CHAPTER17 MICROBIAL SPOILAGE,

INFECTION & CONTAMINATION

CONTROL
2.1 PHARMACEUTICAL
INGREDIENTS SUSCEPTIBLE TO
MICROBIAL ATTACK

Therapeutic agents- under

laboratory conditions, it has been
show that a variety of
microorganisms can metabolize a
wide assortment of drugs, resulting
in loss of activity.
-in practice, reports of drug
destruction in medicines are less
frequent
Fats and oil- usually attacked
extensively when dispersed in
aqueous formulations such as oil-inwater emulsions; fungal attack has
been reported
Sweetening, flavoring & coloring
agents- ready substrates for
microbial growth [Pseudomonas
spp., Ps. aeruginosa]
Preservatives & disinfectants- can
be metabolized by a wide variety of
Gram-negative bacteria, although
most commonly at concentrations
below their effective use levels.

2.2 OBSERVABLE EFFECTS OF

MICROBIAL ATTACK ON
PHARMACEUTICAL PRODUCTS
- Early indications of spoilage are often
organoleptic, with the release of
unpleasant smelling & tasting
metabolites such as sour fatty acids,
fishy amines, bad eggs, bitter, earthy
or sticky tastes and smells

- unappealingly discolored by microbial

pigments
2.3 FACTORS AFFECTING
MICROBIAL SPOILAGE BY
PHARMACEUTICAL PRODUCTS

TYPES & SIZE OF

CONTAMINANT
INOCULUM

-Low levels of contaminants may not

cause appreciable spoilage,
particularly if theyre unable to
replicate in a product
-Examples:
1. Raw materials were unusually
contaminated [Ex: syringe
contaminated= levels of
contaminant]
2. Lapse in the plant-cleaning
protocol
3. A biofilm detached itself from
within supplying pipeworks
4. Product had been grossly misused
during administration; multiplies
infection and contaminant

NUTRITIONAL FACTORS

-The use of crude vegetable/ animal

products in a formulation providers
an additionally nutritious
environment
-even demineralized water prepared
by good ion-exchange methods will
normally contained sufficient
nutrients to allow significant growth

of many waterborne Gram-negative

bacteria such as Pseudomonas spp.

2.3.3 MOISTURE CONTENT;

Aw
WATER ACTIVITY (
)

-the the solute concentrations, the

its water activity
-most microorganisms grow best in
A
dilute solutions ( w )
-the

Aw

of aqueous formulations

can be to increase resistance to

microbial attack by the addition of
/ concentrations of sugars/
polyethylene glycols
[microorganisms will not grow]
2.3.4 REDOX POTENTIAL
- Microbes require compatible
terminal electron acceptors to permit
their respiratory pathways to
functions
2.3.5. STORAGE
TEMPERATURE
- Around neutrality bacterial spoilage
is more likely above pH 8 [e.g. soapbased emulsions] spoilage is rare
-products with pH levels [e.g. fruitjuice-flavoured syrups with a pH 34], mould or yeast attack is more
likely
-Yeast can metabolize organic acids
and raise the pH to levels where
secondary bacterial growth can
occur.

2.3.6. PACKAGING DESIGN

-design inhibits exposure to
contaminants/microbial
- self-sealing rubber wads must be
used to prevent microbial entry into
multidose injection contaminers

4. SOURCES & CONTROL

OF CONTAMINATION

4.1 IN MANUFACTURE
- Have a standard protocol to ensure
quality of products; beneficial to
consumers
-quality must be built into the
product at all stages of the process
and not simply inspected at the end
of manufacture:
A. Raw materials, particularly water
and those of natural origin, must be a
microbiological standard
B. All processing equipment should
be subject to unplanned preventive
maintenance and should be properly
cleaned after use to prevent crosscontamination between batches
C. Manufacture should take place in
suitable premises supplied with
filtered air [enough space for
working environment]
D. Staff involved in manufacture
should not only have good health but
also personal hygiene

E. The end-product requires suitable

packaging which will protect it from
contamination during its shelf life

- spot checks occasionally revealed

medicines of unacceptable quality
and so necessitated product recall

4.2.1 HUMAN SOURCES

- Topical products are considered to
be most at risk, as the product will
probably applied by hand, thus,
introducing contaminants from the
resident skin flora of staphylococci
-Micrococcus spp. & diphtheroids
but also perhaps transient
contaminants, such as Pseudomonas
or coliforms which would normally
be rermoved with effective handwashing
1. Self-infection

5.2 IN USE
-Medicines used in the home arent
less often contaminated but also
contain levels of contaminants &
fewer pathogenic organisms than in
hospital [factor: location that
contaminates drugs]
6. FACTORS DETERMINING
OUTCOMES OF A
MEDICAMENT-BORNE
INFECTION
-A pt.s response to the microbial
challenge of a contaminated
medicine may be diverse and
unpredictable

Patient Medicine
*human to products
2. Cross-infection
Patient X Medicine Patient Y,Z
Nurses hands
*cross contamination- humans to
prod. To humans [ex: drug]

-Clinical reactions may not be

evident in 1 pt., yet in another maybe
disputable
-factors:
A. type & degree of microbial
contamination

5 EXTENT OF MICROBIAL
CONTAMINATION

B. Route of administration

5.1 IN MANUFACTURE

C. Pt.s resistance

- Non-sterile products was routinely

found to be contaminated with
Bacillus subtilis, Staph.albus, yeast
& moulds

6.1 TYPE & DEGREE OF

MICROBIAL CONTAMINATION
-Microorganisms that contaminate
medicines & cause disease and pt.s
may be classified as true pathogens
or opportunist pathogens [ex:

Clostridium tetani & Salmonella

spp.]
-factors: population[affected] such as
compromised hospital pt.s i.e.
elderly, burned, traumatized or
immunosuppressed
6.2 ROUTE OF
ADMINISTRATION
- Contaminated products injected
directly into the bloodstream or
instilled into the eye cause the most
serious problem [fast spread of
infection due to circulation of blood]
-Acidity of the stomach may provide
a successful barrier depending on
whether the medicine is taken on an
empty/full stomach [acidity= empty
stomach]
6.3 PT.S RESISTANCE
-Hospital patients are more exposed
& susceptible to
infection(nosocomial) than those
treated in the general community
[factor: location]
7. PRESERVATION OF
MEDICINES USING
ANTIMICROBIAL AGENTS:
BASIC PRINCIPLES
7.1 INTRODUCTION
- An antimicrobial preservative
may be included in a formulation to
minimize the risk of spoilage
-Preservation should never be added
to mask poor manufacturing

processes [ex: Hepa lane, they

thought that if you cook it again
microbes will be removed]
7.2 EFFECTS OF
PRESERVATIVE
CONCENTRATION TEMP. &
SIZE OF INOCULUM
- Changes in the efficacy of
preservatives vary exponentially
with changes in concentration
-A reduction in temp. from 30C 20C could result in a significantly
reduced rate of kill for E.coli [meet
the temp. for organism reduces its
bacterial growth]
- conc.= more effective substance
8. QUALITY ASSURANCE &
CONTROL OF MICROBIAL
RISK IN MEDICINES
8.1 INTRODUCTION
*Quality Management System
[QMS]:
a. Quality Assurance= planned &
systematic activities implemented in
a quality system so that quality
requirements for a product/service
will be fulfilled.
>EX: before and after, clean the
working area; daily checking of
temp. of incubator
b. Good Pharmaceutical
Manufacturing Practice [GPMP] =
encompasses beyond manufacturing;
instructions & procedures are written

in ambiguous language especially the

materials

8.5 POSTMARKET
SURVEILLANCE

>ex: sufficient & appropriately

trained personnel

-Constant study

8.4 QUALITY CONTROL

PROCEDURES
-observation technique & activities
used to fulfill requirements for
quality
-evaluation to indicate needed
corrective responses
-ex: intervally check if + control can
show + results to the expected
outcome

-statistics
*are conducted to ensure the safety
of the consumers