WEEK 9 - ATMPs From Clinical Trials to Licensed Products Flashcards
(17 cards)
What are ATMPs
ATMPs - Advanced Therapies Medicinal Products
ATMPS - are biological products
- NOT small molecules
- can be cells, tissues
Medicinal Product = used to diagnose, prevent or cure disease
NOTE:
- Novel therapy
- Can be challenging to work with
- Can be mixed / delivered with medicinal devices e.g. eyedrops, dressings etc.
What are the 3 types of ATMPs
Classification of ATMPs
- Somatic cell therapy medicinal product
- contains cells or tissues that have been manipulated to alter biological characteristics for therapeutic purpose
- Tissue engineered product
- designed to regenerate, repair or replace human tissue
- may contrain cells, scaffolds
- Gene therapy medicinal product
- Most commonly used
- use recombinate nucleic acids to regulate, repair or replace genetic sequences
Autologous vs Allogenic
Autologous:
- Using cells derived from patient themselves
- Reduces risk of immune rejection
Allogenic:
- Using cells derived from a donor
What are the regulatory framework for ATMPs in the UK
Health Safety Executive (HSE) GMO Regulations 2014
- AIM: regulate GMO
- Containment measures to protect human health + environment
- Risk assessment
- Accident reporting
- Classify products
- class 1 and 2 = low risk to human (what’s seen in hospitals)
- class 3 and 4 arent seen in NHS
What assessment must be cacrried out when a new medicinal product is brought to hospital
Risk Assessment
- Asses if have capacity + capability to deliver products
- Asses product / agent
- Assess preparation and storage
- Assess risks for patient and staff
- Risk assess waste, i.e. how waste is generated, excess, clinical waste etc.
- Is spillage skip required for waste / broken products
- Tracking system (to know whats happened with product since arrival in pharmacy to adminstration in pt)
List key regulatory bodies and their roles
- MHRA
- EU Tissues and CEll directives
- incoporate EU guideliens - HRA
- look after clinical trials - HTA (human tissue authority)
- In charge of human cell products
- e.g. CAR T
- Health and Safety Executive
- look into genetically modified organsims
- make sure thet are safe for the people handling the medicine, patients and environment
NOTE:
- HAve to comply with all legislation = challenging
Explain the 2 types of Gene Therapy (medicinal product)
Genetically Modified Organism (GMO) MP
- Use GMO as vector to enter cells + change genome
Example:
1. In Vivo - admisntser ATMP directly inot tissue + change in cells happens in body
2. Ex Vivo - genetically engineering cells outside of the body
- cells get taken from pt, sent to lab, genome is modified then ATMP is administered
- e.g. CAR T cells
Non GMO Gene Therapy MP
Example:
1. mRNA immunotherapies
2. CRISPR
What is the GCP
GCP - Good clincal practice
Good Clinical Practice (GCP):
- SI 2006 No.1928: The Medicines for Human Use (CT) Regulations 2006 incorporates principles of GCP
What is a pharmacists role in delivering of ATMPs
- Clinical Trials
- Currently 36 ATMPs coming through over next few years
- All may not be successful
- Licensed Products
- Chief pharmacist is responsible for governance and management in NHS
What may Pharmacist be involved
6 Key things
- Governance
- overseeing, traceability - Conducting risk assessments
- identifying + mitigating risks - Reviewing contracts
- negotitating contarcts + supply aggreements
- ensuring fair for pts and NHS - Storage and Procurement
- ensure no product are wasted, can be expensive per dose - Handling and Preparation
- waste and destruction
- shedding / spillages
- PPE, admistartion - Logistics and Operational
OTHER:
Setting up clinical trials
Pharmacy assessors who review every product
Quality assurance
In NICE give professional opinions
In hospitals, may do risk assessments to assess if its safe
CAR T Cells Info
- Collect T cells from pt (autologous MP)
- Normal T cells are genetically enginereed in lab to have CAR on its surface
- Receptor is specifc to recognise anitgen on tumour cell surface
- CAR T cell will bind to antigen + cause destrcution of tumour cell
CAR = chimeric antigen receptor
CAR T Related Toxicities
When CAR T binds and causes apotosis ALSO produces a cytokine release
- Toclizuman given to reduce inflam.
Cytokine Release Syndrome (CRS)
- Has 4 grades
- Immune system gets over activated
- Severe systemic inflammatory response triggered by cytokine release
- Onset: 1-3 days after CAR T infusion
- Duration: up to 7 days
Symptoms:
- Fever >38ºC
- Hypotension
- Hypoxia
Immune-effector Cell Associated Neurotoxicity Syndrome (ICANS)
- Has 4 grades
- Cytokines diffuse into brain / disrupt BBB = brain inflammation
- Onset: 4 days post infusion
- Duration: 2-4 days
Symptoms:
- ICE score from 0-9
- Seizures
- Focal odema
- Changes in responsiveness
- Reduced attention span
OFF target effects
- CAR T cells may target other cells that are not tumour cells
Pharmacy Involvement in CAR Ts
- Bridging therapy of chemo
- to prevent disease progressing, ensure disease is stable for when CAR T cell prodcut arrives
- CAR T cell may be delievred within 1 months
- Correct storage and administartion of therapy
- Manage toxicities
- Monitoring
- followed up acute in hospital + for approx 15 years after
Pharmacy Considerations for In-Vivo Gene Therapy
example = LUXturna eye gene therapy
- Kept at cold temp.
- Paperwork (high cost drug, requires funding from NHS)
- Transport logistics
- handling, preparation, administartion of drug - Monitoring
- immunoreactions in liver = monitro transaminases - Counsel pts
- if around pregnant, immunouspressed people
- shedding in tears, may need waste bins
Pharmacy Considerations for Tissue EngineeringTherapy
e.g. Spherox
- Ordering and tissue collection
- check its safe and secure
- as its an autologous MP ensure givien to right patient
- Product reciept and storage
- Transportation
- Monitoring
- Data collection
- Risk Assessments
To apply knowledge to real world examples
CAR T cells = most commonly used and most successful example of an ATMP
- Currently have 15 licensed ATMPs in UK
FUTURE:
- More ATMPs moving towards 1st or 2nd line than last resort
- Harmonisation of drug approval i.e. if approves in America,a pproved in UK
- Improved manufacturing process
