Evaluation of quality and interchangeability of medicinal products Training workshop for evaluators from National Medicines Regulatory Authorities in East Africa Community September 2007, Dar Es Salaam, Tanzania Presented by Rutendo Kuwana Principles of regulation of medicinal products The life cycle

Principles of medicine regulation 2 | MEDICINE APPROVAL PROCESS FLOW Application Review Additional Data Approval Variations/Amendments PMS Renewal

Principles of medicine regulation 3 | Receipt of application Application Administrative information Declarations from applicant Complete dossier Date of application Other foreign registrations Application Review Approval Variations/Amendments PMS Renewal

Principles of medicine regulation 4 | Evaluation of application Review – Standard Report Manufacturing site – address, GMP status, full contact details API Manufacturing site API ROS/Specifications FPP Formulation, Specifications, methods of analysis Shelf life Safety and efficacy data Product info + label Application Review Approval Variations/Amendments PMS Renewal

Principles of medicine regulation 5 | Approval of Application Approval Certification Database Conditions of authorisation Application Review Approval Variations/Amendments PMS Renewal

Principles of medicine regulation 6 | Variation of approved information Variations/Amendments Manufacturing site API Manufacturing site API ROS/Specifications FPP Formulation, Specifications, methods of analysis Shelf life Safety and efficacy data Product info + label Application Review Approval Variations/Amendments PMS Renewal

Principles of medicine regulation 7 | Market Surveillance Post Market Surveillance ADR Product Defects Inspections Laboratory analysis Recalls/withdrawals Application Review Approval Variations/Amendments PMS Renewal

Principles of medicine regulation 8 | Re-evaluation/Retention Renewal Regular (e.g. every 3 years) Payment of fees Update of information, specifications, methods of analysis Confirmation of safety, efficacy Public interest Application Review Approval Variations/Amendments PMS Renewal

Drug Information and Control of Promotion

Principles of medicine regulation 10 | n To understand the role of product information n To understand the minimum content of product information n Appreciate the need for the control of product promotion n Understand the different methods available for the control of promotion Objectives Product information and control of promotion

Principles of medicine regulation 11 | The quality of a drug is not only its identity, purity, strength, safety, efficacy. It is also: n Compliance with regulation n product information n Labelling n patient insert,etc.

Principles of medicine regulation 12 | The quality of the information accompanying a drug is as important as the quality of the active substance Product information n Label n leaflets/inserts A drug is a chemical substance + information

Principles of medicine regulation 13 | Product information n Summary of product characteristics submitted as part of the marketing authorization application n Agreed statement between the competent drug regulatory authority and the marketing authorization holder on the approved conditions of use of a product n Content and status is usually defined in law and should be publicly available n Dictates how the product may be promoted to health professionals and the public n For drug to be exported, a copy of the approved product information must accompany the certificate of marketing authorization (WHO-Certification Scheme)

Principles of medicine regulation 14 | Product information content: (WHO Ethical criteria) n International Non-proprietary Name(INN) of each active substance n Pharmacological data - brief description of pharmacological effects and mechanism of action n Clinical information: - Indications - Dosage regimen and relevant pharmacokinetic data: è average and range for adults and children è dosage interval è average duration of treatment è special situations,e.g., renal failure, etc that require either increased or reduced dosage

Principles of medicine regulation 15 | Product information content: (WHO Ethical criteria) n Contra-indications n Precautions and warnings (reference to pregnancy, lactation, etc. adverse effects n Drug interactions including drug used for self-medication n Over dosage: è brief clinical description of symptoms è non-drug treatment and supportive therapy è specific antidotes

Principles of medicine regulation 16 | Product information content: (WHO Ethical criteria) Pharmaceutical information n dosage form n strength of dosage form n excipients n storage conditions and shelf-life n pack sizes n description of the product and package n legal category n name and address of manufacturer(s) and importer(s)

Principles of medicine regulation 17 | Labelling:information on the immediate or outer packaging/container n usually defined in drug laws n The content has to be consistent with the product information n Serves as a source of information for the distributor/dispenser, prescriber, and consumers

Principles of medicine regulation 18 | Labelling:content n The name of the product n Active ingredient (s)( INN) and amount present n Net contents-number of dosage units, weight, volume n Batch number n Expiry date - uncoded form n Storage conditions or handling precautions n Directions for use n Warnings and precautions n Name and address of manufacturer/company/suppliers General: primary and secondary containers

Principles of medicine regulation 19 | Labelling content: WHO manual on assessment n Name of active ingredient(s) and amount /dosage unit n Dosage form/route of administration n Net contents/container n Batch number n Expiry date n Name and address of the manufacturer/supplier Ampoules:

Principles of medicine regulation 20 | Promotion is a persuasive communication that seeks to influence the attitudes, beliefs and behaviour of people UnawareawarenessInterest Trial Use

Principles of medicine regulation 21 | Promotional methods Direct –TV advertising, radio, print media (journals, newspapers, magazines), Internet, direct mailings, pamphlets –Personal selling - sales representatives, house to house peddlers Indirect –Disease awareness campaigns –Sponsorship of information materials-helplines –Links with patient groups –Sales promotion - gifts and samples –Public relations - sponsored symposia, ADR studies

Principles of medicine regulation 22 | Control of promotion n Government DRA control - pre-approval - surveillance è monitoring very difficult è requires resources n Industry self-regulation - UK- ABPI, Australia-APMA, IFPMA è Needs strong association è Enforcement difficult - no sanctions n Enforced self-regulation - self regulation with sanctions n Tripartite regulation- industry, DRA, public interest groups

Principles of medicine regulation 23 | Control of promotion n Promotion should be consistent with national health policies and comply with drug regulations n Should comply with the particulars listed in the product information n Should contain reliable claims, without misleading or unverifiable statements n should contain no omissions which lead to health risks n Should not be designed so as to disguise its real nature, for example, as educational or scientific activities n should encourage rational use of the medicinal product

Principles of medicine regulation 24 | Patient information n Should be accurate & comprehensive n Improve health and enhance outcomes of medical treatment n Empower consumers to make informed decisions n Improve communication between the patient and the health care provider n Should be written in a simple, clear and easily readable language Principles