FDA Q&A with Jim Strickland


Question:  Barron’s reports in an article on Heather Bresch from Mylan, that the FDA had not inspected some foreign manufacturing plants in 13 years, attributing the figure to Peggy Hamburg.  Can you comment? 

Response: Yes, as noted in this fact sheet, the FDA has only had resources to conduct inspections of foreign generic drug manufacturers about once every 7 to 13 years. http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDASIA/ucm310992.htm

Question: Pew reports to me that 80% of APIs are foreign sourced, and 40% of all medications are foreign made.  Can you confirm these figures or give me your own?

Response: In a 2012 speech, FDA Commissioner Margaret A. Hamburg, M.D., said this, “…up to 40% of all drugs Americans take are imported…and up to 80% of the active pharmaceutical ingredients in those drugs come from foreign sources.”  http://www.fda.gov/NewsEvents/Speeches/ucm294978.htm

Question: GDUFA is aimed at speeding approvals and stepping up inspections of foreign manufacturers.  What’s the timetable for these stepped up inspections to begin.

Response: To clarify, the Generic Drug User Fee program is aimed at funding all aspects of generic drug review, not just inspections. The program is up and running, we have collected almost $125 million in fiscal year 2013 user fees that will help us begin recruiting and training additional staff we need to achieve the program’s performance goals. A key feature of the new program is requiring manufacturers to self-identify to help us build a new database of facilities. As a result, we now have a list of 2,000 foreign and domestic facilities involved in supplying generic drug products to the U.S. market. Before the user fee program, the disparity in the degree of oversight experienced by domestic versus foreign facilities created an uneven playing field. Within five years, we will be able to conduct biennial inspections for both domestic and foreign facilities, allowing us to identify any noncompliant players in the drug supply chain -- wherever they are based – so we can focus on the generic drug industry worldwide.  (More information: http://www.fda.gov/NewsEvents/Speeches/ucm340870.htm)

Question: While FDA tests generics for bio equivalence, I’m told they do not test actual therapeutic results.  Please explain exactly how FDA tests a generic before approval, and whether FDA relies on the manufacturer’s data or whether FDA tests themselves.

Response: The FDA does some drug testing, but generally for both brand name and generic drugs, the sponsors of the application do the testing and submit their results to us. Drug companies must submit an abbreviated new drug application (ANDA) for approval to sell a generic product. That process does not require the drug sponsor to repeat costly animal and clinical research on ingredients or dosage forms that are already FDA-approved for safety and effectiveness. 

The generic drug approval process as established by the Hatch-Waxman Amendments does not require generic drug manufacturers to submit nonclinical or clinical studies to establish the safety and efficacy of the active ingredient. This is because these safety and efficacy data were previously documented during the approval process for the brand product. It is assumed that, if the active ingredient was shown to be safe and effective after it is absorbed into the bloodstream, any drug product giving rise to blood concentrations of active ingredient to the same rate and extent will produce the same effect.

The generic drug manufacturer must submit data to the FDA to prove its drug is the same as (bioequivalent) the brand name drug. For example, after the patient takes the generic drug, the amount of drug in the bloodstream is measured.  If the levels of the drug in the bloodstream are the same as the levels found when the brand name product is used, the generic drug will work the same. Through review of bioequivalence data, FDA ensures that the generic product performs the same as its respective brand name product. All generic manufacturing, packaging, and testing sites must pass the same quality standards as those of brand name drugs, and the generic products must meet the same exacting specifications as any brand name product. In fact, many generic drugs are made in the same manufacturing plants as brand name drug products.

Question: Why did the OGD go so long without leadership from 2010 to 2012, and with Geba gone after such a short time, should the public have confidence in FDA’s handling of generics…considering they account for 84% of drug sales?

Response: The Office of Generic Drugs has not gone without leadership. Interim leadership has been appointed during gaps and there has been consistent involvement of the Center for Drug Evaluation and Research's director, Dr. Janet Woodcock.  As well, much of the Office's scientific and professional staff has remained consistent over the years.

Question: Why did FDA only test 150 mg generic Wellbutrin instead of the 300 mg as well? 

Response: To clarify, the FDA did not do the original testing and standard procedure is that the companies do the testing. At the time of the approval of the Teva/Impax drug Budeprion XL 300 mg, FDA permitted Impax, and other sponsors of the same product, to conduct bioequivalence studies on the 150 mg strength of the drug and to extrapolate the results to establish bioequivalence of the 300 mg product. Typically, FDA’s Center for Drug Evaluation and Research recommends that the highest strength of a drug be used to establish bioequivalence to support a generic drug approval. In the case of extended-release bupropion, the 300 mg strength of the drug was not used in bioequivalence studies due to concerns that this higher strength of the drug could cause seizures in healthy adult volunteers.  Therefore, FDA granted Impax a waiver, and the company was not required to perform a bioequivalence study at the 300 mg strength but, instead, performed its bioequivalence studies on the next lower strength, 150 mg. This practice is known as “waiving up.”  When it is thought that a bioequivalence study using the higher strength of a drug product line may cause unacceptable adverse events in healthy adult volunteers, FDA may recommend or consent to “waiving up.” More information: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm322160.htm

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