I had posted this before, but the E-Mail PO returned an undecipherable
message, so that I do not know if in fact it has been sent out. MM
=================================
After reading all the complaints about DRUG SPECIFICATIONS /Generics,
below, I felt that the misconceptions of drug manufacturing and
regulations should be set straight. The Internet provided some of the
following information.
The USP [United States Pharmacopeial Convention] and NF [National
Formulary] establishes standards for the manufacture and distribution of
drugs and related products in the US, and develops drug information that
is recognized by Federal and state legislation
http://www.usp.org/
It is available in a hardcover Edition
and on CD-ROM
and on CD-ROM in Spanish
It has become the worldwide standard of excellence
as the official compendia of acceptable
standards for
Strength
Quality
Purity
Packaging
Labeling
Storage
For drugs and excipients, the USP and NF are two of the world's most
trusted references. These combined resources, published once every five
years, contain over 3,700 monographs and also provide standards for
devices, diagnostics,
nutritional supplements, botanicals, and compounded pharmaceuticals.
The USP and NF are essential resources for pharmaceutical scientists who
must comply with official standards and for health care professionals
who are concerned about standards for articles used in their practice.
The USP/NF establishes standards for all human drugs used in this
country, and has become the standard for most of the world, BUT only
after the FDA [Food and Drug Administration] has approved them. This
approval comprises a comprehensive
and exhaustive review of all the chemical, biological, pharmacological,
and physical data provided by the manufacturer. When the FDA is
satisfied that a drug has met all the requirements stipulated in the CFR
[Code of Federal Regulations], the USP takes over the jurisdiction of
establishing the standard for the drug, BUT the FDA is the agent
responsible for enforcing these standards. After a drug has been
approved and a standard established, ALL subsequent manufacturers [e.g.,
generics] of the same drug, usually after expiration of the patent or by
license, MUST be the same standards of strength, quality, and purity
established in the original drug application.
The USP/NF compendium comprises descriptions and assays of each drug
entity and major dosage forms. Assay methodology for determining the
strength, quality, and purity of a drug depends to a large extend upon
its nature and manufacturing process. For instance, a vaccine is
usually testing 'in vivo', whereas a manufactured chemical substance
will normally be assayed by physico-chemical means. The method of
choice nowadays is HPLC [High Performance Liquid Chromatography] which
has largely replaced absolete methods because it is capable of achieving
all the desired purposes of the monograph, i.e., it provides the
qualitative and quantitative results required by law. The assays must
also be able to give accurate and precise results, where accuracy
reflects deviation from the true value and precision is a measure of the
repeatability of the test. The purer the drug substance, better
accuracy and precision can be achieved. However, drug dosage forms are
formulated with a great variety of excipients, and compressing tablets
or filling capsules identically within a range of let's
say 5% may not be easy to achieve. The monograph for Carbidopa in
Sinemet specifically requires that its content not deviate by more than
10% of the labeled amount; that variation is an aggregate of every step
in the manufacture of the drug product. When the product does not meet
the specified requirements, the FDA has the authority to take corrective
legal actions.
==================================
Will Johnston wrote:
> The variability from batch to batch of the name brand stuff can vary
as
> much or more than the variation between the generic and the name brand
> stuff. I have found more variation in Sinemet than in the generic
> equivalent from TEVA.
and Carol Walton wrote:
> My name is Carol Walton and I am a member of the Parkinson Alliance
> Executive Committee--I am usually silent on the listserv but I am
catching
> up on e-mail having just returned from the East--I was told by one of
the
> drug companies that there can be at 20% difference --plus or
minus--when
> different companies make generic drugs--therefore you could be taking
a
> brand name drug--switch to a generic and have a 40% difference--some
> companies and now trying to set a standard since this can be
devastating
> especially with Parkinsons medications--I hope some others answer you
also
> since I am not an expert in any way shape or form--but I hope this
helps
> and you might run this by your pharmacist--good luck--carol walton
and Nigel Harland wrote:
> Does anyone know what Quality Control tolerances are applied
>during the production runs of the meds' that we take? The reason I ask
>is that on several occasions recently I have experienced severely
>delayed "kick-in" of Madopar, which I normally have few problems with
so
>long as I stick to the same dosing regime.
>Having worked in a Quality Control environment for Coca-Cola and
>Schweppes soft drinks who apply strict tolerances on both the volume
and
>strength of their products, I know from experience that problems with "
>out of spec' " product do happen, especially at the start and end of
>production runs, and despite the best efforts of the Quality control
>departments some of these below standard products occasionally escape
the
>net and reach the consumer.
>Do the same problems exist in the production runs of Drugs? Could my
>delayed "kick-in" be due to a sub-standard batch of Madopar capsules?
or
>should I be looking elsewhere for the cause of the problem?
--------------------
and George J. Lussier wrote:
> This morning I read Carol Walton's posting on generics and was
reminded that
> back in 6/96 I wrote a brief note on the same issue.Sad to say that I
never
> could track down the FDA's Blue book or Red book or which ever book
> contained such a standard. And as I recall there was very little
interest
> from the list at that time. Perhaps today?
>
> >6/09/96 George Lussier wrote:
> >"Did you know that a GENERIC drug maker is allowed to make his drug
with
> >a leeway of 20%, more or less than the brand name drug. That means
that you
> >may be getting 20% more or less of the primary ingredient when you
shift
> >from the brand name to a Generic. AND if you shift from one generic
to
> >another the difference could be as much as 40%!!! Do you believe it?
I'm
> >trying to track down the chapter and verse via the FDA"
>
and Gerry & Brig Haines wrote:
> This has been mentioned often, if you are dealing with a drugstore
like
> Walgreen or Eckert, etc,,,,, according to a pharmacist, they put
contract out
> on generic drugs, therefore you can get a different supplier every
month. If
> you deal with a pharmacy as Athena, again according to a pharmacist.
you will
> have the same supplier month after month because they are a
distributor and
> deal with the same supplier every month. I hope I reported this
correctly.
> Gerry
>
Gerry,
> Even with the same supplier every month the problem still persists.
One
>batch of generics may vary +/- 20% according to FDA regs.The FDA regs
are
>the problem not the supplier.
> george
>george,
>that's interesting. :-)
>it's not often I hear the FDA being the problem.
>all the more power to ya
>Bonnie daughter of Jim 77/3
