1. 13/06/2008SAPRAA-Salma Ismail FEEDBACK ON AFRICA REGULATORY CONFERENCE FEBRUARY 2008

2. 13/06/2008SAPRAA-Salma Ismail  The Importance of Pharmaceutical R&D  Role of Africa in Clinical Development – Regulatory Implications  Accelerating Access of Medicines to Address Diseases of PublicHealth Importance  EU Regulatory Assessment Using Article 58  WHO Prequalification Scheme  Biosimilars  Update on ICH-GCG and Interface with Regional Harmonisation Initiatives TOPICS ADDRESSED:

3. 13/06/2008SAPRAA-Salma Ismail  Experience and Successes of EU Accession  Update on SADC Including the Perceived Benefits and Challenges of Harmonisation  ICH Quality  Quality Risk Management  GMP and the Pharmaceutical Inspection Cooperation Scheme  Journey into PIC/S  WHO Certification Scheme  The Place of the CPP in Guaranteeing Quality, Safety, and Efficacy  The Roles of the WHO IMPACT Groups  Industry Perspective of Counterfeits – Regulatory Implications  Addressing the Counterfeit Issue TOPICS ADDRESSED:

4. 13/06/2008SAPRAA-Salma Ismail Update on SADC Including the Perceived Benefits and Challenges of Harmonisation

5. 13/06/2008SAPRAA-Salma Ismail The Southern African Development Community Angola, Botswana, Democratic Republic of Congo, Lesotho, Madagascar (membership pending), Malawi, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Swaziland, Tanzania, Zambia and Zimbabwe.

6. 13/06/2008SAPRAA-Salma Ismail To build a Region in which there will be a high degree of harmonization and rationalization to enable the pooling of resources to achieve collective self-reliance in order to improve the living standards of the people of the region. SADC OBJECTIVE:

7. 13/06/2008SAPRAA-Salma Ismail implement a harmonized Pharmaceutical Programme -SADC Health Protocol and the SADC Health Policy. Programme purpose: – to enhance the capacities of Member States to effectively manage diseases and medical conditions that are of major concern to public health in the Region such as HIV and AIDS, TB, Malaria and other communicable diseases. HARMONIZED PHARMACEUTICAL PROGRAMME

8. 13/06/2008SAPRAA-Salma Ismail numerous challenges related to Harmonizing the Regulation of Medicines. different stages of development in terms of regulatory capacities in the Region some regulatory authorities have more advanced systems than others. setback due to the emergence of: – multidrug resistant Tuberculosis –high incidences of the HIV and AIDS; –prevalence of resistant malaria parasites to affordable medicines; – and resistance of mosquitoes to insecticides. fight against proliferation of substandard and counterfeit medicines within the Region. The Region has not been spared in terms of human resource for health constraints due to brain drain. SADC CHALLENGES:

9. 13/06/2008SAPRAA-Salma Ismail SADC GUIDELINES HAVE NOW BEEN FINALIZED & APPROVED Registration of medicines Licensing of pharmaceutical establishments; Licensing for export / import; Post-marketing surveillance; Medicines Donations; Recalls, Stability and Validation; Biavailability/bioequivalence Advertising and promotion of medicines; Clinical trials; and Nutritional supplements

10. 13/06/2008SAPRAA-Salma Ismail CONTACT Joseph Mthetwa Senior Programme Manager for Health and Pharmaceuticals Directorate for Social and Human Development and Special Programmes Southern African Development Community Secretariat (SADC) Kgale View Offices Private Bag 0095 Gaborone Botswana Tel: +267 3951863 Fax: +267 3972848 / +267 3181070 Mobile: +267 71720972 E-mail: JMthetwa@sadc.int; or josephmthetwa@yahoo.co.uk

11. 13/06/2008SAPRAA-Salma Ismail WHO Certification Scheme

12. 13/06/2008SAPRAA-Salma Ismail The WHO Certification Scheme Is an administrative tool developed in response to the requests of WHO Member States Is a voluntary/non binding agreement between WHO Member States Is information exchange mechanism on the quality of imported drugs Is intended to give assurance to countries that are importing pharmaceutical products but have no capacity or limited capacity to assess the safety, efficacy and the quality of the drugs they import Is intended to facilitate availability and trade in pharmaceuticals by ensuring safety, efficacy and quality

13. 13/06/2008SAPRAA-Salma Ismail Three types of certificates are issued under the current Scheme Certificate of a Pharmaceutical Product (Product Certificate) or CPP Model Batch Certificate of a Pharmaceutical Product Model Statement of Licensing Status of Pharmaceutical Product (s)

14. 13/06/2008SAPRAA-Salma Ismail Issuing a certificate The certifying authority is responsible for assuring the authenticity of the certified data. Certificates should not bear the WHO emblem, but a statement should always be included to confirm whether or not the document is issued in the format recommended by WHO.

15. 13/06/2008SAPRAA-Salma Ismail Advantages of the Scheme: It uses standard format It can enable importing countries to get all the information they need to know about the product they import It can enhance the exchange of information between countries and can lead to harmonisation of information It can oblige certifying authorities to disclose important information to the importing country

16. 13/06/2008SAPRAA-Salma Ismail Limitations of the Scheme Rely on the honesty and competence of the issuing authorities –A certificate is as good as the certifying authority Requirements differ in countries for MA –More applies to generic drugs? Counterfiet certificates reality – Sample of fake logo from web site

17. 13/06/2008SAPRAA-Salma Ismail WHO’s recommendation Communicate directly with the issuing authorities to build confidence and trust Contact the certifying authority and ask for the duplicate of the certificate to be sent directly, if in doubt Seek assistance from WHO

18. 13/06/2008SAPRAA-Salma Ismail Problems Consistency with WHO Certification Scheme –WHO format not adopted in all issuing countries, authorities continuing to issue Free Sales Certificates e.g. France Embracing the Spirit of the Scheme by Issuers and Recipients –CPPs cannot be issued if the product is not exported from the country (but does have MA) –Receiving countries do not accept CPPs for products that are not marketed in the issuing country Long delays in issuance of CPPS Excessive demands from recipients…

19. 13/06/2008SAPRAA-Salma Ismail What are the issues? Can all national regulators assess and inspect all the new innovative products that come to their markets? Does repetitive assessment and inspections give added value? How to build confidence in scientific assessments carried out by other parties? How regulators can best contribute to the public health with the resources they have?

20. 13/06/2008SAPRAA-Salma Ismail What is a Free Sale Certificate? issued by the national health authorities product specific States product is for "free sale" within the country of origin. the product is not necessarily licensed/ the product is of a quality suitable for being placed on the market. does not guarantee that the product in question is marketed in the country of origin.

21. 13/06/2008SAPRAA-Salma Ismail What is a CPP (Certificate of Pharmaceutical Product)? issued by the national health authorities-request from –manufacturer, –customer or –authorities in the importing country. product specific states whether or not the product is marketed in the country of origin. states that manufacturer of product complies with GMP and that they are inspected regularly by the national health authorities. The World Health Organization (WHO)- standard format for this type of certificate and recommends that this format is used instead of the Free Sale Certificates. A CPP (WHO format) generally covers the need for overall documentation regarding the product as well as the manufacturer. It should therefore not be necessary to request any of the certificates mentioned above. The certificate is also called a WHO certificate.

22. 13/06/2008SAPRAA-Salma Ismail CPP has two DISTINCT parts –Evidence of Positive Quality, Safety and Efficacy (QSE) Review assurance of QSE without the cost and time of a large local regulatory infrastructure –Evidence of Compliance with Good Manufacturing practice (GMP) Certification of GMP for issuing country’s sourcing route

23. 13/06/2008SAPRAA-Salma Ismail WHO Prequalification Program

24. 13/06/2008SAPRAA-Salma Ismail PREQUALIFICATION PROGRAMME A United Nations Programme managed by WHO Vision Good quality medicines for everyone. Key output The list of prequalified medicinal products: – HIV/AIDS, malaria, tuberculosis and for reproductive health produced by the Programme is used principally by United Nations agencies — including UNAIDS and UNICEF — to guide their procurement decisions. –the list -a vital tool for any agency or organization involved in bulk purchasing of medicines, be this at country level, or at international level, as demonstrated by the Global Fund to Fight AIDS, Tuberculosis and Malaria.

25. 13/06/2008SAPRAA-Salma Ismail Is quality of medicines still a big problem? Panama case in 2006. It turned out the cause of death of more than forty five persons was simple. The cough syrup and potentially other medicines produced in the governmental pharmaceutical factory were contaminated. The death were caused by diethylene glycol (DEG) found in medicines. DEG is a chemical cousin of antifreeze and used widely by various industries. It is toxic to the kidneys and can cause deadly renal failure.

26. 13/06/2008SAPRAA-Salma Ismail How it works Any manufacturer wishing their medicines to be included in the prequalified products list are invited to apply. present extensive information on the product (or products) submitted to allow qualified assessment teams to evaluate its quality, safety and efficacy. The manufacturer: open its manufacturing sites to an inspection team which assesses working procedures for compliance with WHO Good Manufacturing Practices (GMP). Alternatively, the inspections carried out by stringent regulatory bodies are recognized and their work is not duplicated by WHO. assessment teams: include experts from some of the national regulatory authorities of the European Union as well as Canada and Switzerland. The prequalification process takes a minimum of three months if the product meets all the required standards.

27. 13/06/2008SAPRAA-Salma Ismail Assessment procedure- Product dossiers  Innovator products Abridged procedure if approved by stringent authorities like EMEA and US FDA Assessment reports from Drug Regulatory Authorities (DRSs), WHO Certificate of Pharmaceutical Product (CPP), batch certificate, update on changes Trusting scientific expertise of well-established DRAs  Multisource products Full dossier with all data and information requested Quality : information on starting materials and finished product including API details, specifications, stability data, formulation, manufacturing method, packaging, labelling etc Efficacy and safety: Bio-equivalence study or clinical study report US FDA tentative approvals for ARVs – recognition scientific assessment based on information exchange (Confidentiality agreement between US FDA and WHO); the same approach apply for EU Art 58 and Canadian JCPA procedure)

28. 13/06/2008SAPRAA-Salma Ismail The list of medicines Medicines which have been found to meet the required standards In soliciting applications from companies, WHO does not question whether the products presented are patented or generic,

29. 13/06/2008SAPRAA-Salma Ismail Why the prequalification is needed?  Risks Sourcing of poor quality products or even counterfeit medicines  risk to patients, toxic reactions, treatment failure, resistance  bad quality (generic) products undermine public confidence  Problems Millions of people living with HIV/AIDS, tuberculosis and malaria, have no or limited access to treatment Substandard and counterfeit products in different countries Weak or absent QA systems of medicines supply chain Lot of money invested in procurement  products with very different quality sourced

30. 13/06/2008SAPRAA-Salma Ismail Article 58 EMEA's Scientific Opinion European legislation (Regulation 726/2004) excluded licensure of vaccines and other medicinal products for exclusive use outside the European Community. concern since licensure of priority vaccines for developing countries would become the responsibility of the national regulatory authorities (NRAs) of user countries, which, in the past, relied on the regulatory evaluation of the NRA of the country of origin to assure quality. To ensure no disruption in the supply of vaccines and medicinal products that are important for developing countries a consultation and collaboration between EMEA and WHO led to the Article 58 in the new Regulation. Article 58 establishes a mechanism whereby the EMEA may give a Scientific Opinion, in the context of cooperation with WHO, for the evaluation of certain medicinal products for human use intended exclusively for markets outside the Community. The procedure for implementation of Article 58 Scientific Opinion procedure, effective since May of 2005 begins with the request from the company to EMEA to assess the eligibility of the product for Scientific Opinion. WHO's input takes place in two instances: evaluation of eligibility of the vaccine for Scientific Opinion by EMEA; participation of experts proposed by WHO in the product evaluation process. So far, one vaccine has gone through the review by WHO and deemed eligible for Scientific Opinion. There is indication that a few more vaccines will follow shortly.

31. 13/06/2008SAPRAA-Salma Ismail IN CONCLUSION It's not enough to have lived; we should be determined to live for something. May I suggest that it be creating joy for others, sharing what we have for the betterment of personkind, bringing hope to the lost and love to the lonely.