Regulation of cellular therapy in Australia.

Use of cellular products for therapeutic purposes has predominantly been unregulated in Australia until recently. Transplant of haemopoietic progenitor cells (HPC) for bone marrow regeneration is now a routine treatment for many disorders with an established mechanism of facility accreditation. However, other cellular therapies do not have any form of accreditation, are not well evaluated and may be associated with significant risks. On 31 May 2011 the Therapeutic Goods Administration (TGA) implemented a long heralded regulatory biologicals framework for cell and tissue based therapies. The framework currently excludes human HPC, organs for direct transplantation and reproductive materials which are already covered by various forms of existing peer review and accreditation. This new framework is a practical approach for applying regulation based on the risk of the product to the recipient with four classes of product. Class 1 is reserved for the least regulated products and currently does not contain any proposed products. Class 2 will be for minimally manipulated products which will only require manufacturing compliance and evaluation against product and other mandatory standards before entry onto the Australian Register of Therapeutic Goods (ARTG). Class 3 and 4 products will be more than minimally manipulated and these cells and tissues may be used in a non-homologous manner. Class 3 and 4 products will represent a spectrum of risk where Class 4 therapies will represent the highest potential risk to the recipient, with the same requirements for Class 2 approvals but with additional requirements for comprehensive evaluation of a dossier for quality, safety and efficacy of the product. The extent of this quality, safety and efficacy data will depend upon the nature of the product and its associated risks, but will be more comprehensive for Class 4 as opposed to Class 3 products. The only truly contentious feature of this framework is the extremely high cost for dossier evaluation and the puzzling absence of an orphan drug scheme for biologicals.

Platelet activation in the hypertensive disorders of pregnancy.

OBJECTIVE: The purpose of this study was to determine whether platelet activation occurs only in preeclampsia or also in normal pregnancy. STUDY DESIGN: Thirty women with preeclampsia, 30 women with gestational hypertension, 20 women with essential hypertension, 30 pregnant women with normotension, and 30 nonpregnant women were recruited at St George Hospital, Sydney, Australia. Platelet activation was determined by flow cytometry on whole blood samples. RESULTS: Platelet activation was similar in all groups, except the group with preeclampsia. Compared with normal pregnant women, women with preeclampsia had significantly greater CD62 expression (1.35% vs 0.61%; P =.002), CD63 expression (1.73% vs 0.95%; P <.0001) and annexin V binding (1.03% vs 0.66%;P =.03) and significantly fewer circulating platelet microparticles (33 vs 49 x10(9)/L; P =.001). This was unrelated to other parameters that included platelet counts. Women with gestational hypertension in whom preeclampsia developed did not have enhanced platelet activation profiles. CONCLUSION: Platelet activation is increased in preeclampsia but not in other hypertensive disorders or in normal pregnancy. This may be part of the pathophysiologic factors of preeclampsia complications but is not predictable by the platelet count and is not apparent in all women with preeclampsia.

Ex vivo expansion of functional T lymphocytes from HIV-infected individuals.

This study was designed to define the conditions for expansion of functional T lymphocytes from human immunodeficiency virus (HIV)-infected subjects, with the ultimate goal of using these cells for immunotherapy. The most appropriate culture conditions for good T cell proliferation included stimulation with anti-CD3 and anti-CD28 coated microspheres, and propagation in Aim V serum-free media with 20 U/ml interleukin-2 (IL-2), supplemented with decreasing concentrations of serum for the initial 8 days. Under these conditions, a 14-day culture period yielded approximately a 10,000-fold expansion of T lymphocytes from HIV-infected donors. The cultured cells comprised approximately 15% CD4+ cells and 70% CD8+ cells. These cells retained functional capacity as assessed by cytotoxicity towards HIV proteins, and production of IL-2 and interferon-gamma (IFN-gamma). Viral replication within the culture system was controlled, but not eliminated, without the requirement for antiviral agents. These culture conditions were demonstrated to be suitable for larger scale expansion of cells in hollow fibre bioreactors. This methodology provides a suitable means of producing large quantities of functional T cells for use in autologous immunotherapy protocols.