The U.S. Food and Drug Administration today approved Eloctate, Antihemophilic Factor (Recombinant), Fc fusion protein, for use in adults and children who have Hemophilia A. Eloctate is the first Hemophilia A treatment designed to require less frequent injections when used to prevent or reduce the frequency of bleeding.
Eloctate is approved to help control and prevent bleeding episodes, manage bleeding during surgical procedures, and prevent or reduce the frequency of bleeding episodes (prophylaxis). Eloctate consists of the Coagulation Factor VIII molecule (historically known as Antihemophilic Factor) linked to a protein fragment, Fc, which is found in antibodies. This makes the product last longer in the patient’s blood.
“The approval of this product provides an additional therapeutic option for use in the care of patients with Hemophilia A,” said Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research.
Hemophilia A is an inherited, sex-linked, blood clotting disorder, which primarily affects males, and is caused by defects in the Factor VIII gene. Hemophilia A affects 1 in every 5,000 males born in the United States. People with Hemophilia A can experience repeated episodes of serious bleeding, mainly into the joints, which can be severely damaged by the bleeding.
The safety and efficacy of Eloctate were evaluated in a clinical trial of 164 patients that compared the prophylactic treatment regimen to on-demand therapy. The trial demonstrated that Eloctate was effective in the treatment of bleeding episodes, in preventing or reducing bleeding and in the control of bleeding during and after surgical procedures. No safety concerns were identified in the trial.
Eloctate received orphan-drug designation for this use by the FDA because it is intended for treatment of a rare disease or condition.
Eloctate is manufactured by Biogen Idec, Inc., Cambridge, Mass.
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.
In order to equip pharma manufacturing units for GMP compliance, Maharashtra Food and Drug Administration (FDA) is in the process of drafting a proforma to help 1703 existing manufacturers do self auditing of their units in accordance to global standards. The proforma will help generate a self inspection report of the unit for further review and recommendation from the state FDA for effective global compliance.
The proforma likely to be available soon to the manufacturers is the outcome of the fact that Indian pharma companies are of late being targeted in many importing countries and regulated markets. Regulatory regimes in the respective countries are being tightened by raising barriers to protect the domestic industry.
Says Maharashtra FDA Commissioner Mahesh Zagade, “With complaints received from countries like Vietnam very recently regarding supply of not of standard quality drugs, it becomes the responsibility of the Indian regulatory authorities to ensure that position of Indian pharma industry is not compromised in the international market. The objective is to account for what goes out of India.”
An FDA official further explains that generic drugs produced in the country have made inroads in both developing and developed markets of the world. Doing inspection through a set of procedures, therefore, is the need of the hour.
Audit readiness of pharma manufacturing units has also become a focus area following the US FDA’s workshops on GMP and CGMP compliance for the first time in four cities of India in partnership with Central Drugs Standard Control Organisation (CDSCO) last month. The US FDA –CDSCO workshops conducted recently covered relevant topics for Indian regulatory requirements like process validation, enforcements and computer system validation based on out of specific information. The workshops were held in Hyderabad, Goa, Chandigarh and Ahmedabad.
US-based online compliance and regulatory learning solutions company Underwriters Laboratories (UL) Eduneering, which trains drug regulators to ensure safety of FDA related pharma products is also planning to equip leading Indian pharma companies on maximizing compliances related to consent decree, Form 483, data integrity and quality management systems. This would entail maintenance of electronic records for inspection readiness of Indian companies.
The Union health ministry’s high power committee (HPC) headed by Prof P N Tandon, constituted to evaluate the ongoing activities of the Indian Council of Medical Research (ICMR), has recommended to the ICMR for the creation of “Harvest Group” to identify leads from extramural research towards making products, processes and other deliverable for the benefit of the Indian public health system.
The committee further recommended for strengthening the BSL-IV lab of the NIV, Pune through adequate staff and infrastructure development to make it fully functional. It also recommended that strategies should be explored to improve the use of mass-media for better projection of ICMR’s scientific activities to enhance public awareness.
The committee in its recent report further notes that the periodicity of publication of Indian Journal of Medical Research (IJMR) should be increased to fortnightly in view of the highest impact factor of IJMR among all biomedical journals in India. It further recommended that the ICMR institutes should have MOU with medical colleges, universities, research institutes, in the region for promoting collaborative biomedical research and human resource development.
The panel also recommended for strengthening of various programmes towards creation of more short and long term fellowships for young scientists from SAARC and other developing countries with specific focus on South Asian and African countries. It further noted in its report that the mechanisms to identify and avoid duplication of funding of research projects should be strengthened through involving sister agencies like DBT, CSIR, DST, etc through DHR mechanism.
The union health ministry had constituted the high power committee in December, 2012 to evaluate the ongoing activities of the ICMR with the mandate of whether the ongoing schemes of the XI Plan need to be continued in XII Plan or dissolved forthwith; in case if they are to be continued then the need for improvement; phasing expenditure in XII Plan for each component of the scheme; and setting of physical and financial milestones/targets for the XII Plan for each component.
Scientists sporting white coats and safety gloves are working in a bright Food and Drug Administration (FDA) lab on an incredible project.
They are part of FDA’s MSC Consortium, a large team of FDA scientists studying adult mesenchymal stem cells (MSCs)—cells that could eventually be used to repair, replace, restore or regenerate cells in the body, including those needed for heart and bone repair.
The scientists’ investigational work is unprecedented: Seven labs at FDA’s Center for Biologics Evaluation and Research formed the consortium to fill in gaps in knowledge about how stem cells function.
“This research aims to facilitate development of this important class of innovative medical products,” explains Carolyn A. Wilson, Ph.D., associate director for research at the center. “It’s the first time we’ve done anything like this, and it’s proven to be a very useful approach. It’s worked so well because this is a huge, complicated project that requires expertise in many different technologies and methods.”
The research could ultimately be key to the advancement of personalized medicine, the practice in which medical treatment is tailored to the needs of an individual patient. “It’s not science fiction,” says Steven R. Bauer, Ph.D., chief of the Cellular and Tissue Therapy Branch in FDA’s Office of Cellular Tissue and Gene Therapies. “For me, regenerative medicine is the most exciting part of what we regulate in our office.”
So What Are Stem Cells?
There are two basic kinds of stem cells that are currently useful in the field of regenerative medicine: multipotent and pluripotent stem cells. Multipotent stem cells are generally taken from adults and can divide and develop into many different cell types. Pluripotent stem cells can develop into any type of cell in the body. Both types could divide to replenish cells damaged by injury, illness or normal wear. When stem cells divide, the new cells can either remain stem cells or develop into a new type of cell with a more specific function.
Two types of pluripotent stem cells exist: human embryonic stem cells and induced pluripotent stem cells, which are created by reprogramming adult cells that had already changed into a mature type of cell.
FDA’s MSC Consortium is not studying stem cells taken from embryos. “We’re looking at a particular kind of multipotent adult stem cell—the MSC—which is being used in a lot of regenerative medicine clinical trials,” adds Bauer.
The group is currently studying eight unique cell lines, each acquired from commercial sources and sourced to one of eight distinct, adult donors. (Males and females age 22 to 47 donated stem cells from bone marrow.)
The cells under study are multipotent: “They can differentiate (mature into) at least three cell types: bone, fat and cartilage, primarily,” Bauer explains. “They can also differentiate into nerve cells, liver cells and a kind of cell called ‘stroma’ that is in the bone marrow and supports blood forming cells. Then, for investigational clinical uses, they’ve been used for repairing hearts, repairing bone and repairing cartilage.”
Why Is FDA Studying These Cells?
In addition to differentiating into a variety of replacement cell types, MSCs can limit a patient’s immune response. So they can potentially be taken from one human donor and placed into a different recipient with less possibility of rejection.
But growing stem cells and making sure they are safe and effective is challenging, which is one reason why stem-cell based clinical trials have not yet resulted in a marketed product.
“The major challenge is that cells are much more complex than traditional products that FDA regulates. And they have the ability to respond to their environment,” Bauer explains. “Taking them out of the body and manufacturing them—that is, growing large numbers of them—or isolating them can change their biology. And it can change the way they behave if they are put back into the patient.”
For instance, if cells are manufactured in large quantities outside their natural environment, they may become ineffective or develop harmful characteristics. For example, they can produce tumors, severe immune reactions or growth of unwanted tissue. So FDA is trying to develop methods that would predict with more certainty how manufactured or isolated adult stem cells will behave in patients.
What’s Being Done?
In the labs, cells are suspended in a nutrient liquid solution and grown in sterile containers called tissue culture flasks. Cells then multiply and go through three, five or seven generations of growth.
FDA scientists are using a variety of cutting-edge methods to characterize cells and then determine if any of these characteristics can predict the behavior of the cells in biological assays or in animal models. The next step will be to determine if any characteristics they measure will predict the safety or effectiveness of stem-cell based products in patients.
Specifically, scientists will continue studying whether factors such as different methods of growing the cells, donor age or gender affects the cells’ quality and performance. This research will ultimately provide new tools to the community of academic and private industry scientists who are interested in evaluating and developing stem cells into new clinical treatments.
“The consortium has shown that widely accepted ways to identify and characterize MSCs do not reveal some important biological differences between batches of these cells,” Bauer says. So the consortium seeks to demonstrate ways to better characterize MSCs that will be used in clinical trials. That’s important because, if investigators can improve the tools used to characterize MSCs used for clinical trials, the data generated from their studies could also improve because their MSC products will be more predictable, he adds.
And the improved predictability of their products will, in turn, allow FDA scientists to more easily evaluate the safety and effectiveness of new stem cell technologies—a key part of the regulatory science that is the foundation of FDA decisions.
Agency scientists already have published six papers in scientific journals such as Tissue Engineering and Cytotherapy. “We’re hoping this project will inspire people to do more research in this area,” Bauer says.
Stem cells, like other medical products intended to treat, cure or prevent disease, require FDA approval before they can be marketed. “It is important for FDA to maintain a sound regulatory science research program to promote the development of safe and effective products in emerging areas that hold great promise,” Bauer says.
“My colleagues and I hope our scientific findings will be helpful in the field of regenerative medicine, including the ability to repair or even replace organs and tissues more safely and effectively than traditional means,” he adds. “Although there are many scientific hurdles to overcome before the use of stem cells reaches its full potential, I think this medicine will eventually have the capacity to do that.”
This article appears on FDA’s Consumer Updates page, which features the latest on all FDA-regulated products.
Mylan Inc., a global pharmaceutical company committed to setting new standards in health care, has launched carboplatin injection, 50 mg/5 ml, in multi-dose vials, which is the generic version of Bristol-Myers Squibb‘s Paraplatin injection.
Mylan received final approval from the US Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product, which is indicated for the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents.
Mylan also received final approval for carboplatin injection, 150 mg/15 ml, 450 mg/45 ml, 600 mg/60 ml, in multi-dose vials, and intends to launch these presentations subsequently.
Carboplatin injection, 50 mg/5 ml, 150 mg/15 ml, 450 mg/45 ml, and 600 mg/60 ml had US sales of approximately $30.4 million for the 12 months ending March 31, 2014, according to IMS Health. This launch bolsters Mylan’s growing portfolio of cancer treatment and supportive care products.
Currently, Mylan has 299 ANDAs pending FDA approval representing $105.2 billion in annual brand sales, according to IMS Health. Forty-one of these pending ANDAs are potential first-to-file opportunities, representing $25.4 billion in annual brand sales, for the 12 months ending December 31, 2013, according to IMS Health.