Flashcards in Nancy: Plant Design Deck (22):
What is the purpose of designing a manufacturing process?
1. Can determine the cost of the manufacture
2. Form of dose (tablet, suspension)
3. Formulation of API (excipient)
4. Stability of formulated dose
5. Sterility level
6. Dictate: individual processes, packaging and order of processes
7. Plant clean level, size of plant and physical layout plant
How are small molecule drugs such as tablets in delivery, orally, stability and sterility?
1. Delivery: simple tablet form
2. Oral: No enteric pathogens and avoid spoilage
3. Stability: High, no special conditions needed
4. Sterility: Raw materials likely to be clean, formulate in clean environment and equipment sanitation and QC needed
How are therapeutic monoclonal antibodies (targets specific antigens) used in injections in: delivery, parentally, stability and sterility?
1. Delivery: need to be simple for direct injection and dose control
2. Parental: SAL (sterility assurance level), has to be sterile
3. Stability: Low, cannot be dried, must be in solution
4. Sterility: Formulated antibody solution must be sterilised and have antiviral treatment before packaging
How are Eye drop drug solutions used in: delivery, ocular, stability and sterility?
1. Delivery: Direct dropper or administation or multi-use dropper
2. Ocular: mid level sterile
3. Stability: Low, cannot be dried, needs to be in solution
4. Sterility: Could design different processes depending on preference, single use disposable? Multi use?
What is the design decisions when making sterile products for a typical parental solutions?
1. Manufacture and formulate
2. Filter and sterilise
3. Aseptic fill
4. Aseptic packaging
What is the design decisions when making sterile products for a dressing, syringes that are all in plastic and paper laminated packaging?
1. Manufacture and formulate
3. Sterilise in bulk by gamma irradiation
What are the four key concepts plant design revolves around?
1. GMP (Good manufacturing practice)
2. Special building features- organisation, keeping it clean
3. Importance of workers
4. QA and QC (plus regulatory submission)
What is the basis of modern GMP (good manufacturing process)? (IMPORTANT)
Cannot be tested into a batch of product but must be built into each batch of the product during all stages of manufacturing
What is the main leading body that maintains the cGMP guidelines?
1. WHO (world health organisation)
2. EU guide to GMP
What does plant design mainly revolve around?
Simple flow of material which:
1. Controls quality (must be high quality and consistent) and safety of inputs
2. Safeguards during processing
3. Ensures quality is preserved after distribution (prevent cross contamination)
zones physically seperate each level of operation
What are the main sources of contamination?
1. Supply chain:
All ingredients, API, excipients, water and packaging
Equipment and people
Droplets and humans shed skin
How are sources of contamination managed in plant design?
1. Building design and fittings all focussed on avoiding any material or microbial contamination
2. Once all input elements are checked and recorded as:
- Clean and pure
3. Plant designed to keep them this way
Give examples of what the critical processing area involves?
2. Processing fill and finish
What is the purpose of the clean area?
1, Protective envelope to minimise risk to critical area
What is the transition zone?
1. Brings people
2. Material from external to M' fact in controlled manner
What is the external area?
1. Street office
Describe what the conditions are like in the clean room (middle floor)?
1. Air supply
2. Air distribution
3. Filtration of air supply
4. Materials of construction
5. Operating procedures
Regulated to control air-bourne particle concentrations
How are workers dressed in the plant?
1. Personal gowns
2. Shouldn't shed any particles as it will get into product
3. Cover all hairs and beards
What are the interior surfaces in a plant like?
1. Smooth with no cracks (easy to clean)
2. Bacteria and dust get trapped in cracks
3. Impervious doesn't let liquid in
4. Filtration and fillings
What is classified by the regulation?
1. HVAC (heating, ventilation, air condition)
2. Room construction
3. Room finishes
4. Air change rates (AC/h)
5. Fixtures and fittings
6. Personal gowns
Why must air flow be controlled?
1. Flow always clean- less clean zones: air pressure controlled
2. Conventional turbulent flow
3. Laminar HEPA (high efficiency air filter) filtered flow