Small Scale Manufacturing - Et al

Question 1

What is mAB glycosylation?

Answer 1

The addition of a glycan molecule attatched to Asn297

Allows many different glycoforms to be possible

• These effect activity, solubility and PK

Question 2

What is a fusion protein?

Answer 2

Consists of an Fc region of an IgG antibody and a target receptor

Question 3

What are 4 ways that mABs can be damaged in an infusion bag?

Answer 3

Adsorption to the bag

Aggregation of the mABs (not just one aggregate, but a mixture!)

Fragmentation

Denaturation

Question 4

What is the effect of concentration on biopharmaceuticals?

Answer 4

High –> Adsorption is more likely, as is precipitation

Low –> Less stable, and weakened effects of stabilised excipients. May also leach from the container

Question 5

How are biopharmaceuticals stored?

And what is the shelf-life?

Answer 5

2-8 degrees C (avoiding temeprature cycling)

24-48hrs once diluted

Question 6

What are the 4 types of anti-oxidants that could be added to a biopharmaceutical preperation?

Answer 6

Thiol-containing AAs

Amine-containing AAs

Alcohol-containing AAs

Metal-chelating agents

Question 7

What is Good Clinical Practise (GCP)?

Answer 7

Guidlines to be followed during clinical trials to ensure the rights and well-being of the clinical trial subjects are protected

Question 8

What is an IMP?

Answer 8

Investigational Medicinal Product (IMP)

A pharmaceutical form of an active substance of placebo being tested as a reference in a clinical trial

Question 9

What are ATIMPS?

Answer 9

Advanced Therapy Investigational Medicinal Products (ATIMPS)

Gene Therapy

Somatic cell Therapy

Tissue Engineered

Question 10

What is reconstitution?

Answer 10

Dissolving or dispersing the IMP for administration to the clinical trial patient

Or diluting the IMP with another substance that is used as a vehicle for delivery

Question 11

What is an ADC?

Answer 11

Antibody Drug Conjugate (ADC)

An antibody with a cytotoxic warhead

Due to the increased targetting from the mAb, there are less off-target effects/damage

Question 12

Name 2 types of drug classes that couldnt be used, due to being too toxic, if they were not bound as part of an ADC

Answer 12

Maytansinoids

Auristatins

Both inhibitors of tubulin reorganisation

Question 13

When would you use a peripheral vein for an IV infusion?

Answer 13

When it is going on for 5 days or less (short term)

Infusions are (or nearly are) iso-osmotic and have a pH between 5-9

Patient factors must also be considered

Question 14

What type of drugs can be given through a midline?

Answer 14

Any drugs that can be given via a peripheral vein

Question 15

What is the most common complication due to midlines and peripheral catheters?

Answer 15

Phlebitis

Question 16

What are the three types of CVAD catheter?

Answer 16

Non-tunneled

Skin-tunneled

Implantable port

Question 17

What is an ATMP?

Answer 17

Advanced Therapy Medicinal Product (ATMP)

Classified as one, or combinations of the other….

• Gene Therapy
• Somatic Cell Therapy (SCT)
• Tissue Engineered Product (TEP)

Question 18

Who is responsible for the governance and management of ATMPs?

Answer 18

The chief pharmacist

Question 19

What is a GMO?

Answer 19

Genetically Modified Organism (GMO)

An organism that in which the genetic material has been altered in a way that couldnt be done naturally via mating or natural recombination

Question 20

In terms of GMOs, what has the greatest risk…..1 or 4?

Answer 20

4

Question 21

For GMOs, does class 1 waste have to be inactivated first?

Answer 21

Nope (unless doesnt meet the following criteria….)

Only class 2

Question 22

In what type of aseptic conditions is gene therapy done in?

Answer 22

Negative pressure room

Positive pressure isolator

Question 23

How are CAR-T cells stored?

Answer 23

Cryogenic temperatures (155 degrees C) in vapour phase nitrogen (VPN)

Question 24

What is the most common diluent for reconstitution of biopharmaceuticals?

Answer 24

Sodium Chloride 0.9% (or 0.45%)

Can use Glucose 5%, but unsuitable for most