ANSWER: FDA has asked that within 30 days, companies respond with their plans to either repeat their bioequivalence studies at a site other than Panexcell or Synchron, or voluntarily withdraw their products from the market. FDA has changed the therapeutic equivalence (TE) rating for the affected generic products in Approved Drug Products with Therapeutic Equivalence Evaluations (commonly referred to as the “Orange Book”) to “BX.” This means that the data are insufficient to show that the generic products affected provide the same therapeutic effect as the brand name product. A drug with a “BX” rating is still approved and can be prescribed but is not recommended as automatically substitutable at the pharmacy (or by a pharmacist) for the brand-name drug.
ANSWER: FDA continues to conduct an investigation of postmarket safety reports for marketing applications of drugs that relied on bioequivalence studies conducted at Panexcell and Synchron facilities for approval, and to date has not identified reports that raise signals of serious safety risks with these products.
FDA monitors adverse event reports for brand name and generic drugs. The monitoring of adverse events, including reports of therapeutic inequivalence, is one aspect of the overall FDA effort to evaluate the safety of all drug products. Many times, reports of adverse events describe a known reaction to the active drug ingredient.
Reports are monitored and investigated, when appropriate. Complaints related to therapeutic inequivalence are carefully investigated. The investigations may lead to changes in how a product (brand name and generic counterparts) is used or manufactured.
Patients should not make changes to their treatment except in consultation with their health care professional. If you, or those under your care, are taking any products with a therapeutic equivalence rating of “BX” and have concerns, contact the prescribing health care provider to discuss whether or not a different drug would be more appropriate.
ANSWER: FDA has restrictions on what it can legally disclose, because it is confidential information whether a particular drug applicant uses a particular contract research organization for studies it submits. Currently FDA has not identified any approved, marketed brand name products affected by the data integrity issue. However, if you are concerned about whether a generic drug you are taking has a “BX” rating, you can go to the Orange Book website and look up that drug. Type in the name of your drug and, in the list that comes up, look for the name of the manufacturer that appears on the bottle. Then look, for the drug and manufacturer, in the column TE Code. If the code is “BX,” you may wish to consult with your health care provider about continued use of the drug. (Many drugs have a “BX” rating for reasons unrelated to this action, but the drugs affected by this action have, as noted, had their ratings changed to “BX.”)
You can also look up your drug in the Orange Book by the drug’s new drug application (NDA) number or abbreviated new drug application (ANDA) number. To find the ANDA or NDA number you will first need to find the National Drug Code (NDC) number listed on the bottle, or ask your pharmacist if this information is not available. You can enter the NDC number into the National Drug Code Directory to find the NDA or ANDA number for your drug. Once you have the NDA or ANDA number you can search the Orange Book website with that number.
ANSWER: A drug with a “BX” rating is still approved and can be prescribed but is not recommended as automatically substitutable at the pharmacy (or by a pharmacist) for the brand-name drug. To market a generic drug, a manufacturer must demonstrate, among other things, that its product is bioequivalent to an FDA-approved reference listed drug. Bioequivalent products are those that demonstrate a similar rate and extent of absorption of the therapeutic ingredient (the drug and/or active metabolite). Methods to establish bioequivalence vary by the type and nature of the drug. FDA publishes recommendations on how to establish bioequivalence for many drugs on the FDA website.
Generic drugs that are pharmaceutically equivalent and have been shown to be bioequivalent to the reference listed drug generally are given a therapeutic equivalence (TE) code of therapeutically equivalent (or “AB”). TE codes are a standard format for representing known information about a specific generic drug. TE codes provide guidance to health care professionals regarding whether different prescription drug products are therapeutically equivalent to one another. More complete information about the coding system is on the FDA’s website.
ANSWER: FDA has notified Panexcell and Synchron that it is their responsibility to develop, implement, and execute corrective and preventive actions that are sufficient to ensure these, and similar types of violations do not occur in future studies conducted by either site. Panexcell and Synchron will be required to address these system-wide failures to ensure sustained compliance with FDA regulations. FDA will work with Panexcell and Synchron to ensure that the corrective and preventative actions are adequate.
ANSWER: These are two different companies, and their inspections were not associated. However, during FDA’s assessment of these companies, we realized there were similar data integrity violations. In an effort to be fair and consistent in our activities, we are managing both situations through similar steps and timeframes.