ATMPs Flashcards
What are ATMPs?
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
What is gene therapy?
Therapy based on the introduction of genetic material into cells to compensate for abnormal genes or to make beneficial proteins.
What can gene therapies be used for?
Tissue regeneration ( loss of sight)
Cancer therapies
Treatment of inherited disease
What’s germ line gene therapy?
Modification of germ cells to produce heritable effects
DNA transferred to germ cells (eggs or sperm) remove heritage disorder
What is somatic gene therapy?
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
What is cell therapy?
Administration of cells or stem cells to the body with therapeutic purposes
Give examples of what cell therapy can help treats
Treatment of cartilage defects
Products against immune diseases
Treatment of Parkinson’s Alzheimer’s ALS
product for cardiac repair
Skin replacement
Cancer immunotherapy
What is immune therapy?
Cellular immunotherapy uses immune or other cell types for modulation of host immune system or direct elimination of pathogen or tumour
What are tissue engineered products?
Tissue engineered products use a combination of cells and engineered cells to promote regeneration or restore function
Give an example of an immune therapy
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
How many ATMPs are on the market as of 2018?
500 clinical trials using ATMPs in EU
12 ATMPs approved
Market :
- 3 withdrawn
- 1 suspended
- 8 licensed ATMPs
What we’re the 12 authorised ATMPs?
Chondrocelect - withdrawn 2016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Provenge- sCTMP - MA withdrawn may 2015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
Describe an example of an approved in vivo gene therapy
Glybera
- treatment of Lipoprotein lipase deficiency
- replication deficient adeno- associated viral vector designed to deliver and express human LPL gene variant LPLS447X
Give an example of an approve ex vivo gene therapy
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)
What is In vivo gene therapy?
Direct delivery of genetic material into the body
What is ex vivo gene therapy?
Extracting desired cells genetically modifying it and re inserting into body
Give an example of an approved somatic cell therapy medicinal product ( sCTMP)
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
Give an example of an approved tissue engineered product (TEP)
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
List the steps in the cell therapy process (12 steps)
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)
What are the challenges of ATMPs?
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
What’s the difference between autologous vs allogenic cell therapies
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
What type of processing is required for autologous therapies?
Scale out manufacturing approach
Parallel processing of multiple, separate products
Amenable for automation
Donor variability and lots of testing
What type of processing is required for allogenic therapies?
Pharmaceutical model bulk manufacture “off the shelf” in the future
Amenable for scale up
Need to maintain CQAs during scale up
