创新生产和制造以应对Covid-19的挑战

To accelerate vaccine production and supply involves collaboration with more than 20 supply partners in more than 15 countries, supported by more than 20 analytical testing sites.

Our supply chain includes multiple manufacturing facilities across each stage of production - drug substance, drug product, and finished packaging. These partners will collaborate with us throughout the entire manufacturing process, receiving support and technical guidance.

我们的批量供应能力的核心是定义生产过程的化学，制造和控制（CMC）。在CMC期间，我们正在开发一个优化，可重复的制造过程，该工艺可提供最大的收率，并确保在我们的供应链中高质量的产品。

This manufacturing process is then transferred to our partners to establish supply at their respective facilities. Because quality testing is required throughout the manufacturing process, as well as to support product release in market, we have also built an extensive analytical network and are rapidly transferring our analytical methods to these laboratories.

Our procurement team is also working to secure and accelerate a global supply chain of critical raw materials, reagents and consumables in collaboration with our suppliers to enable rapid manufacturing and quality testing.

一目了然地做疫苗

These are the crucial manufacturing processes needed to create a vaccine on an unprecedented scale:

• CMC -A commercial manufacturing process has been developed from an initial small-scale process before rapidly scaling to increase productivity yields, all the time ensuring purity of the final product. This consistent process is employed by each manufacturing facility we are collaborating with.
• 病毒种子库存和寄主细胞库 -这些起始材料被世界各地的制造商使用来启动疫苗生产。
• Drug substance –宿主细胞生长在一系列具有量表的生物反应器中，并被病毒种子感染以产生最终的疫苗分子。采取一系列过滤和色谱步骤来收集和净化疫苗。
• 药品 -The drug substance is combined with buffers to achieve a final formulation and then filled into multi-dose vials, which are labelled and packaged.
• Testing and quality control –在整个制造过程中，对每批进行了广泛的测试。质量控制措施在生产的各个阶段采用，以确保一致性和质量。

Ensuring the vaccine produced is of consistent, high quality, the production process utilises living ‘producer cells’ derived from a human cell line, created more than 50 years ago. The cells are altered to act as ‘mini factories’ to produce the vaccine rapidly.

Growth of the producer cells takes place in single use bioreactors, which reduces the risk of cross contamination and enhances biologic and process safety. Conditions including pH and temperature are very tightly controlled to ensure growth occurs at an optimal rate.

一旦生产者细胞达到包含所需病毒颗粒浓度的生长阶段，就会收获载体疫苗。使用裂解化学物质释放疫苗，细胞破裂。然后，培养物进行了一系列过滤步骤，以去除细胞碎屑，然后进行一系列过滤过程，以提高疫苗产物的产量和清晰度。使用正常的流量过滤（NFF），将培养物穿过一系列膜，这些膜含有不同尺寸的孔径，可滤除不同尺寸的细胞碎屑和废物产物。在此阶段，一些样本也可以去除以创建另一批矢量疫苗工作库存。

Membrane chromatography is then carried out to further purify the product. This ‘giant’ chromatography step can be carried out at large scale and works by the vaccine selectively binding to its surface, which is then released as the purified product. Finally, ultrafiltration re-buffers the viral vector vaccine into its final formulation.

The final drug substance is transported for ‘fill and finish’ into multi-dose vials and packaged into cartons. The finished drug product is anticipated to be stored and transported at 2-8^oC, pending ongoing stability studies. Final determination of temperature and shelf life will only be made once sufficient data has been collected for the vaccine over time and approval by regulators.

Safety and quality standards of vaccine manufacturing are of paramount importance and quality testing is required throughout the process, as well as to support product release authorisation in the markets and regions. Numerous tests are carried out at each step of the drug substance and drug product manufacturing processes and quality control measures are employed throughout to ensure consistency and quality of the vaccine. In total, more than 60 tests per batch are conducted to ensure safety, purity and efficacy.

质量测试

We use various technology platforms such as polymerase chain reaction (PCR) to rapidly identify the vaccine and sequencing technology to verify the adenoviral vector carries the spike protein genetic code, high pressure liquid chromatography (HPLC) to assess purity and anion exchange chromatography (AEX) to measure viral titer. In addition, researchers from Bristol University have recentlyconfirmed载体疫苗准确地遵循了编程的遗传指令，通过高级测序和蛋白质分析技术在细胞内形成尖峰蛋白。¹

还可以通过测试确定疫苗等因素，例如热，光，辐射，环境变化以及与容器材料的相互作用的影响。在生产过程的每个阶段定义了存储和处理条件，以优化产品稳定性，保质期并确保保持安全性，质量和功效。鉴于需要在速度下进行进展，稳定性测试是与药物制造和随着时间收集的数据并行进行的，以确定疫苗传输和储存的最佳温度范围。

All manufacturing partners are subject to Current Good Manufacturing Practice (CGMP) and appropriate Quality Systems leading to licensure in their specific supply region. The manufacturing process is used by our partners at their respective facilities and we are rapidly transferring our analytical methods to ensure a repeatable manufacturing process that ensures high-quality product across our supply chain.

AstraZeneca has committed to the global development and production of a potential vaccine for COVID-19 to ensure supply for as many countries as possible, at no profit during the pandemic period. We have built a global supply network adhering to the highest quality and safety standards with a capacity so far towards three billion doses. We have done this so that if clinical trials show the vaccine is safe and effective and approvals for use are received from regulators, the governments and multilateral organisations that we have formed agreements with can then work to ensure fair allocation and distribution of the vaccine within their countries and regions.