Law and Admin Flashcards
What’s new in legislation world
- Canada added to White List in EMA
- Part IV – ATMPs
- Annex 21 – Importation of medicinal products
- Windsor arrangement
- Annex 16 has been incorporated into PIC/S (along with Annex 13)
- EU vet regulation 2019/6
- New Annex 1
What are the Yellowcard and Black Triangle schemes?
Yellowcard = MHRA system for reporting issues with medicinal products, e.g. side effects, adverse events, counterfeit or fakes
EMA Black triangle = under intensive surveillance where we only have limited data of in market use. Used for new APIs, new combinations, new route of administration / drug delivery systems.
What are the 7 EMA scientific committees
CHMP – committee for medicinal products for human use
CVMP – committee for medicinal products for veterinary use
PRAC – pharmacovigilance risk assessment committee
COMP – committee for orphan medicinal products
HMPC – committee for herbal medicinal products
CAT – committee for advanced therapies
PDCO – paediatric committee
EMA – what is it and what does it do?
Responsible for scientific evaluation, supervision and safety monitoring of medicines in 27 MS and the EEA countries
Facilitates development and access to medicines, evaluate applications for marketing authorisations, monitor the safety of medicine across their lifecycle and provide reliable info on human and vet medicines in lay language
Provides a legal framework for pharmaceuticals to ensure medicines are safe. Based on Directive 2001/82/EC, 2001/83/EC and regulation 726/2004 (centralised authorisation procedure)
Grants licences under the centralised procedure, does not audit sites but delegates this duty to the MS competent authorities, the EMA passes an opinion which the European Commission considers when granting an authorisation.
7 scientific committees and a number of working parties which conduct the scientific work of the agency
Committee will provide scientific advice to companies researching and developing new meds, prepare scientific guidelines and regulatory guidance to help companies prepare marketing authorisation applications, contribute to the harmonisation of regulatory requirements in the EU and internationally. They will appoint a rapporteur and a co-rapporteur.
Operates databases
What are the EMA operated databases?
Eudralex – legislation and guidance
EudraGMP – licences and GMP certs
Eudra CT – CTAs
Eudravigilance – PV reporting
What is NIMAR
Northern Ireland MHRA Authorised Route.
A list of prescription only medicines that can be supplied to NI if considered safe in GB to ensure supply of medicines. Mitigates risk of supply in NI from GB where the size of market means manufactures can’t be bothered with it.
Where do you find the rules for variations?
2012/1916 schedule 10A
EU 1234/2008
What are the variation types?
Type 1 a – minor variations 12 months
Type 1 a IN- immediate notification within 14 days
Do and Tell
Answer provided within 30 days of submission
Type 1b- minor variation. 30 days from confirmation, hear nothing go ahead
Tell, Wait, Do
Type 2- major variations Wait for approval
Normally 60 days for first review but can then be extended almost as they wish
FLU - there’s a fast track process
Urgent Safety restrictions
If you’ve raise the issue then tell and get answer in 24 hrs
If authorities raise it then must submit variation within 15 days
Examples of Ia variation
Change in name or API, starting material etc where site stays the same. Also dp manufacturer if not certifying there.
<10 fold in API batch size or reduction
Tightening of limits, addition of new in process test & limits
Minor changes to quantitive composition wrt excipients
Minor change to manufacturing process for OSD and oral solutions
Change in coat weight or capsule shell (cosmetic only)
Change to composition of primary pack for solid form
Change to primary pack supplier
Examples of IaIN variation
Change to name of active substance
Change to name / address of manufacturer and test site inc release site if satisfactory inspection and appropriately authorised
Tightening of specification of dp subject to official batch release
Change to shape, debossing or other markings
Change to secondary or packing site
Change to pack size within preapproved range.
Change to packaging that includes product information.
Reduction in shelf life
New CEP from approved manufacturer.
Examples of Ib variation
> 10 fold increase in batch size of API
Increasing / decreasing scale of biological / immunological with no change to process (e.g. duplication of line)
Addition or replacement of an in-process test as a
result of a safety or quality issue
Change to liquid API primary pack material
Extension or introduction of an API re-test
period/storage period supported by real time
data
Change in storage conditions of the active
Substance
Change to breakline
Change to manufacturing site where not meeting conditions of 1aIN
Minor change to manufacturing process for oral suspensions
> 10 fold increase in batch size
Change to type of container for Solid, semi-solid and non-sterile liquid pharmaceutical forms
Change to pack size outside the range currently
approved
Extension of shelf life
Examples of Type II variation
Pretty much anything steriles or biological / immunological
New API manufacturer, new route of synthesis, substantial change to process
New herbal geographical source , manufacturing route or production
Changing quality critical in process tests
Changing flu strain
Changing the design space
Changes to formulation (excipients or api) that have a quality critical function
What is the new EU veterinary regulation?
2019/6
What is the new vet variation regulation?
What are the two variation types?
2021/17
Variations Not Requiring Assessment VNRA
Variations Requiring Assessment VRA
What is Role and legal status of the BP?
BP is an annually published collection of quality standards for medicinal products in the UK.
BP is governed under 2012/1916, legal basis is 1968 medicines act. 2012/1916 talks about routine updates to the content.
Actual BP itself contains monographs for drug substances, excipients and formulated preparations.
What is PIC/S and how is it applied?
(Chris Expects Trouble Half the Time) -Cooperation, exchange, training, harmonization of GMP and Tech standards
- Strengthen Cooperation to maintain confidence
- Provide framework for Exchange of info
- Coordinate mutual Training for inspectors
- Harmonization of GMP
- Harmonization of Technical standards
54 authorities, harmonised GMP and quality systems for MP, treaty between countries to recognise inspections
Pharmaceutical Inspection Co-operation Scheme
What are the requirements for a PQR (drug product)
Scrap Divers Wear PVC
S - Starting materials and packing review - source and supply chain
C - Critical IPC and finished product test results review
R - Rejected batches
P - Previous CAPA review
P - Planned Changes
D - Deviations
V - Variations
R - Recalls, returns, complaints
S - Stability review
P - Post marketing commitments
V - Validation / qualification of utilities
C - Chapter 7 outsourcing review
Who would you involve in a product recall? Detail the process
- Logistics - to find out where it is, how quickly it flies off the shelf
- Legal
- Medical - patient impact assessment of defect
- PV - trends of complaints, product history
- Production - if involved in defect generation
- QC - for testing input (if required)
- QA
- Comms team if thinking class 1 recall
What are the recall classes and how long before you initiate recall?
Class 1 – Critical defect
Class 2 – Major defect
Class 3 – Minor defect
Class 4 - Caution in Use
or no recall
Mandated recall initiate times:
Intercity 125 : within 1 day, within 2 days (48 hrs), within 5 days
What is ICH and how is it applied?
International Council for Harmonization
5 steps to implementing the guidelines. 1 = consensus its required, 2 = technical document generated and adopted, 3 = regulatory consultation, 4 = adoption (who’s gonna when it’s finished), 5 = implemented. ICH was founded by EC, US and Japan, but now has more members.
ICH is not technically law – it’s for harmonization. Once it’s at step 5, update national / regional procedures as required.
What are the EU GMP regs / directives?
2017/1569 – GMP for IMPS (regulation)
2017/1572 – GMP for medicinal products (directive)
What’s the structure of an MIA?
- MIA Number
- Name of MA holder
- Address of site manufacturing and importing and Legally registered address
- Scope of license and dosage forms
- Name of MHRA rep granting license
- Date
- Variation history
- Sites covered (separate annexes for each)
- Product types allowed for Manufacture and Import
- Names of Production Manager, QPs, RPs, Heads of Quality, Heads of Manufacture and Quality Control
- date of inspection on which authorisation granted and scope of last inspection
- Products authorised to be manufactured/imported
- Name and address of testing laboratories
- Name and address of warehouses
For MIA IMPs there is no product list, just the types of products you can import that are IMP.
What is the current UK legislation?
1968 Medicines Act. Came about as an output from the Thalidomide scandal
2012/1916 Human Medicines Regulations
2004/1031 Clinical Trial Regulations as amended by 2019/744
2013/2033 Veterinary Medicines Regulations
Medicines and Medical Devices Act 2021
Medical Devices Regulation 2002/618
The Misuse of Drugs Act 1971
2001/3998 - Misuse of Drugs Regulations 2001
What does 2001/3998 misuse of drugs regs 2001 include?
Schedules 1 - 5 list the drugs in classification of reducing seriousness and who can prescribe them plus how they must be stored
WDA structure?
- Name and address of applicant
- WDA authorisation text
- WDA number and holder
- MHRA approver
- Variation history
- Scope of the WDA - what each place can hold
- Names of the RPs
What’s the DMRC and Veterinary equivalent?
- Defective Medicines Report Centre. Role is to minimize the hazards posed by distribution of defective medicines.
- For veterinary, is a report form online that goes to the VMD.
Where are the legal duties for a QP in 2013/2033?
Schedule 2 para 11
They are the same as human MP duties.
What are the duties relating to the Vet QPPV (schedule 1)
Establishes and maintains a system that collects and collates details of all suspected adverse reactions reported to the marketing authorisation holder;
Answers any request from the Secretary of State for information on the benefits and risks afforded by a veterinary medicinal product fully including the volume of sales of the veterinary medicinal product concerned and, if available, details of prescriptions;
What is the EDQM and what do they do?
European Directorate for the Quality of Medicines & Healthcare
The EDQM is a directorate of the Council of Europe. It has responsibility for:-
* Maintaining the European Pharmacopoeia
* Supplying chemical reference substances (CRS) and biological reference preparations (BRP) as well as reference spectra for the tests and assays to be carried out in accordance with the official methods prescribed in the European Pharmacopoeia.
* Implement the CEP process for ‘Certification of Suitability to the monographs of the European Pharmacopoeia’.
Talk to me about CEPs?
CEPs are recognised by the signatory parties of the Convention on the Elaboration of a European Pharmacopoeia, i.e. all Council of Europe member states and the European Union. They are also recognised by other countries, e.g. Canada, Australia, New Zealand, Tunisia and Morocco
The CEP certifies that by applying the relevant monographs of the Ph. Eur., if necessary with an annex attached to the certificate of additional tests and their limits, it is possible to check whether or not the quality of the substance is suitable for use in medicinal products.
In other words, it ensures that all possible impurities from this particular route (including source materials) can be fully controlled by the requirements of the monographs and any additional tests added to the certificate. The CEP certifies that the active substance complies with Ph Eur and the monograph is enough to control quality.
A CEP says nothing about the GMP used to manufacture the AS.
How do you report an animals reaction to medicine or microchip?
There’s a form on the GOV website
What’s different about importing a veterinary product?
They can be imported by any number of different people:
1) The holder of the MA
2) WDA holder
3) A vet or pharmacist can import anything
4) A QP that is permitted to supply that product.
What’s POM-V and who can prescribe?
Prescription Only Medicine – Veterinarian.
A veterinary medicinal product which may only be supplied to the client once it has been prescribed by a veterinary surgeon following a clinical assessment of an animal, or a group of animals, under the veterinary surgeon’s care
What’s POM-VPS and who can prescribe?
Prescription-Only Medicine – Veterinarian, Pharmacist, Suitably Qualified Person (SQP)
A medicine for food-producing animals (including horses).
Prescribed by any Registered Qualified Person (RQP means a veterinarian, pharmacist or an appropriately qualified SQP).
A clinical assessment of the animal(s) is not required when prescribing this category of veterinary medicine and the animal does not have to be seen by the prescriber. However sufficient information about the animal and the way it is kept must be known to the prescriber in order to prescribe and supply appropriately.
Non-Food Animal Medicine – Veterinarian, Pharmacist, Suitably Qualified Person
A medicine for companion animals may be supplied by any RQP (a veterinarian, pharmacist or Suitably Qualified Person) provided the requirements for supply are met. These medicines do not require a prescription
When do contract labs not need a GMP licence from MHRA
When they do EM for non-steriles
When do contract labs need to have a GMP certificate and be inspected by MHRA?
MHRA inspects labs used for:
* testing medicinal products (inc IMPS) if used for batch release
* testing radiopharms
* stability testing
* EM and process sim for steriles
* Biological testing as per Annex 2
All labs doing this stuff need to be listed on the MIA and MAH licences.
What do brokers do?
Brokers act as intermediaries in transactions and do not physically handle the products. A broker does not buy or sell the products, They also don’t buy / sell products, own the products or physically handle the products.
What do brokers need?
Brokers need to be registered with MHRA
Brokers need a QMS and follow GDP.
They need to keep a record of all brokerings.
Brokers need to be able to participate in recalls and inform of suspected falsified medicines
Brokers need to verify their customers have appropriate authorisations
What types of site licenses are available?
MIA
WDA
MIA IMP
Specials Licence
Veterinary Licence
API registration
Broker registration
What are the acts of Parliament relevant to pharmaceutical industry
Human Medicines Act 1968
Misuse of Drugs Act 1971
Medicines and Medical Devices Act 2021
What is the international recognition procedure
Process MHRA uses to streamline drug approval (but can still reject). Recognises the approval in certain countries
What are the IRP countries?
Japan
EU
Switzerland
US
Singapore
Australia
Canada
JESUS AC
How long does a CEP last?
Fist issue must be revalidated within 5 years. After that eternity
What are conditional marketing authorisations (CMAs)
The MHRA has introduced a national Conditional Marketing Authorisation (CMA) scheme for new medicinal products in Great Britain effective from 1 January 2021.
The scheme is intended for medicinal products that fulfill an unmet medical need. Examples would be for serious and life-threatening diseases where no satisfactory treatment methods are available or where the product offers a major therapeutic advantage.
The MHRA may grant a CMA where comprehensive clinical data is not yet complete, but it is judged that such data will become available soon.
What types of parallel import are there
Simple – manufacturer and importer are the same group (i.e. same origin)
Complex – different importer and maker and one other complication
Eg. New excipient
New API route to UK registered product
Sterile with something different
Its controlled release
Its MDI
Its MDPI
Flu vaccine
Standard –
Diff manufacuter
What is the Single Inspection Programme (SIP)?
Reduces foreign inspections as one agency will inspect for all.
UK MHRA, Australian TGA and Health Canada have established a pilot
programme to coordinate GMP
inspections of foreign manufacturing sites of common interest.
Each authority has agreed to extend the scope of an inspection to
cover products of interest to one another, where possible
With respect to VMD, do you have to test each batch on import?
Not if they are from a CERS (country with equivalent regulatory standard).
Basically EU and works like MRA
