Videira Mafalda A, Llop Jordi, Sousa Carolina, Kreutzer Bruna, Cossío Unai, Forbes Ben, Vieira Isabel, Gil Nuno, Silva-Lima Beatriz
Departamento de Farmácia Galénica e de Tecnologia Farmacêutica, Faculdade de Farmácia da Universidade de Lisboa, iMed.ULisboa-Research Institute for Medicines and Pharmaceutical Sciences, Lisbon, Portugal.
Radiochemistry and Nuclear Imaging Group, CIC biomaGUNE, Donostia-San Sebastián, Spain.
Front Med (Lausanne). 2020 Feb 27;7:50. doi: 10.3389/fmed.2020.00050. eCollection 2020.
In recent years inhaled systems have shown momentum as patient-personalized therapies emerge. A significant improvement in terms of therapeutic efficacy and/or reduction adverse systemic effects is anticipated from their use owing these systems regional accumulation. Nevertheless, whatever safety and efficacy evidence required for inhaled formulations regulatory approval, it still poses an additional hurdle to gaining market access. In contrast with the formal intravenous medicines approval, the narrower adoption of pulmonary administration might rely on discrepancies in pre-clinical and clinical data provided by the marketing authorization holder to the regulatory authorities. Evidences of a diverse and inconsistent regulatory framework led to concerns over toxicity issues and respiratory safety. However, an overall trend to support general concepts of good practices exists. Current regulatory guidelines that supports PK/PD (pharmacokinetics/pharmacodynamic) assessment seeks attention threatening those inhaled formulations set to be approved in the coming years. A more complex scenario arises from the attempt of implementing nanomedicines for pulmonary administration. Cutting-edge image techniques could play a key role in supporting diverse stages of clinical development facilitating this pharmaceutics take off and speed to patients. The ongoing challenge in adapting conventional regulatory frameworks has proven to be tremendously difficult in an environment where market entry relies on multiple collections of evidence. This paper intention is to remind us that an acceptable pre-clinical toxicological program could emerge from, but not only, an accurate and robust data imaging collection. It is our conviction that if implemented, inhaled nanomedicines might have impact in multiple severe conditions, such as lung cancer, by fulfilling the opportunity for developing tailored treatments while solving dose-related toxicity issues; the most limiting threat in conventional lung cancer clinical management.
近年来,随着患者个性化疗法的出现,吸入系统显示出发展势头。由于这些系统的区域蓄积作用,预计其使用将在治疗效果和/或减少全身不良反应方面取得显著改善。然而,无论吸入制剂获得监管批准所需的安全性和有效性证据如何,它仍然是进入市场的一个额外障碍。与正式的静脉注射药物批准不同,肺部给药的应用范围较窄可能取决于上市许可持有人向监管机构提供的临床前和临床数据存在差异。监管框架多样且不一致的证据引发了对毒性问题和呼吸安全性的担忧。然而,支持良好实践一般概念的总体趋势是存在的。当前支持药代动力学/药效学(PK/PD)评估的监管指南值得关注,因为这关系到未来几年即将获批的那些吸入制剂。肺部给药纳米药物的尝试带来了更复杂的情况。前沿成像技术在支持临床开发的不同阶段可能发挥关键作用,推动这种药物制剂的发展并加快其惠及患者的速度。在市场准入依赖多种证据收集的环境中,调整传统监管框架面临的持续挑战已被证明极其困难。本文旨在提醒我们,一个可接受的临床前毒理学计划可能源自准确且可靠的数据成像收集,但不仅限于此。我们坚信,如果实施,吸入纳米药物可能会对多种严重疾病产生影响,例如肺癌,通过抓住开发定制治疗方案的机会,同时解决剂量相关的毒性问题,而这正是传统肺癌临床管理中最具限制的威胁。