Development of scale-up strategies for ReFilx: a novel soft tissue filler - I2I Phase 1

据估计，2015年约有25,000名加拿大女性和292,130名美国女性分别被诊断出患有乳腺癌。在几项随机对照试验证实了保乳手术(BCS)或肿块切除加放射治疗的安全性和有效性后，它已取代乳房切除术成为BC的首选外科治疗方法。然而，在接受BCS的患者中，通常会观察到不良的美容效果和不规则的软组织缺陷。除了损害患者的美观外观外，软组织缺陷也是心理痛苦的主要来源。因此，对于乳房软组织缺陷的矫正存在着巨大的未得到满足的需求，目前使用许多关键意见临床医生认为不满意的其他技术来满足这一需求的成功有限。利用过去十年来构思和研究的创新生物材料科学，首席调查员(PI)开发了ReFilx，用于纠正肿块切除术后观察到的不规则乳房缺陷。ReFilx结构具有及时的生物降解率，同时能够立即支持乳房的形状和形状，允许组织生长来取代材料并保持形状。它吸收的副产品被监管机构认定为无毒的水平。通过使用猪模型的两项初步研究，我们已经确定了一种满足植入标准的ReFilx配方。在这项NSERC I2I应用中，我们建议通过开发和验证ReFilx合成所涉及的原材料的放大策略以及最终形成的构件的制造来支持该产品的商业化。这将通过两个关键里程碑来实现：(1)开发预聚体的放大战略和(2)开发用于高通量和可重复制造的ReFilx结构的原型。开发和验证这些工艺将反过来加快并降低从实验室向商业生产过渡的成本。

Approximately 25,000 Canadian and 292,130 American women were estimated to be diagnosed with breast cancer (BC) in 2015, respectively. After several randomized controlled trials confirming the safety and efficacy of breast conserving surgery (BCS) or lumpectomy with radiation, it has replaced mastectomy as the preferred surgical treatment for BC. However, poor cosmetic outcomes and irregular soft tissue defects are commonly observed in patients that undergo BCS. In addition to impairing the patients' aesthetic appearance, soft tissue defects are a main source of psychological distress. Thus, there is a large unmet need for the correction of soft tissue defects in the breast which is currently being accommodated with limited success using other technologies that many key opinion clinicians recognize as being non-satisfactory. Using innovative biomaterials science conceived and studied over the past decade, the principle investigators (PIs) have developed ReFilx for the correction of irregular breast defects observed after lumpectomy. ReFilx constructs have a timely biodegradation rate while enabling immediate support for breast shape and form, allowing tissue ingrowth to replace the material and maintain the form. It resorbs into by-products at levels recognized by regulatory agencies as being non-toxic. Through two pilot studies using a pig model, we have identified a ReFilx formulation that satisfies the implant criteria. In this NSERC I2I application, we propose to support the commercialization of this product through development and validation of scale-up strategies for the raw materials involved in ReFilx synthesis, as well as the fabrication of the final formed constructs. This will be accomplished through two key milestones: (1) develop a scale-up strategy for the pre-polymer and (2) develop prototypes for high through-put and reproducible fabrication of ReFilx constructs. Developing and validating these processes will in turn expedite and reduce the cost of transitioning from laboratory to commercial production.******