EU-GMP therapeutic and medical cannabis
EU-GMP and GMP design of therapeutic and medical cannabis facilities: cultivation, extraction and purification, all the way to active ingredients and medicines.
Standards GMP · EU-GMP · GACP · Health Canada · ANSM · ISO 22000 · ISO 14644 · ASME-BPE · ISPE · ATEX · NFPA · WHMIS
PBE Expert is a consulting engineering firm specializing in the GMP design (GPP, GMP) of automated medical cannabis cultivation facilities, supercritical CO₂ extraction of THC and CBD oils (API, DMF), cleanrooms and GMP layouts. Our team includes a Health Canada scientific expert and a MAPAQ expert.
Our projects use a range of cultivation and extraction technologies, with the environmental and dehumidification control required by GMP, EU-GMP, Health Canada’s regulations on cannabis for medical purposes, the ANSM, the rules for natural health products, and the ISO 22000 and ATEX standards.
We work only on projects for medical and pharmaceutical use: cultivation, drying, milling and bagging, extraction and purification of active ingredients, wax removal, and manufacturing of value-added pharmaceutical and nutraceutical products.
EU-GMP therapeutic cannabis
From plant to medicine, in eight steps.
Good agricultural and collection practices (GACP) govern cultivation. As soon as the plant is cut, EU-GMP takes over to protect the active ingredient, all the way to the finished drug.
- 01
Cultivation
Mother plant, cloning or tissue culture, nursery, vegetative growth, then flowering.
- 02
Drying
5 to 15 days, depending on size, room temperature and humidity.
- 03
Trimming
Cutting the flowers, after drying: fresh material deteriorates and grows bacteria and mold.
- 04
Curing
Curing lets the plant and its trichomes, rich in CBD and THC, mature.
- 05
Primary packaging
Protecting the material before extraction and storage.
- 06
Extraction
Separating cannabinoids and terpenes, without solvents.
- 07
Purification
Molecular distillation, chromatography and winterization: a high-purity oil.
- 08
Oil packaging
The active ingredient, ready for formulation into drugs or natural health products.
From harvest on, EU-GMP applies
CBD or THC
One plant, more than 150 active ingredients.
CBD and THC share the same chemical formula, but not the same spatial arrangement, or the same effects. For therapeutic use, non-psychoactive CBD is preferred.
CBD · cannabidiol
Non-psychoactive. Preferred for therapeutic uses.
THC · delta-9-tetrahydrocannabinol
Strongly psychoactive. Used for therapeutic purposes only.
- Morocco1 %
- North America0,3 %
- Europeabout 0.2%
Morocco, once known for its high-THC strains, is now adapting its crops to therapeutic standards.
Choosing wisely
Four ways to grow, none of them perfect.
The choice comes down to cost, target volume, and the pros and cons. Indoor growing is the therapeutic industry’s favorite: outdoors, there is little control, and purification is expensive.
Mobile vertical racking
Many projects delivered by the PBE Expert team, with their advantages and the regulatory points to get right.
Floor growing
The classic canopy, simple to operate.
Vertical rotary growing
Very costly, so rarely chosen.
Greenhouse
Halfway between indoor and outdoor; it takes a greenhouse that prevents condensation and suits the Canadian climate.
Extraction: what the pharmaceutical industry accepts
- Supercritical CO₂ extraction
- Ultrasonic extraction, developed with Polytechnique Montréal
- Microwave extraction
- Ice-water extraction, with care
- Ethanol
- Butane and other hydrocarbons
Solvents leave residues and do not meet pharmaceutical standards.
What we design
Critical equipment, from greenhouse to lab.
HVAC and dehumidification are the biggest item: the slightest weakness creates condensation, and therefore mold.
Facilities
- HVAC and dehumidification
- Cleanroom panels
- Racking, LED lighting and irrigation
- Building management (BMS, BAS) and ERP
- R&D laboratories
- Grinding (trimming)
- Disinfection and odor removal
Process
- Full-spectrum LED lighting
- Clean-out-of-place (COP) tanks and washers
- Clean-in-place (CIP)
- Sterilizers
- Purified water
- Dust collectors and vacuum systems
- Air showers
- Compressed air
- Laminar airflow
Clean utilities
- Process compressed air
- Laminar airflow
- Purified water
- Clean-in-place
- Process vacuum system
Tissue culture
Multiplying genetically identical plants in a sterile environment: genetic control, disease elimination, and rapid large-scale propagation. It requires a sterile laminar-flow area, an autoclave, an incubator, a microscope, a pH meter and artificial lighting.
All the way to the finished product
From natural health products to drugs.
Formulation, drug master file (DMF) development and natural health product registration (NPN) with Health Canada, in EU-GMP-compliant facilities.
CBD oils
Chronic pain, insomnia, anxiety.
Capsules
Halal, kosher and vegan labeling; softgels and gummies.
Dermocosmetics
Hair and skin care, anti-aging cream and CBD sunscreen.
Herbal supplements
Sleep, stress and anxiety, diabetes, prostate health, memory, detox, weight management.
Plus high-value products to register: infused olive oil, hot cannabinoid infusions, essential oils, tea extracts, CBD gummies.
Markets: Canada, Europe and Australia; specialty stores, supermarkets, pharmacies and online sales.
Partnered drug development
- Pharmaceutical laboratories: Morocco, Australia, Canada, Switzerland, United States
- Universities: France
Products and processes
Therapeutic cannabis
From plant to medicine.
EU-GMP governs the whole chain, from growing the plant to the finished medicine. We design every step to clear that bar.
The right standard at every step
Good agricultural and collection practices (GACP) govern cultivation; EU-GMP takes over from harvest onward, first for the active ingredients, then for the medicine.
Solvent-free extraction
Processes accepted in pharmaceuticals, such as supercritical CO₂ extraction, keep residues out of the active ingredient. We have also worked on new extraction technologies with Polytechnique Montréal.
Critical parameters under control
Environmental parameters (CEP), process parameters (CPP) and quality attributes (CQA): water, air and growing medium are controlled to prevent bacteria, yeast and mold.
The right growing method
Indoor, greenhouse or vertical growing on mobile racks: we choose with you based on cost, target volume and regulatory requirements.
All the way to the finished product
Purification, formulation and industrial scale-up, for CBD-based drugs or natural health products.
Our services in this industry
Each service in detail, as we deliver it in this industry.
Facility design14 items
- Analysis of preliminary requirements (PURS), laws and regulations
- Selection of cannabis extraction and THC and CBD purification technologies
- Classification and specifications of cannabis-specific security systems (vault)
- Specifications for production skids, processes, layout, cleanrooms and classified areas
- Irrigation water and greenhouse air conditioning specifications
- Clean utility and pharmaceutical system specifications
- Establishment and cannabis producer licenses, drug (DIN) and natural health product (NPN) registration
- Business plan, feasibility study and project management
- Cultivation site design, industrial master plans and Site Master File (SMF)
- UV bio-decontamination of cannabis plants, air and irrigation water
- Selection of cannabis drying and milling technologies, ATEX safety, energy efficiency
- Irrigation water, lighting, air conditioning and CO₂ specifications
- Specifications for compact indoor cannabis growing equipment
- Specifications for controlled environments and air conditioning in indoor growing (temperature, humidity, illuminance in lux)
Clean systems integration15 items
- Functional analysis of processes, clean utilities and pharmaceutical systems
- Cross-matrix of equipment, utilities, systems, production rooms and infrastructure
- Specifications for storage areas, the THC vault, cold rooms and quality control (QC) laboratories
- Analysis of flows, contamination and cross-contamination (CCC) risks
- Functional and technical program (PFT)
- Specifications for personal protective equipment (PPE), explosion-proof equipment and containment
- Preserving the integrity and asepsis of rooms, equipment and products (THC, CBD…)
- Gowning and personal protective equipment (PPE)
- Risk management, impact assessment and mitigation (RAPA, GAPA): ICH Q9, FMEA, ATEX
- Design of the warehouse, push-back racking, THC vault, cold rooms and quality control (QC) laboratory equipment: physicochemical testing, microbiology, R&D
- Selection and layout of manufacturing equipment and systems
- Treatment of hazardous chemical effluents (OEL): gaseous, liquid and solid
- Support with environmental certificate of authorization (CA) applications
- Energy efficiency, energy, water and material balances, renewable energy integration (trigeneration)
- Support with certificate of authorization (CA) applications and environmental impact studies
Process engineering (ASME-BPE)18 items
- Development of PURS, URS, BOD, detailed design, PFD and P&ID, critical process parameter (CPP) specifications, 3D drawings and performance specifications
- 3D design of cannabis extraction and THC and CBD ingredient purification technologies
- Development of PURS, URS, BOD, detailed design, PFD, P&ID and critical process parameters (CPP): material and interior finish specifications
- Sanitary design: fewer dead legs, optimized slopes and velocities
- Specifications for valves (diaphragm, block-and-bleed), tri-clamp (TC) fittings, pumps, filters and heat exchangers
- 3D design of manufacturing equipment and process skids
- 3D design of formulation, mixing and filling tanks
- 3D design of filling and primary and secondary packaging machines
- 3D design of clean-in-place (CIP) and sanitization skids
- 3D design of process transfer lines (orbital welding)
- 3D design of clean utilities, generation and distribution: PW, PCA, N2, CO₂
- 3D design of pharmaceutical systems: HVAC, FFU, CIP, vacuum, drainage…
- 3D design of containment equipment: isolators, RABS, IBCs, biosafety cabinets
- 3D design of protective equipment: laminar airflow hoods, weighing booths (UDAF), LEV
- Interlocks between process equipment, systems and building safety systems
- Automation, PLCs, SCADA, integration, BMS, BAS, ERP, SAP, Industry 4.0
- 3D design of cannabis drying and milling systems, ATEX safety, energy efficiency
- 3D design of supercritical CO₂ cannabis oil extraction, THC and CBD ingredient purification and dewaxing
Layouts and technical specifications15 items
- Classified areas (grade D, ISO Class 8, CNC) and integration into architectural drawings (3D)
- Building environmental conditions and product properties into the layout: hygroscopic, electrostatic, chemical containment OEL 1–6, explosive and flammable ATEX 1–4
- Development of URS and critical environmental parameters (CEP)
- Layout of personnel, equipment, raw material, primary and secondary packaging material, finished product and waste flows
- Functional grouping, pressure, cleanliness and room classification cascades: classified areas, ATEX, relative humidity, BSL, OEL
- Physical separations (personnel airlocks, PAL; material airlocks, MAL; corridors), plus mechanical, procedural and gowning separations
- Review and approval of airflow diagrams: HVAC, FFU and laminar flow
- Weighing and sampling booths (UDAF)
- Quarantine, stability and release areas for raw materials and drug products (ERP)
- Design of vaults for controlled substances (alcohol, cannabis, THC), QPIC services
- Explosive atmospheres (NFPA, ATEX), biological (BSL) and chemical (OEL) containment
- Quality control laboratory layout: physicochemical testing, microbiology, R&D
- UV bio-decontamination of cannabis plants, air and irrigation water
- Warehouse design: UV bio-decontamination of air and exhaust, odor control, push-back racking, −20 °C freezers, 2–8 °C cold rooms
- In-process controls (IPC): plant cultivation, THC and CBD oil extraction, finished dosage forms
CQV, CSV & maintenance11 items
- Traceability matrix: mapping URS requirements to validation
- Validation Master Plan (VMP)
- Predictive, systemic and preventive maintenance plan
- Metrology: instrument calibration program and traceability
- Temperature and humidity mapping: cold rooms, warehouses, freezers, incubators, ovens and depyrogenation ovens, autoclaves, freeze dryers
- Commissioning: DQ, FAT, SAT
- DQ, IQ and OQ qualification of equipment, classified manufacturing rooms and laboratory (QC) equipment: refrigerators and freezers, autoclaves, isolators, ovens, stability chambers, CIP, HVAC, PW, compressed air, N2
- Sampling plan, bracketing matrix and MACO
- Process, cleaning and sterilization validation (FDA 2011, ANSM 2015)
- Sterilization cycle development
- Computerized system validation (CSV): BMS, PLCs, ERP and SAP software qualification (GAMP, 21 CFR Part 11), data integrity
Compliance audit and GMP FormAction™10 items
- Site GMP compliance certification and licenses
- GMP compliance audit and pre-approval inspection (PAI)
- Inspection readiness plan and procedure: before, during and after
- Corrective and preventive actions: CAPA, RAPA, GAPA
- Remediation plans
- Setting up and managing a change control system
- Continuous improvement and supplier qualification quality audits
- Drafting and review of quality agreements (QAA)
- Drafting the Site Master File (SMF)
- FormAction™: PBE Expert, CPMT-approved training organization (No. 0059104), CIPE and OIQ
Construction project management (EPCMV)13 items
- Engineering, validation and construction project management
- Owner’s engineer services, supplier and contractor selection
- Project schedule, workforce planning, subcontractor coordination
- Cost management, control and optimization
- Technical follow-up and support, shop drawing review and approval
- Approval of monitoring, health and safety plans and procedures (ATEX, NFPA)
- Equipment accessibility, receiving, installation follow-up and commissioning
- Supervision and approval of on-site execution plans
- Engineering tests, troubleshooting and process PLC configuration
- Quality management and control of the work and of facility performance
- Construction progress reports, benchmarking and certificate of completion
- Production and approval of as-built drawings
- Certificate of conformity, release of payments, client acceptance of the facility
Quality assurance and EMA-Annex 1 compliance12 items
- Quality assurance and batch release
- QPIC services for controlled substances and cannabis (THC) vault management
- Procedure writing: SOPs and work instructions
- Operations and health and safety support
- Change control, CAPA, failure mode and effects analysis (FMEA)
- Root cause analysis (RCA)
- Annual product review (APR), IT and data integrity, process capability
- Risk management, assessment and mitigation, impact study (RAPA, GAPA): FMEA, ICH Q9, ATEX, FMD-135
- Industry 4.0: digitization, data collection and integrity, ERP, SAP
- Cannabis producer licenses, DIN (THC) and NPN (CBD) registrations
- Regulatory affairs: drug (DIN) and natural health product (NPN) registration
- Drug Establishment Licences (DEL) and Medical Device Establishment Licences (MDEL)
Pharmaceutical
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