仿制药真的能媲美专利药吗？（节选）

    去年10月，美国食品和药物管理局（Food and Drug Administration，简称FDA）做出了一项极不寻常的举动：宣布该机构此前已批准的一种仿制药——广泛应用的抗抑郁症剂安非他酮的仿制品——与专利药在“生物等效性”上并不相同。FDA决定撤销批准。

    监管机构的举动震动了市场。负责销售该药的梯瓦制药公司（Teva Pharmaceuticals）决定立即停止销售，其它公司也在FDA的要求下对旗下的安非他酮仿制药进行试验。许多医生和医学会一直在私下探索一个近乎异端的问题：仿制药真的与专利品牌药一模一样吗？而他们表示，在相当多的情况下，答案都是否定的。FDA此次出手，更是为他们的行为注入了新的动力。

    如果你是外行，你也许这么看仿制药：他们和专利药完全一致，只是包装不同。仿制药厂商之所以能以极其低廉的价格出售药品，是因为他们没有巨额的药品研发和市场推广费用。

    所以，这就解释了为什么美国医药界在2012年开出的处方中，超过80%的都是仿制药。根据美国仿制药协会（Generic Pharmaceutical Association）的数据，无品牌的仿制药去年一共为美国人民节省了1,930亿美元医药费。

    不过，仿制药和专利药的差别可比你想像的要大得多。首先，专利药厂商在专利过期、或者遭到质疑时，并不会将其制造方法拱手让出。专利只列出了药品成分，并没有详细解释制造药品的过程。事实上，制造仿制药通常需要逆向工程，得出的结果绝非专利药的复制品，仅仅只是其近似值。

    FDA的相关规定也明确承认这点。它的“生物等效性”的界定范围大得有些让人惊讶：仿制药的有效成分在人体血液内的最高浓度必须不低于专利药的20%并且不高于25%。这意味着那些标榜着“原汁原味”的仿制药，其有效成分与专利药的差别可能高达45%。

    仿制药与专利药还存在其它差别。虽然仿制药必须含有与专利药一致的有效成分，但其其它成分，也就是通常所说的辅料，可以不同。事实上，这些辅料的品质通常要低于专利药。这样的差别会影响到“生物利用率”——人体血液系统所能够吸收的药品数量。美国心脏协会（American Heart Association）最近指出，“一些通常被认为可有可无的辅料，如酒精糖、环糊糖和聚山梨醇酯八十等，可能会改变药物溶解率，从而影响到其生物利用率。”

    译者：项航

    In October the Food and Drug Administration took a highly unusual step: It declared that a generic drug it had previously approved -- a version of the popular antidepressant Wellbutrin -- was not in fact "bioequivalent" to the name-brand version. The FDA withdrew its approval.

    The federal action shook the business. Teva Pharmaceuticals (TEVA), which marketed the generic in question, has stopped selling it, and other companies are now testing their versions of Wellbutrin at the FDA's request. The episode is bringing momentum to a movement that has been quietly building among many doctors and medical societies that are increasingly willing to ask a question that borders on heresy: Are generics really identical to the branded products they are meant to replicate? To a surprising degree, they say, the answer is no.

    If you're a layperson, this is the way you probably think of generics: They're the exact same products in different packaging; generics companies can sell such medications for a fraction of the cost of the originals because they don't have to spend huge sums on drug development and marketing.

    That apparent miracle explains why more than 80% of all U.S. prescriptions dispensed in 2012 were generic. Using nonbranded medications saved Americans $193 billion this past year, according to the Generic Pharmaceutical Association.

    But generic drugs diverge from the originals far more than most of us believe. For starters, it's not as if the maker of the original pharmaceutical hands over its manufacturing blueprint when its patent runs out or is challenged. The patent reveals the components, but it doesn't explain how to make the drug. In reality, manufacturing a generic requires reverse engineering, and the result is an approximation rather than a duplicate of the original.

    The FDA's rules effectively acknowledge that. The agency's definition of bioequivalence is surprisingly broad: A generic's maximum concentration of active ingredient in the blood must not fall more than 20% below or 25% above that of the brand name. This means a potential range of 45%, by that measure, among generics labeled as being the same.

    There are other differences. The generic must contain the same active ingredient as the original. But the additional ingredients, known as excipients, can be different and are often of lower quality. Those differences can affect what's called bioavailability -- the amount of drug that could potentially be absorbed into the bloodstream. As the American Heart Association recently noted, "Some additives traditionally thought to be inert, such as alcohol sugars, cyclodextrans, and polysorbate-80, may alter a drug's dissolution, thereby impacting its bioavailability."