MICROBIAL SPOILAGE

Infection risk and contamination control

Pharmaceutical products
*prevention *treatment *diagnosis components/ingredients GMP *safety *efficacy *quality stable acceptable

sterility acceptable microbial limits

Spoilage

deterioration
* physical property
* chemical property

WASTAGE MICROBIAL CONTAMINATION

PHARMACEUTICAL PRODUCTS SUSCEPTIBLE

TO MICROBIAL ATTACKS Therapeutic agents Surface-active agents Non-ionic surfactants Organic polymers Humectants Fats and oils Sweetening, flavoring, colouring agents Preservatives, disinfectants

RATE OF DETERIORATION

Depends on:

Molecular structure of the chemical Physico-chemical property of a particular environment Type and quantity of microbes Availability of metabolites for use as another energy source = more synthesis and multiplication

OBSERVABLE EFFECTS OF MICROBIAL ATTACK

ON PHARMACEUTICAL PRODUCTS

Organoleptic

Smell (unpleasant/sickly) Taste (sour, fishy, bad eggs, bitter, earthy, sickly) Color (pigmented) Viscosity/consistency/texture (thickening, less viscous, slimy, creaming, cracking) Sedimentation of suspended ingredients Gaseous metabolites (visible bubbles)

FACTORS AFFECTING MICROBIAL SPOILAGE OF

PHARMACEUTICAL PRODUCTS Type and size of contaminant inoculum Nutritional factors Moisture content: water activity Redox potential Storage temperature pH Packaging design Preservatives

HEALTH HAZARDS OF CONTAMINATED

PHARMACEUTICAL PRODUCTS Outbreaks of infection Detrimental to immunocompromised Secondary infections, localized or systemic infections (such as sepsis, including those caused by toxins) Death

See p 280 table 17.1 (contaminants of pharmaceutical products)

SOURCES AND CONTROL OF CONTAMINATION

Source IN MANUFACTURE *Industry Material at risk of contamination 1 Raw materials 2 Processing equipment 3 Cleaning equipment 4 Air 5 Staff 6 Packaging Control of contamination High microbiological std Maintenance (cleaning) Maintenance Filtration Hygiene practices Intact, sterile

*Hospital

1 Water 2 Environment 3 Packaging

Monitoring GMP Thorough washing & drying

SOURCES AND CONTROL OF CONTAMINATION

Source How contamination occurs Application by hand Control of contamination Hand hygiene Use of suitable, disposable applicators Use of disposable dispensers Individualized packs Non-touch techniques Use of individual supplies in small quantities

IN USE *Human

*Environmental

splash-back mechanism Air contamination Use of stock solutions

SOURCES AND CONTROL OF CONTAMINATION

Source IN USE *Equipment How contamination occurs Re-use of applicators Use of contaminated equipment Use of contaminated cleaning agents Control of contamination Use of disposable applicators Proper maintenance of equipment Use disinfectants for intended use only Follow recommended use of disinfectants

EXTENT OF MICROBIAL CONTAMINATION

In manufacture

Outbreaks of infection

In use
Home use: less often to be contaminated but contains lower /fewer organisms when used in small quantities Depends on storage conditions

FACTORS DETERMINING THE OUTCOME OF MEDICAMENT-BORNE INFECTION

Type and degree of microbial contaminantion Route of administration Resistance of patient

PRESERVATION OF MEDICINES USING ANTIMICROBIAL AGENTS Minimizes risk of contamination Kills low levels of contaminants introduced during storage or repeated use Usually non-selective in action May cause hypersensitivity reactions Consider factors that influence anti-microbial activity

EFFECT OF PRESERVATIVE CONCENTRATION,

TEMPERATURE AND INOCULUM SIZE

Concentration: varies depending on agent used Temperature: varies depending on agent used Preservatives are used up as they inactivate contaminating organisms

FACTORS AFFECTING THE AVAILABILITY OF

PRESERVATIVES Interaction with the solution Number of contaminants pH Efficiency in multiphase systems (formulation) Container or packaging (adsorption, volatilization, etc.)

QUALITY ASSURANCE AND CONTROL OF

MICROBIAL RISK IN MEDICINES

QMS

Effective QAP in

Formulation Design Development

Examples: Preservative challenge test (D-value) GMP (manufacture, control of ingredients, plant construction, process validation, production and cleaning) Bioburden assay Pyrogen testing (Limulus test) Toxin detection Test for signs of physico-chemical spoilage Post-market surveillance