|May 2013, Volume XXIII, No. 3|
Regulatory & Legislative Highlights
By Deepen Joshi
Regulatory & Legislative Highlights, a regular feature of the Boston Area Chapter Newsletter. It reviews recent actions by the FDA and other regulatory agencies and governmental bodies, both federal and regional, with the potential to impact the pharma, biotech and device industries, and related fields.
The City of Cambridge should not enact an ordinance to regulate the use of "nanoparticles," according to a report recently released by the city's public health department. Instead, the city should collect information on a voluntary basis from businesses and researchers who work with nanoparticles, the report says. "Until you know more about what's going on, plowing ahead with a regulatory requirement might overshoot the mark," said Sam Lipson, the director of environmental health at the Cambridge Public Health Department.
In 2006, Berkeley, California, became the first US city to regulate nanoparticles as potentially hazardous chemicals. The Berkeley ordinance requires that companies and research labs tell the city how much of the material is stored on their premises on a typical day, where the material came from, what it's used for, and anything they know about how the material can affect human health and the environment.
In January 2007, the Cambridge City Council asked the health department to study the Berkeley ordinance and report on whether Cambridge should enact a similar regulation. A committee headed by Lipson met with officials from companies involved in nanotechnology, researchers from Harvard University and the Massachusetts Institute of Technology, and environmental health and safety specialists. The committee concluded that there isn't enough information about the health effects of nanoparticles to justify a law to regulate their use.
Future scientific discoveries may justify tougher regulation of nanoparticles, Lipson said. He wants the health department to issue updates of the report every two years. Meanwhile, the committee will call for a voluntary program to take an inventory of Cambridge businesses and research labs that work with nanoparticles. The list would be compiled with help from the Cambridge Fire Department, which already keeps track of hazardous chemicals stored by companies. The committee also suggests that the public health and fire departments devise a program to inform businesses and researchers of the latest health and safety information about nanoparticles. The program would also help nanoparticle users develop safe material handling and storage practices. In addition, the committee recommends a public education program to inform citizens about safety issues related to nano materials. (Source: Hiawatha Bray, The Boston Globe, 28 July, 2008)
The FDA has cleared AlloMap, a non-invasive test that uses molecular expression techniques to assist doctors in managing heart transplant patients post-surgery for potential organ rejection. AlloMap measures genetic information contained in the white blood cells from a patient's blood sample. AlloMap was developed by XDx Inc. of Brisbane, California.
Nearly every cell of the body contains a full set of chromosomes and identical genes but only a fraction of these genes are turned on or expressed in any given cell. Gene expression occurs when certain molecular information contained within DNA is transcribed to create molecules known as RNA. These molecules in turn make the proteins that perform most of the critical functions of cells.
Following a heart transplant, physicians regularly monitor patients for transplant rejection, a significant risk to patient survival. Rejection occurs when the patient's immune system fails to accept the new organ and begins to attack it. Successful heart transplants depend on a balanced immune system response-a response that is suppressed enough to accept the new organ but strong enough to protect the patient from infections. Clinicians often rely on heart biopsy to gauge whether a patient is rejecting the transplanted heart. However, biopsies are difficult to perform and can be risky for the patient.
AlloMap is the third in vitro diagnostic multivariate index assay (IVDMIA) cleared by the FDA. IVDMIAs are medical devices that combine the values of multiple variables to yield a single, patient-specific result. (Source: FDA Website, 27 August, 2008)
The FDA has approved Nplate (romiplostim), manufactured by Amgen of Thousand Oaks, California. Nplate is the first product that directly stimulates the bone marrow to produce needed platelets in patients with a rare blood disorder that can lead to serious bleeding. The condition is known as chronic immune thrombocytopenic purpura (ITP), a disease that results in a low number of platelets. In patients with chronic ITP, the immune system is believed to destroy platelets and the patient's bone marrow is often unable to compensate for this loss.
The estimated 140,000 people with chronic ITP are prone to bruising and at risk for life-threatening bleeding. Current medical treatment includes corticosteroids and immunoglobulin. Surgery to remove the spleen may help some patients. Nplate is approved only for patients with chronic ITP who do not respond sufficiently to current treatments.
A Risk Evaluation and Mitigation Strategy (REMS) has been developed to address the risks of Nplate therapy. Under the FDA Amendments Act of 2007, FDA has determined that a REMS is necessary for the benefits of Nplate to outweigh the risks of the product. The REMS will include a Medication Guide for patients and requires that all prescribers and patients enroll in a special program to track the long term safety of Nplate therapy. (Source: FDA Websit, e22 August, 2008)
The FDA has approved the first generic versions of Risperdal (risperidone) tablets. Risperdal is an antipsychotic drug used for the treatment of schizophrenia, bipolar disorder, and other psychiatric conditions. Varying strengths of risperidone tablets, manufactured by TEVA Pharmaceuticals USA, have been approved. The labeling of the generic risperidone may differ from that of Risperdal because some uses of the drug are protected by patents and exclusivity.
The generic risperidone products will have the same safety warnings as Risperdal, including a Boxed Warning that cautions that older patients with dementia-related psychosis treated with atypical anti-psychotic drugs are at increased risk of death compared with those taking placebo. Risperdal, and other antipsychotic medications, are not FDA-approved to treat dementia-related psychosis. The decision to use antipsychotic medications in the treatment of patients with symptoms of dementia is left to the discretion of the physician. Such use is often called "off-label" use and falls within the practice of medicine. (Source: FDA Website, 30 June, 2008)
The FDA has approved a novel genetic test for determining whether patients with breast cancer are good candidates for treatment with the drug Herceptin (trastuzumab). The SPOT-Light HER2 CISH kit, manufactured by Invitrogen of Carlsbad, California, is a test that measures the number of copies of the HER2 gene in tumor tissue. This gene regulates the growth of cancer cells. Patients who over-produce HER2 protein are typically treated with the drug Herceptin, which targets HER2 protein production. This helps to stop the growth of HER2 cancer cells.
A healthy breast cell has two copies of the HER2 gene, which sends a signal to cells, telling them when to grow, divide and make repairs. Patients with breast cancer may have more copies of this HER2 gene, prompting them to overproduce HER2 protein so that more signals are sent to breast cells. As a result, the cells grow and divide much too quickly.
The SPOT-Light test counts the number of HER2 genes in a small sample of removed tumor. The removed piece is stained with a chemical that causes any HER2 genes in the sample to change color. This color change can be visualized under a standard microscope, eliminating the need for the more expensive and complex fluorescent microscopes required to read assays already on the market. Unlike existing tests, the SPOT-Light allows labs to store the tissue for future reference. (Source: FDA Website, 8 July, 2008)
The FDA has announced that it is revising the way it communicates to drug companies when a marketing application cannot be approved as submitted. Under new regulations that govern the drug approval process, FDA's Center for Drug Evaluation and Research (CDER) will no longer issue "approvable" or "not approvable" letters when a drug application is not approved. Instead, CDER will issue a "complete response" letter at the end of the review period to let a drug company know of the agency's decision on the application. The letter will describe specific deficiencies and, when possible, will outline recommended actions the applicant might take to get the application ready for approval.
Currently, when assessing new drug applications, the FDA can respond to a sponsor in one of three types of letters: an "approval" letter, meaning the drug has met agency standards for safety and efficacy and the drug can be marketed for sale in the United States; an "approvable" letter, which generally indicates that the drug can probably be approved at a later date provided that the applicant provides certain additional information or makes specified changes (such as to labeling); or a "not approvable" letter, meaning the application has deficiencies generally requiring the submission of substantial additional data before the application can be approved.
"Complete response" letters are already used to respond to companies that submit biologic license applications. The process for drugs and biologics will be consistent under the new regulations. (Source: FDA Website, 9 July, 2008)
The FDA has announced it is launching a two-year fellowship program aimed at attracting scientists, engineers and health professionals to the agency. The FDA Commissioner's Fellowship Program will provide participants with advanced training in the scientific analysis involved in the safety and regulatory decisions unique to the agency's mission.
Applicants are being considered for the first entering class of the program, which will begin in October 2008. The agency is seeking physicians, microbiologists, chemists, statisticians, pharmacists, biomedical engineers, nutritionists, veterinarians and other science professionals. Applicants should have a doctoral degree in medicine or another scientific field; engineers must have at least a bachelor's degree. Between 30 and 40 applicants will be accepted for the first entering class.
The FDA Commissioner's Fellowship Program will include coursework and extensive hands-on experience in FDA regulatory science including regulatory review opportunities. More than 20 courses and seminars will be offered on topics including FDA law, ethics and decision making, biostatistics, clinical trial design, population science and epidemiology, risk assessment, international activities, budgeting and operations, leadership, and public policy. A full listing of courses is available at http://www.fda.gov/commissionersfellowships/default.htm. (Source: FDA Website, 17 July, 2008)
The FDA has issued a final regulation that makes early phase 1 clinical drug development safe and efficient by enabling a phased approach to complying with current good manufacturing practice (CGMP) statutes and FDA investigational requirements.
To facilitate this new approach, the regulation exempts most phase 1 investigational drugs from the requirements in 21 CFR part 211. FDA will continue to exercise oversight of the manufacture of these drugs under FDA's general statutory CGMP authority and through review of investigational new drug (IND) applications. A companion guidance recommends an approach for complying with CGMP statutory requirements such as standards for the manufacturing facility and equipment, the control of components, as well as testing, stability, packaging, labeling, distribution, and recordkeeping.
When FDA originally issued CGMP regulations for drug and biological products (21 CFR parts 210 and 211), the agency stated that the regulations applied to all types of pharmaceutical production, but explained in the preamble to the regulations that FDA was considering proposing regulations more appropriate for the manufacture of drugs used in investigational clinical trials.
Manufacturers will continue to submit detailed information about relevant aspects of the manufacturing process as part of the IND application. The FDA may inspect the manufacturing operation, suspend a clinical trial by placing it on "clinical hold," or terminate the IND if there is evidence of inadequate quality control procedures that would compromise the safety of an investigational product. (Source: FDA Website, 18 July, 2008)
The FDA has cleared a test that can help determine what type of cancer cells are present in a malignant tumor. The Pathwork Tissue of Origin test compares the genetic material of a patient's tumor with genetic information on malignant tumor types stored in a database. It uses a microarray technology to analyze thousands of pieces of genetic material at one time. The test considers 15 common malignant tumor types, including bladder, breast, and colorectal tumors. The Pathwork Tissue of Origin test is the second in vitro diagnostic multivariate index assay (IVDMIA) device to be cleared by the FDA.
Microarray technology can simultaneously measure gene expression levels of large numbers of genes. Small DNA fragments are placed or arrayed on a slide and then RNA, which has been extracted from the tumor tissue and labeled with a fluorescent marker, is spread over this "microarray."
Pathwork's proprietary software converts the scanned image data to gene expression measurements. The gene expression patterns are compared with known gene expression patterns in the database that correspond to different tumor types. PathChip, the gene expression array used in the Pathwork Tissue of Origin test, is custom-designed for Pathwork Diagnostics of Sunnyvale, Calif., by Affymetrix Inc., of Santa Clara, Calif. PathChip is the first custom Affymetrix gene expression array to be cleared for diagnostic use. (Source: FDA Website, 18 July, 2008)
The FDA is strengthening and improving the workings of one of its most valuable resources: advisory committees.FDA may pose questions to an advisory committee about a specific product. The committee votes on the questions after reviewing briefing materials which contain background information such as available studies on the product. Improvements have been made in several areas, including procedures for determining conflicts of interest, and public availability of Advisory Committee members' financial interest information and waivers. For complete information please refer to the FDA website. (Source: FDA Website)
The FDA has approved this year's seasonal influenza vaccines that include new strains of the virus likely to cause flu in the US during the 2008-2009 season. The six vaccines and their manufacturers are: CSL Limited, Afluria; GlaxoSmithKline Biologicals, Fluarix; ID Biomedical Corporation of Quebec, FluLaval; MedImmune Vaccines, FluMist; Novartis Vaccines and Diagnostics Limited, Fluvirin; and Sanofi Pasteur, Fluzone.
This season's vaccines contain three strains of the influenza virus that disease experts expect to be the most likely cause of the flu in the US. Each season's vaccines are modified to reflect the virus strains most likely to be circulating. The closer the match between the circulating strains and the strains in the vaccines, the better the protection. There is always a possibility of a less than optimal match between the virus strains predicted to circulate and what virus strains end up causing the most illness.
Each year, experts from the FDA, World Health Organization, CDC and other institutions study virus samples and patterns collected throughout the year from around the world in an effort to identify strains that may cause the most illness in the upcoming season. Based on those forecasts and on the recommendations of its Advisory Committee, the FDA decides on the three strains that manufacturers should include in their vaccines for the US population. The FDA makes this decision early in the year so that manufacturers have enough time to produce the new vaccines. (Source: FDA Website, 5 August, 2008)
The FDA has approved Xenazine (tetrabenazine) for the treatment of chorea in people with Huntington's disease. Chorea is the jerky, involuntary movement that occurs in people with this disease. Xenazine is a new orphan drug, manufactured by Prestwick Pharmaceuticals of Washington, DC, and is the first treatment of any kind approved in the US for any symptom of Huntington's disease. Currently there are no other drugs that are FDA-approved to treat chorea.
Huntington's disease is a rare, inherited neurological disorder affecting about 1 in 10,000 people in the US. The disease results from genetically programmed degeneration of brain cells. The deterioration causes uncontrolled movements, loss of intellectual faculties, and emotional disturbance. Huntington's disease is passed from parent to child through a gene mutation. Each child of a parent with the disease has a 50 percent chance of inheriting the mutation.
Xenazine decreases the amount of dopamine available to work at relevant synapses in the brain. Dopamine is a chemical that communicates between certain nerve cells in the brain. In patients with Huntington's disease, this system is overactive and results in the abnormal movements called chorea. Xenazine decreases the amount of dopamine available to interact with certain nerve cells, thereby decreasing the involuntary movements.
Xenazine has been approved with a required Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of the drug outweigh its risks, particularly the risks of depression and suicidal thoughts and actions. (Source: FDA Website, 15 August, 2008)
Medco Health Solutions, the nation's leading pharmacy benefit manager, has announced that it and the FDA have entered into a research partnership to study genetic testing and the impact of genetics on the efficacy of prescription drugs. The announcement adds credence to the emerging science of personalized medicine and will expand the body of evidence for the consideration of personal genetics in how doctors prescribe drugs.
Unique differences in an individual's genes can cause variations in how many prescription drugs are metabolized in the body. These differences affect the speed of which a patient metabolizes medication - affecting safety or efficacy from too high or low of a dose. Such a situation can be dangerous or potentially deadly in the case of common medications like warfarin or codeine.
RxHub, launched by a consortium of the nation's leading pharmacy benefit managers and SureScripts, a system sponsored by retail pharmacies have announced that they would merge their industry-leading systems in an effort to further the adoption and use of ePrescribing technologies. The research agreement extends to August 31, 2010, during which time Medco will deliver a series of reports to the FDA about pharmacogenomic testing. The topics to be studied will address the safety of prescription drugs, physician participation in pharmacogenomics testing, the usefulness of the tests in prescribing, and quantifying prescription information about drugs that have genetic information in their labels. (Source: Medco Health Solutions, Inc. Website)
Health and Human Services (HHS) Secretary Mike Leavitt has announced a groundbreaking program designed to enhance the safety of medical products exported to the United States. Secretary Leavitt made the announcement in a speech to hundreds of industry leaders at an Import Safety Summit in Washington.
Historically, US authorities have primarily relied on intervening at the border to intercept unsafe goods. The new initiative is a pilot project the FDA is undertaking with its counterparts in the European Union and Australia to jointly plan, allocate for and conduct inspections of drug-manufacturing facilities. The project will initially focus on makers of active pharmaceutical ingredients. If successful, this program could expand to include other types of manufacturing facilities. The novel collaboration will allow HHS/FDA to more fully take advantage of information gathered by trusted inspection and regulatory systems in other countries. (Source: Health & Human Services Website, 9 July, 2008)
Chapter Manager: Amy Poole, CAMI - Tel: 1.781.647.4773 and E-mail: firstname.lastname@example.org