FDA Letter on Generic Drugs

[James Love <love@cptech.org>]

Does anyone know much about this?  Jamie

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                      Therapeutic Equivalence of Generic Drugs
                            Letter to Health Practitioners

January 28, 1998

Dear Colleague:


As you may be aware, certain individuals and groups have appeared
recently before state legislatures, state boards of pharmacy, and drug
utilization review committees, to express concerns about the
interchangeability of certain products they characterize as narrow
therapeutic index (NTI) drug products. A particular concern being raised
by them is whether the safety and efficacy profile of these products
could change if a switch were made from a brand-name product to an
FDA-designated therapeutically equivalent generic product. FDA wishes to
comment on the issue of interchanging any brand-name drug with a
therapeutically equivalent generic drug and requests that you inform
your association's members of this information.

For both brand-name and generic drugs, FDA works with pharmaceutical
companies to assure that all drugs marketed in the U.S. meet
specifications for identity, strength, quality, purity and potency. In
approving a generic drug product, the FDA requires many rigorous tests
and procedures to assure that the generic drug is interchangeable with
the brand-name drug under all approved indications and conditions of
use. For these reasons, FDA approved product labeling does not recommend
that any additional tests need to be performed by the health care
provider when a switch occurs from a brand-name drug product to a
generic equivalent drug product, from a generic equivalent to a
brand-name product drug, or from one generic product to another when
both are deemed equivalent to a brand-name drug product. Brand-name drug
products and therapeutically equivalent generic drug products are
identified in the FDA publication, "Approved Drug Products with
Therapeutic Equivalence Evaluations," frequently called the "Orange
Book." 

In addition to tests performed prior to market entry, FDA regularly
assesses the quality of products in the marketplace and thoroughly
researches and evaluates reports of alleged drug product inequivalence.
To date, there are no documented examples of a generic product
manufactured to meet its approved specifications that could not be used
interchangeably with the corresponding brand-name drug. Questions have
been raised in the past, as well, regarding brand name and generic
products about which there could be concern that quality failures might
represent a public safety hazard. FDA has performed post-marketing
testing on many of these drugs to assess their quality. In one instance,
more than 400 samples of 24 marketed brand-name and generic drug
products were tested and found to meet the established standards of
purity and quality. Because
patients may pay closer attention to their symptoms when the
substitution of one drug product for another occurs, an increase in
symptoms may be reported at that time, and anecdotal reports of
decreased efficacy or increased toxicity may result. Upon investigation
by FDA, no problems attributed to substitution of one approved drug
product for another has occurred. 

FDA works with both brand-name and generic drug product manufacturers
after a drug product is in the marketplace to assure its quality. For
example, brand-name and generic drug product manufacturers may want to
change the drug formulation, site of manufacture, or manufacturing
process after the drug is in the marketplace. These types of changes can
be put in place only after the drug manufacturer provides the FDA with
sufficient evidence that the drug identity, strength, quality, purity
and potency will not change. 

There are products in which small changes in the dose and/or blood
concentration could potentially result in clinically important changes
in drug efficacy or safety. Usually, these drugs require frequent
adjustments in the dose of the drug and careful patient monitoring
irrespective of whether the drug is a brand or generic drug product.
These drugs may sometimes be described in FDA approved drug labeling as
narrow therapeutic range drugs. 

FDA may recommend to the manufacturers additional tests for approval of
both brand-name and generic products, depending on the complexity of a
drug substance or drug product and also depending on whether small
changes in the dose and/or blood concentration could result in changes
in drug efficacy or safety. It may also require additional tests for
certain post-approval changes in manufacturing. The agency's
recommendation to the manufacturer for these additional tests is
designed to give the practitioner and patient additional assurance of
product quality and interchangeability. These additional requirements
should
not be construed to mean that additional clinical scrutiny is necessary
when interchange occurs. If anything, the additional tests required of
pharmaceutical manufacturers are designed to reduce, not increase,
concerns on the part of patients and practitioners. 

Based on FDA's determination of therapeutic equivalence between generic
and innovator drug products, the FDA concludes that: 

-	Additional clinical tests or examinations by the health care provider
are not needed when a generic drug product is substituted for the
brand-name product.  

-	Special precautions are not needed when a formulation and/or a
manufacturing change occurs for a drug product provided that the change
is approved according to applicable laws and regulations by the FDA. 

-	As noted in the "Orange Book," in the judgment of the FDA, products
evaluated as therapeutically equivalent can be expected to have
equivalent clinical effect whether the product is brand name or generic
drug product.

-	It is not necessary for the health care provider to approach any one
therapeutic class of drug products differently from any other class,
when there has been a determination of therapeutic equivalence by FDA
for the drug products under consideration. 

In considering drug product selection decisions, FDA acknowledges and
supports the importance of good communication between the patient and
the health care provider, particularly with regard to medications that
require frequent monitoring of performance. We hope this information is
useful to health care providers when making decisions regarding drug
product selection. We thank you for seeing that this information reaches
the members of your organization. 

Sincerely,
Stuart L. Nightingale, M.D.
Associate Commissioner for Health Affairs



February 4, 1998
http://www.fda.gov/cder/news/nightgenlett.htm 

-- 
James Love
Consumer Project on Technology
P.O. Box 19367, Washington, DC 20036
love@cptech.org | http://www.cptech.org
202.387.8030, fax 202.234.5176