AABB CellSource - January 2014

January 2014


Updated Crosswalks Are Available

The Alliance for Harmonisation of Cellular Therapy Accreditation, or AHCTA — composed of representatives from the different standards-setting organizations — created a series of crosswalks, which are posted on its website. Alliance members periodically revise the crosswalks, which are categorized by specific topic areas. Updated documents addressing "Comparison of Donor Standards" and "Comparison of Objectives, Scope and Definitions" are now available. Additional documents on other topic areas will be posted as they are revised.

Seeking Input on Survey to Assist in Cell Processing Recommendations for Laboratory Staff

AHCTA is conducting a survey that is designed to assist in the development of recommendations for qualifications, training and competency for cell processing laboratory staff. If you have not already completed the survey, please take a few minutes to answer the questions aimed at learning more about staff responsible for the processing of minimally manipulated products like hematopoietic progenitor cells, or HPCs, for stem cell transplantation.

'Eye Catching': Cambridge University Team Inkjet- Prints Cells From the Eye

A group of researchers from the University of Cambridge have used inkjet printing technology to successfully print cells taken from the eye for the very first time. The study, published in the journal Biofabrication, has shown that cells derived from a mature central nervous system organ, the eye, can be printed using a piezoelectric inkjet printer — a device that ejects the cells through a sub-millimeter diameter nozzle when a specific electrical pulse is applied. The breakthrough could lead to the production of artificial tissue grafts made from the variety of cells found in the human retina and may aid in the effort to cure blindness.

Creating 3-D Kidney Parts From iPS Cells

A Japanese research team from Kumamoto University has successfully created three-dimensional kidney parts from human induced pluripotent stem, or iPS, cells. The achievement is expected to lead to the reproduction of kidneys and the understanding of kidney disease mechanisms. The team succeeded in creating glomeruli, which filter out waste products from blood, and renal tubules, which reabsorb substances essential for the human body. The reproduced tissues, approximately two millimeters in length, produced kidney-specific proteins but no urine.

Creating Personalized Cell Therapy Treatment for Fecal Incontinence

Norgine B.V. and Innovacell announced they have entered into a collaboration and an exclusive licensing agreement for the regions of Europe; South America and Central America; and Middle East and North Africa for ICEF15. ICEF15 is intended for both men and women suffering from fecal incontinence with sphincter weakness or damage. ICEF15 is a personalized cell-based product concept based upon proliferating myoblasts from biopsies taken from the patients' own muscle. Through this collaboration, Innovacell will co-develop ICEF15 with Norgine and Norgine will commercialize the product through its sales and marketing operations. The start of the ICEF15 phase IIb clinical trial is imminent. It is anticipated that the first patient will be dosed in the first quarter of 2014.

Mayo Clinic and Collaborators Develop New Tool for Transplanting Stem Cells Into Beating Heart

Mayo Clinic researchers and colleagues in Belgium have developed a specialized catheter for transplanting stem cells into the beating heart. The novel device includes a curved needle and graded openings along the needle shaft, allowing for increased distribution of cells. The result is maximized retention of stem cells to repair the heart.

Heart Disease Therapy Cleared for Phase II Clinical Trial to Be Funded by CIRM

A stem cell therapy developed by Capricor Therapeutics, Inc. aimed at treating patients who have had a heart attack received approval to begin a phase II clinical trial funded by California's stem cell agency, the California Institute for Regenerative Medicine, or CIRM. The treatment uses unrelated donor-derived stem cells, called cardiosphere-derived cells that are then infused into a patient's artery with the aim of reducing scarring caused by heart attacks. In a phase I clinical trial designed to test the safety of the therapy, the cells were introduced into 14 patients and found to be safe.


Stem Cells as Delivery Vehicles of Novel Therapeutics for Brain Diseases

Marie Csete MD, PhD

Stem cells that demonstrate tropism toward pathologic conditions of the brain are being modified to carry a variety of therapies directly to the local site of brain pathology. This natural tropism is particularly important in the brain, where site-selective delivery of therapies is problematic. For example, delivery of chemotherapy specifically to brain tumors is hampered by the blood brain barrier (BBB) and getting around it is technically challenging, prompting development of new devices and methods for intra-arterial, intranasal and stereotactic surgical delivery of chemotherapeutic drugs. All of these approaches carry an inherent risk of damage from the procedure itself. In addition, spillover of toxic therapies into normal brain tissue can have devastating results. This short review highlights a variety of approaches to modifying stem cells to carry therapeutics specifically to sites of pathology in the brain. Read more


AABB Updates Web Page With a Summary of Regulations

The AABB International Competent Authorities Web page has been updated with a summary of cellular therapy-related regulations in Canada and Mexico. The summaries also include links to applicable guidelines, resources and regulations.

FDA Releases Draft Guidance on Tests for Screening HCT/P Donors for T. pallidum Infection

In a "Federal Register" notice, dated Nov. 5, the Food and Drug Administration issued a draft guidance, "Use of Donor Screening Tests to Test Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) for Infection with Treponema pallidum (Syphilis)," dated October 2013. The draft guidance provides establishments that make HCT/P donor eligibility determinations with updated recommendations concerning donor testing for evidence of T. pallidum infection — the causative agent of syphilis — for which all HCT/P donors must be tested in accordance with 21 CFR 1271.85(a)(5). A proposed recommendation states that an appropriate FDA-licensed, approved or cleared donor screening test should be used in accordance with the manufacturer's instructions, unless an exception under 21 CFR 1271.90 applies. FDA also clarifies that diagnostic tests or pre-amendment devices are no longer adequate for T. pallidum testing of HCT/P donors.

The 2013 guidance will supersede the relevant testing recommendations in section IV.A of the August 2007 final guidance, "Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)," which permitted the use of diagnostic and pre-amendment devices (i.e., non-treponemal tests). The 2007 guidance also allowed HCT/P donors to be determined as eligible when "the specimen tests positive or reactive on a non-treponemal screening test for syphilis and negative or nonreactive on a specific treponemal confirmatory test (e.g., fluorescent treponemal antibody with absorption test), so long as all other required testing and screening are negative or nonreactive." The recommendations in the 2013 guidance will apply to all HCT/Ps recovered after the final guidance is implemented. AABB is developing comments on the draft guidance to submit before FDA's deadline of Feb. 3, 2014. To contribute comments for consideration of inclusion, please send feedback to regulatory@aabb.org.

CBER's Cellular, Tissue and Gene Therapies Advisory Committee Set to Meet in February

The FDA's Center for Biologics Evaluation and Research, or CBER, posted information about the next Cellular, Tissue and Gene Therapies Advisory Committee, CTGTAC, meeting that will be held on Feb. 25-26 in Gaithersburg, Md. During this meeting, which is open to the public, the committee will discuss topics that include oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease or for the treatment of infertility and updates on guidance documents from the Office of Cellular, Tissue and Gene Therapies, or OCTGT, CBER. Specifically, the draft guidance "Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products," mentioned below, will be discussed on Feb. 26. The FDA website provides instructions for individuals interested in presenting either written or oral statements.

Comment Period Extended for FDA Draft Guidance on Clinical Trials for Cell Therapy Products

In a Nov. 20 "Federal Register" notice, the FDA changed the due date for comments on the draft guidance, "Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products," from Nov. 22, 2013, to May 9, 2014. The new deadline will allow for public discussion of the draft guidance at the Feb. 25-26 CTGTAC meeting. The discussion was originally scheduled for the October 2013 CTGTAC meeting, which was cancelled.

The draft guidance provides recommendations to assist sponsors in designing phase one trials and some phase two trials that focus on the initial evaluations of the safety, tolerability or feasibility of investigational cellular and gene therapy products. The document highlights product-specific considerations for the following elements of a clinical study: trial objective(s), study population, use of a control group and blinding procedures, dose selection and escalation schedules, treatment plans, monitoring, and follow-up activities. When finalized, this guidance will apply only to cellular and gene therapy products regulated under Section 351 of the Public Health Service Act as biological products.

Reduced Drying Time Approved for ChloraPrep Skin Prep Products

The Center for Drug Evaluation and Research at the FDA has approved new labels that reflect shortened drying times for CareFusion's ChloraPrep products aimed at reducing bacteria on the skin. Among other uses, these products are employed to scrub the arms of donors prior to the collection of blood and cellular therapy products. According to CareFusion's letter to clinicians, the revised label directs users to "allow the area to air dry for approximately 30 seconds" when products are applied to dry sites (e.g., abdomen or arm). The FDA approved the label changes on Oct. 10, 2013.

In early 2013, AABB alerted its members that the drying time listed on the package insert for these products — which contain 2 percent chlorhexidine gluconate and 70 percent isopropyl alcohol — had changed from "approximately 30 seconds" to "minimum of 3 minutes." The revision was not in response to an issue with improper disinfection due to the shorter drying time. Rather, it responded to well-documented risks of patient injury in surgical settings using alcohol-based skin antiseptics and ignition sources — such as electrocautery devices and open lasers. AABB, America's Blood Centers, the American Red Cross and the manufacturer worked with the FDA to obtain revised labeling instructions for ChloraPrep products that are used on dry sites in a setting without ignition sources. During the revision process, FDA made it possible for blood establishments to continue use of their "current approved" standard operating procedures.

AABB Summarizes Final Rule for Medicare 2014 Hospital Outpatient Services; Bundling Same-Day Services Impacts Payment Rates for Many Cellular Therapy Services

The Centers for Medicare and Medicaid Services, or CMS, published its final rule governing payment policies and rates for the Medicare Hospital Outpatient Prospective Payment System, or OPPS, for 2014. The rule, issued late by CMS because of the government shutdown, includes relatively modest reductions in payments for several frequently transfused blood products. Payments for transfusion services, apheresis and stem cell processing, as well as most blood processing codes, will increase substantially. However, these increases likely are due to the bundling of these activities with same-day services, in particular laboratory tests. AABB has prepared a summary of the major provisions of the rule affecting the transfusion medicine and cellular therapy community. The new payment system took effect on Jan. 1.

FDA Publishes Final Guidance on Preclinical Considerations for Cell and Gene Therapy Products

The Food and Drug Administration announced the availability of a final guidance for industry, "Preclinical Assessment of Investigational Cellular and Gene Therapy Products," in a Nov. 25 "Federal Register" notice. The final guidance provides recommendations and considerations for sponsors and individuals that design and implement preclinical studies and development programs for cell and gene therapy products. These recommendations update and supersede those made in section VIII of the guidance document, "Guidance for Human Somatic Cell Therapy and Gene Therapy," dated March 1998. The updates reflect scientific advancements in the field as well as experience gained from a review of investigational new drug, or IND, applications and biologics license applications, or BLAs, conducted by the Office of Cellular, Tissue and Gene Therapies at the Center for Biologics Evaluation and Research. In response to comments received on the draft version of the guidance, the agency also reorganized several sections and incorporated editorial changes for improved clarity. The final guidance will serve as an instrumental tool by helping ensure that preclinical studies are well-designed and provide adequate data to demonstrate that an investigational therapy is safe to administer to humans under an IND application. When submitting a BLA, the preclinical data will be used to help establish the therapy's safety profile.


Guidance in Developing Commercializable Autologous/Patient-Specific Cell Therapy Manufacturing

Manufacturing cells at the scale-out level is important in furthering their potential for therapeutic applications. S. Eaker et al. discuss the processes that are required for scale-out at the manufacturing level and the questions that can be addressed at the bench level. The authors provide some guidance in the form of topics (e.g., good manufacturing processes, scalability, role of technology transfer office, cell sources, culture procedures, assays) that can be addressed early in the development process to improve the chances of the product being a successful candidate for future commercialization.

Ex Vivo Expansion of Cord Blood-Derived Hematopoietic Stem and Progenitor Cells — Basic Principles, Experimental Approaches and Impact in Regenerative Medicine

Hematopoietic stem cells and progenitor cells, or HSCs and HPCs respectively, play key roles in the production of mature blood cells and in the biology and clinical outcomes of hematopoietic transplants. Ex vivo expansion of human umbilical cord blood-derived HSCs and HPCs has become a priority in the biomedical field to produce cells on a clinical scale. Recent studies suggest that HSCs also may give rise to non-hematopoietic cells, such as neural, cardiac, mesenchymal and muscle cells. P. Flores-Guzman et al. give an overview of the different approaches that have been used to expand hematopoietic cells from umbilical cord blood and review the effect that such procedures have had in the clinic. The impact on regenerative medicine of potential alternatives for the treatment of neural, metabolic, orthopedic, cardiac and neoplastic disorders due to plasticity as well as the possibility of producing non-hematopoietic cells on a clinical scale are discussed.

Mesenchymal Stem Cells: Environmentally Responsive Therapeutics for Regenerative Medicine

MSC, are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro. The availability and versatility of MSC make them an excellent treatment option for a wide variety of clinical pathologies. M.B. Murphy et al. state that it falls to the scientific community to create guidelines for the optimal administration of MSC-based therapies. Their review covers a brief history of MSC, their anti-inflammatory, immunomodulatory and paracrine effects, and the current status of MSC-based therapies for a multitude of clinical applications.


Stay Current With AABB Audioconferences and Webinars

The 2014 audioconference schedule is posted on the AABB website. Upcoming audioconferences include:

03/19 Contract Writing: Understanding Common Contracts in Cellular Therapy (#144807)
03/26 Impact of the Affordable Care Act on Stem Cell Transplants (#144800)

The AABB Center for Cellular Therapies also offers a variety of topics in its webinar series where experts share their knowledge and experience, answer questions from participants and provide valuable resources. The hour-long interactive webinars consist of 45-50 minutes of presentation, followed by a 10-15 minute period for questions and answers. CME credits are available for the live sessions. Upcoming webinars include:

02/27 The Future Direction of the Blood Banking Industry in Regenerative Medicine (#1412)
03/11 Ex-vivo Expansion of Cord Blood Derived Hematopoietic Stem Cells (#1413)
04/10 Potency Assays for HPC Products (#1414)

Education on Demand

Recorded versions of the webinars are available through the AABB Marketplace.

Recordings of past audioconferences on topics in cellular therapies are available through the Live Learning Center.

Videos and Manuscripts: 'Transfusion' Call for Authors

AABB's "Transfusion" journal reports on the latest technical advances, features opposing viewpoints regarding controversial issues and presents key conference proceedings. In addition to blood banking and transfusion medicine topics, "Transfusion" presents submissions concerning transplantation and hematopoietic, cellular and gene therapies. There are a variety of sections in the journal including Transfusion Clips (short videos), one-page reports, reviews, case reports, "How Do I" (opinion sections), clinical research articles and letters to the editor. Find a section to which you would like to contribute and submit one today!

Donor Suitability Tool Available From the WMDA

The World Marrow Donor Association, or WMDA, has launched a handbook for blood stem donation, "A gift for life." The book describes factors that contribute to the success of a blood stem cell registry, how registries can remain successful in the future and valuable considerations when setting up and running a registry. This comprehensive book is intended for both registry personnel and professionals involved in blood stem cell donation, as well as people interested in setting up a new registry. Copies of the book can be ordered through the WMDA.


Did You Hear the Latest?

Members of the AABB Center for Cellular Therapies subsections participate in an assortment of interactive activities such as journal clubs and presentations on timely topics and challenges, and they work in teams to develop tools and reference materials. The materials or "projects" produced by the subsections are located on the AABB Center for Cellular Therapies website.

Cord Blood Subsection — Asia-Pacific Group: Members located in the Asia-Pacific Region now have available a group in which they can directly participate in live discussions with fellow group members. The group meets via telephone on the second Wednesday of each month at a time convenient for countries included in the region. The group initially met in September and has enjoyed a gradual increase in the number of participants. If you are interested in participating and would like more information, contact celltherapy@aabb.org.

Novel Therapies and CT Product Development Subsection: The leaders of this subsection, Drs. Pampee Young (Vanderbilt University) and Magali Fontaine (University of Maryland School of Medicine), invited Dr. Abba Zubair (Mayo Clinic) to lead a journal club discussion on "Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies." The journal club and other subsection activities provide an opportunity to develop professional skills and network with individuals who have similar interests.

Product Manufacturing and Testing Subsection: This subsection began 2014 with new leadership — Drs. David Stroncek (NIH) and Vasiliki Kalodimou (Maternity & Research Hospital, Greece). Check out its projects pages to see if this topic area interests you and join the dynamic group!


Editor: Christina Celluzzi
Contributors: Rafael Cassata, Marie Csete, Naynesh Kamani, Kathy Loper, and Katherine Bricceno

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