Facility design Flashcards
New Facility/Changes to Facility Considerations (PLUG PEP FC)
PRODUCT TYPE
Sterile or Non-sterile
Highly sensitising or highly potent (penicillins (AB), cephalosporins (AB), steroids, hormones, cytotoxics) Separate production area or possibly separation though control
LICENCE MA, MIA
MANUFACTURING/PACKAGING PROCESS
Operations being performed
Room classification – cleanrooms required?
EQUIPMENT
Product dedicated/Multi-product
Design
Cleaning
FLOW (Materials and People)
UTILITIES
HVAC, Water, Steam, Compressed Gases, Temperature, Humidity, Pressure Cascades
GOODS RECEIPT/STORAGE
CONTAMINATION CONTROL
Cleaning – routine disinfection/sanitisation
Environmental Monitoring Programme
Gowning
PEOPLE
Legislation/Guidance for Facility Design and Operation
ISPE baseline guides Vertical (facility type) and Horizontal (utility system)
ISPE GAMP Guides for Good Automated Manufacturing Practice for computer systems and validation of automated systems
EN285 Steam sterilisers
EN554 Steam sterilisation validation and control
EN1822 HEPA filters
EN779 Lower efficiency filters
ASTM International Standards filter testing, c/room clothing particulate levels
Facility airflow considerations
- Grade D: >20 air changes/hr
- Differential Pressures
- C/room at overpressure
- Exhaust air filtered via HEPA filter
Technology Transfer
Transfer of manufacturing process and control tests between sites
Scale up of the process to full scale manufacturing
Objective: Demonstrate product can be consistently manu to approp quality level. Must comply with registered specs & be bioequiv to product used in CTs.
Key elements of technology transfer:
Manage via Change Control
Variations to MA and MIA
Establish TT team (cross-site and cross-departmental)
Approved TT plan details of what is being transferred
Manufacturing / Packaging / Analytical Methods / Cleaning process and methods
Equipment requirements
Material requirements inc. transportation
Product development and validation history (M3)
All relevant documentation supplied before TT (inc. PQRs)
Gap assessment at receiving site identify gaps (reg & tech)
Training requirements visit to transferring site pre TT
Consider placebo/training batch manufacture to determine capability
QRA review existing QRAs for impact
TT process documented:
TT Project Plan
Protocol inc. pre-defined acceptance criteria, CPPs & CQAs
Final report documents results and outcome of TT
Technical assessment of materials/equipment inc. CPPs
Method transfer for analytical methods
Validation of process & equipment at receiving site following TT
Stability batches placed on stability following TT
Management of post transfer activities ongoing support, consider QTA
Knowledge transfer NB and often overlooked
HVAC
- Provide high quality filtered air, particulates and bacteria free
- Protect product from risk of contam. and cross contam.
- Remove contaminated air through air change rates & airflow
- Maintain air flows and pressure diff between areas & outside
- Provide comfortable working environment (temp/RH)
Facility Contamination and Cross-Contamination
Principle of GMP to prevent mix-ups, contamination & cross-contamination
Controls inc. technical & organisational measures, dedicated facilities, closed systems, cleaning and CV
Organisational: Separation of critical activities and certain product categories
Campaign working
Cleaning between campaigns
Work upwards in strengths
Technical: Design of premises and utilities. Layout designed to give suitable:
Materials and equipment flows
Personnel access
Maintenance access
Finishes to allow adequate cleaning and achieve required environmental stds
Ventilation systems designed to provide product protection
Cleaning Validation/Verification
Clean Room Classifications
Uncontrolled: No filtered air supply
Controlled: Filtered air supply, input air quality specified but room not classified, limited EM. E.g. non-sterile dosage form manufacture using moderate efficiency filters (EU8) and 6-12 air changes per hour.
Classified: Room air quality specified and monitored in line with room classification (ISO 14644/Annex 1). Required for sterile manufacture, ‘high risk’ non sterile dosage form manufacture, e.g. liquids, creams, ointments, inhalers. HEPA filtration with minimum >20 air changes per hour
Facility Finish and Design
Varies depending on use ISPE guidance for rec’d finishes defined by area type
Non-sterile facility: Smooth cleanable surfaces, no hard to clean areas, smooth covered walls, floors, ceilings, services enclosed, trapped drains only, controlled access, change facilities, controlled materials entry and exit, effective ventilation
Sterile facility: Smooth non-shedding surfaces, coved walls, floors and ceilings, no dust traps, flush fittings and glazing, no drains, multi stage personnel changing facilities, controlled materials entry and exit, through sterilisers or using sanitisation process, multi stage processing cleanrooms
Legislation/Guidance for API Facility Design/Operation
EudraLex Vol 4 Part II
ISPE Baseline Guide for APIs detailed guidance on finishes and HVAC design.
Buildings and facilities should be designed and constructed to:
Facilitate cleaning, maintenance & operations approp to type & stage of manu.
Minimise potential contamination.
Level of GMP applied increases throughout the manufacturing process. Standards for final stage of API manufacture should be the same as the first stage of dosage form production.
Steriles products full GMP throughout API manufacture
Facility Utility Considerations
HVAC: Controlled by Building Management System that maintains the environment.
Temperature, Humidity
Pressure Differentials/Cascades to maintain positive/ negative environment
Negative Pressure: Contain in room – Clean Corridor Concept (Room - to corridor)
Positive Pressure: Push out of room – Cleanroom Concept (Room + to corridor)
HVAC Air Supply filtered (HEPA filters where appropriate)
Airflow and air changes
Water: Grade of water depends on use (EMA Water Quality Guideline)
Steam Quality:
Plant/boiler steam: Mainly used for heating
Clean steam: Meet pharm. stds for chemical purity, be sterile and pyrogen free. Used in sterilisation process and for SIP of product contact surfaces.
Compressed Gases: Receipt (tankers) and testing control NB, routine monitoring for particulates, moisture and oxygen.
Drainage and venting systems
Vacuum systems
Heating and cooling fluid systems
Bulk storage systems for solvents, reagents and raw materials
Facility flow
Logical and orderly flow for people/materials/equipment
One way flow desirable but not essential
Differential pressures: maintain positive/negative environment
API Specific: Protect from insects, birds etc. as API production equipment can be located outside provided a closed process is used
