Abstract
Regulatory Wire
EMA Releases Guidance on Stem Cell-Based Medicine
The European Medicines Agency has released new guidance on medicines based on stem cells. The guidance covers the different types of stem cells used in medicines, and the considerations that companies need to take into account when developing medicines including stem cells or developed from stem cells.
The paper applies directly to those companies pursuing marketing authorization for stem cell-based products. According to the document, the paper “should be read in conjunction with existing guidance on cell-based medicinal products (Guideline on human cell-based medicinal products [EMEA/CHMP/410869/2006]) which addresses general aspects of cell-based medicinal products.”
Specifically, the paper provides key quality considerations for manufacturers, including purity of the stem cells. The document states that, “the aim should be to maximize the active components and minimize features which do not contribute, or may negatively impact on therapeutic activity/safety.” The document points out that pre-clinical and clinical testing needs to take account of the cells' properties, ensuring that the possible risks of tumor development and rejection by the body are studied adequately and balanced against their benefits for patients.
EMA's Committee for Advanced Therapies adopted the final reflection paper on Jan. 14, 2011. Comments from a May 2010 public workshop and a public consultation period were considered in drafting the final document. A complete copy of the report can be found here:
NHGRI Outlines Vision for Future Genomic Research
To celebrate the 10-year anniversary of the publication of the human genome sequence and to publicize its vision for the future, the National Human Genome Research Institute (NHGRI) held a symposium on February 11, 2011 called “A Decade with the Human Genome Sequence: Charting a Course for Genomic Medicine,” on the NIH campus 1 .
The symposium featured talks on topics that reflect the current—and projected—effect of genomics in diagnostic medicine and therapeutics, in personal genetics, and in ethical, legal, and social spheres.
In tandem with the symposium, the NHGRI released its formal plan for the next phase of genomics research. This new blueprint, produced in consultation with the research community over the past two and a half years, is framed in terms of five research domains. They span activities from basic research into how the human genome is organized and functions to clinical applications that will use knowledge of the genome and genomic technologies to improve medical care and health maintenance. The research domains are: * Understanding the structure of genomes * Understanding the biology of genomes * Understanding the biology of disease * Advancing the science of medicine * Improving the effectiveness of healthcare
The plan envisions continuing to expand the understanding of the biology of the genome, including creating more diverse and complete catalogs of genomic and other “-omic” information, along with new tools and technologies to develop and interrogate those catalogs.
The plan also calls for new technologies to measure the interaction between the environment, behavior and genes and for routine clinical applications of genomic tools such as newborn genetic screening and other types of diagnostic screening. It also calls for electronic medical records systems that integrate family histories and genomic data to generate personalized diagnoses, treatments, and prevention plans.
The plan anticipates the increasingly important role of multidisciplinary and international teams for collaboratively producing and analyzing comprehensive sets of data about a condition. Rapid data release for immediate research applications, which has been essential to genomic research, will continue to be fundamental for the field's success, according to the plan.
Beyond technology, the plan notes that educational efforts will be critical to making genomic medicine practical for both clinicians and the public. Healthcare providers must be trained to interpret genomic information and to use it in counseling patients. Health consumers will need to familiarize themselves with genomic medicine so they can understand their personal risks, participate in clinical decisions, make the best use of new therapeutics and, if they so choose, modify their behaviors in response to genome-based health information. Legislators and policymakers must craft policies that continue to promote the confidentiality of participation in genomics research. Other policies will be needed to protect individual privacy and access to health coverage, and to encourage investment in genomic health technologies through intellectual property incentives.
In a press release 2 , NHGRI director Dr. Eric Green noted that “our base-pairs-to-bedside plan maps the next steps in the herculean endeavor not only to discover medical secrets hidden within the human genomes, but to bring those discoveries to the practitioner and patient,” Dr. Green further said. “All of us in this field share a sense of urgency about using genomics for clinical applications. The challenges are enormous, but we believe that, working together, the goal of improving human health is within reach.” (sk)
FDA Releases New Guidance Document on Potency Testing
The FDA's Center for Biologics Evaluation and Research (CBER) has released a new document entitled “Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products". The document provides manufacturers of cellular and gene therapy (CGT) products with recommendations for developing tests to measure potency. The recommendations are intended to clarify the potency information that could support an investigational new drug application (IND) or a biologics license application (BLA). The guidance announced in this notice finalizes the draft guidance of the same title dated October 2008.
Potency is defined by CBER as “the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result1.”
Potency tests, along with a number of other tests, are performed as part of product conformance testing, comparability studies, and stability testing. These tests are used to measure product attributes associated with product quality and manufacturing controls, and are performed to assure identity, purity, strength (potency), and stability of products used during all phases of clinical study. Similarly, potency measurements are used to demonstrate that only product lots that meet defined specifications or acceptance criteria are administered during all phases of clinical investigation and following market approval.
The document makes recommendations for key questions encountered by manufacturers of cellular and gene therapy products including: “What should be measured for potency? What analytical methods may be used to measure potency? And when should potency assay development begin?” A complete copy of the document may be found here:
Science Wire
Genetic Cause of Rare Disease Identified by NIH
Clinical researchers at the National Institutes of Health's Undiagnosed Diseases Program (UDP) have identified the genetic cause of a rare and debilitating vascular disorder not previously explained in the medical literature 1 . The adult-onset condition is associated with progressive and painful arterial calcification affecting the lower extremities. The rare arterial condition caused by calcium buildup in arteries below the waist and in the joints of patient's hands and feet has been observed in nine individuals from three unrelated families, who are the only people known to have the disorder. The researchers refer to the condition as ACDC, or arterial calcification due to CD73 deficiency. Although symptoms of the disorder include leg and joint discomfort, medical evaluations of the patients ruled out rheumatoid arthritis or other joint-related problems. Genetic analyses performed by the NIH researchers suggested a novel disorder and pinpointed the cause of the condition as mutations, or variants, in the NT5E gene.
In one of the families with five affected siblings, clinical researchers suspected a recessive inheritance, in which offspring receive two copies of a gene variant—one from each parent—that produces disease symptoms only when combined. The researchers analyzed DNA from all members of the family to compare the parents' DNA to that of their affected children. This allowed researchers to detect genomic regions where the siblings' DNA contained two copies of a particular DNA segment compared to their parents' DNA, which contained just a single copy.
The comparison revealed one such region, which the researchers subsequently analyzed for sequence variants not present in a population of 200 unaffected people. The siblings all had the same variant in a gene called NT5E. This gene normally produces the CD73 protein, which is involved in adenosine metabolism in a way that prevents the arteries from calcifying. The researchers also detected variants in NT5E in all the other affected research subjects. The researchers performed laboratory tests to characterize the molecular basis of the arterial calcification disorder and to validate various molecular activities in cells with NT5E variants.
This is the first novel disease identified by the NIH's UDP since its founding in May 2008. The NIH UDP is an initiative jointly led by the National Human Genome Research Institute (NHGRI), the NIH Clinical Center and the NIH Office of Rare Diseases. Since its founding, more than 200 medical cases have been enrolled from among more than 1,200 sets of patient records submitted by patients seeking answers to mysterious disorders. The program's goal is to provide answers to patients with difficult-to-diagnose conditions and to advance medical knowledge about both rare and common diseases. For more information, visit:
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