This is from Mary Shomon's site on About.com (Although it's off-topic for
now, thyroid discussions happen from time to time here):


If Synthroid is Safe and Effective, Why Won't It Apply for FDA Approval Like
its Competitors?
by Mary J. Shomon

Apparently, my article from February 15, 2001, titled "Synthroid Still Lacks
Approval Necessary to Remain Legally on the Market After August 14, 2001"
raised concern among the management of Knoll Pharmaceuticals, the
manufacturer of Synthroid.
Thanks to a friendly reader and her pharmacist, I received a copy of the
following letter, dated February 22, 2001, which according to the
pharmacist, was being aggressively distributed by Knoll to doctors and
pharmacists around the country, as a response to my article.
First, read the actual letter being sent by the Synthroid manufacturer, then
let's take a look at some of the concerns it raises.

February 22, 2001
Dear Dr. ___________:
As you know, millions of patients rely on SYNTHROIDR (levothyroxine sodium
tablets, USP) every day to control hypothyroidism. As the makers of
SYNTHROID, we are grateful for your support and proud of the role we play in
maintaining your patients' good health.
Unfortunately, it has come to our attention that inaccurate and misleading
information has been circulating about SYNTHROID.
We are writing today to set the record straight. Here are the facts:
SYNTHROID has been recognized as safe and effective for more than 40 years
To ensure product quality, we manufacture SYNTHROID in strict accordance
with all FDA rules and regulations and subject to FDA inspection.
We are pleased to note that SYNTHROID continues to meet those regulations
and our manufacturing facility routinely passes inspection, including
meeting all standards for stability and potency
Because of the long history of use, Knoll Pharmaceutical Company was able to
petition the US Food and Drug Administration (FDA) to recognize SYNTHROID as
"generally recognized as safe and effective." This action complies with the
FDA August 1997 Federal Register Notice regarding oral levothyroxine
products and is an acceptable alternative to filing an NDA
We do not foresee any circumstances under which SYNTHROID will fail to be
available for hypothyroid patients. We will continue to support SYNTHROID
for physicians and the more than 9 million patients who rely on it.
We hope this reassures you of our continuing commitment to you and your
patients. Many people depend on SYNTHROID. We work hard to remain worthy of
their trust.
Sincerely,
David R. Hathaway, MD
VP, Medical Affairs Gary D. Dolch, PhD
VP, Quality Assurance


The Real Facts About Synthroid and the New Drug Application
The above letter is an example of the lengths to which the marketing
department of Knoll Pharmaceutical will go to maintain market share for
their product.
Now, let's take a look at the actual facts.
Synthroid has never gone through the Food and Drug Administration (FDA)
approval process. It was grandfathered in under the FDA's recognition of the
safety and effectiveness of the natural desiccated thyroid drug, Armour
Thyroid, which is made from the gland of pigs, and contains two forms of
thyroid hormone, T4 and T3. Synthroid, however, is a synthetic drug that
contains the synthetically manufacturered form of only one hormone, T4.
While the manufacturer states that "Synthroid has been recognized as safe
and effective for more than 40 years," in 1997, the FDA said otherwise when
they issued a very unusual requirement that levothyroxine drugs -- including
Synthroid -- be required to go through a new drug application (NDA) process,
as if they were a new drug that had never been on the market before.
In issuing its requirement for an NDA, the FDA stated:
"...no currently marketed orally administered levothyroxine sodium product
has been shown to demonstrate consistent potency and stability and, thus, no
currently marketed orally administered levothyroxine sodium product is
generally recognized as safe and effective." -- U.S. FDA
The FDA itself, therefore, contradicts Synthroid's statement.
The letter claims that "...our manufacturing facility routinely passes
inspection." Patients, however, should ask what this has to do with ensuring
product quality and safety, given that the FDA has called for the drug --
and not a facility -- to go through the NDA process in order to ensure
product quality, safety and effectiveness for patients.
While the letter indicates that Knoll has filed a petition with the US FDA
to recognize Synthroid as "generally recognized as safe and effective," such
status has not been granted by the FDA to Synthroid to date.
Again, the FDA's justification for the nearly unprecedented act of calling
for new drug application on a drug that had been on the market for more than
40 years was that "No currently marketed orally administered levothyroxine
sodium product is generally recognized as safe and effective."
The letter states that "We do not foresee any circumstances under which
SYNTHROID will fail to be available for hypothyroid patients."
This seems to be an optimistic statement, given that, as indicated above,
the FDA clearly stated that "No levothyroxine sodium product is generally
recognized as safe and effective," and has so far failed to approve Knoll's
application for such status, yet has reviewed and approved Unithroid, the
levothyroxine product manufactured by Jerome Stevens Pharmaceuticals, in
August of 2000.
In the meantime, as of March 2001, Knoll has still not filed an NDA for
Synthroid, but has managed to force the FDA to extend its original deadline
of August 2000 to the new deadline of August 2001, mainly to accommodate a
variety of bureaucratic requests made by Knoll.
What's Legal? What's Approved? And By When?
As of March 30, 2001, Unithroid is the only FDA-approved levothyroxine
product on the market, and recently, the FDA has made Unithroid the
"Reference Drug Listing" for levothyroxine.
Synthroid, Levoxyl, Levothroid and the other competitors are still legal to
sell, because the FDA deemed them necessary drugs that should remain legal
to sell while the NDA process was completed. They are NOT, however, products
that have gone through the FDA approval process.
If your doctor or pharmacist tells you otherwise, they are misinformed.
In order to remain legally available after August of 2001, Synthroid and the
other levothyroxine products besides Unithroid will either need to receive
an approved NDA, or will have to successfully argue, as Synthroid is
attempting, that these NDA requirements do not apply to their product, and
they should be exempt from the application process, instead receiving what's
known as "Generally Recognized as Safe and Effective (GRAS/E)" status. This
status would allow them to bypass the NDA testing and approval process.
It is not likely that the deadline will be further extended, as seen in a
recent letter from the FDA's Association Commissioner for Regulatory
Affairs, Dennis E.Baker, to representatives of Jerome Stevens
Pharmaceuticals, in which he states "At present, the August 14, 2001,
deadline remains in place, and FDA has no plans to extend the date by which
levothyroxine sodium products must have approved applications."
Benefits to Patients of the Drugs Going Through the New Drug Application
Process
Full Information About Safety, Effectiveness, Doses and Side Effects-- The
New Drug Application process is a detailed process in which a drug
manufacturer must scientifically demonstrate to the FDA that the drug being
submitted is safe and effective, at what doses it works best, and what side
effects it causes.
This is important -- potentially even life-saving -- information that is
essential for health professionals to properly prescribe, pharmacists to
properly dispense, and patients to safely take levothyroxine.
Information About Side Effects -- Because levothyroxine sodium products are
prescription drugs currently marketed without approved NDAs, manufacturers
until now have been required to report only those adverse drug experiences
that are unexpected and serious.
They are not required to report all adverse drug experiences, including
expected or less serious events. Once approved via NDA, however, all adverse
drug experiences, including expected or less serious events, are
periodically required to be filed with the FDA. This sort of information on
side effects and problems is information that is essential for patient
safety.
Ensured Stability, Potency and Safety for Patients -- In approving Unithroid
last August, the FDA wrote:
Although oral levothyroxine drugs products have been marketed in the United
States since the 1950's, the approval of Unithroid represents the first time
that a single ingredient oral levothryoxine product has been approved by the
FDA.
The unapproved thyroid hormone replacement products that have been on the
market have been associated with stability and potency problems. These
problems have resulted in product recalls and have the potential to cause
serious health consequences to the public.
With the approval of the NDA for Unithroid, patients and physicians now have
available to them an oral levothryroxine sodium drug product that has been
determined to be safe and effective by the FDA and that also meets FDA
standards for manufacturing processes, purity, potency, and stability. -- US
FDA
Questions Patients Should Ask
Ask yourself why the FDA would have taken the unusual step of calling for a
new drug application on a drug that had been available for decades unless
there were, as they stated, safety and effectiveness concerns that posed a
clear risk to public health.
Synthroid is the top-selling thyroid drug on the market, and one of the top
five drugs sold in the United States.
Its manufacturer, Knoll, was a division of one huge multinational company
BASF, until it was recently sold to another huge multinational drug company,
Abbott Labs. One would think that Synthroid would be easy to obtain approval
for, especially vis a vis an unknown product of a small family-owned drug
manufacturer, which, while it was making levothyroxine products for ten
years, has never had a well-known brand name, marketing clout, or any
influence with the FDA.
Yet the Jerome Stevens company was able to apply for and receive approval
for its levothyroxine product, within the FDA's original deadline of August
of 2000. One needs to ask how a "little guy" like Jerome Stevens was able to
obtain approval within the three-year deadline, when the uncontested
industry giant has yet to even apply, more than 3 1/2 years after the FDA
called for new drug applications.
Given that the FDA, in approving a levothyroxine product, continued to
discuss the stability and potency problems and serious health consequences
of the other products, it seems that it's in the public's best interest for
all levothyroxine products to go through the approval process. Ask why and
how, at this late point, the FDA would possibly reverse this concern and
grant "generally recognized as safe and effective" status to Synthroid or
any other levothyroxine product while still claiming to protect public
health.
If you want to take Unithroid, and your pharmacist tells you that they
cannot get Unithroid for you, ask them why they are not carrying the only
FDA-approved levothyroxine product?
Are they financially benefitting by offering only competitors' product? Are
they receiving financial incentives for promoting one particular
levothyroxine?
And if they refuse to get Unithroid -- which is being marketed through
Watson Pharmaceuticals, and is easily available to all US pharmacies -- then
ask your pharmacy if they would like you to take your business elsewhere, to
another pharmacy that is not unduly influenced by drug company marketing,
and will make the only FDA-approved levothyroxine available to patients.
Ask yourself why is Knoll Pharmaceutical attempting to bypass the NDA
process for Synthroid, therefore effectively bypassing important safety
measures for patients?
It would seem that it can only benefit the more than 9 million patients
taking levothyroxine products that all the competing drugs available --
including Synthroid -- be required to go through this same evaluation
process, in order to ensure product safety and effectiveness.
In Knoll's letter, they state, "Many people depend on SYNTHROID. We work
hard to remain worthy of their trust."
Ask yourself if the more than 9 million thyroid patients taking
levothyroxine products should ultimately trust a product that has not gone
through FDA approval.
Ask yourself if the more than 9 million patients taking levothyroxine should
be able to take their drugs each day, secure in the knowledge that all
levothyroxine products on the market have met the same stringent safety and
effectiveness standards.