319 - Making Medicines For Pharmacy Flashcards
What is the medicines act?
Governs the control of medicines for human use and for veterinary use, which includes the manufacture and supply of medicines.
What is the Orange Guide?
- rules and guidance for pharmaceutical manufacturers and distributors
- EU guides to good manufacturing practice and good distribution practice
- EU directives on manufacturing, wholesale distribution and good manufacturing practice
- code of practice for qualified persons and guidance for responsible persons
- standard provisions for manufacturers licenses
- standard provisions for wholesale dealers licenses
- guidance on reporting defective medicines
- voluntary inspections for good (research) clinical practice and manufacturing of active pharmaceutical ingredients
What does CLP stand for?
CLP is classification, labelling and packaging.
What is CLP?
The CLP regulation is an EU regulation which aligns the EU system of classification, labelling and packaging of chemical substances and mixtures to those globally.
What does COSHH stand for?
Control of Substances Hazardous to Health (2002)
What are the responsibilities set out in COSHH?
- states requirements imposed on employers to protect employees and other persons from the hazards of substances used at work by risk assessment, control of exposure, health surveillance and incident planning
- There are also duties on employees to take care of their own exposure to hazardous substances
What does GMP stand for?
GMP is good manufacturing practice.
What are the aspects of GMP?
- GMP covers all aspects of production from the starting materials, premises, and equipment to the training and personal hygiene of staff. (people, premises, processes, products and procedures)
- These guidelines provide minimum requirements that a manufacturer must meet to assure that their products are consistently high in quality, from batch to batch, for their intended use
- it is Quality control - process of sampling, testing and comparing results with pre-agreed specifications as part of the overall quality assurance (QA) process
What is QA? (acronym)
QA is quality assurance
What does QA of the aseptic process include?
- validation of
- equipment
- processes
- techniques
- staff involved in preparation
- control of processes by use of
- SOPs
- monitoring
- training
- competency assessment
- supervision
- sel-inspection
- change control
When is validation used in the aseptic process?
Validation is used when a new aseptic unit is commissioned, new equipment, new processes, new techniques, new staff
What is the purpose of validation as part of quality assurance in the aseptic process?
Validation shows that under simulated conditions, aseptic products can be consistently prepared to the required quality. (ie broth tests)
How should spillages be dealt with?
- dealt with immediately
- other staff should be made aware and minimise the number of people in the area
- spill should be cordoned off
- SOP - follow it
- spill kit should be readily available
- if it involves liquid - use an absorbent cloth
- if it involves powder - use a damp cloth
- all contaminated substances/surfaces should be washed down with copious amounts of water
- report it
What are the key points of fire safety?
- mandatory fire training
- different alarms
- small fires - put out, if trained
- assembly point
- keep fire doors shut
- keep fire exits clear
- know where extinguishers are
- follow SOP
- hit fire alarm if find fire
What is the difference in expiry date for a licensed and unlicensed manufacturing unit?
- unlicensed - maximum of 7 days
- licensed - stability data to back up expiry
What are the differences between licensed and unlicensed production units making batches?
- unlicensed - yes small (expiry 1 week)
- licensed - yes, large (stability data)
What are the differences between licensed and unlicensed production units in dispensing from a prescription?
- unlicensed - making for a patient with prescription
- licensed - can make whatever, whenever
What are the differences between licensed and unlicensed units for the supply of products?
- unlicensed - only make products for themselves, cannot be supplied outside
- licensed - can sell ‘outside’
What is a dispensing error?
A dispensing error is a deviation in the dispensed preparation from the prescribed order.
What are possible causes of errors?
- distractions
- transcription errors
- incompetency/lack of training
- checking error/worksheet
- not following SOPs
- time constraints
How does quality assurance reduce errors?
- understanding GMP
- understanding validation procedures
- correct training & training manuals
- SOPs - for everything
- auditable
How do risk assessments reduce errors?
- identify risk/harm to patient/employee and impact of that
- will identify process and should give outcome (risk score)
How does quality control (QC) reduce errors?
- analytical testing
- checking products to make sure they have the correct formulation
- monitor validation
- check SOPs
- perform audits
What does training do to reduce errors?
- rigorous and continuous training
- complete validations
- follow SOPs
- training manual
What is a clinical trial?
A clinical trial is a testing of a new medicine or medical device to evaluate whether it is safe and effective for people to use.
What are the aims of a clinical trial?
- safety
- side effects
- better than current treatment options
- help people feel better
Who regulates clinical trials?
Run in accordance with European legislation and government bodies (MHRA)
What is the role of the MHRA in clinical trials?
- assess and process applications from companies to conduct clinical trials
- provide clinical trial authorisations
What is the role of the qualified person in clinical trials?
- named on license
- responsible for overseeing the overall production process
- products - fit for use (GMP)
- responsible for releasing products
What is an example of a grade A clean room area?
An isolator is an example of a grade A clean room area.
What activities might be undertaken in a grade A clean room area?
- sterile products
- infusions
- eye drops
- TPN
- cytos
- mabs
What PPE should be worn in a grade A clean room area?
- mob cap
- gown/boiler suit + hood
- boots/overshoes/clogs
- gloves
- mask
What is an example of a grade B clean room area?
The room the isolator is in is a grade B clean room area.
What activities are undertaken in a grade B clean room area?
- sterile products
- infusions
- eye drops
- TPN
- cytos
- mabs
(same as grade A)
What PPE should be worn in a grade B clean room area?
- mob cap
- gown/boiler suit + hood
- boots/overshoes/clogs
- gloves
- mask
(same as grade A)
What is an example of a grade C clean room area?
The background environment for isolators is an example of a grade C area.
What activities are undertaken in a grade C clean room area?
- sterile products
- infusions
- eye drops
- TPN
- cytos
- mabs
- non-sterile manufacturing specials
What PPE should be worn in a grade C clean room area?
- mob cap
- gown/boiler suit + hood
- boots/overshoes/clogs
- gloves
- mask
What is an example of a grade D clean room area?
The support room is an example of a grade D clean room area
What is made in a grade D clean room area?
- non-sterile products
- specials manufacture
What PPE should be worn in a grade D clean room area?
gloves & aprons
What personal hygiene requiements are there in a pharmacy production unit?
- no makeup
- no jewellery
- no eating
- no drinking
- no smoking
- no chewing gum
- shower daily
- clean uniforms
- exfoliate regularly
What are the stages of the handwashing technique?
- palm to palm
- right palm over left dorsum with fingers interlaced, and vice versa
- palm to palm with fingers interlaced
- backs of fingers to opposing palm with fingers interlocked
- rotational rubbing of right thumb clasped over left palm and vice versa
- rotational rubbing backwards and forwards with clasped fingers of right hand in left palm and vice versa
- wrists are rubbed
How should you wear a mob cap?
Tuck hair in. One also used for beard.
What are the features of a gown in a clean room?
A gown is single weave with a collar (do it up).
Gowns are anti-shedding and anti-static.
What are the features of clogs for clean room clothing?
Clogs are anti-static and have a non-porous sole. Clogs are thick enough to protect the wearer (in case of broken glass) and are waterproof.
What are the features of the gloves used in the clean room?
Gloves are powder-free as powder has microbes. They are impermeable to hand oil and should make a good seal around the wrist.
What technique should be used to don gloves in the aseptic room?
The non-touch technique should be used to don gloves.
What are the two main types of contamination?
- particulate contamination
- microbial contamination
Where does microbial contamination come from?
- water
- raw materials
- personnel
- equipment
What are the consequences of microbial contamination on medicinal products?
- spoilage - product is unfit for use if the microorganism uses the product as a growth medium
- transmission of disease to the user - microorganism may induce disease to the user of the product without producing spoilage
How is the introduction of microbial contamination via water controlled in pharmacy?
- use suitable types of water in pharmacy and pharmacy production
Which type of raw materials are often heavily contaminated with microorganisms?
plant or animal extracs or minerals such as talc
How can equipment be a source of microbial contamination?
The cleaning fluid for the equipment could become contaminated.
Inadequate cleaning may also leave residues of cleaning product which may act as a growth medium.
What are the two main types of particulate contamination?
- instrinsic contamination
- extrinsic contamination
What is intrinsic particulate contamination?
Intrinsic particulate contamination comes from the raw materials and packaging components used in the production of pharmaceutical products.
What is extrinsic particulate contamination?
Extrinsic particulate contamination is generated mainly from environmental contaminants, processing equipment and operators.
What are different microbial and physical testing methods?
- settle plates
- contact plates
- swabs
- finger dabs
- active air sampling
- airflow counts
- hand washing technique
What are the consequences of contamination in manufactured products?
- patient suffers
- product contaminated
- counts higher than orange guide states
Why might there be bacteria in productions?
- poor hand washing
- didn’t use no-touch/aseptic technique
- isolator filters aren’t working properly
Why might there be high particle counts?
- HEPA filter not working
Why might there be growth on settle plates?
- not cleaning isolator properly
- plates not sterilised properly
Why might there be growth on contact plates?
- insufficient cleaning
- operator technique
Why might there be high microbe counts?
- HEPA filter
- dual doors open
What does PPM stand for?
PPM is planned preventative maintenance
What is the aim of PPM?
- prevent breakdown or failure of equipment
- prevent failure of equipment before it actually occurs
- keep any disruption to patients care to a minimum
- increase the lifetime of the equipment
How often should HEPA filters be checked?
(PPM: HEPA filters checked for efficiency and changed if necessary)
Annually
How often should the plant room be checked?
(PPM: plant checked to make sure that all parts are working efficiently and any parts replaced have deteriorated)
Annually
How often should isolator gauntlets/sleeves be checked?
(PPM: check for wear and tear and replace if worn)
bi-daily
How often should extensive particle checks of the clean room and air flow checks on the room and isolators take place?
(PPM: specialised equipment is used to check the particle count of the room and the air flow of the isolators and room)
3 monthly
How often should maintenance checks of the isolator/laminar flow cabinets take place?
(PPM: manufacturing company of isolator/laminar flow to check the isolator/laminar flow is working efficiently and replace any worn parts)
6 monthly
In aseptic production what techniques are used?
- ‘no touch’ technique
- spraying and wiping
- standard operating procedures (SOPs)
What is the ‘no touch’ technique?
The no-touch technique involves not touching critical areas - i.e the tops of vials.
What equipment is used in aseptic production?
- isolator
- laminar flow
- syringes
- needles/filter needles
- chemo spikes
- venting devices
What protective clothing is worn in aseptic production?
- gown
- mob cap
- gloves
- overshoes
- boots
- clogs
- aseptic suit
- mask
What products are produced in aseptic production?
- eye drops
- TPN
- chemotherapy
- CIVAS
- mabs
- talc
What does CIVAS stand for?
CIVAS is centralised intravenous additive services
What methods of disinfection are used in aseptic production?
- spraying in and wiping
- cleaning of equipment
What techniques are used in non-sterile production?
- handwashing
- filtration
- mixing
- dissolving
- crushing
- in-process checks
- trituration
- filing
What equipment is used in non-sterile production?
- syringes
- balances
- fume cupboard
- hot plate
- heated slabs
- counting triangle
- conical measure
- sonic bath
- pestle and mortar
- laminar flow
- isolator
What protective clothing is used in non-sterile production?
- gloves
- mob caps
- gown
- goggles
- mask
What products are made in non-sterile production?
- powders
- creams
- ointments
- suspensions
- capsules
- external products
What methods of disinfection are used in non-sterile production?
- spraying down before and after with 70% IMS
- washing of equipment with hot soapy water an then rinsing with distilled water
Who uses sterile production?
Sterile production is used by large pharmaceutical companies.
What techniques are used in sterile production?
- mass production
- filing
- filtering
- mixing
- capping
What equipment is used in sterile production?
- autoclaves
- balances
- mixers
- laminar flow cabinet
- membrane filter
- bottle and capsule filling machines
- isolator
What clothing is used in sterile preparation?
- gown
- boots
- suit
- hood
What products are made in sterile preparation?
- creams
- oitments
- eye drops
- injections
- pastes
- infusion bags
- WFI
What methods of sterilisation are used in sterile production?
- autoclave
- dry heat/ovens
- filtration
- gaseous
- radiation
Which type of plates are used to grow yeasts and moulds?
Sabouraud dextrose agar are used for yeasts and moulds
What type of plates are used in active air sampling?
Tryptone soy agar and sabouraud dextrose
How should an air sampler be cleaned?
The sampling head of the equipment should be thoroughly disinfected before use, preferably autoclaved.
What types of manufacturing errors need to be recorded?
- incorrect final volume
- temperature
- drawing insufficient quantity from a vial
- weight of bag
- expiry dates not clear
- worksheet amendment
- wrong vehicle
- lost label –> reconciliation
- colour changes
- needle-stick injury
- any variation from SOP
- particles
- anomaly
What details need to be included on a worksheet?
- name of product
- identifying batch number (product)
- method
- suppliers name, batch number, expiry date
- date prepared
- expiry date + time (product)
- initials of staff preparing and checking
- signature/initials of authorised pharmacist
- signature/inital of authorised pharmacist for release
- label reconciliation
- patient’s name + DOB + weight + ward
- comments section (for deviations/unusual events)
- who devised worksheet, when it is for review
- where did the worksheet come from
What is the purpose of labelling?
- to identify the contents of the container
- clear instructions
What information should be included on labels for manufactured products?
- patient’s name + location
- hospital address
- batch number
- expiry date and time
- patient’s NHS number
- drug name
- drug strength (mg)
- volume/quantity
- name of vehicle
- final volume
- route of admin
- date prepared
- cautionary labels
- storage requirements
TRUE or FALSE
Only positive statements should appear on labels.
TRUE!
Only positive statements should appear on labels.
ie. ‘for intravenous use only’ not ‘not for intravenous use’
What is packaging?
Packaging is the enclosing of a physical object, typically a product that will be offered for sale.
What are the functions of packaging?
- to enclose the product - protect from physical damage, light, airbourne contamination
- to group things together - for efficiency
What does the type of packaging chosen depend on?
- the sensitivity of the product
- the types of damage they are likely to incur
- the value of the product
- the size of the product
- the weight of the product
What are commonly used packaging materials?
- foil / bubble wrap (protection, insulation)
- cardboard (cheap, stiff & durable, readily available)
- plastic (cheap, transparent)
- glass (non-reactive, inert)
- ice packs
- reusable wooden box
What is primary packaging?
The packaging that touches the product. (blister pack, bottle, ampoule)
What is secondary packaging?
The secondary packaging is the box it comes in. Encloses everything, keeps it together.
What are the features of secondary packaging?
- keeps it safe
- selling point
- can be removed without damaging the product
What are the features/purpose of transport packaging?
- rigid, strong, safe
- plastic - reuasable
- maintain cold chain
- clearly marked - where its going, cyto, heavy, fridge
- cyto - spillkit instructions
What is the cold chain?
The cold chain is the series of actions and equipment applied to maintain a product within a specified low-temperature range from production to consumption
What is the purpose of the cold chain?
- protects expiry date
- stability data
What temperature are pharmacy fridges set to?
2ºC - 8ºC
What should be in place to advice what to do with waste medicines?
There should be an SOP in place for the handling of returned or unused products.
Define the term photodegradation?
Photodegradation is the breakdown of a product in the presence of light.
How often should pharmacy fridge temperatures be checked?
Ideally every morning.
What are the four catergories waste is classified into?
- cytotoxic
- sharps
- non-hazardous clinical
- general
What type of waste is methotrexate tablets?
Methotrexate tablets are cytotoxic waste.
What type of waste are syringes used to draw up cisplatin?
Syringes used to draw up cisplatin are cytotoxic waste.
What type of waste are atenolol tablets?
Atenolol tablets are non-hazardous clinical waste.
What type of waste are paper towels?
Paper towels are general waste.
What type of waste is an insulin pen needle?
An insulin pen needle is sharps waste.
What type of waste are needles used to make epirubicin?
Needles used to make epirubicin are cyto sharps.
What type of waste is a broken glass ampoule of WFI?
A broken glass ampoule of WFI is sharps waste.
What type of waste are gloves used to make a non-sterile product?
Gloves used to make a non-sterile product are general waste.
What type of waste are finasteride tablets?
Finasteride tablets are non-hazardous waste.
What type of waste are cardboard boxes?
Cardboard boxes are general wastre.
What is the definition of quality assurance?
Quality assurance are systems that ensure that manufactured products are the required quality for their intended use.
What are the overlapping areas that quality assurance encompasses?
- product design
- good manufacturing practice (GMP)
- quality control (QC)
- process development
What is quality assurance about? (summary)
- about the future as well as the present
- looks at the process
- ensures is fit for purpose
What is quality control?
Quality control ensures that a satisfactory quality of materials and products is used. This involves sampling, testing, documentation and release procedures. Only when materials and products are of a satisfactory quality are they released for use.
What is the role of quality control?
- carries out analytical function. QC uses physical and chemical test methods.
- verifying role because it acts after the event. Do not prevent errors occuring, but will identify a faulty batch before distribution
It is important that a QC department is ………….. from the production unit.
It is important that a QC department is independent from the production unit.
A QC assessment of the final product should include:
A QC assessment of the final product should include:
- the production conditions the product was made in
- results of in-process testing
- a review of manufacturing documentation
- examination of the final finished pack
What is quality control about? (summary)
- focuses on systems that are in place now
- focuses on the product
- check suitability of products & the environment
What are three differences between QC and QA?
- QA looks at the future, as well as the present
- QA looks at the process, QC looks at the product
- QC looks at the environment
Name five parts of the quality assurance system and for each one discuss why it’s important they are in place.
- premises
- product
- package
- use of product
- people to make
(check this is correct, then why we need it)
What should be included if transporting cytotoxics?
If transporting cytotoxics, there should be details included of contacts and actions to be taken in an emergency.
What important legislation should be considered in regards to storage and distribution?
Health and safety should be considered relating to potential hazards during storage and distribution. COSHH should be complied with at all times.
What types of testing of manufactured products are there?
- sterility
- in-process tests (finger dabs + environmental monitoring)
- examine containers
- chemical analysis of raw materials and the final product
- pyrogen testing
What are the types of in-process testing?
- testing of the products for quality, strength, identity & weight
- particle count testing
- temperature testing
- pressures (from differentials, isolators)
- volume checks
- calibration of equipment
- finger dabs
What is a pyrogen?
A pyrogen is a type of gram negative bacteria that causes a rise in body temperature (fever producing).
What are the tests for pyrogens?
- bacterial endotoxin test
- rabbit test
What is the product formulation defined as?
Product formulation is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product.
The word formulation is often used in a way that includes dosage form eg capsules, suspension, solution
What factors have to be considered when creating the product formulation?
- compatibility of ingredients
- pH
- solubility
- polymorphism
- particle size
What is the definition of validation?
Validation is the procedure which is used to prove that the various production procedures, equipment and materials will produce accurate results.
Why is validation important?
- ongoing process
- ensures competence & desired results
- gives an audit trail of quality monitors in aseptic technique
What types of operator validations are there?
- broth test
- hand validation (finger dabs)
- aerosol tests
- dressing validation
What is the importance of record keeping in relation to validation?
- audit trail - proves has been trained
- product recall
Where will sterile and non-sterile products be held post production whilst awaiting the QC to carry out appropriate tests?
Following production, the finished products in non-sterile and sterile production will be held in quarantine or pre-release area.
Who carries out the tests on quarantined manufactured products?
The QC will carry out the appropriate tests on the quarantined manufactured product.
What should the pharmacist be satisfied with (wrt manufactured product) before release?
- carry out visual inspection of the product
- ensure product complies with prescription and the label is correct
- product has been produced in accordance with approved and validated SOP
- be aware of environmental & microbial results of production unit
- monitoring records (cleaning, pressure differentials) are completed
- ensure starting material checks (batch no + exp date) complete
In large organisations who should be in charge of product recalls?
In a large organisation the method for recalling products should be carried out and coordinated by a designated person. This person should operate separately from both sales and marketing teams.
What has to be issued at the end of a product recall?
The product recall process has to be recorded and a final report issued.
Who should be aware of all recall operations?
Both the QP and the manager of QC should be aware of all recall operations.
What is the method for cleaning the isolator?
top → back → front → bottom
work from high to low, from clean to dirty
work in straight, parallel, overlapping strokes
What are cytotoxic drugs?
Cytotoxic drugs are harmful (toxic) to cells (cyto).
They are used to destroy or inhibit the growth of rapidly dividing cells such as cancer cells.
What are monoclonal antibodies (mabs)?
Monoclonal antibodies are antibodies that are made by identical immune cells that are all clones of a unique parent cell.
What is CIVAS (definition, not acronym)?
CIVAS includes the preparation of antibiotics, antiemetics, analgesics etc. that are to be administered intravenously
What is an intrathecal injection?
Any drug that is administered into the spinal canal
(e.g. methotrexate)
What is TPN?
Total parenteral nutrition (TPN) is a way of supplying all the nutritional needs of the body by bypassing the digestive system and dripping nutrient solution directly into a vein.
What are radiopharmaceuticals?
Radiopharmaceuticals are drugs that carry a limited degree of radioactivity, and are usually used in nuclear medicine as an alternative to standard radiation for the treatment of certain cancers as well as a diagnostic tool to allow better internal imaging of certain organs and arteries.
What is a syringe driver?
A syringe driver may help control pain, sickness, agitation or fits. A syringe driver helps reduce symptoms by delivering a steady
flow of injected medication continuously under the skin. It’s sometimes called a continuous subcutaneous infusion.
