Pharmaceutical Regulation & Quality Management – Comprehensive Review

These 103 question-and-answer flashcards cover regulatory pathways, GMP/GDP/GCP requirements, quality-management principles, clinical-trial roles, risk management, cleanroom classifications, data integrity, and other critical concepts discussed in the lecture notes.

What is Scientific Advice as it pertains to the drug life-cycle?

Early or ongoing guidance from regulators (e.g., EMA) on study design, endpoints, and regulatory expectations to reduce marketing-authorisation failure risk.

Define Good Distribution Practice (GDP).

A quality system ensuring medicines are stored, transported, and handled under conditions that preserve their quality and integrity throughout the supply chain.

Which regulatory body authorises products via the centralised procedure?

The European Medicines Agency (EMA).

What is the Centralised Authorisation Process?

An EMA-managed procedure allowing one EU-wide marketing-authorisation application that yields a single approval valid in all EU/EEA states; mandatory for certain innovative medicines.

Define Parallel Importation within the EU.

Importing a medicine authorised in one EU country into another without the original manufacturer’s involvement, provided the product is essentially the same.

List three attributes of the Centralised Authorisation Procedure.

Single EU application/evaluation, one authorisation valid in all EU/EEA states, mandatory for specified innovative/high-risk medicines (managed by EMA, approved by EC).

Who regulates medicinal products in Ireland and give three responsibilities.

HPRA; grants marketing authorisations, performs inspections, and monitors safety (pharmacovigilance).

List three responsibilities of the Marketing Authorisation Holder (MAH).

Ensure product quality/safety, maintain pharmacovigilance, submit PSURs and variations.

Give two responsibilities of the Qualified Person (QP).

Certify each batch meets GMP and MA, review all manufacturing/quality documentation before release.

Who is the Responsible Person (RP) and list three responsibilities.

GDP-designated individual who ensures GDP compliance, manages the quality system/traceability, and handles recalls/complaints.

What are the four categories of ICH guidelines?

Quality (Q), Safety (S), Efficacy (E), Multidisciplinary (M).

Define Validation in the pharmaceutical industry.

Documented evidence that a process, procedure, or system consistently produces a product meeting predetermined specifications and quality attributes.

State three main objectives of an Operational Qualification (OQ).

Verify equipment functions across its operating range, confirm performance under simulated production, identify/document critical parameters.

List three reasons for performing an Installation Qualification (IQ).

Ensure equipment is installed per design, confirm correct utility connections, document materials/components used.

What is the difference between a record and a report?

A record is raw data evidence (e.g., batch record); a report interprets/summarises information (e.g., deviation report).

Define Critical Quality Attribute (CQA).

A physical, chemical, biological, or microbiological property that must be within specified limits to ensure product quality, safety, and efficacy.

What are the GAMP guidelines?

Good Automated Manufacturing Practice: a risk-based, life-cycle approach for validating automated systems in pharma manufacturing.

List key considerations for an effective internal audit programme.

Trained independent auditors, risk-based planning, timely follow-up, and clear documentation/reporting.

Describe the role of Change Control in a QMS.

Ensures all changes to facilities, systems, equipment, or documents are reviewed, justified, approved, and implemented in a controlled way.

When must a deviation be recorded in the QMS?

Whenever there is a planned or unplanned departure from approved processes, procedures, or specifications.

Define Quality Risk Management (QRM).

Systematic process to assess, control, communicate, and review risks to product quality throughout the lifecycle.

Name the three criteria used to evaluate risk in a risk assessment.

Severity, Probability, Detectability.

List the three objectives of ICH Q10 (Pharmaceutical Quality System).

Product realisation, state of control, continual improvement.

What is an Investigational Medicinal Product (IMP)?

Any pharmaceutical form of an active substance or placebo used in a clinical trial, including authorised products used differently or for new indications.

Define Good Clinical Practice (GCP).

International ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials to protect participants.

Explain Informed Consent.

Process whereby participants voluntarily agree to join a study after full disclosure of its nature, risks, benefits, and their rights.

What is a double-blind clinical trial?

A study in which neither participants nor investigators know who receives the investigational product versus placebo, minimising bias.

Who are the main stakeholders in a clinical trial?

Sponsor, Investigator, Ethics Committee, Regulatory Authority.

Role of the ethics committee in a clinical trial.

Protect participants’ rights, safety, and well-being by reviewing protocols, consent forms, and monitoring compliance.

Explain the investigator’s role in clinical trials.

Conduct the study at site, obtain informed consent, ensure protocol compliance, and safeguard subject safety.

What is the Summary of Product Characteristics (SmPC)?

Regulatory document for healthcare professionals detailing a medicine’s properties, indications, dosage, contraindications, and side effects.

List three items a Package Leaflet must contain in the EEA.

Medicine name/strength, usage and dosage instructions, possible side effects (plus storage info, etc.).

Define Active Pharmaceutical Ingredient (API).

The active substance in a medicine responsible for its therapeutic effect, produced chemically or biologically.

What is meant by Active Substance?

Interchangeable with API; the biologically active component responsible for a medicine’s intended effect.

Outline activities requiring an Active Substance Registration.

Manufacture, import, or distribution of an active substance; supplying it to medicinal-product manufacturers; ensuring GMP compliance and documentation.

Which activities occur in a Grade A cleanroom?

High-risk aseptic operations such as sterile filling and open handling of sterile components.

List the four cleanroom grades per Annex 1.

Grade A, Grade B, Grade C, Grade D.

What is primary packaging? Give an example.

Material directly contacting the product, e.g., a blister pack or an injection vial.

Name two tests on plastic primary-packaging containers.

Extractables & leachables testing; moisture-barrier/permeability testing.

What is the temperature range for cold-storage goods?

2 °C to 8 °C.

Define the acronym ALCOA (or ALCOA++).

Attributable, Legible, Contemporaneous, Original, Accurate (+ Complete, Consistent, Enduring, Available for ALCOA++).

Define Data Integrity and outline ALCOA++ principles.

Assurance that data are complete, consistent, and accurate; ALCOA++ guides documentation to maintain integrity (Attributable, Legible, etc.).

List three requirements for using electronic signatures.

Uniquely assigned to one person, secure against misuse, linked to records so alterations are detectable.

Purpose of the EudraGMDP database.

EU database listing manufacturing/distribution authorisations and GMP/GDP certificates to enable compliance verification and transparency.

Give three reasons why regulation is important in pharmaceuticals.

Ensure safety/efficacy, protect public health, maintain high manufacturing standards (also supports trust and trade).

Identify the two types of documentation used in pharma.

Records (raw data) and Reports (summaries/evaluations).

What is the National Authorisation process for medicinal products?

Country-specific application to a national authority (e.g., HPRA); approval valid only in that country.

List the four EU variation categories.

Type IA, Type IAIN, Type IB, Type II.

Describe Change Control in a pharmaceutical QMS.

Formal system to assess, approve, and implement changes without compromising product quality.

Typical activities in a Grade D cleanroom.

Less critical tasks like solution preparation, component staging, or support for higher-grade areas.

Difference between Type IA and Type IAIN variations; give examples and required documents.

Type IA: minor, low-risk (e.g., QP address change); Type IAIN: minor but immediate notification needed (e.g., new packaging site). Docs: cover letter, variation form, supporting data (updated SmPC/GMP certs).

What is meant by the benefit-to-risk ratio?

Comparison of a medicine’s therapeutic benefits to its potential risks; must be positive for approval.

Describe Class 1 recall requirements per HPRA.

Serious health risk; immediate product withdrawal and urgent communication to healthcare professionals.

Restate the definition of Validation in pharma.

Documented evidence that a process, system, or equipment consistently yields results meeting predetermined criteria, ensuring quality and compliance.

Differentiate between a record and a report; give one example each.

Record = raw data (e.g., temperature log); Report = analysis/summary (e.g., deviation investigation report).

What are the three categories of ATMPs?

Gene therapy, Somatic-cell therapy, Tissue-engineered products.

State two compliance criteria for cleanroom grades A–D (Annex 1).

Airborne particulate limits and microbial contamination thresholds (also pressure differentials, air-change rates).

Restate the temperature range for refrigerated goods.

2 °C to 8 °C.

Restate: What is primary packaging? Give an example.

Material in direct contact with product, e.g., tablet blister pack.

Name two tests that may be performed on plastic primary packaging.

Compatibility testing; extractables & leachables studies.

Define Active Substance (refresh).

Biologically active component intended for disease diagnosis, cure, mitigation, treatment, or prevention.

What are the GAMP guidelines (refresh)?

Risk-based validation framework for automated pharma systems across their life-cycle.

Define Critical Quality Attribute (CQA) (refresh).

A property that must stay within limits to ensure desired product quality (e.g., pH, sterility).

Define a cleanroom in pharmaceutical manufacturing.

Controlled environment minimising particulate/microbial contamination through filtered air, garments, and controlled access.

Purpose of Post-Authorisation Safety Studies (PASS).

Monitor a medicine’s real-world safety, identify risks not seen in trials, and reassess benefit–risk balance.

Define Corrective Action and Preventative Action.

CA: eliminate causes of identified non-conformity; PA: eliminate causes of potential non-conformity to prevent occurrence.

List two studies on plastic immediate packaging.

Extractables & leachables; barrier/permeability testing.

List three HPRA responsibilities.

Grant marketing authorisations, perform GMP/GDP/GCP inspections, monitor adverse events (pharmacovigilance).

What is a Type II variation? Give an example.

Major change possibly affecting quality/safety/efficacy, e.g., adding a new therapeutic indication; requires full evaluation.

Explain accelerated stability testing.

Exposes products to elevated conditions to predict shelf life and storage needs faster than real-time studies.

List three responsibilities of the Responsible Person (RP).

Ensure GDP-compliant storage/distribution, maintain QMS, approve returns and manage recalls.

Explain the Benefit-to-Risk ratio (refresh).

Assessment of therapeutic benefits versus potential risks; must favour benefits for product approval.

Define Pharmacovigilance.

Science and activities of detecting, assessing, understanding, and preventing adverse effects or other medicine-related problems.

List the four cleanroom grades per Annex 1 starting with the cleanest.

Grade A, Grade B, Grade C, Grade D.

List three responsibilities of the MAH (refresh).

Maintain product quality/safety, uphold pharmacovigilance, submit variations/renewals.

What is the National Approval process for medicinal products?

Application to a single national authority; approval limited to that country.

Identify three approaches to cleaning verification.

Swab sampling, rinse sampling, visual inspection (also marker compounds).

State the three objectives of ICH Q10 (refresh).

Product realisation, state of control, continual improvement.

Define Validation (refresh).

Documented process giving high assurance a system/process consistently meets specifications and quality attributes.

Who regulates medicines in Ireland and give three responsibilities (refresh).

HPRA; grants authorisations, approves/inspects clinical trials, monitors safety via pharmacovigilance, conducts GMP/GDP/GCP inspections.

Define Parallel Importation (refresh).

Import/sale of a medicine authorised in one EU state into another without the original manufacturer, relying on mutual MA recognition.

Give three main objectives of an Operational Qualification (OQ) (refresh).

Verify equipment operates within limits, confirm critical components, test alarms/sensors/controls.

Key considerations for effective self-inspection/internal audit.

Planned systematic audits, independent/qualified auditors, corrective actions leading to improvement, risk-based frequency/scope.

Purpose of the EudraGMDP database (refresh).

Provides EU-wide visibility of GMP/GDP certificates and manufacturing/distribution licences for compliance checks.

Describe the SmPC (refresh).

Detailed regulatory document outlining a medicine’s properties, indications, dosage, contraindications, interactions, storage, etc.

Give three mandatory Package Leaflet items for EEA medicines.

Product/active-substance name, indication & dosage, warnings/side effects (plus storage instructions, etc.).

List two tests on plastic primary-packaging containers (refresh).

Extractables & leachables; compatibility or moisture-barrier testing.

Scope of EudraLex Volume 4 Annex 1.

GMP guidelines for sterile product manufacture, including cleanroom classifications and contamination-control strategies.

Give two responsibilities of an EU Qualified Person (QP).

Certify each batch before release; ensure manufacturing complies with GMP and the marketing authorisation.

Role of the ethics committee in a clinical trial (refresh).

Review/approve protocols and consent forms to protect participant rights, safety, and well-being.

Define Informed Consent in a clinical trial (refresh).

Process of providing all study details so participants can voluntarily decide to join.

Differences between Type IA and Type IAIN variations; give two examples and documentation.

IA: minor, no immediate notice (e.g., admin update); IAIN: minor but immediate notice (e.g., QP change). Docs: application, revised annexes, justification.

Activities requiring an Active Substance Registration (refresh).

Manufacture, import, or supply of active substances; major process changes; ensuring GMP documentation.

List requirements to conduct a clinical trial in Ireland.

HPRA approval, ethics approval, suitable investigator/site, GCP compliance, insurance/indemnity.

Gowning requirements for operators entering Grade B or A areas.

Sterile coveralls, hood, face mask, goggles, sterile (double) gloves, sterile footwear; gowning performed in controlled steps.

Define ALCOA for data integrity.

Attributable, Legible, Contemporaneous, Original, Accurate.

Give two attributes of the new Clinical Trial Regulation 536/2014.

Centralised EU submission portal; increased transparency/public access to trial data (also single decision per member state).

What is an Active Pharmaceutical Ingredient (API) (refresh)?

Biologically active component providing therapeutic effect, later combined with excipients into the final dosage form.

Define a double-blind clinical trial (refresh).

Study where neither investigators nor participants know treatment allocation, reducing assessment bias.

What is an Investigational Medicinal Product (IMP) (refresh)?

Active substance or placebo used in a clinical trial, including authorised products used in new ways.