What is Annex 1?
GMP Annex 1 is the EU standard for “The Manufacture of Sterile Medicinal Products”. The manufacture of sterile products is subject to special requirements in order to minimize risks of microbiological, particulate and pyrogen contamination. For this reason, this new standard provides general guidance that should be used in the design and control of facilities, equipment, systems and procedures used for the manufacture of all sterile products applying the principles of Quality Risk Management (QRM), to ensure that contaminations are prevented in the final product. Annex 1 principles include contamination control strategy, design of premises, cleanroom classification, qualification, validation, monitoring and personnel gowning. Some of the most relevant guidelines are set out below.
“In cleanrooms and critical zones, all exposed surfaces should be smooth, impervious and unbroken in order to minimize the shedding or accumulation of particles or micro-organisms.”
“Ceilings should be designed and sealed to prevent contamination from the space above them.”
“Cleanrooms should be supplied with a filtered air supply that maintains a positive pressure and/or an airflow relative to the background environment of a lower grade under all operational conditions and should flush the area effectively.”
Stainless steel in clean environments
Stainless steel furniture and equipment can be found in most types of cleanroom environments, and that’s because of its unique features: stainless steel is durable, attractive, easy to clean, corrosion resistant, and able to withstand vigorous cleanings. In addition, stainless steel is theoretically 100% recyclable and its long-term life makes it an ideal environmental performer compared to other materials. There are more than 50 types of stainless steel grades recognized by the American Iron and Steel Institute (AISI), however the three most common types used in furniture and equipment in cleanrooms, labs, manufacturing facilities and sterile environments are grades 304, 316 and 430.
What is HPL?
High Pressure Laminate (HPL) is a composite material consisting of printed decoration paper fused to multiple sheets of Kraft paper saturated with a synthetic thermosetting resin. Heat and high pressure are used in a special thermosetting process to create flexible, high-density laminate sheets. The countertop surface patterns on the laminates are saturated with melamine and phenolic-based resins to provide higher resistance to abrasion, thermal and impact shock, heat and discoloration. HPL is a standard finish in controlled contamination environments which require low static generation, frequent access or ease of maintenance. It’s easy to clean, making it ideal for places and applications where high levels of hygiene are essential, such as laboratories, hospitals and clinics.
Cleanroom door interlocking system
According to ISO 14644 standard, cleanrooms are required to be equipped with either a soft or a hard interlocking system. The requirement is challenging especially when it comes to the modernization of existing or modular systems. Many of these are not equipped with interlocks so the system must be added later to comply with the standard.
To design an interlocking system is a complex process that takes several factors into consideration:
- Budget
- Field requirements
- Health and safety
Door interlock systems can include any of the following capabilities: connection to HVAC, workflow control, user feedback indication, touch-free access, emergency override operation, access control, and/or forced door and door prop alarms. Some cleanrooms require pressurized air systems to maintain a sterile environment. This requires door interlocks to incorporate a timed delay before entry is granted into the cleanroom so that re-pressurization of the interlock can take place. This is often controlled by a simple timer or a monitored pressure switch. While the air is pressurized, traffic indicator lights are typically also employed to alert personnel when air treatment is complete for safe entry. Some cleanroom locations may not allow any doors to be locked to permit free egress at any time. This is most easily addressed with the use of red/green traffic lights mounted on either side of the doors to indicate when access is allowed. Adding a built-in sounder which annunciates an improper opening can also help minimize such actions. Additionally, with functions like re-pressurization that may be taking place, traffic indicator lights can be used to provide user feedback.
Cleanroom doors
Constructed with materials that minimize particle generation and facilitate easy cleaning, cleanroom doors contribute to the overall integrity of the controlled environment. They are often equipped with features such as interlocking mechanisms to maintain pressure differentials, preventing air exchange between clean and non-clean areas. The design of cleanroom doors prioritizes airtight seals and smooth, non-porous surfaces to minimize the risk of particle accumulation and microbial growth. Additionally, these doors may incorporate advanced technologies like automated opening systems, facilitating hands-free operation to further reduce the risk of contamination.
Sandwich panels
Partition walls and ceilings are built using sandwich panels consisting of a core material between two outer layers, typically composed of smooth and non-porous materials like stainless steel, aluminum or HPL. The core material often consists of substances with excellent insulation properties, such as polystyrene foam, rock wool or aluminum honeycomb. This construction provides a robust, durable, and thermally and acoustically efficient barrier. The modular nature of partition walls and ceilings allows for easy installation, reconfiguration, or expansion of cleanroom spaces to meet evolving production needs. The smooth surfaces of the sandwich panels contribute to the ease of cleaning and minimize particle generation, maintaining the required cleanliness levels.