Contamination of medicinal products

Question 1

What routes are non-sterile?

Answer 1

Oral, rectal, topical and inhaled

Question 2

What routes are sterile?

Answer 2

`Ophthalmic and parenteral

Question 3

Where to biofilms grow on?

Answer 3

Medical devices (Catheters), growth on surfaces in e.g. hospitals, air/water handling systems, biological liquid systems (e.g. dialysis equipment), most infections involve cells growing in biofilms (e.g. wound infections, endocarditis, otitis media, CF)

Question 4

Describe the process of biofilms

Answer 4

1) Initial attachment
2) Irreversible attachment
3) Micro-colony formation
4) Maturation
5) Dispersal

Question 5

What are spores resistant to?

Answer 5

Heat, radiation, desiccation and chemical agents

Question 6

What is bacterial sporulation?

Answer 6

Survival strategy when nutrients become exhausted
Used by some (but not all) gram-positive bacteria

Question 7

Name the 3 types of fungi

Answer 7

Yeasts, multicellular filamentous moulds, macroscopic filamentous fungi

Question 8

Name examples of pathogenic fungi

Answer 8

Candida spp, aspergillus fumigations and dermatophytes

Question 9

Name examples of non-pathogenic fungi

Answer 9

Penicillium species producing penicillins

Question 10

What are the consequences of microbial contamination?

Answer 10

Health hazard - contaminating organism or its toxins can cause disease, depends on patient, product and route of administration
Spoilage - therapeutic breakdown of actives or another component of the formulation, might lose aesthetic appeal (non-compliance), financial implications

Question 11

What is a sterile product?

Answer 11

single-use sterile packs or aseptic manufacture in a clean room

Question 12

What is a non-sterile product?

Answer 12

All products potentially exposed to micro-organisms during storage and multiple use products potentially exposed to microorganisms during use

Question 13

What do preservatives do?

Answer 13

Decrease the risk of microbial contamination throughout product shelf life

Question 14

What are the ideal properties of new antibiotic?

Answer 14

Broad spectrum
Rapid-antimicrobial action
Chemically stable
Effective at product pH
Compatible with the formulation
Physically undetectable
Constitute a small proportion of the product
Cost effective

Question 15

Name the 8 different classes of agents used as a perservative

Answer 15

Organic acids
Parabens, esters of p-hydroxybenzoic acid
Aromatic alcohols
Substituted alcohols
Biguanides
Mercurials
Substituted phenolic agents
Quaternary ammonium compounds

Question 16

Describe organic acids and parabens

Answer 16

Active at low concentrations
Non-toxic, cheap and stable
Reasonable spectrum of activity - bactericidal, fungicidal
Physically undetectable
Long-acting (but not fast acting)

Organic acids
- limited by pH dependence
- work at pH values up to pKa e.g. benzoic acid (pKa 4.2)
Oral products, tablet and capsules at 0.01-0.15%

Parabens
- overcome pH dependence of organic acids
- e.g. methyl paraben (pKa 8-8.5)
Oral products, tablets and capsules at 0.01-0.02%
Used in combination
BUT not very soluble, slow rate of kill

Question 17

What is the challenge test?

Answer 17

Assess activity with product in final container
Inoculate preserved product with 10(5)-10(6) test organisms per ml or per g of product
Incubate at specific temperatures and sample over 28 days
- assess viability by viable count
Preservative adequate if decreased in viability meets

Question 18

What is the suspension test?

Answer 18

Microorganism added to antimicrobials in aqueous solution, samples are taken at specific time intervals, and inoculated in broth with a neutraliser (inactivator broth)
Check for growth/no growth (i.e. does the broth become cloudy) or serial dilution and plating to count survival

Question 19

What factors affect the choice of any preservative?

Answer 19

Intended application - sterile vs non-sterile, route of administration, moisture content, susceptibility to attack
Number and type of microorganism present
Safety, stability and cost
Micro-environment
Properties of chemical agent

Question 20

What are the most likely contaminating organisms (bacteria) in oral products?

Answer 20

E. coli, S. aureus, P. aeruginosa, C. sp.

Question 21

What are the most likely contaminating organisms (fungi) in oral products?

Answer 21

C. sp, other fungi