REGULATORY AFFAIRS
Contents
EXAM OVERVIEW ....................................................................................................................... 2
1. REGULATORY AFFAIRS — INTRODUCTION .............................................................................. 3
2. EUROPEAN LEGALS ............................................................................................................... 5
3. PRODUCT CLASSIFICATION ................................................................................................... 7
4. EU PROCEDURES — BRINGING A PRODUCT TO THE MARKET................................................. 14
5. THE CTD — COMMON TECHNICAL DOCUMENT (THE DOSSIER) ............................................. 20
6. POST-APPROVAL — VARIATIONS, INFORMATION, PHARMACOVIGILANCE ............................. 33
7. PRICING AND REIMBURSEMENT .......................................................................................... 39
ABBREVIATION LIST ................................................................................................................. 45
1
,Exam overview
The written exam consists of 4 questions, each worth 10 points. It accounts for 80 % of the final mark — the
home-work report counts for 20 % (submitting it late, without justification, caps the total at 5/20).
The 4 question types you can expect
# Topic What to be able to do
1 Product classification Given a product, justify its category (MP, MD, cosmetic, food
supplement, biocide …) using presentation and purpose criteria.
2 Procedures to reach the Explain NP / MRP / DCP / CP and decide which one applies for a
market given product.
3 The MAA dossier (CTD) Know how the CTD is organised: 5 modules, what each contains,
key chapter numbers and titles.
4 Quality aspects Apply ICH thresholds (RT / IT / QT), explain QbD, design space,
control strategy, process capability (Cp, Cpk).
5 After submission What else gets checked: pricing, reimbursement, HTA, post-
approval variations, pharmacovigilance.
6 10 abbreviations Full meaning + concise explanation. Comes back EVERY exam.
7 Describe DCP Goal, (dis)advantages, full procedure with timings.
8 Which procedure Pick the right procedure for a product type.
when?
Competences to be reached (course objectives)
• Critically and justifiably classify several health products.
• Discuss different approval procedures for medicines.
• Know content and form requirements of an MAA dossier (the CTD).
• Apply important regulatory (discovery/developmental) aspects, especially quality.
• Define post-approval activities and responsibilities.
• Know the specific RA language with its acronyms.
• Write a scientifically justified, critical home-work report on an actual RA problem.
2
,1. Regulatory Affairs — Introduction
1.1 What is Regulatory Affairs?
Regulatory Affairs (RA) is the discipline that ensures medicines and other health products comply with all
legal and scientific requirements throughout their life cycle. It sits at the centre of every other department
(R&D, QA, manufacturing, clinical, market access, …) and ensures the right information reaches the
authorities at the right time, in the right format.
GxP — Good X Practice
RA itself is governed by GRP (Good Regulatory Practice). It is one of the many "GxPs":
• GMP — Good Manufacturing Practice
• GLP — Good Laboratory Practice
• GCP — Good Clinical Practice
• GDP — Good Distribution Practice
• GEP — Good Experimental / Engineering Practice
• Derivatives: cGMP (current), aGMP (appropriate), GAMP (automated manufacturing) …
Role of the RA manager
• Overall responsibility for getting the product to market on time → coordinates pre-clinical, clinical,
quality groups to deliver the right data on schedule.
• Defines the best strategy: drug vs food vs medical-device path (= classification), and determines which
information authorities will require.
• Acts as the communication hub between disciplines.
• Coordinates Scientific Advice with authorities (e.g. "is this test enough to prove quality?").
• Change-control evaluation: after submission, every change (excipient, supplier, …) must first be
approved by the authorities before being implemented.
• RA intelligence: keeps track of new and draft regulations/guidelines so the company is prepared.
MAH — Marketing Authorisation Holder
1 legal person who holds the marketing authorisation and is ULTIMATELY responsible for the product on the
market. Even when synthesis is outsourced to another GMP company, the MAH must:
• Make sure each supplier follows GMP and the current guidelines.
• Communicate every relevant regulatory commitment to the manufacturing site.
• Organise audits to verify compliance.
• Handle outsourcing & technical agreements, quality defects, complaints, recalls.
• Comply with the Falsified Medicines Directive (FMD) for human medicines.
3
, 1.2 RA within the organisation
3 typical organisational models exist:
• A separate, central RA department, independent of R&D, QA, manufacturing.
• RA embedded inside another department (R&D, clinical, QA, market access …).
• Matrix structures (hybrid local/international) — the RA person reports to two managers: one for
daily/technical tasks, one for regulatory deliverables.
The RA department itself may be split by therapeutic area, life-cycle phase, or scientific discipline (and often
combinations). Key: upper management must be aware of the continuous, critical role of RA.
1.3 Human resources & partners
A good RA professional combines integrity, honesty, high scientific quality, the ability to disagree without
being disagreeable, and a good sense of when to advance or retreat in negotiations with authorities. Liaison
is needed with the agency, the rest of the company, manufacturing sites, suppliers and academic partners.
1.4 Future challenges (R&D)
• Redefine diseases by molecular mechanism (personalised medicine) rather than only symptoms.
• Adapt regulatory frameworks to new tech: big data, Real World Evidence (RWE), machine learning,
biologics (e.g. LBP = Live Biotherapeutic Products), medical devices and their combinations.
• Earlier patient access via progressive marketing authorisation (PMA), adaptive trial designs, new benefit-
risk frameworks.
• Add environmental aspects (the "Green Deal") to the classic Q/S/E triad.
• By 2050: big data + RWE + AI, combination products, new product types, sustainability requirements.
4
Contents
EXAM OVERVIEW ....................................................................................................................... 2
1. REGULATORY AFFAIRS — INTRODUCTION .............................................................................. 3
2. EUROPEAN LEGALS ............................................................................................................... 5
3. PRODUCT CLASSIFICATION ................................................................................................... 7
4. EU PROCEDURES — BRINGING A PRODUCT TO THE MARKET................................................. 14
5. THE CTD — COMMON TECHNICAL DOCUMENT (THE DOSSIER) ............................................. 20
6. POST-APPROVAL — VARIATIONS, INFORMATION, PHARMACOVIGILANCE ............................. 33
7. PRICING AND REIMBURSEMENT .......................................................................................... 39
ABBREVIATION LIST ................................................................................................................. 45
1
,Exam overview
The written exam consists of 4 questions, each worth 10 points. It accounts for 80 % of the final mark — the
home-work report counts for 20 % (submitting it late, without justification, caps the total at 5/20).
The 4 question types you can expect
# Topic What to be able to do
1 Product classification Given a product, justify its category (MP, MD, cosmetic, food
supplement, biocide …) using presentation and purpose criteria.
2 Procedures to reach the Explain NP / MRP / DCP / CP and decide which one applies for a
market given product.
3 The MAA dossier (CTD) Know how the CTD is organised: 5 modules, what each contains,
key chapter numbers and titles.
4 Quality aspects Apply ICH thresholds (RT / IT / QT), explain QbD, design space,
control strategy, process capability (Cp, Cpk).
5 After submission What else gets checked: pricing, reimbursement, HTA, post-
approval variations, pharmacovigilance.
6 10 abbreviations Full meaning + concise explanation. Comes back EVERY exam.
7 Describe DCP Goal, (dis)advantages, full procedure with timings.
8 Which procedure Pick the right procedure for a product type.
when?
Competences to be reached (course objectives)
• Critically and justifiably classify several health products.
• Discuss different approval procedures for medicines.
• Know content and form requirements of an MAA dossier (the CTD).
• Apply important regulatory (discovery/developmental) aspects, especially quality.
• Define post-approval activities and responsibilities.
• Know the specific RA language with its acronyms.
• Write a scientifically justified, critical home-work report on an actual RA problem.
2
,1. Regulatory Affairs — Introduction
1.1 What is Regulatory Affairs?
Regulatory Affairs (RA) is the discipline that ensures medicines and other health products comply with all
legal and scientific requirements throughout their life cycle. It sits at the centre of every other department
(R&D, QA, manufacturing, clinical, market access, …) and ensures the right information reaches the
authorities at the right time, in the right format.
GxP — Good X Practice
RA itself is governed by GRP (Good Regulatory Practice). It is one of the many "GxPs":
• GMP — Good Manufacturing Practice
• GLP — Good Laboratory Practice
• GCP — Good Clinical Practice
• GDP — Good Distribution Practice
• GEP — Good Experimental / Engineering Practice
• Derivatives: cGMP (current), aGMP (appropriate), GAMP (automated manufacturing) …
Role of the RA manager
• Overall responsibility for getting the product to market on time → coordinates pre-clinical, clinical,
quality groups to deliver the right data on schedule.
• Defines the best strategy: drug vs food vs medical-device path (= classification), and determines which
information authorities will require.
• Acts as the communication hub between disciplines.
• Coordinates Scientific Advice with authorities (e.g. "is this test enough to prove quality?").
• Change-control evaluation: after submission, every change (excipient, supplier, …) must first be
approved by the authorities before being implemented.
• RA intelligence: keeps track of new and draft regulations/guidelines so the company is prepared.
MAH — Marketing Authorisation Holder
1 legal person who holds the marketing authorisation and is ULTIMATELY responsible for the product on the
market. Even when synthesis is outsourced to another GMP company, the MAH must:
• Make sure each supplier follows GMP and the current guidelines.
• Communicate every relevant regulatory commitment to the manufacturing site.
• Organise audits to verify compliance.
• Handle outsourcing & technical agreements, quality defects, complaints, recalls.
• Comply with the Falsified Medicines Directive (FMD) for human medicines.
3
, 1.2 RA within the organisation
3 typical organisational models exist:
• A separate, central RA department, independent of R&D, QA, manufacturing.
• RA embedded inside another department (R&D, clinical, QA, market access …).
• Matrix structures (hybrid local/international) — the RA person reports to two managers: one for
daily/technical tasks, one for regulatory deliverables.
The RA department itself may be split by therapeutic area, life-cycle phase, or scientific discipline (and often
combinations). Key: upper management must be aware of the continuous, critical role of RA.
1.3 Human resources & partners
A good RA professional combines integrity, honesty, high scientific quality, the ability to disagree without
being disagreeable, and a good sense of when to advance or retreat in negotiations with authorities. Liaison
is needed with the agency, the rest of the company, manufacturing sites, suppliers and academic partners.
1.4 Future challenges (R&D)
• Redefine diseases by molecular mechanism (personalised medicine) rather than only symptoms.
• Adapt regulatory frameworks to new tech: big data, Real World Evidence (RWE), machine learning,
biologics (e.g. LBP = Live Biotherapeutic Products), medical devices and their combinations.
• Earlier patient access via progressive marketing authorisation (PMA), adaptive trial designs, new benefit-
risk frameworks.
• Add environmental aspects (the "Green Deal") to the classic Q/S/E triad.
• By 2050: big data + RWE + AI, combination products, new product types, sustainability requirements.
4
