E-drug: Re: WHO prequalification withdrawals and bio-tests (cont'd)
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[The message to which Francisco responds never reached the moderator
although he had sent it both to E-drug and to Francisco so you can find
it below. KM]
I'm not sure if it will be useful to go deeper in this debate. It will
be a
decision of the moderators. But I think this message gave me an
opportunity
to more clarification about this uncomfortable issue.
I think it is important to precise some points.
1.- Why, when one ask about pertinence of bioequivalence tests for ARV,
or
any other drugs, automatically somebody assume that one are against the
duty
of demonstrate quality of generic drugs? So, quality is only,
bioequivalence? In other words, the only one and unavoidable way to
demonstrate the quality of a generic version of any drug is
bioequivalence?
(What about intravenous drugs?)
2. Pertinence means that you do some test only when it is really
necessary.
You can ask all producers of generic drugs for radioactive residues
tests ,
but I think it is easy to reach an agreement about pertinence. These
tests
are pertinent only in very small, well defined cases. We can add some
examples: potency (antibiotics), crystallography (crystals), etc. It is
a
joke to make a dissolution or disintegration test for an inhaler.
3. Bioequivalence means similar bioavailability between two
formulations. No
more. No less. In which drugs, for which therapeutic indications, is it
relevant? Is anyone interested in bioequivalence for "memory and
concentration improvers? Is it not true that, for chemical and physical
reasons, most of molecules are not expected to have significant
bioavailability differences? What is the main intention of the
biopharmaceutical classification of the FDA?
4. In this order of ideas, every generic drug must demonstrate quality
by
the pertinent test of the molecule, dosage form and other
specifications.
Don't forget the importance of package and labeling about quality.
Sometime
health authorities reject products due to critical defects on labeling.
And
of course it is relevant I think.
5. So, the question is: Oral dosage forms of ARV need bioequivalence
test?
While this point is properly discussed, let me try to clarify other
issue.
Safety and efficacy are demonstrated by pre-clinical and clinical tests.
No
more. No less. Bioequivalence tests are really far from this kind of
tests.
So, a generic version of any drug must repeat pre-clinical and clinical
tests? The answer is no. Especially, for ethical reasons. Safety and
efficacy need demonstration for a chemical entity, a molecule, and a
particular dosage form. And when safety and efficacy where demonstrated,
it
is necessary to establish a quality standard, both for innovator and
generic
versions. Then, health authorities must decide if a generic version of a
specific drug, need bioequivalence test as a quality assurance
requirement.
Or not.
So, generics do not demonstrate safety and efficacy, and they are not
guilty
about it. Particular conditions of drugs are the reason.
Maybe one can argue that it is not fair with innovators...but I think it
will open other discussion. Very relevant I'm afraid, but not now.
Thanks
Francisco A. Rossi. B.
IPR and access to drugs project.
International Poverty Center.
UNDP - IPEA.
SBS. Ed BNDES, 10 andar.
70076-900 Brasilia D.F. Brazil.
(55 61) 2105 -5005
francisco_rossi@hotmail.com
This issue is crucial.
We are talking about: Efficacy, Safety and Quality,
For generics this standards are also required.
If you have chemical formulary - it can be reproduced by dozens of
professionals. Does it mean that reproduced formulary would have the
same efficacy, safety and quality?
Of cause - no! Somebody have to prove that reproduced (generic)
formulary
fulfil all three standards.
Chemical equivalent is not usually equivalent therapeutically.
We are talking about ARVs.
For everybody (mean who pay for ARVs) very important is to have not
only
GMP (quality).
If ARV is not effective (GCP) we will face resistance. Who would be
happy
with this?
Quality can not be assessed, tested or inspected into the product. It
has
to be built into it.
With limited resources WHO pre-qualification project make a very
important job.
Somebody has to be responsible to prove that product meat
international/WHO
standards (GLP, GCP, GMP).
Suppose, I am person/investor/donor/NGO/etc. I need somebody to prove,
that
my investments would be spend more effectively.
Who will assess evidence..
For local government/budget it can be local regulatory authority.
Internationally I would like to have WHO in this case.
Especially when we are talking about HIV/AIDS in developing world with
weak
regulations, leak of professionals etc.
Those countries need such approval until they would create own
expensive
agencies as FDA or MCA.
Only then local agencies would guarantee on the local/international
level
that quality is built into a product.
Finally. CIPLA and Ranbaxy are good enough.
Generic substitution is very important to accelerate access to drugs.
And at the same time to be sure that generics meet the same
requirements
(in terms of Efficacy, Safety and Quality)
I prefer to use WHO PQ list rather than results of
assessment/registration
of products especially in developing countries.
Dr Alexander Polishchuk
22 Volynska street, #24,
03151, Kiev, Ukraine
Tel: +38044 2429040
Mailto:alexpoly@ln.ua
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