RESP - D. STERILE PRODUCTION-COVERED Flashcards
sterile pharmaceutical products
- free of living microorganisms
- injectable formulations must also be free of particles and pyrogens (LPS endotoxin from gram -ve bacteria)
what products must be sterile
- those in contact within internal organs
- eyes
- broken skin
what is terminal sterilisation
- 1st option as less risky
- product is manufactured, sealed in final container and sterilised (NaCl nebuliser solution BP)
- low risk of microbiological contamination in final product
- not possible iF drug is thermosensitive
what is aseptic production
- more risky
- medium, container, closure sterilised separately then combined in a sterile environment (Na cromoglicate eye drops)
- higher risk of microbial contamination in final product
- sterility assurance and sterility control = crucial
what are 4 terminal sterilisation processes accepted by BP
- moist heat (steam)
- dry heat
- ionising radiations
- gaseous sterilisation
*biocidal - microorganisms killed
what is 1 aseptic production method accepted by BP
- filtration
*microorganisms and particles physically removed from product
- steam
- sterilisation by saturated steam under pressure in autoclave
- 121 degrees Celsius for 15 min or 134 degrees Celsius for 3 minutes (causes less damage)
- very efficient: organisms killed by denaturation or hydrolysis of cell constituents, heat resistant bacteria spores killed
- items packed in porous paper to allow steam penetration and post-sterilisation protection
used for:
- bottled aqueous solutions ie - for injection
- containers
- dressings: saline solution
- instruments
(anything resistant to heat)
- dry heat
- sterilisation in a hot air oven
- 160-180 degrees Celsius for 2 hours
- paraffin is only substance that can resist this
- less efficient than steam as killing microorganisms due to oxidation processes of lipids and proteins so slow death
- preferred over ionising radiations
- destruction of pyrogens (heat resistant)
- items packed in metal boxes to allow contact with heat and post-sterilisation protection
used for:
- glass bottles
- metal surgical instruments
- ionising radiations
- uses accelerated electrons or gamma rays
- biocidal activity due to DNA damage of micro-organisms: slow process
- used for heat sensitive products but
- might cause accelerated degradation of some plastic containers or aqueous drug formulations (as radicals form)
used for:
- ointments
- instruments
- sutures
- UV radiations NOT suitable for sterilisation of pharmaceutical products as
less DNA DAMAGE than ionising
only used for work surfaces
- gaseous methods
- ethylene oxide or formaldehyde (mutagenic and carcinogenic)
- biocidal activity due to chemical modification or proteins and nucleic acids in microorganisms
- not used in hospital but in specialised manufacturing plants
- less efficient
- sterility assurance lower than with heat processes
used for:
- powders
- instruments
in industry
1a. filtration of solutions
- for heat sensitive injectable or ophthalmic solutions
- pore diameter of filters: 0.22 microns (retains smallest viruses/bacteria)
- removal of particles (not suitable for suspensions)
- different types of filter (hydrophilic for aq formulation and hydrophobic for non-aq product)
- work in laminar flow cabinet
1b. filtration of gases
- sterile air in sterile production units and inside laminar airflow cabinet
- high efficiency particulate air (HEPA) filters - in ceiling, remove up to 99.997% of particles >0.3 microns
laminar airflow cabinet
- provides a continuous, unidirectional flow of clean sterile filtered air
- laminar flow needs to be undisturbed: don’t place product behind another that obstructs HEPA filter at back
ANTT principles - aseptic non-touch technique
- ‘critical site’ can’t be touched by a non-sterile item ie:hands, surface of cabinet
- must remain sterile for final product to be sterile
ie:eye dropper, neck of bottle, inside of bottle, lid of bottle, filter
- disinfect laminar airflow cabinet (back to front) and start at ceiling
- disinfect all items that will be placed in cabinet using wipes
- disinfect gloves
- items placed at side not in front to avoid turbulence
aqueous products
steam sterilisation but if product sensitive to heat
aseptic filtration but if product can’t be filtered (suspensions)
aseptic protection from sterile individual components
non-aqueous products
dry heat sterilisation but if product sensitive to heat
ionising radiation but if product is sensitive to radiation
aseptic filtration (hydrophobic filter) but if product can’t be filtered (suspensions)
aseptic protection from sterile individual components
- sterility control
- incubation of whole/portion of product with a nutrient medium under sterile conditions to verify absence of contamination (ie should be no microorganisms)
- legally required
limitations of sterility tests
- product destroyed (can’t apply to specials product made for 1 specific patient)
- few samples from each batch tested
- rely on suitability of culture medium and culture conditions ie - no standard conditions
- doesn’t detect presence of viruses
- sterility assurance
- clean environment
- follow GMP/GWP rules and use correct aseptic procedure
- use contamination free starting materials
- validation and in-process control of sterilisation procedures ie - it occurred as planned
- suitable packaging and storage
regular cleaning/disinfection
- floor and horizontal surfaces cleaned and disinfected every day
- ceiling and walls cleaned and disinfected once a month
design of premises
- separation of storage and preparation areas
- clean = grey, aseptic = white
- different routes for staff and materials
unidirectional flow of sterile products - filtered air at +ve pressure = prevents air from external environment or grey area entering aseptic area
- smooth surfaces and rounded coving to prevent accumulation of dust/microorganisms and easy to clean and disinfect
suitable clothing
- sterile trouser suit, hat, enclosing hair, facemask, gloves, overboots
- non-shedding materials
- non-reusable
strict changing procedure
- passage from outside to clean area via a dividing step-over sill
- outer garments and footwear removed in black area
- hands washed in sink with elbow or foot operated
in process control of procedures: biological indicators
- heat sterilisation
ampoules containing spores of a heat resistant bacteria placed autoclave then incubate - aseptic filtration
filtration of culture of a non-pathogenic bacteria of 0.3microns through 0.22micron pore size filter then incubate - incubation to verify absense of bacterial growth in medium
*incubation time can be a few days for microorganism to grow and multiply in culture medium
