PTM Flashcards
What are the issues with the pharmaceutical industry?
Issues with batch production in pharma
- Batch is very versatile but extremely slow and not very precise.
- There is approximately a 2- year timeframe from the start to the end of the process development (primary manufacturing part only).
- This approach requires capital intensive investment very early in product development to allow the running of clinical studies.
- This same process needs to be able to ramp up to full production.
- Therefore very high cost associated with failure.
- The batch approach is also not very agile to deploy around the world and leads to centralised manufacturing, whereas local production and distributed manufacturing may be important for future cost reduction.
- In batch manufacturing, it is difficult to reconfigure or change the design and this again adds to the cost of the products.
From lectures
- A large % of products in different phases fail, but clinic must be supplied for years and plan for success
- If launched, typically market is supplied for 10 years
- Demand volume is uncertain
- Once patent has expired, product volumes are likely to fall
- Orders must always be fulfilled
- Must manufacture to strict codes
It’s hard to plan
- If product fails, equipment can be reused
- But it is labour intensive and slow in making the product
What is the solution to the problems in the pharmaceutical industry?
Try to be agile instead:
- Repurposed or negligible cost or time to change
- Precise
- Fast to supply
- Low labour
3 ideas:
-
Modularisation
- System is deconstructed into more independent units (modules)
- Useful for reducing the complexity of the system
- Leads to
- Replication, mobility, standardisation means
- Increased speed in delivery and lower cost
- Digitalisation
- Leads to:
- Faster connected, reduction of downtime due to automation
- Data for predictive modelling
- Maintenance, how to do a task, deep learning, automating design
- Leads to:
- Process intensificationusing continuous manufacture
- Footprint is smaller for same output
- Leads to small precise plant
- Continuous processing is a technology that provides, small precise replicatable production.
One approach
- Substituting a number of the batch steps with a continuous process.
- The approach requires the design of a modular continuous manufacturing plant.
- This building-block approach allows
- reconfiguration, agility to deploy, agility to re-usein other processes if the product fails,
- benefit of the precision and higher levels of automation achieved in continuous manufacturing and
- the ability to build closer to the point of distribution rather than have large centralised manufacturing sites.
- Each module is a unit operation and savings will be realised even by replacing a sequence of a few of the batch steps.
It may be noted that pharmaceutical companies are risk averse about moving the entire process to continuous manufacturing because of the challenge of controlling crystallisation and the significant knowledge currently in place that surrounds batch processing in this field.
Give some facts oil and gas in the UK
- Oil and gas provides more than 75% of UK’s total primary energy
- By 2035 will still be 66%
- Electricity, transportation and heating account for roughly one third of the UK’s primary energy demand, with oil for transport and gas for heating dominating these markets.
- Natural gas is the cleanest of all fossil fuels, burning nearly twice as efficiency as coal and producing much less CO2 per unit of energy
What are the different production fluids (oil, gas, etc.)?
Different production fluids
- Crude oil is a mixture of 200 or more organic compounds, mostly hydrocarbons. Graded according to API number (higher API = lighter, thinner crude)
- Natural gas as used by consumers is almost entirely methane. Wellhead gas requires significant additional processing to meet transportation pipeline specifications.
- Condensates or natural gas liquids associated with natural gas are a valuable by product. They are widely used as raw materials for oil refineries and petrochemical plants.
Describe the process of oil production from wellhead to to export?
Production facilities can vary from onshore wells to offshore floating wells.
Process from production wellheads to export:
- Production well head
- Production separators:
- Separate water, crude oil and natural gas
- Gas
- Compressed
- Gas meter
- Pig launcher
- Gas pipeline
- Oil
- Storage
- Crude pump
- Oil meter
- Pig launcher
- Oil pipeline
Describe the production well head
Production well head
- Assembly of valves, spools, pressure gauges and chokes to control production
- Sits on top of the oil/gas well, leading down to the reservoir
- Dry completions are either onshore or on the deck of an offshore structure
- Wet completions are subsea, below the surface
Describe production separators
Production separators:
- Most wells give a combination of gas, oil and water that must be separated
- Gravity separation: well flow is fed into a horizontal vessel
- Residence time is typically 5 minutes, allowing the gas to bubble out, water to settle at bottom and oil to be taken out in the middle
- Pressure is often reduced in several stages (high pressure separator, low pressure separator etc.)
- Horizontal separators:
- large liquid handling capacity
- Sufficient time for settle out of liquid droplets from the gas
- Vertical separators (scrubbers)
- High gas volumes
- Small footprint area
Describe gas compression
Compression
- Gas from separators has lost so much pressure that it must be recompressed to be transported
- Turbine compressors gain energy by using a small proportion of natural gas that they compress
- Turbine operates a centrifugal compressor, which contains a type of fan that compresses and pumps the natural gas
- Compression system includes a large “train” of associated equipment such as scrubbers (removing liquid droplets) and heat exchanges, lube oil treatment etc.
Describe the different types of heat exchangers
Heat exchanger needed after to remove heatShell and tube heat exchangers
- Consists of a bundle of tubes enclosed in a cylindrical shell. The ends of the tubes are fitted into tube sheets, which separate the shell side and tube side fluids. Baffles provided to direct the fluid flow and support tubes.
- Can be heavy and space consuming
- Suitable for high pressure operation
- Robust designs with long operational history
Plate heat exchangers
- Series of corrugated, pressed metal plates clamped together
- Offshore the use of plate heat exchanges has become universal due to compact size and low weight.
- Oil cooling prior to storage or pipeline export and some low-pressure gas duties.
Printed circuit heat exchangers
- Constructed from flat metal plates with chemically milled fluid flow channels.
- High heat transfer surface densities
- Suitable for high pressure applications and wide temp range
- Compact design leading to substantial weight and space savings
- Low maintenance due to corrosion resistant materials and all welded construction
Air cooled heat exchangers
- Where cooling water is too costly.
- Multiple calculations are required to produce an optimum design considering air flow rate, tube design, fin types etc.
What are oil terminals and their functions?
What are gas terminals and their functions?
Oil: processed onshore rather than offshore as it is easier.
Oil terminals are intermediate oil gathering and distribution stations between offshore oil production locations and onshore oil processing facilities (refineries).
Basic functions:
- Reception of crude oil
- Stabilisation of crude oil (dehydration/desalting, gas/water treatment)
- Fractionation of associated gas into propane and butane
- Storage of stabilised crude, LPG
- Export/ shipment of products into tankers for distribution to refineries
Gas terminals:
- Function of the terminal is to process the raw gas to provide sales quality gas and liquid hydrocarbon by products.
- Gas arrives onshore at around 3 degrees.
- Internal cleaning and inspection of the pipeline is done with pigs (dirt/debris/wax/scale removed)
- Inlet gas receiver catches slugs of liquid from the pipeline
What is the detailed process from wellhead to production of oil and gas
Process from production wellheads to export:
Production well head
- Assembly of valves, spools, pressure gauges and chokes to control production
- Sits on top of the oil/gas well, leading down to the reservoir
- Dry completions are either onshore or on the deck of an offshore structure
- Wet completions are subsea, below the surface
Production separators:
- Most wells give a combination of gas, oil and water that must be separated
- Gravity separation: well flow is fed into a horizontal vessel
- Residence time is typically 5 minutes, allowing the gas to bubble out, water to settle at bottom and oil to be taken out in the middle
- Pressure is often reduced in several stages (high pressure separator, low pressure separator etc.)
- Horizontal separators:
- large liquid handling capacity
- Sufficient time for settle out of liquid droplets from the gas
- Vertical separators (scrubbers)
- High gas volumes
- Small footprint area
Gas Compression
- Gas from separators has lost so much pressure that it must be recompressed to be transported
- Turbine compressors gain energy by using a small proportion of natural gas that they compress
- Turbine operates a centrifugal compressor, which contains a type of fan that compresses and pumps the natural gas
- Compression system includes a large “train” of associated equipment such as scrubbers (removing liquid droplets) and heat exchanges, lube oil treatment etc.
Heat exchanger needed after to remove heat
- Shell and tube heat exchangers
- Consists of a bundle of tubes enclosed in a cylindrical shell. The ends of the tubes are fitted into tube sheets, which separate the shell side and tube side fluids. Baffles provided to direct the fluid flow and support tubes.
- Can be heavy and space consuming
- Suitable for high pressure operation
- Robust designs with long operational history
- Plate heat exchangers
- Series of corrugated, pressed metal plates clamped together
- Offshore the use of plate heat exchanges has become universal due to compact size and low weight.
- Oil cooling prior to storage or pipeline export and some low-pressure gas duties.
- Printed circuit heat exchangers
- Constructed from flat metal plates with chemically milled fluid flow channels.
- High heat transfer surface densities
- Suitable for high pressure applications and wide temp range
- Compact design leading to substantial weight and space savings
- Low maintenance due to corrosion resistant materials and all welded construction
Gas meter
Pig launcher
Gas pipeline
Oil: processed onshore rather than offshore. Onshore processing plants called terminals.
Storage
Crude pump
Oil meter
Pig launcher
Oil pipeline
How is a superconducting magnet made?
How to make a superconducting magnet
Wind coils
- 20-50 km wire per magnet
- Wire costs approx. $1/m
- Coil diameters between 1.5-2m
- Coil weights 20-980 kg
Pot coils in epoxy resin
Assemble coils
Check homogeneity at RT
Joint magnet (joints must have resistance <10^-11 ohms@ 4K)
- Pair up leads to cancel forces
- Dissolve copper matrix with conc. Acid
Fit magnet to cryostat (heat transfer to be <1W)
Pressure test cryostat
Chill magnet to 4K using 3,000-5,000 litres of liquid He
Run magnet to field (460-700A DC @10V)
Test magnet and cryostat
Ship magnet (if shipped cold ‘time to dry’ is 20-28 days)
What are the common failure modes for superconducting magnets?
Quench:
- wire stops superconducting, becomes resistive and 1000 litres of liquid He suddenly boil away
Electrical short
Homogeneity
- Lack of either intrinsic or induced by site factors
Decay
- Full field not maintained between service intervals – maximum loss allowed is 0.1ppm/hr
Boil off problems
- Cryostat performance poor – system will require frequent topping up of liquid helium
- Poor vacuum (leak)
- Thermal short
- Poor connection to refrigeration
What are the safety hazards in superconducting magnets?
What are the new trends in superconducting magnets?
What are the safety hazards:
- Strong magnetic fields
- Extreme cold
- Large heavy magnets
- Strong acids – HF and HNO3
What are the new trends:
- Minimum He system/ ‘dry’ system
- Higher fields
- Warm superconductors
- Cheaper systems: suitable for unsophisticated/low tech environments
Explain the puttick grid? Explain the different aspects the puttick grid drives?
Puttick grid
The way a product is manufactured should be governed by:
- Production volume and market uncertainty
- Intrinsic product complexity (including variety)
These aspects drive all relevant parameters:
- Product design & material choice
- Production methods, tooling and equipment choice
- Degree of automation
- Degree of integration
- Location, logistics and distribution
- Assembly configuration choices
- People and organisation
- Production control systems
What are the factors influencing the type of and extent of automation
- Product volume and variety
- Expected product life span
- Market uncertainty
- Process novelty
- Component/task variability
- Precision, cleanliness, quality, regulatory etc.
- Component complexity
What are the different assembly system configurations?
What are the different assembly system configurations?
- Manual: people do the job
- Mechanised: machines help people do the job
- Hard automated: machines do job (same every time)
- Turntable
- Indexing: where different elements of production are at different rotation locations
- Constant velocity: bottle production
- Track
- Pallet based. Asynchronous
- Indexing/synchronous: cars production
- Turntable
- Flexibly automated: robots and other software driven machines do job (can be different)
- Based on off the shelf robots: SCARA, anthropomorphic, cartesian, delta etc.
- Custom multiaxis
What are the examples of the necessary supporting processes and infrastructures?
How much software does an automation system need?
What are the examples of the necessary supporting processes and infrastructures?
- Packaging and feeding
- Order retained: bandoliers, tubes
- Order re-gained: bowl feeders, centrifugal feeds
- Sensory systems: proximity imaging, gauging
- Actuators: pneumatic, hydraulic, servo electric, solenoid
- Conveyors, turntables, x-y tables
- Proprietary operating systems and programming languages
- Message: exploit what’s out there and don’t reinvent the wheel
Why is injection moulding used for manufacturing?
Leading process for manufacturing of plastic products: high volume, identical product
Cost:
- High tooling cost depending on complexity and number of cavities
- Low unit cost
Typical application
- Automotive
- Consumer electronics
- Appliances
- Industrial products
- Household products
Suitability:
- High volume mass production
Quality
- Very high surface finish
- High repeatable process
Related processes
- Reaction injection moulding
- Thermoforming
- Vacuum casting
Speed
- Cycles between 30 and 60 secs
How does an injection moulding machine work?
How does an injection moulding machine look and work?
- Clamping
- Injection
- Cooling
- Ejection
- Plastic granules loaded into hopper
- The screw within a heated barrel forcing the polymer towards the nozzle.
- The clamping of the mould cavity and the mould.
- The injection of the molten polymer (details about runners and shot)
- The cooling of the mould
- The ejection of the component (ejection pins)
- The final removal of the sprue
- Recycling of waste back into the process
Give examples of potential defects that can occur in injection moulded parts.
Which of these issues can CAD solve?
Give examples of potential defects that can occur in injection moulded parts
- Short shot
- Humidity
- Drying used pre process
- Contamination by other coloured granules
- Sink marks or Voids:
- Depressions on one side of a component due to the thicker section or a large feature on the other side. These thicker areas shrink upon cooling to give the depression. The cooling time needs to be sufficient to allow cooling in the mould.
- Knit lines and Weld lines:
- This appears as a discoloured line, where molten plastics meet as they flow from different parts of the mould. The flow fronts do not bond correctly, most often due to partial solidification.
- Warping
- A deformation or bending where there is uneven shrinkage across the component. This is usually due to uneven cooling across the material. Different cooling rates or rapid cooling leads to internal stresses.
- Flash
- If the clamp force is not sufficient, the mould/die are not precisely manufactured, the mould/die are worn or corroded or if the injection pressure is too high, there will be a leak of the polymer around the join leading to flashing.
Which of these issues can CAD solve?
CAD based analysis:
- Warp analysis: used to predict shrinkage as a result of stress on the mould
- Cooling analysis: checks for uniform cooling throughout the mould. Potentially reducing cooling time
What are the important specs for injection moulding?
What are the important specs for injection moulding?
- Clamping force
- Keep as low as possible: reduce wear and tear without generating flash
- Injection pressure
- Mould internal pressure curve
- First speed of filling must be adequate
- Switch over to holding pressure
- No residual pressure when mould is opened
- Mould internal pressure curve
- Shot size: volume of the part plus runners and gates
- Closing force: needed to hold mould for packing and cooling
- Number of cavities x projected parting line part surface x mould cavity pressure
Give a closing force example for injection moulding (see picture)
What are the other techniques for injection moulding?
What are the other techniques for injection moulding?
Gas assisted injection moulding
- Shut off valve closes to prevent plastic material seeping back into injection head. Gas is injected into the core of the plastic, which is still molten. The gas progresses the molten plastic into the extremities of the cavity
Multi shot
Blow moulding
Give some advanced applications of polymers
Advanced applications of polymers:
Self-healing
Drug delivery
- Release from surface
- Diffuse from swollen network
- Release due to erosion
- Efficiency depends on chemical structure and porosity of particle
Organic solar cells
LEDs
- Holes injected into conductive layer, electrons injected in emissive layer, recombine at interface emitting light
What is hydrodynamic volume?
What is hydrodynamic volume?
It is an indication of the expansion factor alpha
High alpha means it is a good solvent
Solvent polymer interactions are higher than polymer polymer interactions
What properties depend on molecular weight?
What are the different measures for molecular weight?
What properties depend on molecular weight?
- Modulus
- Strength
- Viscosity
- Melting temperature
- Glass transition temperature
What is gel permeation chromotography
Gel permeation chromatography
- Type of size exclusion chromatography
- Measures molecular weight distribution and structure
- Separates based on the hydrodynamic volume of the polymer
- Higher MW, higher hydrodynamic volume
- Pores exclude large molecules, so they move faster through the column
Factors affecting GPC spectrum:
- Sample interaction with column
- Temperature
- Flow rate
- Gel permeation chromatography is a separation technique.
- The columns contained insoluble beads with a rigid pore structure.
- The pores can exclude very large molecules, allow partial permeation of medium sized polymers and allow total permeation of smaller molecules.
- The larger molecules therefore don’t have a long residence time in the column and flow through.
- This means the polymers are separated with the largest coming out first and smallest last.
- The full molecular weight distribution can be defined and compared with previous results to see if this is influencing the mechanical behaviour.
What is differential scanning calorimetry?
Differential scanning calorimetry
- Thermal energy of a sample is monitored as a function of temperature
- Measures thermal energy of phase transitions (crystallisation, melting point, Tg)
- Heat capacity increases above Tg
- Heat released on crystallisation and absorbed on melting
- The amount of energy needed to increase the temperature of a sample is measured.
- This detects phase transitions because of the quantity of energy needed to change temperature.
- The glass transition temperature can also be observed.
- Also, the percentage crystallinity can be defined.
What is thermogravimetric analysis?
Thermogravimetric analysis
- Measure thermal stability of a sample
- Mass of a sample is measured as a function of temperature
- Can identify material composition and presence of contaminants
- Characteristics different in inert or oxidising environment
- Derivative curve highlights different mass loss events
- Percentage weight loss can be used to calculate composition
- This thermal technique measures the rate of change in mass as a function of temperature.
- This can identify changes in the oxidative stability and the composition.
- This is a highly sensitive technique and any contamination would be immediately highlighted.
- This technique is often used to identify the percentage of filler in a polymer sample, which also effects the mechanical properties.
What is UV spectroscopy?
UV spectroscopy
- Can identify material composition and presence of contaminants
- Measures absorbance of UV by the sample
- Can be used to identify chromophores
- Absorbance proportional to concentration
What is fourier transform infrared spectroscopy
Fourier transform infrared spectroscopy
- Can identify material composition and presence of contaminants
- Measures vibration and stretching of chemical bonds
- Used to examine structure and presence of functional groups
- Samples can be solid, liquid or gas