Regulation of Medicines

Question 1

Where can legislation for medicines be found

Answer 1

Human Medicines Regulations 2012, as amended:

• System of licensing affecting manufacture, sale, supply and importation of medicinal products
• Part 3. Manufacturing and wholesale dealing
• Part 4. Requirement for authorisation
• Part 5. Marketing authorisations
• Part 6. Certification of homeopathic medicinal products
• Part 7. Traditional herbal registrations
• Part 9. Borderline products
• Part 10. Exceptions to requirements for MAs etc.

The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (removes reference to EU directives)

Question 2

What is the UKs licencing authority

Answer 2

Medicines and Healthcare products Regulatory Agency (MHRA)

no longer the european medicines agency. 2 year transition period => 31 December 2022

Question 3

What brought about an increased level of medicines legislation in the 1960s?

Answer 3

The thalidomide tragedy

Question 4

What are the main objectives of legislation

Answer 4

Safety, quality and efficacy of medicinal products

Withdrawal from use if any inherent danger comes to light

Question 5

What is covered under the MHRAs legislation

Answer 5

Authorised products and investigational medicinal products (IMP) are covered by legislation

Definitions:
Medicinal product
Authorised medicinal product
Relevant medicinal product
What is a borderline product?
What about medical devices?

Question 6

Define meddicinal product

Answer 6

= any substance or combination of substances-
a) presented as having properties of preventing or treating disease in human beings; or

b) that may be used by or administered to human beings with a view to:
i. restoring, correcting or modifying a physiological function by exerting a pharmacological, immunological or metabolic action, or
ii. making a medical diagnosis

Question 7

Define authorised medicinal products

Answer 7

If product has:

a) Marketing authorisation => medicines
b) Certificate of registration => homeopathics
c) Traditional herbal registration => herbal remedies

Question 8

Define a relevant medicinal product

Answer 8

A medicinal product that is not—

a) a registrable homoeopathic medicinal product; or
b) a traditional herbal medicinal product; and

They are medicinal products which hold marketing authorisations

Question 9

Define a borderline substance

Answer 9

A product which it is not easy to distinguish from a medicine, e.g. cosmetics or food supplements, herbal products

However, should any of the above contain

• a pharmacologically active substance or
• make medicinal claims
• claims to treat or prevent disease, or
• to interfere with the normal operation of a physiological function of the human body

They are regarded as medicinal

Question 10

What are medical devices and what do they need to adhere to legislation

Answer 10

Include sutures, dressings, contact lens care products etc

Mandatory
- UKCA mark:
product marking which can be used for medical devices placed on the Great Britain (England, Wales, Scotland) market (in place of CE mark)

• CE mark:
  UKCA mark not recognised in NI. CE or CE UKNI mark for NI
  CE mark needed to place in EEA (and beyond)

CE/UKCA mark = manufacturer claims the product is safe and fit for its intended purpose

CE mark is regarded as equivalent to MA

Covered by the Medical Devices Regulations 2002

Question 11

What stages of medicines development does the legislation cover

Answer 11

Involvement in any of the stages,

• from initial development/ research of an investigational medicinal product (IMP) through to
  final marketing of a medicinal product,

A system of licences and certificates is used

Penalties for non compliance

Question 12

WHich licences are available for medicines

Answer 12

Marketing Authorisation

Certificate of registration

Traditional herbal registration

Manufacturer of Medicines Licence

Wholesaler of Medicines Licence

Clinical Trial Authorisation

Question 13

What are the 4 phases of clinical trials

Answer 13

Phase 1 - Experimental drug (treatment) in small group of people (20-80) for 1st time
To evaluate its safety, determine safe dosage range, identify S/E

Phase 2 - Experimental drug given to larger group of people actually suffering from the disease (100-300)
To see if it is effective and to further evaluate its safety

Phase 3 - Experimental drug given to large groups of people (1,000-3,000)
To confirm effectiveness, monitor S/E, compare to commonly used treatments & collect information to allow safe use

Phase 4 - Post marketing studies
For additional information, incl. risks, benefits & optimal use

Question 14

Which lefislation sets out the need for marketing authorisation

Answer 14

Medicines Act 1968:
Products on the market prior to the licensing requirements of the Medicines Act were granted a Product Licence of Right
[Now relatively obsolete]

All relevant medicinal products must have a Marketing Authorisation
(Before 1994: Product Licence)

Question 15

A relevant medicinal product must be…

Answer 15

… covered by a marketing authorisation
and held by the person responsible for the composition of the product
in the course of a business/profession

So that it can be:

• manufactured or assembled
• imported or exported
• sold or supplied

Question 16

What are the national routes to obtain a marketing authorisation

Answer 16

National Routes:

• Innovative Licensing and Access Procedure (ILAP)
• National Procedure(150-day procedure) – UK, GB, NI
• Rolling review– UK, GB, NI
• ECDecision Reliance Procedure(67-day procedure)
  (For 2 years from 1 January 2021, GB may adopt decisions taken by the European Commission on approval of new MAs through the centralised procedure)
• MR/DCReliance Procedure(67-day procedure)
• Unfettered Access from Northern Ireland(67-day procedure) - GB

NB. National applications intended to cover marketing of a product in Northern Ireland must continue to comply with the requirements of Directive 2001/83/EC, the Community code relating to medicinal products for human use, and Regulation 726/2004 on Community Procedures and Supervision of medicinal products

Question 17

What are the international routes to obtain a marketing authorisation

Answer 17

International routes (collaborative procedures):

• Access consortium- to market a medicine in the UK, Australia, Canada, Singapore and/or Switzerland.
• Project Orbis– programme coordinated by the US Food and Drug Administration (FDA), involving the regulatory authorities of Australia (TGA), Canada (Health Canada), the United Kingdom (MHRA), Singapore (HSA) and Brazil (ANVISA) to review and approve promising cancer treatments.

In addition to the above procedures, the following procedures can be used to obtain a marketing authorisation in Northern Ireland:

Northern Ireland may be included indecentralised or mutual recognition procedure as a Concerned Member State (CMS)

Marketing authorisationsapproved in the European Union centralised procedurewill automatically have effect in Northern Ireland

Question 18

When can the MHRA reject a proposed medicine name

Answer 18

MHRA can reject any name
=> if it considers that the name:
Will cause confusion
Is misleading
Or is otherwise unsafe

Question 19

An application for UK Marketing Authorisation (MA) must include

Answer 19

www.legislation.gov.uk/uksi/2012/1916/schedule/8/made

lots of things…

Question 20

What is the UK?

What is great britain?

Answer 20

UK - United Kingdom (UK) is made up of England, Scotland, Wales and Northern Ireland.

GB - Great Britain is the official collective name of of England, Scotland and Wales and their associated islands. It does not include Northern Ireland

Question 21

When are marketing authorisations granted

Answer 21

Issued if licensing authority satisfied that
Product is safe and efficacious
Facilities for manufacture and quality control are adequate to ensure conformity with specifications

Initially granted for period of 5 years

Must be renewed on expiry

On renewal, must include up to date knowledge and any necessary action

Variations to MAs are common for new products

Question 22

What must the MA holder keep the licencing authority up to date on

Answer 22

Proposed changes in the product or procedures

Fresh information affecting validity of data on which licence was granted

Question 23

What must the MA holder keep records of

Answer 23

Any adverse reports

All sales/ supplies

Sources of all materials

Documents that will facilitate withdrawal or recall

=> And produce a periodic safety update report (PSUR)

Question 24

What are the rules around off label medicines being used in children

Answer 24

The paediatric population ranges from pre-term newborns to adolescents
i.e. it is not homogeneous

Clinical trials for medicinal products are required for each age group

Ethical concerns in paediatric population

Most medicinal products with a MA have only undergone clinical testing in adults

Therefore their use in children is unlicensed or off-label

Question 25

Which regulations surround the use of medicines in children

Answer 25

EU regulations (HMRs 2012) aim to increase the availability of specially adapted medicines for use in paediatric population
Requirement for paediatric data based on a Paediatric Investigation Plan (PIP)
New category of MA
EU: Paediatric Use Marketing Authorisation (PUMA)