Section 11 - Microbial Control Flashcards
When does microbiological contamination become a problem?
When it results in unwanted effects to product or user
What determines the severity of the effects of microbiological contamination?
Nature and number of contaminating organisms
W/ respect to microbiologicals, what are the 2 types of pharmaceutical products available?
1) Sterile products that contain no viable microorganisms
2) Non-sterile products that may contain viable microorganisms, but these should not damage patient or product
Which dosage forms allow for limited microbiological contamination?
- Inhalations
- Tablets
- Oral liquids
- Creams and ointments
What does it mean when a product is allowed limited microbiological contamination?
- May require numbers of microbiological contaminants per unit of volume or weight be limited
- May require specified microbes not be present at all
What causes spoilage of formulation?
- Microorganisms use the product as a growth medium
- Viable cells can produce enzymes to degrade complex macromolecules into easily assimilated nutrients
How are non-sterile pharmaceutical products generally formulated?
To prevent any microorganisms from increasing during shelf life
How do non-sterile aqueous dosage forms and syrups prevent the number of microorganisms from increasing during shelf life?
- Non-sterile aqueous dosage forms usually include antimicrobial preservatives
- Syrups contain high concentrations of sugar (~85%) to resist growth b/c of lack of free water
Which products are self-preserving?
Products containing more than 15% alcohol
What are some possible physical changes caused by microbial contaminants?
- Breakdown of emulsions
- Visible surface growth on solids
- Formulation of slimes, pellicles, or sediments in liquids
- Production of gas, odours, or unwanted flavours
What is an example of a microorganism that won’t product visible signs of spoilage?
Salmonella, presents a serious health hazard but will cause little or no visible spoilage
What is an example of a microorganism that will produce disease w/o producing spoilage of the product?
Corynebacterium diphtheriae
What factors determine risk of infection?
- Species and quantity of microorganisms
- Route of administration
- Susceptibility of px receiving the medication
What are the USP indicator organisms which must not be present? Why were they chosen?
- Staph aureus
- Pseudomonas aeruginosa
- E coli
- Salmonella species
- Chosen b/c they are typical types that could cause infection
What was the contaminating organism in the albuterol event?
P. fluorescens
Which fungi were found in tablets of micronase?
- Penicillium
- Aspergillus
- Paecilomyces
- Botryotrichum
What are the majority of contaminants?
Bacteria, yeasts, and filamentous fungi (molds)
What are the 4 main sources of contamination?
1) Raw materials
2) Personnel
3) Equipment
4) Environment
What should be done to each lot of raw materials?
- Should be evaluated for microbiological suitability
- Those deemed liable to microbiological contamination should be subjected to microbiological tests before use
When is raw material considered high contamination level?
- Unprocessed raw materials of animal, plant or mineral origin
- May contain high bioburden, gram neg, gram pos, mold, microbial pathogens, or objectionable microorganisms w/ an ability to proliferate in or biodegrade the materials
- High risk of microbial contamination
When is raw material considered moderate contamination level?
- Moderately processed natural material or chemicals and their bioburden levels depend on extent and type of manufacturing process
- Predominant organisms are mold and spore forming bacteria
When is raw material considered low contamination level?
- Synthetic materials, or chemically purified natural extract
- Manufacturing processes are too extreme for survival of most microorganisms
- Generally provide poor growth conditions for microorganisms due to antimicrobial properties (bacteriostatic or fungistatic) or low water activity levels
Which organisms are the ones usually found in water?
- Pseudomonas
- Achromobacter
- Alcaligenes
Which type of bacteria will grow rapidly in water under ambient conditions?
Gram negative rods
How is purified water made?
Distillation combined w/ ion exchange or reverse osmosis
How is water for injection made?
Purified water that is also sterilized
What are sources of contamination for water?
- Ion-exchange columns
- Inappropriate storage
Which forms of matter are most susceptible to microbial contamination?
Liquid > semi-solid > solid
What is water activity?
- Measure of degree w/ which water is bound and its availability to support growth
- Ratio of vapor pressure of H2O in product to vapor pressure of pure H2O at the same temp
What is the range of water activity and what is the minimum water activity required for microbial growth?
- Range is 0.1 to 1.0
- Water activity of 0.6 is considered minimum
Which raw materials are known to possess antimicrobial properties?
Acids, alkalis, organic solvents, antibiotics, and fungicides
Which nutrients provide a source for microbial growth?
Proteins, carbs, lipids, vitamins, minerals, and polyalcohols
Which processes are used to treat raw materials to reduce or eliminate microbial contamination?
- Ionizing radiation
- Ethylene oxide
- Thermal methods (autoclaving, dry heat)
- *Important that material not be damaged or altered by the process
What should be done to equipment w/ respect to antimicrobial properties?
- Equipment should be smooth and crevice free, as well as clean and dry
- Need to monitor quality of cleaning and rinsing fluids as well as air quality
What type of environment are sterile products made in?
Environment w/ highly controlled factors
What can be done to decrease bioburden?
- Use of solvent environments that are hostile to microorganisms
- Processes involving heat (distillation, heat sterilization, evaporation, crystallization, drying)
- Some manufacturing processes (manufacture of tablets including mixing, granulation) drying, tableting; drying process)
- Formulation type
Can temperatures of 80-100 C destroy microbes?
No
Can tablet compression destroy bacterial spores?
No, the shearing forces and heat generated during compression may not be sufficient
What should the raw material for sterile products be?
Sterile, or a low bioburden raw material w/ sterility and endotoxin criteria
Which organisms are tested for in USP tests to prove microbial purity of raw materials?
- E. coli
- Salmonella species
- P. aeruginosa
- Staph aurues
- Also includes total aerobic microbial counts (TAMC) for ingredients
What should be done for raw materials w/o compendial microbiological requirements?
- If raw materials for oral dosage form, recommendation is to default to TAMC of no more than 1000 cfu/g or mL, and absence of E coli and Salmonella species
- For raw materials in parenteral proucts, default to TAMC of no more than 100 cfu/g or mL and bacterial endotoxin requirement
What are objectionable organisms for products for immunocompromised px?
- Pseudomonas species
- Staph aureus
- Candida albicans
- Mycotoxin producing fungi
- B cepacia
What should raw material for ophthalmic dosage forms be evaluated for?
- P aeruginosa
- Pseudomonas species
- Staph aureus
- Serratia marcescens
- Serratia liquifaciens
What should raw material for topical dosage forms be evaluated for?
- P aeruginosa
- Klebsiella species
- Staph aureus
- Ser. marescens
- Ser. liquifaciens
- Pseudomonas species
- Clostridium species
- C. albicans
- B. cepacia
What should raw material for genitourinary dosage forms be evaluated for?
- E coli
- Proteus species
- Ser. marcescens
- P aeruginosa
- P multivorans
- C albicans
- Klebsiella species
- Acinetobacter species
- B cepacia
- Molds
