|May 2013, Volume XXIII, No. 3|
Regulatory & Legislative Highlights
by Deepen Joshi, Sepracor, Inc.
On March 9, in conjunction with the issuance of a new Presidential memo on scientific integrity, President Obama signed a Presidential Executive Order removing barriers to responsible scientific research involving human stem cells. This Executive Order revokes that signed by President Bush on June 20, 2007 and the Bush Presidential statement of August 9, 2001 that limited federal funding of research involving human embryonic stem cells.
The previous Administration allowed the NIH to fund human embryonic stem cell research on cell lines created before an arbitrary date, August 9, 2001, but prohibited research on cell lines created after that date. The Executive Order signed by President Obama lifts this restriction.
Under the Obama Executive Order, the Director of NIH is instructed to develop guidelines for the support and conduct of responsible, scientifically worthy human stem cell research, including human embryonic stem cell research, to the extent permitted by law. Doing this will involve gathering the necessary scientific data and published best practices. NIH will then post draft guidelines for public comment, will carefully review all the public responses and will issue final guidance within 120 days of the signing of the Executive Order.
Research involving human embryonic stem cells and human non-embryonic stem cells has the potential to lead to better understanding and treatment of many disabling diseases and conditions. Advances over the past decade in this promising scientific field have been encouraging, leading to broad agreement in the scientific community that the full range of promising stem cell research should be supported by Federal funds. The purpose of the Executive Order is to remove the limitations on scientific inquiry in this area, to expand NIH support for the exploration of human stem cell research, and in so doing to enhance the contribution of America's scientists to important new discoveries and new therapies for the benefit of humankind. (Source: http://www.whitehouse.gov/)
A bipartisan group in Congress wants to give the FDA power to approve copies of biotech drugs. Representative Henry Waxman, a California Democrat and chairman of the Energy and Commerce Committee, and Georgia Republican Nathan Deal introduced legislation to create a pathway for the approval of copies of biotechnology-based medical treatments. There is currently no regulatory process for approving such copies in the US, leaving the drugs' makers insulated from the generic competition the traditional drug industry faces.
President Obama called recently for the creation of a regulatory pathway as part of a plan to reduce overall healthcare costs. "I believe this bill will lead to healthy competition and long-term savings for patients and payers and will preserve innovation to the biotech marketplace," Waxman said in a statement.
The debate over an approval process for biotech copies has dragged on for years, with both the biotechnology and generic drug industries at loggerheads over how much competition-free marketing the original drugs should get. The biotechnology industry has called for up to 14 years of exclusivity for their drugs before a copy could be introduced. But the bill instead mirrors the current system for chemical compounds, which allows for five years of market exclusivity for new drugs and up to three years additional exclusivity for modifications. (Source: Associated Press, The Boston Globe, 12 March, 2009)
President Obama has announced the appointments of Dr. Margaret Hamburg as Commissioner of the Food and Drug Administration, and Dr. Joshua Sharfstein as the Principal Deputy Commissioner.
Dr. Hamburg is a nationally and internationally recognized leader in public health and medicine, and an authority on global health, public health systems, infectious disease, bioterrorism and emergency preparedness. She served as the Nuclear Threat Initiative's founding Vice President for the Biological Program. Before joining NTI, she was the Assistant Secretary for Planning and Evaluation, U.S. Department of Health and Human Services. Prior to this, she served for six years as the Commissioner of Health for the City of New York and as the Assistant Director of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Dr. Joshua M. Sharfstein is Commissioner of Health for the City of Baltimore. He also serves as chair of the board of four affiliated nonprofit agencies. He has been recognized as a national leader for his efforts to protect children from unsafe jewelry and over-the-counter medication, and ensuring Americans with disabilities have access to prescription drugs. He is a member of the Board on Population Health and Public Health Practice of the Institute of Medicine. (Source: http://www.whitehouse.gov/)
The FDA has announced the launch of a voluntary pilot program that would help promote the safety of drugs and active drug ingredients produced outside the US. The FDA plans to select 100 applicants to participate in the Secure Supply Chain pilot program.
The goal of the pilot is to allow FDA to determine the practicality of developing a secure supply chain program. Such a program would assist the agency in its efforts to prevent the importation of drugs that do not comply with applicable FDA requirements by allowing the agency to focus its resources on foreign-produced drugs that fall outside the program and that may not be compliant. It will also expedite the entry of products meeting the pilot's criteria into the United States.
Each applicant may designate up to five drugs for selection in the pilot program. To qualify, applicants will need to meet the pilot's criteria, including a requirement that they maintain control over the drugs from the time of manufacture through entry into the United States. A secure supply chain will help mitigate risks such as contamination and counterfeiting. (Source: FDA Website, 14 January, 2009)
Eli Lilly and Daiichi Sankyo won the backing of a US panel to introduce the first rival to the blood-thinner Plavix, the world's second-biggest drug. FDA advisors voted 9 to 0 that prasugrel should be approved to reduce the risk of blood clots in patients with heart problems who undergo procedures to keep their arteries open. The FDA usually follows the recommendations of its panels, though it isn't required to do so.
Prasugrel, to be marketed as Effient, is critical to Lilly's plans to replace revenue when its top-selling antipsychotic, Zyprexa, loses patent protection in 2011. Analysts say prasugrel, if approved, may take up to a fifth of market share from Plavix, which generated $8.1 billion in 2007 sales for makers Bristol-Myers Squibb and Sanofi-Aventis. (Source: The Boston Globe, 4 February, 2009)
As Woburn strives to become a Massachusetts leader in biotechnology research, the city is also attempting to regulate the expanding industry locally so it may protect residents from potential dangers.The City Council agreed last week to adopt the Planning Board's recommendations to create new local laws prohibiting the most hazardous types of biotech research in Woburn and to change zoning regulations to differentiate between biological testing and all other types of research. The Council also agreed to reinstitute the dormant Biomedical Oversight Committee.
The proposed new regulations will prohibit the most hazardous types of research from being done in the city. As part of a national safety protocol for laboratory workers, every research lab is ranked on a biosafety-level scale based on the dangers of the materials being tested. Biosafety Level-1 is akin to a laboratory at a high school or vocational school. BSL-2 is common at most hospitals. BSL-3 and BSL-4 involve the most dangerous testing on potentially harmful or lethal agents.
Pete Abair, director of economic development for the Massachusetts Biotechnology Council, said biotech companies seeking lower rents and shorter commutes for their employees are expanding north and west out of Cambridge along major highways and public transportation routes. Woburn has more than 30 such companies, trailing Cambridge and Waltham as a center of Massachusetts biotech activity. Abair, whose group encourages communities to keep oversight of the industry and calm residents' fears, said biotech will continue to grow and Woburn should balance any proposed municipal regulation against the benefits the industry provides. (Source: The Boston Globe, March 5, 2009)
The FDA has announced that a facility owned by India-based Ranbaxy Laboratories falsified data and test results in approved and pending drug applications. The facility, Paonta Sahib, has been under an FDA Import Alert since September 2008. To date, the FDA has no evidence that these drugs do not meet their quality specifications and has not identified any health risks associated with currently marketed Ranbaxy products.
The affected applications are for drugs that fall into three categories: Approved drugs made at the Paonta Sahib site for the US market; drugs pending approval at the FDA that are not yet marketed; and certain drugs manufactured in the United States that relied on data from the Paonta Sahib facility.
On Sept. 16, 2008 the FDA issued two warning letters and instituted an Import Alert barring the entry of all finished drug products and active pharmaceutical ingredients from Ranbaxy's Dewas, Paonta Sahib and Batamandi Unit facilities due to violations of US cGMP regulations. That action barred the commercial importation of 30 different generic drugs into the US and remains in effect. (Source: FDA Website, 25 February, 2009)
The FDA has announced that California device manufacturer Cardinal Health 303, formerly known as Alaris Medical Systems, and three of its top executives have signed an amended consent decree to correct violations of cGMP requirements in the company's infusion pumps. Infusion pumps are devices intended for controlled delivery of intravenous solutions and medications to patients.
Under the terms of the amended consent decree, Cardinal 303 agrees to comply with the cGMP requirements and Quality System regulations in the designing, manufacturing, processing, packing, repacking, labeling, holding or distributing of its infusion pumps. Cardinal 303 also must retain an independent expert consultant to inspect all of its infusion pump facilities and recall procedures, and certify to the FDA that corrections have been made.The amended consent decree also authorizes the FDA, in the event of future violations, to order Cardinal 303 to cease manufacturing and distributing, to recall products, and to take other actions. The defendants may be required to pay damages of $15,000 per day if they fail to comply with any provisions of the decree, plus an additional $15,000 for each violation, up to $15 million per year. (Source: FDA Website, 19 February, 2009)
The FDA has issued a public health advisory concerning three confirmed and one possible report of progressive multifocal leukoencephalopathy (PML), a rare brain infection, in patients using the psoriasis drug Raptiva (efalizumab). Three of those patients have died. All four patients were treated with the drug for more than three years. None of the patients were receiving other treatments that suppress the immune system.
PML is caused by a virus that affects the central nervous system. PML usually occurs in people whose immune systems have been severely weakened. It leads to an irreversible decline in neurologic function and death. Symptoms may include unusual weakness, loss of coordination, changes in vision, difficulty speaking and personality changes. There is no known effective prevention or treatment.
Psoriasis is a chronic disease, for which a number of effective therapeutic options are available, including four other approved biologic agents, ultraviolet light therapy, and the drugs cyclosporine, acitretin, and methotrexate. Generally, treatment for psoriasis patients involves a rotation of therapies.
The FDA strongly recommends that health care professionals carefully monitor patients on Raptiva, as well as those who have discontinued the drug, for any signs or symptoms of neurologic disease, and that they periodically reassess the benefits of continued treatment. (Source: FDA Website, 19 February, 2009)
The FDA has approved Uloric (febuxostat) for the management of gout, a painful form of arthritis. Uloric works by reducing levels of uric acid, a waste product that is produced during digestion or ordinary metabolism. If uric acid levels in the blood are too high, crystals may form in the big toe, foot, ankle, or knees. Formation of these crystals can cause an attack of sudden burning pain, stiffness and swelling known as gout.
Although a causal relationship was not established, there was also a numerically higher rate of cardiovascular deaths, non-fatal heart attacks and non-fatal strokes in patients treated with Uloric than treated with allopurinol. The number of cardiovascular events was small in the clinical trials and the higher rate seen with Uloric may have occurred by chance. As a condition of approval, Takeda will be required to conduct a study to further assess the drug's cardiovascular safety.
An FDA Arthritis Advisory Committee met to discuss the safety and efficacy of Uloric. While the committee was concerned about the possibility of increased cardiovascular risk with Uloric, they concluded that the numerically higher rate of cardiovascular events may have occurred by chance but recommended that more data be collected after Uloric is approved. (Source: FDA Website, 13 February, 2009)
The first data offering health care professionals a better look into the genetic basis of certain types of adverse drug events has been released by the FDA and the International Serious Adverse Event Consortium (SAEC). The SAEC is a nonprofit partnership of pharmaceutical companies, the Wellcome Trust and academic institutions focused on research relating to the genetics of drug-induced serious adverse events.
The data are focused on the genetics associated with drug-induced serious skin rashes, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, and helps better predict an individual's risk of developing these reactions. Both skin conditions appear as allergic-like skin reactions associated with blistering and peeling, and are considered life-threatening. Medications causing these serious allergic reactions should be discontinued; and if such signs and symptoms are not quickly recognized, these reactions can be fatal.
The samples from the initial serious skin rash cases and matched controls were collected by GlaxoSmithKline plc, London, UK and donated to the consortium for this research. By pooling these samples, the SAEC has identified numerous genetic associations that may contribute to an individual's risk of developing serious drug-induced skin reactions. The data was compiled and analyzed just 16 months after the consortium was launched. (Source: FDA Website, 10 February, 2009)
The FDA has posted two new quarterly reports listing the drugs that are under evaluation for potential safety issues. The latest reports cover the second quarter (April-June) and the third quarter (July-September) of 2008. In addition, the FDA is updating an earlier report on the first quarter (January-March 2008).
This posting is the latest in a series of quarterly reports describing new safety information or potential signals of serious risks based on a review of reports submitted to FDA's Adverse Event Reporting System (AERS). The AERS database contains millions of reports of adverse events submitted to FDA by drug manufacturers, health care professionals and patients. The FDA Amendments Act of 2007 directed the FDA to conduct regular, bi-weekly, screening of the AERS database and to provide new drug safety information to the public on a quarterly basis.
The FDA has not concluded that the drugs listed actually have the reported risks and has not identified a causal relationship between the drug and the listed risk. Drug products are only on the list because FDA has identified a potential safety issue. The reports are available at: http://www.fda.gov/cder/aers/potential_signals/default.htm (Source: FDA Website, 6 February, 2009)
The FDA has approved the first ablation catheters for the treatment of atrial fibrillation (uncoordinated contractions of the upper heart chambers), one of the most common types of arrhythmias, affecting more than two million Americans. Atrial fibrillation is usually treated with drugs and, in certain severe cases, with open heart surgery. Catheter ablation should be used only after drug treatment has failed to adequately control the symptoms of the condition.
While atrial fibrillation is a major risk factor related to stroke, there is no conclusive evidence that links the treatment of symptoms by ablation to a reduction in stroke. Therefore, the FDA agrees with the American College of Cardiology, the American Heart Association and the European Society of Cardiology, which recommend that patients at risk for stroke continue to take blood-thinning medications after ablation procedures for atrial fibrillation.
As a condition of approval, manufacturer BioSense Webster of Diamond Bar, California must establish a physician training program and conduct postmarket studies to collect data on these devices' long-term safety and effectiveness (including incidence of stroke, mortality, cardiac arrest, major bleeding, and pulmonary vein stenosis), and the effect of physicians' experience in operating the device on procedural safety. (Source: FDA Website, 6 February, 2009)
The FDA has issued a final guidance for industry on the regulation of genetically engineered (GE) animals under the new animal drug provisions of the Federal Food, Drug and Cosmetic Act (FFDCA). The guidance, titled "The Regulation of Genetically Engineered Animals Containing Heritable rDNA Constructs," clarifies the FDA's statutory and regulatory authority, and provides recommendations to producers of GE animals to help them meet their obligations and responsibilities under the law.
Genetic engineering generally refers to the use of recombinant DNA (rDNA) techniques to introduce new characteristics or traits into an organism. When scientists splice together pieces of DNA and introduce a spliced DNA segment into an organism to give the organism new properties, it is called rDNA technology. The spliced piece of DNA is called the rDNA construct. A GE animal is one that contains an rDNA construct intended to give the animal new characteristics or traits.
The FFDCA defines "articles (other than food) intended to affect the structure or any function of the body of man or other animals" as drugs. An rDNA construct that is in a GE animal and is intended to affect the animal's structure or function meets the definition of an animal drug, whether the animal is intended for food or used to produce another substance. Developers of these animals must demonstrate that the construct and any new products expressed from the inserted construct are safe for the health of the GE animal and, if they are food animals, for food consumption. (Source: FDA Website, 15 January, 2009)
Chapter Manager: Amy Poole, CAMI - Tel: 1.781.647.4773 and E-mail: firstname.lastname@example.org