ATMPs

Question 1

What are ATMPs?

Answer 1

Advanced therapy medicinal products

Medicinal products which are prepared industrially or manufactured by a method involving an industrial process.

Three categories :
1) gene therapies
2) somatic cell therapies
3) tissue engineered products

Question 2

What is gene therapy?

Answer 2

Therapy based on the introduction of genetic material into cells to compensate for abnormal genes or to make beneficial proteins.

Question 3

What can gene therapies be used for?

Answer 3

Tissue regeneration ( loss of sight)

Cancer therapies

Treatment of inherited disease

Question 4

What’s germ line gene therapy?

Answer 4

Modification of germ cells to produce heritable effects

DNA transferred to germ cells (eggs or sperm) remove heritage disorder

Question 5

What is somatic gene therapy?

Answer 5

Modification of stomatic cells to cure an individual - not heritable

Place human gene in somatic cells

Somatic cells are all cells that don’t produce eggs or sperm

Patient specific

Question 6

What is cell therapy?

Answer 6

Administration of cells or stem cells to the body with therapeutic purposes

Question 7

Give examples of what cell therapy can help treats

Answer 7

Treatment of cartilage defects

Products against immune diseases

Treatment of Parkinson’s Alzheimer’s ALS

product for cardiac repair

Skin replacement

Cancer immunotherapy

Question 8

What is immune therapy?

Answer 8

Cellular immunotherapy uses immune or other cell types for modulation of host immune system or direct elimination of pathogen or tumour

Question 9

What are tissue engineered products?

Answer 9

Tissue engineered products use a combination of cells and engineered cells to promote regeneration or restore function

Question 10

Give an example of an immune therapy

Answer 10

CAR-T cell therapy

T cells have receptors that recognise antigens on pathogens or cancer cells

Sometimes cancer cells have antigens that the immune system cannot recognise and so the immune system may not send T cells to fight the cancer cells

Chimeric antigen receptor created and put onto T cells

New receptor enables them to find cancer cells and kill them

Question 11

How many ATMPs are on the market as of 2018?

Answer 11

500 clinical trials using ATMPs in EU

12 ATMPs approved

Market :
- 3 withdrawn
- 1 suspended
- 8 licensed ATMPs

Question 12

What we’re the 12 authorised ATMPs?

Answer 12

Chondrocelect - withdrawn 2016
Glybera - MA ended oct 2017
MACI - MA suspended sept 2014
Provenge- sCTMP - MA withdrawn may 2015
Holoclar
Imlygic
Strimvelis
Zalmoxis
Chondrosphere
Alofisel
Kymriah
Yescarta

Question 13

Describe an example of an approved in vivo gene therapy

Answer 13

Glybera
- treatment of Lipoprotein lipase deficiency
- replication deficient adeno- associated viral vector designed to deliver and express human LPL gene variant LPLS447X

Question 14

Give an example of an approve ex vivo gene therapy

Answer 14

Strimvelis
- CD34+ cells transduced with retro viral vector that encodes for the human ASA cDNA sequence
- treatment of patients with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID)

Question 15

What is In vivo gene therapy?

Answer 15

Direct delivery of genetic material into the body

Question 16

What is ex vivo gene therapy?

Answer 16

Extracting desired cells genetically modifying it and re inserting into body

Question 17

Give an example of an approved somatic cell therapy medicinal product ( sCTMP)

Answer 17

Provenge
- autologous peripheral blood mononuclear cells activated with PAP-GM-CSF (sipuleucel T)
- treatment of asymptomatic or minimally symptomatic metastatic (non-visceral) castrate resistant prostate cancer

Blood taken re-engineered and reinserted

Wasn’t in demand so was withdrawnin may 2015

Question 18

Give an example of an approved tissue engineered product (TEP)

Answer 18

Holoclar
-ex-vivo expanded autologous human corneal epithelial cells containing stem cells
- treatment of adult patients with moderate to several limbal stem cell deficiency unilateral or bilateral due to physical or chemical ocular bonds

Replace damaged cells outer layer of eye

Healthy limbal tissue extracted from patient
Cells then grown in a lab
Then frozen until surgery
Cells grown on protein called fibrin

Question 19

List the steps in the cell therapy process (12 steps)

Answer 19

1) tissue acquisition
2) primary cell isolation
3) cell culture
4) harvest
5) volume reduction
6) washing
7) formulate and fill
8) cryopreservation
9) storage and inventory
10) testing and release
11) shipping logistics
12) end used ( handling delivery)

Question 20

What are the challenges of ATMPs?

Answer 20

They can be extremely expensive this high cost can be due to the need for running clinical trials, the cost of manufacturing ( vectors, products )
There are also stringent regulations behind creating these ATMPs as they need to be safe

Shelf life can also be a limitation and can increase costs

For example provenge can cost up to 93,000 dollars glybera can cost up to 1 million

Question 21

What’s the difference between autologous vs allogenic cell therapies

Answer 21

Autologous stem cells are from the patients body, engineering and reinserted and allogenic stem cells are donated from another person engineered and inserted into the patient

Question 22

What type of processing is required for autologous therapies?

Answer 22

Scale out manufacturing approach

Parallel processing of multiple, separate products

Amenable for automation

Donor variability and lots of testing

Question 23

What type of processing is required for allogenic therapies?

Answer 23

Pharmaceutical model bulk manufacture “off the shelf” in the future

Amenable for scale up

Need to maintain CQAs during scale up