藥品法規的差異性對台、美原料藥產業的影響

Abstract

藥品是確保人類健康延續生命不可或缺的物品。藥品的服用會直接影響人體，因此藥品的製造需要完善的設計，縝密的監控，及高度的法規來控制其品質並確保其安全性及有效性。藥品除了受每個國家個別的法規管理之外，由於市場全球化，國際間也在推動管理標準及相互認證，以避免研究資料及審查時間的重複與浪費，也進以確保人民可以快速的取得優良品質的救命藥品。因此，法規的管理及其所帶來對產業的影響即是本論文所探討之重點。\n相較於一般較熟悉的藥品製劑產業，原料藥雖僅為製藥產業的中游原料且市值也相對小，但由於是藥品中之有效成份，其品質及其物理性及化學特性卻是影響藥品的關鍵因素。近年來台灣原料藥廠因品質好且技術層次較中國及印度高，而價格又比日本等先進國家便宜，因此台灣原料藥廠紛紛站上國際舞台，供貨給歐、美等高法規限制市場，擴大了其市場及產能。而國內製藥產業的主力-學名藥，除了供給國內需求之外，也在主管關機台灣食品藥物管理局近年來推動並實施了許多與國際接軌的法規後，紛紛嘗試出口藥品至東南亞國家以外之歐、美市場。但國內學名藥廠所使用之原料藥大部分為國外進口，其中又以中國及印度為主，雖近年來國內並沒有發生因原料藥品質問題所產生重大事件，但病人與醫生對於國內學名藥之療效無法與原廠藥相同的聲音一直存在。鑿於藥品是使用在病人身上的最終產品，任何一個好品質的藥品，除了製造過程應嚴謹處理外，都應從源頭管理，即是其主成分:原料藥。原料藥非最終消費產品，原料藥大部分是化學合成，其生產廠是化學工廠的延伸，因此法規的管理與藥品也略有不同。一般化學品並准也不能直接使用在人體，不需要藥品的法規來管理，而同屬化學品之原料藥 因其對人體生命的重要性及其嚴重性，如何適當管理是一個很嚴肅卻較少人研究的課題。台灣現行原料藥的法規尚未像製劑產品一樣的與國際同步，且對進口原料藥及國內產製之原料藥的管理規範亦不盡相同。 因此本論文將探討國際上針對原料藥品質控管之規範，比較美國及台灣原料藥上市規範，並加入台灣產業實務上操作之狀況與意見，綜合考量後提出針對原料藥管理台灣法規面的相關建議。\n近年來各個跨國性的大藥廠紛紛將原料藥委外製造或對外購買，加上又一波的專利藥品即將到期，台灣原料藥廠可否把握此機會再創另一高峰令人期待。同時，雖然台灣製藥產業大多以生產學名藥為主，目前尚未有從新藥開發並經過臨床試驗到審核上市的案子，但由於台灣的研發能力高，且已有幾個由台灣廠商研發並經過初期臨床試驗後就技轉給國際大藥廠的案例。因此本論文也將探討我國針對新成分原料藥之法規是否能有助於原料藥產業及促進新藥之研發上市。

Drug product is indispensable to maintain health and prolong human life; since drug consumption directly affects human body, to control the quality of a drug product and ensure its safety and effectiveness, the manufacture of drug product needs to be well designed, monitored and regulated strictly by laws. In addition to being controlled and regulated by individual regulatory system in every countries, as the market is globalized, the activity of harmonizing the regulation requirements between each health authorities and setting the international standards are also been working on in order to avoid wasting of resources of industries on repeating work of preparing the similar drug dossiers on the same product for launching in different countries; it is also to speed up the review process for drug approval so that patient would have quicker access to high quality of drug products. Therefore, the main focus of this paper is to discuss the regulation of Active Pharmaceutical Ingredient (also called drug substance) and its impacts to the industry.\nAlthough comparing to the drug product/medicine industry, which people are more familiar with, API is only one of the components of drug product with smaller market value, yet as API is the main active ingredient of the drug product, its physical and chemical properties are the key factors affecting the drug product, its formulation and dosage form. In recent years, Taiwan API manufacturers become well-known on the international market due to its high quality in special nichec, and advanced technology with fairly reasonable price. Local API mnufacturers started exporting APIs to regulated markets such as the United States and Europe. As for local drug product manufacturers, which are mainly generic manufacturers/companies, while meeting the local needs, they also strive to export drug products not only to South East Asia but also slowly to the US and EU markets. However, most APIs which local generic companies use are imported from China and India, which the regulated level is not as high. Although there has not been any major quality issue with API, yet there are noises from the doctor and patient that the efficacy of generic drug can hardly deem to be the same as the originator`s brand name drug. As drug product is the end product which is consumed by patients, any “good quality” drug product should not only be well controlled with strict monitoring of manufacturing process, but starting from the beginning - API sourcing. Yet, the regulations of API should be different from drug product as API is not the end product and it is mostly chemically synthesized. Normally chemicals are not allowed to be used directly on human bodies and therefore do not need to be regulated; however, as API is a chemical compound, which would have direct and serious effect on human, how to management and regulat API properly is a less discussed but serious topic. The current regulations of drug substance in Taiwan have not been as “internationalized” like drug product, and there are also different policies for imported API and locally produced API. Therefore, this paper will introduce the current internal standard on controlling the API quality, and will compare the regulation systems of API registration in the US and Taiwan with practical practice going on in the industry. After the comprehensive introduction and evaluation, comments and suggestions will be proposed.\nIn recent years, many multinational drug product companies tend to have contract manufacturers to manufacture or outsource the needed API; in addition, many API compound patents will be expired soon, it is exciting to see if Taiwan API manufacturers can catch thess opportunities, expand their business and bring it to the next level. Although Taiwan pharmaceutical industries are more specialized in generic product, and there has not been any case of new drug development from drug discovery, clinical study, to product launch. However, as there are successful cases of licensing out brand new drug candidates to multinational companies after preliminary clinical study or even early clinical trial study, with strong search and development capability in Taiwan, therefore, the topic of how the brand new drug substance are regulated are also discussed to see if the current regulation can help the growth of API industry and enhance research and development of new drug products.