GOOD MANUFACTURING PRACTICE FOR BIOPROCESS ENGINEERING (ERT 421). Huzairy Hassan School of Bioprocess Engineering UniMAP. What is Bioprocess Engineering?.
GOOD MANUFACTURING PRACTICE FOR BIOPROCESS ENGINEERING(ERT 421)
School of Bioprocess Engineering
Bioprocess Engineers work at the frontiers of biological and engineering sciences to “Bring Engineering To Life” through the conversion of biological materials into other forms needed by mankind.
Application areas associated: poduction of biofuels, design and operation of fermentation systems, development of food processing systems, application and testing of product separation technologies, design of instrumentation to monitor and control biological processes.
What is GMP ?
those activities performed throughout the project life-cycle, which ensures that it will be easy and natural to operate the completed facility in accordance with current Good Manufacturing Practice.
means from project inception through feasibility studies / conceptual design, engineering, construction, installation, start-up, operation, maintenance to final plant decommissioning or modification.
GMP is controlled by the US Code of Federal Regulation (CFR) 21 in the USA.
- US Code of Federal Regulations CFR 21 Parts 210 and 211 (Drugs and products)
- EU GMP Directive 91/356/EEC, Commission Directive Laying Down the Principles and Guidelines of GMP .
2) Guides, guidelines, point to consider
- FDA Guide to Inspection of Bulk Pharmaceutical Chemical Manufacturing
- FDA Guide to Inspection of Validation of Cleaning
- means what the facility is used for
3) Category of the product and production processes employed
- most active ingredients are manufactured by;
4) Facility and Market locations
- cGMPs regulations are produced by a number of different countries or groups of countries world-wide, in addition to WHO. Clarification should be sought from the pharmaceutical manufacturer before the design commences.
- closed or open (piping and equipment, expose to environment- measure to prevent contamination)
- level of batch to batch integrity required (simultaneous filling self-emptying vessels, cleaning, drying, sterilization between batches)
-site location and layout – existing site, brown and green field, and overall site layout
-facility layout – cored vs. linear layout, transfer corridor, segregation of areas, environment, containment strategy, security etc.
3) Automation Strategy issues
- level of technology, use of design tools and models
- availability / redundancy, modularization / expansion
- instrumentation / cabling / field devices
- paperless batch records, electronic signatures.
4) Flow issues
- people (security, access, occupancy level)
- equipment (mobile or fixed, use of hard piping, cross-
- components / materials (materials handling systems, cross-
contamination / mix-ups)
5) Regulatory issues
- stage of development and production, category of the product (sterile medical, biological medical, herbal medicinal, medical gases, liquid, creams, tablets etc) and production process employed, facility location etc.
6) Validation Strategy issues
- validation required, validation team(s), validation plan(s).
1)Facilities and environment
- local environmental considerations
- suitability / acceptability of physical segregation of processes for manufacturing and holding products
- overall layout of the facility
- general layout of production processes
- assessment of the environmental classification of the various areas against the level of quality required by the product
- airflow regime (turbulent or laminar)
- air pressure differentials between areas
- humidity, etc.
2) Services and Utilities
example: high purity water systems – WFI systems
- assessment of the proposed water quality against the level of quality required by the product
- materials of construction (piping, gaskets, valve diaphragms)
- internal surface finishes (electropolishing, passivation)
- water pre-treatment and control
- system sizing
- key design considerations (flow rates, minimum deadlegs with no cavities, vents, drainage air gaps)
- use of security devices
- instrumentation and control of critical process parameters (T, velocity, etc.)
- adverse operating conditions
Typical GMP criteria for WFI
- quality to conform to compendia requirements (USP)
- production to be by distillation (ex: RO) from purified water and to conform to USP
- WFI to be sterile and pyrogen free with an action limit set to less than 10 CFU/100ml (Colony Forming Units) with a sample size of between 100 and 300 ml and an endotoxin level < 0.25 EU/ml.
3) Personnel Flows
--> the influence personnel have on the quality of the product that might be caused by their contact with the product.
4) Material Flows
all the movement of materials
5) Equipment Design
- pedigree of the machine (established for pharmaceutical use/ specially developed prototype)
- pedigree of the manufacturer
- materials of construction and surface finishes of primary and secondary contact parts (i.e. primary – direct product contact; secondary – contact with local environment)
- equipment sizing
- instrumentation and control of critical process parameters
- methods and adequacy of cleaning and sanitization
For equipment and pipework that does not come into contact with the product components, there are no specific GMP requirements.
1)Organizing the GMP design review team
2) Information required to perform the review
- specification of the pharmaceutical product and manufacturing process
- specification of the equipment and facility
3) Divide-up the facility into manageable sized areas
- Bulk pharmaceutical chemical manufacturing
- secondary manufacturing
1)Find SOP for:
- Storing and Using Poisonous or Toxic Chemicals
- Personal Hygiene
2)What is HACCP?