EWU PHRM 410 Lecture Slide 1.pdf

8/10/2019 EWU PHRM 410 Lecture Slide 1.pdf

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HRM 410 Lecture 1: Mohammad

awsar Sharif Siam, DOP, EWU

MKSS 1

Safeguarding public health

Drug regulation andlicensing

Mohammad Kawsar Sharif Siam

Lecturer, DOP, EWU

Slide 2

Overview

What makes a Medicinal Product

How a medicine is licensed in the

EU

Lifecycle of a Medicine

After the presentation you should be

able to:

Describe the key types of regulatory

involvement for a new medicinal

product

Describe the type of informationrequired to obtain a Marketing

Authorisation

Discuss the ways in which a product

may be developed after a Marketing

Authorisation is granted


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MKSS 2

Slide 3

Medicinal ProductActive substance (API)

Excipients

Dosage form

Packaging

Product Information

Product name Label/PIL SPC or SmPC

What is a Medicinal product?

Brand vs Generic

Brand = innovator product,

eg Panadol tablets (GSK)

Generic = copy of active

substance and dosage formof Brand product,

eg Paracetamol tablets(Boots, Tesco, Asda)

Slide 4

Types of Regulation

Quality

Safety

Efficacy

Value for money

Compliance


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MKSS 3

Slide 5

Value for money

Is the medicine cost effective ?

Cost vs Benefit

Health Technology assessments

National Institute for Health and Clinical Excellence

(NICE)

Scottish Medicines Consortium

Pricing authorities

Slide 6

Quality, safety & efficacy

is the medicine well made?is the medicine safe for intended use?does the medicine work for intended use?

Risk vs benefit

Medicines Regulatory Agencies - Assessors

is the organisation complying with the relevant rules?

Medicines Regulatory Agencies - Inspectors


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MKSS 4

Slide 7

Major Regulatory Agencies

USA Food and Drug Administration (FDA)Japan Ministry of Health and Welfare

Canada Health Products & Food BranchAustralia Therapeutic Goods AdministrationChina SFDA

EU European Medicines Agency (EMA)

National Competent Authorities (NCA)

MHRA (UK)Afssaps (FR)

BfArM (DE)

Slide 8

MEDICINES CONTROL IN EU

Human Medicines: vaccines, toxins or serum blood

products, radio pharmaceuticals, herbals, homeopathic

Medicinal Devices

Veterinary Medicines

Feed Additives


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MKSS 5

Slide 9

Current EU pharmaceutical legislation

Comprises:

Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March2004 laying down Community procedures for the authorisation and supervision ofmedicinal products for human and veterinary use and establishing a European MedicinesAgency.

Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004amending Directive 2001/83/EC on the Community code relating to medicinal products forhuman use.

Directive 2004/24/EC of the European Parliament and the Council of 31 March 2004amending, as regards traditional herbal medicinal products, Directive 2001/83/EC on theCommunity code relating to medicinal products for human use.

The consolidated Directive 2001/83/EC of the European Parliament and of the Council of6 November 2001 on the Community code relating to medicinal products for human use asamended by Directive 2002/98/EC, Directive 2004/24/EC and Directive 2004/27/EC

Regulation (EC) No 1234/2008 of the European Parliament and of the Council of 24November 2008 concerning the examination of variations to the terms of marketing

authorisations of medicinal products for human and veterinary use (the variations regulation)

Regulation (EU) No 1235/2010 of the European Parliament and of the Council of 15December 2010 amending, as regards pharmacovigilance procedures for theauthorisation and supervision of medicinal products for human and veterinary use (the newpharmacovigilance regulation - entry into force July 2012)

Slide 10

Developing a new medicine

Pre-clinical Phase 1 Phase 2 Phase 3Life cycle

management

Discovery:

Identification of

target

active

Development:

Chemistry

Toxicology

Animal models

Early human

exposure:

Safety in

humanvolunteers

PK

Pharmaceutical development

Clinical trials

Proof of concept

Dose finding

Proof of efficacy

Common side

effects

MA Approval

MA

application


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MKSS 6

Slide 11

Life cyclemanagement

Developing a new medicine Regulatory

involvement

MAapplication

Pre-clinical Phase 1 Phase 2 Phase 3

Pharmaceutical development

Clinical trials

Rationale

Dosing regimen

Safety Investigations

Manufacture

Scientific advice

InspectionsGLP GCP GMP GPV

MA Approval

Clinical Trial ApplicationProduct Licence

Product Information

Dosage form

Packaging

Manufacture & Supply

Pharmacovigilance

Slide 12

Clinical Trial Applications

Governed by Clinical Trial Directive (Directive 2001/20/EC)- Published April 2001; Implemented by May 2004

Need authorisation for commencing or conducting a clinical trial,- authorised by the NCA- has a favourable opinion by an ethics committee.

Assessment by NCAs:- Is the existing safety knowledge of a new drug sufficient to proceed

with a new trial- is the trial designed so that it will capture new safety signals/adverse

events/side effects- Is the drug manufactured appropriately

Risks (of trial) vs benefit (of new knowledge)


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MKSS 7

Slide 13

Pre-clinical Phase 1 Phase 2 Phase 3

Discovery:

Identification of

target

active

Development:

Chemistry

Toxicology

Animal models

Early human

exposure:

Safety in

human

volunteers

PK

Clinical trials

Proof of concept

Dose finding

Proof of efficacy

Common side

effects

MAapplication

Obtaining a Marketing Authorisation -

what is assessed?

Slide 14

Modules

1

2

3

4

5

Dossier - CTD

MA internal database

Production/Control sites

Manufacturer/QC/batch release Distribution

Ownership

- responsibility (MAH/contractor)

Product Information

Product name Label/PIL SPC

Obtaining a Marketing Authorisation -

what else is assessed?

Medicinal ProductActive

Excipients

Dosage form

Packaging


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MKSS 8

Slide 15

M4 - Non-clinical:are there any seriousunwanted effects in

animals of relevance

to humans?

M3 - Quality:Is the product well

made?

M5 - Clinical:

Pharmacology, safety,efficacy (statistical)

is the medicine safe for

intended use?

does the medicine work forintended use?

Slide 16

What is assessed (Quality, Efficacy, Safety):

Pharmaceutical (Module 3): How is the active substance and product made ? How long is it stable ? (shelf life) Does it need to be kept cold? (Storage conditions)

Non-clinical (Module 4): Does it have any serious unwanted effects in animals of relevance to humans?

Pharmacological (Module 5):

Where does the active act in the body? How long does it stay in the body? How is it removed from the body? Are there any relevant drug-drug interactions ?

Clinical (Module 5 Efficacy, Safety): Does it treat the condition it will be indicated for ? Has the right dose been chosen ? Does it have any serious unwanted effects ? (side effects) Have the right patients been studied? Is it likely to work in a wider group of patients ?

Statistical (all, particularly Module 5): Have they studied enough patients to draw these conclusions? Can the results be explained by chance or other reasons? How did they cope with missing data?


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MKSS 9

Slide 17

Summary of Product Charactaristics (SmPC or

SPC)

Defines the licensed use of a product:

provides information for prescribers on how to use the medicinal product safelyand effectively- what the medicine is used for and by which patients (indications)- Dose & how often it should be taken (posology)- When not to use (contraindications)- Things to be aware of to maximise safe use of the product (warnings &

precautions, interactions, use during pregnancy etc)- Known side effects

Provides the information that should be included in the Patient InformationLeaflet- Lay translation- Rules on presentation (font size, readability etc)

Limits the advertising claims for a product

Slide 18

Summary of Product Charactaristics (SmPC)


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MKSS 10

Slide 19

Other Regulatory requirements

Identifying and managing risk:

- Pharmacovigilance system

- Risk Management Plan

- (Risk minimisation measures)

Paediatric Investigation Plan

- Needs according to age bands

- Obligatory, deferral or waiver

Advertising / educational materials pre-vetting

Slide 20

Application assessment process

Assessment

Application

submitted

MAH

response

AR RFI

LOQ

consultation

Assessment

ARFinal Decision

consultation


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MKSS 11

Slide 21

European licensing routes to obtain

Marketing Authorisation for humanmedicines

National

- Single Member State

- ie MA only valid in that MS

Mutual Recognition / Decentralised

- Selected Member States

- Can withdraw from individual MS

Centralised

- All Member States

- Compulsory route for certain product types and therapeutic areas

Slide 22

National MR / DCP Centralised

Submission NCA RMS + CMS EMA

Assessment NCA RMSon behalf of CMS

Rapporteur (NCA)

Co-Rapporteur(NCA)

ConsultationExternal

Expert(s)CMSs CHMP (MSs)

Communicationwith applicant

NCARMS

on behalf of CMSEMA

Licence issuer NCA RMS + CMS NCAsEU Commision

EMA


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MKSS 12

Slide 23

UK External Advice

Commission on Human Medicines (CHM) Independent experts appointed by Ministers established 2005 (replaced Medicines Commission & CSM)

Expert Advisory Groups- Chemistry, Pharmacy & Standards EAG- Pharmacovigilance EAG- Clinical Trials EAG- Paediatric Medicines EAG- Patient & Public engagement EAG

- Therapeutic area EAGs:- Biologicals & Vaccines EAG

- Cardiovascular, Diabetes & Renal, Respiratory & Allergy- Gastroenterology, Rheumatology, Immunology & Dermatology- Medicines for Womens Health- Neurology, Pain & Psychiatry- Oncology & Haematology

Slide 24

Quality WorkingParty

European Expertise

Scientific AdviceWorking Party

European Experts List

CHMP COMP

PDCO

Temporary WPsSafety Working

Party

Efficacy

Working Party

Scientific

Advisory Group

Biologicals

Working Party

Source EMA


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MKSS 13

Slide 25

Co-ordination group for Mutual Recognition and

Decentralised Procedures (CMDh)

Responsible for smooth functioning of MRP + DCP (scientific

and regulatory)

- any question related to MAs in more than one M/S

- Rules of Procedure

- Transparency

Avoid referrals to CHMP

Ensure consistency of standards

Good quality decisions for Public Health

Harmonisation of SPCs

Harmonised view on interpretation of legal framework

Regulatory memory

Variations grouping

Slide 26

Lifecycle management what happens after MA grant?


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MKSS 14

Slide 27

Medicinal ProductAPI

Excipients

Dosage form

Packaging

Modules1

2

3

4

5

Dossier - CTD

Product Information

Product name Label/PIL SPC

Production/Control sites

Manufacturer/QC/batch release Distribution

Ownership

- responsibility (MAH/contractor)

MA internal database

Marketing Authorisations - need for change

Slide 28

Types of Variation

Type IA Type II

Evaluation Procedure adapted to the level of risk

Changes not requiring

any prior approval

Changes requiring

prior approval

Type IB ExtensionDesignSpace

Variations

Do & tell Tell, wait & doNo submissionreqd if within

an approved

design space


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MKSS 15

Slide 29

Lifecycle management

New uses

(Medical variations)New safety data

(Medical variations)

Changes in production(Pharmaceutical variations)

Pharmacy/GSL

availability

(legal status

reclassification) Periodic review

(PSURs & Renewals)

Article 61(3)

(Label & leaflet changes)

Slide 30

The Yellow Card SchemeThe Yellow Card Scheme Reports submitted in

confidence by:

- Any health professional

- Patients and their

representatives

Reports from pharmaceutical

companies legal obligations

~22,000 reports received

annually

More than 600,000 UK

reports received to date


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MKSS 16

Slide 31

Black Triangle SchemeBlack Triangle Scheme Intensive monitoring scheme for new products where

knowledge of risk benefit profile is limited Report all reactions for medicine, including non-serious

Black triangle symbol printed next to product name in

BNF, SmPC, advertising material, etc.

assigned to:

New active substances

Established active substances if product:

Contains a new combination of active substances Is administered by a novel route or dug delivery

system

Is for significant new indication which may alter

the risk benefit profile of the substance

Slide 32

Reasons for adding a Black TriangleReasons for adding a Black Triangle

New Formulation e.g. Requip XL (ropinirole)

New Combination e.g. Competact (pioglitazone &metformin)

New Indication e.g. Viread (Tenofovir Disoproxil forChronic Hepatitis B)

New route of administration e.g. Hycamtin (oral topotecan)

New Delivery System e.g. NuvaRing (ethinylestradiol &etonogestrel)

Reformulation in view of the risk of medication error e.g.NovoSeven (recombinant factor VIIa)


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MKSS 17

Slide 33

Slide 34

Meaning of scientific data


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MKSS 18

Slide 35

Periodic Reviews

Focus on safety

PSURs (Periodic Safety Update Reports)

- Safety of New Products reviewed frequently

- Less frequent reviews as safety becomes known

Renewal

- after 5 yrs of grant of MA, then unlimited validity

Community referrals- Resolve differences between MAs for similar products

(different Member States)

- Review Serious public health issues

Slide 36

Pharmacy/GSL

availability


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MKSS 19

Slide 37

Any questions?

Slide 38

Crown copyright 2011

The materials featured within this MHRA presentation are subject to Crowncopyright protection. Any other copy or use of Crown copyright materialsfeatured in this presentation, in any form or medium, is subject to priorapproval of the MHRA which has Delegated Authority from Her Majesty'sStationery Office (HMSO) to administer Crown copyright for MHRAoriginated material. Applications should be in writing, clearly stating the

proposed use/reuse of the information, and should be sent to the MHRA atthe following address: Conference and Education Function, MHRA, 151Buckingham Palace Road, Victoria, London SW1W 9SZ. or [email protected]. You may not sell or resell any informationreproduced to any third party without prior agreement. The permission toreproduce Crown copyright protected material does not extend to anymaterial in this pack which is subject to a separate licence or is thecopyright of a third party. Authorisation to reproduce such material must beobtained from the copyright holders concerned.


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Slide 39

Useful links

EMEA: http://www.ema.europa.eu/emaEudraLex* - The Rules Governing Medicinal Products in the European Unionhttp://ec.europa.eu/health/documents/eudralex/vol-2/index_en.htm

CMDh / Heads of Medicines Agencies http://www.hma.eu/

MHRA http://www.mhra.gov.uk/index.htm

FDA Legal framework:

http://www.fda.gov/

ICH: www.ich.org

eMC: http://www.medicines.org.uk/emc

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EWU PHRM 410 Lecture Slide 1.pdf

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