History of Regulations (Ch. 2)

Question 1

When was the EU formed?

Answer 1

1957: EEU - European Economic Union was formed to create a single European market to allow people, products, and services to move freely
Renamed to the EU in 1992

Question 2

What is the benefit of harmonized legislation?

Answer 2

No conflicting requirements, and all countries are in agreement

Question 3

What is the structure of EU legislation (primary, secondary, etc.)?

Answer 3

Primary Legislation: EU Treaty
Secondary Legislation: Directives and regulations, decisions, opinions, and recommendations
Other: Guidances (MEDDEVs), harmonized standards,

Question 4

What is a directive?

Answer 4

Directive: obliges Member States to implement its provisions into National Laws

Question 5

What is a regulation?

Answer 5

Regulation: directly applicable in all Member States, and obliges Member States to remove any conflicting provisions from national legislation

Question 6

What is the EU MDR regulation?

Answer 6

EU Medical Devices Regulation (EU MDR):

Regulation (EU) 2017/745

Question 7

What is the EU IVDR regulation?

Answer 7

EU In Vitro Diagnostics Regulation (EU IVDR):

Regulation (EU) 2017/746

Question 8

What are EPARs?

Answer 8

EPAR: European Public Assessment Reports

- contain detailed info on the approval/rejection of a product

Question 9

What are NPARs?

Answer 9

NPAR: National Public Assessment Reports

- contain approval/rejection info on a national level

Question 10

TRUE/FALSE: Patient involvement and representation in the regulatory process is increasing.

Answer 10

True

Question 11

What is the purpose of the Transparency Directive (Council Directive 1989/105/EEC)?

Answer 11

Transparency Directive (Council Directive 1989/105/EEC): 
Includes minimum procedural safeguards ensuring national cost-containment measures regulating the pricing of medicines were transparent

Question 12

What is the BeNeLuxA Initiative?

Answer 12

BeNeLuxA Initiative:

Collaboration on pharmaceutical pricing

Question 13

What is the purpose of the Falsified Medicines Directive (FMD, Directive 2011/62/EU)?

Answer 13

Falsified Medicines Directive (FMD, Directive 2011/62/EU):

- To prevent the distribution of falsified medical products, includes authenticity features

Question 14

What are the two types of harmonized product legislation?

Answer 14

1. The Traditional Approach

2. The New Approach

Question 15

What is the Traditional Approach?

Answer 15

Traditional Approach:

Implies the inclusion of detailed technical specifications in the law - highly detailed, extensive laws

Question 16

What is the New Approach?

Answer 16

New Approach:
Includes Essential Requirements for safety and performance in the core legal text, and publishing the technical specification in harmonized standards - reduces regulatory burden, increases development
(introduced in the 1980’s)

Question 17

Pharmaceutical and medical device regulations are based on what principle?

Answer 17

A positive balance between benefit and risk principle

Question 18

What is the first European Medicinal Products Directive?

Answer 18

Council Directive 65/65/EEC

- detailed requirements for medicinal products for human use and MA requirements

Question 19

What is the Centralized Procedure?

Answer 19

Centralized Procedure:

Enables a single medicinal product MA for the entire EU

Question 20

What is the National Procedure?

Answer 20

National Procedure:
For medicinal products that are not qualified for centralized approval, and are intended for marketing in only one EU Member State

Question 21

What is the process for the Mutual Recognition Procedure and the Decentralized Procedure?

Answer 21

The MAA is evaluated by one Member State (Reference Member State: RMA), and the evaluation is recognized by other Member States

Question 22

When do the Mutual Recognition Procedure and the Decentralized Procedure apply?

Answer 22

Mutual Recognition Procedure: Applies if the applicant already has an MA in one EU Member State
Decentralized Procedure: Applies if the applicant seeks simultaneous authorization in more than one Member State

Question 23

Directive 2001/83/EEC was an act of codification, what were the benefits of this?

Answer 23

Codification combined the contents of all previous directives and simplified, unified, and clarified all regulatory requirements

Question 24

What is the purpose of the Variations Directive, Commission Regulation (EC) No. 1234/2008?

Answer 24

Variations Directive, Commission Regulation (EU) No. 1234/2008:
To address variations/extensions to marketing authorizations

Question 25

What are biologics?

Answer 25

Vaccines, blood derivatives, allergens, somatic cells, gene therapies, and tissue proteins

Question 26

What is the VAMF?

Answer 26

VAMF: Vaccine Antigen Master File | - allows a single evaluation of a vaccine antigen

Question 27

What is the BWP?

Answer 27

BWP: Biologics Working Party | - Provides recommendations on all matters related to biological and biotechnical medicines

Question 28

What is the purpose of the Regulation (EC) No. 1394/2007 (ATMPs)?

Answer 28

Regulation (EC) No. 1394/2007: Included ATMPs in the pharmaceutical regulation (ATMP: Advanced Therapy Medicinal Products)

Question 29

What is the purpose of the Directive 2004/27/EC (biosimilars)?

Answer 29

Directive 2004/27/EC: | Added requirements for an MAA based on the demonstration of similarity of two biological medicinal products

Question 30

What two areas do veterinary regulations cover?

Answer 30

1. Veterinary medicines' quality, safety, and efficacy (mirror human medicines) 2. Safety of residues in treated animals' foodstuffs

Question 31

What is the purpose of Directive 2004/24/EC (herbal products)?

Answer 31

Directive 2004/24/EC: | Established a simplified application for traditional herbal medicinal products

Question 32

What is the CE mark?

Answer 32

``` Conformite Europeenne (CE), or European Conformity Mark Indicates the product complies with all applicable EU legislation and can be considered the "passport" to the EU single market ```

Question 33

What is the difference between Essential Requirements and technical requirements?

Answer 33

Essential Requirements for safety and performance: included in the legal texts Technical specifications and requirements: Described in standards

Question 34

What is standardization?

Answer 34

Standardization: | The process of drafting standards and then the standard being approved by a recognized standardization body

Question 35

What is a harmonized standard?

Answer 35

- A harmonised standard is a European standard developed by a recognised European Standards Organisation: CEN, CENELEC, or ETSI - Can use harmonised standards to demonstrate that products, services, or processes comply with relevant EU legislation.

Question 36

Where does the Commission publish harmonized standards?

Answer 36

The Official Journal

Question 37

What is the Blue Guide?

Answer 37

Blue Guide: A guide to the implementation of directives based on the New Approach and the Global Approach (has a blue cover)

Question 38

What is presumption of conformity (as relates to harmonized standards)?

Answer 38

Presumption of conformity: means that if the product complies to the harmonized standard, the product is presumed by the Member States to be in conformity with the Essential Requirements

Question 39

What is the core legal framework for medical devices?

Answer 39

Council Directive 90/385/EEC: AIMDD (Active Implantable Medical Devices) Council Directive 93/42/EEC: MDD (Medical Devices Directive) Directive 98/79/EC: IVDD (In Vitro Diagnostics Medical Devices Directive)

Question 40

What are the key elements of the MDD?

Answer 40

- Conformity assessment procedure routes - Classification Rules based on risk - Notified body approval / CE-mark

Question 41

What are the 4 classes of medical devices?

Answer 41

Class I: low-risk Class IIa and IIb: medium-risk Class III: high-risk

Question 42

What are Notified Bodies?

Answer 42

Notified Bodies: Private organizations with special legal status that are designated by national competent authorities to check manufactures' conformity assessment procedures and grant certificates according to the requirements

Question 43

What is Directive 2007/47/EC?

Answer 43

Directive 2007/47/EC: Amended 93/42/EEC and 90/385/EEC, included software, added checks of representative samples of design dossiers by notified bodies, and extended clinical evaluation obligations

Question 44

What are IVDs?

Answer 44

IVD: In Vitro Diagnostic Medical Device Reagents, reagent products, calibrators, control materials, kits, instruments, apparatus, equipment or systems to be used for the in vitro examination of human samples to make a medical diagnosis

Question 45

True/False: The MDD and IVDD classification systems are rule based.

Answer 45

False - The IVDD classification system is not rule-based, but instead includes a list of regulated products. (To be updated in the IVDR)