
- In access to sterile areas, in addition to particle control, it is crucial to control biological contamination. Materials entering these areas must be sterilized or introduced by procedures that guarantee the absence of contaminants.
- For materials that cannot be sterilized by heat, SAS or airlocks incorporating a biocide decontamination system such as vaporized hydrogen peroxide (VHP), peracetic or glutaraldehyde are used.
- SAS with VHP require an independent open-cycle ventilation system (HEPA supply and exhaust) to facilitate removal of the biocide after decontamination and to prevent dispersal to other areas. Airlocks with VHP should also not be connected to the general HVAC system.
- It is essential that the doors of these SAS and airlocks are completely watertight to prevent leakage of the biocide into occupied areas. Static or dynamic(compressed air inflatable) seals can be used, the latter being more suitable for airlocks with heavy wheeled equipment traffic as they do not require a step in the threshold.
- Typical cycles of a VHP decontamination SAS include:
- Pre-treatment: Temperature and humidity conditioning.
- Injection: Introduction of the VHP until the specified concentration is reached.
- Contact: Maintenance of concentration for a certain period of time.
- Ventilation: Injection and extraction of ultra-filtered air to reduce the concentration of VHP to safe levels (< 1ppm for personnel).
- A PLC control system is essential for the management and timing of the cycle phases, as well as for implementing protections and managing cycle aborts.
SAS and Locks Qualification
- Any SAS or airlock requires full qualification, including:
- DQ (Design Qualification): Ensure that the solutions adopted are fit for purpose.
- IQ (Installation Qualification): Verify correct installation.
- OQ (Operational Qualification): Validate operation and set timings, interlocks and safeties.
- PQ (Performance Qualification): Validate performance under conditions of use.
- For SAS and sluices with VHP, qualification should verify the effectiveness of the decontamination cycle in reducing the bioburden.
Building Materials
The materials and technical characteristics of SAS and airlocks must comply with GMP guidelines, being inert, without particle detachment and easily cleanable, avoiding cavities and hard-to-reach corners. Pharmaceutical sandwich panels, sealed joints and PVC or resin flooring are commonly used. SAS are often constructed in stainless steel, using grades such as AISI 304 or, for more demanding corrosion resistance requirements, AISI 316L. Ease of cleaning is a primary criterion, over aesthetics in all cases.
———
In summary, the design and qualification of SAS and airlocks for the safe transfer of materials in cleanrooms, especially when incorporating VHP decontamination, requires a detailed understanding of GMP regulations, airflow and pressurization principles, decontamination technologies and qualification aspects to ensure the integrity of the controlled environment and the quality of the drug product.
