????去年10月，美國食品和藥物管理局（Food and Drug Administration，簡稱FDA）做出了一項極不尋常的舉動：宣布該機構(gòu)此前已批準的一種仿制藥——廣泛應(yīng)用的抗抑郁癥劑安非他酮的仿制品——與專利藥在“生物等效性”上并不相同。FDA決定撤銷批準。

????監(jiān)管機構(gòu)的舉動震動了市場。負責銷售該藥的梯瓦制藥公司（Teva Pharmaceuticals）決定立即停止銷售，其它公司也在FDA的要求下對旗下的安非他酮仿制藥進行試驗。許多醫(yī)生和醫(yī)學會一直在私下探索一個近乎異端的問題：仿制藥真的與專利品牌藥一模一樣嗎？而他們表示，在相當多的情況下，答案都是否定的。FDA此次出手，更是為他們的行為注入了新的動力。

????如果你是外行，你也許這么看仿制藥：他們和專利藥完全一致，只是包裝不同。仿制藥廠商之所以能以極其低廉的價格出售藥品，是因為他們沒有巨額的藥品研發(fā)和市場推廣費用。

????所以，這就解釋了為什么美國醫(yī)藥界在2012年開出的處方中，超過80%的都是仿制藥。根據(jù)美國仿制藥協(xié)會（Generic Pharmaceutical Association）的數(shù)據(jù)，無品牌的仿制藥去年一共為美國人民節(jié)省了1,930億美元醫(yī)藥費。

????不過，仿制藥和專利藥的差別可比你想像的要大得多。首先，專利藥廠商在專利過期、或者遭到質(zhì)疑時，并不會將其制造方法拱手讓出。專利只列出了藥品成分，并沒有詳細解釋制造藥品的過程。事實上，制造仿制藥通常需要逆向工程，得出的結(jié)果絕非專利藥的復(fù)制品，僅僅只是其近似值。

????FDA的相關(guān)規(guī)定也明確承認這點。它的“生物等效性”的界定范圍大得有些讓人驚訝：仿制藥的有效成分在人體血液內(nèi)的最高濃度必須不低于專利藥的20%并且不高于25%。這意味著那些標榜著“原汁原味”的仿制藥，其有效成分與專利藥的差別可能高達45%。

????仿制藥與專利藥還存在其它差別。雖然仿制藥必須含有與專利藥一致的有效成分，但其其它成分，也就是通常所說的輔料，可以不同。事實上，這些輔料的品質(zhì)通常要低于專利藥。這樣的差別會影響到“生物利用率”——人體血液系統(tǒng)所能夠吸收的藥品數(shù)量。美國心臟協(xié)會（American Heart Association）最近指出，“一些通常被認為可有可無的輔料，如酒精糖、環(huán)糊糖和聚山梨醇酯八十等，可能會改變藥物溶解率，從而影響到其生物利用率。”

????譯者：項航

????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."