Small Scale Manufacturing - Maria Connolly

Question 1

What was the NHS Carter Report?

Answer 1

About being able to use part vials correctly (cost effective)

Question 2

What does CIVAS stand for?

Answer 2

Central Intravenous Additive Service

Question 3

What is the preferable tonicity of IV products?

Answer 3

Isotonic

Question 4

What are the 3 types of container for IV products?

Answer 4

PVC –> DEHP containing which can cause harm, and will cause oxygen and moisture loss

EVA –> No leaching of plasticisers (like PVC), but poor barrier to oxygen

Multilayer –> Best option given the others

Question 5

What is and isnt allowed in SC/IM/IA formulations?

Answer 5

Volume less than 2mL

Particulates are okay (unlike IV)

Question 6

If an IV drug is hypertonic, where can it be given?

Answer 6

Central Vein –> With over 10% glucose

Peripheral Vein –> With less than 10% glucose

Question 7

How do we calculate the maximum dose of starting material in respect to endotoxin levels?

Answer 7

M = K/EL

K = Max dose for the route (IV = 350, IA = 14)

EL = Endotoxin limit of the starting material that you’re using

Question 8

What are the benefits of using the Cytotoxic Handbook or CIVA Handbook over Trissel?

Answer 8

Trissel –> No peer review, so may not be valid

Handbook –> Written and reviewd by aseptic pharmacists

Question 9

What are most CIVAS drug recalls due to?

Answer 9

Labelling errors

Question 10

Define…

Hazard

Risk

Answer 10

Hazard –> The potential to cause harm

• Can be natural (flood/earthquake) or work (carcinogenic)

Risk –> The likelihood of harm

Question 11

Name the 5 categories that would make a drug hazardous

Answer 11

Carcinogenicity

Teratogencity

Reproductive toxicity

Organ toxicity at low doses

Genotoxicity

Question 12

Why is it not appropriate to wait for indisputible evidence of harm when giving cytotoxic drugs and looking for safety data?

Answer 12

As often there is a several year latency period following exposure for anything to go wrong

So need to know what may happen, as cant be waiting years after giving loads out!

Question 13

Why do we need to consider the possibility of cytotoxics vaporising?

Answer 13

As 5-FU and cyclophosphamide are vaporised at room temeprature, and not filtered by HEPA filters

So they keep flowing round the aseptic suite –> Required external ducting or a gas adsorption system

Question 14

What are the 4 aspects of administrative control?

Answer 14

Education and training

Avaliability of information

SOPs/Polices

Surveillance/Monitoring

Question 15

What type of pressure is used when manufacturing cytotoxics?

Answer 15

Negative pressure

This ensures if there are gases exposed that they move away from the manufacturer

Question 16

What are the best type of gloves?

Answer 16

Nitrile or neoprene

Best to have multi-layers

All gloves permeability will increase with time

Question 17

What does an EU directive say about resheathing needles?

Answer 17

That it shouldnt be done in a healthcare setting! (eg, by nurses administrating it)

Once used it should be thrown in the correct bin

Question 18

Name 2 quick testing methods of an aseptically made drug, and 2 end process tests

Answer 18

Quick Test –> Flame photometry and UV absorption

End Process –> HPLC and Atomic Absorption

Question 19

Why, when filling vials, do we want as little head space as possible?

Answer 19

Improves dissolution

Makes it less viscous and so easier to remove

Reduces the amount of drug that is left in the vial (residual)

Question 20

What is the term ‘Dead Space’, in terms of filling needles?

Answer 20

The fluid remaining within the needle

And between the syringe hub and the plunger

Can use speciallsed ‘low-dead space syringes’ to reduce this, but it is always present!

Question 21

Why is air often a problem (inside the products) in the manufacturing of aseptic products?

Answer 21

Can cause air embolisms

Can result in an incorrect amount of drug being given

Can reduce stability of the drug

Question 22

What role would the following people have in radiopharmacy?

Doctor

Physicist

Chemist

Answer 22

Doctor –> Every patient needs to be looked after by a specific doctor….but not all will have a licence to request a scan

Physicist –> Maintain the imaging equipments quality

Chemist –> Often make up the chemcials which are then injected by the patient for imaging purposes

Question 23

What is the benefit of nuclear imaging over X-rays?

Answer 23

Nuclear isotopes can show us the function (not just the structure)

It’ll show the change as it occurs, as opposed to post event (look your arm is broken, thats cool!)

Question 24

How does a gamma camera work?

Answer 24

Detects gamma radiation (via a sodium iodide crystal that produces a light pulse)

A collimator absorbs any scatter to give a clearer image

Question 25

Why is **Tc99m often used in radiopharmacy**?

Answer 25

**Easy to manufacturer** --\> From molidnium by passing saline through the molidnium device **Short half life** (6hrs) **Decays to stable isotopes**

Question 26

What are the **6 main differences between radiopharmacy and aseptic manufacture**?

Answer 26

**No prescription!** **Aseptic technique** --\> Different protective clothing, and must be far away from the drug as possible **Legislation** **Purchasing of goods is very different** **Dose calculations** --\> Need to be done for the time of administration (need to account for decay) **Quality Control**

Question 27

What is **DMSA**?

Answer 27

**Dimercaptosuccinic Acid** (DMSA) Used in kidney scanning (especially in paediatrics) Passes through the glomerulus, but is reabsorbed readily in the distal tubule

Question 28

How are **radioactivity lung scans done**?

Answer 28

Radioactive aerosol is inhaled (Krypton-81) and imaged A particualte is also injected (MMA) that sticks in the alveoli (cold spots = no perfusion) These images are then compared

Question 29

What is used for the following scans... **Thyroid** **Bone**

Answer 29

**Thyroid** --\> Pertechnetate (TcO4) **Bone** --\> Organic phosphate complex, with its uptake dependent on bone turnover

Question 30

What are the **2 primary goals of PN**?

Answer 30

Provide adequate calories and proteins whilst maintaining fluid balance Prevent malnutrition and associated complications

Question 31

**Why do you often add 400% more vitamin C** (ascorbic acid) than you need to PN?

Answer 31

As oxygen will oxidise it in the bag, catalysed by copper and sunlight

Question 32

What is the **solubility of Calcium and Phosphate** affected by in **PN**?

Answer 32

**The salt** --\> monobasic much more soluble than dibasic **Concentration** **pH** --\> Monobasic made more readily at lower pHs **Other ingredients**

Question 33

What is the **maximum concentration of glucose that can be given via peripheral veins**?

Answer 33

15% 20% via central veins

Question 34

What is the **problem with lipids in PN**?

Answer 34

Very unstable and will precipitate easily Precipitate at low pHs (below 6) More positivly charged molecules (Cu2+ over H+) will destabilise further, as will a decreased lipid concentration

Question 35

What is the **impact of amino acids in PN**?

Answer 35

Chelate with cations Buffer TPN, whilst also stabilising other components like lipids

Question 36

When adding **vitamins and trace elements** to PN, where do you put them?

Answer 36

**Vitamins** --\> Add to fat **Trace elements** --\> Add to AA/glucose bag

Question 37

What type of **phosphate salts** should be used when making **PN**?

Answer 37

Organic

Question 38

How should **PN be stored and given**?

Answer 38

**Stored** --\> In a fridge **Administered** --\> At room temperature (allowed to warm for an hour before administration....otherwise can cause cardiac arrests!)

Question 39

When making a cream extemporaneously, **what should the tile and other equipment be sprayed with immediately** before preperation?

Answer 39

Industrial methylated spirits

Question 40

What is it important for **intrathecal injections** **not** to contain?

Answer 40

Preservatives