Microbial Control of Non-sterile Pharmaceuticals Flashcards
There are 2 types of pharmaceutical products available, what are they?
- sterile products which contain no viable micro-organisms
2. non-sterile products that may contain viable micro-organisms but these should not damage patient or product
Limited microbiological contamination tolerated in non sterile products such as what?
- inhalations
- tablets
- oral liquids
- creams
- ointments
(may require numbers or microbiological contaminants per unit volume or weight)
Microorganisms use the product as a ______ when formulations spoil
growth medium
How do tablets and powders limit microbial growth?
they do not have enough water to allow growth
Syrups contain high concentrations of ___ to resist growth owning to the lack of free water
syrups
Products containing more than _____ such as elixirs and spirits are usually self preserving
15% alcohol
What physical, chemical or aesthetic changes to a product may bacteria have that make it unfit for use?
- active drug constituents may be metabolized
- physical changes include:
- breakdown of emulsions
- visible surface growth on solids
- formation of slimes, pellicles or sediments in liquids
- production of gas, odours or unwanted flavours
Why is salmonella so dangerous in a medicine?
- represents a serious health hazard although it causes little to no visible damage
Risk of infection from a contamination depends on what?
- species and quantity of microorganisms
- route of administration
- susceptibility of the patient receiving the medication
What are the typical organisms that can cause infection that the USP indicates must be not present in the medicine?
Staphylococcus aureus, Pseudomonas aeruginosa, E.coli and Salmonella spp
The majority of contaminant sin medications are what?
- bacteria, yeasts and filamentous fungi (mold)
Many of the ingredients in formulations can become growth substrates when what occurs?
- water activity, pH and temperature are suitable for infection
What are the most common sources of contamination?
- raw materials
- personnel
- equipment
- environment
What are raw materials?
- an active or inactive substance used in the manufacture of a pharmaceutical dosage form
What microorganisms have raw material been known to have?
- Clostridia sp, pseudomonas aeriginosa, Stap. aureus, Strep. feacalis, E. coli, Salmonella spp, Preteus, Citrobacter, and Kleibsiella sp
What is the high contamination level of raw material?
- unprocessed raw materials of animal, plant or mineral origin
- may contain high bioburden, gram negative, gram positive, told, microbial pathogens, and objectionable microorganisms with an ability to proliferate in or biodegrade the material
- high risk
What is the moderate contamination level of raw material?
- moderately processed natural material or chemicals and their bioburden levels depend on extent and type of manufacturing process
- the predominant organisms are old and spore forming bacteria
What is the low contamination level of raw materials?
- synthetic materials or chemicals purified natural extract
- manufacturing processes are too extreme for survival of most organisms
- generally provide poor growth conditions for microorganisms, due to antimicrobial properties or low water activity levels
What are the usual waterborne organisms found in products?
- pseudomonas-achromobacter-alcalingenes type (some gram negative species)
How is purified water made to ensure that there are no microorgansims within?
- made by distillation combined with ion exchange or reverse osmosis; water for injection is purified water which is also sterilized
What are potential sources of contamination in transferring microorganisms?
- ion exchange columns and inappropriate storage
How does the physical state of the medium affect the risk of microbial contamination?
- risk of microbial contamination is solid
What is water activity?
measure of the degree with which water is bound and its availability to support growth. Water activity ranges from 0.1 to 1.0 and water activity of 0.6 is considered as the minimum requirement for microbial growth
How does the USP <1112> define water activity?
defines it as the ratio of vapour pressure of water in product to vapour pressure of pure water at the same temperature. It is numerically equal to 1/100 of the relative humidity (RH) generated by the product in a closed system
What are inherent antimicrobial properties?
- antimicrobial properties will increase the microbiological safety and stability of the raw material. Raw materials such as acids, alkalis, organic solvents, antibiotics and fungicides are known to possess antimicrobial properties
What nutrients are important for microbial growth?
proteins, carbs, lipids, vitamins, minerals and polyalcohols
What techniques are used to treat/reduce or eliminate microbial contamination?
- ionizing radiation, ethylene oxide or thermal methods like autoclaving and dry heat
What are potential sources of contamination from humans?
- contamination arises from a variety if sources including skin shed and hair which usually carries both non-pathogenic and potentially pathogenic organisms
What must be worn in the workplace to prevent contamination?
- appropriate clothing commercially available which completely shields the product from body surfaces
- important that personnel understand and appreciate the problems and significance of microbial contamination
What should equipment be like to avoid microbial contamination?
- equipment should be smooth and crevice free as well as easy to clean and dry
- quality of cleaning and rinsing fluids also need to be considered
- usually written policies and procedure in place as well as extensive documentation
What can reduce the bioburden (solvent materials)
use of hostile solvent environments can reduce the bioburden
What kind of solvents can inactivate, kill, inhibit/provide poor growth opportunities for microorganisms?
- organic solvents like acids, alkalis, salts, alcohols or surfactants are involved in this process
Processes using ___ may reduce the bioburden. These are steps like…?
Heat
Steps like distillation, heat sterilization, evaporation, crystallization or drying can kill or reduce bioburden in raw materials
Most _____ forms of bacteria cannot survive temperatures above 60 degrees
vegetative
Explain why drying associated with tablets is not sufficient to destroy bacterial spores
- temperatures of 8-100 degrees are not reliable to destroy microbes since the heat is essentially try heat
- the shearing forces and heat generated during tablet compression may also not be sufficient to destroy bacterial spores
How can formulation type reduce bioburden?
- low water activity in solid dosage forms will reduce microbial growth and spoilage
- the use of antimicrobial preservatives in formulations like non-sterile liquids, topical, creams and ointments an reduce microbial growth in the produce
- raw material for sterile products need to be either sterile or a low bioburden raw material
Microbial purity tests are done against what organisms?
- E coli, Salmonella sp, P. aeruginosa, S. aureus
- also includes total aerobic microbial counts for ingredients (TAMC)
What should be done for a sample that does not have in-house specifications for microbial growth?
- if raw material is for oral dosage form, recommend is to default to TAMC of not more than 1000 cf./g or ml and absence of E.coli and Salmonella
- for raw materials used in parenteral products, defaulting to TAMC of not more than 100 cfu/g or ml and bacterial endotoxin requirements
With patients that are immunocompromised, what other micro-organsims need to be watched for?
testing for enteric organisms such as pseudomonas sp, S aureus, C. albican, mycotoxin prorducing fungi and B cepacia may be necessary
For ophthalmic dosage forms, what other organisms need to be tested for?
- in addition to P. aeruginosa, the raw materials should be evaluated for other pseudomonas sp, S. aureus, Serrate marcescens, Ser liquidifaciens
