Plasma master file, TSE/BSE evaluation and related EU requirements MCQs With Answer

Introduction: This quiz set covers Plasma Master File (PMF) concepts, transmissible spongiform encephalopathy (TSE)/bovine spongiform encephalopathy (BSE) evaluation, and related European Union regulatory requirements relevant to plasma‑derived and animal‑sourced biologicals. It is tailored for M.Pharm students preparing for regulatory and quality roles. Questions focus on PMF purpose and content, donor and material sourcing controls, prion biology and resistance, risk assessment and mitigation strategies, validation expectations for viral and prion safety, and how EU authorities and guidance oversee these areas. Use these items to test understanding of dossier requirements, safety measures, and EU expectations for plasma and animal‑derived starting materials.

Q1. What is a Plasma Master File (PMF) in the EU regulatory context?

• A clinical trial document describing plasma donor adverse events
• A regulatory dossier describing plasma collection, testing, pooling, manufacturing and quality controls for plasma‑derived products
• A pharmacopoeial monograph setting assay limits for plasma proteins
• An internal quality manual used only by transfusion centers

Correct Answer: A regulatory dossier describing plasma collection, testing, pooling, manufacturing and quality controls for plasma‑derived products

Q2. Who typically holds and maintains the Plasma Master File?

• The national competent authority of each EU Member State
• The marketing authorisation holder (MAH) for the finished product
• The plasma fractionation company or central plasma supplier
• An independent contract research organisation (CRO)

Correct Answer: The plasma fractionation company or central plasma supplier

Q3. How is a PMF used in the marketing authorisation process for a plasma‑derived medicinal product?

• It replaces Module 4 (non‑clinical) of the CTD
• It is referenced by the marketing authorisation dossier to justify source and manufacturing controls
• It is optional and not examined by regulators
• It only documents clinical safety data

Correct Answer: It is referenced by the marketing authorisation dossier to justify source and manufacturing controls

Q4. Which of the following is a primary purpose of a PMF?

• To list pricing and commercial terms for plasma purchases
• To provide detailed evidence of donor screening, testing, traceability and viral safety measures
• To describe adverse event reporting requirements for hospitals
• To act as a pharmacovigilance database for plasma products

Correct Answer: To provide detailed evidence of donor screening, testing, traceability and viral safety measures

Q5. Which item should NOT be included in the PMF?

• Summary of donor selection and deferral criteria
• Validation reports for virus removal/inactivation steps
• Individual donor names and personal identifiers linked to plasma units
• Description of plasma pooling strategy and traceability systems

Correct Answer: Individual donor names and personal identifiers linked to plasma units

Q6. What is the causative agent class for TSE/BSE?

• Bacteria
• Prions (misfolded proteins)
• Enveloped RNA viruses
• DNA viruses

Correct Answer: Prions (misfolded proteins)

Q7. Which bovine tissue is classically defined as specified risk material (SRM) for BSE and requires special controls?

• Muscle meat from young calves under 6 months
• Brain and spinal cord from cattle over a defined age
• Milk and milk products from all dairy cattle
• Blood collected from healthy adult cattle

Correct Answer: Brain and spinal cord from cattle over a defined age

Q8. For sourcing bovine‑derived materials used in medicinal products, EU expectations generally require:

• No documentation of origin if suppliers are reputable
• Sourcing only from countries or herds with negligible or controlled BSE risk and appropriate certification
• Use of any bovine material if heat‑treated for 60 minutes
• Only sourcing from animals older than 10 years

Correct Answer: Sourcing only from countries or herds with negligible or controlled BSE risk and appropriate certification

Q9. Which statement best describes prion resistance to common inactivation methods?

• Prions are readily inactivated by standard solvent/detergent (S/D) treatment
• Prions are highly resistant; S/D treatment is ineffective and special removal/validation is required
• Prions are inactivated by simple filtration through 0.22 µm filters
• Prions are eliminated completely by routine pasteurisation at 60°C for 30 minutes

Correct Answer: Prions are highly resistant; S/D treatment is ineffective and special removal/validation is required

Q10. Which manufacturing controls can contribute to reduction of prion infectivity in plasma‑derived products?

• Validated partitioning during fractionation and prion‑removal steps such as nanofiltration and specific chromatography
• Only viral inactivation by solvent/detergent without validation studies
• Sterile filtration through 0.45 µm filters as the sole measure
• Storage at room temperature for extended periods

Correct Answer: Validated partitioning during fractionation and prion‑removal steps such as nanofiltration and specific chromatography

Q11. Under EU regulatory expectations, is a specific TSE risk assessment required for medicinal products containing or derived from animal materials?

• No, TSE assessments are only required for food products
• Yes, manufacturers must perform and document a TSE risk assessment and mitigation measures
• Only if the product is intended for veterinary use
• Only if the product contains brain tissue

Correct Answer: Yes, manufacturers must perform and document a TSE risk assessment and mitigation measures

Q12. Which donor deferral policy is commonly applied to reduce vCJD risk in blood/plasma donors in EU guidance?

• No deferral related to geographic exposure is ever applied
• Deferral of donors who received a transfusion in a country with significant BSE exposure during defined periods
• Permanent deferral of all donors who consumed beef at any time
• Deferral only for donors with a family history of cardiovascular disease

Correct Answer: Deferral of donors who received a transfusion in a country with significant BSE exposure during defined periods

Q13. Can a PMF be referenced confidentially by multiple marketing authorisation holders?

• No, a PMF can be used by only one MA holder ever
• Yes, with appropriate confidentiality arrangements and regulatory referencing it may be referenced by multiple MA holders
• Yes, but only if the MA holders are in the same company group
• No, PMFs are publicly published documents available to all

Correct Answer: Yes, with appropriate confidentiality arrangements and regulatory referencing it may be referenced by multiple MA holders

Q14. Which European bodies are primarily involved in evaluating TSE/BSE aspects of medicinal products?

• European Medicines Agency (EMA) and competent national authorities
• European Central Bank and World Health Organization
• European Food Safety Authority only
• European Court of Justice

Correct Answer: European Medicines Agency (EMA) and competent national authorities

Q15. When should a PMF be updated and the changes notified to regulators?

• Only when the company decides to rebrand the product
• Whenever there are significant changes in plasma sourcing, manufacturing process, viral/prion safety measures or quality controls
• Every ten years regardless of changes
• Never; PMFs are static documents

Correct Answer: Whenever there are significant changes in plasma sourcing, manufacturing process, viral/prion safety measures or quality controls

Q16. Which validation data is expected in the PMF regarding viral safety?

• Validation of sterility testing only
• Validation studies demonstrating removal or inactivation of relevant model viruses and, where applicable, prion reduction/removal data
• No validation is required if donors are screened
• Only retrospective clinical surveillance data is sufficient

Correct Answer: Validation studies demonstrating removal or inactivation of relevant model viruses and, where applicable, prion reduction/removal data

Q17. What documentation does the EU expect for animal‑derived starting materials used in medicinal products?

• No documentation beyond supplier invoices
• Detailed documentation of species, tissue of origin, geographic origin, SRM exclusion and relevant TSE/BSE risk categorisation
• Only a certificate stating “animal origin” is required
• Only a manufacturing date and batch number

Correct Answer: Detailed documentation of species, tissue of origin, geographic origin, SRM exclusion and relevant TSE/BSE risk categorisation

Q18. How does large plasma pooling influence infectious risk and regulatory expectations?

• Pooled plasma reduces infectious risk and therefore no viral safety steps are needed
• Pooled plasma can increase the chance of introducing an infectious agent, so robust donor screening and validated viral reduction/removal steps are required
• Pooled plasma is banned in the EU
• Pooled plasma eliminates prion risk by dilution alone

Correct Answer: Pooled plasma can increase the chance of introducing an infectious agent, so robust donor screening and validated viral reduction/removal steps are required

Q19. In the Common Technical Document (CTD), the PMF content and references are most appropriately placed in which module?

• Module 1 — Administrative information
• Module 2 — Summaries, not linked to quality
• Module 3 — Quality (pharmaceutical documentation)
• Module 5 — Clinical study reports

Correct Answer: Module 3 — Quality (pharmaceutical documentation)

Q20. Which TSE/BSE risk categories are commonly used in EU assessments of source animals and materials?

• Negligible, controlled, and undetermined/unknown risk categories
• High, medium, and low risk only with no further nuance
• Class A and Class B only
• Type I, Type II, and Type III based on protein content

Correct Answer: Negligible, controlled, and undetermined/unknown risk categories

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