1. Evaluation of quality and interchangeability of medicinal products Training workshop for evaluators from National Medicines Regulatory Authorities in East Africa Community 10-14 September 2007, Dar Es Salaam, Tanzania Presented by Rutendo Kuwana Principles of regulation of medicinal products The life cycle

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

3. 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

4. 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

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

6. 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

7. 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

8. 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

9. Drug Information and Control of Promotion

10. 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

11. 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.

12. 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

13. 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)

14. 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

15. 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

16. 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)

17. 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

18. 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

19. 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:

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

21. 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

22. 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

23. 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

24. 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