Law and Admin Flashcards
What are some changes the QP needs to be aware of?
Windsor Framework
Supply chain for Northern Ireland
Medicinal products intended for the UK market (including NI) must: (i) be authorized by the MHRA; and (ii) bear a clear “UK only” label, which may be placed anywhere on the pack.
Effective from 1 January 2025
What are the legal duties of a QP
Defined in HMR (SI2012:19196) schedule 7 part 3
- each batch of medicinal products manufactured checked in accordance with national regulations
- Each batch has undergone a full qualitative analysis and quantitative analysis of all the active substances, all other tests or checks necessary to ensure the quality of medicinal products in accordance with the requirements of the MA
- Certification is recorded in a register or equivalent document.
Difference between legal duties for UK and EU QP
EU QP complies with 2001/83
Also includes safety features
What countries does the UK have an MRA with?
UK MRA’s are:
EEA
Australia
Canada
Israel
Japan
New Zealand
Switzerland
United States of America
Which products does the MRA not apply to?
Australia
Advanced Therapy Medicinal Products
Canada
Medicinal products derived from human blood or blood plasma
Advanced Therapy Medicinal Products
Israel
Medicinal gases
Homeopathic products
Medicinal products derived from human blood or blood plasma
Advanced Therapy Medicinal Products
Japan
Medicinal gases
Medicinal products derived from human blood or blood plasma
Advanced Therapy Medicinal Products
New Zealand
Advanced Therapy Medicinal Products
United States of America
Vaccines
Advanced Therapy Medicinal Products
Medicinal products derived from human blood or blood plasma
What do you know about the International Recognition Procedure?
It is effective from 01 Jan 2024,
New licensing route for medicines (pre and post authorisation procedures) allows the MHRA to conduct targeted assessments by recognising approvals from trusted partner agencies.
Approved Reference Regulators are Australia, Canada, European Commission, Japan, Switzerland, Singapore and the USA
Recognition A and B (different timelines). B is for: ATMP, First-in-class new active substance, Incorporates novel or cutting-edge technologies, Fractionated plasma product
Where can the Routine duties be found. Can you state them?
Annex 16
- All activities associated with manufacture and testing of the medicinal product have been conducted in accordance with the principles and
guidelines of GMP. - The entire supply chain of the active substance and medicinal product up to the stage of certification is documented and available for the QP. This should include the manufacturing sites of the starting materials and packaging materials for the medicinal product and any other materials
deemed critical through a risk assessment of the manufacturing process. - All audits of sites involved in the manufacture and the testing of the been carried out and that the audit reports are available.
- All sites of manufacture, analysis and certification are compliant with the terms of the MA for the intended territory.
- All manufacturing activities and testing activities are consistent with those described in the MA.
- The source and specifications of starting materials and packaging materials used in the batch are compliant with the MA.
- Active substances manufactured in accordance with GMP and distributed in accordance with GDP
- Importation of AS comply with the requirements of Article 46(b) of Directive 2001/83/EC.
- Excipients have been manufactured in accordance with GMP.
- TSE status known and compliant with MA
- All records are complete and endorsed by appropriate personnel. All
required in-process controls and checks have been made. - All manufacturing and testing processes remain in the validated state.
Personnel are trained and qualified as appropriate. - Finished product quality control (QC) test data complies with the Finished
Product Specification described in the MA, or where authorised, the Real
Time Release Testing programme. - Post-marketing commitments relating to on-going stability data continues to support certification.
- Change impact evaluated and additional checks and tests are complete.
- Investigations to batch certification including OOS and OOT.
- Complaints, investigations or recalls do not negate conditions for certification.
- Required TA’s in place.
- SI programme is active and current.
- Distribution and shipment arrangements are in place.
- Safety features have been affixed to the packaging.
What are the legal duties of an IMP QP?
SI 2004:1031 Part 6 Section 43
EU regulation 536/2014 and Regulation 2017/1569
- Manufactured and assembled to GMP, PSF and appropriate authorisations,
- import from outside the EU/EEA then it is made to GMP equivalent to UK GMP
- testing carried out to comply with PSF
- Certify and document in a register or equivalent
What are the legal duties of a QP for Veterinary Products?
SI 2013:2033 Schedule 2 Part 1 Section 11
EU regulation 2019/6
- Manufactured and assembled to GMP, and marketing authorisation
- import from the EU/EEA to carry out full qualitative analysis, quantitive of actives, other tests show compliance to MA
- Where MRA applies, accept on CofA.
- Certification on a control report
What are the different types of variations?
Type 1 - prior approval not required
- 1A - submit within 12 month of change
- 1AIN - notify immediately after implementation
Type 2 - prior approval required
Type 1B - neither type 1A or 2
Updates to legislation a QP needs to be aware of
Brexit
FMD
EU - CT Regs
Name the countries approved for import by the MHRA
Regulation 18A of the Human Medicines Regulations 2012 will allow importation of human medicines into Great Britain under a UK wholesale dealer’s licence from the following countries, provided that the UK wholesale dealer confirms that each batch has been certified by a Qualified Person (QP) in a listed country
EU countries, plus Iceland, Liechtenstein and Norway.
What are the safety features?….Are they required for all products?…What about IMPs
Directive 2011/62/EU (FMD) introduced requirement for all prescription medicinal to have safety features. - to enable verification of individual packs - tamper evidence seals of outer packaging.
Delegated regulation 2016/161 (to apply from Feb 2019).
Safety features required for the sale, distribution and supply of products:
- 2D barcode, and human readable format containing the following:
1. Product Code – Name, common name, pharmaceutical form, strength, pack size and type
2. Serial Number – numeric or alphabetic – must be randomised and comprise a max of 20 characters
3. National Reimbursement Number (if present)
4. Batch Number and Expiry Date
- Tamper-evident device
European Medicines Verification System <EMVS> to allow verification of authenticity by Wholesalers & distributers. verified and decommissioned before being dispensed. High risk also verified at the wholesaler.</EMVS>
Required for prescription but some exceptions e.g. Homeopathic, ATMPs, Radiopharmaceuticals, Medicinal gases, Electrolyts
Not required for non prescription, unless in the annex (omeprazole, also national CAs can add)
Not required for IMP but tamper evidence is required anyway and the IRT (interactive Response Tech) tracks.
You have an API manufactured and tested in India, Drug Product Manufactured and Tested in the US, Imported into Germany, QP in the UK
- Licences for all Sites (MIA in EU and MA), Check GMP certificates of API+DP manufacturer, API QP dec, Excipient risk assessment
- Import: DP import testing (if it’s not on the MRA), API cert of conformity (not required as not being imported to EU)
- Supply chain: mapped and risk assessed
- Audits: manu & test of DP and manu of API (conf distribution and storage arrangements)
- Reference: (at manu site or import testing site) and retention (at QP release site) samples
- Stability: does not NEED to be in the EU
- Batch release: per annex 16
- QTA: Details above , including QP shared responsibilities.
What is the regulatory basis for the QP?
Directive 2001/83/EC: (41 and 48) : MAH must have at least one QP, (49) qualifications/practical experience, (50) ‘transitional’ QPs who acted as a QP pre 20 May 1975, (51) legal responsibilities, (52) MS ensures duties of the QP are fulfilled. Directive 2001/83/EC needs to be transposed into National Law of each MS.
SI: 2012-No.1916 (17 parts and 35 schedules). Most relevant parts for the QP are Schedule 7: QP: educational requirements, experience and responsibilities
What is a directive?
Unlike regulations, Directives are interpreted into national laws (S.I. in the UK)
How are the regulations transposed into UK law?
Regulations have binding legal force throughout every Member State and enter into force on a set date.
What information is contained in a PSF?
EU GMP Volume 4 Annex 13:
A Product Specification File is a file containing or referring to all info needed to draft the instructions on: processing, packaging, QC, batch release and shipping of an IMP.
PSF is continually updated through development (with version control). Includes the following, at a minimum:
- Protocol
- Randomisation codes
- Approved label copy
- Manufacturing methods
- Specs and test methods for starting materials, packaging materials, Intermediate, bulk and finished product
- Stability data
- Storage and shipping conditions
- QTA
What changes to EU GMP guidance does the QP need to be aware of?
Annex 1: (PC Dani 5)
- PUPSIT will stay
- CCI expectation is 6 monthly to annual CCI checks (some MS require all batches)
- Distilation is no longer the only process for WFI production
- Align with PIC/S - i.e. there was US involvement
- New technology (isolators/RABS must be used)
- ICHQ9 and Q10 principles incorporated
- 5um particle monitoring in qualification of cleanroom not required
Annex 15: refers to the EMA guidance regarding a full toxicological assessment to derive a safe HBEL. A subsequent Q+A (2016) introduces the concept of “non highly hazardous” products which considers the 1/1000th minimum therapeutic dose approach as sufficiently conservative.
Annex 17: to become real time release
This will no longer only relate to Sterility testing - based on risk
Annex 21- Importers of Medicinal Products
To clarify requirements re: sampling and testing of imported products. (Physical and FISCAL importation)
ATMP GMP
Published as Vol 4 Part 4.
EP for Water for Injection (WFI)
EP for WFI revised, allowing Osmosis
What are the legal duties of the PVQP?
This was changed by amending Dir 2010/84/EU, The only QP PV info included in 2001/83/EC is:
- needs to be permanently available 24/7 and contact should be available to the CAs
- shall reside and operate in the EU
- shall be responsible for the establishment and maintenance of the pharmacovigilance system.
Further duties detailed in the Guidelines on Good PV Practices (GVP) and Eudralex volume 9, such as:
- Pharmacovigilance System master file (PSMF)
- Back up
- Safety profiles, Concerns and commitments relating to safe use
- Submit Data for PV correctly , and prompt response to requests
What is the difference between PIC and PIC/S?
PIC (founded 1970): The Pharmaceutical Inspection Convention - a legal agreement between reg authorities of countries with treaty status (for human or veterinary use).
PIC/S: The Pharmaceutical Inspection Co-operation Scheme (founded 1995) - An informal extension of PIC (49 authorities world wide - EU countries, north american countries, Australasian and some asian, some south america and south africa - detailed on PIC/S website……), as EU law did not allow individual EU countries to sign agreements with other non EU PIC countries. only the commission could sign agreements and they arn’t a member of PIC.
