Contents

Part 1: Introduction

Part 2: Phases of Clinical Trials of Investigational New Drugs

Part 3: Investigational New Drugs Requirements

Part 1: Introduction

Definition of an Investigational Product? ?試驗藥物的定義

ICH GCP defines an investigational product as,

“A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial” (ICH GCP 1.33).

ICH GCP將試驗藥物定義為：屹篓，

“在臨床試驗中測試或用作參考的活性成分或安慰劑的藥物形式”（ICH GCP 1.33）

This may include a marketed product that is being used in a different form than the one it was approved for, or a marketed product being used for an unapproved or new indication.

這可能包括以不同于批準(zhǔn)的形式使用的上市產(chǎn)品仪搔，或用于未批準(zhǔn)或新適應(yīng)癥的上市產(chǎn)品。

Definition of an Investigational New Drug? ?研究新藥的定義

The Code of Federal Regulations (CFR) defines an investigational new drug as: "...a new drug or biological drug that is used in a clinical investigation."

聯(lián)邦法規(guī)（CFR）將試驗新藥定義為： “……用于臨床研究的新藥或生物藥物。”

In the U.S. Food and Drug Administration (FDA) regulations, an investigational new drug is any substance (such as a drug, vaccine or other biological product) for which FDA approval is being sought.

在美國食品和藥物管理局（FDA）法規(guī)中，研究新藥是指尋求FDA批準(zhǔn)的任何物質(zhì)（如藥物、疫苗或其他生物制品）。

A drug may be considered “new” even if it has been in use for years if a change is proposed in its use, formulation, route of administration, use in patient population where risk would be increased, or packaging. For example, years ago the FDA approved a drug to treat high blood pressure. The manufacturer of the drug now wants to test it as a treatment for anxiety in adults. This new use of the drug would be considered investigational.

如果建議改變藥物的使用恳蹲、配方、給藥途徑俩滥、在風(fēng)險增加的患者群體中的使用或包裝嘉蕾，即使藥物已使用多年，也可能被認(rèn)為是“新的”霜旧。例如错忱，幾年前FDA批準(zhǔn)了一種治療高血壓的藥物。該藥物的制造商現(xiàn)在想測試它作為成人焦慮癥的治療方法挂据。這種藥物的新用途將被視為是研究性的以清。

In a study protocol and other documents, an investigational new drug may be referred to as the “study drug,” “experimental product,” “experimental drug,” “new intervention,” or similar term. Investigational new drugs are regulated under CFR Title 21 Part 312 (21 CFR 312).

在研究方案和其他文件中，實驗性新藥可以被稱為“研究藥物”崎逃、“實驗產(chǎn)品”掷倔、“實驗藥物”、“新干預(yù)措施”或類似的術(shù)語个绍。實驗性新藥受CFR Title 21 Part 312 (21cfr 312)的監(jiān)管勒葱。

Labeling of an Investigational New Drug? ?試驗新藥的標(biāo)簽

The labeling of an investigational new drug:

Ⅰ、Must include the following statement: “Caution: New Drug — Limited by Federal (or United States) law to investigational use.”

Ⅱ巴柿、Must not be false or misleading and should not imply that the drug is safe or effective for the investigational purpose.

試驗新藥的標(biāo)簽：

1错森、必須包括以下聲明：“警告：新藥-受聯(lián)邦（或美國）法律限制用于研究用途±航啵”

2、不得為虛假或誤導(dǎo)殃姓，且不得暗示該藥物在研究目的上是安全或有效的袁波。

Control of an Investigational New Drug? ?研究新藥的控制

An investigational new drug may be given to participants only under supervision by the principal investigator or by a sub-investigator. (Usually, the person supervising the administration of an investigational new drug is a physician.) The investigator cannot supply the investigational new drug to any person who is not authorized to receive it.

研究新藥只能在主要研究者或副研究者的監(jiān)督下給予參與者瓦阐。（通常，監(jiān)督研究新藥管理的人員是醫(yī)生篷牌。）研究人員不能向未經(jīng)授權(quán)接受試驗新藥的任何人提供試驗新藥睡蟋。

Research that involves the use of controlled substances must comply with U.S. Drug Enforcement Administration regulations (21 CFR 1300-end). When studying an investigational new drug that is considered a controlled substance, the investigator must take adequate precautions to prevent theft or diversion of the?drug into illegal channels of distribution. Such precautions include storing the investigational new drug "in a securely locked, substantially constructed cabinet or other securely locked, substantially constructed enclosure, access to which is limited."

涉及使用受管制藥物的研究必須符合美國藥物管制局的規(guī)定(21 CFR 1300-end)。當(dāng)研究一種被認(rèn)為是管制物質(zhì)的實驗性新藥時枷颊，研究人員必須采取充分的預(yù)防措施戳杀，以防止盜竊或?qū)⑺幬镛D(zhuǎn)移到非法分銷渠道。這些預(yù)防措施包括將研究用的新藥儲存在“一個安全鎖住夭苗、結(jié)構(gòu)牢固的柜子或其他安全鎖住信卡、結(jié)構(gòu)牢固的外殼中，進(jìn)入該外殼是受限制的题造“剑”

Promotion of and Charging for Investigational New Drugs? ?研究性新藥的推廣和收費

Neither an investigator nor a sponsor may promote (that is, endorse or advertise) an investigational new drug as safe or effective for the investigational purpose. In addition:

研究者或贊助商不得為研究目的宣傳(即，認(rèn)可或宣傳)一種實驗性新藥為安全或有效界赔。此外:

Ⅰ丢习、An investigational new drug cannot be distributed commercially or in a test market.

Ⅱ、An investigation cannot be prolonged “after finding that the results of the investigation appear to establish sufficient data to support a marketing application.” In other words, if there is good evidence that the investigational new drug is safe and effective, the study should be stopped and no other participants enrolled.

Ⅲ淮悼、Charging for an investigational new drug in a clinical trial is not permitted without approval from the FDA unless the drug is being provided for treatment use.

1咐低、研究新藥不能在商業(yè)或試驗市場上銷售。

2袜腥、在發(fā)現(xiàn)調(diào)查結(jié)果似乎建立了支持營銷申請的足夠數(shù)據(jù)后见擦，調(diào)查不能延長換句話說，如果有充分證據(jù)表明試驗新藥是安全有效的瞧挤，則應(yīng)停止該研究锡宋，且不得招募其他參與者。

3特恬、未經(jīng)FDA批準(zhǔn)执俩，不允許在臨床試驗中對研究新藥收費，除非該藥物用于治療用途癌刽。

Part 2: Phases of Clinical Trials of Investigational New Drugs? ?研究新藥臨床試驗的階段

Clinical trials of an investigational new drug are generally conducted in four phases, Phase 1 to Phase 4. Phase 0, or “exploratory” trials, also exist as small clinical trials (sometimes only a few participants) that involve dosing at a sub-therapeutic level. Phase 0 trials are not as prevalent as Phases 1-4. Each phase is designed to find out different information. Although the phases of a trial are usually conducted sequentially (one after another), they sometimes overlap.

研究新藥的臨床試驗通常分四個階段進(jìn)行役首，第一階段至第四階段。0期或“探索性”試驗也作為小型臨床試驗（有時只有少數(shù)參與者）存在显拜，涉及亞治療水平的劑量衡奥。與第一階段相比，第四階段試驗并不普遍远荠。每個階段都是為了找出不同的信息矮固。雖然試驗的各個階段通常是按順序（一個接一個）進(jìn)行的，但有時會重疊譬淳。

Individuals may be eligible for studies in different phases, depending on their age, general condition, the type and stage of their disease, and previous therapy, if any.

個人可能有資格參加不同階段的研究档址，這取決于他們的年齡盹兢、一般情況、疾病的類型和階段以及以前的治療（如果有）守伸。

PHASE 1 Trials

Phase 1 trials are the first studies of an investigational new drug in humans. They are usually conducted in healthy volunteers. In some cases, Phase 1 trials may be conducted in individuals who have the disease the drug is intended to treat. Phase I trials generally involve between 20 and 80 participants.

第一階段試驗是首次在人類身上研究一種試驗性新藥绎秒。他們通常在健康志愿者中進(jìn)行。在某些情況下尼摹，可能會對患有該藥物擬治療疾病的個人進(jìn)行Ⅰ期試驗见芹。第一階段試驗通常涉及20至80名參與者。

Phase 1 trials are designed to:

Ⅰ蠢涝、Make a preliminary determination of the drug's safety in humans.

Ⅱ玄呛、Identify some of the side effects associated with the drug's use.

Ⅲ、Begin to define a safe therapeutic (healing) dose range.

第一階段試驗旨在：

1惠赫、初步確定該藥物在人體內(nèi)的安全性把鉴。

2、確定與藥物使用相關(guān)的一些副作用儿咱。

3庭砍、開始定義安全的治療（愈合）劑量范圍。

PHASE 2 Trials

Phase 2 trials are usually conducted in individuals who have the disease the drug is intended to treat or are at high risk for developing the disease. Phase 2 trials are larger than Phase 1 trials but still relatively small, usually involving no more than several hundred participants.

第二階段試驗通常在患有該藥物擬治療的疾病或處于疾病高風(fēng)險的個體中進(jìn)行混埠。第二階段試驗比第一階段試驗大怠缸，但仍然相對較小，通常不超過幾百名參與者钳宪。

Phase 2 trials are designed to:

Ⅰ揭北、Begin to evaluate the drug's effectiveness in treating or preventing the disease or condition of interest.

Ⅱ、Determine the optimal dosing of the drug.

Ⅲ吏颖、Determine the common short-term side effects and risks associated with the drug.

第二階段試驗旨在：

1搔体、開始評估藥物在治療或預(yù)防感興趣的疾病或狀況方面的有效性。

2半醉、確定藥物的最佳劑量疚俱。

3、確定與藥物相關(guān)的常見短期副作用和風(fēng)險缩多。

PHASE 3 Trials

Phase 3 trials are conducted after preliminary evidence from Phase 1 and 2 trials suggests that the investigational new drug is safe and effective. They usually include between several hundred and several thousand participants.

第三階段試驗是在第一階段和第二階段試驗的初步證據(jù)表明研究新藥是安全有效的之后進(jìn)行的呆奕。他們通常包括幾百到幾千名參與者。

Phase 3 trials are designed to:

Ⅰ衬吆、Gather additional information about the drug's safety and effectiveness to evaluate whether its benefits outweigh its risks.

Ⅱ梁钾、Compare it to other commonly used treatments for the same condition (if available) or compared to a placebo. These studies can be performed in a blinded manner.

Ⅲ、Evaluate interactions with other treatments that may be used at the same time as the investigational new drug.

Ⅳ逊抡、Provide adequate information to determine the indication for which the drug will be labeled if it is approved for marketing as well as any limitations on the drug's use that should be stated in the labeling. For example, if there were insufficient information to show that a drug can safely be given to children, the labeling would restrict the drug's use to adults.

第Ⅲ階段試驗旨在：

1姆泻、收集有關(guān)藥物安全性和有效性的額外信息，以評估其益處是否大于風(fēng)險。

2拇勃、將其與相同條件下的其他常用治療方法（如有）或安慰劑進(jìn)行比較蛾娶。這些研究可以盲法進(jìn)行。

3潜秋、評估可能與試驗新藥同時使用的其他治療的相互作用。

4胎许、提供足夠的信息峻呛，以確定批準(zhǔn)上市的藥物將被貼標(biāo)簽的適應(yīng)癥，以及標(biāo)簽中應(yīng)說明的藥物使用限制辜窑。例如，如果沒有足夠的信息表明一種藥物可以安全地給兒童服用，那么標(biāo)簽將限制成年人使用該藥物肤无。

PHASE 4 Trials

Phase 4 trials are conducted after the drug or treatment has been approved for marketing. They are designed to:

Ⅰ论泛、Continue testing the drug or treatment to collect additional short-term safety information.

Ⅱ、Collect information about the effect of the drug or treatment in various populations.

Ⅲ所禀、Collect information about side effects associated with long-term use of the drug.

第四階段試驗在藥物或治療被批準(zhǔn)上市后進(jìn)行方面。其目的是：

1、繼續(xù)測試藥物或治療色徘，以收集額外的短期安全信息恭金。

2、收集藥物或治療對不同人群的影響信息褂策。

3横腿、收集與長期使用藥物相關(guān)的副作用信息。

Part 3: Investigational New Drugs Requirements? ?研究性新藥要求

The Investigational New Drug Application? ?研究性新藥應(yīng)用

A sponsor who wishes to conduct a clinical trial that involves an investigational new drug must submit an Investigational New Drug application (IND) to the FDA. In IND studies, the IND holder is considered to be the sponsor.

發(fā)起人希望進(jìn)行涉及臨床試驗新藥的臨床試驗斤寂，必須向FDA提交臨床試驗新藥申請(IND)耿焊。在IND研究中，IND持有人被認(rèn)為是發(fā)起人遍搞。

Information that must be provided in an IND? ?IND中必須提供的信息

Information that must be provided in an IND includes the following:

IND中必須提供的信息包括：

Ⅰ罗侯、The identity and contact information of the sponsor and the phase (or phases) of the trial.

Ⅱ、A commitment that an IRB will be responsible for initial and continuing review of the trial.

Ⅲ尾抑、The name of the drug, a list of its active ingredients, and its dosage and route of administration.

Ⅳ歇父、The objectives and planned duration of the proposed clinical trial(s).

Ⅴ、A brief description of the plan for investigating the drug, including:

? ?i再愈、The reasoning behind the drug or the study,

? ?ii榜苫、The indication(s) to be studied,

? ?iii、The kinds of clinical trials to be conducted in the first year after the IND submission,

? ?iv翎冲、The estimated number of patients who will be given the drug in the clinical trial(s), and

? ?v垂睬、Any serious risks that are anticipated on the basis of animal studies or previous human studies of this drug or related drugs.

Ⅵ、For most trials, a copy of the investigator's brochure.

Ⅶ、A protocol for each planned study. (See related material summarized from The Research Protocol module.)

Ⅷ驹饺、The identities and qualifications of all investigators. (As demonstrated in a Curriculum Vitae and Form FDA 1572. Click here for instructions on completing Form FDA 1572.)

Ⅸ钳枕、The criteria for patient selection and exclusion and an estimate of the number of patients to be studied.

Ⅹ、A summary of previous experience with the drug in both animal and human studies, including (if relevant):

? ?i赏壹、Previous INDs,

? ?ii鱼炒、Experience with the drug in other countries,

? ?iii、Known safety issues, chemistry and manufacturing information, and

? ?iv蝌借、Dependence and abuse potential.

1昔瞧、主辦方的身份和聯(lián)系方式以及試驗階段。

2菩佑、IRB將負(fù)責(zé)試驗的初始和持續(xù)審查的承諾自晰。

3、藥物名稱稍坯、有效成分清單酬荞、劑量和給藥途徑。

4瞧哟、擬定臨床試驗的目標(biāo)和計劃持續(xù)時間混巧。

5、藥品調(diào)查計劃的簡要說明绢涡，包括：

（1）藥物或研究背后的原因牲剃，

（2）要研究的適應(yīng)癥;

（3）IND提交后第一年進(jìn)行的臨床試驗種類;

（4）預(yù)計將在臨床試驗中使用該藥物的患者人數(shù)，以及

（5）根據(jù)本藥物或相關(guān)藥物的動物研究或先前的人體研究雄可，預(yù)期存在的任何嚴(yán)重風(fēng)險凿傅。

6、對于大多數(shù)試驗数苫，一份調(diào)查員的小冊子聪舒。

7、每個計劃研究的方案虐急。(參見研究協(xié)議模塊總結(jié)的相關(guān)材料箱残。)

8、所有調(diào)查人員的身份和資格止吁。(如履歷和FDA 1572表格所示被辑。點擊此處查看填寫FDA 1572表格的說明。)

9敬惦、患者選擇和排除的標(biāo)準(zhǔn)和估計的患者數(shù)量的研究盼理。

10、該藥物在動物和人類研究中的經(jīng)驗總結(jié)俄删，包括(如相關(guān)):

（1） 以前的IND宏怔，

（2）在其他國家使用該藥物的經(jīng)驗奏路，

（3）已知安全問題、化學(xué)和制造信息臊诊，以及

（4）依賴和濫用的可能性鸽粉。

When an IND Goes Into Effect? ?當(dāng)IND生效時

An IND is considered safe to proceed 30 calendar days after the FDA receives it unless:

Ⅰ、The FDA notifies the sponsor that the investigation described in the IND is subject to a clinical hold, or

Ⅱ抓艳、The sponsor receives written permission from the FDA to begin the study before 30 days have elapsed.

在FDA收到IND后的30個日歷日內(nèi)触机，IND被認(rèn)為是安全的，除非：

Ⅰ玷或、FDA通知申辦方IND中描述的調(diào)查將被臨床擱置威兜，或

Ⅱ、申辦方收到FDA的書面許可庐椒，在30天內(nèi)開始研究。

At the sponsor's request, the FDA will provide advice on specific matters relating to an IND. Meetings between a sponsor and the FDA are frequently useful, and the FDA encourages such meetings to the extent that FDA resources permit.

應(yīng)贊助商的要求蚂踊，F(xiàn)DA將就與IND相關(guān)的具體事項提供建議约谈。贊助商和FDA之間的會議通常是有用的，F(xiàn)DA鼓勵在FDA資源允許的范圍內(nèi)舉行此類會議犁钟。

IND Exemptions for Studies of Lawfully Marketed Drugs? ?IND對合法銷售藥物研究的豁免

Studies of lawfully marketed drugs are exempt from the IND regulations if they meet all five of the criteria listed in 21 CFR 312.2(b)(1). The first four of these criteria are straightforward and need no special comment.

如果合法上市藥物的研究符合21 CFR 312.2（b）（1）中列出的所有五項標(biāo)準(zhǔn)棱诱，則可免于遵守IND法規(guī)。這些標(biāo)準(zhǔn)中的前四個很簡單涝动，無需特別評論迈勋。

Ⅰ、study is not intended to support approval of a new indication or a significant change in the product's labeling.

Ⅱ醋粟、The study is not intended to support a significant change in the product's advertising.

Ⅲ靡菇、The study is conducted in compliance with Institutional Review Board (IRB) and informed consent regulations.

Ⅳ、The study will not be used to promote non-approved indications.

1米愿、本研究不支持批準(zhǔn)新的適應(yīng)癥或產(chǎn)品標(biāo)簽的重大變更厦凤。

2、本研究無意支持產(chǎn)品廣告的重大變化育苟。

3较鼓、本研究按照機(jī)構(gòu)審查委員會（IRB）和知情同意條例進(jìn)行。

4违柏、本研究不會用于推廣未經(jīng)批準(zhǔn)的適應(yīng)癥博烂。

The final criterion, however, requires interpretation.

然而，最終標(biāo)準(zhǔn)需要解釋漱竖。

The investigation does not involve a route of administration, dosage level, use in a patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug.

調(diào)查不涉及給藥途徑禽篱、劑量水平、患者群體中的使用闲孤，或顯著增加與藥物使用相關(guān)的風(fēng)險（或降低風(fēng)險可接受性）的其他因素谆级。

It is the investigator's responsibility to determine whether an IND is necessary for a study that involves a marketed drug. A critical question in determining whether such a study is exempt from IND regulation is whether the study “significantly increases the risk” associated with use of the drug.

研究者有責(zé)任確定IND對于涉及上市藥物的研究是否必要烤礁。確定此類研究是否免于IND監(jiān)管的一個關(guān)鍵問題是，該研究是否“顯著增加”與藥物使用相關(guān)的風(fēng)險肥照。

If an investigator is quite sure that a drug study does not require an IND, he or she can simply not submit an IND application. If the investigator is doubtful about whether an IND is required, or wishes to have proof of the IND-exempt status of a study, the IND application can be submitted with an exemption from IND guidelines requested, and FDA staff will review the application to determine whether the study is exempt. The review is limited to critical safety concerns (dose, schedule, route, and patient population). If, after this limited review, the FDA determines that a study is exempt from the requirement for an IND, it performs no further review of the application. The FDA sends a letter to the sponsor giving notice of the exemption. Prior to submission of the application, the sponsor can also set up a pre-IND meeting with the FDA in order to discuss any questions or concerns.

如果研究人員非常確定藥物研究不需要IND脚仔，他或她可以不提交IND申請。如果研究人員懷疑是否需要IND舆绎，或希望獲得研究的IND豁免狀態(tài)的證明鲤脏，則可以提交IND申請，并要求豁免IND指南吕朵，F(xiàn)DA工作人員將審查申請以確定研究是否豁免猎醇。審查僅限于關(guān)鍵安全問題（劑量、時間表努溃、路線和患者群體）硫嘶。如果在本次有限審查后，F(xiàn)DA確定某項研究不受IND要求的約束梧税，則不會對該申請進(jìn)行進(jìn)一步審查沦疾。食品和藥物管理局向申辦方發(fā)送了一封信，通知其豁免第队。在提交申請之前哮塞，申辦人還可以與FDA召開IND前會議，以討論任何問題或擔(dān)憂凳谦。

IND Protocol Amendments? ?IND協(xié)議修正案

The sponsor of an IND must submit a protocol amendment to the FDA:

Ⅰ忆畅、To describe any change in a Phase 1 protocol that significantly affects the safety of participants; or

Ⅱ、To describe any change in a Phase 2 or Phase 3 protocol that significantly affects the safety of participants, the scope of the investigation, or the scientific quality of the study.

IND的發(fā)起人必須向FDA提交一份方案修正案：

Ⅰ尸执、描述第一階段方案中顯著影響參與者安全的任何變化家凯；或

Ⅱ、描述第2階段或第3階段方案中顯著影響參與者安全性如失、調(diào)查范圍或研究科學(xué)質(zhì)量的任何變化肆饶。

The following are examples of changes that would require the submission of a protocol amendment to the FDA:

Ⅰ、An increase in drug dosage or in the duration of participants' exposure to the drug.

Ⅱ岖常、A significant change in the study design, such as the addition or elimination of a control group.

Ⅲ驯镊、The addition of a new test or procedure to improve monitoring for, or to reduce the risk of, an adverse event, or the dropping of a test intended to monitor safety.

Ⅳ、The protocol amendment can be implemented at study sites after the amended protocol has been submitted to and approved by the reviewing IRB, and submitted to the FDA..

以下是需要向FDA提交方案修正案的變更示例：

1竭鞍、增加藥物劑量或在參與者接觸藥物的時間內(nèi)板惑。

2、研究設(shè)計的重大改變偎快，如增加或消除對照組冯乘。

3、增加新的檢測或程序晒夹，以改善對不良事件的監(jiān)測或降低風(fēng)險裆馒，或放棄旨在監(jiān)測安全的檢測姊氓。

4、在修改后的方案提交給審查IRB并獲得批準(zhǔn)喷好，并提交給FDA后翔横，可在研究地點實施。

A protocol change that is intended to eliminate an apparent immediate hazard to participants may be implemented immediately, provided that:

Ⅰ梗搅、The FDA is subsequently notified of the change by a protocol amendment, and

Ⅱ禾唁、The reviewing IRB is also notified of the change in accordance with the IRB's rules.

可立即實施旨在消除對參與者造成明顯直接危害的方案變更，前提是：

1无切、FDA隨后通過方案修訂通知變更荡短，以及

2、根據(jù)IRB的規(guī)則哆键，審查IRB也會收到變更通知掘托。

IND Safety Reports? ?IND安全報告

Sponsors must promptly review and investigate all information they receive relevant to the safety of an investigational new drug that is received from any source, foreign or domestic, including information derived from:

發(fā)起人必須立即審查和調(diào)查從任何來源（國外或國內(nèi)）收到的與試驗新藥安全性相關(guān)的所有信息，包括來自以下方面的信息：

Ⅰ籍嘹、Clinical or epidemiological studies,

Ⅱ烫映、Animal studies,

Ⅲ、Commercial marketing experience,

Ⅳ噩峦、Reports in the scientific literature,

Ⅴ、Unpublished scientific papers, and

Ⅵ抽兆、Reports from foreign regulatory authorities.

1识补、臨床或流行病學(xué)研究，

2辫红、動物研究凭涂，

3、商業(yè)營銷經(jīng)驗贴妻，

4切油、科學(xué)文獻(xiàn)報道，

5名惩、未發(fā)表的科學(xué)論文

6澎胡、來自外國監(jiān)管機(jī)構(gòu)的報告。

The sponsor must notify the FDA of any unexpected fatal or life-threatening experience associated with the use of the drug as soon as possible but not later than 7 calendar days after the sponsor's initial receipt of the information. Sponsors must provide written notification to the FDA and to all investigators participating in a trial within 15 calendar days of any adverse event that is:

申辦方必須盡快通知FDA與藥物使用相關(guān)的任何意外的致命或危及生命的經(jīng)歷娩鹉，但不得晚于申辦方最初收到信息后的7個日歷天攻谁。贊助商必須在出現(xiàn)任何不良事件的15個日歷日內(nèi)向FDA和所有參與試驗的研究者提供書面通知，即：

Ⅰ弯予、Both serious and unexpected, and

Ⅱ戚宦、Reasonably likely to have been caused by the investigational new drug.

1、嚴(yán)重和意外锈嫩，以及

2受楼、合理可能是由試驗新藥引起的垦搬。

Subsequent, appropriate follow-up information must also be submitted, as it becomes available.

隨后，還必須提交適當(dāng)?shù)暮罄m(xù)信息艳汽，因為這些信息是可用的猴贰。

The sponsor must also provide written notification of any finding from tests in laboratory animals that suggests a significant risk for human participants. The written notification must be provided as soon as possible and no later than 15 calendar days after the sponsor receives the information.

贊助人還必須提供書面通知，說明在實驗室動物試驗中發(fā)現(xiàn)的對人類參與者有重大風(fēng)險的任何發(fā)現(xiàn)骚灸。書面通知必須盡快提供糟趾，且不得遲于贊助商收到信息后15個日歷日。

IND Information Amendments and Annual Reports? ?IND信息修訂和年度報告

A sponsor must file an information amendment to report essential information about the IND that is not within the scope of a protocol amendment, IND safety report, or annual report. The following are examples of information that requires the filing of an information amendment:

Ⅰ甚牲、New information about technical features of the drug, such as its toxicology or chemistry.

Ⅱ义郑、Discontinuation of a clinical investigation.

贊助商必須提交信息修正案，以報告不在方案修正案丈钙、IND安全報告或年度報告范圍內(nèi)的有關(guān)IND的基本信息非驮。以下是需要提交信息修正案的信息示例：

1、關(guān)于藥物技術(shù)特征的新信息雏赦，如毒理學(xué)或化學(xué)劫笙。

2、臨床研究的中止星岗。

Within 60 days of the first anniversary of the date the IND went into effect, and every subsequent year, a sponsor must submit a brief report of the progress of the investigation. This annual report must include:

Ⅰ填大、A brief summary of the status of each study in progress or completed.

Ⅱ、A summary of the most frequent and most serious adverse experiences.

Ⅲ俏橘、A summary of all IND safety reports submitted.

Ⅳ允华、A list of participants who died during participation in the investigation, with the cause of death for each participant.

Ⅴ、A list of participants who dropped out as a result of any adverse experience, whether or not the adverse experience is thought to be related to the investigational new drug.

Ⅵ寥掐、A summary of the general investigational plan for the upcoming year.

Ⅶ靴寂、An updated Investigator's Brochure, if available.

Ⅷ、A summary of any foreign market developments.

Ⅸ召耘、A summary of any outstanding business with the FDA regarding the IND (i.e. a response to an FDA request for information).

自IND生效之日起一周年后的60天內(nèi)百炬，以及隨后的每一年，申辦人必須提交一份調(diào)查進(jìn)展的簡要報告污它。該年度報告必須包括：

1剖踊、每項正在進(jìn)行或已完成的研究狀態(tài)的簡要總結(jié)。

2衫贬、最常見和最嚴(yán)重的不良經(jīng)歷總結(jié)蜜宪。

3、提交的所有IND安全報告的摘要祥山。

4圃验、參與調(diào)查期間死亡的參與者名單，每個參與者的死因缝呕。

5澳窑、因任何不良經(jīng)歷而退出的參與者名單斧散，無論不良經(jīng)歷是否被認(rèn)為與試驗新藥有關(guān)。

6摊聋、下一年度總體調(diào)查計劃概要鸡捐。

7、更新的研究人員手冊（如有）麻裁。

8箍镜、任何國外市場發(fā)展的總結(jié)。

9煎源、與美國食品和藥物管理局有關(guān)IND的任何未決業(yè)務(wù)的摘要（即對美國食品和藥物管理局信息請求的回復(fù)）色迂。