[英文分析]为什么生物制造是那么艰苦？

StephenW

http://www.technologyreview.com/business/37955/page1/
Why Is Biomanufacturing So Hard?

Overhauling the manufacturing of biological drugs could make the process more reliable, improving access for patients.

    Friday, July 15, 2011
    By Emily Singer



Earlier this year, the Cambridge-based biotech firm Genzyme announced the latest in a series of manufacturing delays for Fabrazyme, a biological drug that treats a rare genetic disorder, after one lot of the drug was found to be contaminated. The news followed a more severe setback in 2009, when both Fabrazyme and another drug were contaminated with a virus; the problem closed the manufacturing plant and created major shortages.

Genzyme isn't alone in these issues. Biologics—drugs made through a biological process rather than chemical synthesis, a category that includes recombinant proteins, vaccines, and antibodies—are the fastest-growing segment of the pharmaceutical industry. In 2008, nearly 30 percent of revenue from the top 100 drugs came from biologics, a figure that is expected to rise to 50 percent by 2014.

But the same factors that make biologics powerful drugs also make them a challenge to manufacture. They typically mimic proteins and other molecules found in living organisms and can target harmful entities, such as some cancer cells, with great accuracy; many of the most promising new drugs for cancer and other diseases fall into this class. Biologics tend to be larger, more complex molecules than drugs synthesized through chemical reactions, which adds to production challenges and makes them costly. A single dose of some biologic therapies can cost $10,000.

Biologics are most often produced by cells growing in a bioreactor, a vat designed to maintain carefully calibrated conditions. Because the cells are alive, "every time you run a reactor, the result can be a bit different," says Chris Love, a chemical engineer who is part of MIT's Biomanufacturing Research Program. This inherent variability makes the process both expensive and unpredictable.
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Another issue is that for biologics to win approval from regulatory agencies, it's not enough for the drug itself to be approved, as is the case with small-molecule drugs; the manufacturing procedure must be approved as well. While this is important for safety's sake, it also makes it costly to change the production process after it's been approved, and that discourages innovation. "By the time the drug is in the marketplace, you are working with old technology," says Charles Cooney, a chemical engineer at MIT. "You have to lock in the technology many years before launch of a commercial product."

And even when developing experimental drugs, makers tend to stick with methods that have previously been proved safe. As a result, new advances in systems biology and microtechnology have not been integrated into biomanufacturing, says Love.
He and other researchers hope to change that by making biomanufacturing more predictable. One of Love's goals is to make sure the cells that produce these expensive drugs are as productive as possibly, which should bring costs down. To do that, researchers take advantage of the natural differences in productivity among cells. They foster mutations to create genetic variability and then use microchips to analyze the behavior of individual cells, choosing the most prolific for larger-scale production.

A second major challenge in biomanufacturing is ensuring the quality of the drugs, which is complicated because protein-based drugs must fold into a three-dimensional shape and must have the appropriate chemical tags. And because these drugs are produced under conditions favorable to microbes, they can be infected with viruses. "Many mistakes are made because we don't have the right analytics to measure the product or process," says Cooney. "Manufacturing sits on a critical path between science and the patient and should be integrated into the continuum of drug development. I think most companies know they need to invest early on in manufacturing, but they don't put enough effort into process development early on."

StephenW

谷歌翻译不是100％准确，仅供参考.

为什么是生物制造这么辛苦？

检修生物药品的生产，可以使这一过程更加可靠，改善患者的访问。

2011年7月15日（星期五）
由Emily Singer


今年早些时候，位于剑桥的生物技术公司Genzyme公司宣布Fabrazyme，治疗一种罕见的遗传性疾病的生物药物的生产延误系列的最新的，很多的药物后，被发现受到污染。消息接踵而至，2009年更严重的挫折，Fabrazyme和另一种药物时带有病毒的污染;问题关闭了制造工厂，创造了重大的短缺。

Genzyme公司不单单是这些问题。通过生物过程，而不是化学合成的，一个类别，其中包括重组蛋白，疫苗和生物制剂的药物抗体是医药行业增长最快的部分。 2008年，从排名前100位药品收入的近30％来自生物制剂，一个数字，预计到2014年上升50％。

但相同的因素，使生物制剂有效的药物也使他们制造的一个挑战。他们通常是模仿蛋白质和其他分子在生物体中发现，可以针对有害的实体，如一些癌细胞，丝丝入扣，许多最有前途的癌症和其他疾病的新药物属于这一类。生物制剂往往是更大，更复杂的分子比，通过化学反应，这更增加了生产的挑战，使他们昂贵合成药物。单剂量的一些生物疗法可以花费10000美元。

生物制品是最经常产生生长的细胞在生物反应器中，精心校准的条件下保持了增值税。克里斯说：“爱谁是麻省理工学院的生物制造研究计划的一部分，是一位化学工程师，因为细胞是活的，”每次运行的反应堆，结果可以是一个有点不同。这种固有的变异过程既昂贵和不可预知的。

另一个问题是，为生物制剂，以赢得监管机构的批准，它没有足够药物本身批准，与小分子药物的情况下，制造过程必须批准。虽然这是很重要的，为了安全起见，它也使得它被批准后，它的昂贵，改变生产工艺，并阻碍了创新。 “时间的药物在市场上，你是旧的科技工作，”查尔斯库尼说，在麻省理工学院的化学工程师。 “你一定要锁定在多年以前推出的商业产品的技术。”

即使开发实验性药物，决策者倾向于坚持先前已被证明安全的方法。因此，在系统生物学和微的新进展并没有被集成到生物制造的说，爱。
他和其他研究人员希望改变，生物制造更可预见的。爱的目标之一是确保细胞产生这些昂贵的药物都可能生产，这应该带来成本下降。要做到这一点，研究人员采取生产力的细胞之间的自然差异的优势。他们培养突变的遗传变异，然后用微芯片来分析单个细胞的行为，选择最丰富的较大规模的生产。

第二个生物药品生产企业的主要挑战是确保药物的质量，这是复杂的，因为基于蛋白质的药物，必须折叠成一个立体的形状，必须有相应的化学标记。而且，由于这些药物有利于微生物的条件下产生的，他们可以感染病毒。 “库尼说：”很多错误，因为我们没有正确的分析来衡量产品或工艺，。制造“坐落在一个科学和病人之间的关键路径，并应纳入到药物开发的连续，我想大多数公司都知道他们需要的初期投资在制造业，但他们没有投入足够的努力早在发展过程“。

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