Chris Fanelli从合规角度解释了新兴细胞和基因治疗面临的独特挑战与机遇，他提出了买家在尽职调查和收购后阶段可用于评估GxP合规性的一些方法。

Chris Fanelli explains how emerging cellular and gene therapy companies present unique challenges and unique opportunities from a compliance perspective. He explores some of the tools that buyers can use to assess GxP compliance at the due diligence and post-acquisition stages.

细胞和基因疗法为治疗严重疾病提供了开创性的新机遇。对许多人来说，这些先进疗法在治疗严重危及生命的疾病方面取得持续进展至关重要。每年向世界各地卫生当局提交的IND和上市申请数量飙升，证明了这一点。

Cellular and gene therapies offer truly ground breaking new opportunities for the treatment of serious diseases. For many, these and other advanced therapies are critical to making continued progress in treating serious, often life-threatening diseases. This is evidenced by the dramatic increase in the number of INDs and marketing applications being filed each year with health authorities around the world.

虽然很容易被这些创新产品的前景所吸引，但细胞和基因治疗初创公司的潜在买家应该以适当的怀疑态度，并带着问题来对待调查，旨在评估GxP的合规性，以及后期临床开发的规模扩展和最终商业生产的可能性。

While it’s hard not to get caught up in the promise of these innovative products, potential buyers of cellular and gene therapy start-ups should approach diligence with an appropriate level of skepticism and a long list of questions. These should be aimed at assessing both GxP compliance and the likelihood of successfully scaling up to support later-stage clinical development and, ultimately, commercial manufacturing.

通常，使用细胞和基因疗法等先进疗法的患者群体的病情大多极其严重。在许多情况下，这种治疗手段已经是患者最后的希望。这吸引了许多极具天赋的医疗和生物技术专业人士来使用这些创新产品疗法。治疗本身就具有压力，特别是与传统药物治疗相比，这种压力会因时间紧迫而加剧。

It is often the case that for advanced therapeutics such as cellular and gene therapies, the patient population is extremely sick. In many instances, the therapy is the last hope for treatment. This draws extremely talented medical and biotech professionals to these innovative products. It also creates pressure which can be compounded by the very tight timelines, especially compared to traditional pharmaceuticals.

例如，对于CAR-T产品，从血液分离到生产、检测、放行和输注的时间表是以天或周为单位，几乎没有误差。此外，由于患者通常病得很重，因此不能中途失败再重新开始。但没有人的时间表是百分百完美的，看似很小的变化都会对下游产生重大影响。特别是在许多情况下，主要的起始物料是来自病情严重患者的细胞。

For example, for CAR T products, the timeline from apheresis to manufacturing, testing, release, and infusion is measured in days or weeks, and there is little to no room for error. Further, because the patients are often so sick, failing and starting over isn’t an option. Nobody is perfect 100% of the time, and seemingly small changes can have major impacts downstream, especially when, in many cases, the primary starting material is the cells from very sick patients.

这与大规模生产传统小分子的情况非常不同，传统小分子生产的投入、工艺和产出都可以受到严格的质量控制，如果出现任何偏差，整个批次都将被拒绝。

This can be a very different situation from the large scale manufacturing of a traditional small molecule, where there will be an input, a process, and an output which can be strictly quality controlled, and where if any deviation occurs an entire batch will be rejected. Cellular and gene therapy companies may be focused on manufacturing from an R&D perspective and on getting a product to patients as quickly and efficiently as possible. This can create different challenges for quality and compliance than those experienced by traditional manufacturers.

在遵守监管机构的GxP要求时，为重病患者提供产品的紧迫性会遭受压力，其中许多要求显然不适合这些创新产品。在美国，我们已经看到这种紧迫性可能导致产品与FDA的合规要求有一定差距。这些合规差距会延误开发和批准，并导致卫生当局采取强制措施。而当交易结束后，从监管角度来看，卖方的合规差距问题就会变成买方的合规差距问题。从研发的角度来看，细胞和基因治疗公司可能专注于生产，并尽可能快速有效地将产品送到患者手中。因此与传统生产商相比，将会给生产质量和合规性带来不一样的挑战。

The urgency of getting products to very ill patients can also create tensions when complying with regulators’ GxP requirements, many of which do not clearly fit these innovative products. In the U.S., we have seen that this tension can result in compliance gaps with FDA’s requirements. These compliance gaps can delay development, delay approval, and lead to enforcement action by health authorities. And after the close of a transaction, the seller’s compliance gaps become the buyer’s compliance gaps from a regulatory perspective.

因此，对于细胞和基因治疗公司的潜在买家来说，真正熟悉产品、工艺和目标公司的质量理念至关重要。在尽职调查阶段，要了解目标公司如何调查和处理失败问题，特别是在临床开发环境中，要了解目标公司是否在质量上进行了投资。买家还应该看看目标公司正在做什么，为从临床到商业的快速过渡做好准备，因为许多先进的治疗方法都受益于快速通道、加速批准和优先审查等快速批准途径。在尽职调查阶段之后，实现投资价值通常包括制定和部署首天计划，以确保尽职调查期间发现的任何合规差距得到充分解决。

It is therefore critical for a potential buyer of a cellular and gene therapy company to truly familiarize itself with the product, the process, and the target company’s quality mindset. At the due diligence stage, this means understanding how the target approaches and investigates failures, especially in the clinical development setting, and whether the target has invested in quality. One should also look at what the target is doing to prepare for the potential of a rapid transition from clinical to commercial, as many advanced therapies benefit from expedited approval pathways such as fast track, accelerated approval, and priority review. Beyond the due diligence stage, realizing the value of the investment often includes the development and deployment of a day-one plan to ensure that any compliance gaps identified during due diligence are fully addressed.