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