Law and Admin Flashcards
What are the MRA approved countries list for batch importation?
Isreal
Australia
Swi
NZ
Can
JP US
EU/EEA
Certain restrictions for ATMPs, Blood products, Medicinal gasses, Homeopathics
When do you need MIA? When do you need WDA?
MIA- Manufacture and importation licence- allows manufacture, import and distribution for products made at that site.
WDA- when you import and distribute products from other sites.
What is the role of PIC/s?
Pharmaceutical inspection co-operation scheme.
Set standards for inspectorates globally, train auditors from national authorities and provide audit guidance (aid memoirs).
You need to recall material. What actions do you need to take?
May be prior to root cause
Understand where the batches are
Determine how far into supply chain you recall to
Inform all competent authorities
Market specific recall actions
Secure storage
What are API importation controls?
New MA or variation requires API QP declaration approval
If 3rd country and not approved for active substance manufacture to UK GMP, needs to have national competent authority approval from country of manufacture
GDP guidance 2015/c95/01
EUFMD 2011/62/EC
What controls measures are in place for excipients?
Guidance present in Eudralex vol 4 section 3 - excipients RA.
-2015/c95/02 GDP guidance
What is present in the non- clinical module of the CTD?
Toxicology information
Interactions
ADR
Carcinogenicity
Sensitisation
Max dose in animals
What are responsibilities of QPPV
Monitor market reported ADRs
Create and maintain effectiveness of PV system
Prepare PV reports
Respond to HA requests
What types of licenses are available- Human? Veterinary?
Human;
MIA
WDA (H)
MIA IMP
MS Specials Licence
MeAT- ATMPs
Vet;
ManA
ManSA
SAM
WDA(V)
API registration
Broker registration
What is contained in manufacturing licence?
- Section 1A + B
○ MIA number
○ Legal basis
○ Version number
○ Name of holder
○ Address of holder
○ Name of responsible officer issuing licence
○ Date
○ Annexes attached
○ MIA holder requirements- Section 2
○ Variations to the licence - Section 3
○ Details relating to each site licence
○ Manufacturing operations Authorised
○ QC testing authorised
○ Importation activities authorised - Annexes
○ Name of QPs and manufacturing leads
○ Contract laboratories
Storage sites
- Section 2
What is contained in site master file?
Guidance document in part 3 eudralex volume 4
1. General information on the manufacturer
2. PQS elements
3. Personnel
4. Premises and equipment
5. Documentation
6. Production activities on site
7. QC
8. Distribution/ complaints and recall
9. Self inspection
Appendixes
- Copy of site licence
- Copy of GMP certificate
- Contract manufacturers and QC labs
- Key personnel
- Key equipment
- Water systems
- Plant layouts
What is in the CTD and where do you find guidance on this?
Common technical document- contains;
Module1- Regional information
Module 2- Quality, non clinical summary/overview, clinical summary/overview
Module 3- Quality module
Module 4- Non clinical study reports
Module 5- Clinical study reports
Format found in ICH M4 and M8
What is contained in the Quality module of the CTD?
P.3.2S- Drug substance
-General Information
-Characterisation
-Manufacture
-Control of DS
-Stability
-Container closure
-Reference standards
P.3.2P Drug product
-Description and composition
-Pharm Dev
-Manufacturing process and controls
-Excipient control
-Control of DP
-Reference standards
-Stability
-Container closure system
What are the routes of MA application in the EU? Who reviews them?
National procedure- One country
Mutual recognition procedure- MA in one country and others recognise
Decentralised- Apply to one reference country and many others at same time
Centralised- through EMA, EU wide application
CHMP and CVMP review applications.
What are the MA application routes for the UK?
Who reviews within the MHRA?
What licences do the MHRA currently issue?
National procedure
Reliance procedure (IRP)
Innovative licencing and access pathway
CHM (commission for human medicines)
VPC (Veterinary Product committee)
PLUk PLNI, PLGB
What do you know about IRP?
International recognition procedure
Approval in a listed country means a streamline review of the MA for the UK (reliance procedure).
Countries are;
EU/EEA
Japan
USA
Canada
Singapore
Switzerland
Australia
What is the structure of the PhEur? Where is legal basis of EU and BP?
General notices- Basic understanding
General chapters- General methods, analytical methods
General monographs- Dosage forms, groups of products
Individual monographs- Mandatory quality aspects
EU- 2001/83/EC
UK- 2012/1916
What is the structure of a monograph? Who issues them?
Description
Production
Characteristics
ID
Test/assay
Storage
Labelling
EDQM issue monographs- council of Europe.
BP commission- prepares and publishes the BP.
What do you know about CEPs?
How long are they valid for?
Certificate of suitability to PhEur issued by EDQM.
Covers substances defined in monographs
Covers products at risk of TSE
Quality of the final material can be controlled by using the monograph
Not a GMP certificate- doesn’t qualify quality of manufacture.
Valid for 5 years.
What is the organisation of the MHRA?
UK department of health
Located in canary wharf
Executive team and Agency board
Science and innovation
Healthcare quality and access
Safety and Surveillance
Within healthcare quality and access;
-Innovative Devices
-Innovative Medicines
-Authorisation lifecycle
-Population health
-Standards and compliance
>Compliance teams, GLP,GDP, GMP
What is the role of EMA?
European medicines agency
-Co-ordinate resources of member states
-Support with scientific advice (NPI)
-Maintain Eudravigillence and EudraGMP databases
- Co-ordinate inspection responses.
What is the role of the DMRC?
Defective medicines reporting centre
Assess impact of defective medicines to public health
Ensure medicines availability and safety
Respond to yellow cards (Sentinel system)
How does the reporting of defective veterinary medicines work?
VMD defect reporting
Rapid alert notification
Defect report form on website
Recall class 1,2,3
Yellow card system
What is the role of the VMD?
Veterinary medicines directorate
Part of DEFRA
Links to MHRA and Health department
Review licence applications
Co-ordinate inspection programme
Co-ordinates yellow card reporting system.
What is the role of CHMP and CVMP?
Committee for medicinal products for human use;
- Assess new MA applications
-Assess variations to MAs
- Review safety assessments
-Power to change, suspend or revoke MAs
Committee for veterinary products for animal use. As above for vet products.
Describe the MHRA recall classifications
Class 1
- National patient safety alert
- Risk of death or disability
- Immediate recall initiation
- Patient level
Class 2
- Mistreatment or harm to patients
-Not life threatening
- 48 hours to recall
- Pharmacy and wholesale
Class 3
- Defect unlikely to cause harm
- MA non compliance, specification non compliance.
- 5 days
-Pharmacy and wholesale
Class 4
- Caution in use notice
- No threat, minor packaging defect
- Also used when supply constraints do not support recall.
What is the legal basis for Pharmacovigilance and where is further guidance? How would you describe PV?
2001/83/EC
Regulation 726/2004
2012/1916
Eudralex volume 9
ICH E2
Safety profile of the drug in use
Monitoring for previously unseen ADRs.
What are the responsibilities of the QPPV?
Legal basis in 2001/83 and 2012/1916
Responsibilities;
Establish and maintain PV system
Prepare PV reports
Support HA questions and provide safety information.
What are the PV requirements of the MA holder?
Prepare periodic safety update reports
Prepare individual case study reports
Prepare and maintain PV master file
Have a QPPV permanently at their disposal
What is the adverse event process for veterinary products and for human IMP products?
What is required in the event of an IMP PV issue?
Vet- Suspect adverse reaction surveillance
IMP- Suspect Unexpected Severe Adverse Report
IMP SUSAR- Report to competent member state and ethics board.
What is currently in place for NI supply of medicines from GB?
Bridging regulation 2022/642
GB can export GB tested ad QP certified material to NI…..IF….
- Meets full EU law within MA
- Can’t legally be sold in EU
- Scanning a pack in EU leads to error code on EMVO.
What will change in 2025 for GB supply to NI?
Windsor framework
-January 1st 2025 the MHRA will issue UK wide product licences inclusive of NI
-Packs of product authorised across UK
- No longer require security features
-Labelled/Artwork as ‘For UK Only’
-6M stickering allowed before artwork updated.
What is required to be in place for EU supply of products to UK?
No import testing requirements
QP cert in EU
Verification of QP cert in UK by responsible person
RP is responsible for system used to verify EU QP cert
GB warehouse must have WDA
What was Brexit amendment to CT SI 2004/1031 in the UK?
SI 2019/744
What are the different legislations controlling medicines in the UK?
2012/1916- Human medicines regulation
2004/1031- clinical trials for human use
2013/2033- Veterinary medicines
2003/1680- Specials for human use
What are the obligations of an MIA holder?
Inform regulator of any changes to licence
Manufacture to GMP
Ensure starting materials conform to GMP
Allow access of inspectors onto site
Only manufacture products within scope of authorisation
Allow QP to carry out duties
Maintain staff, equipment and premises as required
Report any suspect or confirmed falsified material to MHRA
What are the obligations of an MA holder?
Notify MHRA of date of product on market
Notify MHRA if cancelling/withdrawing/not renewing MA.
Provide sales volume information
Maintain up to date with scientific advancements and vary MA accordingly
Provide safety information regarding products to MHRA
What is the PV regulation?
EU Regulation 726/2004
What are the EU White list countries? What does this list mean?
USA
JP
Australia
Switzerland
Israel
Canada
Taiwan
Brazil
South Korea
What are the EU MRA Countries, What do these mean?
USA
Japan
Australia
Switzerland
Israel
NZ
Canada
