methods of sterilization
membrane filter materials include (9)
cellulose acetate, cellulose nitrate, flurocarbonates, acrylic polymers, polycarbonate, polyester, PVC, nylon, polytef (teflon)
which gas is commonly recommended for sterilization in pharmaceutical preps?
ethylene oxide
the gases used for sterilization,
ethylene oxide, propylene oxide, hydrogen peroxide, chloride dioxide, peracetic acid, ozone
medical and surgical supplies and appliances (catheters, needles, and plastic disposable syringes) in FINAL PLASTIC PACKAGING
gas sterilization
most injections prepared from chemically pure medicinal products are stable at
room temp
ionizing radition: short or long exposure times?
short
In dry heat sterilization, individual units to be sterilized should be large or small?
small as possible
example of biological indicator
spores
what is not useful for oils, fats, oleaginous preps and preps not penetrated by moisture or for exposed powders that may be damaged by the condensed moisture?
steam sterilization
what is useful for aq. solutions in sealed containers (ampoules), bulk solutions, glassware, surgical dressings and instruments?
steam sterilization
5 methods to sterilize
steam, dry heat, filtration, gas, ionizing radiation
destruction and complete removal of all living organisms and their spores from a pharmaceutical preparation
sterilization
For labeling purposes, revised injectable product nomenclature became official in the USP ____.
23
After filling, all samples are inspected and any particulate containing samples are rejected. Depending upon the material, inspectors can detect particles of _________ while automatic systems can detect even smaller particulates.
25 - 50μm
most common used filter for sterilization is?
0.2mcm since this is the size of the smallest baceria
dextrose injection NMT USP EU
0.5
gentamicin USP EU
0.71
labels must state
1. Name of the preparation 2. For a liquid preparation, the percentage content of drug or the amount of drug in a specified volume 3. For a dry preparation, the amount of active ingredient present and the volume of liquid to be added to prepare a solution or suspension 4. Route of administration 5. Statement of storage conditions and an expiration date 6. Name of the manufacturer and distributor 7. An identifying lot number capable of yielding the complete manufacturing history of the specific package, including all manufacturing, filling, sterilizing and labeling operations
USP 797 includes
1. On establishing beyond use dates 2. Compounding radiopharmaceuticals and allergen extracts 3. Characteristics of a quality assurance program 4. Verification of compounding accuracy and sterility 5. Finished preparation release checks and test 6. Elements of quality control
Hazardous drugs must be compounded under conditions that protect the health care professionals that come into contact with the agents
1. PPE. 2. Training for all personnel who come into contact with the material. 3. Verification of compounding techniques must be done annually.
Each individual monograph for the official injection states
1. type of container permitted (single or multiple dose), 2. type of glass preferred for the container, 3. exemptions, if any, to usual package size limitations, 4. and any special storage instructions.
a typical dry heat sterilization is conducted at what temp and how long?
150-170C for 2 hours
process with ethylene oxide takes how long?
4-16 hours
main target site of ionizing radiaion
DNA
disadvantages of EtO
Excessively long cycle Safety concerns - carcinogenic to humans Toxicity issues - toxic residues on surgical instruments and tubing EtO is flammable Requires special room conditions, safety equipment and separate ventilation systems Relatively high costs for maintenance, servicing and consumables
What has the FDA endorsed as a replacement for the rabbit test?
LAL test
more common bacterial endotoxin test
Limulus Amoebocyte Lysate Test in which the pyrogen containing sample causes gel formation in the lysis product of amoebocyte cells of the giant horseshoe crab
advantages of EtO
Low temperature High efficiency - destroys microorganisms including resistant spores Large sterilizing volume/chamber capacity Non-corrosive to plastic, metal and rubber materials
True/False: Gas can permeate through many polymeric materials.
True
examples of single dose containers
ampules and single-dose vials
frequently, the integrity of suspensions and emulsions are destroyed by
autoclaving
what kind of properties does ethylene oxide possess?
bactericidal, fungicidal, virucidal, sporicidal, and protozocidal
preparation of specific microorganisms resistance to a particular sterilization process and used to monitor sterilization cycle and/or periodically revalidate the process
biological indicator
guidelines produce the minimum practice and quality standards for ________ are found in the USP 797
compounded sterile preps (CSPs)
microbial kill by dry heat is thought to be by dehydration of the microbial cell followed by slow OXIDATION
dry heat sterilization
what is very effective for sterilizing glassware and surgical instruments?
dry heat sterilization
what method if generally employed for substances that cannot be or are not effectively sterilized by moist heat?
dry heat sterilization
what other factors are important of the removal of microorganisms through filtration?
electrical charge on filter and organism, pH of solution, temperature, pressure/vaccuum applied to the system
two main types of radiation
electromagnetic and particulate
physical removal of microorganisms by retention by sieving mechanism or absorption on the filter medium
filtration
what method is used for heat-sensitive solutions?
filtration
examples of substances requiring dry heat sterilization
fixed oils, glycerin, petroleum, mineral oil, paraffin, various heat-stable powders
disadvantages of filtration
fragility of membrane, large volumes are often time intensive, can only be used for SOLUTIONS, filter can remove drug and reduce the activity/potency
discoloration of some glasses and plastics butyl and chlorinated rubbers are degraded changes in potency can occur
gamma radiation
which sterilization method is thought to be through the interference of the metabolism of bacterial cell wall?
gas
certain heat-labile enzyme preps such as certain antibiotics and other drugs: must be final tested for ABSENCE of chemical reaction and the other deleterious effects on the drug substance resultant from the interaction of gas
gas sterilization
Since dry heat is less effective in killing microorganisms than moist heat, what is required?
higher temperatures and longer exposure periods are required
how is dry heat sterilization carried out?
in ovens that are heated by gas or electricity
How to achieve higher temperatures?
increase pressure
the appropriate type of glass suitable for each parenteral prep is usually stated in the
individual monograph
the relatively low percentage of water in spores makes their destruction much EASIER or MORE difficult?ddd
more difficult
what two rays have good penetrative power?
only γ-rays and β-rays
what type of rays are used for sterilization of pharmaceutical products?
only γ-rays and β-rays
poor penetration of electrons due to density of product significant product heating may take place at high doses
particle radiation
what kind of materials can ionizing radiation affect?
polyethylene, polypropylene, silicone rubber, teflon, glass
what is part of the physical collection of GMP?
proper documentation/collection of data
USP traditional pyrogen test
rabbit and body temp monitoring for a period of time
Dry heat sterilization: increased temp shortens needed exposure times
reduced temp increases exposure times needed
endotoxin is
thermostable and water soluble
How are ovens controlled?
thermostatically controlled
process of gas sterilization is a balance between the variables of (4)
time, temp, humidity, and gas conc
most biologic products should be stored
under refrigeration
characteristic of membrane filter
very uniform with high degree of porosity
particulate radiation
α-rays, β-rays (high-speed/high-beam electrons or cathode rays), neutron and protons
eletromagnetic radiation
γ-rays, X-rays, ultraviolet (UV), infrared (IR), microwave, and visible light
