Prequalification and ADP

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Medicines - Quality Control and Quality
Assurance WHO Normative Functions in the field of
pharmaceuticals
PSM Technical Briefing Seminar 8 12 October,
Geneva
Dr Lembit Rägo Coordinator Quality Assurance and
Safety Medicines (QSM) Medicines Policy and
Standards (PSM) WHO Headquarters, Geneva,
Switzerland ragol_at_who.int
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Quality of medicines remains a problem in many
countries tragedy in Panama in 2006

• The medical nightmare of Lucia Cruz, a
  74-year-old grandmother, began in mid-September
  2006 when she realized that she had not urinated
  in two days. She was sent to the hospital but her
  condition went from bad to worse. Nausea and
  vomiting came first. Then she could not breathe.
  Her kidneys continued to fail, her arms and legs
  got swollen and eventually she died. When she
  died, her physician told the family to cremate
  the body in case she carried a mysterious disease
  that might spread.
• As it turned out the cause of death of more than
  30 other persons was more simple. The cough
  syrup and potentially other medicines produced in
  the governmental pharmaceutical factory were
  contaminated.
• The death were likely 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.
• Pictures. 1. Waiting for answer. 2. A popular
  medicine in Panama that turned to be a killer. 3.
  Medicines traced down and removed from supply
  chain

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Usual perceptions may not help in Making
judgements about medicines
Taste
Smell
Appearance
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Medicines and Myths Policies and Politics

• Medicines are one of the most common object of
  all type of myths
• Polices and politics is often not based on
  evidence or science
• Judgments about medicines should be science
  based, not perceptions etc.

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Why Stringent Standards for Medicines?

• Medicines are different from other goods as
  patients (consumers) and even health care
  professionals are not able to judge their
  "quality" or "fitness for use"
• " drugs are a public good and not simply just
  another commodity first for their high social
  value, and then because consumers and prescribers
  are unable to assess their quality, safety and
  efficacy" (Dr Gro Harlem Brundtland, former
  Director General of the World Health
  Organization)
• This is the reason why medicines belong to one of
  the most regulated group of products

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What Standards for Medicines?

• Medicines must meet quality, safety and efficacy
  criteria.
• These three sets of requirements are
  complementary to each other and each product has
  to be of good quality, safe and efficacious.
• It is possible that a product is of good quality,
  but may not necessarily be effective or safe
• It is possible that a product is effective, but
  may not necessarily be of good quality or safe
• It is possible that a product is safe but may not
  be of good quality or effective

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What type of medicines we have? 1. Innovator
products

• For these products one has to prove their safety,
  efficacy and quality. Basis for these criteria is
  created by respective scientific disciplines.
  Implementation is executed through respective
  laws and regulations.
• Proving safety and efficacy is the key for these
  products. It is based on the results of
  pre-clinical (i.e. animal toxicology) and
  clinical (clinical studies carried out in healthy
  volunteers and patients) research
• Innovator (or originator) products
• New innovative products that nobody yet has
  marketed, usually based on the new active
  ingredient (chemical compound which is
  responsible for its effects in human subjects)
• The manufacturer has also to prove that its
  processes to produce the product and methods
  invented to control its quality are meeting
  established quality requirements.

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What type of medicines we have? 2. Generic
products interchangeability a key

• The term generic product has somewhat different
  meanings in different jurisdictions. Therefore,
  term multisource pharmaceutical product is
  preferred by WHO. Generic products may be
  marketed either under the approved nonproprietary
  name or under a brand (proprietary) name. They
  may be marketed in dosage forms and/or strengths
  different from those of the innovator products.
• Where the term generic product is used, it means
  a pharmaceutical product, usually intended to be
  interchangeable with the innovator product, which
  is usually manufactured without a license from
  the innovator company and marketed after expiry
  of the patent or other (e.g. data) exclusivity
  rights.
• Multisource pharmaceutical products are
  pharmaceutically equivalent products that may or
  may not be therapeutically equivalent.
  Multisource pharmaceutical products that are
  therapeutically equivalent are interchangeable

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What type of medicines we have?

• Other products us as medicines
• Traditional medicines such as traditional Chinese
  medicine or in Europe in some countries
  homeopathic medicines
• Herbal medicines
• .

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What standards are need for generic medicines?

• For generic medicines the manufacturer has to
  prove that the product meets all quality
  requirements
• In case of safety and efficacy it refers to the
  originator's research
• To prove the therapeutic interchangeability it
  has, as a rule, to carry out bioequivalence
  studies (small scale clinical trials in healthy
  volunteers to examine if the test drug has
  essentially the same blood concentration pattern
  of active ingredient as the originator.
• It is assumed that if the blood concentrations
  are essentially the same the safety and efficacy
  profile is also the same.

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What is WHO doing to help the countries?

• Normative functions
• Capacity building
• Prequalification
• "Three in one" more tuned to real public health
  problems, immediate feedback, better quality,
  higher efficiency

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WHO normative documents

• The Expert Committee documents pass wide
  international consultation and are finally
  adopted by the Committee composed of outstanding
  international technical experts
• New TRS No 943 with 41st Report from 2007
• Updated PQ general procedure
• PQ of QC labs procedure

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Bookorders_at_who.int
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Are there alternative regulatory pathwaysfor
products of public health needs?

• EU Article 58
• US FDA tentative approvals linked to PEPFAR
• Canadian Access to medicines scheme
• WHO cooperation with the above mentioned
• Confidentiality agreement with US FDA in place
  and working CA with Health Canada expected by
  March 2007
• How better use the synergies?

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Instead of conclusions

• Thank you for listening