Technology transfer and scale-up of the Flublok® recombinant hemagglutinin (HA) influenza vaccine manufacturing process
Technology transfer and scale-up of the Flublok® recombinant hemagglutinin (HA) influenza vaccine manufacturing process
复制标题
DOI：
10.1016/j.vaccine.2014.07.074
复制
发表时间：
2014-09-22
期刊：
影响因子：
5.5
通讯作者：
Cox, Manon M. J.
中科院分区：
文献类型：
--
作者：
Buckland, Barry;Boulanger, Robert;Cox, Manon M. J.
Protein Sciences Corporation（PSC）基于杆状病毒感染的昆虫细胞培养物，以650 L规模可重现地生产了多种不同的血凝素（HA）蛋白抗原。值得注意的是，这些HA蛋白抗原是通过与FDA批准的第一种重组流感疫苗（Flublok（R））的生物许可申请（BLA）中所述相同的通用生产工艺生产的。该技术是独特设计的，使得疫苗组成的变化可以容易地从一种HA蛋白抗原适应到另一种。在这里，我们提出了一种候选疫苗，以打击最近出现的H7N9病毒作为一个例子，从所需HA的遗传序列开始，杆状病毒的产生，并以纯化的蛋白抗原结束在GMP条件下，在38天内完成了10 L规模的生产（或疫苗组分）。在2 L、10 L、100 L、100 L和100 L规模下实现了相同的工艺性能。650 L和2500 L规模。举例说明了该技术如何在100天内从基准650 L规模设施转移到2500 L规模的改造微生物设施，其中包括设施工程变更的时间。Flublok（R）的技术转让和规模扩大这一过程对于在全球范围内迅速制造疫苗以预防大流行性流感具有重要意义。所描述的技术不具有与基于蛋的制造所面临的蛋适应菌株中的突变相同的脆弱性，并导致疫苗效力的损失。(C)2014爱思唯尔有限公司版权所有。
Multiple different hemagglutinin (HA) protein antigens have been reproducibly manufactured at the 650 L scale by Protein Sciences Corporation (PSC) based on an insect cell culture with baculovirus infection. Significantly, these HA protein antigens were produced by the same Universal Manufacturing process as described in the biological license application (BLA) for the first recombinant influenza vaccine approved by the FDA (Flublok (R)). The technology is uniquely designed so that a change in vaccine composition can be readily accommodated from one HA protein antigen to another one. Here we present a vaccine candidate to combat the recently emerged H7N9 virus as an example starting with the genetic sequence for the required HA, creation of the baculovirus and ending with purified protein antigen (or vaccine component) at the 10 L scale accomplished within 38 days under GMP conditions.The same process performance is being achieved at the 2 L, 10 L, 100 L, 650 L and 2500 L scale. An illustration is given of how the technology was transferred from the benchmark 650 L scale facility to a retrofitted microbial facility at the 2500 L scale within 100 days which includes the time for facility engineering changes.The successful development, technology transfer and scale-up of the Flublok (R) process has major implications for being ready to make vaccine rapidly on a worldwide scale as a defense against pandemic influenza. The technology described does not have the same vulnerability to mutations in the egg adapted strain, and resulting loss in vaccine efficacy, faced by egg based manufacture. (C) 2014 Elsevier Ltd. All rights reserved.