Fine chemicals and APIs
Active pharmaceutical ingredients (APIs), flammable solvents and explosive products: safe, GMP-compliant facilities in Canada, the United States, Europe and North Africa.
Standards GMP · FDA · ANSM · Health Canada · GCC · ISO 14644 · ASME-BPE · ISPE · ICH Q9 · FMEA · ATEX · NFPA · HSE
PBE Expert brings fine chemicals and API manufacturing its expertise in process engineering, layouts, validation, calibration, maintenance, quality assurance, and GMP and ASME-BPE compliance. Our team includes a Health Canada scientific expert.
Equipment, clean utilities and systems are designed to ATEX and NFPA standards to protect facilities against explosion hazards. Our layouts control clean environments (ISO 14644-4), cross-contamination, crossing flows and safety (FMEA).
Flammable solvents
ATEX zones, mapped at the layout stage.
Around a reactor and its solvents, every volume is assigned a zone. The zone dictates the equipment allowed, the ventilation and the grounding.
- Zone 0An explosive atmosphere is present continuously: inside the reactor and the drum.
- Zone 1One may form during normal operation: around the manway, the vent and the filling point.
- Zone 2One is unlikely, and short-lived if it occurs: the envelope around the installation.
Products and processes
Our services in this industry
Each service in detail, as we deliver it in this industry.
Facility design10 items
- Analysis of preliminary requirements (PURS), laws and regulations
- Site design, industrial master plans and Site Master File (SMF)
- Specifications for production skids, processes, layout, cleanrooms and classified areas
- Clean utility and clean system specifications
- Specifications for storage areas, cold rooms and quality control (QC) laboratories
- Analysis of flows, contamination and cross-contamination (CCC) risks
- Protective equipment specifications
- Functional and technical program (PFT)
- Gowning and personal protective equipment (PPE)
- Establishment licenses, drug (DIN) and natural health product (NPN) registration
Clean systems integration10 items
- Functional analysis of processes, clean utilities and clean systems
- Verification of purity and risk level
- Cross-matrix of equipment, utilities, systems, production rooms and infrastructure
- Selection and layout of manufacturing equipment and systems
- Preserving the integrity and cleanliness of rooms, equipment and products
- Risk management, impact assessment and mitigation (RAPA, GAPA): ICH Q9, FMEA, ATEX
- Design of the warehouse, push-back racking, cold rooms and quality control (QC) laboratory equipment: physicochemical testing, microbiology, R&D
- Treatment of hazardous effluents (ATEX, NFPA): gaseous, liquid and solid
- Support with environmental certificate of authorization (CA) applications
- Energy efficiency, energy, water and material balances, renewable energy integration (trigeneration)
Process engineering (ASME-BPE)15 items
- Sanitary design and process engineering (ASME-BPE), basic and detailed, 3D drawings and performance specifications
- 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
- 3D design of clean systems: HVAC, FFU, CIP, vacuum, drainage…
- 3D design of protective equipment: laminar airflow hoods, weighing booths (UDAF), LEV
- Design of the warehouse, push-back racking, cold rooms and quality control (QC) laboratory equipment: physicochemical testing, microbiology, R&D
- Interlocks between process equipment, systems and building safety systems
- Automation, PLCs, SCADA, integration, BMS, BAS, ERP, SAP, Industry 4.0
Layouts and technical specifications13 items
- Classified areas (grades A, B, C, D, ISO Class 5–8) and integration into architectural drawings (3D)
- Building environmental conditions and product properties into the layout: hygroscopic, electrostatic, explosive and flammable ATEX 1–4, biological containment BSL-1 to BSL-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
- 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), LEV
- Warehouse design, push-back racking, 2–8 °C cold rooms
- Quarantine, stability and release areas for raw materials and drug products (ERP)
- Explosive atmospheres (NFPA, ATEX) and chemical containment (OEL)
- Quality control laboratory layout: physicochemical testing, microbiology, R&D
- Building environmental conditions and product properties into the layout: hygroscopic, electrostatic, explosive and flammable ATEX 1–4, chemical containment OEL 1–6
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, freeze dryers
- Commissioning: DQ, FAT, SAT
- DQ, IQ and OQ qualification of equipment, classified manufacturing rooms and laboratory (QC) equipment: refrigerators and freezers, ovens, stability chambers, CIP, HVAC, PW, compressed air
- 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, licenses and permits
- 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)
- GMP 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 compliance9 items
- Quality assurance and batch release
- 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
- Regulatory affairs: drug registration (DIN) and Drug Establishment Licences (DEL)
Pharmaceutical
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