Law & Admin Flashcards
What are the legal duties of the commercial QP and where to find?
As referenced in Statutory instrument 2012/1916 Sch. 7 Pt. 3.
The GB QP must ensure that:
- The batch has been m&t iaw NATIONAL LAW and the requirements of the MA.
- IMPORTED product from countries NOT on the ‘countries approved for import list’ have been tested for FULL
QUALITATIVE ANALYSIS, and QUANTITATIVE ANALYSIS at least the ACTIVE SUBSTANCES,
- All SAFETY FEATURES are affixed to packaging as per market requirements.
- Certification is RECORDED IN REGISTER or equivalent.
What are the non-delegable duties?
- Certification is permitted under the terms of the MIA
- Additional responsibilities and duties of National
Legislation have been complied with. - Certification is recorded in a register or equivalent.
Legal Duties of the IMP QP and where to find?
UKSI 2004/1031 Part 6 section 43
The GB IMP QP must ensure that:
- The batch has been manufactured and checked in
accordance with GMP, and the PSF, and in compliance with the authorisation in place (for
example, a CTA).
- Imported product has been manufactured and tested in
accordance with GMP or equivalent,
- Imported comparators have been manufactured In
accordance with GMP or equivalent or tested,
- Certification is recorded in a register or equivalent.
Delegable duties
- GMP has been complied with.
- The entire supply chain is documented, available to the QP,
preferability in the format of a comprehensive diagram. - All sites involved in the manufacture and testing of the
product and manufacture of the API have been audited and the
audit reports available to the QP. - All sites of manufacture, analysis and certification comply
with the terms of the MA. - All manufacturing activities and testing activities are
consistent with the MA. - The source and specification of all starting materials and
packaging materials comply with the MA, and a supplier
quality management system is in place. - All APIs used have been manufactured in accordance with
GMP and where relevant, distributed in accordance with GDP. - Imported APIs for human medicines comply with the
falsified medicines directive requirements, i.e. a written
confirmation of GMP compliance from countries not on the
white list. - Human medicines excipients used have been manufactured
in accordance with an appropriate level of GMP. - Where relevant, the TSE status of all materials complies
with the MA. - All records are complete and endorsed by appropriate
personnel. All in process controls and checks are complete. - All manufacturing and testing processes remain in the
validated state. Personnel are trained or qualified where
required. - QC data continues to meet the registered specification, or
where authorised, the Real Time Release Testing programme. - All post marketing commitments have been addressed.
The ongoing stability data continues to support certification. - The impact of any change to product manufacture or
testing has been evaluated and any additional checks and tests
are complete. - Any investigations pertaining to the batch in question have
been completed to a sufficient level to support certification. - All ongoing complaints, investigations and recalls do not
negate the conditions for certification of the batch in question. - All required technical agreements are in place.
- The self-inspection programme is current and active.
- Appropriate arrangements are in place for distribution and
shipping. - Product for the EU market has the required safety features.
How are they different commercial vs IMP QP?
QP Viva Flashcard: Commercial vs IMP Responsibilities
- Legislation & Licence
• Commercial:
• SI 2012/1916 – Human Medicines Regulations
• Requires MIA (Manufacturer’s Licence)
• IMP:
• SI 2004/1031 – Clinical Trial Regulations
• Requires MIA(IMP) licence
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- Basis for Batch Certification
• Commercial:
• Complies with Marketing Authorisation (MA)
• IMP:
• Complies with CTA, IMPD, and Product Specification File (PSF)
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- Documentation
• Commercial:
• QP certification logged in register
• IMP:
• QP issues formal batch certificate (filed in Trial Master File)
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- Release Process
• Commercial:
• Single-step release: QP certification → batch can be sold
• IMP:
• Two-step release:- QP certification
- Sponsor’s regulatory release (after ethics & CTA approvals)
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- GMP Requirements (Sliding Scale)
• Commercial:
• Full validation of process & methods expected
• IMP:
• Phase-appropriate GMP
• Early phases: limited validation allowed (risk-based)
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- Packaging & Labelling
• Commercial:
• Follows MA-approved pack & label
• IMP:
• Must meet Annex 13
• Includes trial-specific info, expiry, blinding, etc.
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- Comparators / Placebos
• Commercial:
• Not applicable
• IMP:
• QP ensures quality & traceability of comparators, placebos, rescue meds
• May require testing or repackaging under GMP
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- Regulatory Changes
• Commercial:
• Release only if MA variation approved
• IMP:
• Confirm CTA amendments or PSF updates are approved before release
What regal duties of VET QP?
UKSI 2013/2033
The VET QP ensure that
- Each batch batch is manufactured in compliance with GMP and tested in compliance with the terms of the MA.
- Certification recoded as register and draw up a control report.
- Ensure each imported (out side of CERS: countries with Equivalent Regulatory Standards) batch has undergone full qualitative and quantitative analysis of at least all the active substances, and all the other tests necessary.
Are you aware of any recent legislation changes in the UK?
- Windsor Framework
- Point of Care - Modular Manufacturing
- Changes to Clinical Trials regulations
- Veterinary medicine legislation 2013/2033 update
- International Recognition Procedure
What is WF?
- Ensure the smooth flow of POM medicines between GB and NI while protecting the EU single market
- by ‘UK only’ label (grace period by June 25)
- MHRA has become independent competent authority in the UK including NI
- FMD repealed
WF - please talk about product categories, licence changed, packaging material?
- Product Categories (Law & Admin)
Under the Windsor Framework, medicines supplied in Northern Ireland (NI) are permanently regulated by the MHRA, and not the EMA, which is a key divergence from the original Northern Ireland Protocol. This change applies to:
• Human Medicines, including Prescription-only (POM), Pharmacy (P), and General Sales List (GSL).
• Biological products and ATMPs—included within the MHRA’s scope for NI. - Licensing
Previously, products supplied to NI had to follow EU centralised or mutual recognition procedures. Now, under the Windsor Framework:
• UK-wide licences (PL) apply to NI too.
• The MHRA is the sole licensing authority for GB and NI.
• This simplifies QP responsibilities—one licence, one regulator. - Packaging Materials (Pharmaceutical Packaging – QP Study Guide Section i)
• All packs for UK (GB and NI) must now carry the “UK Only” label.
• The Falsified Medicines Directive (FMD) no longer applies in NI—so no 2D barcode or anti-tampering device is required for UK-only packs.
• For a transition period, stickers stating “UK Only” are permitted.
Packaging control expectations for the QP include:
• Ensuring packaging and labelling changes (e.g., “UK Only”) are reflected in the approved MA and artwork approval systems.
• Oversight of line clearance, reconciliation, and visual/automated checks to prevent pack mix-ups (as per QP Study Guide).
• Managing change control for printed component updates and revalidations as needed.
Whether WF applied to veterinary products and where would you check to find?
- WF apply to human medicines
- can check via:
MHRA guidance, VMD website
What is POC and modular manufacturing?
- Regulation 2025/87
- Scope: Short shelf-life human meds (e.g. ATMPs)
- Purpose: Flexibility in ATMP manufacturing
- Model: Hub (MIA, MIA/IMP, MA) + Bespoke sites (e.g. hospitals)
- Controlled by:
Decentralised Manufacturing Master File (DMMF)
Pharmacovigilance
What is the role of EDQM?
- A directorate of the COUNCIL of EUROPE, NOT for the EU (located in Strasbourg, FRA)
- European Pharmacopoeia: Developing and maintaining quality standards for medicines and substances.
- CEP Certification (Certificate of Suitability to the Monographs of the Ph. Eur.): Used to demonstrate API compliance with the Ph. Eur.
- OMCL Network: Coordinates a network of Official Medicines Control Laboratories for independent medicine testing.
- Also involved in blood transfusion, organ transplantation, cosmetics, and healthcare standards.
What is the role of ICH?
- The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
- Harmonising Guidelines of drug registration (regal enforcement when adopted)
- Members (over 50)
Founding regulatory/ industry members (EU, US, Japan)
Standing regulatory members
Regulatory/ industry members
Observers (e.g. WHO)
What ICH guidelines are there?
Q -Quality
Product development, GMP, PQS
S - Safety
Preclinical toxicology
E - Efficacy
Clinical trial design and conduct
M - Multidisciplinary
Cross-cutting tools (e.g. CTD, digital standards)
What are the implementation steps in ICH guidelines?
Step 1 – Consensus Building
•Expert Working Group (EWG) is formed with experts from ICH members.
•They draft the guideline and reach scientific consensus on the technical content.
•Once agreed, the draft is submitted to the ICH Management Committee.
Step 2 – Confirmation of Consensus & Drafting for Public Consultation
•The ICH Assembly confirms that consensus has been reached.
•The guideline is now considered a Step 2 document.
•It is released for regional public consultation (e.g. in the EU, US, Japan).
Step 3 – Regulatory Consultation & Discussion
•Each ICH region conducts public consultation.
•Comments are collected, reviewed, and incorporated by the EWG.
•The EWG works to resolve any issues raised and finalises the text.
•Once consensus is reached again, it becomes a Step 3 document.
Step 4 – Adoption of Harmonised Guideline
•The ICH Assembly formally adopts the harmonised guideline.
•It now becomes an official ICH Guideline.
Step 5 – Implementation
•Each regulatory authority (e.g. FDA, EMA, PMDA) implements the guideline according to their local procedures.
•This could involve integration into legislation, regulatory expectations, or guidance documents.
What are the current updates of ICH guidelines?
- ICH Q2(R2) & ICH Q14 – Finalized (Step 4) in November 2023
Q2(R2): Revision of the guideline on Analytical Validation. It now includes:
•Expanded scope to include multivariate and complex analytical procedures.
•Clarity on validation of methods developed using QbD and PAT principles.
Q14: A brand-new guideline on Analytical Procedure Development, promoting:
•A lifecycle approach.
•Risk-based method development.
•Flexibility in regulatory submissions by supporting structured method development.
- ICH E19 – Finalized (Step 4)
•E19: Focuses on Optimization of Safety Data Collection in late-stage pre-approval clinical trials.
•Allows targeted safety data collection in specific situations, minimizing unnecessary burden on trial sites while maintaining patient safety.
•Useful in trials where safety profile is well understood. - ICH M11 – Ongoing (Step 2 in 2023, progressing)
•M11: Clinical electronic Structured Harmonized Protocol (CeSHarP).
•Aims to standardize the format and content of clinical trial protocols.
•Will make trial design and submission more interoperable and efficient. - ICH E6(R3) – Draft (Step 2 in May 2023)
•A major overhaul of Good Clinical Practice (GCP) guidelines.
•Emphasis on risk-based, proportionate approaches.
•Modernization to accommodate digital trials, decentralized approaches, and new tech.
What is the role of PIC/S?
- Pharmaceutical Inspection Co-operation Scheme
- Participants 56 countries including the MHRA (UK), FDA (US), PMDA/PMDA-OMI (Japan), TGA (Australia), and most EU member states.
- Harmonising GMP inspection procedure worldwide.
- NON REGAL ENFORCEMENT
Are you aware of any recent legislation changes in the EU?
- EU Clinical Trials Regulation (CTR 536/2014)
*Centralised EU clinical trial applications now submitted via the CTIS portal.
*Replaces Directive 2001/20/EC. - EU GMP Annex 1 Revision (Sterile Medicinal Products)
*Introduces stricter requirements for Contamination Control Strategy, visual inspection, PUPSIT, and cleanroom classification. - EU Pharmaceutical Legislation Reform – Revision of Directive 2001/83/EC
*Still under discussion in 2025.
*Focuses on access to medicines, incentives, AMR, and regulatory simplification. - EU Artificial Intelligence (AI) Act
*Risk-based classification of AI systems, including potential applications in automated GMP systems.
*Relevant to data integrity, AI-assisted decision-making, and GxP software. - EU Packaging and Packaging Waste Regulation (PPWR)
*Will set new rules on packaging design, labelling, reuse, and waste reduction.
*May affect secondary/tertiary pharma packaging, especially in relation to tamper-evidence and sustainability goals.
Are you aware of any recent GMP changes in the EU?
- Annex 1 – Sterile Medicinal Products
•Fully revised and came into effect August 2023, with a transitional period until August 2024 for certain elements (e.g. CCS and lyophiliser loading).
•Strengthens expectations around contamination control strategy, PUPSIT, QRM, cleanroom classification, and visual inspection — all directly relevant to aseptic and radiopharmaceutical production. - Annex 21 – Importation of Medicinal Products
•Clarifies requirements for imports from non-MRA countries, including supply chain traceability, documentation, and site oversight. - Implementation of ICH Q12, Q13, and Q14
•Adopted into EU GMP:
•Q12: Lifecycle management and change control.
•Q13: Continuous manufacturing.
•Q14: Analytical procedure development (alongside revised Q2 on method validation). - Annex 3 – Manufacture of Radiopharmaceuticals
•Still in force but due for revision.
•A draft revision is anticipated to align Annex 3 with the principles of revised Annex 1, especially for aseptic radiopharmacies and short-shelf-life products. - Annex 4 (Veterinary Medicinal Products) and Annex 5 (Immunological VMPs)
•Updates are underway, currently in draft or consultation phase.
•Intended to align veterinary GMP with recent updates in human GMP, and with EU Regulation (EU) 2019/6 on veterinary medicinal products.
What are expected changes in up coming UK CT regulation update?
- Legislative Update
•The current legislation is based on SI 2004/1031, which implemented the old EU Clinical Trials Directive (2001/20/EC).
•The new UK clinical trials framework will replace this, aiming to be more flexible, efficient, and supportive of innovation. - Risk-Proportionate Approach
•Clinical trials will be regulated based on the risk to participants rather than a one-size-fits-all model.
•Enables more streamlined requirements for low-intervention trials, supporting academic and early-phase research. - Simplified Application Process
•A combined regulatory and ethics review will be introduced, led by the MHRA in collaboration with the Health Research Authority (HRA).
•Expected to significantly reduce start-up timelines. - Greater Use of Digital and Decentralised Trials
•The new framework supports remote monitoring, e-consent, and digital data capture, aligning with modern trial conduct practices. - Transparency and Public Involvement
•Sponsors will be required to register trials, publish results, and involve patients more actively in trial design and conduct. - Alignment with International Standards
•The UK aims to remain globally competitive, so the new rules will align with ICH GCP (R3) and support mutual recognition where possible, while still being independent of the EU CTR.
Are you aware of recent VET regulation update?
Under new requirement, QP must ensure the quality of returned veterinary medicines following a recall:
*Veterinary QPs must carry out a documented risk assessment before any returned product is considered for resale.
*The QP must ensure the returned stock was stored in line with conditions described in the SmPC, and there must be no confusion or risk of mix-up.
*If these criteria aren’t met, the returned product must not be returned to the market.
Can you discuss some of the key Primary Legislations relevant to medicinal Products in the UK?
Medicines Act 1968
•This is the foundational legislation for the control of medicines in the UK.
misuse medicines act 1972
Can you explain the differences with Secondary legislation？
Primary legislation
Acts of Parliament
- Sets legal framework
- Passed by Parliament
- Example: Medicines Act1968
Secondary legislation
- Also called delegated/subordinate legislation
- Made under authority of primary legislation
- Provides detailed rules
- Made by Ministers or regulatory bodies
- Quicker to amend
- Example: Statutory Instruments (SIs) like Human Medicines (Amendment) Regs
The role, legal status, and structure of both the British and European Pharmacopoeias,
British & European Pharmacopoeias
Role:
- Provide official standards for the quality of medicines and substances.
- Used for QC testing, release, and regulatory compliance.
Legal Status:
BP:
- Legal standard in the UK, under HMR 2012.
- Mandatory for licensed medicines in the UK.
Ph. Eur.:
- Legal in all Council of Europe countries.
- Binding in EU and UK (post-Brexit, UK still adopts it unless diverged).
Structure - Volume 1-5 + Vet BP:
1 & 2 - Monograph for Medicinal Substances
3 - General and Specific Monograph for FORMULATED preparations
4 - Herbal, Blood, Immunological, Radio pharmaceutical products
5 - Infrared Reference Spectra, Appendices ( Analytical methods, microbiology, sterility, etc)
6 - Vet pharmacopoeia
What are the relations of EMA, CHMP, EDQM
European Commission (EU decision maker) - EMA (EU centralised medicine authority) - CHMP (scientific committee)
Council for Europe (high level political body) - EDQM for Ph. Eur, CEP, OMCL, blood product
What is the process of CEP application
- Submission Dossier to EDQM
- Assessed by EDQM
- Inspection by EDQM
- Granting CEP
Can you explain what a Mutual Recognition Agreement?
- Formal Agreement between UK and I JUS CANE countries (LEGALLY BINDING TREATY) of BatATCH TESTING of human medicines will be accepted.
- Formal Agreement with I JUS BACKE countries of NON requirement of WRITTEN CONFORMATION.
Can you give examples of some countries with which the UK has an MRA with and what it entails?
EXEMPTION:
Australia
ATMP
Canada
Blood
ATMP
Israel
Medicinal gases
Homeopathic products
Blood
ATMP
Japan
Medicinal gases
Blood
ATMP
New Zealand
ATMP
United States of America
Vaccines
ATMP
Blood
Switzerland
No restriction
Can you explain what the Single Inspection Program is?
The Single Inspection Program (SIP) is a pilot initiative designed to enhance global collaboration in Good Manufacturing Practice (GMP) inspections. It involves regulatory authorities working together to inspect manufacturing sites of shared interest, especially in third countries (outside their own jurisdictions).
Key Features:
• Collaborative Global Initiative:
Launched by Health Canada, Therapeutic Goods Administration (TGA, Australia), and Medicines and Healthcare products Regulatory Agency (MHRA, UK).
• International Regulatory Alignment:
All participating authorities are members of:
• PIC/S (Pharmaceutical Inspection Co-operation Scheme)
• ICMRA (International Coalition of Medicines Regulatory Authorities)
• Access Consortium
• Shared Inspection Responsibility:
Authorities agree to rely on each other’s inspection reports and findings, reducing the need for duplicate inspections of the same third-country manufacturing sites.
• Focused on Foreign Sites of Common Interest:
Targets facilities that supply medicines across multiple regions (e.g., a manufacturer exporting to Canada, UK, and Australia).
• Benefits to Industry and Regulators:
• Reduces regulatory burden on manufacturers
• Increases inspection efficiency
• Improves oversight of global supply chains
• Fosters stronger international collaboration
What is differences in the Single Inspection Program and MRA?
SIP
- Scope: GMP INSPECTION
- Cooperation Sheme (NON-LEGALLY BINDING)
Can you explain some of the changes that Brexit has had on MRAs?
- MRA -> approved countries for import list
- UK became 3rd county from EU
- UK QP certification not accepted by EU, but UK still accept EU QP cert.
- WDA: RPI to check EU QP cert
- MIA/IMP: IMP QP oversite
Can you give us a summary of some of the key updates and changes to EU GMP?
- Annex 1 in great detail
- Annex 4 & 5 draft revision in some detail
- Draft Annex 11 revision in some detail
Can you tell me upcoming changes to clinical trials in the UK, how will this impact QP?
- Risk-Based Approach
o Under the upcoming UK Clinical Trials legislation, a risk-proportionate approach will be adopted.
o For low-intervention trials (similar to “low-risk” EU trials), a notification scheme may apply—meaning the MHRA may not require full assessment, only a notification, but ethics approval will still be required.
o This is intended to reduce burden while maintaining participant safety. - Single Application Process
o The UK will implement a combined review service that integrates MHRA and REC (Research Ethics Committee) review through a single application via IRAS (Integrated Research Application System) .
o This simplifies the submission and speeds up timelines (e.g. 30 days for review). - Updates to NIMPs and Labelling Flexibility
o Greater clarity will be provided on the definition and regulatory treatment of Non-Investigational Medicinal Products (NIMPs).
o In some cases, NIMPs may not need the same level of oversight or QP certification.
o Also, labelling requirements for IMPs and auxiliary medicines will become more flexible—for example, allowing pre-printed labels or reduced information in some trial types (especially when the investigator already has relevant data).
Bonus point you could add (optional):
* Transparency and Reporting: Results must be published within 12 months of trial completion, and shared with participants in plain language summaries.
You can say:
“These changes support a more flexible and pragmatic clinical trial environment post-Brexit. As a QP, I need to understand how these changes affect QP certification, NIMP classification, and whether an IMP needs to undergo full regulatory review or just a notification. It also impacts how I assess risks and label requirements for each batch.”
What are the structure of the MHRA?
CRPD, NIBSC and Inspectorate
What do you know about CPRD and its role?
Clinical practice research datalink- using anonymised NHS patient data, provide research service
How are vaccines released in UK ? What is role of NIBSC ?
Independent batch test by national control laboratory required as well as QP release.
NIBSC is organise national control laboratories.
What about VMD structure?
- Jurisdiction of Department for food and environment local affairs
- Delegate GMP inspection to MHRA
What do you know about the VMD and their relationship to the MHRA?
Veterinary Medicine Directorate - control licencing, inspection, pharmacovigilance of VM. Delegate GMP some part of inspection to MHRA is site has both human and vet manufacturing licence.
What laws are applicable to veterinary medications?
- VET Reg 2013/2033
- Animal Welfare ACT 2006
- The Misuse of Drugs Regulations 2001
- VICH
What is the content of PSF and impd ?
Product Specification File (PSF)
Defined in Annex 13.
Used by the QP as a working GMP document to ensure all necessary specifications and instructions are in place for certification.
Contents typically include:
* Specifications and analytical methods for:
* API, excipients, and packaging materials
* Intermediate, bulk, and finished products (including CQAs, CPPs, and acceptance criteria)
* Manufacturing process description (with critical steps and in-process controls)
* Packaging and labelling instructions, including:
* Randomisation code for blinded trials
* Approved label copy
* Stability data (supporting shelf-life and storage)
* Storage conditions (for raw materials and finished product)
* Primary container details
* Quality Technical Agreement (QTA) references where applicable
Note: The PSF is a GMP document, not submitted to regulators, but used to ensure batch certification and traceability.
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Investigational Medicinal Product Dossier (IMPD)
Required for Clinical Trial Applications (CTA) in the UK and EU.
Regulatory document containing quality, non-clinical, and clinical data to support the use of the IMP in humans.
IMPD = similar to CTD Modules 2 and 3, especially:
- Quality section (Module 3 equivalent)
Covers both active substance and finished product.
Active Substance:
* General information (e.g. name, structure, INN)
* Manufacturer details
* Description of the manufacturing process (with CPPs, CQAs, control strategy)
* Specifications and analytical methods (including impurities testing)
* Stability data and retest period
* Primary packaging details
Finished Product:
* Description and composition
* Manufacturing process and in-process controls
* Specifications and analytical methods (including for excipients if needed)
* Container closure system
* Storage conditions and shelf life
* Stability studies (real-time and accelerated)
- Non-clinical section (Module 4 equivalent)
- Pharmacology
- Pharmacokinetics (ADME)
- Toxicology data
- Clinical section (Module 5 equivalent)
- Summary of clinical experience or justification for the trial
- Investigator’s Brochure (submitted alongside IMPD)
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Viva Tip:
You can say:
“The PSF is a GMP-controlled document that supports QP certification, while the IMPD is a regulatory document submitted for CTA approval. The PSF contains practical manufacturing, testing, and labelling details, whereas the IMPD includes full quality, non-clinical, and clinical summaries to justify the use of the IMP in human trials.
What is Misuse act, when was it started. What are the different schedules/classes ?
Model QP Viva Answer:
The Misuse of Drugs Act 1971 is the primary UK legislation controlling certain substances that are liable to misuse or cause harm. It was introduced in 1971 and came into force in 1973. Its purpose is to prevent the misuse of controlled drugs by restricting their possession, supply, manufacture, and distribution unless authorised.
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Drug Classification under UK Law
There are two systems of classification in the UK:
- Drug Classes (A, B, C) – under the Misuse of Drugs Act 1971
These are based on harm potential and determine the criminal penalties for unlawful possession or supply.
• Class A – Most harmful (e.g. heroin, cocaine, MDMA, LSD, methadone, morphine)
• Class B – Intermediate risk (e.g. cannabis, ketamine, codeine, barbiturates)
• Class C – Least harmful (e.g. benzodiazepines, anabolic steroids, tramadol)
This classification is relevant for criminal enforcement but not for how medicines are regulated in clinical use.
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- Drug Schedules (1 to 5) – under the Misuse of Drugs Regulations 2001
These govern how controlled drugs can be used medically or industrially, and determine prescription, storage, and record-keeping requirements.
Schedule
Examples
Controls
Schedule 1
LSD, raw cannabis (non-medicinal)
No medical use, research only. Requires Home Office licence.
Schedule 2
Morphine, methadone, fentanyl, cocaine
POM, CD register required, locked storage, witnessed destruction.
Schedule 3
Temazepam, buprenorphine, midazolam
POM, no CD register, some require safe custody, 28-day script validity.
Schedule 4
Part I: Diazepam, zopiclone Part II: Anabolic steroids
POM, no CD register or safe custody; 28-day validity; import/export restrictions.
Schedule 5
Low-strength codeine (e.g. OTC co-codamol)
P/POM, minimal controls, no register or safe custody, invoices retained 2 years.
QP Relevance:
As a QP, I must ensure:
• Compliance with CD laws under the 1971 Act and 2001 Regulations for any batch containing controlled substances.
• That the site holds the correct Home Office licences for handling Schedules 1–3 drugs.
• That controlled drugs are stored securely, especially Schedules 2 and 3, and recorded in CD registers where required.
• For clinical trials, that IMP labels, QTA responsibilities, and storage conditions align with CD requirements.
• That import/export of IMPs involving controlled substances is licensed appropriately.
Failing to comply with CD law could not only breach GMP, but also lead to criminal penalties—so it’s an essential part of my batch certification checks.
What is RPI explain its checks. What is the similarity between QP oversight and RPI release?
RPI stands for Responsible Person (Import). This is a regulatory role introduced after Brexit under the Human Medicines Regulations 2012 (as amended), specifically to cover the importation of licensed medicinal products from countries on the MHRA’s “approved country for import” list, such as EU/EEA countries.
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RPI Role and Checks:
For commercial licensed products imported into Great Britain (GB) from an approved country (e.g. EU), RPI release is required instead of UK QP certification. The RPI does not re-certify the batch, but performs a documentary check to ensure:
1. The product was QP-certified in the EU/EEA.
2. The product is the same as that authorised in the UK (same MA, strength, form, etc.).
3. The product has been stored and transported appropriately, with no evidence of tampering or temperature excursions.
4. The supplier is authorised, and the supply chain is secure.
This is documented in an RPI release log prior to being placed on the UK market.
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Similarity to QP Oversight (for IMPs):
For Investigational Medicinal Products (IMPs) imported from the EU/EEA, the UK permits recognition of EU QP certification, but a UK-based QP must still provide “QP oversight” at the UK MIA(IMP) site.
Key similarities between RPI release and QP oversight:
• Both apply to imported products from the EU/EEA.
• Both rely on EU QP certification, and do not require re-certification in the UK.
• Both involve checks on supply chain, transport, labelling, and documentation before release (for commercial supply or for use in a clinical trial).
• Neither performs full product testing or manufacturing review—they are document-based release checks.
In both cases, the UK ensures that imported batches are safe, compliant, and traceable, even if re-certification or re-testing is not required.
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QP Relevance:
As a QP, I must understand when full QP certification is required versus when RPI release or QP oversight applies. For IMPs, I retain personal responsibility for ensuring that imported EU-certified batches meet the CTA and UK GMP standards before use in trials, even if re-certification is not needed.
Could you talk to us about differences around the certification of biological products ?
Biological products, such as monoclonal antibodies, vaccines, blood-derived products, and cell/gene therapies, have additional requirements and considerations compared to conventional chemically-synthesised medicines due to their complexity, variability, and sensitivity.
Here are the key differences that affect QP certification:
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- Specific QC Requirements:
The specifications for biological products typically include tests not required for standard small-molecule drugs. These may include:
• Potency assays (bioactivity)
• Sterility and mycoplasma testing
• Appearance checks (e.g. turbidity, colour)
• Cell viability/count (for cell-based therapies)
• Identity and purity, often using complex assays like ELISA or PCR
Due to inherent biological variability, tight control of critical quality attributes (CQAs) and validation of analytical methods are essential.
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- Certification Before Completion of All Tests:
In some cases—especially for short shelf-life or patient-specific biologicals (e.g. autologous cell therapies)—the QP may be required to certify the batch before all QC test results are available, such as full sterility or mycoplasma results.
In such cases, certification is based on:
• Completion of critical tests (e.g. identity, endotoxin, appearance, key safety markers)
• A documented risk assessment agreed between the QP and the responsible clinician
• Regulatory approval or pre-authorisation (especially for unlicensed or compassionate-use cases)
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- Possibility of Use of a Defective Product:
Due to the personalised and non-replaceable nature of some biologicals (e.g. autologous CAR-T cells), there may be rare situations where product defects are known, but the product is still administered based on a clinical benefit-risk assessment.
This would require:
• Documented QP and clinician agreement
• Patient consent
• Regulatory authority notification and/or approval
• Documentation in the QP certification statement and batch record
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- Independent Batch Testing by a National Control Laboratory (NCL):
Certain biologicals, such as vaccines, blood products, and some ATMPs, require Official Control Authority Batch Release (OCABR) or NIBSC testing (UK’s National Institute for Biological Standards and Control) before release to market.
The QP must ensure:
• The correct sample is submitted to the national control lab
• The batch is not released until the OCABR certificate or equivalent is received
• The testing requirement is understood during planning and lead time management
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In Summary:
Biological product certification differs from standard medicines due to:
• More complex specifications (potency, sterility, mycoplasma, etc.)
• The need for flexibility in certification timing
• Additional risk-based decisions involving QP and clinical teams
• The requirement for independent batch release testing by national authorities
As a QP, I must be fully aware of these requirements, ensure robust quality systems are in place, and liaise with regulators and clinicians when necessary to ensure patient safety and product compliance.
What is regulation 174?
Question: What is Regulation 174?
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Model Answer:
Regulation 174 of the Human Medicines Regulations 2012 provides a legal basis for the temporary authorisation of an unlicensed medicinal product in the UK in response to certain public health emergencies, such as a pandemic or serious outbreak of infectious disease.
It allows the MHRA (UK regulator) to authorise a product that does not yet hold a full UK Marketing Authorisation (MA) to be supplied to patients when:
• There is a suspected or confirmed public health threat, and
• There are no suitable licensed alternatives available, and
• The potential benefit outweighs the risk in the emergency context
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Key Features:
• Used during the COVID-19 pandemic to authorise early use of vaccines (e.g. Pfizer/BioNTech) before formal MA was granted.
• Authorisation is granted at the Secretary of State’s discretion, based on MHRA assessment.
• The product remains unlicensed, and its supply is restricted to defined settings and populations.
• It includes conditions around pharmacovigilance, labelling, storage, and clinical oversight.
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QP Relevance:
As a QP, if I am involved in the supply of a Regulation 174 product (e.g. a COVID-19 vaccine), I must ensure that:
• The product is manufactured in compliance with GMP
• The batch has been certified by a QP under EU or UK GMP
• All conditions of the Regulation 174 authorisation (e.g. storage, labelling, usage restrictions) are fully met
• Pharmacovigilance and traceability systems are in place
Although the product is unlicensed, its supply must still meet high quality standards and be justified based on risk-benefit in the emergency setting.
Do you know any updates from a biologicals perspective in the last year?
Yes, there have been recent developments in the regulation of biologicals, particularly for ATMPs. One key update is the MHRA’s planned implementation of a new regulatory framework for point-of-care (PoC) and modular manufacturing, expected to become applicable from mid-2025.
This framework is designed to provide greater flexibility for the manufacturing of ATMPs, especially those with a short shelf-life, in hospital or mobile settings.
The proposed model follows a “hub-and-spoke” system, where:
• A centralised hub site holds the manufacturing licence and oversees quality and compliance.
• The spoke sites (e.g. hospitals or mobile units) may not be licensed themselves but are controlled via a DMMF (Distributed Manufacturing Master File) maintained at the hub.
• The hub retains responsibilities for pharmacovigilance, traceability, and product oversight across the network.
This approach supports scalable, localised manufacturing, which is particularly important for personalised and time-sensitive biologicals like autologous CAR-T cell therapies.
Can you delegate your legal duties? As a QP how would ensure certification in a register?
No, a Qualified Person (QP) cannot delegate their legal duty to certify a batch. Certification is a personal legal responsibility under EU and UK legislation (e.g. Human Medicines Regulations 2012 and EU GMP Annex 16). While tasks may be delegated, the act of certification must be performed only by the QP.
To ensure that QP certification is properly recorded in the register, I would:
• Implement a robust SOP describing the certification process, including how entries must be made in the register (electronic or paper-based).
• Ensure all relevant staff are trained on the SOP, especially those supporting the QP in documentation or record-keeping.
• Perform regular internal audits or self-inspections to verify the accuracy, completeness, and integrity of the QP certification register.
• Use a deviation and CAPA system to capture and investigate any issues with certification or record-keeping, ensuring root causes are addressed and preventative actions are implemented.
What is 536/2014? From the new detailed commission guideline (new Annex 13) what are the principles UK decided to adopt?
Regulation (EU) No. 536/2014 is the Clinical Trial Regulation (CTR) that replaced Directive 2001/20/EC in the EU. It aims to harmonise the assessment and supervision processes for clinical trials throughout the EU via a centralised EU portal and database (CTIS).
However, because the UK left the EU before the CTR came into application (31 January 2022), the UK did not adopt 536/2014. Instead, the UK continues to follow Directive 2001/20/EC and the older version of Annex 13 (as part of EudraLex Volume 4).
From the new Detailed Commission Guidelines (effectively replacing Annex 13 in the EU under the CTR), the UK has chosen to retain the following principles from the old Annex 13:
• The two-step release process: QP certification followed by sponsor release.
• Labelling requirements remain consistent with the old Annex 13, unless updated under UK legislation.
Who is RPI? How is he/she different to RP role?
The Responsible Person (import), or RPi, is a role required for the importation of medicinal products from an EEA country into Great Britain under a Wholesale Dealer’s Licence (WDA(H)). The RPi is responsible for verifying that each batch has been certified by a Qualified Person (QP) in the EU/EEA and that it has been transported under appropriate conditions before being released for further distribution in the UK.
This role differs from the standard Responsible Person (RP), who is responsible for ensuring GMDP compliance of all wholesale activities under the WDA(H), including storage, distribution, and supply of medicines within the UK.
How long is the register kept for?
5 years
What is Regulatory and Technical Green light, and what are the responsibilities of a Sponsor?
Regulatory and Technical Green Light – Sponsor Responsibilities
• Regulatory Green Light refers to the approval of a clinical trial by both the MHRA (clinical trial authorisation) and a recognised Research Ethics Committee.
• Technical Green Light refers to the QP certification of the Investigational Medicinal Product (IMP), confirming that it has been manufactured and released in compliance with the clinical trial authorisation, GMP, and the approved protocol.
The Sponsor is responsible for ensuring that both green lights are in place before the trial can commence. While the Sponsor retains overall responsibility, the technical green light process may be delegated to a Qualified Person (QP).
What are the two laws governing UK medicines?
SI 2012/1916 and SI 2004/1031 are the two main statutory instruments governing medicinal products in the UK—one for general medicinal products and the other specifically for clinical trials.”
Can you give an overview of what Annex 21 is about?Does it impact IMPS?
Overview of Annex 21:
Annex 21 defines the GMP responsibilities and expectations for sites involved in the importation of medicinal products into the EU/EEA from third countries (i.e. countries outside the EU/EEA).
Scope – What types of products are covered?
Annex 21 applies to all medicinal products for human and veterinary use, including:
• Commercially authorized products
• Investigational medicinal products (IMPs)
• Bulk medicinal products
• Intermediate products
• Biological and biotechnology-derived products
• Radiopharmaceuticals
• Advanced therapy medicinal products (ATMPs)
This includes products that are:
• Manufactured in a third country and imported into the EU/EEA
• Intended for further processing or final use (e.g. packaging, labelling, direct supply)
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Key Requirements:
• Manufacture and testing:
Products must be manufactured and tested in compliance with EU GMP (Parts I, II, and applicable annexes).
• Identity testing:
Each batch must undergo identity testing upon importation, unless a derogation has been granted by the competent authority or justified via risk assessment.
• QP Certification:
A Qualified Person (QP) must certify each batch before it is released for sale or for clinical trial use in the EU.
• Pharmaceutical Quality System (PQS):
Importers must maintain a robust PQS, ensuring oversight, traceability, deviation/CAPA management, and supplier qualification (including third-country sites).
• Roles and responsibilities:
There must be clear definition of responsibilities between:
• The third-country manufacturer
• The importer
• The EU-based QP
• Applicable to different product stages:
Includes import of finished dosage forms, bulk, or intermediates for further processing or packaging.
Tell us about the update of Orange Guide 2022?
-1. MHRA Organisational Structure Updates:
• The updated guide reflects the MHRA’s revised internal structure following Brexit.
• New sections outline how the MHRA has adjusted its regulatory roles, including functions split between licensing, inspection enforcement, and vigilance.
• There is more clarity on how the MHRA interacts with UK-based and international stakeholders post-EU exit.
2. Annex 13 – Clinical Trials (Old vs New):
• The old Annex 13 was aligned with EU Clinical Trials Directive 2001/20/EC.
• Post-Brexit, the UK retained its own version of Annex 13, which has been included in full in the Orange Guide 2022.
• This UK-specific Annex 13 continues to govern the manufacture and importation of Investigational Medicinal Products (IMPs).
• While the EU has moved on to Regulation (EU) No. 536/2014 (Clinical Trial Regulation), the UK still operates under the Clinical Trials Regulations 2004, so the UK Annex 13 remains relevant.
3. GDP Regulations Included:
• The 2022 edition also includes the full text of the MHRA Green Guide (Good Distribution Practice), which was not part of previous Orange Guides.
• This allows manufacturers to have a single reference point for both GMP and GDP requirements, especially important for MIA holders with WDA responsibilities or integrated supply chains.
What were the changes due to Brexit, what would Windsor framework have impact on
Brexit:
- MRA -> approved countries for import list
- UK became 3rd county from EU
- UK QP certification not accepted by EU, but UK still accept EU QP cert.
- WDA: RPI to check EU QP cert
- MIA/IMP: IMP QP oversite
Ni protocol, NIMAR, MHRA solos competent authority, FMD repealed.
Windsor Framework - UK ONLY label to protect EU market
What are the contents of the PSF?
- Specifications and analytical methods for starting materials, packaging materials;
- Intermediate, bulk and finished product;
- Manufacturing methods;
- In-process testing and methods;
- Approved label copy;
- Relevant clinical trial protocols and randomisation codes, as appropriate;
- Relevant technical agreements with contract givers, as appropriate;
- Stability data;
- Storage and shipment conditions.
When would you consider import testing for IMP?
- Imported comparator products from 3rd country (not GMP equivalent)
- PSF ask to do
- when deviation during shipment
ICH vs PIC/S
Question: What’s the difference between ICH and PIC/S?
Model Answer: ICH develops scientific/technical guidelines; PIC/S focuses on harmonisation of GMP inspections. ICH guidance is not law unless adopted into national legislation; PIC/S supports GMP inspectorates.
Tips: ICH = industry guidance; PIC/S = regulatory inspector guidance.
- EDQM
Question: What is the function of EDQM?
Model Answer: European Directorate for the Quality of Medicines. Issues CEPs, coordinates OMCL network, provides Ph. Eur. standards and reference materials. Supports blood/tissue regulation under Council of Europe.
Tips: Mention CEPs and their role in MA submissions.
What is a control report in the context of veterinary medicines (2019/6)?
Model Answer:
A control report is a formal QP-authored document confirming that the batch was manufactured and tested in accordance with GMP and the marketing authorisation. It must include confirmation of compliance with all quality specifications and reference test results (e.g., CoA, CoC). It can be used across the EU to support batch release decisions by authorities like the VMD.
Tips:
• Mention that the term “control report” is specific to Regulation (EU) 2019/6 (veterinary medicines).
• Clarify it’s conceptually similar to the human QP release statement but includes more detail and traceability.
• Acknowledge the lack of a standardized template—firms define their own format.
Q: Describe the key differences between veterinary and human medicines from a QP perspective.
Model Answer:
• Regulatory body: VMD for veterinary medicines, MHRA for human medicines.
• Batch release: Veterinary QP must prepare a control report; MHRA requires QP certification in the batch register.
• Testing: Some vaccines or biologics may require VMD batch review before release; fewer EU Official Control Authority Batch Release (OCABR)-type requirements.
• Inspections: VMD inspections may have different emphasis and frequency. Some companies report a lower bar compared to MHRA.
• Importation: Veterinary biologics may not need re-testing if from recognised countries (e.g., Switzerland, Ireland).
Tips:
• Show awareness of the VMD’s unique requirements (e.g., animal test certificates).
• Use Regulation 2019/6 to back up your understanding.
• Be ready to explain clinical trials for animals = “field studies”
What are the key regulatory changes under the Windsor Framework?
• Model Reference: MHRA Windsor Framework Guidance, Sept 2024 webinar
• Key Points:
• PLGB replaces PL and PLNI across UK
• No FMD in NI
• MHRA responsible for licensing across UK
• “UK Only” packs mandated
• Tip: Have 3–5 regulatory changes ready, with ability to explain why they matter to a QP.
Does the Windsor Framework apply to veterinary medicines or radiopharmaceuticals? Why not?
• Model Reference: VMD Brexit Guidance
• Tip: Say no—veterinary medicines fall under VMD jurisdiction. VMD taking a separate route, extension to 2025. Radiopharmaceuticals often excluded from serialization mandates.
Why do you need to keep up to date with regulatory updates as a QP?
As a QP, one of my non-delegable legal duties is to ensure that the product is manufactured in compliance with national law. Regulatory changes directly impact my ability to meet this obligation.
Is MRA for Human medicine and Vet medicine different?
Yes - CERS (Countries with Equivalent Regulatory Standard) as per VMD guidance,
I U S C A N (i.e. without Japan)
