bacteria 5,6

Question 1

when does microbial contamination occur

Answer 1

during manufacturing process and products escape quality assurance checks

Question 2

what are the impacts of microbial contamination

Answer 2

medicine unfit for use, potential litigation, financial loss, limits supply to patients, health hazards, infections, endoxins

Question 3

what medicine components/pharmaceutical ingredients are at risk of microbial attacks

Answer 3

active drugs- metabolised to less potent/chemically inactive forms

non/anionic surfactants- alkyl/alkylbenzene sulphonates are readily metabolised

organic polymers (thickening agents)- microbial depolymerisation

humectants- readily metabolised in low amounts

fats/oils- attacked when dispersed in aqueous formulations

sweeteners/flavourings/colouring agents- substrates for bacteria, high conc are resistant to degradation

Question 4

how to resist microbial contamination

Answer 4

use preservatives

Question 5

what are visible signs of contamination

Answer 5

unpleasant smell, sour taste, appearance change, texture/viscosity changes, sedimentation, production of bubbles, cracking, change in efficacy

Question 6

what causes viscosity and textures to change when a medicine component is contaminated

Answer 6

metabolism of thickening agents or sugar polymerisation

Question 7

what are preservatives used for

Answer 7

resist microbial contamination

Question 8

factors that affect/cause microbial contamination of a pharmaceutical product

Answer 8

type/size of inoculum, nutritional factors, moisture content (greater solute conc=lower water activity), redox potential, storage temp, pH, packaging design protection of microorganisms in pharmaceutical products

Question 9

list some non-antibiotic antimicrobials available

Answer 9

antiseptics, disinfectants, preservatives, creams/ointments, disinfectant sprays, biocides, alcohol based gel scrubs

Question 10

describe how the non-antibiotic antimicrobial, antiseptics, work

Answer 10

destruction/inhibition of microorganisms on living tissue, against sepsis, prevents systemic infection, non toxic to host, ex vivo use (wounds, mouth)

Question 11

what is ex vivo

Answer 11

outside living body

Question 12

what is sepsis

Answer 12

body doesnt respond properly to an infection

Question 13

describe how the non-antibiotic antimicrobial, disinfectants, work

Answer 13

removes microorganisms from inanimate objects/surfaces, kills/reduce numbers to a level that is acceptable for defined purpose, most are too toxic to use on body tissue

Question 14

describe how the non-antibiotic antimicrobial, preservatives, work

Answer 14

added to pharmaceutical,cosmetics,foods to prevent microbial contamination, non toxic, lower activity level than antiseptics and disinfectants

Question 15

what trait must a preservative have to be considered efficient

Answer 15

effective against two bacterias, a yeast and a mould

Question 16

a chemical exhibits antimicrobial activity if…

Answer 16

it interacts and enters a host cell

Question 17

how do non-antibiotic antimicrobials initially interact with the cell wall/membrane

Answer 17

electrostatic or hydrophobic interactions

Question 18

how do non-antibiotic antimicrobials enter a cell

Answer 18

porin channels or diffusion

Question 19

what affects the efficacy of a biocide

Answer 19

affinity for structural/molecular components

Question 20

what is the rate of non-antibiotic antimicrobials activity affected by

Answer 20

temperature, concentration pH, solubility, type/form of microorganisms present

Question 21

how do biocides work/exhibit antimicrobial activity

Answer 21

structural damage to cell wall/membrane or interactions with cellular components

Question 22

why is resistance to biocides not often seen

Answer 22

biocides are short lasting

Question 23

which type of bacteria is more resistant to biocides

Answer 23

gram-negative

Question 24

list the 5 methods of sterilisation

Answer 24

moist heat (steam), dry heat, ionising radiation, gas, filtration

Question 25

describe how moist heat (steam) is used for sterilising, what it is used to sterilise and its lethal effects

Answer 25

used for: culture media, medical implements (tools), aq injections, ophthalmic preparations lethal effects: denaturation of enzymes or destruction of cell steams at 121-134c for 20 minutes on phase boundary with water in an autoclave 2 types of steams: wet steam (boiled within autoclave) and dry steam (boiled externally and supplied under pressure)

Question 26

what is an autoclave

Answer 26

pressure vessel

Question 27

why is dry steam preferred over wet steam in moist heat sterilisation

Answer 27

wet steam soaks the load preventing steam penetration

Question 28

describe how dry heat is used for sterilising, what it is used to sterilise and what is its lethal effects due to

Answer 28

used for: medical implements, glassware, non aqueous thermo stable liquids, powders lethal effects due to oxidative processes, less effective than moist sterilisation involves higher temps, 160-180 up to 2 hours, effective destruction of bacterial endotoxins produced by gram negative bacteria works by conduction, heat absorbed by exterior surface then pass inward to the next layer until entire object reaches proper temp to achieve sterilisation

Question 29

describe how ionising radiation is used for sterilising, what it is used to sterilise and what its lethal effects are due to

Answer 29

used on: dry products, finish and packaging components, medical implements, medical implants lethal effects due to microbial DNA damage, leads to cell death as consequence of ionisation and free radical production or excitation from uv uses accelerated electrons/gamma rays/UV light, exposure to 25 kGy for effective kill bacterial resistance to irradiation depends of effectiveness of their repair mechanism, UV is less effective as it has lower energy so less DNA damage

Question 30

what is UV ionising radiation sterilisation useful for

Answer 30

water sterilisation

Question 31

describe how gas is used for sterilising, what it is used to sterilise and what its lethal effects are due to

Answer 31

used for: reusable medical implements, pharmaceutical components (glassware, plastics, syringes), medical equipment lethal effects due to alkylation of sulfhydryl, amino, hydroxyl and carboxyl groups on proteins and nucleic acids uses chemically reactive gases that are toxic to the operator (eg. formaldehyde, hydrogen peroxide, ethylene oxide) lethality non uniform with increasing conc, temp, humidity

Question 32

describe how filtration is used for sterilising, what it is used to sterilise

Answer 32

used for: most pharmaceutical solutions and suspensions, biological products (depends on size), air involves passing substance through a filter (0.22um) under pressure, removes bacteria instead of destroying, particles entrapped within mesh

Question 33

what does the efficiency of filtration sterilisation depend on

Answer 33

adsorption, material entrapped, charge effects, mesh structure, depth, initial bioburden

Question 34

what is bioburden

Answer 34

number of contaminated microorganisms in a material before sterilisation procedure is carried out

Question 35

what is quality assurance

Answer 35

arrangements put in place to ensure final product is at quality required for its purpose

Question 36

what does good quality mean

Answer 36

fit for its therapeutic purpose, safe for adminsitration

Question 37

what is good manufacturing practise (GMP)

Answer 37

part of quality assurance that ensures the product is consistently manufactured -includes control of ingredients, plant construction, process validation, production, cleaning

Question 38

what is quality control

Answer 38

part of quality assurance that conducts test at each stage of manufacture, products not released until they pass the test

Question 39

what is in process control

Answer 39

any test on product during manufacture -ensures manufacturing equipment/environment is checked before and after use -test/controls must be documented to confirm pass criteria has been met

Question 40

what is quality risk management and what happens when a deviation occurs

Answer 40

systemic process for identification, assessment and control of risks to quality of pharmaceutical products across product lifestyle when deviation occurs, quality management system initiates tests to determine cause and identify corrective actions and risks asses and confirms effectiveness of change

Question 41

what is HACCP and its steps

Answer 41

hazard analysis of critical control points= risk assessment tool for evaluating steps of a manufacturing process and in response to a deviation -analyses/identifies potential hazards, determines critical control points (CCP) to control hazard and limit control of CCP, establish in house control methods to contain CCP hazards and corrective measures to correct CCP, confirm HACCP regime is functioning and then documentation of above

Question 42

name 5 main sources of contamination during pharmaceutical manufacturing process

Answer 42

raw materials- can carry natural bioburden equipment- used in processing/holding/transferring/packaging, generation of dust and aerosols, improper cleaning personnel- person to person contact, poor hygiene, natural flora atmosphere- source of dust and particles including microorganisms and spores packaging- some dont appropriately exclude microbial contaminants during storage

Question 43

ways to control microbial contamination

Answer 43

environmental hygiene- disinfect areas, no stagnant water or any water, clean air, educate workers quality of starting materials- correctly stored, free from bacteria and endotoxins, raw materials stored correctly to prevent contamination, quality checks process design- user defined requirements, installation and monitoring of equipment, fully defined/evaluated/validated manufacturing process quality control and documentation- environmental monitoring in process and out of hours, personnel training, documentation of raw materials/packaging materials/intermediate products required for each batch (traceability), room classifications qualified prior to use packaging/storage- keeps contents in and contaminants out, clean, suitable for purpose, store at appropriate temperature

Question 44

what does sterile mean

Answer 44

free of viable microorganisms -product must undergo sterilisation process to ensure minimum level or sterility assurance

Question 45

what are sterile products

Answer 45

medicines that are administered directly to blood stream or body tissue -sterile avoids possibilities of microbial degradation or infection

Question 46

what is sterility assurance limit (SAL)

Answer 46

numerical value that predicts the probability that microorganisms has survived sterilisation process -acceptable probability for a pharmaceutical product post sterilisation is 10^-6

Question 47

what is the aim of sterility testing

Answer 47

attempts to reveal presence or absence of viable microorganisms in a sample, only small portion of batch is tested (40-60 out of >100,000), must be conducted in a suitable environment and be validated

Question 48

if product is manufactured aseptically what is the only available analytical method

Answer 48

sterility testing, show regulatory authorities the sterility status of it

Question 49

describe sterility test environment

Answer 49

strictly controlled as aseptic processing environment, isolator technology, hydrogen peroxide gassing, environmental monitoring, ISO class 5/GMP grade A

Question 50

list pharmacopeial requirements for sterility testing

Answer 50

-for products that cant be filtered and medical devices, use membrane filtration or direct inoculation (?) -media used FTM and TSB -incubate samples for 14 days at 2 different temperatures to allow microbial growth of bacteria/fungi/yeast

Question 51

what is FTM and TSB

Answer 51

FTM=fluid thioglycollate medium TSB=tryptic soy broth

Question 52

describe the observations/interpretations of results of sterility test

Answer 52

-samples comply or dont (its either a yay or a nay) -turbidity/growth indicates noncompliance -test complies if no evidence of microbial growth is found

Question 53

4 reasons sterility tests can be invalid

Answer 53

1. data of microbiological monitoring of sterility testing facility shows a fault 2. review of testing procedure reveals fault 3. microbial growth found in negative control 4. after determination of identity of microorganisms isolated from test, growth of species ascribed unequivocally to faults with respect to materials/techniques used when conducting sterility test (?)

Question 54

limitations of sterility test

Answer 54

-can only recognise microorganisms able to grow under conditions of the test -sample size restricted, only provides gross estimate of state of sterility of product -sample size set arbitrarily so doesnt provide statistically significant population to estimate sterility -results cant be used independently to determine sterility of a batch

Question 55

what does the susceptibility of microorganisms to biocides depend on

Answer 55

the microorganism and stage of life cycle

Question 56

what is bioburden

Answer 56

number of contaminated microorganisms in a material before sterilisation procedure is carried out