Department of Justice files consent decree of permanent injunction against Ranbaxy

January 25, 2012. The Department of Justice, on behalf of the U.S. Food and Drug Administration, has filed a consent decree of permanent injunction against generic drug manufacturer Ranbaxy in the U.S. District Court of Maryland. The consent decree was filed against Ranbaxy Laboratories, Ltd., an Indian corporation and its subsidiary Ranbaxy Inc., headquartered in Princeton, N.J. Ranbaxy Labs.’ Dale Adkisson, senior vice president, head of global quality and Arun Sawhney, chief executive officer and managing director, and Ranbaxy, Inc.’s Venkatachalam Krishnan, regional director Americas, were also named as defendants. The consent decree will address outstanding current good manufacturing practice (CGMP) and data integrity issues at Ranbaxy’s Paonta Sahib, Batamandi and Dewas, India facilities as well as CGMP issues at Ranbaxy Inc.'s wholly owned subsidiary Ohm Laboratories facility located in Gloversville, N.Y. 

Ranbaxy’s Paonta Sahib, Batamandi, and Dewas, India facilities have been on FDA import alert since 2008 and Ranbaxy has closed its  Gloversville facility. The public should not be concerned that any drugs from those facilities are currently in the U.S. market. FDA recommends that patients not disrupt their drug therapy because this could jeopardize their health. Individuals who are concerned about their medications should talk with their health care professional.

The consent decree requires that Ranbaxy comply with detailed data integrity provisions before FDA will resume reviewing drug applications containing data or other information from the Paonta Sahib, Batamandi, and Dewas facilities.  Specifically, Ranbaxy must:

(1) hire a third party expert to conduct a thorough internal review at the facilities and audit applications containing data from the affected facilities;

(2) implement procedures and controls sufficient to ensure data integrity in the company’s drug applications; and

(3) withdraw any applications found to contain untrue statements of material fact and/or a pattern or practice of data irregularities that could affect approval of the application. 

In addition, the consent decree prevents Ranbaxy from manufacturing drugs for introduction to the U.S. market and for the President’s Emergency Plan for AIDS Relief (PEPFAR) Program at the Paonta Sahib, Batamandi, Dewas, and Gloversville facilities until drugs can be manufactured at such facilities in compliance with U.S. manufacturing quality standards. 

“Because this company continued to violate current good manufacturing practice regulations and falsify information on drug applications, the FDA took these actions in an effort to protect consumers,” said Dara Corrigan, FDA associate commissioner for regulatory affairs. “The FDA continues to be committed to protecting consumers from potentially unsafe products that may be offered on the market.”

Under this agreement, once Ranbaxy has achieved compliance with the data integrity requirements, a third party expert must conduct audits of the facilities to confirm that compliance is being maintained.  The company must authorize an individual to be responsible for all quality assurance and quality control activities to ensure that drugs have the required safety, identity, strength, quality, purity, and potency and are in compliance with the law and the decree.  In addition, they must establish an Office of Data Reliability to conduct pre-submission audits of all applications submitted from any facility after entry of the decree.

Ranbaxy has agreed to relinquish any 180-day marketing exclusivity that it might have for three pending generic drug applications, and the firm has further agreed to relinquish any 180-day marketing exclusivity that it may have for several additional generic drug applications if it fails to meet certain decree requirements by specified dates.

The consent decree contains liquidated damages provisions to cover many potential violations of the law and the decree. In addition to a provision requiring Ranbaxy to pay $15,000 in liquidated damages for each day defendants violate the law or the decree at the facilities covered by the decree and an additional sum of $15,000 for each overall violation of the law and the decree, the decree states that:  (1) if defendants distribute any drug from the facilities covered by the decree, Ranbaxy shall pay liquidated damages equal to two times the retail value of such drug, not to exceed 10 million dollars in any one calendar year; and (2) if defendants submit an untrue statement in connection with any application they file with FDA, Ranbaxy shall pay up to three million dollars in liquidated damages for each such statement, not to exceed 30 million dollars in any one calendar year. 

The decree also permits FDA to order additional Ranbaxy facilities to be covered by the decree if the agency discovers through an inspection that the facility is not operating in compliance with the law and/or has serious data integrity issues. 

The decree was filed on January 25, 2012, and is subject to court approval.x

FDA approves Inlyta to treat patients with a type of advanced kidney cancer

Jan. 27, 2012. The U.S. Food and Drug Administration today approved Inlyta (axitinib) to treat patients with advanced kidney cancer (renal cell carcinoma) who have not responded to another drug for this type of cancer.

Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes in the kidney. Inlyta works by blocking certain proteins called kinases that play a role in tumor growth and cancer progression. Inlyta is a pill that patients take twice a day.

“This is the seventh drug that has been approved for the treatment of metastatic or advanced kidney cell cancer since 2005,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Collectively, this unprecedented level of drug development within this time period has significantly altered the treatment paradigm of metastatic kidney cancer, and offers patients multiple treatment options.”

Recently approved drugs for the treatment of kidney cancer include sorafenib (2005), sunitinib (2006), temsirolimus (2007), everolimus (2009), bevacizumab (2009) and pazopanib (2009).

The safety and effectiveness of Inlyta were evaluated in a single randomized, open-label, multi-center clinical study of 723 patients whose disease had progressed on or after treatment with one prior systemic therapy. The study was designed to measure progression-free survival, the time a patient lived without the cancer progressing. Results showed a median progression-free survival of 6.7 months compared to 4.7 months with a standard treatment (sorafenib).

The most common side effects observed in greater than 20 percent of patients in the clinical study were diarrhea, high blood pressure (hypertension), fatigue, decreased appetite, nausea, loss of voice (dysphonia), hand-foot syndrome (palmar-plantar erythrodysesthesia), weight loss, vomiting, weakness (asthenia) and constipation.

Patients with high blood pressure should have it well-controlled before taking Inlyta. Some patients who took Inlyta experienced bleeding problems, which in some cases were fatal. Patients with untreated brain tumors or gastrointestinal bleeding should not take Inlyta.

Inlyta is marketed by New York City-based Pfizer Inc.

For more information:

FDA: Office of Hematology and Oncology Products

FDA: Approved Drugs: Questions and Answers

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.x

FDA completes work on three drug user fee programs

FDA.For Immediate Release: Jan. 13, 2012. The U.S. Food and Drug Administration has completed its recommendations for three user fee programs that will help speed safe and effective drugs and lower-cost generic drug and biosimilar biological products to patients, FDA Commissioner Margaret A. Hamburg, M.D. said today. The recommendations were transmitted to Congress today by Health and Human Services Secretary Kathleen Sebelius.

The programs include the fifth authorization of the Prescription Drug User Fee Act (PDUFA), and new user fee programs for human generic drugs and biosimilar biological products. Work on the proposals was concluded before the agency’s mid-January deadline.

Under a user fee program, industry agrees to pay fees to help fund a portion of the FDA’s drug review activities while the FDA agrees to overall performance goals such as reviewing a certain percentage of applications within a particular time frame.

“These final recommendations offer a great example of what can be achieved when the FDA, industry and other stakeholders work together on the same goal,” Hamburg said. “At a time of greater budgetary constraint, user fees provide a critical way for leveraging appropriated dollars, ensuring that FDA has the resources needed to conduct reviews in a timely fashion.” 

Said Hamburg: “Human drug user fees have revolutionized the drug review process in the United States since they were adopted 20 years ago, allowing the FDA to speed the application review process without compromising the agency’s high standards.”

The proposed user fee programs for generic drugs and biosimilars are modeled on the successful PDUFA program “which has ensured a predictable, consistent, and streamlined premarket program for prescription drugs,” Hamburg said.  As a result of the continued investment of PDUFA resources, the United States now leads the world in first introduction of novel drugs.

PDUFA was created by Congress in 1992 and must be reauthorized every five years. The current program, known as PDUFA IV, will expire on Sept. 30, 2012, unless reauthorized by Congress. FDA’s recommendations for PDUFA V were developed in consultation both with drug industry representatives and with patient and consumer advocates.

Under the recommendations, fees paid by industry would support continued timely review of critical prescription drugs, as well as advance the development of drugs for rare diseases, provide for enhanced communication with small or emerging companies, increase the use of standardized electronic data to improve quality and efficiency, and foster the use of new clinical endpoints that improve drug development times and help address unmet medical needs.

The proposed new Generic Drug User Fee program would provide the FDA with needed funding at a time when generic drug applications are on the rise. Generic drug user fees would help ensure consumers timely access to safe, high-quality and effective generic drugs, which account for two-thirds of all prescriptions dispensed in the U.S.

The FDA receives 800 to 900 new generic-drug-related applications annually. These applications are increasingly complex and frequently involve products manufactured outside of the U.S. In exchange for fees on facilities and product applications, the proposal includes performance metrics such as review timeframes and a commitment to achieve parity between surveillance inspections of foreign and domestic establishments by the 2017 fiscal year. As a result, FDA expects that the proposal would effectively eliminate the review backlog and significantly reduce review times.

A biosimilar is a biological product that is highly similar to a U.S.-licensed reference biological product notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product. The proposed Biosimilar and Interchangeable Products User Fee program is intended for products approved under a new abbreviated approval pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological product. The Affordable Care Act of 2010 contains a subtitle called the Biologics Price Competition and Innovation Act (BPCI) of 2009, which established this pathway.

Prior to it becoming law, competition in the biologic drug market was stifled. Enactment of BPCI will spark the development of a new segment of the industry, where companies will be able to develop alternative products. This will help spur innovation, improve consumer choice and drive down costs.

The recommended user fee program for biosimilars includes fees for products in development to generate revenue in the near-term and to provide FDA with the resources needed to support development-phase meetings with sponsors of biosimilar biological product candidates.

For more information:

Prescription Drug User Fee Act

     

Prescription Drug User Fee Act: PDUFA V Reauthorization

 

PDUFA V Reauthorization Goal

 

PDUFA V Statutory Language

 

Generic Drug User Fees

 

Generic Drug User Fee Act Program Performance Goals and Procedures

 

Generic Drug User Fees Statutory Language

 

Biosimilar and Interchangeable Products User Fees

 

Biosimilar Biological Product Authorization Performance Goals and Procedures

 

Biosimilar Statutory Language   

x

FDA to protect important class of antimicrobial drugs for treating human illness

FDA NEWS RELEASE. For Immediate Release: Jan. 4,2012. The U.S. Food and Drug Administration today issued an order that prohibits certain uses of the cephalosporin class of antimicrobial drugs in cattle, swine, chickens and turkeys effective April 5, 2012.

Antimicrobial drugs are important for treating disease in both humans and animals. This new order takes into consideration the substantial public comment FDA received on a similar order that it issued in 2008, but revoked prior to implementation.

FDA is taking this action to preserve the effectiveness of cephalosporin drugs for treating disease in humans. Prohibiting these uses is intended to reduce the risk of cephalosporin resistance in certain bacterial pathogens.

Cephalosporins are commonly used in humans to treat pneumonia as well as to treat skin and soft tissue infections. In addition, they are used in the treatment of pelvic inflammatory disease, diabetic foot infections, and urinary tract infections. If cephalosporins are not effective in treating these diseases, doctors may have to use drugs that are not as effective or that have greater side effects.  

In its order, FDA is prohibiting what are called “extralabel” or unapproved uses of cephalosporins in cattle, swine, chickens and turkeys, the so-called major species of food-producing animals. Specifically, the prohibited uses include:

using cephalosporin drugs at unapproved dose levels, frequencies, durations, or routes of administration;

using cephalosporin drugs in cattle, swine, chickens or turkeys that are not approved for use in that species (e.g., cephalosporin drugs intended for humans or companion animals);

using cephalosporin drugs for disease prevention.

In 2008, FDA issued and then revoked an order that prohibited extralabel uses of cephalosporins in food-producing animals with no exceptions. Today’s announcement responds to public comment and includes the following exceptions, which protect public health while considering animal health needs:

The order does not limit the use of cephapirin, an older cephalosporin drug that is not believed by FDA to contribute significantly to antimicrobial resistance.

Veterinarians will still be able to use or prescribe cephalosporins for limited extra-label use in cattle, swine, chickens or turkeys as long as they follow the dose, frequency, duration, and route of administration that is on the label.

Veterinarians may also use or prescribe cephalosporins for extralabel uses in minor species of food-producing animals such as ducks or rabbits.

"We believe this is an imperative step in preserving the effectiveness of this class of important antimicrobials that takes into account the need to protect the health of both humans and animals," said Michael R. Taylor, Deputy Commissioner for Foods.

The new order of prohibition has a comment period that will begin on Jan. 6, 2012 and close on March 6, 2012. To comment on the order of prohibition, visit www.regulations.gov and enter FDA-2008-N-0326 in the keyword box. Following the comment period, the FDA will consider the comments prior to the order of prohibition going into effect on April 5, 2012.

Questions and Answers on FDA's Cephalosporin Order of Prohibition 

Media Inquiries: Siobhan DeLancey, 301-796-4668, siobhan.delancey@fda.hhs.govx

Implementation of Office of Management and Budget Guidance on Drug-Free Workplace Requirements

Federal Register/Vol.76,No.236/Thursday, December ,2011/Rules and Regulations.The Department of Agriculture (USDA) is removing its regulation implementing the Governmentwide common rule on drug-free workplace requirements for financial assistance, currently located within part 3021 of Title 7 of the Code of Federal Regulations (CFR), and issuing a new regulation to adopt the Office of Management and Budget (OMB) guidance at 2 CFR part 182. This regulatory action implements OMB's initiative to streamline and consolidate into one title of the CFR all Federal regulations on drug-free workplace requirements for financial assistance. These changes constitute an administrative simplification that would make no substantive change in USDA's policy or procedures for drug-free workplace.

This direct final rule is effective on February 6, 2012 without further action. Submit comments by January 9, 2012 on any unintended changes this action makes in USDA's policies and procedures for drug-free workplace. All comments on unintended changes will be considered and, if warranted, USDA will publish a timely withdrawal of the rule inthe Federal Register.

You may submit comments, identified by docket number and/or RIN Number, by any of the following methods:

Federal eRulemaking Portal: http://www.regulations.gov.

Follow the instructions for submitting comments.
Email: james.mcstay@cfo.usda.gov. Include [docket number and/or RIN number] in the subject line of the message.
Fax: James McStay at (202) 690-1529.
Mail: OCFO/CTGPD, Room 3409-A, Stop 9010, 1400

Independence Avenue SW., Washington, DC 20250-9010.
Hand Delivery/Courier: OCFO/CTGPD, Room 3409-A, 1400
Independence Avenue SW., Washington, DC 20250.

All submissions received must include the agency name and RIN for this rulemaking. All comments received will be posted without change to http://www.regulations.gov, including any personal information provided.FOR FURTHER INFORMATION CONTACT: James McStay, (202) 720-0589, Email: james.mcstay@cfo.usda.gov; or Steve Lowery, (202) 720-1568, Email: steve.lowery@osec.usda.gov.

Implementation of Office of Management and Budget Guidance on Drug-Free Workplace Requirements

[Federal Register Volume 76, Number 236 (Thursday, December 8, 2011)].[Rules and Regulations].[Pages 76609-76611].From the Federal Register Online via the Government Printing Office [www.gpo.gov]. [FR Doc No: 2011-31467]x

FY2011 Innovative Drug Approvals

FDA is approving innovative drugs earlier and faster than any other country in the world, while at the same time making sure that Americans’ medicines are safe and effective.

Over the last several years, FDA has improved the quality and speed of its drug approval process, making new treatments available for millions of Americans suffering from various serious health problems.

In Fiscal Year 2011 FDA approved 35 innovative drugs that offered important advances in treatment for hepatitis C, late-stage prostate cancer, lupus, drug resistant skin infections, pneumonia, and other serious and life-threatening diseases. This is among the highest number of approvals in the past decade, surpassed only by 2009 (37).

The report, FY 2011 Innovative Drug Approvals, provides details of how FDA used expedited approval authorities, flexible clinical trial requirements and resources collected under the Prescription Drug User Fee Act (PDUFA) to boost the number of innovative drug approvals.

• Printer Friendly PDF (4.84MB)
• Persons with disabilities having problems accessing the above pdf file may call 301-796-4800 for assistance.
• Executive Summary
• Press Release - FDA: Successful year for new drug approvals