IMP Flashcards
What is meant by GCP?
ICH E6
Patient protection through study
Ethics and scientific data accuracy
Declaration of Helsinki
Benefits > Risks
What is contained in CT protocol?
Document describing the trial
-RODS
- Rationale
-Organisation
- Design
- Statistical plan
Types of clinical trial
- Open study
- Single blind
- Double Blind
- Double Blind, Double dummy- active and placebo treatments all look the same
What are phases of clinical trial?
Phase Zero- Human micro dosing. PK information
Phase 1- First time in man. Male healthy volunteers. Toxicity, dose/effect, Max tolerable dose, PK
Phase 2- Therapeutic exploratory
- Relevant patient groups
- Efficacy +Bioavailability
- Dose definition
Phase 3- Therapeutic confirmatory
- Population depends on rarity
- dosages/precautions, CIs, Interactions
-Long term data
- Comparator data
Phase 4- Therapeutic use
- Dose optimisation
- May be post market commitment
-Post market surveillance
What is a NIMPS? How are they controlled?
Non investigational medicinal products
- Rescue medications, End point radiolabels, challenge agents.
- No trial labelling
- Licenced product- If not, sponsor holds responsibility for GMP standards.
- Must be characterised in study
What UK Legislation controls IMPs?
SI 2004/1031
Amended by Brexit 2019/744
What are API requirements for IMPs?
Do not need to follow chapter 2
Section 19 details requirements for IMPs
API will need GMP certification upon MA approval.
What is UK CT application process?
-IRAS (integrated research application system)
- Combined ethics/regulatory review
- Through MHRA
-No access to CTIS or EUDRAGMP
What controls are in place for importing IMPs from EU to UK?
-EU/EEA are approved country
-QP certification on import not required
-Importer needs MIA IMP
-QP assurance system to check EU QP cert
- IMP not available until QP named on UK MIA IMP has verified the EU certification.
- IMPs only distributed to sites named on CTA
-Up to date PSF available to QP
- MHRA authorises trial before IMP is available
-GB reference and retention samples not required.
What controls are in place for supplying IMPs from UK to EU? What is EU legislation?
-EU regulations 536/2014 and 2017/1569 apply
- QP declaration has to accompany CTA
-Sponsor must be in the EU
- NI supply- IMPs can be supplied from GB, QP cert in GB, testing in EU/GB/NI as long as equivalent.
What changes were brought about by EU clinical trial directive?
535/2014 and 2017/1569
Simplified application process through CTIS.
Transparency of data- publicly available
Safety reporting simplified- one single report, not all ADRs require reporting, serious ones go through EudraVigilance database.
What is contained in a PSF?
Trial code, sponsor, indication, trial type.
Approved label and example of one
Randomisation code data
Manufacturing/testing procedures/packaging
Protocol
In process tests
Technical agreements
Specifications
Stability requirements
Storage and distribution requirements
Version history
What is contained in a CTA?
What is the structure of the IMPD?
Within a CTA there is the;
IMP dossier
Clinical trial protocol
Investigator brochure
QP declaration if required
Overall risk benefit assessment
Structure of the IMPD;
- CTD format following ICH M4/8
- Non clinical and available clinical data
- Quality module contains DS and DP data.
What level of detail is required for IMP Dossiers?
Guidance in 536/2014 (table)
If IMP is already authorised medicine, then just the summary of product characteristics.
Sliding scale of data requirements based on authorisation status of product, dosage form and active substance authorisation.
What are the systems used to apply for clinical trials in the EU and UK?
Where is the UK clinical trial data published?
EU- CTIS
UK- IRAS
UK trial data is published on ISRCTN (WHO publication)
