k****i
发帖数: 1126 | 1 Investigations covered under the IDE regulation are subject to differing
levels of regulatory control depending on the level of risk. The IDE
regulation distinguishes between significant and nonsignificant risk device
studies and the procedures for obtaining approval to begin the study differ
accordingly. Also, some types of studies are exempt from the IDE regulations.
Significant Risk Device
A significant risk device presents a potential for serious risk to the
health, safety, or welfare of a subject. Significant risk devices may
include implants, devices that support or sustain human life, and devices
that are substantially important in diagnosing, curing, mitigating or
treating disease or in preventing impairment to human health. Examples
include sutures, cardiac pacemakers, hydrocephalus shunts, and orthopedic
implants. Guidance on distinguishing between significant risk and
nonsignificant risks studies are outlined in the document 'Significant Risk
and Nonsignificant Risk Medical Device Studies'.
Studies of devices that pose a significant risk require both FDA and an
Institutional Review Board (IRB) approval prior to initiation of a clinical
study. FDA approval is obtained by submitting an IDE application to FDA (§
812.201).
In order to conduct a significant risk device study, a sponsor must:
submit a complete IDE application (§812.202) to FDA for review and obtain
FDA approval of the IDE;
submit the investigational plan and report of prior investigations (§812.
253 and §812.274) to the IRB at each institution where the investigation is
to be conducted for review and approval; and
select qualified investigators, provide them with all necessary information
on the investigational plan and report of prior investigations, and obtain
signed investigator agreements from them.
Upon receipt of an IDE application, sponsors are notified in writing of the
date that FDA received the original application and the IDE number assigned
(Receipt of supplements and amendments are not acknowledged). An IDE
application is considered approved 30 days after it has been received by FDA
, unless FDA otherwise informs the sponsor prior to 30 calendar days from
the date of receipt, that the IDE is approved, approved with conditions, or
disapproved. In cases of disapproval, a sponsor has the opportunity to
respond to the deficiencies and/or to request a regulatory hearing under 21
CFR Part 16.
Once an IDE application is approved, the following requirements must be met
in order to conduct the investigation in compliance with the IDE regulation:
Labeling - The device must be labeled in accordance with the labeling
provisions of the IDE regulation (§812.55) and must bear the statement "
CAUTION - Investigational Device. Limited by Federal (or United States) law
to investigational use."
Distribution - Investigational devices can only be distributed to qualified
investigators §812.43(b)6.
Informed Consent - Each subject must be provided with and sign an informed
consent form before being enrolled in the study. 21 CFR 507, Protection of
Human Subjects, contains the requirements for obtaining informed consent.
Monitoring - All investigations must be properly monitored to protect the
human subjects and assure compliance with approved protocols under §812.468.
Prohibitions - Commercialization, promotion, and misrepresentation of an
investigational device and prolongation of the study are prohibited (§812.
79).
Records and Reports - Sponsors and investigators are required to maintain
specified records and make reports to investigators, IRBs, and FDA (§812.
14010 and §812.15011).
Nonsignificant Risk Device
Nonsignificant risk devices are devices that do not pose a significant risk
to the human subjects. Examples include most daily-wear contact lenses and
lens solutions, ultrasonic dental scalers, and foley catheters.
A nonsignificant risk device study requires only IRB approval prior to
initiation of a clinical study. Sponsors of studies involving nonsignificant
risk devices are not required to submit an IDE application to FDA for
approval. Submissions for nonsignificant device investigations are made
directly to the IRB of each participating institution. Sponsors should
present an explanation to the IRB where the study will occur of why the
device does not pose a significant risk. If the IRB disagrees and determines
that the device poses a significant risk, the sponsor must report this
finding to FDA within five working days [§812.150(b)(9)]. FDA considers an
investigation of a nonsignificant risk device to have an approved IDE when
IRB concurs with the nonsignificant risk determination and approves the
study.
The sponsor also must comply with the abbreviated IDE requirements under §
812.2 (b)12:
Labeling - The device must be labeled in accordance with the labeling
provisions of the IDE regulation (§812.513) and must bear the statement "
CAUTION - Investigational Device. Limited by Federal (or United States) law
to investigational use.";
IRB Approval – The sponsor must obtain and maintain Investigational Review
Board (IRB) approval throughout the investigation as a nonsignificant risk
device study;
Informed Consent – The sponsor must assure that investigators obtain and
document informed consent from each subject according to 21 CFR 5014,
Protection of Human Subjects, unless documentation is waived by an IRB in
accordance with §56.109(c);
Monitoring - All investigations must be properly monitored to protect the
human subjects and assure compliance with approved protocols (§812.46).
Guidance on monitoring investigations can be found in "Guideline for the
Monitoring of Clinical Investigations15";
Records and Reports - Sponsors are required to maintain specific records and
make certain reports as required by the IDE regulation.
Investigator Records and Reports – The sponsor must assure that
participating investigators maintain records and make reports as required (
see Responsibilities of Investigators); and
Prohibitions –Commercialization, promotion, test marketing,
misrepresentation of an investigational device, and prolongation of the
study are prohibited (§812.716).
IDE Exempt Investigations
All clinical investigations of devices must have an approved IDE or be
exempt from the IDE regulation. Investigations that are exempted from 21 CFR
81217 are described in §812.2(c) of the IDE regulation. Studies exempt
from the IDE regulation include:
1.a legally marketed device when used in accordance with its labeling
2.a diagnostic device if it complies with the labeling requirements in §809
.10(c) and if the testing:
a.is noninvasive;
b.does not require an invasive sampling procedure that presents significant
risk;
c.does not by design or intention introduce energy into a subject; and
d.is not used as a diagnostic procedure without confirmation by another
medically established diagnostic product or procedure;
Additional guidance for an in vitro diagnostic device studies can be found
in "Regulating In Vitro Diagnostic Device (IVD) Studies18."
3.consumer preference testing, testing of a modification, or testing of a
combination of devices if the device(s) are legally marketed device(s) [that
is, the devices have an approved PMA, cleared Premarket Notification 510(k)
, or are exempt from 510(k)] AND if the testing is not for the purpose of
determining safety or effectiveness and does not put subjects at risk;
4.a device intended solely for veterinary use;
5.a device shipped solely for research with laboratory animals and contains
the labeling "CAUTION – Device for investigational use in laboratory
animals or other tests that do not involve human subjects."
Depending upon the nature of the investigation, those studies which are
exempt from the requirements of the IDE regulation may or may not be exempt
from the requirements for IRB review and approval under Part 5619 and the
requirements for obtaining informed consent under Part 5020. For guidance
regarding the applicability of these regulations with respect to
investigations being conducted under the provisions of §812.2(c), contact
the reviewing IRB and/or the IDE Staff at (301) 796-5640.
Who Must Apply for an IDE
The sponsor of the clinical trial is responsible for submitting the IDE
application to FDA (§812.4021) and obtaining Institutional Review Board (
IRB) approval before the study can begin. Foreign companies wanting to
conduct a clinical study in the U.S. MUST have a U.S. sponsor (§812.1822).
Under certain circumstances, the clinical investigator may wish to submit an
IDE and would, therefore, also act as the sponsor of the study.
When to Apply
Study approval must be obtained PRIOR to enrolling patients at the study
site. Each site must have approval from the reviewing IRB for that site
prior to beginning the study. For significant risk device studies, in
addition to IRB approvals, the sponsor must also have an approved IDE from
FDA prior to beginning the study at any site. The review of applications to
FDA and to the IRBs are independent and, therefore, may be submitted
simultaneously.
Pre-IDE Process
Sponsors are encouraged to contact FDA to obtain further guidance prior to
the submission of an IDE application. This will be especially beneficial to
new sponsors who have not previously had contact with the agency and for
sponsors proposing to study new technologies or new uses for existing
technologies. Early interaction with the agency should help to increase the
sponsor's understanding of FDA requirements, regulations, and guidance
documents, and will allow FDA personnel to familiarize themselves with the
new technologies. Increased interaction between FDA and sponsors should help
to speed the regulatory process and minimize delays in the development of
useful devices intended for human use. The communication with FDA may take
the form of a "Pre-IDE" meeting and/or a "Pre-IDE" submission.
Informal Guidance Meeting
Sponsors are encouraged to meet with the ODE reviewing division before the
IDE application is submitted for review so that the reviewing division can
provide any advice/guidance which can be used in the development of
supporting pre-clinical data or the investigational plan for incorporation
into the IDE application. These meetings may take the form of telephone
conference calls, video conferences, or face-to-face discussions. The
sponsor should contact the reviewing division directly or may contact the
IDE staff for assistance.
Formal Guidance Meetings
Determination Meeting - A sponsor or applicant anticipating the submission
of a PMA may submit a written request to discuss the type of valid
scientific evidence that will be necessary to demonstrate that the device is
effective for its intended use. This meeting is to focus on the broad
outline of clinical trial design. The request and summary information for a
meeting should be submitted as a pre-IDE submission and identified as a
determination meeting request. FDA’s determination is provided to the
applicant in writing within 30 days following the meeting.
Agreement Meeting - A sponsor or applicant may submit a written request for
a meeting to reach an agreement with FDA regarding FDA's review of an
investigational plan (including a clinical protocol). The request and
summary information should be submitted as a pre-IDE submission and
identified as an agreement meeting request. This meeting should take place
no later than 30 days after receipt of the request. The written request
should include a detailed description of the device, a detailed description
of the proposed conditions of use of the device, a proposed plan (including
a clinical protocol) for determining whether there is a reasonable assurance
of effectiveness, and, if available, information regarding the expected
performance of the device. If an agreement is reached between FDA and the
sponsor or applicant regarding the parameters of an investigational plan (
including a clinical protocol), the terms of the agreement are put in
writing and made part of the administrative record by FDA.
Additional guidance can be found in:
"Early Collaboration Meetings Under the FDA Modernization Act (FDAMA), Final
Guidance for Industry and CDRH Staff23"
"Goals and Initiatives for the IDE Program24," Blue Book Memorandum #D95-1
Pre-IDE Program: Issues and Answers25 - Blue Book Memo D99-1, March 1999
Pre-IDE Submissions
In addition to telephone contacts and informal or formal guidance meetings,
sponsors may submit preliminary information as a "pre-IDE" submission.
Sponsors are encouraged to submit pre-IDE submissions while the sponsor is
preparing the formal IDE submission whenever the sponsor requires informal
FDA guidance on troublesome parts of the IDE application, e.g., clinical
protocol design, pre-clinical testing proposal, pre-clinical test results,
protocols for foreign studies when the studies will be used to support
future marketing applications to be submitted to FDA.
Upon completion of the review of the pre-IDE submission, the reviewing
division will issue a response to the sponsor in a timely manner, usually
within 60 days of receipt. The response may take the form of a letter or
comments provided during a meeting or telephone conference call. If FDA's
response is provided via comments during a meeting or a telephone conference
call, a memo of the meeting or conference call will be prepared.
A pre-IDE submission must be clearly identified as such, submitted in
duplicate, and addressed to:
U.S. Food and Drug Administration
Center for Devices and Radiological Health
Document Mail Center – WO66-G609
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
FDA Action on IDE Applications
Approval or Disapproval §812.30
FDA will notify the sponsor in writing of the date it receives an IDE
application. FDA may approve, approve with modification, or disapprove an
IDE application. FDA may request additional information about an
investigation. The sponsor may provide the requested information or the
sponsor may treat such a request as a disapproval of the application and
request a hearing in accordance with 21 CFR 16.
The clinical investigation may begin after FDA and the IRB approves an IDE
for the investigation. An investigation may begin 30 days after FDA receives
the IDE application for the investigation of a device if IRB approval has
been obtained unless FDA notifies the sponsor that the investigation may not
begin.
Grounds for disapproval or withdrawal
FDA may disapprove or withdraw approval of an IDE application if FDA finds
that:
1.The sponsor has not complied with applicable requirements of the IDE
Regulation, any other applicable regulations or statutes, or any condition
of approval imposed by an IRB or FDA.
2.The application or a report contains untrue statements or omits required
material information.
3.The sponsor fails to respond to a request for additional information
within the time prescribed by FDA.
4.There is reason to believe that the risks to the human subjects are not
outweighed by the anticipated benefits to the subjects or the importance of
the knowledge to be gained, that informed consent is inadequate, that the
investigation is scientifically unsound, or that the device as used is
ineffective.
5.It is unreasonable to begin or to continue the investigation due to the
way in which the device is used or the inadequacy of:
(i) the report of prior investigations or the investigational plan; (ii) the
methods, facilities, and controls used for the manufacturing, processing,
packaging, storage, and, where appropriate, installation of the device; or (
iii) the monitoring and review of the investigation.
Notice of Disapproval or Withdrawal
If FDA disapproves an IDE application or proposes to withdraw approval, FDA
will notify the sponsor in writing. A disapproval order will contain a
complete statement of the reasons for disapproval and will advise the
sponsor of the right to request a regulatory hearing under 21 CFR 16. FDA
will provide an opportunity for a hearing before withdrawal of approval
unless FDA determines that there is an unreasonable risk to the public
health if testing continues.
-References
21 CFR 812.226
21 CFR 812.327
21 CFR 812.3028 | s**********8
发帖数: 25265 | 2 赞, 众人拾柴火焰高嘛
device
differ
regulations.
【在 k****i 的大作中提到】
: Investigations covered under the IDE regulation are subject to differing
: levels of regulatory control depending on the level of risk. The IDE
: regulation distinguishes between significant and nonsignificant risk device
: studies and the procedures for obtaining approval to begin the study differ
: accordingly. Also, some types of studies are exempt from the IDE regulations.
: Significant Risk Device
: A significant risk device presents a potential for serious risk to the
: health, safety, or welfare of a subject. Significant risk devices may
: include implants, devices that support or sustain human life, and devices
: that are substantially important in diagnosing, curing, mitigating or
| k****i
发帖数: 1126 | 3 恩那，俺会啥就给上啥。
【在 s**********8 的大作中提到】
: 赞, 众人拾柴火焰高嘛
:
: device
: differ
: regulations.
| s**********8
发帖数: 25265 | 4 不会的也要上. 吹牛谁不会
【在 k****i 的大作中提到】
: 恩那，俺会啥就给上啥。
| k****i
发帖数: 1126 | 5 俺要基本以事实为基础，稍微带点忽悠。
【在 s**********8 的大作中提到】
: 不会的也要上. 吹牛谁不会
| s**********8
发帖数: 25265 | 6 we r so different.
【在 k****i 的大作中提到】
: 俺要基本以事实为基础，稍微带点忽悠。
| f******w
发帖数: 10267 | 7 哇，天天都学新东西啊！这个版太好了，太尉说的以灌为主，学术为辅。看来学术也还
是有人关心的哈。。。
我也给我们版做个广告吧，就是出门右转，MedicalPractice，欢迎大家光临。太尉，
看在乡党的份上，你就别收我广告费了，呵呵。 | s**********8
发帖数: 25265 | 8 哪敢啊? 倒贴还来不及.
【在 f******w 的大作中提到】
: 哇，天天都学新东西啊！这个版太好了，太尉说的以灌为主，学术为辅。看来学术也还
: 是有人关心的哈。。。
: 我也给我们版做个广告吧，就是出门右转，MedicalPractice，欢迎大家光临。太尉，
: 看在乡党的份上，你就别收我广告费了，呵呵。
|
| k****i
发帖数: 1126 | 9 那我就更要经常来了，给你整整风～～～
【在 s**********8 的大作中提到】
: we r so different.
| Y*********e
发帖数: 4847 | 10 上门女婿？
【在 s**********8 的大作中提到】
: 哪敢啊? 倒贴还来不及.
| | | k****i
发帖数: 1126 | 11 那是在美国practic medicine的中国MD的班马？
【在 f******w 的大作中提到】
: 哇，天天都学新东西啊！这个版太好了，太尉说的以灌为主，学术为辅。看来学术也还
: 是有人关心的哈。。。
: 我也给我们版做个广告吧，就是出门右转，MedicalPractice，欢迎大家光临。太尉，
: 看在乡党的份上，你就别收我广告费了，呵呵。
| s**********8
发帖数: 25265 | 12 西宾吧. 人都有娃了.
【在 Y*********e 的大作中提到】
: 上门女婿？
| s**********8
发帖数: 25265 | 13 nice
【在 k****i 的大作中提到】
: 那我就更要经常来了，给你整整风～～～
| f******w
发帖数: 10267 | 14 对，现在主力们都是在美国行医的，还有正在考医的，本来是包括所有医疗行业，昨天
有护士抗议说他们的声音太小。
【在 k****i 的大作中提到】
: 那是在美国practic medicine的中国MD的班马？
| f******w
发帖数: 10267 | 15 是嘉宾！
【在 s**********8 的大作中提到】
: 西宾吧. 人都有娃了.
| k****i
发帖数: 1126 | 16 偶这种学医的，但是铁定心思不做医生但是在MEDICAL DEVICE里混的你们欢迎吗？
【在 f******w 的大作中提到】
: 对，现在主力们都是在美国行医的，还有正在考医的，本来是包括所有医疗行业，昨天
: 有护士抗议说他们的声音太小。
| s**********8
发帖数: 25265 | 17 楞的. 你可以来当斑主了.
【在 k****i 的大作中提到】
: 偶这种学医的，但是铁定心思不做医生但是在MEDICAL DEVICE里混的你们欢迎吗？
| k****i
发帖数: 1126 | 18 木有空灌水，今天是比较清闲，呵呵。
【在 s**********8 的大作中提到】
: 楞的. 你可以来当斑主了.
| s**********8
发帖数: 25265 | 19 好. 那就多坐会.
【在 k****i 的大作中提到】
: 木有空灌水，今天是比较清闲，呵呵。
| f******w
发帖数: 10267 | 20 欢迎啊，欢迎各种声音。觉得医学跟medical device和药学都有很大的相关性，而这种
相关性，三个领域互相不理解。
【在 k****i 的大作中提到】
: 偶这种学医的，但是铁定心思不做医生但是在MEDICAL DEVICE里混的你们欢迎吗？
| | | s**********8
发帖数: 25265 | 21 闹得. device和pharmaceutical overlap很多. 比如combo device, CMC section 和
drug都是一样的.
【在 f******w 的大作中提到】
: 欢迎啊，欢迎各种声音。觉得医学跟medical device和药学都有很大的相关性，而这种
: 相关性，三个领域互相不理解。
| k****i
发帖数: 1126 | 22 了解device的医生大多是外科或者GYN，medical practice那边内科的比较多吧。
【在 s**********8 的大作中提到】
: 闹得. device和pharmaceutical overlap很多. 比如combo device, CMC section 和
: drug都是一样的.
| s**********8
发帖数: 25265 | 23 也就知道咋用, 真正的研发也不懂吧.
【在 k****i 的大作中提到】
: 了解device的医生大多是外科或者GYN，medical practice那边内科的比较多吧。
| k****i
发帖数: 1126 | 24 我们研发新的device都会找医生来试，提建议，帮助design的。
【在 s**********8 的大作中提到】
: 也就知道咋用, 真正的研发也不懂吧.
| s**********8
发帖数: 25265 | 25 那些是investigator, 不一样的.
【在 k****i 的大作中提到】
: 我们研发新的device都会找医生来试，提建议，帮助design的。
| s**********8
发帖数: 25265 | 26 sponsor, investigator, patient, FDA, IRB 做clinical trial的五个party?
【在 k****i 的大作中提到】
: 我们研发新的device都会找医生来试，提建议，帮助design的。
| k****i
发帖数: 1126 | 27 我们不光用他们做investigator，很多医生直接参与我们design and re-design. They
provided us lots of feedback before the device is final designed.
【在 s**********8 的大作中提到】
: 那些是investigator, 不一样的.
| s**********8
发帖数: 25265 | 28 那他们就是你们得consultant, 跟你们是一伙的.
做clinical trial的医生, 必须做financial interest disclosure才能做.
They
【在 k****i 的大作中提到】
: 我们不光用他们做investigator，很多医生直接参与我们design and re-design. They
: provided us lots of feedback before the device is final designed.
| s**********8
发帖数: 25265 | 29 那他们不能做investigator.
They
【在 k****i 的大作中提到】
: 我们不光用他们做investigator，很多医生直接参与我们design and re-design. They
: provided us lots of feedback before the device is final designed.
| k****i
发帖数: 1126 | 30 An consultant can be an investigator, as long as he discloses the financial
stuff.
【在 s**********8 的大作中提到】
: 那他们就是你们得consultant, 跟你们是一伙的.
: 做clinical trial的医生, 必须做financial interest disclosure才能做.
:
: They
| | | s**********8
发帖数: 25265 | 31 not that easy bah. this is confliction of interest which may catch FDA's
eyeball and need more objective scientific judgment.
理论上可以, 实际上要proceed with caution.
but it is a good topic, we should dig more into this.
financial
【在 k****i 的大作中提到】
: An consultant can be an investigator, as long as he discloses the financial
: stuff.
| s**********8
发帖数: 25265 | 32 找到一个文献, 贴上来.
【在 s**********8 的大作中提到】
: not that easy bah. this is confliction of interest which may catch FDA's
: eyeball and need more objective scientific judgment.
: 理论上可以, 实际上要proceed with caution.
: but it is a good topic, we should dig more into this.
:
: financial
| k****i
发帖数: 1126 | 33 Ideally, you should avoid consultant or anybody who has conflict of interests.
In reality, they are more familiar with the new product and get much better
training than others, so we will still use them as investigators. However,
we will have DSMB to make sure the judgement is objective.
【在 s**********8 的大作中提到】
: not that easy bah. this is confliction of interest which may catch FDA's
: eyeball and need more objective scientific judgment.
: 理论上可以, 实际上要proceed with caution.
: but it is a good topic, we should dig more into this.
:
: financial
|
|
