FDA and Clinical Trials

Mimi Riley, UVA School of Law, at the Darden Life Science BootCamp, April 16 2010.

ISO 14155:2011 -- For Design Medical Device Clinical Trials

ISO 14155:2011 addresses good clinical practice (GCP) for the design, conduct, recording and reporting of clinical investigations carried out in human subjects to assess the safety or performance of medical devices for regulatory purposes. It does not apply to in vitro diagnostic medical devices.

ISO

April 4, 2012 - FDA Releases Updated “Bad Bug Book” with New Features

The second edition of the Bad Bug Book, published by the Center for Food Safety and Applied Nutrition, of the Food and Drug Administration (FDA), U.S. Department of Health and Human Services, provides current information about the major known agents bacteria, viruses, parasites, and natural toxin that can contaminate food and cause illness. the book includes five new chapters (on Cronobacter, Enterococcus, Francisella tularensis, phytohaemagglutinin, and venomous fish).  

FDA Posted Recently Updated Guidance Documents (Feb., 2012)

Guidance for Sponsors, Investigators, and Institutional Review Boards: Questions and Answers on Informed Consent Elements,21 CFR § 50.25(c) (Small Entity Compliance Guide)

Guidance for IRBs,Clinical Investigators,and Sponsors: IRB Continuing Review After Clinical Investigation Approval

Guidance for Industry and FDA Staff: FDA Acceptance of Foreign Clinical Studies Not Conducted Under an IND, Frequently Asked Questions

Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: Public Availability of Advisory Committee Members' Financial Interest Information and Waivers, Final Guidance

FDA -- Effects of Ischemia Reperfusion Injury on Outcomes in Kidney Transplantation; Public Workshop (September, 2011)

Last year FDA sponsored a public workshop of Ischemia Reperfusion Injury (IRI) and Downstream Effects on Long Term Outcomes in Kidney Transplant Recipients to facilitate and encourage the development of therapeutic modalities for the management of this condition and related indications. The workshop topics included, cellular and molecular mechanisms of IRI; utility of biomarkers for early IRI identification and long-term outcomes; agents for potential mitigation of IRI; animal models of IRI and DGF/SGF; the approval process for devices in kidney preservation; clinical trial designing, end points and study population (renal recipients).
Workshop Agenda
Workshop transcript Day 1
Workshop transcript Day 2

FDA 21 CFR Covers Primary Regulations for Conducting of Investigational Device Exemptions Medical Device Clinical Studies

21 CFR 812, Investigational Device Exemptions (IDE)

It covers the procedures for the conduct of clinical studies, application, responsibilities of sponsors and investigators, medical device labeling, records, and reports.

21 CFR 820 SubpartC, Design Controls of the Quality System Regulation

It provides the requirement for procedures to control the design of the device.

21 CFR 50, Protection of Human Subjects

It provides the requirements and general elements of informed consent.

21 CFR 56, Institutional Review Boards

It covers the procedures and responsibilities for an IRB that approves clinical investigations protocols.

21 CFR 54, Financial Disclosure by Clinical Investigators

It covers the disclosure of financial compensation to clinical investigators that are part of the FDA’s assessment of the reliability of the clinical data.

Clinical Study with Medical Devices

A significant risk device study, a sponsor must:
Clinical studies with medical 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 (§812.20).

• Submit a complete IDE application  (§812.20) to FDA for review and obtain FDA approval of the IDE; submit the investigational plan and report of prior investigations(§812.25 and §812.27) 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.

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. 

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.

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 812 are described in §812.2(c) of the IDE regulation. Studies exempt from the IDE regulation include

• a legally marketed device when used in accordance with its labeling
• a diagnostic device if it complies with the labeling requirements in §809.10(c) and if the testing:
• is noninvasive;
• oes not require an invasive sampling procedure that presents significant risk;
• does not by design or intention introduce energy into a subject; and
• is not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure; "Regulating In Vitro Diagnostic Device (IVD) Studies."

• consumer preference testing, testing of a modification, or testing of a combination of devices if the device(s) are legally marketed device(s) with 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;

• a device intended solely for veterinary use;

•  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 56 and the requirements for obtaining informed consent under Part 50.

国家食品药品监督管理局要求西安杨森制药有限公司对“楷莱”、“万珂”采取措施控制风险

2011年12月08日 发布

根据欧洲药品管理局最新公告，英国、法国药品监管机构和美国食品药品管理局于2011年11月7日-11日对Ben Venus Laboratories公司（简称“BVL公司”）在美国的生产场地进行联合GMP检查，发现其无菌灌装过程质量管理存在缺陷。该公司生产的楷莱（通用 名“盐酸多柔比星脂质体注射液”）、万珂（通用名“注射用硼替佐米”）在我国上市使用。为保证公众用药安全，国家食品药品监管局组织对上述产品可能存在的 风险进行了评估。
　　盐酸多柔比星脂质体注射液在临床上用于治疗艾滋病相关的卡波氏肉瘤，在我国注册生产企业还有上海复旦张江生物医药股份有限公司和石药集团中奇制 药技术（石家庄）有限公司。注射用硼替佐米在临床上用于治疗多发性骨髓瘤和套细胞淋巴瘤，在我国注册的生产场地只有BVL公司，且临床上无其他同类替代药 品。上述两种药品均为临床必需药品。综合考虑上述情况，国家食品药品监管局决定采取以下措施防范可能存在的风险：
　　一、要求代理进口BVL公司上述两种药品的西安杨森制药有限公司采取切实有效的措施控制风险，立即按照《药品召回管理办法》的规定主动召回市场上所有批号的楷莱；立即停止销售万珂，不再使用于给新患者。
　　二、要求西安杨森制药有限公司采取有效方式告知医生和患者可能存在的风险，对正在使用楷莱治疗的患者，建议改用其他同类药品；对于正在使用万珂 治疗的患者，应与医生和患者协商，在患者知情并同意的情况下，方可继续使用，并进行用药登记，做好临床使用和不良反应监测工作，保证临床用药安全。
　　国家食品药品监管局已将上述决定通知了西安杨森制药有限公司。西安杨森制药有限公司正在按照国家食品药品监管局的要求开展相关工作。
European Medicines Agency gives interim recommendations to deal with shortcomings in quality assurance at Ben Venue Laboratories