E-DRUG: Country of Origin

E-drug: Country of Origin
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     Dear edruggers,
  this is a tricky issue and requires relatively long
     comments.
     
     The principles are:
     - the country of origin is the country of origin of the exportation,
     - the manufacturer who last touched - including packaging - the
     product before this enters the distribution channel, i.e. the
     manufacturer that puts the product on the market is the one and only
     one that bears the entire responsibility for the product quality,
     - no drug should be imported unless it has a marketing authorization
     in the importing country,
     - there is no magic administrative replacement for technical
     assessment and judgement.
     
     The issue of country of origin is an issue only at the time of assessing
     an application for a marketing authorization. After that, a product must
     simply comply with the marketing authorization.
     
     Now let's see the case presented by Joseph Kwong and see how the
     principles fit in it.
     
     Case: Final dosage form manufactured in country A, packaged in country
     B, exported from country B to country C. The product is a generic or
     branded generic, i.e. the safety and efficacy profile does not need to
     be assessed.
     
     The country of origin is country B.
     
     The authority of country C needs to obtain a WHO-type certificate from
     the authorities of country B. At this point, if they decide to rely on
     the authority of country B and the product has a marketing
     authorization in country B, then country C can assume that the GMP
     profile of the manufacturer and the quality dossier of the product
     have been assessed by country B and found acceptable. At this point
     country C needs to ascertain 1) whether QC lab methods for the final
     dosage form are applicable at the national QC lab, i.e. whether they
     will be able to carry out routine controls on the imported product, 2)
     whether the product information and labelling are acceptable, and 3)
     whether there is need to assess interchangeability with any
     pharmaceutically equivalent product already on the market of country
     C. If all this is in order, than role of country A is not an issue,
     and a marketing authorization can be granted.
     
     Now let us see what happens if, after receiving the WHO-type
     certificate from country B, the authority of country C decides that it
     does not want to rely on the authority of country B. Then, country C
     needs to ask the applicant to submit a full data set to assess the
     quality profile of the product as well as WHO-type certificates for
     all manufacturers involved including those of country A if applicable,
     plus detailed information on the manufacturing process to carry out
     its own assessment of the GMP profile of all the manufacturers
     involved - in this case, since country C does not rely on decisions
     made by country B, it is likely to entail carrying out its own
     inspection in country B and, depending on the circumstances and how it
     decides to rely on the decisions of country A, maybe also in country
     A. It may seem difficult and expensive to do, but remote assessment of
     manufacturers is not an easy task.
     
     There is another possibility, after receiving the WHO-type certificate
from
     country B, the authority of country C decides that it does want to
rely on
     the authority of country B, but the product has no marketing
authorization
     in country B. Then, country C needs to ask the applicant to submit
WHO-type
     certificates for all manufacturers involved including those of
country A
     if applicable, plus full data set to assess quality, plus detailed
     information to explain why the product needs to go through country B and
     why it has no marketing authorization in country B. Then, it is a
matter of
     technical judgement.
     
     One critical aspect of this case is to ascertain why a product mainly
     manufactured in country A should come from country B. In the absence of
     a logical explanation (like for example the case of two separate plants
     of the same company) one should be careful. In any case, considering A
     the country of origin is always wrong because it may shadow the role of
     what is done in country B, and it permits manufacturers of country A
     and B to escape responsibility putting the blame on each other
     endlessly. These considerations are applicable in the same way even if
     a product is entirely manufactured in country A, simply stored in
     country B, and exported from country B. The key issues are why should
     it go to country B and is there any authority in country B who is aware
     of this operation. Finally, there is nothing wrong in asking WHO-type
     certificates for all manufacturers involved and not only for the one
     responsible for releasing the final product.
     
     I hope I have not been too boring, but I have had no time to be more
     concise.
     
     Valerio Reggi
     Division of Drug Management and Policies
     WHO, Geneva
     
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