Sterile Product Requirements Flashcards
General sterile requirements
Sterile
Particulate free
Sources of microbial contamination
Raw material
Water supply
Air supply
Processing operations
Equipment
Employees
Environment
Sterility
Complete destruction of all living organisms and their spores or complete removal
Sterility assurance level
1/10^6
Approaches to sterility
Initial control
Terminal sterilization
Aseptic processing
Preservatives
D-value
Time in minutes required to destroy 90% of microbes
Biological indicator
Specific microorganism resistant to a particular method of sterilization
Validation of sterility
At known level and known D-value survival should be less than or equal to 10^-6
Steam sterilization
Moist heat causes irreversible denaturation of essential proteins
D= 1min at 121 degrees C
USP: 120 C at 15 psi for 20 min
Steam sterilization works for
Equipment
Single dose in a sealed container
Steam sterilization damages
Oils
Proteins
Powders
Dry heat sterilization
Dehydration, denaturation, and slow burning or oxidation
D= 3 min at 160 degrees C
USP: 160-170 C for more than 2 hours
Dry heat sterilization works for
Fats and oils/petroleum semi-solids
Dry items
Radiation sterilization
Irradiation creates free radicals leading to cell damage and death
Gamma radiation
Radiation sterilization orks for
Pharmaceuticals
Medical devices
Radiation sterilization damages
Biologic drugs
Gas sterilization
EO is alkylating agent—reacts with amine group on DNA
Must be allowed to dissipate after sterilization
Gas sterilization works for
Heat and moisture sensitive materials
Medical devices
Sterilization would not work on
Coronavirus
Pseudomonas diminutive organism
Particulate matter tests
Check sterile products for particulate matter
Limit is 50 particles of 10+ micromolar per mL
Before dispensing sterile products
Pharmacists should check for particulates by swirling the solution and looking at it against light and dark backgrounds
Sources of particulate matter
bacteria/fungi
Incomplete dissolution of drug
Precipitate from incompatible mixtures
Glass particles from ampules
Particles from rubber stoppers
Particles from plastic
Particulates and the IV route
Can be emboli leading to thromboembolism or phlebitis
Thromboembolism
Embolism of thrombus
Phlebitis
Inflammation of the vein
Reduced when IV infusions are filtered
Depth filter
Substances that trap particles in channels
Screen Filter
Surface filtration
Microbial filter
0.22 micromolar
Final filter
Particulate or microbial; in-line filter for IV
Issues with filtration
Drug loss
Protein absorption especially at low C
When is filtration preferred
Solutions that are unstable by thermal, chemical, or radiation sterilization
When are preservatives required
In multiple-dose products
What solutions are susceptible to microbial contamination?
Aqueous solutions, emulsions and suspensions
What solutions may not need preservatives?
Ph<3
Ph>9
Hydroalcoholic: >15% alcohol
Hypertonic solutions: 67% sucrose
Adverse reactions
Death of neonates: benzoyl alcohol
Intrathecal and epidural toxicity
Long-term Parenteral drug treatment
Pyrogens
Fever causing organic molecules from microbial contamination
Primary source: water
LPS
From the cell wall of bacteria
