Microbial spoilage, infection risk

and contamination control

Spoilage deterioration of pharmaceuticals
GPMP Good Pharmaceutical Manufacturing
practice quality, safety, efficacy, stability,
acceptable to patients
Consequences of contamination:
Spoiled product
Threat of litigation
Health hazard to patients

Pharmaceutical ingredients
susceptible to attack
Therapeutic agents
Less potent/inactive; thalidomide

Surface-active agents
(anionic surfactant, soap)

Non-ionic surfactants
Increasing chain length and branching decrease
ease of attack; Pseudomonas in quaternary
ammonium antiseptics

Organic polymers
Thickening & suspending agent; agar

Pharmaceutical ingredients
susceptible to attack
Humectants
Glycerol / sorbitol to reduce water loss

Fats and oils

Hydropobic; fungal attack

Sweetening, flavouring & coloring agents

Pseudomonas

Preservatives and disinfectants

Gram negative; Pseudomonas in eye drops

Observable effects
of microbial attack
Smell, sour taste fatty acids and their ketonic
oxidation products
Discoloration by microbial pigments
Loss of viscosity & sedimentation
Gaseous metabolites seen as trapped bubbles
within viscous formulations

Factors affecting microbial spoilage

Type / size of contaminant inoculum
Raw materials contaminated, lapse in plantcleaning protocol, biofilm, product was grossly
misused during administration
Lag period before spoilage begins

Nutritional factors
Metabolic adaptability

Factors affecting microbial spoilage

Moisture content water activity
The greater the solute concentration, the lower is
the water activity. Most ogranisms grow best in
dilute solutions (high Aw).
Tablet film coating greatly reduces water vapor
uptake during storage while allowing ready
dissolution in bulk water.

Factors affecting microbial spoilage

Redox potential
Ability of organism to grow in an environment

Storage temperature
Spoilage occurs over -20 to 60 degrees C
Deep freeze at -20C for long-term storage
Short term storage of dispensed TPN

pH
Bacterial spoilage more likely at neutral pH.

Factors affecting microbial spoilage

Packaging design
Control entry during storage and use
Medicines rely on their low Aw to prevent
spoilage

Protection of microbes w/in pharmaceutical

products
Surfactants, suspending agents, proteins can
increase the resistantce of orgs to preservatives

Hazard to Health
Salmonella in pacreatin and thyroid extract
Loss of sight; burn patients
Surfactants increase resistance of
microorganisms.
Pseudomonas in TPN fluids
HIV infection infection of hemophiliacs
CJD from human growth hormone
Contaminated IV fluid; moral

Sources of control of
contamination
I. In manufacture
Raw materials, processing equipment, cleaning
equipment, area with filtered air, personal and
production hygiene, suitable packaging
Hospital manufacture
Water - > 80C & circulated a flow rate of 1-2 m/s to prevent
the build up of bacterial biofilms in the piping.
Environment - GMP
Packaging & re packaging

II. In use (human, environment & equipment

sources)

Sources of control of
contamination
II. In use cross infection (human,
environment & equipment sources)
improvements in packaging & changes in nursing
practices
Human- topical products are most at risk
Pseudomonas
environmental airborne; static level of 10^210^3/g or per mL
Equipment reuse, cosmetic products, humidifier,
incubators, ventilators, resuscitators

Extent of microbial contamination

Specific product / Isolated incident
In manufacture
Thyroid tablets with Salmonella
Hydrocortisone eye ointment with Pseudomonas

In use
Heavy contamination 18 % > 10^4 CFU/g or
CFU/mL

Factors determining the outcome

of a medicament-borne infection
Type and degree of microbial contamination
Route of administration
epidural

Resistance of the patient

 QMS
QA
QC