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?
536/2014 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)
What are the key points raised in the EMA guidance for sponsors?
QP certification and regulatory release
Un-Blinding arrangements must be in place at CT sites by time of first IMP receipt
Outlines requirements of GDP
Technical agreement required with manufacturer.
What are the activities of ethics board? What are key documents associated with ethical approval?
Review data to be generated from trial is proportional to risk and patient interference
Key documents- Patient consent form and informed consent.
What are the different study designs of clinical trials?
Open- both investigator and patient are unblinded
Single blind- Just patient is blinded
Double blind- Both investigator and patient are blinded
Double blind, double dummy- as above but with placebo control for IMP and comparator.
Crossover- change from one medicine to another part way through the trial to identify difference.
What are some different types of trial based on authorisation of medicine being investigated?
Authorised medicine- used in trial as per SMPC
Authorised medicine- new indication
Authorised medicine- new condition of use
Non Authorised IMP- New compound.
If you import commercial material for use in your trial- What licences may you need?
If the material is to be used as an IMP then import with MIA.
If the material is to be used as a NIMP and is authorised in the UK/EU then use WDA (RPi importation in UK from EU)
If the material is NOT authorised, then require to import under a specials licence.
What would you expect to be validated for each phase of clinical trials?
Any phase;
- Aseptic validation via media fill
- Viral inactivation validation of biologics
Phase 1- Control of degradation and impurities. Validate ID, assay and Impurity method (LOD/LOQ)
Phase 2- Full analytical method validation
Phase 3- Full process validation, tight specifications.
What controls would you expect for IMP packaging?
Pack placebo first
Pack in increasing potency
Some camera technology
100% label check
Clear SOPs and training per IMP batch
Blinding checks
What is on an IMP label?
Where is guidance for this?
What is on Primary Label?
Annex 13
Sponsor name/Address/Contact
Dosage form
Number of units
Trial ID
Patient ID
Randomisation code
Storage condition
Keep Out Of Reach Of Children
For Clinical Trial Use Only
Directions for use
Batch number
Expiry
If Open Label study- Name and strength of medicine.
Primary Label;
Name of Sponsor
Dosage form, route of admin, quantity
Batch number
Trial code
Patient ID
What is the role of the sponsor in CTs?
Management and oversight of trial
Ethics approval oversight
Safety reporting
SUSAR reporting
Contractual arrangements
GCP at trial site (unblinding)
