ROGO

Question 1

General considerations for a clean room

Answer 1

1. Logical layout
2. Airflow + air supply
   
   • Clean room tech. founded upon use of high efficiency particulate air (HEPA) filters
   • HEPA filters remove 99.9997% of particles 0.3 micrometres or larger
   • HEPA filtered provides products with protection from airborne contaminants by contnuously sweeping away ‘personnel derived’ particulates from the immediate work area using laminar airflow
3. Surfaces
   
   • ​​Smooth flat + impervious to minimise reservoirs/traps for particulates + microorganisms
   • Junctions between walls + ceiling should be seamless + windowsills should be avoided
4. Ease of cleaning + disinfection

Question 2

Personnel Training

Answer 2

1. Good personal hygiene
2. Clothing
3. Personal protective equipment
4. Good aseptic technique + good manufacturing practice
5. Movement within manufacturing area

Question 3

Terminal Sterilisation

Answer 3

Sterilisation is the last step in the manufacturing process once the product is sealed within final container

Question 4

Aseptic Processing

Answer 4

Procedure in which the medicine, container and closure are sterilised separately the combined together to give the final product

• Risk of microbial contamination > when products are terminally sterilised
• Aseptic technique used in manufacturing products which are terminally sterilised to maintain a low level of contamination in the beginning stages of production

Question 5

What are the main sources of contamination?

Answer 5

1. Personnel
2. Air in surrounding environment

Question 6

What are clean rooms?

Answer 6

Controlled environments where parameters (e.g. airflow, microbial + particculate quality of air, equipment surfaces, room surfaces, + personnel) are all monitored + must meet all specific requirements.

Question 7

Why is it important to specify brand of Amphotericin B used?

Answer 7

Dosage recommendations differ between brands due to differences in their pharmacodynamics + pharmacokinetics

Question 8

What is a common cause of morbidity + mortality in cancer patients?

Answer 8

Systemic fungal infections especially those with chemotherapy induced neutropenia

Question 9

Molecular target of AmBisome

Answer 9

Ergosterol (a component of fungal membranes)

• Binding of amphotericin to ergosterol causes fungal cell death by induing pores to form, leading to increased membrane permeability

Question 10

How can we prevent an allergic reaction prior to giving Amphotericin-containing products (including AmBisome)?

Answer 10

Administer a test dose of 1 mg over 10 minutes before treatment

Question 11

How do we avoid dosage miscalculations for amphotericin B?

Answer 11

BNF states to state brand dispensed

Question 12

AmBisome may not fully dissolve.

How do we prevent large particles entering IV bag?

Answer 12

Using a 5 micrometre needle to transfer contents

Question 13

What is AmBisome composed of?

Answer 13

Each vial contains:

• 50 mg of amphotericin (50,000 units) encapsulated in liposomes
• 900 mg Sucrose

Question 14

How sould AmBisome be administered?

Answer 14

IV infusion over 30-60 minute period

Question 15

What is the recommended AmBisome IV concentration infusion?

Answer 15

0.20 mg/ml to 2.00 mg/ml

Question 16

Daily dose of AmBisome

Answer 16

3.0 mg/kg of body weight + increased stepwise to 5.0 mg/kg

Question 17

What is AmBisome compatible with?

Answer 17

• Water for Injections
• 5% Glucose

Question 18

What is AmBisome incompatible with?

Answer 18

• Saline solutions
• Drugs
• Electrolytes

Question 19

What is used to transfer AmBisome into a sterile container with Glucose?

Answer 19

5 micrometre filter needle

(to filter out particles not bacteria)

Question 20

What can cause precipitation of AmBisome

Answer 20

• Other solutions
• Bacteriostatic agent

Question 21

An in-line membrane filter is used for the IV infusion of AmBisome.

What should the mean pore diameter be?

Answer 21

The mean pore diameter of the filter should not be less than 1.0 micrometres

Question 22

How do we flush the IV line?

Answer 22

An existing IV line is flushed with 5% Glucose prior to infusion of AmBisome

Question 23

When is it good practice NOT to dispose needles + syringes together?

Answer 23

Where a syringe has to have needle removed when attaching a transfer device or a filter then needle has to be carefully re-sheathed

Question 24

What is the shelf life of AmBisome after reconstitution?

Answer 24

Glass vials + propylene syringes up to 7 dyas at 2-8 degrees celsius

Question 25

When is a hypodermic needle used?

Answer 25

A syringe to inject medication into the body or as part of a procedure for making meds in a SPU

Question 26

Difference between Luer-slip + Luer lock?

Answer 26

Luer slip - needle slips on + off syringe Luer-lock - needle = screwed + locked onto syringe to create a leak-free seal

Question 27

What fitting do most SPUs have?

Answer 27

Luer-lock

Question 28

How many times can you use mos needles?

Answer 28

Single use

Question 29

How can you maintain needle sterility?

Answer 29

Protective packaging Use-by dates Batch/lot numbers Aseptic technique

Question 30

Safe use of needles to avoid accidents

Answer 30

Fit needle onto syringe whilst it is still in its sheath Unsheath + resheath using NeedleSafe Keep hand benhind needle tip @ all times Minimise handling, do not pass needle from hand to hand Used needles must be placed into sharps bin

Question 31

What are Needle Stick injuries?

Answer 31

Skin punctures caused by hypodermic needles

Question 32

What is the no touch technique?

Answer 32

Never to touch any critical site when making a sterile product

Question 33

What is a critical site?

Answer 33

Any part of a sterile product/equipment used in its preparation that must remain sterile to prevent contamination of the final product

Question 34

Quality control system for Aseptic Dispensing

Answer 34

Operator Training Standard operating procedures Environmental monitoring Broth transfer tests

Question 35

How many decimal places is it appropriate to work with?

Answer 35

3 ## Footnote *No trailing zeros*

Question 36

Rate what movement has the highest no. of particles dispersed/min from lowest

Answer 36

1. Sitting still (100k particles/min) 2. Gentle movement of arms, hand + head (500k particles/min) 3. Active movement of arms, hands + head (1 million/min) 4. Change from sitting to standing/reverse (2.5 million/min) 5. Walking (10 million/min)

Question 37

When prepaing cytotoxic chemotherapy, which helps prevent operator exposure?

Answer 37

Negative pressure hoods Full length suits when using open devices Double gloving with nitrile rubber gloves Chemotherapy never produced on an open bench

Question 38

What is sterility?

Answer 38

Absence of viable microorganisms

Question 39

Sterility of a product cannot be guaranteed by testing. How can we be assured of sterility?

Answer 39

Application of a suitably validated production process

Question 40

Principles of GMP

Answer 40

* Qualified personnel with appropriate training * Adequate premises * Suitable production equipment, designed for easy cleaning + sterilisation * Adequate precautions to minimise the bioburden prior to sterilisation * Validated procedures for all critical production steps * Environmental monitoring + in-process testing procedures

Question 41

Methods of terminal sterilisation

Answer 41

Steam Dry heat Ionising radiation

Question 42

What is the nominal pore size of a bacteria-retentive membrane?

Answer 42

0.22 micrometres or less

Question 43

How is solute loss during filtration?

Answer 43

Adsorption on to the filter

Question 44

Why is sterilisation by filtration used?

Answer 44

For solutions/liquids not stable enough to withstand terminal sterilisation by autoclaving (e.g. products which are thermo-labile) ## Footnote *Not a terminal sterilisation method*

Question 45

Why is filtration not a terminal sterilisation method?

Answer 45

It is followed by aseptic transfer of the sterilised solution into the final container which is then sealed

Question 46

Why is filtration different from other methods of sterilisation?

Answer 46

Process physically removes microorganisms

Question 47

Major mechanisms of filtration

Answer 47

1. Sieving particles out that are larger than the pore size 2. Adsorption 3. Deposition in the filter bed 4. Retention in capillary films within the filter bed

Question 48

Factors to consider when choosing a filter

Answer 48

1. **Pore size -** a pore size of 0.2 micrometres or less 2. **Inertness -** filter does not shed fibres into the product during filtration. Filter should not leach chemical substances into the product. 3. **Flow rate -** adequate flow rate achieved

Question 49

What are the 2 main types of filter types?

Answer 49

1. **Depth filters** 2. **Membrane filters**

Question 50

What is the preferred type of filtration?

Answer 50

Membrane filters Made from cellulose esters (or other polymers)

Question 51

Membrane filters have a low dirt handling capacity. (e.g. easily clogged by particles just larger than their pore diameter) How can we extend its working life?

Answer 51

Using a prefilter decreases blockage of final filter

Question 52

How can we reduce particulate contamination?

Answer 52

Pre-filtered water is used Polarised light viewer/strong light with the naked eye can check for particles in pre-filtered water

Question 53

What is laminar airflow?

Answer 53

Movement of air within confined boundaries @ uniform velocity + along parallel flow lines

Question 54

What do we use to filter air supply?

Answer 54

HEPA filters Continuous unidirectional flow of filtered air sweeps away any airborne contaminants generated by operator during manipulations within cabinet

Question 55

How can the air be displaced?

Answer 55

Horizontal Vertical

Question 56

What happens of airflow is physically obstructed?

Answer 56

Cause downstream turbulence This increases risk of product contamination

Question 57

Rate how much saliva travels when: * talking * coughing * sneezing

Answer 57

Talking = 2-3 feet Coughing = 4-6 feet Sneezing = 10-15 feet

Question 58

Assess operator's aseptic technique

Answer 58

Universal operator broth transfer tests Finger dabs