Contamination

Non-viable contaminates?

Particulates, microbial products → toxins, metabolites, pyrogens

Viable contaminates?

Bacteria, viruses, fungi

Significance of contamination?

Health hazard, cause spoilage, therapeutic breakdown of any part of formulation, patient compliance, financial implications

Assessment of contamination?

Oral preparations

Sources of contamation?

Air, raw materials, Packaging, Equipment, Premises, People

Common microbes in air?

Spore formers, Bacillus, Clostridium

Non Spore formers, Staph, Strep → Gram +ve normally

Moulds

Yeats

Reduced air contamination?

Filtration → HEPA, UV light, chemicals

Common microbes in water?

98% Gram -ve

Pseudomonas

E.coli

Some Gram +ve

Micrococcus

Bacillus

Potable water?

Non sterile contains ions Chlorine → initial washing if using purified

Purified Water?

Potable water purified by ion exchange, distillation, reverse osmosis

Non sterile → washing containers

Water for injections BP

Distilled water, free from pyrogens

Sterile water for injections?

Autoclaved in suitable container

Sterile solutions

Water storage and distribution to minimise bacterial growth?

Temp 80C

Circulate water at positive pressure

Decrease pipeline

Use appropriate pluming materials

Include sterilisation system

Water Treatment?

Chemical → Hypochlorite and Cl2 gas

Filtration 0.2mm pore size filter and coarse prefilter

UV light → 254n light

Raw materials of Natural origin?

High levels of microflora, consider sterilisation

Raw materials Synthetic origin?

Low levels of microflora

Storage?

Dry materials → at specific moisture content

Wet materials → aim to lower moisture content, store at constant temp

Packaging cardboard?

If wet can have

Penicillium, Aspergillus, Bacillus, Pseudomonas

Packaging Glass?

Contamination on storage, decrease by cleaning and drying before use

Packaging Reusable?

Must be thoroughly washed and dried before use

Decreasing contamination of buildings?

Good design

Validating cleaning methods → spores

Reducing dust and use clean room → moulds, biofilms

Reduce personnel contamination?

Training, clothing, hygiene

Clean room

Controlled environment, filtered re-circulated air, control temp and humidity, at positive pressure

SAL for Aseptic manufacture?

10^-3

Disinfection?

Process of removing microorganisms of surfaces of inanimate objects

High level disinfectants?

Destroys all microorganism

Except prions

Aldehydes, Hypochlorites, Peroxygens

Intermediate level disinfectant?

Destroys all bacteria and most viruses, fungi

Not bacterial spore, some viruses, prions

Alcohols, Biguanides, Iodine/idophore, Phenolics, QACs

Low Level disinfectant?

Destroys most bacteria and some viruses, fungi

Not TB, some viruses and fungi, bacterial spores, prions

Phenolics

Ideal properties for disinfectants?

Broad spectrum

Rapid Kill (5 mins)

Must damage material being disinfected

Easy to prepare and use

Stable

Inexpensive

Antisepsis?

The destruction or inhibition of microorganism on living tissue

How to reduce skin flora before surgery?

Pre-op surgical scrubs

Patients pre-operation

What do alcohol gels not kill?

C. diff, noravirus

What are the 2 types of bacteria on skin?

Resident → Gram +ve, Transient -ve → antiseptics aim to remove all microbes off skin

Adequate spectrum of antimicrobial activity?

Immediate activity (1 min)

Persistent activity (how long for)

Cumulative (residual) antimicrobial effects after repeated use

Non toxic

Cost Motivation to use

Common Antiseptics?

70% Isopropyl alcohol

Factors affecting choice of chemical agent?

Intended application, No.& type micro-org present, Environmental factors, Safety, stability, cost, ease of use, Properties of chemical agent

Factors affecting disinfectant chosen?

Degree of killing needed, composition of surface being cleaned, degradation, absorption

Factors affecting antiseptic chosen?

Toxicity

Risk increases with broken skin

Choice of chemical agent Number of microorganisms?

High bioburden

High concentrations and longer exposure times

Biofilms x100 more resistant to disinfectants

Choice of chemical agent type of microorganism?

Prions, Spores, Mycobacteria, small non enveloped viruses, Gram negative bacteria, Fungi, Large non enveloped bacteria, Gram positive bacteria, Lipid enveloped viruses

Choice of chemical agent environmental?

Organic matter can decrease antimicrobial activity, chemically inactivate, absorption to the bacteria surface

Divalent cations decrease activity stabilise bacterial cell wall, block disinfectant absorption sites

What do chelating agents do?

Mop up cations and increase efficacy

Choice of chemical agent: safety?

D → some require extractor fan, skin protection

A → risk when applied to broken skin

Choice of chemical agent stability?

Unstable compounds stored in inactive form

Choice of chemical agent Concentration/ dilution?

High concentration increases efficacy and decreases exposure time but dilution does not always effect killing capacity in the same way

Dilution coefficient?

Shows what happens when decrease conc by half how much killing capcity goes down by

Choice of chemical agent Exposure time

Longer exposure time increases efficacy

Antimicrobial must stay wet

Disinfection/Decontamination Policy?

Gives info about which agents to use for specific purposes and how to use them

Suspension Test?

Quantitative test Calculates concentration of disinfectant/ antiseptic required to kill 99.999% of organisms

Time kill?

Quantitative test remove samples of microbe and anti microbial and determine viable count, time intervals short, repeat regularly to control resistance

Minimum Inhibitory Concentration (MIC):

Semi Qualitative: MIC is lowest concentration showing no growth (overnight culture)

Disc test

Qualitative indication of susceptibility to chemical agents (overnight growth)

Aliphatic alcohol examples?

Ethanol, Isopropanol

50% -90%

Antiseptic skin cleansing

Intermediate disinfection

Aliphatic alcohol advantages?

Broad range of activity against bacteria

Rapid kill

Water soluble

Relatively non toxic

No residues

Aliphatic alcohol disadvantages?

Not sporicidal

Isopropanol not virucudal

Poor penetration of organic matter

High dilution coefficient

Flammable

Aldehydes examples?

Glutaraldehyde (2%), Formaldehyde (2-4%) Ortho-phthalaldehyded 0.5%

Uses liquid or vapour sterilisation

High level disinfection

Biguanides examples?

Chlorhexidine

Uses surgical skin prep

Antiseptic hand wash

Health care antiseptic

Mouth wash

Halogens examples?

Liquid CL2

Iodine

Halogen liquid Cl2?

active against bacteria, fungi, viruses and spore

Irritant Rapid kill

Uses Water purification, disinfection

Hypochlorites Advantages?

Readily available

Cheap, compatible

Broad spectrum

Active against bacteria fungi, viruses

Rapid kill

Hypochlorites Disadvantages?

Corrosive

Irritant

Inactivated by organic matter

Uses Disinfectant 1-10%

Antiseptic 0.5%

Iodine Advantages?

Broad spectrum bacteria, viruses, fungi, spores

Rapid kill

Less affected by pH, temp and organic matter that Cl2

Iodine disadvantages

Stains skin and fabric

Irritant

Uses disinfectant and Antiseptic

Iodophores?

Allows slow release of I2 complex

povidone-iodine 10% betadine

Antiseptic Topical

Surgical scrub

Pre/Post OP cleaning

Put into wound dressing

Ensure contact for more than 2 mins to allow iodine to relase

Heavy metals advantages

Silver

Broad spectrum antimicrobial

Non toxic but expensive

Heavy metals uses?

Antiseptic Silver nitrite Silver sulfadiazine

In wound dressings

Medical devices, Catheters, breathing tubes, joint replacements

Peroxygen compunds?

Hydrogen peroxide, sterilant 35% liquid/vapour

Disinfectant/ antiseptic

Peracetic acid

sterilant 0.1-35% liquid/vapour medical equipment

Peroxygen compunds Advantages?

Powerful antimicrobials and sporicides

Active in presence of organic matter

Peroxygen compounds disadvantages

Unstable in sunlight

Irritant

Corrosive

Uses → used together

Biofilms and water purifications

Why are phenolic not used alone

Too toxic

Substituted phenols examples?

Cresols, Xylenols, Ethyl phenols, High boiling point phenolic tar acid

Substituted phenols advantages?

Broad spectrum rapid kill cheat not affected by organic matter

Substituted phenols disadvantages

Not sporicidal

Leaves residues

Uses Cresols disinfectants household

Xylenols and ethyl phenols, hospital disinfectants

High boiling point phenolic tar acids

Good rapid antimicrobial activity

cheap

but irritant

Activity decreased by organic matter and dilution

Uses General household disinfectants

Quaternary Ammonium Compounds (QAS) examples?

Benzalkonium chloride

Cetrimide

Quaternary Ammonium Compounds (QAS) advantages?

Water soluble

Most effective at pH 7-8.5

Stable

Non toxic

Non corrosive

Broad spectrum

Active at low conc

Quaternary Ammonium Compounds (QAS) disadvantages?

Not sporicidal

Activity decrease by organic matter

Uses disinfectants, antiseptics and preservatives

Combinations?

Can over come limitations such as persistent residual activity, better spectrum of activity, Synergy