FEEDBACK ON AFRICA REGULATORY CONFERENCE

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FEEDBACK ON AFRICA REGULATORY CONFERENCE

• FEBRUARY 2008

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TOPICS ADDRESSED

• The Importance of Pharmaceutical RD
• 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

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TOPICS ADDRESSED

• 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

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Update on SADC Including the Perceived Benefits
and Challenges of Harmonisation
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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.

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SADC OBJECTIVE

• 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.

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HARMONIZED PHARMACEUTICAL PROGRAMME

• 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.

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SADC CHALLENGES

• 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.

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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

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CONTACT

• Joseph MthetwaSenior Programme Manager for
  Health and PharmaceuticalsDirectorate for Social
  and Human Development and Special
  ProgrammesSouthern African Development Community
  Secretariat (SADC)Kgale View OfficesPrivate Bag
  0095GaboroneBotswanaTel       267
  3951863Fax      [phone] / 267
  3181070Mobile   [phone]E-mail
   JMthetwa_at_sadc.int or  josephmthetwa_at_yahoo.co.uk

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WHO Certification Scheme
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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

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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)

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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.

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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

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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

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WHOs 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

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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

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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?

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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.

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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.

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CPP has two DISTINCT parts

• Evidence of Positive Quality, Safety and Efficacy
  (QSE) Reviewassurance 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
  countrys sourcing route

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WHO Prequalification Program
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PREQUALIFICATION PROGRAMME A United Nations
Programme managed by WHO

• VisionGood 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.

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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.

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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.

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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)

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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,

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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

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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.

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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.