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cGMP Biopharmaceutical Facility Basic Construction cGMP Biopharmaceutical Facility Basic Construction Manufacturing Facilities Different types of facility and factory engineering Primary business plan Specification Systems Consultants, Audit, accreditation body Instrument suppliers Project engineering Main Utilities (W,E,G) Contractor(s) NEW PLANT Location, road and traffic connection Project Engineering Raw Materials Civil Engineering Suppliers? Mechanical engineering Contractors Electrical Engineering Legalization TechnologyProduct(s) Scheduling and Logistic Chemical Engineering Human Resource Marketing and client net-work Types of Biopharmaceutical Facilities Engineering • Conventional • Modular Design Technology / application • Product Based Platform • Cell Factory Based Platform Process Biosafety Class • Dedicated Facility • Multi-purpose Facility • BS1, BS2, BS3 Modular facility is more than prefabricated building!!! Modular concept in Pharmaceutical and Biopharmaceutical Facilities Life-time of Modular Biopharmaceutical Plant Conventional vs Modular Design Conventional Modular Time Speed may governed by many factors (location related) Can cut 6 to 12 months of the project schedule Facility final quality Quality may effected by the level of skilled worker in the area, available raw materials for major construction Allow design of complex, high-quality project in are where is a shortage of skilled worker Site disruption High Low Safety during manufacturing High risk Low risk Cost Usually less than modular by 30% (material, labor cost) Usually higher than conventional 30% Design change Easier if Could be done if consider in the initial Engineering Value (Company assess) Less than Modular High value factory (more attractive for investors) Technology Application Product Platform Based Cell Factory Platform Based Manufacturing facility is designed for one product or certain group of products Flexible platform structure Rigid platform structure Preferable in mid- and small pharmaceutical company Example: Insulin Production in Novo Nordisk and Elli Lilly Preferable for TollManufacturing facility Product Based Platform vs Cell factory Based Platform Product Based Platform Cell factory Based Platform Less Flexible More flexible Dedicated for one product (or branch of product) Can produce different types of products from the same biofactory (without or with minimal modification) Limited use as Toll-Manufacturing Less Expensive For well-establish products Low-Value facility (in case of sale) Easily applied as Toll-Manufacturing More expensive For well-establish products and new products High-value facility (in case of sale) Biosafety Level BSL AGENTS PRACTISE SAFETY EQUIPMENT (Primary Barriers) FACILITIES (Secondary Barriers) 1 Not known to consistently cause disease in healthy human adults Standard animal care and management practice, including appropriate medical surveillance programs As required for normal care of each species Standard animal facility • no recirculation of exhaust air • directional air flow recommended • Handwashing sink recommended 2 Associated with human disease. Hazard: Precutaneous exposure, ingestion, mucous membrane exposure A BSL-1 practice plus: • Limited access • Biohazard warning signs • Sharps precautions • Biosafety manual • decontamination of all infections wastes and of animal cages prior to washing A BSL-1 equipment plus primary barriers: containment equipment appropriate for animal species, PPEs, laboratory coats, gloves, face and respiratory protection as needed A BSL-1 facility plus: • autoclave available • handwashing sink available in the animal room • mechanical cage washer used Biosafety Level (cont.) BSL AGENTS PRACTISE SAFETY EQUIPMENT (Primary Barriers) FACILITIES (Secondary Barriers) 3 Indigenous or exotic agents with potential for aerosol transmission: disease may have serious health effects A BSL-2 practice plus: • controlled access • decontamination of clothing before laundring • cages decontaminated before bedding removed • disinfected foot bath as needed A BSL-2 equipment plus • Containment equipment for housing animals and cage dumping activities •Class I or II BSCs available for manipulative procedures (inoculation, necropsy) that may create infectious aerosols. PPEs appropriate respiratory protection. A BSL-2 facility plus • physical separation from access corridors • self-closing, double door access • sealed windows • autoclave available in facility 4 Dangerous or exotic agents that pose high risk of life treating disease; aerosol transmission, or isolated agents with unknown risk of transmission A BSL-3 practice plus: • entrance through change room where personal clothing is renoved and laboratory clothing is put on; shower on exiting • all wastes are decontaminated before removal from the facility A BSL-3 equipment plus • Maximum containment equipment (i.e. Class III BSC or xxx containment equipment in combination with full body, airsupplied positive pressure, personnel suit) used for all procedures and activities A BSL-3 facility plus • separate building or isolated zone • dedicated supply and exhaust vacuum and decontamination systems • other requirement outlined in the lab Special Safety Requirement High Sporulating fungal cultivation Pichia pastoris cultivation Vaccine production using pathogens Vaccination plan Air born spore Controlled access Using of toxic, flammable substrate (methanol) Spore germinating in filter system and surface Special equipment Design Special treatment of biomaterial HVAC (differential pressure) Recommended Facility and Practice for BSL 2 & 3 BSL Agents Practice Safety Equipments (Primary Barriers) Facilities (Secondry Barriers) 2 Associated with human disease. Hazard comes from autoinoculation, Ingestion, mucous membrane exposure Standard Microbiological Practice plus • Biohazard sign • sharps precautions • Biosafety manual defining any needed waste decontamination or medical surveillance policies Primary barriers involving Class I physical containment devices used for all manipulations of agents that cause splashed or aerosols of infectious materials; personnel protection equipment involving protective lab, clothing, gloves, respiratory protection when required Open bench top sink required plus autoclave available 3 Indigenous or exotic agents with potential for aerosol transmission: disease may have serious or lethal consequences Similar to BSL-2 Similar to BSL-2 BSL-2 plus • physical separation from access corridors • self-closing double door access •Exhaust air not recirculated •Negative airflow into laboratory Primary Business Plant (Cost Estimation) Technology Facility required (Process availability) GMP requirement Technical Decision Facility Cost Process Cost Reviewing by consultation committee Project Cost (35%) Let’s Start Our Facility! Project Concept Project Objective (product, market etc) Project Basic Idea Technical data, Know-How, Consultant Basic design Develop Options Change / Revision Review Options Complete Concept Overall Cost Estimation Project Contractor(s) Fully Turn-Key approach (including Technology Transfer) • (Build/ Design/ cGMP/ Validation. Etc…) • Plus (Know-How, trainning, SOP, PV) Fully Turn-key approach • (Build/ design/ cGMP/ Validation, etc…) Major Contractor Approach • (Building, electrical, equipment, HVAC) Fully Client Managed • all contracts managed by the client (sometimes, more than 30 contracts!) What are the cGMP regulation which we should follow in our new facility? Would you like to continue? No or Yes Go to next lecture