Microbial Control of Non-sterile Pharmaceuticals

Question 1

There are 2 types of pharmaceutical products available, what are they?

Answer 1

1. 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

Question 2

Limited microbiological contamination tolerated in non sterile products such as what?

Answer 2

• inhalations
• tablets
• oral liquids
• creams
• ointments
  (may require numbers or microbiological contaminants per unit volume or weight)

Question 3

Microorganisms use the product as a ______ when formulations spoil

Answer 3

growth medium

Question 4

How do tablets and powders limit microbial growth?

Answer 4

they do not have enough water to allow growth

Question 5

Syrups contain high concentrations of ___ to resist growth owning to the lack of free water

Answer 5

syrups

Question 6

Products containing more than _____ such as elixirs and spirits are usually self preserving

Answer 6

15% alcohol

Question 7

What physical, chemical or aesthetic changes to a product may bacteria have that make it unfit for use?

Answer 7

• 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

Question 8

Why is salmonella so dangerous in a medicine?

Answer 8

• represents a serious health hazard although it causes little to no visible damage

Question 9

Risk of infection from a contamination depends on what?

Answer 9

• species and quantity of microorganisms
• route of administration
• susceptibility of the patient receiving the medication

Question 10

What are the typical organisms that can cause infection that the USP indicates must be not present in the medicine?

Answer 10

Staphylococcus aureus, Pseudomonas aeruginosa, E.coli and Salmonella spp

Question 11

The majority of contaminant sin medications are what?

Answer 11

• bacteria, yeasts and filamentous fungi (mold)

Question 12

Many of the ingredients in formulations can become growth substrates when what occurs?

Answer 12

• water activity, pH and temperature are suitable for infection

Question 13

What are the most common sources of contamination?

Answer 13

• raw materials
• personnel
• equipment
• environment

Question 14

What are raw materials?

Answer 14

• an active or inactive substance used in the manufacture of a pharmaceutical dosage form

Question 15

What microorganisms have raw material been known to have?

Answer 15

• Clostridia sp, pseudomonas aeriginosa, Stap. aureus, Strep. feacalis, E. coli, Salmonella spp, Preteus, Citrobacter, and Kleibsiella sp

Question 16

What is the high contamination level of raw material?

Answer 16

• 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

Question 17

What is the moderate contamination level of raw material?

Answer 17

• 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

Question 18

What is the low contamination level of raw materials?

Answer 18

• 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

Question 19

What are the usual waterborne organisms found in products?

Answer 19

• pseudomonas-achromobacter-alcalingenes type (some gram negative species)

Question 20

How is purified water made to ensure that there are no microorgansims within?

Answer 20

• made by distillation combined with ion exchange or reverse osmosis; water for injection is purified water which is also sterilized

Question 21

What are potential sources of contamination in transferring microorganisms?

Answer 21

• ion exchange columns and inappropriate storage

Question 22

How does the physical state of the medium affect the risk of microbial contamination?

Answer 22

• risk of microbial contamination is solid

Question 23

What is water activity?

Answer 23

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

Question 24

How does the USP <1112> define water activity?

Answer 24

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

Question 25

What are inherent antimicrobial properties?

Answer 25

- 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

Question 26

What nutrients are important for microbial growth?

Answer 26

proteins, carbs, lipids, vitamins, minerals and polyalcohols

Question 27

What techniques are used to treat/reduce or eliminate microbial contamination?

Answer 27

- ionizing radiation, ethylene oxide or thermal methods like autoclaving and dry heat

Question 28

What are potential sources of contamination from humans?

Answer 28

- contamination arises from a variety if sources including skin shed and hair which usually carries both non-pathogenic and potentially pathogenic organisms

Question 29

What must be worn in the workplace to prevent contamination?

Answer 29

- 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

Question 30

What should equipment be like to avoid microbial contamination?

Answer 30

- 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

Question 31

What can reduce the bioburden (solvent materials)

Answer 31

use of hostile solvent environments can reduce the bioburden

Question 32

What kind of solvents can inactivate, kill, inhibit/provide poor growth opportunities for microorganisms?

Answer 32

- organic solvents like acids, alkalis, salts, alcohols or surfactants are involved in this process

Question 33

Processes using ___ may reduce the bioburden. These are steps like...?

Answer 33

Heat Steps like distillation, heat sterilization, evaporation, crystallization or drying can kill or reduce bioburden in raw materials

Question 34

Most _____ forms of bacteria cannot survive temperatures above 60 degrees

Answer 34

vegetative

Question 35

Explain why drying associated with tablets is not sufficient to destroy bacterial spores

Answer 35

- 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

Question 36

How can formulation type reduce bioburden?

Answer 36

- 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

Question 37

Microbial purity tests are done against what organisms?

Answer 37

- E coli, Salmonella sp, P. aeruginosa, S. aureus | - also includes total aerobic microbial counts for ingredients (TAMC)

Question 38

What should be done for a sample that does not have in-house specifications for microbial growth?

Answer 38

- 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

Question 39

With patients that are immunocompromised, what other micro-organsims need to be watched for?

Answer 39

testing for enteric organisms such as pseudomonas sp, S aureus, C. albican, mycotoxin prorducing fungi and B cepacia may be necessary

Question 40

For ophthalmic dosage forms, what other organisms need to be tested for?

Answer 40

- in addition to P. aeruginosa, the raw materials should be evaluated for other pseudomonas sp, S. aureus, Serrate marcescens, Ser liquidifaciens