Law & Admin Flashcards

Question

What are the relations of EMA, CHMP, EDQM

Answer 1

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

Answer 2

1. Submission Dossier to EDQM 2. Assessed by EDQM 3. Inspection by EDQM 4. Granting CEP

Answer 3

- 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.

Answer 4

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

Answer 5

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

Answer 6

SIP - Scope: GMP INSPECTION - Cooperation Sheme (NON-LEGALLY BINDING)

Answer 7

- 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

Answer 8

RP (Responsible Person) – Ensures GDP compliance, customer qualification, storage, transport, and system oversight for WDA operations. RPi (Responsible Person for Import) – Specific to importation from EEA to GB. Ensures that imported batches have valid QP certification in EEA and supports oversight during importation. Only RP is involved in UK domestic wholesale distribution. RPi applies when importing from EU.

Answer 9

- Annex 1 in great detail - Annex 4 & 5 draft revision in some detail - Draft Annex 11 revision in some detail

Answer 10

0. Clinical Trial Regulation (CTR) went live April 11, 2025 1. 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. 2. 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). 3. 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.”

Answer 11

CRPD, NIBSC and Inspectorate

Answer 12

Clinical practice research datalink- using anonymised NHS patient data, provide research service

Answer 13

Independent batch test by national control laboratory required as well as QP release. NIBSC is organise national control laboratories.

Answer 14

- Jurisdiction of Department for food and environment local affairs - Delegate GMP inspection to MHRA

Answer 15

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.

Answer 16

- VET Reg 2013/2033 - Animal Welfare ACT 2006 - The Misuse of Drugs Regulations 2001 - VICH

Answer 17

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. ⸻ 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: 1. 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) 2. Non-clinical section (Module 4 equivalent) * Pharmacology * Pharmacokinetics (ADME) * Toxicology data 3. Clinical section (Module 5 equivalent) * Summary of clinical experience or justification for the trial * Investigator’s Brochure (submitted alongside IMPD) ⸻ 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.

Answer 18

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. ⸻ Drug Classification under UK Law There are two systems of classification in the UK: 1. 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. ⸻ 2. 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.

Answer 19

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. ⸻ 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. ⸻ 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. ⸻ 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.

Answer 20

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: ⸻ 1. 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. ⸻ 2. 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) ⸻ 3. 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 ⸻ 4. 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 ⸻ 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.

Answer 21

Question: What is Regulation 174? ⸻ 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 ⸻ 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. ⸻ 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.

Answer 22

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.

Answer 23

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.

Answer 24

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.

Answer 25

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.

Answer 26

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).

Answer 27

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.”

Answer 28

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) ⸻ 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.

Answer 29

-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.

Answer 30

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

Answer 31

* 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.

Answer 32

- Imported comparator products from 3rd country (not GMP equivalent) - PSF ask to do - when deviation during shipment

Answer 33

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.

Answer 34

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.

Answer 35

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.

Answer 36

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”

Answer 37

• 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.

Answer 38

• 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.

Answer 39

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.

Answer 40

Yes - CERS (Countries with Equivalent Regulatory Standard) as per VMD guidance, I U S C A N (i.e. without Japan)

Answer 41

Commercial: UK SI 2012/1916 Schedule 7 part 3 IMP: UK SI 2004/1031 part 3 section 46 Vet: 2013/2033 schedule 2 part 1

Answer 42

I mentioned I subscribed to NSF and RSSL quarterly updates, I mentioned Pete Gough’s updates are very helpful. I am a member of PQG and also, I personally put these changes in mind maps which helps me to remember these changes.

Answer 43

MA, MIA, MS • ManA, ManSA • MIA (IMP) • MaAT • WDA

Answer 44

Here I gave them DHSC, DASH portal, specific person dealing with DASH, SMP and SPP and finally I said MHRA has asked for our RMP in the previous audit around these.

Answer 45

Annex 16 update – enhanced QP supply chain traceability duties. Annex 15 (Validation) – updates in draft. Annex 4 & 5 – revision ongoing since 1997. Artificial Intelligence in GMP being considered.

Answer 46

Q14 (Analytical Procedure Development) finalised – linked with Q2R2. Draft revisions for Q1 to Q5 stability and quality guidelines.

Answer 47

Remote inspection guidance. New members: Saudi Arabia, Taiwan.

Answer 48

Can find in EU GMP part 3. The QP declaration is a formal statement confirming that the active substance used in a medicinal product has been manufactured in compliance with GMP standards. It is required for: -New marketing authorization applications. -Variations to existing authorizations. -Renewals of marketing authorizations. The declaration must be based on audits and assessments of the active substance manufacturer and is crucial for ensuring the integrity of the supply chain. Contents: 1. Name and address of API manufacturer 2. name of API 3. Audit details (date, authority name, outcome of audit) 4. Justification section 5. QP declaration

Answer 49

A Qualified Person (QP) should be familiar with the Human Medicines Regulations 2012 (SI 2012/1916) and, in particular, the following key Schedules and Parts relevant to QP responsibilities: • Schedule 7, Part 3 – Duties of a QP (for both commercial and investigational products) • Schedule 24 – Packaging requirements • Schedule 27 – Leaflet and labelling requirements • Schedule 31 – Sampling and testing of medicinal products • Schedule 34 – Amendments to existing legislation Additionally, QPs should be familiar with related Parts of the regulations such as: • Part 3 – Manufacture and wholesale dealing • Part 5 – Marketing authorisations • Part 11 – Pharmacovigilance • Part 13 – British Pharmacopoeia standards

Answer 50

• Replaces MR/DC procedures with Reference Regulator Scheme. • Route A: Two-year MA can convert to national. • Route B: Ten-year-old MAs reviewed for changes before approval. • Participating countries: EU, Canada, Australia, Switzerland, Japan, Israel

Answer 51

• Ensures GDP compliance (storage, distribution, falsified medicines, customer qualification). • May oversee release from warehouse, especially for short shelf-life products (conditional release possible, certification still mandatory). • Responsible for: • Bona fide checks • Chain of custody • Maintaining quality systems for WDA(MH) site • Temperature and distribution oversight • Hosting MHRA inspections • Signing pedigree statements (when applicable)

Answer 52

⸻ Model Answer: The legal duties of a Veterinary QP are primarily set out in the Veterinary Medicines Regulations 2013, specifically SI 2033 Schedule 2, Part 1. These duties closely mirror those of a commercial QP for human medicines, with the key requirement that a veterinary medicinal product must: * Be manufactured in accordance with its Marketing Authorization (MA). * Comply with Good Manufacturing Practice (GMP). * For imported products, be sourced from countries with equivalent GMP standards (not limited to EU/EEA). Additionally, the Veterinary QP is responsible for batch certification, ensuring that products are safe, efficacious, and of the right quality before release. A recent legal update introduced via SI 2024/567 imposes new duties on the Veterinary QP in relation to product recalls. Specifically, if a product is returned (e.g., following a recall), the Veterinary QP must verify that: * The product is not counterfeit. * Traceability requirements are met. This ensures that returned products can only be re-introduced into the supply chain if they maintain integrity and meet legal traceability standards. This new legal duty strengthens supply chain security and aligns with pharmacovigilance principles, ensuring that only genuine, traceable products are available on the market. These requirements are legally binding as they are embedded in statutory legislation (SI 2024/567), making them part of the Veterinary QP’s legal obligations. If required, I would refer directly to SI 2033 and SI 2024/567 for compliance, and ensure that the site’s PQS incorporates appropriate procedures for verification of returned products, including counterfeit checks and traceability assessments.

Answer 53

⸻ Model Answer: Yes. An Act of Parliament is primary legislation. It forms the foundation of the law and is passed through Parliamentary procedures, starting as a Bill, debated in the House of Commons and House of Lords, and once approved, it receives Royal Assent and becomes law. An example of an Act of Parliament is the Human Medicines Act 1968, which provides the legal framework for regulating medicinal products in the UK. In contrast, a Statutory Instrument (SI) is secondary legislation (also known as delegated legislation). It is made by government ministers or regulatory bodies (such as the MHRA or VMD) under the powers granted by an Act of Parliament (the enabling Act). SIs are used to add detail, make updates, or implement technical changes without the need to pass a new Act through Parliament. This allows for flexibility and timely updates to legislation, especially in technical or fast-moving areas like medicines regulation. For example: • The Human Medicines Regulations 2012 (SI 2012/1916) is an SI made under the Human Medicines Act 1968. • The Veterinary Medicines Regulations 2013 (SI 2013/2033) is an SI made under the Veterinary Medicines Act. • A recent example is SI 2024/567, which introduced new legal duties for Veterinary QPs regarding counterfeit verification and traceability during product recalls. These SIs are legally binding and can either follow: • Negative resolution procedure (automatically becomes law unless Parliament objects within a set timeframe), or • Affirmative resolution procedure (requires active approval by Parliament). The MHRA Orange Guide provides interpretation and practical guidance on how SIs are applied within medicines regulation. ⸻ Buzzwords: • Primary legislation • Act of Parliament • Bill → Royal Assent → Act • Secondary legislation / Statutory Instrument (SI) • Delegated legislation • Enabling Act • MHRA / VMD • HMR 2012 (SI 1916) • Veterinary Medicines Regulations 2013 (SI 2033) • SI 2024/567 (Veterinary QP duty) • Negative / Affirmative resolution procedure • MHRA Orange Guide (interpretation tool)

Answer 54

⸻ Model Answer: Yes. The Common Technical Document (CTD) is a harmonised format used internationally for submitting marketing authorisation applications (MAAs). It is designed to streamline regulatory submissions across ICH regions (EU, US, Japan) and is defined under the ICH M4 guideline. The CTD structure consists of five modules: 1. Module 1 – Regional Administrative Information: • Contains country-specific documents, such as the Summary of Product Characteristics (SmPC), artwork, QP declarations, variation history, and pharmacovigilance system information (e.g., PSMF location). • This module is not harmonised globally—it varies by regulatory authority. 2. Module 2 – Overviews and Summaries: • Contains summaries of the Quality, Non-clinical, and Clinical data found in Modules 3-5. • Supports assessors with high-level summaries to interpret the detailed data. 3. Module 3 – Quality: • This is the most relevant module for QPs during batch certification. • Includes detailed information on: • Active Substance (API): Manufacturer details, control of materials, specifications, and stability data. • Finished Drug Product: Manufacturing process, container closure system, product specifications, control of critical steps, and stability data. • QP certification requires confirmation that the batch complies with the Marketing Authorisation (MA), and Module 3 is where the GMP compliance, specifications, and manufacturing details are verified. 4. Module 4 – Non-clinical Reports: • Contains toxicology, pharmacology, and safety pharmacology studies (primarily animal data). 5. Module 5 – Clinical Reports: • Includes clinical trial data (human data), efficacy, and safety studies. ⸻ Electronic CTD (eCTD) – ICH M8: • The electronic version of the CTD (eCTD) is described in ICH M8. • M8 provides the technical specifications for submitting the CTD in electronic format to regulatory authorities. • The eCTD format improves regulatory efficiency by allowing structured data exchange, navigation, and lifecycle management. ⸻ Application to IMPDs (Investigational Medicinal Product Dossier): • The IMPD follows a similar structure to the CTD, particularly for Module 3 (Quality). • IMPDs contain evolving data, especially in Modules 4 and 5 (non-clinical and clinical), as clinical trials progress through phases. • For QP batch certification of IMPs, Module 3 (Quality section) remains the most critical area: • Ensuring compliance with the Product Specification File (PSF). • Ensuring alignment with the Clinical Trial Authorisation (CTA) and GMP requirements. ⸻ Summary of ICH References: • ICH M4: Defines the CTD structure (Modules 1-5). • ICH M8: Defines the eCTD format (electronic submission). ⸻ Buzzwords: • CTD – Common Technical Document • ICH M4 – CTD structure • ICH M8 – eCTD format (electronic submission) • Modules 1-5 • Module 3 – Quality (QP focus) • IMPD – Investigational Medicinal Product Dossier • Product Specification File (PSF) • Clinical Trial Authorisation (CTA) • Evolving data (IMPD) • QP certification

Answer 55

Model Answer: Yes. Pharmacovigilance (PV) refers to the monitoring, detection, assessment, and prevention of adverse effects or other drug-related problems. It is a legal requirement for Marketing Authorisation Holders (MAHs) to operate a compliant pharmacovigilance system. Key elements of a PV system include: 1. QPPV (Qualified Person for Pharmacovigilance): • The QPPV is legally responsible for ensuring the ongoing safety monitoring of a medicinal product. • In the UK post-Brexit, the QPPV can reside either in the UK or EU. • If the QPPV is based in the EU, a National Contact Person for Pharmacovigilance (NCPP) must be appointed in the UK (per MHRA guidance). • The QPPV must ensure that the Pharmacovigilance System Master File (PSMF) is maintained and accessible. 2. PSMF (Pharmacovigilance System Master File): • The PSMF documents the entire pharmacovigilance system used by the MAH. • Key contents include: • Details of the QPPV. • Organogram of the pharmacovigilance system. • Processes for signal detection and management of Individual Case Safety Reports (ICSRs). • Periodic Safety Update Reports (PSURs). • Audit trails of PV activities and corrective actions. • Risk Management Plans (RMPs) and any Post-Authorization Safety Studies (PASS) commitments. 3. Other pharmacovigilance tools: • PSURs: Regular safety updates, submitted to regulators to provide a benefit-risk evaluation over time. • ICSRs: Individual reports of adverse events (spontaneous, clinical trial data). • RMP (Risk Management Plan): Outlines strategies for identifying, characterizing, and minimizing risks. • PASS (Post-Authorization Safety Studies): Additional safety studies conducted after product approval to further investigate safety concerns or verify safety in specific populations. ⸻ QP Considerations regarding Pharmacovigilance during Batch Certification: • As a QP, while certification is primarily focused on GMP compliance, I must ensure that the product is compliant with the Marketing Authorisation, which includes pharmacovigilance commitments. • Specifically, I would check that: • The MAH’s PV system is in place and compliant (including the QPPV and PSMF). • Safety updates, such as PSURs, are current for the product. • Any relevant pharmacovigilance actions (e.g., RMP updates, PASS requirements) have been implemented and reflected in the product’s labeling or MA. • For recalls, ensuring that pharmacovigilance reports (e.g., adverse events) have been considered as part of the recall decision process. • Good PV practice (GVP) modules provide detailed guidance on these expectations. ⸻ Buzzwords: • Pharmacovigilance (PV) • QPPV (Qualified Person for Pharmacovigilance) • National Contact Person for Pharmacovigilance (NCPP) • PSMF (Pharmacovigilance System Master File) • ICSRs (Individual Case Safety Reports) • PSURs (Periodic Safety Update Reports) • RMP (Risk Management Plan) • PASS (Post-Authorization Safety Studies) • GVP modules (Good Pharmacovigilance Practices) • QP considerations for MA compliance • Benefit-risk evaluation

Answer 56

An unexpected deviation, as defined in Annex 16 of EudraLex Volume 4, refers to a minor, unplanned departure from registered manufacturing or control processes, where the final product still meets all approved specifications (e.g. identity, purity, strength, quality, safety). Key conditions for handling an unexpected deviation include: • It must not be a repeat occurrence. • A thorough root cause investigation must be conducted. • CAPA (Corrective and Preventive Actions) must be implemented. • The product’s quality, safety, and efficacy must not be compromised. • Quality Risk Management (QRM) principles should guide the decision. In contrast, a Batch-Specific Variation (BSV) is a regulatory procedure used to request approval to release a specific batch or small number of batches that deviate from the terms of the Marketing Authorisation (MA). BSVs are submitted as Type II variations and require: • Approval from the competent authority (e.g., MHRA) before batch release. • A detailed justification, including impact assessment and rationale for stock continuity. • Documentation showing that product quality and patient safety are not affected. • A fee, often several thousand pounds (e.g. ~£11,000 for expedited cases). Importantly, if a batch is out-of-specification (OOS), it cannot be released under unexpected deviation and must follow the BSV route with competent authority approval. ⸻ Buzzwords: • Annex 16 • Unexpected deviation • Batch-Specific Variation (BSV) • Type II variation • Marketing Authorisation (MA) • QRM principles • CAPA • Competent authority approval • OOS batch

Answer 57

under the EU Variations Guideline (C(2013)2804 final): ⸻ Type IA (Do and Tell – Minor) • Definition: Minor changes with no impact on quality, safety, or efficacy. • Notification: Within 12 months of implementation. • Examples: • Change of MAH name or address (same legal entity). • Deletion of a manufacturing site no longer used. • Tightening of specification limits (within approved ranges). • Minor updates to analytical methods (e.g. editorial corrections). • Update to ATC code or pharmacopoeial compliance. ⸻ Type IAIN (Immediate Notification – Minor) • Definition: Subset of Type IA, but requires immediate notification due to oversight needs. • Notification: Within 14 days of implementation. • Examples: • Change of QPPV contact details or location of the Pharmacovigilance System Master File (PSMF). • Change of batch release site name/address (site remains the same). • Change in the invented name of a centrally authorised product. ⸻ Type IB (Tell, Wait, and Do – Moderate Impact) • Definition: Changes not qualifying as IA or II; modest potential impact; requires assessment. • Notification: Submit and wait 30 days for approval before implementation. • Examples: • Change to the product name (for nationally authorised products). • Minor manufacturing process changes (e.g. new intermediate step). • Updates to analytical methods (not covered under IA). • Changes to labelling or PIL wording that affect readability but not safety-critical info. • Addition of a packaging site (if conditions for IA aren’t met). ⸻ Type II (Major Variation – Significant Impact) • Definition: Changes likely to affect quality, safety, or efficacy; requires full assessment. • Notification: Submit and wait for approval (usually 60 days or longer). • Examples: • New therapeutic indication or change in dosage regimen. • Significant manufacturing process change (e.g. new synthesis route). • Addition of a new manufacturing site for a biological API. • New safety data: adding contraindications or major adverse reactions. • Change in formulation (quantitative or qualitative).