“OUR INDUSTRY IS POISED TO TRANSLATE OUR MOST PROMISING SCIENTIFIC BREAKTHROUGHS INTO MEANINGFUL TREATMENTS CAPABLE OF TACKLING THE MOST URGENT AND VEXING MEDICAL CHALLENGES OF OUR TIMES. WE STAND COMMITTED TO DRIVING PROGRESS FOR PATIENTS TODAY – AND HOPE FOR TOMORROW.”
“我们的行业准备把我们最有希望的科学突破转化为有意义的治疗方法，以应对我们这个时代最紧迫、最令人头痛的医疗挑战。我们致力于推动进步，为今天的病人，也为明天的希望。”
CHAIRMAN & CEO, MERCK
默克公司董事长兼首席执行官
KENNETH C. FRAZIER
来源 | PhRMA 编译 | Tony 个人微信公众号：药事谷
For patients, new medicines offer fewer side effects, fewer hospitalizations, improved quality of life, increased productivity, and importantly, extended lives. But developing medicines is a long, complex process.
对病人而言，新药副作用更小，需要的住院治疗更少，可以提高生活质量，增加生产效率，重要的是延续生命。但药物开发是一个长期和复杂的过程。
The rapid pace of scientific advances is enabling a greater understanding of diseases at the molecular level. In turn, scientific, technical, and regulatory challenges related to drug development create complexities as companies often focus their R&D where the science is difficult and the failure risks are higher.
科技的快速发展增强了在分子层面对疾病的理解。相应的，与药物开发相关的科学的、技术的、和法规的挑战变得复杂，这正如制药公司通常关注于研发，技术复杂且失败的风险更高。
As a result, the process for researching and developing new medicines is growing in difficulty and length. On average, it takes at least ten years for a new medicine to complete the journey from initial discovery to the marketplace, with clinical trials alone taking six to seven years on average. The average cost to research and develop each successful drug is estimated to be $2.6 billion.
结果，研发新药的难度和时长在增加。平均而言，一个新药完成初始研究到上市需要花费至少10年时间，其中临床试验需要单独花费6~7年时间。成功开发一个新药的平均花费在26亿美元。
This number incorporates the cost of failures – of the thousands and sometimes millions of compounds that may be screened and assessed early in the R&D process, only a few of which will ultimately receive approval. The overall probability of clinical success (the likelihood that a drug entering clinical testing will eventually be approved) is estimated to be less than 12%.
这一数字包括了开发失败的花费 – 在早期研发阶段可能筛选成千的、有时候成百万的化合物，仅有少数可以获得最终批准。整体上临床试验成功的可能性低于12%。
While these numbers are daunting, a deeper understanding of the rigorous R&D process can explain why so many compounds do not make it and why it takes such a large, lengthy effort to get a new medicine to patients.
然而这些数字是令人气馁的，对严格的研发过程更深入的理解能够解释为什么这么多化合物没有成功，以及病人获得新药为什么需要花费如此巨大的努力。
Success requires immense resources — the best scientific minds, highly sophisticated technologies, ever-evolving manufacturing processes, and complex project management. It also takes persistence and, sometimes, luck. Ultimately, though, the process of drug discovery brings hope and relief to millions of patients.
成功需要大量的资源–-好的科学思维、高度复杂的技术、未曾涉及的制造流程、和复杂的项目管理。它同样需要坚持，有时也需要运气。尽管如此，最终药物研发过程带来希望和解救数以百万的病人。
The discovery process includes the early phases of research, which are designed to identify an investigational drug and perform initial tests in the lab. This first stage of the process takes approximately three to six years. By the end, researchers hope to identify a promising drug candidate to further study in the lab and in animal models, and then in people.
研发过程包括研发的早期阶段，此阶段被设计用来鉴定药物并在实验室进行最初的测试。此最初阶段花费大概3~6年时间。最后，研究人员希望得到一个有前途的候选药物，用以在实验室、动物模型和人体内进行深入研究。
Pre-Discovery
研究前
UNDERSTAND THE DISEASE OR CONDITION
理解疾病或病症
Recent advances in molecular medicine and powerful tools to enhance computational capacityare enabling researchers to better understand the inner workings of human disease at the molecular level. As our knowledge of disease increases, so does the potential of discovering and developing innovative medicines.
当前在分子医学用于增强计算能力的强大工具方面的进步，使得研究人员在分子水平能更好的理解人类疾病的内在运作机制。随着我们关于疾病知识的增长，研发创新药的潜力也在增长。
Biopharmaceutical companies perform basic research independently and in partnership with researchers and others from across the biomedical research ecosystem, including disease foundations and patient groups, venture capital, and pre-competitive consortia.
制药公司独立进行基础的研究，同时和研究人员、以及来自医疗研究生态系统的其他成员进行合作，包括疾病基金、病人组织、风投、和国际财团。
Personalized Medicine
个体化医疗
Advancements in science and technology are changing the way we define disease, develop drugs and prescribe treatments. Armed with a greater understanding of disease biology, it has become evident that a patient’s response to treatment— with respect to both safety and efficacy—is greatly dependent upon his or her molecular profile and genetic makeup.
科技的进步正改变我们对疾病、开发药物、和处方治疗的定义。通过对疾病生物学更深的理解，已经开始证实病人对治疗的反应—安全性和有效性—很大程度上依赖他/她的分子概况和基因组成。
The promise of personalized medicine (or precision medicine) is to get the right treatment to the right patient at the right dose the first time, through the use of molecular diagnostic tests and targeted therapies. Personalized medicines can potentially offer patients faster diagnoses, fewer side effects and better outcomes.
个体化医疗（或精准医疗）的目标是通过使用分子诊断测试和精准治疗在第一时间用正确的剂量对正确的病人实施正确的治疗。个体化医疗能够潜在的为患者提供更快速的诊断，更少的副反应，和更好的治疗效果。
These advances offer great promise, but also add complexity to the R&D process. In order to ensure the safety and efficacy of personalized therapies that are used alongside diagnostics, clinical trial protocols must be modified and enhanced.
这些进步给予了强大的希望，但也给研发过程增加了复杂性。为了确保诊断过程中个体化治疗的安全性和有效性，必须修改和强化临床试验方案。
This may entail the use of additional procedures and resources, as well as new or innovative forms of data collection. Additionally, by their very nature, the patient population identified to respond to targeted therapies is narrower, which makes patient recruitment more difficult.
这可能使用额外的程序、资源、和新的或创新的数据收集形式。此外，由于其特殊属性，对靶向治疗起作用的病人群体更窄，这使得病人招募更加困难。
Despite these challenges, America’s biopharmaceutical companies are committed to advancing personalized medicines. In fact, a recent industry survey revealed that 42% of new medicines in the pipeline have the potential to be personalized medicines.
尽管有众多挑战，美国的生物制药公司致力于推动个体化药物开发。事实上，近期一个行业调查显示，研发管线上42%的新药具有成为个体化药物的潜力。
Building on Setbacks
在挫折中前进
As researchers and scientists investigate new compounds, they are building off of a growing body of evidence that has accumulated over time, illuminating pathways of disease and providing insight into the optimal drug targets.
当研究人员和科学家研究新的化合物时，着时间的推移，他们正在逐渐积累越来越多的证据，疾病路径和最佳药物靶点也将越来越明晰。
Along the way, investigators uncover important milestones that may lead to new treatments, but there are also often many dead ends and setbacks, which may lead researchers down a new route, or force them to take a step back. While these stumbling blocks can be disappointing, they are an integral part of a complex research and development process; both the setbacks and successes provide invaluable knowledge that help guide and direct researchers to get one step closer to the next advance.
行进的道路上，研究人员揭示了可能导致新疗法的重要里程碑，但经常也会遇到死胡同和撤退的时候，这可能导致研究人员终止一条新路线，或强迫他们后退一步。尽管巨大的阻碍可能令人失望，但它们是复杂研发过程不可分割的一部分；挫折和成功提供了无价的知识，帮助引导研究人员向下一个进展更近一步。
Target Identification and Validation
靶点的鉴别和验证
CHOOSE A MOLECULE TO TARGET WITH A DRUG
选择一个药物靶向分子
Armed with an idea, researchers work to identify biological targets for a potential medicine. A drug target is a molecular structure in the body that, when it interacts with a potential drug compound, produces a clinical effect (treatment or prevention of a disease, for example).
有了一个想法，研究人员为一个潜在的药物鉴定生物学靶点。一个药物靶点在体内是一个分子结构，当它与一个潜在的药物相互作用时，会产生临床效果（如，治疗或预防疾病）。
The investigators conduct studies in cells, tissues and animal models to determine whether the target can be influenced by a medicine. Target validation is crucial to help scientists identify the most promising approaches before going into the laboratory to develop potential drug candidates, increasing the efficiency and effectiveness of the R&D process.
研究人员在细胞内、组织和动物模型上进行研究，来确定靶点是否受到药物影响。在进入实验室开发候选药物之前，靶点验证对帮助确认最有前景的药物至关重要，这可以增加研发过程的有效性和效率。
Drug Discovery
药物研究 FIND A PROMISING MOLECULE (A “LEAD COMPOUND”) THAT COULD BECOME A NEW MEDICINE
寻找一个可能成为新药有前景的分子（先导化合物）
After learning more about the underlying disease pathway and identifying potential targets, researchers then seek to narrow the field of compounds to one lead compound – a promising molecule that could influence the target and, potentially, become a medicine.
在学习了更多关于潜在疾病路径和鉴定潜在靶点的知识后，研究人员寻求缩小化合物的范围以得到一个先导化合物 — 一个能够作用于靶点并能够成为药物的有前景的分子。
They do this in a variety of ways, including creating a molecule from living or synthetic material, using high-throughput screening techniques to select a few promising possibilities from among thousands of potential candidates, identifying compounds found in nature, and using biotechnology to genetically ngineer living systems to produce disease-fighting molecules.
获得先导化合物有多种途径，包括从有生命的或合成的材料中创造分子，使用高通量筛选技术从成千的候选药物中筛选少数有前途的可能成药的化合物，使用生物技术到基因工程生命系统来制造对抗疾病的分子。
Even at this early stage, investigators are already thinking about the final product, and how it will be administered to patients (for example, whether it is taken in pill form, injected, or inhaled). In turn, they must also consider the formulation (the design of dosage forms) of a medicine and how easily it can be produced and manufactured.
尽管这是在早期阶段，但研究人员已经正在考虑最终的药物产品将如何被病人服用（如，药丸的给药形式，注射或）。相应的，他们必须考虑药物制剂（剂量设计）以及药物如何能更容易的被生产制造出来。
Biopharmaceutical R&D Ecosystem: Delivering New Medicines to Patients
生物医药研发生态系统：将新药带给病人
“TODAY, MOST IMPORTANT DEVELOPMENTS IN MEDICAL SCIENCE TYPICALLY BEGIN IN LABORATORIES, SUCH AS THE DISCOVERY OF SPECIFIC NEW BIOLOGICAL MOLECULES, PROCESSES, OR PATHWAYS, OR INNOVATIVE APPLICATIONS OF EXISTING KNOWLEDGE. IN MOST CASES, THESE DISCOVERIES IN AND OF THEMSELVES HAVE LIMITED EFFECT BEYOND MEETING A FAIRLY NARROW RESEARCH GOAL. THEIR REAL IMPACT FOR PUBLIC HEALTH GENERALLY COMES AFTER SEVERAL MORE SIGNIFICANT STEPS - INCLUDING FURTHER R&D, TESTING, APPROVAL BY APPROPRIATE REGULATORY BODIES (SUCH AS THE FDA), MANUFACTURING, AND DISTRIBUTION.”
当今，大多数医药科学的发展通常是在实验室进行的，如新生物学分子、过程或路径的科学发现，或已有知识的创新应用。这对公众健康的影响通常在经历几个重要步骤后才会体现出来，包括深入的研发，测试，监管机构的批准（比如FDA），生产和销售。
NATIONAL INSTITUTES OF HEALTH, OFFICE OF TECHNOLOGY TRANSFER
美国国立卫生研究院（NIH）技术转化办公室
The Biopharmaceutical Research Ecosystem Drives Innovation
生物医药研发生态驱动创新
The close and synergistic relationship between sectors in the biopharmaceutical research ecosystem is among our greatest strength in ensuring a robust national biomedical research capacity, making the United States the worldwide leader in biopharmaceutical innovation. Drug discovery and development occurs as a result of many forms of collaboration, with learnings emerging from many disciplines as the result of multiple feedback loops.
生物制药研究生态系统中各部门之间密切和协同的关系, 是我们确保强大的国家医学研究能力的最大力量之一，这将使美国成为全球生物医药创新领导者（美国人民傲气满满啊）。药物的研发是由于多种形式的合作而产生的, 来自许多学科的新成果都是由多个反馈环产生的。
Biopharmaceutical companies have formed a growing number of formal and informal partnerships with researchers in government, academic, patient and disease groups, and others in the biomedical ecosystem.
生物制药公司已经与政府研究人员、学术机构、患者和疾病组织以及生物医疗系统中的其他人员建立起数量不断增长的正式和非正式的伙伴关系。
Each partner brings different strengths and expertise to the partnership but all have the same goal of improving health outcomes for patients in the United States and around the world. Partnerships range from basic research, to identifying drug targets, to collaborations around innovative clinical trials.
每个成员将不同的优势和专家知识带给合作伙伴，所有人都有同一个目标，那就是改善美国和全球病人的健康。合作关系遍及基础研究，鉴定药物靶标，再到创新的临床试验合作。
While the basic science providing a foundation to discover and develop drugs is often initiated in academia, industry often partners and contributes to basic research. It is primarily the biopharmaceutical industry where the crucial disciplines of medicinal chemistry, process chemistry and formulation, drug metabolism and pharmacokinetics, and safety sciences are practiced at a scale and level of integration necessary in order to bring a new medicine to the patients that need them.
学术机构通常进行基础研究为药物开发提供基础，而工业界往往是合作伙伴，并对基础研究作出贡献。为了将新药带给需要它的病人，生物制药工业在大规模和需要诚信的水平上实践药物化学的重要原则、化学工艺和制剂学、药物代谢和药物动力学、和安全科学方面至关重要的。
Studies that document the complementary roles of the public and private sectors have demonstrated that between 67% and 97% of drug development is conducted by the private sector.
关于公共和私人机构互补作用的研究已经表明，介于67%到97%的药物开发是由私立机构开展的。
The Importance Of Strong Intellectual Property Protections
强力保护知识产权的重要性
Intellectual property (IP) protections provide incentives for companies to make the long, costly investments that lead to medical advances and balances those with the desire for increased competition by timely entry of generics and biosimilars.
知识产权保护激励制药公司进行长期的和花费巨大的投资，这将促进医疗的进步，以及通过仿制药和生物类似药的及时进入来平衡竞争加剧的需求。
Strong IP protections, in the form of patents and exclusivity, provide the opportunity for companies to potentially recoup investments made to develop new medicines and to fundfuture research.
强力的知识产权保护， 以专利和独占权的形式为制药公司潜在的回收投资来开发新药和资助未来的研究提供机会。
Patents grant inventors the exclusive right with respect to their inventions without others being able to copy and sell it for a set period of time. Data exclusivity (DE)* runs concurrently with patents and prohibits third parties for a set period of time from using or relying upon an innovator’s valuable clinical data to obtain FDA approval for their product.
专利给予发明者关于其发明的市场独占权，在一个设定的时期内其他人不能够仿制和销售。数据排他性 (DE) * 与专利同时运行, 并禁止第三方在一段时间内使用或依赖于创新者的宝贵临床数据以获得 FDA 对其产品的认可。
There are also two key targeted incentives:
还有两个关键的目标激励措施：
Under the Best Pharmaceuticals for Children Act, companies can receive an additional six months of exclusivity upon the completion and submission of pediatric studies that meet the terms of a written request from FDA.根据最佳儿童药物法案，制药公司可以在完成并提交符合FDA书写要求的儿童用药研究后，获得额外6个月的独占期。
Under the Orphan Drug Act, seven years of market exclusivity (i.e., another product for same disease or condition cannot be approved during the seven years) is available to the first sponsor obtaining FDA approval of a designated drug to treat a rare disease or condition根据孤儿药法案，FDA批准用于治疗罕见疾病或病症的药物，首次申请可以获得7年的市场独占权（例如，其他治疗相同疾病或病症的药物在此7年内不能被批准）。
* FDA grants five years of DE after initial approval for small molecule drugs (new chemical entities); up to three years for new uses or other conditions of use; and twelve years for biologic medicines.
* FDA为小分子药物（新化学实体）首次获批后授予5年的数据独占权；新用途或其他使用条件授予至多3年数据独占权；和生物制品12年数据独占权。
Early Safety Tests
早期安全性测试
PERFORM INITIAL TESTS ON PROMISING COMPOUNDS
对有前景的化合物进行初步测试
Establishing the safety of a drug before use in humans begins early in the development process, as lead compounds go through a series of tests to provide a preliminary assessment of safety. Scientists assess how the body processes the investigational compound, also referred to as pharmacokinetics. They also evaluate the impact the investigational compound has on various functions within the body, or the pharmacodynamics.
早期的开发过程中，在用于人体之前证实药物的安全性，因此先导化合物会经过一系列的检测来提供早期的安全性评估。科学家评价研究的化合物在体内的过程，也被称为药动学。他们也评估研究的化合物在体内对各种人体功能的影响，也被称为药效学。
Successful drugs must be:
成功的药物必须是：
absorbed into the bloodstream,
吸收进入血液
distributed to the proper site of action in the body,
分布到体内合适的作用部位
metabolized efficiently and effectively,
高效和有效的代谢
successfully excreted from the body, and成功的从体内排泄，和
demonstrated to be not toxic in the tests performed.
开展的测试证明没有毒性
Normally performed in living cells, in animals and via computational models, these studies help researchers prioritize lead compounds early in the discovery process.
通常试验通过计算模型在活体细胞、动物中进行，这些研究帮助研究人员在开发的早期阶段优先确定先导化合物。
Lead Optimization
优化先导化合物
ALTER THE STRUCTURE OF LEAD CANDIDATES TO IMPROVE PROPERTIES
改善先导化合物结构以改善性能
Lead investigational compounds that survive the initial screening are then “optimized,” or altered to make them more effective and safer. By changing the structure of a compound, scientists can give it different properties. For example, they can make a compound less likely to interact with other chemical pathways in the body, thus reducing the potential for side effects.
先导化合物在早期的筛选中存活下来，然后进行“优化”或做一些改变使之更加有效和安全。通过改变化合物的分子结构，科学家可以让它具有不同的性质。例如，可以使一个化合物不怎么与体内的其他化学路径发生相互作用，从而减少潜在的副反应。
Hundreds of different variations or “analogues” of the initial leads are produced and tested. The resulting compound is the candidate drug which will undergo years of further testing and analysis before potentially being reviewed and assessed for approval by the U.S. Food and Drug Administration (FDA).
数以百计的先导化合物的不同变体或“类似物”被制备出来并进行测试。在FDA批准药物而进行审评和评估之前，最终的化合物作为候选药物将经历数年的进一步测试和分析。
Preclinical Testing
临床前试验
LAB AND ANIMAL TESTING TO DETERMINE IF THE DRUG IS SAFE FOR HUMAN TESTING
实验室和动物试验确定药物进行人体试验是否安全
With one or more lead compounds identified, researchers turn their attention to extensive testing to determine if they are ready to be studied in humans.
当一个或更多的先导化合物被鉴定出来，研究人员将注意力转移到拓展性测试，以决定是否为在人体内进行研究做好准备。
Scientists carry out both in vitro and in vivo tests. In vitro tests are experiments conducted in the lab (“vitro” is “glass” in Latin) and in vivo studies are those in living cell and tissue cultures and animal models (“vivo” is “life” in Latin).
科学家们开展体外和体内的测试。体外测试在实验室开展(“vitro” is “glass” in Latin)，体内研究在活体细胞、组织培养和动物模型中进行（“vivo” is “life” in Latin）。
Through these techniques, scientists work to understand how the drug works and what the potential side effects on humans might be. The FDA requires extremely thorough preclinical testing before the candidate drug is allowed to be studied in humans.
通过这些技术，科学家努力工作以理解药物如何工作的，以及可能对人体可能产生哪些潜在副作用。在候选药物开展人体试验之前，FDA需要极其严格的临床前测试。
During this stage scientists also must determine how to make large enough quantities of the drug to use in clinical trials. Techniques for making a drug on a small scale to use in this preclinical stage may not translate easily to larger production.
在此阶段，科学家们还必须决定如何使得足够数量的药物用于临床试验。临床前小规模的药物制备技术转移到大生产不是那么容易。
Production of the medicine will need to be scaled up even more if it is approved for use in the general patient population. After starting with thousands of candidate compounds, preclinical testing is used to identify one or more lead compounds that will go on to be studied in clinical trials.
尽管药物获得批准用于普通病人群体，但仍然需要药物的制造规模放大研究。开启对数以千计的候选化合物的临床前研究后，临床前测试用于鉴定一个或更多的先导化合物以用于后续的临床试验。
Adapting to Increased Uncertainty
适应增加的不确定性
As our scientific understanding advances, revealing the underlying complexities of disease, clinical trials have also become more complex. Planning and executing a clinical trial is an extremely rigorous process, with more procedures required, more data collected, and more numerous eligibility criteria for study enrollment than ever before.
随着我们科学理解力的进步和对疾病复杂性的揭示，临床试验也变得更加复杂。临床试验的设计和执行是个极其严格的过程，比以往需要更多的程序，更多搜集的数据，和更多的合格的标准。
For example, the average form used to collect data for each patient expanded in length by 227% between 2000 and 2011, reflecting the growing challenges of conducting clinical trials.
例如，用于收集每个病人信息的表格从2000年到2011年长度增加了227%，反映出开展临床试验不断增长的挑战。
Many factors contribute to the increasing challenges and costs of developing medicines, including:
许多因素助长了增加的挑战和药物开发的成本，包括：
Changing science – researchers are targeting more complex diseases where the science is difficult and failure risks higher改变科学——研究人员瞄准的是更复杂的疾病，因为科技的困难，失败的风险更高。
Increasing regulatory requirements
增加的法规要求
More testing against comparator drugs
比对比药物更多的测试
Increased challenges related to clinical trial recruitment and retention
与临床试验的招募和保留相关的挑战增加
Larger clinical trial sizes
更大的临床试验规模
Greater focus on targeting chronic and degenerative diseases
慢性和退行性疾病的重点关注
The biopharmaceutical industry is approaching these challenges head on, continually adapting to produce innovative treatments more efficiently. Researchers are exploring ways to reduce development times and increase the odds of success using new research models, new clinical trial designs and methodologies, innovative approaches to patient recruitment, and sophisticated methods of analyzing data.
生物制药行业正面临这些挑战, 不断更有效的适应生产创新疗法。研究人员正在探索减少开发时间的方法, 利用新的研究模式、新的临床试验设计和方法学、对患者招募的创新方法以及分析数据的复杂方法来增加成功的几率。
Clinical Trial Success Depends on Volunteers
临床试验的成功依赖于志愿者
An incredible amount of planning goes into the design and conduct of each clinical study. Outlined in the protocol are plans for all aspects of the trial from data collection methods to the timing of dosing to safety measures. None of this plan can go forward, though, without the volunteers who participate in the research studies. In many early clinical studies, healthy volunteer participants are essential in order for researchers to confirm that the candidate medicine can be safely tolerated.
设计和开展临床试验需要大量的计划。方案描述了临床试验的所有方面，从数据收集到给药时间再到安全性测量。然而，没有志愿者参与研究，那么任何计划都无法推进。在许多早期临床研究中，健康志愿者的参与为研究人员确定候选药物是安全耐受是必要的。
In later studies, clinical trials enroll patients who have the condition that the medicine is designed to address: their participation is crucial, so researchers can evaluate the effectiveness of the medicine, and understand if adjustments in dosing and timing are needed.
随后的临床试验会招募具有药物所治疗的适应症的病人：他们的参与至关重要，因此研究人员能够评估药物的有效性，弄清楚剂量和时间是否需要调整。
It can takes months, or even years, to recruit and enroll volunteers to participate in studies, and recruitment is a particular challenge for trials focused on rare diseases and pediatric indications.
招募志愿者参与临床试验会花费数月甚至数年时间，对于罕见病和儿科适应症的临床试验来说，志愿者招募相当具有挑战性。
It can be difficult to find volunteers for clinical trials, as there are often specific requirements for enrollment, based on the nature of the condition being studied and the patient group that is expected to benefit from the new medicine. Likewise, many people are not aware of the opportunities they might have to participate in a trial. Patients choose to participate for many different reasons, including the desire to get the most cutting edge care available and to help advance science.
基于研究情况的性质和病人组希望从新药中获益，招募工作通常有具体的要求，因此为临床试验找到志愿者是困难的。同样的，很多人没有意识到他们参与临床试验可能拥有的机会。病人选择参与试验有许多不同的原因，包括希望获得最先进的治疗和帮助科学进步。
The Development Process
开发流程
A candidate drug must go through extensive studies in humans and demonstrate that it is safe and effective before receiving approval from the FDA. This process involves three phases of clinical trials, each with its own specific goals and requirements. Companies identify physician researchers to conduct the research and work with them to carry out the procedures of each trial according to a detailed plan, or protocol.
候选药物必须在人体内经过广泛的研究，在获得FDA批准前证明其安全有效。这个过程包括三个时期的临床试验，每一期试验都有其各自的目标和要求。制药公司确定医生来执行临床研究，根据详细的计划或方案，和他们一起工作并执行每一期试验的程序。
The clinical trials process is both expensive and time-consuming, and ends more often in failure than success. Less than 12% of the candidate medicines that enter clinical testing make it to approval. From start to finish, the clinical development phase takes an average of six to seven years. There are many people involved in the process, including doctors, nurses, lab technicians, clinical trial support team members, and clinical trial managers, among others.
临床试验过程不仅昂贵而且耗时，而且失败多于成功。进入临床试验的候选药物最终获批的少于12%。从开始到结束，临床开发阶段平均花费6到7年时间。很多人参与到这个过程，包括医生、护士、实验室技术人员、临床试验支持团队、和临床试验管理人员及其他。
Clinical trials are a significant undertaking, requiring extensive infrastructure, investment, careful regulation, safety measures, and coordinated planningacross stakeholders, as well as regulators at the FDA. The biopharmaceutical industry accounts for the vast majority of investment into clinical trials and related activities; in 2013 alone, biopharmaceutical companies sponsored 6,199 trials across the U.S. involving 1.1 million participants.
临床试验是一项意义重大的工作, 需要广泛的基础设施、投资、谨慎的监管、安全措施以及各利益攸关方以及FDA的监管机构的协调规划。生物制药业占了临床试验和相关活动的绝大部分投资；仅在 2013年, 生物制药公司就在美国发起了6199项试验, 涉及110万参与者。
Investigational New Drug Application and Clinical Trial Planning
新药临床试验申请和临床试验计划
FILE IND WITH THE FDA BEFORE CLINICAL TESTING CAN BEGIN; ENSURE SAFETY FOR CLINICAL TRIAL VOLUNTEERS
在临床试验开始之前向FDA提交资料，确保临床试验志愿者的安全
Before any clinical trial can begin, companies must file an investigational new drug (IND) application with the FDA. The application includes the results of the preclinical work, the candidate drug’s molecular structure, details on how the investigational medicine is thought to work in the body, a listing of any potential side effects as indicated by the preclinical studies, and manufacturing information. The IND also provides a detailed clinical trial plan that outlines how, where and by whom the studies will be conducted.
在所有临床试验开始之前，制药公司必须向FDA提交新药临床试验（IND）申请。该申请包括临床前工作的结论，候选药物的分子结构，研究的药物如何在体内运作的细节，列出临床前研究显示的任何潜在副反应，和生产信息。IND申请同样提供临床试验方案的细节，概述临床试验如何开展、哪里开展、由谁开展。
All INDs are submitted to the FDA and proceed after 30 days if there is no additional feedback or restriction given from the agency.
所有的临床试验需向FDA提交申请，如果没有收到反馈或被拒绝，30天后便可开展试验。
In addition to the IND application, all clinical trials must be reviewed, approved and monitored by the institutional review board (IRB) or ethics committee (EC) at the institutions where the trials will take place. The IRB/EC has the responsibility to protect research participants, and has the right to disapprove the study protocol or require changes before approving the planned clinical trials and allowing any participants to enroll. This process includes the development of appropriate informed consent documents, which will be required from all clinical trial participants.
提交临床试验申请后，所有的临床试验会经过机构审评委员会（IRB）或临床试验机构的伦理委员会（EC）的审评、批准和监测。IRB/EC有责任保护受试者，并且有权利在开展临床试验和受试者入组之前，不予批准临床试验或要求做出变更。该过程包括建立合适的知情同意书，这对所有临床试验受试者都是必需的。
The clinical trial research team, including the nurses and clinical investigators, continually monitor trial participants and collect data that will be carefully reviewed and tracked by the company supporting the research.
包括护士和临床研究者在内，临床研究团队持续监测受试者并收集数据，这将被制药公司仔细的评审和跟踪用来支持临床研究。
Whenever a volunteer in the trial experiences a serious adverse drug reaction, the company sponsoring the research must provide a report of the event to the FDA and the IRB. The FDA or the company can stop the trial at any time if problems arise.
无论何时，当志愿者在临床试验中遇到严重药品不良反应时，临床研究申办方必须向FDA和IRB提供事件的报告。FDA或制药公司可以在出现问题的时候随时停止试验。
In some cases, a study may be stopped because the candidate drug is performing so well that it would be unethical to withhold it from the patients in the trail who are not receiving the candidate drug and the company may accelerate development.
某些情况下，临床试验可能因候选药物表现太好而中止，在没有接受候选药物的患者中扣留药物是不道德的, 公司会加速药物开发。
Companies also ensure that the trials are conducted correctly and with integrity, and that clinical trial results are publicly disclosed at the appropriate time.
制药公司也需要确保正确、诚信/完整的开展试验，并在适当的时候公开临床试验结果。
Innovative Trial Designs and Methodologies
创新的试验设计和方法学
Innovative study designs and methodologies are transforming the way clinical research is conducted. In adaptive clinical trials, for example, researchers use accumulating data to modify aspects of the study (e.g., dosing, sample size, patient population) as it is under way, without undermining the validity and integrity of the trial, or having to redo the trial or conduct an additional study.
创新的研究设计和方法学正在改变临床研究的方式。例如, 在适应性临床试验中, 研究人员使用积累的数据来修改研究的各个方面 (例如, 剂量、样本大小、病人数量), 而不损害试验的有效性和完整性, 或必须重做试验或进行额外的研究。
Many new approaches for clinical trials are using novel drug development tools, such as biomarkers, to identify patients that may respond to a therapy. Basket studies in oncology, for example, identify a common genetic mutation across a variety of cancer types and enroll patients whose tumors have that mutation, regardless of the type of cancer they have, to test the effect of a single medicine. Conversely, umbrella studies test the impact of different medicines on different genetic mutations within a single type of cancer.
很多临床试验新方法使用了新颖的药物开发工具，例如生物标记物，来鉴别病人可能对药物有反应。例如肿瘤学中的篮子研究，通过大量的肿瘤类别来鉴别普遍的基因突变，进而不管是什么癌症类别，病人具有这种基因突变便被招募来测试此单一药物的效果。相反的，雨伞试验则测试不同的药物对同一癌症类别、不同基因突变的效果。
Innovative trial designs are capitalizing on the rapid pace of science, providing the possibility for researchers to shorten trials, improve success rates and increase the efficiency of clinical research.
创新的试验设计正在利用科学的快速进步为研究人员提供缩短试验的可能性，提高成功率以及提高临床研究的效率。
Industry's Clinical Trial Principles
行业的临床试验原则
PhRMA member companies have a longstanding commitment to sponsoring clinical research that fully complies with all legal and regulatory requirements, as well as international agreements. In addition, PhRMA has set out voluntary principles reflecting member companies’ commitment to the highest standards for ethics and transparency in the conduct of clinical trials.
PhRMA成员公司长期致力于赞助完全符合法规和国际协议的临床研究。此外，PhRMA已制定了自愿原则，反映出成员公司致力于临床试验中伦理和透明度的最高标准。
*PhRMA（Pharmaceutical Research and Manufacturers of America 美国药物研究和制造商协会）
PhRMA’s Principles on the Conduct of Clinical Trials and Communication of Clinical Trial Results are designed to help ensure that clinical research conducted by America’s biopharmaceutical companies continues to be carefully conducted and analyzed, and that the resulting information is communicated to health care professionals and patients in a way that is informative and meaningful.
PhRMA 的临床试验和临床试验结果沟通的原则旨在帮助确保美国生物制药公司进行的临床研究继续被仔细地进行和分析,由此产生的信息传达给医护人员和病人的方式是翔实和有意义的。
Phase I Clinical Trial
I 期临床试验
INITIAL SAFETY TESTING IN A SMALL GROUP OF HEALTHY VOLUNTEERS
一小群健康志愿者的初步安全测试
In Phase I trials the candidate drug is tested in people for the first time. These studies are usually conducted with a small number of healthy volunteers, generally 100 or less. The main goal of a Phase I trial is to assess the safety of the medicine when used in humans.
I期临床试验是候选药物在人体内的首次测试。这通常在少数健康志愿者身上完成，一般为100例或更少。I期临床试验的主要目的是评估当人使用药物时的安全性。
Researchers look at the pharmacokinetics of a drug: How is it absorbed? How is it metabolized and eliminated from the body? They also study the drug’s pharmacodynamics: Does it cause side effects? These closely monitored trials are designed to help researchers determine what the safe dosing range is and if the candidate medicine should move on to the next stage of development.
研究人员观察药物的药动学：它是如何被吸收的？它是如何被代谢和从体内排泄的？他们也研究药物的药效学：它会引起副作用吗？这些严密的监测试验用于帮助研究人员确定安全的剂量范围，以及候选药物是否应该进入下一个开发阶段。
Phase II Clinical Trial
II 期临床试验
ASSESS SAFETY AND EFFICACY IN A SMALL GROUP OF PATIENTS
通过一小群患者评估安全性和有效性
In Phase II trials researchers evaluate the candidate drug’s effectiveness in 100 to 500 patient volunteers with the disease or condition under study. Many Phase II trials study patients receiving the drug compared with patients receiving a different treatment, either an inactive substance (placebo), or a different drug that is usually considered the standard of care for the disease.
II期临床试验会有100到500例有相关疾病或病症的病人志愿者参与，研究人员以此评估候选药物的有效性。许多II期临床试验接受药物治疗的病人会与接受不同治疗的病人进行对比，要么是一个无活性的物质（安慰剂）或是普遍认为是该疾病治疗标准的另一个药物。
Researchers also analyze optimal dose strength and schedules for using the drug and examine the possible short-term side effects (adverse events) and risks associated with the drug. If the drug continues to show promise, they prepare for the much larger Phase III trials.
研究人员同样会分析选择的剂量和用药时间表，以及检查与药物相关的短期副作用（不良事件）和风险。如果药物持续表现良好，他们将准备进行更大规模的III期临床试验。
Phase III Clinical Trial
III 期临床试验
DEMONSTRATE SAFETY AND EFFICACY IN A LARGE GROUP OF PATIENTS
在一大群患者中证明安全性和有效性
Phase III trials generate statistically significant data about the safety, efficacy and the overall benefit-risk relationship of the investigational medicine. Phase III trials may enroll 1,000 to 5,000 patients or more across numerous clinical trials sites around the world. This phase of research is essential in determining whether the drug is safe and effective. It also provides the basis for labeling instructions to help ensure proper use of the drug (e.g., information on potential interactions with other medicines, specific dosing instructions, etc.)
III期临床试验会产生关于药物安全性、有效性、和总体获益-风险关系统计学意义的数据。III期临床试验可能招募1000到5000例病人或在世界范围内更多交叉的临床研究机构。此阶段的研究对确定药物是否安全有效是必需的。它也将为标签说明提供基本信息从而帮助确保合理用药（如，与其他药物发生潜在相互作用的信息，详细的剂量介绍，等。）
Phase III trials are both the costliest and longest trials, often encompassing hundreds of study sites at hospitals and centers both across the U.S. and around the world. Coordinating all the sites and the data coming from the clinical trial sites is a monumental task. Companies must coordinate closely with staff at each trial site, as well as with the IRB/EC that is monitoring the study and the FDA. Often, a clinical research organization (CRO) will work with a company to aid in recruitment and day-to-day operations of the trial.
III期临床试验最烧钱也最耗时，通常包含来自美国和世界各地数百家医院的研究机构和中心。协调所有的临床研究机构和来自各机构的数据是一项艰巨的任务。制药公司必须与研究机构的员工、监测临床试验的IRB/EC、以及FDA进行紧密协作。通常，临床研究组织（CRO）在试验过程中与制药公司一起工作帮助志愿者招募和日常运营。
In addition, the company’s manufacturing scientists are working to ensure high quality production of the medicine for use in the trials, as well as planning for the full-scale production of the medicine after approval. Meanwhile, the company is working to assemble and prepare the complex application required for FDA approval.
此外, 该公司的制造科学家正在努力确保高品质的药品生产在试验中使用, 以及计划在批准后的药品的全面生产。同时，制药公司正为药品获得FDA批准整合和准备复杂的申请。
Regulatory Review and Approval
法规的审评与审批
After determining that the results of the clinical trials indicate the compound is both safe and effective, the sponsoring company submits a new drug application (NDA) or biologics license application (BLA) to the FDA requesting approval to market the drug. These applications contain the results and data analysis from the entire clinical development program, as well as the earlier preclinical testing and proposals for manufacturing and labeling of the new medicine— which can run 100,000 pages or more.
在确定临床试验表明药物安全、有效后，申办方公司向FDA提交新药上市申请（NDA）或生物制品许可申请（BLA）要求批准药品上市。这些申请包含所有临床开发项目的结果和数据分析，早期临床前研究，和新药的制造和标签方案 — 这些文件可能有10万页或更多。
In order to accelerate the availability of medicines to patients with serious diseases or where there is an unmet medical need, the FDA implements expedited approaches to accelerate the development and review of new medicines, such as:
为了增加患有严重疾病或未满足的医疗需求的病人对药物的可及性，FDA执行加速程序来药物的开发和审评，如：
Fast Track: expedites the review of drugs that treat serious conditions and fill an unmet medical need.快速跟踪：加快对治疗严重疾病和满足未满足的治疗需求的药物的审评。
Breakthrough Therapy: expedites the development and review of drugs that may demonstrate substantial improvement over available therapy.突破疗法：加快比已有疗法显示出明显优势的药物的开发和审评。
Accelerated Approval: accelerates approval for drugs that address a serious condition or fill an unmet medical, based on a surrogate or an intermediate clinical endpoint.加速批准：根据替代品或中间临床终点，对解决重大疾病或填补未满足的医疗需求的药物加速批准
Priority Review: accelerates FDA evaluation of drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. Scientists, physicians and statisticians at the FDA review the data from all of the studies on the compound and, after weighing the benefits and risks of the potential medicine, decide whether to grant approval. Occasionally the FDA will ask for additional research before granting approval or convene an independent expert advisory panel to consider data presented by the FDA and the company.优先审评：如果批准可以显著提高治疗、诊断、或预防严重疾病的安全性和有效性，FDA会加快药物的评价。FDA的科学家、医生、和统计学家们会审评来自化合物的所有研究数据，在权衡药物的获益和风险之后，决定是否批准。偶尔的，FDA会在批准前要求制药工作进行额外的研究或召集独立的专家咨询会来考虑FDA和制药公司呈现的数据。
Manufacturing
生产
HIGH QUALITY, LARGE SCALE PRODUCTION OF NEW MEDICINES
高质量，新药的大规模产品
Approved medicines may be used by as many as millions of people or by only a very narrow patient population. Biopharmaceutical companies strive to manufacture high quality medicines available to patients for many years.
获批的药物可能被用在数以百万计的人身上或用于小范围病人群体。生物制药公司努力生产病人可获得的高质量药物花费多年时间。
Manufacturing facilities are constructed to the highest standards to ensure that safety and quality are built into each step of the manufacturing and production process. Companies must adhere to the FDA’s good manufacturing practices (GMP) regulations, and they also must constantly update, overhaul, or even rebuild facilities when new medicines are approved, as each new medicine is manufactured differently.
生产设施以最高标准建造，以确保生产和制造过程每一步的安全和质量。制药公司必须遵守FDA的药品生产质量管理规范（GMP），且必须持续更新、检修、或重新建设设施，因为当新药获批后，其制备工艺会有不同。
Advanced Manufacturing
先进的制造
Recent advances in science have propelled biopharmaceuticals into a new realm of
manufacturing complexity. Biologics, in particular, have created growing challenges for biopharmaceutical companies. These molecules are derived from living cells, and their manufacturing requires multiple steps that use robust technology to ensure purity, consistency and quality.
科学的最新进展推动生物医药进入制造复杂性的新境界。尤其是生物制品，给生物制药公司制造了不断增长的挑战。这些分子来源于活体细胞，它们的生产需要多个步骤使用稳健的工艺来确保纯度、一致性和质量。
Companies are implementing advanced manufacturing techniques to keep pace with rapid advances in science and medicine. They use cutting edge materials and emerging science capabilities (e.g., nanotechnology and continuous manufacturing) that are leveraged through close coordination of information, automation, computation, software, sensing, and networking to manufacture these complicated medicines. The scientific, R&D-driven manufacturing capability of the U.S. biopharmaceutical sector will be a crucial part of the health and economic well-being of the U.S. in the future.
制药公司使用先进的生产技术以跟上医药和科学的快速进步。他们使用前沿的材料和新兴的科学能力（如，纳米技术和连续生产），这些都是通过密切协调信息、自动化、计算、软件、传感、和网络来些复杂的药物。美国生物制药商科学的、研发驱动的制造能力将成为未来美国的健康和经济福祉的重要部分。
I'm Not Average: Matt Ellefson
我不是普通人：Matt Ellefson
When Matt Ellefson developed a cough, he didn’t think much of it. He assumed it was caused by the cold winter air, but as the weeks passed his cough lingered. Then he began coughing up blood.
当Matt Ellefson患了咳嗽，他并没有想太多。他认为这是冬天的冷空气引起的，但几周之后他的咳嗽依旧在徘徊，然后他开始咳血。
Within hours of going to the emergency room, Matt was diagnosed with advanced non-small cell lung cancer, and the prognosis was not good. With treatment, he faced a 5-year survival rate of less than 5%. His diagnosis in December 2009 was a complete shock. He was a nonsmoker who lived a healthy and fit lifestyle.
在去急诊室的几个小时内, Matt 被诊断为晚期非小细胞肺癌, 预后不好。治疗后, 他面临着5年的生存率不到5%。2009年12月的诊断完全令他震惊。他不吸烟，生活方式健康。
Soon after being diagnosed, Matt enrolled in an aggressive clinical trial. After 5 months, his cancer went into remission. One year later, his cancer resurfaced and it had spread. Treatment options were limited.
在被确诊后不久, Matt 就参加了一个积极的临床试验。5月后, 他的癌症开始缓解。一年后, 他的癌症再次重新露面，治疗是有限的。
While waiting for his doctor to conduct follow-up testing, he learned about a targeted gene therapy that had been recently approved. However, the odds were still against him. Patients typically developed resistance to the medicine in 8 months.
在等待他的医生进行随访测试时, 他了解到了最近批准的一种靶向基因治疗。然而他仍然可能失败。患者通常在8月内对药物产生抗药性。
Three years later Matt is living an active, happy life, with his disease under control thanks to advances and innovations in cancer medicines. He runs marathons, participates in cycling competitions, and explores the world with his family.
由于抗癌药物的创新和进步，他的病情得到了控制，三年后的Matt生活积极、快乐。他跑马拉松, 参加自行车比赛, 和他的家人一起探索世界。
If he does become resistant to his current medicine, there are 3 new drugs that have been approved, so now he has other options. He has hope because of the progress made in cancer research.
如果他开始耐受当前的药物，那么已经有3个新药获得批准，所有他还有其他选择。由于癌症研究的进步他充满希望。
Post Approval Research and Monitoring
批准后的研究和监测
Research on a new medicine does not end when the discovery and development phases are completed and the medicine is available to patients. On the contrary, companies conduct extensive post-approval research to monitor safety and long-term side effects, and may also pursue research into new indications for the medicine in different disease areas, age groups, or other patient populations.
当研发阶段完成且病人已能够获得药物，新药的研究并未结束。相反，制药公司开展大量的获批后研究来监测安全性和长期副反应，以及研究可能对药物在不同疾病领域、年龄组、或病人人群中发现新适应症。
Safety Monitoring and Research
安全性监测与研究
ONGOING REPORTING AND DATA COLLECTION
持续的报告和数据收集
The FDA requires that companies monitor approved medicines for as long as they stay on the market and require companies to submit periodic reports on safety and tolerability.
FDA要求制药公司对获批的药物进行上市后监测，提交安全性和耐受性方面周期性报告。
Companies must also report any serious and unexpected adverse events that occur from use of the medicine to the FDA in an expedited manner. The FDA sometimes requires companies to conduct Phase IV clinical trials, which evaluate the longterm safety or effects in specific patient subgroups.
公司还必须报告任何严重和意外的不良事件, 从使用药物到FDA的快速途径。FDA 有时要求公司进行第四阶段临床试验, 评估特定患者亚群的长期安全性或影响。
The FDA may also require implementation of a risk evaluation and mitigation strategy (REMS) when it determines that it is necessary to ensure, through the accumulation of additional evidence, that the medicine’s benefits outweigh its risks over time.
若通过对其他证据的评估来确保药物的获益大于风险是有必要的，FDA可能会要求制药公司执行风险评估和减低策略（REMS）。
*REMS：Risk Evaluation and Mitigation Strategy，风险评估和减低策略
A REMS can be required before or after FDA approval and can apply to one drug or a class of drugs. As an example, a REMS may outline specific safety procedures for health care providers before dispensing a drug, such as patient education of warning signs of infection.
对REMS的要求可能在FDA批准前或批准后，它也可以在一个或一类药物中执行。例如，调配药物之前，REMS可能为医护人员概括出特定的安全性程序，如感染警告标识的病人教育。
Research on Maximizing Therapeutic Value
治疗价值最大化的研究
ADDITIONAL BENEFITS REVEALED OVER TIME
随着时间的推移, 额外的好处显露出来
Although FDA approval of a new medicine is a critical milestone, in many cases it is the “starting point,” where data accumulated through ongoing research and the real-world clinical use of the medicine uncovers additional therapeutic value.
尽管FDA批准一个新药是至关重要的里程碑，但很多情况下这也是“起点” — 通过进行中的研究收集数据以及药物在真实世界的临床使用揭示额外的治疗价值。
Additional clinical value of therapies is realized over time though many different pathways, leading to expanded and improved use of a drug, including:
随着时间的推移，通过许多不同的途径，药物额外的临床价值被认识，这导致药物使用的扩大和改善，包括：
Greater value in original indication than initially seen in trials
在最初适应症上的价值比起初临床试验看到的更大
Earlier use of the medicine
药物提早使用
New indications in other diseases
其他疾病的新适应症
Combination use with other treatments
与其他治疗的联合
New formulation or method of delivery
新制剂或给药方式
Use in targeted patient subpopulations
用于目标亚群病人
The discovery and development of new medicines is a long, complex and rigorous process. Every step is aimed at bringing effective medicines to patients as quickly as possible, while ensuring the highest possible level of safety. It takes an average of ten years to develop a potential new medicine.
新药的开发是一个耗时长、复杂和严格的过程。每个步骤都以将有效的药物尽可能快的带给病人为目标，同时确保最高水平的安全性。开发一个潜在的新药平均需要花费10年时间。
Advances in our understanding of human biology and disease are opening up exciting new possibilities for potential new treatments and cures to meet patient needs. As the complexity of the science increases and R&D challenges mount, researchers are continually adapting and innovating to speed medical advances.
我们对人类生物学和疾病的理解的进步正在为潜在的新疗法和治疗方法开辟新的机会，满足病人的需求。随着科学的复杂性和研发挑战的增加，研究人员正在不断地适应和创新, 以加速医疗的进步。
Researchers are working every day in labs across the U.S. and around the world to turn scientific promise into new medicines for patients. Research-based biopharmaceutical companies are committed to advancing science and developing innovative medicines.
在美国及世界范围的研究人员为了将科学承诺变成病人所需的新药正在实验室日以继夜的工作。研发型生物制药公司致力于科技进步和创新药开发。
Realizing the promise and potential of the pipeline will require increased collaboration and convergence across a range of sectors and fields to harness novel scientific approaches, massive amounts of data and computational capabilities, and a range of new technologies. The scope of scientific and technological challenges and opportunities are heralding a new era of collaborative activity across a range of stakeholders.
要实现管道的承诺和潜力，就需要在一系列领域加强协作和融合，以利用新的科学方法、大量数据和计算能力，以及一系列新技术。科学和技术挑战的范围和机会都预示着协同活动的整个范围内的利益相关者的新时代。
Ensuring a favorable policy and regulatory environment is critical to sustaining the vibrant life sciences ecosystem in the U.S. and fostering the development of new medical advances against our most costly and challenging diseases.确保良好的政策和监管环境对维持美国生机勃勃的生命科学生态系统至关重要, 并促进发展新的医药进步, 以抵御我们最昂贵和最具挑战性的疾病。
联系客服
