GMP Facilities for Pharmaceutical Laboratories Manufacturing Medicinal Cannabis
With the significant growth of the global medicinal cannabis market and an increasingly regulated industry worldwide in recent years, it has become essential to develop and improve various types of engineering processes, as well as architectural designs and Good Manufacturing Practice Standard Operating Procedures (GMP SOPs) that can be applied and adapted to different types of laboratories for cultivation, drying, primary and secondary conditioning, and also to the processes involved in the manufacturing of derivatives such as extraction and purification for the production of APIs, including manufacturing intermediates up to the final medicinal product.
Cannabis product manufacturers must balance their need for a fast return on investment with the fact that the U.S., Canada, Europe, and other parts of the world are beginning to treat cannabis products exactly like any other conventional pharmaceutical product.
This represents a truly significant shift that requires an in-depth study of how the GMP concept can be adapted to this type of laboratory, with specific equipment for a defined manufacturing process. Executing projects with a pharmaceutical GMP concept in the cannabis field requires knowledge and experience in global standards, architectural planning, and various branches of engineering, as well as overall project coordination to ensure quality and proper validation procedures.
GMP architectural knowledge in the design of cleanrooms and laboratory processes for manufacturing cannabis-derived medicines can play a key role in the pharmaceutical industry, which is highly competitive and regulated. The cannabis-related industry includes many processes carried out in cleanrooms, from cultivation in highly controlled microclimates to drying, distillation, extraction, and the manufacturing of the final product.
Specific Issues in Cannabis Facilities
Cannabis cleanroom projects have all the same requirements as any pharmaceutical cleanroom. This includes particle control, prevention of cross-contamination between chemotypes, microbial contamination, and maintaining specific environmental conditions.
As the industry grows, environmental standards are emerging ranging from ISO 8 to ISO 5, to improve the handling of cannabis products.
The regulations and standards to be met vary depending on the type of applications and the industry in which the company is involved. A cleanroom facility used for the sterile preparation of hazardous drugs is completely different from one designed for conventional pharmaceutical products or microelectronics. Depending on your industry and application, you may need to comply with an ISO Class 5 to 8 standard, as well as FDA regulations and ISO-14644 parts 1/2/3/4.
In the pharmaceutical field, you will undoubtedly need to meet GMP standards and classifications when designing your facility. You must ensure that the architectural design, room temperatures, humidity, pressure cascade, lighting systems, and equipment comply with the established regulations in order to obtain the necessary certification and final validation.
Architectural Design of the Cleanroom
First of all, based on your business plan, you must determine the quantity and types of final cannabis products you intend to manufacture at your facility. This will define the number of rooms required, as well as the size and equipment needed for the different phases of the process.
The intake room (Indock) for the entry of raw materials into the facility and their storage must also be considered, along with waste management and the storage of the finished product in specific rooms. In addition, all other areas of the process should be planned according to the manufacturing stages and the ISO classification required for each zone.
The entire transformation process has specific requirements depending on the manufacturing stage being implemented. In the case of derivative production (solid and semi-solid pharmaceutical products), the most commonly used solvents are Ethanol (extraction), n-Heptane (purification), and n-Pentane (cannabinoid crystallization). CO₂ is a fluid used for the extraction of liposoluble compounds in complex matrices, and some methods use it under supercritical conditions (SFE extraction). Ultimately, to obtain high-quality concentrates, properly dried and cured cannabis flower is used, as this is where the active compounds of interest are concentrated.
Currently, pharmaceutical laboratories are choosing ethanol for the extraction process due to its significant advantages over other solvents, including its relatively low toxicity. However, like other solvents, it is flammable, which requires the design and certification of facilities with explosion-proof (ATEX) components, including panels, floors, and ceilings made with certified fire-resistant materials.
Cleanroom Facility Design
This entire project process must be accompanied from the beginning by a Validation, Qualification and Calibration Master Plan, along with a technical report or Site Master File (SMF) that describes the facility and covers all stages of the process, from the executive project to the commissioning procedures.
It is essential to study all phases of the process, considering the flow of materials, products, and personnel, and to plan elements such as doors, windows, SAS, workbenches, and airlocks or passthroughs. All of this is specified in the corresponding SOPs related to Facilities, Layouts, and Flows, which are typically requested by regulatory agencies during the preliminary document review and/or on-site inspection.
It is also important to define which processes will be carried out inside the cleanroom and which can be performed outside, in Non-Classified Controlled Areas (CNC). The more work is done inside the cleanroom, the greater the generation of heat and particles, which will require more powerful HVAC systems and, therefore, higher costs.
It is recommended to follow Annex VII of the GMP Guide published by the Spanish Agency of Medicines and Medical Devices (AEMPS), which replicates the annex corresponding to the European Eudralex Vol IV guide. This document defines the regulatory classification of each cannabis-derived product and the use of classified rooms depending on each case.
In Annex I GMP, we can find the Classification of Cleanrooms and Clean Air Devices, as well as the limits for microbial contamination.
Since the HVAC system is the heart of your cleanroom, it should not be taken lightly. You will need an experienced engineering team to analyze all aspects of the HVAC system in order to design and build a comfortable cleanroom in line with the project’s requirements.
In addition to comfort, HVAC systems for cleanrooms differ from conventional systems by:
- Higher air supply
- Specific airflow patterns
- Use of high-efficiency filters
- Pressure differentials between rooms
Increased air supply provides more air changes per hour in the rooms, with HEPA (High-Efficiency Particulate Air) filters that filter the air pushed into the room multiple times per hour, according to the classification requirements and the volume of the constructed room.
HVAC design for cleanroom areas is determined by the environmental quality of the room (ISO class or Grade), but also by the temperature, humidity, and the pressure differential required between rooms. These prescribed conditions are dictated by the process carried out in the cleanroom and the comfort of the personnel working inside it. The precision of temperature and relative humidity (RH) (+/-) is also an important factor in HVAC system design. The heat produced by both users and equipment must be offset by air conditioning (Validation of operating conditions). Therefore, it is important to know how many people will be working in the cleanroom, which equipment will be installed, and how much heat they generate (in watts).
The principles of automation systems can be applied to your laboratory through a Parameter Control and Automation Software.
This can help you manage energy consumption and costs. You can also configure your control system to turn off the lights, adjust temperatures based on current occupancy or outside weather conditions, or manage air quality (particles) and the humidity of the supplied air.
All your lighting, security, heating and cooling, fire protection, and any other systems in your laboratory can be connected to your automated HVAC systems, such as chillers, cooling towers, boilers, and pumps.
Once everything is adjusted to your optimal settings, you’ll find that not only is everything easier to manage, but resources are no longer wasted due to inefficient configurations. At the same time, you can have a real-time alarm system connected to any mobile phone to notify you of any relevant alarm situation in the facility. An alarm system is essential for the qualification of the entire system and the assurance of pharmaceutical product quality, both in the manufacturing area and in storage before release.
It is essential to integrate all parts of a project under a single direction, including design, engineering, material selection, installation, commissioning, validations/qualifications, and quality systems. Proper project management must take into account several key aspects, such as:
Comprehensive overall project management: technical aspects, cost-related factors, scheduling, and, above all, coordination of all tasks to ensure the final success, including:
- Coordination and management of multiple simultaneous projects and contractors
- Civil works
- Interior architecture: cleanroom panels and accessories
- Energy management techniques
- Air handling and treatment systems
- Electrical and control systems
Your architecture and engineering team must have the knowledge and highly qualified professionals, supported by a broad network of collaborators and specialists in various fields, capable of addressing all aspects related to the comprehensive management of your specific “cannabis laboratory” project. This can be developed as a turnkey solution or by covering only specific parts of the project, ensuring proper coordination with all other participants.
The Quality Assurance (QA) department, together with the Technical Management and the Production Manager, will be responsible for carrying out the Design Qualification (DQ) of the facility in your laboratory, based on predefined specifications, to be integrated into a Pharmaceutical Quality System.
