Small Scale Manufacturing - Maria Connolly Flashcards
What was the NHS Carter Report?
About being able to use part vials correctly (cost effective)
What does CIVAS stand for?
Central Intravenous Additive Service
What is the preferable tonicity of IV products?
Isotonic
What are the 3 types of container for IV products?
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
What is and isnt allowed in SC/IM/IA formulations?
Volume less than 2mL
Particulates are okay (unlike IV)
If an IV drug is hypertonic, where can it be given?
Central Vein –> With over 10% glucose
Peripheral Vein –> With less than 10% glucose
How do we calculate the maximum dose of starting material in respect to endotoxin levels?
M = K/EL
K = Max dose for the route (IV = 350, IA = 14)
EL = Endotoxin limit of the starting material that you’re using
What are the benefits of using the Cytotoxic Handbook or CIVA Handbook over Trissel?
Trissel –> No peer review, so may not be valid
Handbook –> Written and reviewd by aseptic pharmacists
What are most CIVAS drug recalls due to?
Labelling errors
Define…
Hazard
Risk
Hazard –> The potential to cause harm
- Can be natural (flood/earthquake) or work (carcinogenic)
Risk –> The likelihood of harm
Name the 5 categories that would make a drug hazardous
Carcinogenicity
Teratogencity
Reproductive toxicity
Organ toxicity at low doses
Genotoxicity
Why is it not appropriate to wait for indisputible evidence of harm when giving cytotoxic drugs and looking for safety data?
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!
Why do we need to consider the possibility of cytotoxics vaporising?
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
What are the 4 aspects of administrative control?
Education and training
Avaliability of information
SOPs/Polices
Surveillance/Monitoring
What type of pressure is used when manufacturing cytotoxics?
Negative pressure
This ensures if there are gases exposed that they move away from the manufacturer
What are the best type of gloves?
Nitrile or neoprene
Best to have multi-layers
All gloves permeability will increase with time
What does an EU directive say about resheathing needles?
That it shouldnt be done in a healthcare setting! (eg, by nurses administrating it)
Once used it should be thrown in the correct bin
Name 2 quick testing methods of an aseptically made drug, and 2 end process tests
Quick Test –> Flame photometry and UV absorption
End Process –> HPLC and Atomic Absorption
Why, when filling vials, do we want as little head space as possible?
Improves dissolution
Makes it less viscous and so easier to remove
Reduces the amount of drug that is left in the vial (residual)
What is the term ‘Dead Space’, in terms of filling needles?
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!
Why is air often a problem (inside the products) in the manufacturing of aseptic products?
Can cause air embolisms
Can result in an incorrect amount of drug being given
Can reduce stability of the drug
What role would the following people have in radiopharmacy?
Doctor
Physicist
Chemist
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
What is the benefit of nuclear imaging over X-rays?
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!)
How does a gamma camera work?
Detects gamma radiation (via a sodium iodide crystal that produces a light pulse)
A collimator absorbs any scatter to give a clearer image
Why is Tc99m often used in radiopharmacy?
Easy to manufacturer –> From molidnium by passing saline through the molidnium device
Short half life (6hrs)
Decays to stable isotopes
What are the 6 main differences between radiopharmacy and aseptic manufacture?
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
What is DMSA?
Dimercaptosuccinic Acid (DMSA)
Used in kidney scanning (especially in paediatrics)
Passes through the glomerulus, but is reabsorbed readily in the distal tubule
How are radioactivity lung scans done?
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
What is used for the following scans…
Thyroid
Bone
Thyroid –> Pertechnetate (TcO4)
Bone –> Organic phosphate complex, with its uptake dependent on bone turnover
What are the 2 primary goals of PN?
Provide adequate calories and proteins whilst maintaining fluid balance
Prevent malnutrition and associated complications
Why do you often add 400% more vitamin C (ascorbic acid) than you need to PN?
As oxygen will oxidise it in the bag, catalysed by copper and sunlight
What is the solubility of Calcium and Phosphate affected by in PN?
The salt –> monobasic much more soluble than dibasic
Concentration
pH –> Monobasic made more readily at lower pHs
Other ingredients
What is the maximum concentration of glucose that can be given via peripheral veins?
15%
20% via central veins
What is the problem with lipids in PN?
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
What is the impact of amino acids in PN?
Chelate with cations
Buffer TPN, whilst also stabilising other components like lipids
When adding vitamins and trace elements to PN, where do you put them?
Vitamins –> Add to fat
Trace elements –> Add to AA/glucose bag
What type of phosphate salts should be used when making PN?
Organic
How should PN be stored and given?
Stored –> In a fridge
Administered –> At room temperature (allowed to warm for an hour before administration….otherwise can cause cardiac arrests!)
When making a cream extemporaneously, what should the tile and other equipment be sprayed with immediately before preperation?
Industrial methylated spirits
What is it important for intrathecal injections not to contain?
Preservatives
