Human medicines: Regulation, Licensing, and Advertising

In the UK there are different licencing arrangements, what are these split into? (this is a badly worded question)

Great Britain and Northern Ireland

What does MA stand for?

marketing authorisation

What did the Human Medicines Regulations 2012 state (the relevant bits)?

a person may not or offer to sell or supply a medicinal product unless the product had a UK MA

What does MHRA stand for?

Medicines and Healthcare products Regulatory Agency

What are the exceptions to the rule around MA?

a pharmacy does not have to have an MA for manufacturing

What is the MHRA responsible for ensuring?

• medicines, medical devices and blood components meet the applicable standards of safety, quality and efficacy

• the supply chain for the above is safe and secure

• promote international standardisation and harmonisation to assure the effectiveness and safety of biological medicines

• education of public and health professionals about the risks and benefits of products and devices

• research and development

• influencing UK,EU and international regulatory frameworks so that they’re risk-proportionate and effective at protecting public health

What are centrally authorised products?

if a medicine is granted a licence by the European Medicines Agency this licence is valid across the whole of the EU and no additional approvals are required

What is grandfathering?

centrally authorised products that were authorised before Brexit that automatically got a UK marketing authorisation when Brexit happens, this is happening up to 2023

What does a cap stand for?

a centrally authorised product

What is a MA?

a licence issued by the MHRA for a specific medicinal product

What is required for a MA?

• the applicant (company) must be registered with the MHRA

• an application form with adequate evidence of safety and efficacy must be submitted to be reviewed by the MHRA and access the risk vs benefit

What is a conditional MA?

a marketing authorisation granted if the medicinal product meets an unmet medical need for a serious/life threatening condition where there is a lack of data at the point in time but it is expected to be available soon for a full review by the MHRA

What can a holder of a MA do?

• sell, supply, offer for sale or supply, or export the product

• procure its sale, supply or exportation

• procure its manufacture or assembly

What does SPCs stand for?

Summary Product Characteristics

When does a SPCs need to be legally created?

when a medicinal product is granted a MA

What is a SPCs?

a description of a medicinal products properties and conditions associated with it’s use, it provides all the information on the safe and effective use for healthcare professionals

What specific information is required for a full application for a MA?

• pharmaceutical form

• composition

• physical characteristics

• medicinal use

• method of manufacture and assembly

• quality control procedures

• containers and labelling

• adverse reactions

• reports of experimental studies, biological studies, and clinical trials and studies

What added information is required for the MA if the product is made abroad?

documentary evidence of authorisation relating to manufacture, assembly etc.

Why would you submit an abridged MA application?

if there is data from a previous application or similar very well documented product

What is a generic medicinal product and what are the requirements surrounding them?

once a patent on a new drug has ended, generic versions of the product is made with the same quantity and quality of the active substance, have the same bioequivalence with studies and have the same pharmaceutical form

What is the definition of manufacture?

any process carried out in the course of making the product, doesn’t include dissolving, dispensing, diluting or mixing the product with a vehicle to administer the product

What is the definition of assemble?

enclosing the product in a container and then it is labelled, or labelling a product that is already in a container, before the product is sold or supplied

What does ML stand for?

manufactures licence

What does WDA stand for?

wholesale distribution authorisation

Who issues the ML and WDA?

MHRA

What do you need before you can apply for a MA?

a ML

What is the purpose of a ML and WDA?

they are a requirement to manufacture or assemble human medicines or import them other than to an approved country

What does GMP stand for?

good manufacturing practice

What are the rules of the GMP?

• be of consistent high quality

• be appropriate to their intended use

• meet the requirements of the MA or product specification

How is compliance with the ML checked?

the MHRA inspects ML holder’s premises for an initial visit and regular inspections

What does QP stand for?

qualified person

What information about the production manager and QP is required for the ML?

their qualifications

Who issues a WDA?

MHRA

What does the WDA allow you to do?

• sell, supply, offer for sale or supply P, POM, GSL and traditional herbal medicines on a wholesale basis

• import unlicenced medicinal products from countries in the EEA

• Export medicinal products to countries in the EEA

What does the WDA detail?

• the specific premises from which the distribution may be carried out

• outline the responsible person

• detail of the emergency plan for product recall

• record keeping needed

What are the 5 key aspects the MHRA consider as part of the application approval possess for MLs and WDAs?

1. the operations proposed to be carried out in pursuance of the licence

2. the premises in which those operations are to be carried out

3. the equipment which is or will be available on those premises for carrying out those operations

4. the qualifications of the persons under whose supervision those operations will be carried out

5. the arrangements made or to be made for ensuring the safe keeping of, and the maintenance of, adequate records in respect of medicinal products manufactured or assembled in pursuit of the licence

Who is the regulatory body for granting authorisations for clinical trials?

MHRA

What does IMPs stand for?

Investigation medicinal products

What is an IMP?

any medicinal product that is being tested within a trial or any product used as a refence in a trial

What is a non-IMP?

is a product not classed as an IMP taken by subjects during a trial

Who reviews clinical trial IMPs (CTIMPS)?

the MHRA and a research ethics committee

How many key phases are their of clinical trials?

4

What happens in a phase I clinical trial?

a new product is tested on a small group of healthy volunteers, looking at the dosage, safety and side effects

What happens in a phase II clinical trial?

a larger group made up of individuals with the disease/condition you are targeting, looking at effectiveness, comparing with a placebo, and side effects

What happens in phase III clinical trials?

a much larger number of individuals, looking at effectiveness, long term use and maybe other countries (to increase diversity), comparing to other existing drugs that treat the same condition

What happens in a phase IV clinical trial?

the now licenced drug is monitored for side effects, effectiveness, safety profile, and drug interactions (that were not picked up on) when used in a real life setting, for longer periods of time

What does the human medicines regulations 2012 state around pharmacovigilance?

• MHRA has a responsibility for pharmacovigilance

• there must be a process to capture and evaluate information about medicines

• measures must be put in place to minimise and prevent risk

• the MA holder must operate and maintain a pharmacovigilance system

• the MA holder must have an appropriately QPPV permanently at its disposal

• the QPPV must reside and operate in the UK or EEA/EU

• the QPPV is responsible for the establishment and maintenance of the pharmacovigilance system for UK authorised products

• the licence holder has to evaluate information to consider options to minimize and prevent risk

What does QPPV stand for?

qualified person for pharmacovigilance

What is the _____card scheme?

voluntary reporting scheme where anyone can report suspected issues or adverse effects of a medicine

What is the missing word: the ______card scheme?

yellow

What happens to the reports from the _____card scheme?

the MHRA reviews them and if necessary takes action to minimise risk and maximise benefits for the patients and the public

What is the advantages of the ____card scheme?

it provides an early warning of safety issues

What are the challenges with the ____card scheme?

under-reporting, unreliable, varies, patchy, vague, it’s complex

What report outlined the reforms needed to the _____card scheme?

the 2020 Cumberlege report

What should you report to the _____card scheme?

all serious suspected adverse drug reactions especially in children, over 65s, biological medicines and vaccines, complementary medicines and any effects associated with delayed drug effects and interactions

What does ADR stand for?

adverse drug reaction

What do new medicines have in the BNF, SPC and on their? And what does it mean?

a black triangle, that the medicines are being observed more closely

Why does the black triangle scheme exist?

Some rare or long latency reactions to drugs are only seen in the general population who are taking it for long periods of time, it confirms the benefit/risk profile that is established in clinical trial development, ensures that previously unrecognised side effects can be identified as quickly as possible.

When is the black triangle reviewed?

5 years after marketing however there is no fixed limit

What is Pharmacovigilance?

the continuous monitoring of drugs that are already on the market to ensure their safety and efficacy as they are used in real-world settings

Who maintains the list of black triangle drugs?

MHRA

How many key categories of medicines recalls are there?

4

What does NAtPSA stand for?

National Patient Safety Alert

What causes a class 1 medicines recall?

a defect that presents risk of death or disability

What happens in a class 1 medicines recall?

alerts are issued via the central alerting system or NPSA on the MHRA website, immediate action is taken

What causes a class 2 medicines recall?

the defect could cause mistreatment or harm but it is not life-threating or serious

What happens in a class 2 medicines recall?

action is taken within 48 hours

What causes a class 3 medicines recall?

a defect that is unlikely to cause harm, the recall is often carried out for non-compliance with the MA or specifications

What happens in a class 3 medicines recall?

action is taken within 5 days

What is a class 1 medicine recall also known as?

NAtPSA

What is a caution in use?

when a class 4 medicine recall cannot take place due to supply concerns an alert mau be issued to provide advice to HCPs

What causes a class 4 medicines recall?

minor defects in packaging or printed materials

What is a company-led medicines recall/notification?

when the licence holder is able to identify affected costumers and contact them directly and it is not necessary to issue a pan-NHS/healthcare system alert

What is a falsified medicine?

a fake medicine that is designed to mimic real medicines

What are the issues with falsified medicines?

• false representation of its identity, source or history

• may contain low quality ingredients, wrong doses, mislabelled, fake packaging

What is a counterfeit medicine?

a medicine that does not comply with intellectual-property rights or that infringe trademark law

Can medicines be both falsified and counterfeit?

yes

What law is advertising covered under?

part 14 of HMR 2012

What is advertising defined as?

anything designed to promote the prescription, supply, sale or use of that medicinal product

What medicines are not allowed to be advertised to the public? And what is the exception?

CDs and POMs except any approved vaccine campaigns

Why is advertising drugs tightly controlled?

to ensure patient safety

What are the general principles of advertising?

• Need a MA, certificate of registration or traditional herbal registration in place

• must comply with particulars in SPC

• should not be misleading

• must encourage rational use of product - objectively without exaggerating properties

What are the rules around hospitality?

• only give to healthcare professionals qualified to prescribe or supply

• must be reasonable to main objective of meetings held only for scientific or professional purposes

• no person may supply/promise gifts, financial advantage or benefit in kind unless it is inexpensive and relevant to the practice or medicine or pharmacy

Who undertakes monitoring of advertising?

UK ASA,a self-regulatory body, health ministers are involved in legal provisions

What does the ASA stand for?

advertising standards authority

What is the guide published by the MHRA providing guidance on advertising and promoting medicines in the UK?

the Blue guide

What are the requirements about the form and content of the medicinal product in an advert?

• it must be clear that it is an advert

• the common name of the active ingredient(s)

• information required for the correct use of the product

• express and clear invitation to carefully read package or leaflet

What is labelling, packaging and leaflets covered under?

Part 13 of the HMR 2012

What is the definition for an immediate packaging/ container?

a container or other form of packaging immediately in contact with the medicinal product

What is the definition of a package?

a container, or any box or packet in which one or more containers of the products are to be enclosed, and then where any box is enclosed in another box

What is the definition of a medicine on prescription?

a medication that has been dispensed against a prescription

What must containers and packages be?

legal, comprehensible, indelible and given in English unless an orphan medicinal product

What is an orphan medicinal product?

a product that is intended for the diagnosis, prevention or treatment of life-threatening or very serious conditions that effect no more than 5 in 10,000 people in the EU

What needs to be included on the label of a medicinal product?

• name, strength and form of the medicinal product

• whether the product is intended for babies, children or adults (if appropriate)

• where the product contains up to three active substances the common name of each active substance

• the month and year of the expiry date

• manufacturer’s batch number

• administration method and if it necessary

• statement of the active substances (details about them)

• pharmaceutical form

• contents by weight, volume or number of doses of the product

• list of excipients (different rules depending on administrative route)

• space for prescribed dose to be indicated (if appropriate)

• warning to store out of reach and sight of children

• any special warnings specific to the product

• special storage precautions

• precautions relating to disposal

• name and address of MA holder

• instructions for use (if not POM)

• information showing classification

• specific information about specific products

What are the rules around the list of excipients on the container or package?

all excipients must be listed for injectables, topicals and eye preparations. all other routes must list all excipients that are known to have a recognised action or effect and included in guidance in HMR

What is required on the container of a blister pack that is labelled legally?

• name, strength and form of medicinal product

• whether product intended for babies, children or adults

• the common name of each active substance (up to 3 active ingredients)

• month and year of expiry

• manufacturer’s batch number

• name and address of MA holder

What is required on the labelling of small packaging or containers?

• name, strength and form of medicinal product

• whether product intended for babies, children or adults

• the common name of each active substance (up to 3 active ingredients)

• month and year of expiry

• manufacturer’s batch number

• administration method and route of administration

• pharmaceutical form and contents by weight, volume, or number of doses of the product

What needs to appear legally on dispensed medicinal products when prescribed?

• name of the patient

• name and address of the supplying pharmacy

• date of dispensing

• name of medicine

• directions for use

• precautions relating to the use of the medicine

• BNF advisory and cautionary labels added by the pharmacist

What is advised to be on the label of a dispensed medicinal product when prescribed?

• ‘keep out of the reach and sight of children’

• ‘use this medicine only on your skin’ where applicable

• addition information that the pharmacist considers to be necessary

• quantity

What is strongly recommended to be included on the label of a dispensed medicinal product in a secure environment? and why?

the prisoner number as a definite patient identifier