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What is Synthroid Hiding?
If Synthroid is Safe and Effective, Why Won't It Apply for FDA Approval Like its Competitors?
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"...what do you think the FDA should do? Should they ignore Synthroid's numerous recalls and potency problems and just say "try to do better"?...And how can you think a drug company that refuses to bring its product up to standard is in your best interest?...I can't see any reason to defend their behavior."
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  Related Resources
•  Food and Drug Administration Approves Unithroid, First New Drug Application for Thyroid Drug Levothyroxine Sodium
•  Synthroid and other Levothyroxine Drugs Have Significant Stability and Potency Problems
• Synthroid Still Lacks Approval Necessary to Remain Legally on the Market After August 14, 2001
• FDA Report on Levothyroxine
 
 Elsewhere on the Web
•  FDA Summary of the New Drug Application Process
•  New Drug Application Process Flowchart
•  Drugs and the New Drug Application (NDA) Process
 
 

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.

(KnollR BASF Pharma letterhead)

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. -- U.S. 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 U.S. 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.





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