[Federal Register Volume 77, Number 45 (Wednesday, March 7, 2012)]
[Proposed Rules]
[Pages 13513-13516]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-5476]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Chapter I

[Docket No. FDA-2012-N-0170]


Modernizing the Regulation of Clinical Trials and Approaches to 
Good Clinical Practice; Public Hearing; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification of public hearing; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a 2-day 
public hearing to obtain input from interested persons on FDA's scope 
and direction in modernizing the regulations, policies, and practices 
that apply to the conduct of clinical trials of FDA-regulated products. 
Clinical trials are a critical source of evidence to inform medical 
policy and practice, and effective regulatory oversight is needed to 
ensure that human subjects are protected and resulting clinical trial 
data are credible and accurate. FDA is aware of concerns within the 
clinical trial community that certain regulations and policies 
applicable to the conduct of clinical trials may result in 
inefficiencies or increased cost and may not facilitate the use of 
innovative methods and technological advances to improve clinical trial 
quality. The Agency is involved in an effort to modernize the 
regulatory framework that governs clinical trials and approaches to 
good clinical practice (GCP). The purpose of this hearing is to solicit 
public input from a broad group of stakeholders on the scope and 
direction of this effort, including encouraging the use of innovative 
models that may enhance the effectiveness and efficiency of the 
clinical trial enterprise.

DATES: Date and Time: The public hearing will be held on April 23 and 
24, 2012, from 8:30 a.m. to 4:30 p.m.

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Individuals who wish to attend or present at the public hearing must 
register on or before close of business on April 2, 2012. To register 
for the public hearing, email your registration information to 
[email protected]. Section IV of this document provides 
attendance and registration information. Electronic or written comments 
will be accepted after the public hearing until May 31, 2012.

ADDRESSES: The public hearing will be held at FDA's White Oak Campus, 
10903 New Hampshire Ave., Bldg. 31, Rm. 1503, Silver Spring, MD 20993-
0002.
    Submit electronic comments to http://www.regulations.gov. Submit 
written comments to the Division of Dockets Management (HFA-305), Food 
and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 
20852. Identify comments with the corresponding docket number found in 
brackets in the heading of this document.
    Transcripts of the public hearing will be available for review at 
the Division of Dockets Management and on the Internet at http://www.regulations.gov approximately 30 days after the public hearing (see 
section VII of this document).
    A live webcast of this public hearing can be viewed at the 
following Web address on the days of the public hearing: http://www.fda.gov/Drugs/NewsEvents/ucm284118.htm. A video record of the 
public hearing will be available at the same Web address for 1 year.

FOR FURTHER INFORMATION CONTACT: Jennifer Hymiller, Food and Drug 
Administration, Center for Drug Evaluation and Research, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6333, Silver Spring, MD 20993-0002, 301-
796-2147, FAX: 301-847-3529, Email: [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Clinical trials that yield reliable data are critical to FDA's 
mission to ensure that drugs, biologics, and medical devices are safe 
and effective. The regulations that govern the conduct of clinical 
trials and the protection of human subjects have been in existence for 
more than 25 years. In the intervening years, there have been dramatic 
changes in the clinical trial enterprise, including increased size and 
complexity of clinical trials, increases in the number of clinical 
trials performed globally, greater use of contract research 
organizations (CROs), participation of vulnerable populations, and 
numerous scientific and technological advances. Given these changes and 
the evolution of the clinical trial enterprise, FDA is evaluating its 
regulatory approach to clinical trial oversight to ensure that it meets 
the regulatory objectives of ensuring human subject protection and the 
quality and integrity of data supporting regulatory decision-making, 
without being unnecessarily burdensome or unduly impeding 
implementation of innovative approaches. FDA has already taken a number 
of steps to improve and modernize its regulations, policies, and 
practices to ensure they provide for optimal clinical trial quality, 
data integrity, human subject protection, and flexibility.
    In 2004, FDA introduced the Critical Path Initiative (CPI),\1\ 
intended to transform the way medical products are developed, 
evaluated, and manufactured. One of the CPI's key areas of focus is 
modernizing clinical trial sciences to make trials safer and more 
efficient. As part of this larger initiative, FDA launched two 
initiatives to specifically address human subject protection, data 
integrity, and clinical trial quality and efficiency.
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    \1\ For more information on FDA's Critical Path Initiative, see 
http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/default.htm.
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    In 2006, FDA launched the Human Subject Protection and Bioresearch 
Monitoring Initiative \2\ aimed at modernizing and strengthening FDA's 
oversight and protection of human subjects and the integrity of data in 
clinical trials. FDA's Office of Good Clinical Practice in the Office 
of the Commissioner is leading this effort. FDA also established a 
Human Subject Protection and Bioresearch Monitoring Council that 
manages and sets FDA policy on bioresearch monitoring, GCP, and human 
subject protection.
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    \2\ For more information on FDA's Human Subject Protection and 
Bioresearch Monitoring Initiative, see http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm226306.htm.
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    In 2007, FDA and Duke University formed the Clinical Trials 
Transformation Initiative (CTTI),\3\ a public-private partnership with 
the goal of improving the quality and efficiency of clinical trials. 
CTTI has been involved in a range of projects, including projects to 
identify best practices for monitoring and designing quality into 
clinical trials, improve serious adverse event reporting to 
investigators, and gather best practices for premarket safety 
surveillance.
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    \3\ For more information on the Clinical Trials Transformation 
Initiative, see https://www.trialstransformation.org/.
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    In 2011, FDA published a Federal Register notice requesting comment 
on the development of a plan for the retrospective review of existing 
FDA regulations \4\ in accordance with Executive Order 13563, 
``Improving Regulation and Regulatory Review.'' As part of this plan, 
FDA is conducting a review of existing regulations to determine which, 
if any, of its rules are outmoded, ineffective, insufficient or 
excessively burdensome and may be good candidates to be modified, 
streamlined, expanded or repealed. The Agency is also evaluating its 
framework for periodically analyzing existing rules.\5\
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    \4\ 76 FR 23520; April 27, 2011.
    \5\ 76 FR 3821.
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    Over the past few years, FDA has issued a number of regulations and 
guidance documents related to clinical trial conduct. The following 
regulations and guidances are highlighted below to exemplify the 
direction and scope of FDA's effort to modernize the regulations, 
policies, and practices that apply to the conduct of clinical trials. 
The CPI, Human Subject Protection and Bioresearch Monitoring 
Initiative, and CTTI have helped inform these regulations and 
guidances:
    1. Investigational New Drug Safety Reporting Requirements for Human 
Drug and Biological Products and Safety Reporting Requirements for 
Bioavailability and Bioequivalence Studies--Final Rule, published 
September 29, 2010 (75 FR 59935);
    2. Investigator Responsibilities--Protecting the Rights, Safety, 
and Welfare of Study Subjects--Final Guidance, published October 26, 
2009 (74 FR 55052);
    3. Oversight of Clinical Investigations: A Risk-Based Approach to 
Monitoring--Draft Guidance, published August 29, 2011 (76 FR 53683);
    4. Electronic Source Documentation in Clinical Investigations--
Draft Guidance, published January 7, 2011 (76 FR 1173);
    5. Adverse Event Reporting to IRBs--Improving Human Subject 
Protection--Final Guidance, published January 15, 2009 (74 FR 2599);
    6. Exception from Informed Consent Requirements for Emergency 
Research--Final Guidance, published April 4, 2011 (76 FR 18558);
    The collaborative effort with CTTI also identified Quality Risk 
Management (QRM) principles and Quality by Design (QbD) as models that, 
with adaptations, could contribute to improved data quality and 
integrity in clinical trials. QRM is a systematic process to identify, 
assess, control,

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communicate, and review the risks associated with a process or 
activity. QbD, a risk-based, quality approach that has been successful 
in the manufacturing arena, emphasizes building quality into a process 
from the beginning. Applied to clinical trials, this approach would 
prospectively define factors most critical to trial quality and data 
integrity (e.g., proper randomization, effective blinding to ensure 
unbiased ascertainment and analysis of study outcomes) and 
prospectively identify risks critical to those factors. The sponsor 
would then design the protocol, oversight and monitoring mechanisms, as 
well as data management, archiving, and analysis processes to eliminate 
or mitigate those risks.
    FDA has also taken steps to improve its clinical trial inspection 
processes and coordinate inspection processes globally. Ongoing efforts 
are aimed at developing new approaches for selecting clinical 
investigator sites for inspection and for improving the warning letter 
process. FDA is also involved in a Good Clinical Practice Initiative 
\6\ with the European Medicines Agency (EMA), in which FDA and the EMA 
have shared information on applications, collaborated on joint and 
observational inspections, participated in bilateral training, and kept 
each other informed of GCP-related legislation, regulatory guidance, 
and related documents. These steps have facilitated improvements in 
FDA's inspection coverage and decision-making processes.
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    \6\ For more information on the EMA-FDA Good Clinical Practice 
Initiative, see http://www.fda.gov/downloads/InternationalPrograms/FDABeyondOurBordersForeignOffices/EuropeanUnion/EuropeanUnion/EuropeanCommission/UCM266259.pdf.
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    In various forums, FDA has been told that certain regulations and 
compliance practices may result in inefficiencies or may not facilitate 
the use of innovative methods to improve clinical trial quality or the 
use of technological advances (e.g., use of the Internet to gather 
data, conduct certain types of research, obtain informed consent). FDA 
has also heard from clinical trial sponsors and CROs that sponsors and 
CROs are reluctant to change their processes related to clinical trial 
oversight and management because of uncertainty about whether new 
processes would be in compliance with applicable regulations. FDA 
recognizes that it must effectively leverage its available resources 
and take additional steps to strategically evolve and modernize its 
regulatory approach to the conduct of clinical trials. FDA is striving 
to align regulatory processes to meet the needs of its many 
stakeholders, including those who design and conduct trials, those who 
participate in trials, and those who depend on the results of those 
trials to make informed health care decisions.

II. Purpose of Hearing

    The purpose of this public hearing is to obtain input from clinical 
trial sponsors, CROs, clinical investigators, academic institutions, 
institutional review boards (IRBs), professional societies, trade 
organizations, patient and consumer groups, and other interested 
parties on the scope and direction of FDA's future efforts to evolve 
and modernize its regulatory approach to the conduct and oversight of 
clinical trials. FDA's primary focus is on good clinical practice, 
including clinical protocol design to ensure the reliability of data, 
safety surveillance and reporting, quality control processes (e.g., 
monitoring and training), quality assurance (e.g., auditing), and any 
other processes directed at ensuring trial quality, data integrity, or 
human subject protection. FDA is interested in ways (e.g., workshops, 
strategic alliances) to foster implementation of innovative methods to 
ensure human subject protection and data quality and integrity, 
including risk-based approaches in the design, oversight, and conduct 
of clinical investigations. FDA is seeking feedback on specific GCP 
regulations, policies, and practices that may need clarification or 
revision to facilitate advances in the ways that clinical trials are 
conducted, remove impediments to the use of innovative approaches, or 
otherwise improve the conduct of clinical trials. FDA also welcomes 
comments on additional issues that will help the Agency modernize its 
oversight and improve the quality and efficiency of clinical trials.

III. Issues for Discussion

    In addition to the general information requests in section II of 
this document, FDA is interested in obtaining information and public 
comment on the following specific issues.
    1. Increasing clinical trial complexity (e.g., participation of 
vulnerable populations, increased frequency of outsourcing) and 
globalization are posing challenges for sponsors, clinical 
investigators, IRBs, patients, and FDA. FDA has been involved in a 
number of efforts to ensure that the Agency's GCP regulations, 
policies, and practices are optimal for ensuring clinical trial 
quality, data integrity, and human subject protection while providing 
flexibility to conduct trials in the 21st century.
    a. What additional efforts should FDA pursue to modernize the 
Agency's GCP regulations, policies, and practices? For example, are 
there specific FDA regulations, guidances, or practices (e.g., 
compliance programs) that should be a high priority for clarification 
or revision? Are there other steps (e.g., pilot projects, strategic 
alliances) that would help ensure clinical trial quality and subject 
safety, provide flexibility, or improve the efficiency of the clinical 
trial process? For each of the suggested efforts, specifically identify 
the reasons that the current approach is not optimal, how the suggested 
effort would ensure clinical trial quality, subject safety, and/or 
improve the efficiency of the clinical trial process, and what the 
preferred priority of the efforts should be.
    b. What efforts could FDA consider that could help mitigate some of 
the challenges resulting from increased clinical trial complexity and 
globalization? For each of the suggested efforts, specifically identify 
how the effort could help mitigate these challenges.
    2. FDA is interested in fostering the use of innovative methods and 
models, including QRM principles and QbD, as well as the use of 
technological advances (e.g., use of the Internet to gather data, 
conduct certain types of research, obtain informed consent). The Agency 
seeks comments on how the use of innovative methods, models, and 
technological advances could contribute to data integrity, clinical 
trial quality, and the safety of human subjects, as well as streamline 
the conduct of clinical trials.
    a. What are some innovative methods or models that facilitate 
building quality into the conduct of trials (e.g., by identifying, 
preventing, or minimizing errors that have the potential to compromise 
human subject safety and data integrity)? FDA requests feedback on 
experiences with implementing such methods or models (e.g., lessons 
learned), as well as data supporting the use of any suggested methods 
or models.
    b. FDA recognizes that the clinical trial process involves various 
stakeholders (e.g., sponsors, CROs, IRBs, investigators, patients) with 
different roles and responsibilities in ensuring human subject 
protection and generating valid study data. What are the specific 
stakeholder challenges presented by FDA's GCP regulations, policies, 
and/or practices to building quality into the clinical trial process 
(e.g., for a study that is conducted and overseen by multiple 
entities)?
    c. What are some ways in which FDA could encourage adoption of 
these

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methods and models? For example, how can FDA support effective 
communication and coordination among all entities involved in the 
conduct of a trial to ensure a focus on the protection of human 
subjects and quality across the clinical trial process?
    d. How should FDA focus its efforts in GCP regulations, policies, 
or practices to facilitate the use of technological advances, while 
maintaining the protection of research participants and the quality and 
integrity of data supporting regulatory decision-making?

IV. Attendance and Registration

    The FDA Conference Center at the White Oak location is a Federal 
facility with security procedures and limited seating. Attendance is 
free and will be on a first-come, first-serve basis. Individuals who 
wish to attend the public hearing must register by sending an email to 
[email protected] on or before April 2, 2012, and provide 
complete contact information, including: Name, title, affiliation, 
address, email, and phone number. Those without email access may 
register by contacting Jennifer Hymiller (see FOR FURTHER INFORMATION 
CONTACT). Because seating is limited, FDA may limit the numbers of 
participants from each organization. Registrants will receive 
confirmation once they have been accepted for participation in the 
hearing. Onsite registration on the day of the hearing will be based on 
space availability on the day of the event starting at 7:30 a.m. If 
registration reaches maximum capacity, FDA will post a notice closing 
the meeting registration for the hearing at http://www.fda.gov/Drugs/NewsEvents/ucm284118.htm.
    Individuals who wish to present at the public hearing must register 
on or before April 2, 2012, through the email 
[email protected], and state this intention on their notice 
of participation. You must provide complete contact information, 
including: Name, title, affiliation, address, email, and phone number. 
FDA has included questions for comment in section III of this document. 
You should identify the topic or section and the number of each 
question you wish to address in your presentation, so that FDA can 
consider that in organizing the presentations. Individuals and 
organizations with common interests should consolidate or coordinate 
their presentations and request time for a joint presentation. FDA will 
do its best to accommodate requests to speak and will determine the 
amount of time allotted for each oral presentation, and the approximate 
time that each oral presentation is scheduled to begin. FDA will notify 
registered presenters of their scheduled times, and make available a 
draft agenda on http://www.fda.gov/Drugs/NewsEvents/ucm284118.htm 
approximately 2 weeks before the public hearing. Once FDA notifies 
registered presenters of their scheduled times, presenters should 
submit to electronic copy of their presentation to 
[email protected] on or before April 16, 2012.
    If you need special accommodations because of disability, please 
contact Jennifer Hymiller (see FOR FURTHER INFORMATION CONTACT) at 
least 7 days before the meeting.
    A live webcast of this public hearing can be viewed at the 
following Web address on the days of the public hearing: http://www.fda.gov/Drugs/NewsEvents/ucm284118.htm. A video record of the 
public hearing will be available at the same Web address for 1 year.

V. Notice of Hearing Under 21 CFR Part 15

    The Commissioner of Food and Drugs is announcing that the public 
hearing will be held in accordance with part 15 (21 CFR part 15). The 
hearing will be conducted by a presiding officer, who will be 
accompanied by FDA senior management from the Office of the 
Commissioner, the Center for Drug Evaluation and Research, the Center 
for Biologics Evaluation and Research, and the Center for Devices and 
Radiological Health.
    Under Sec.  15.30(f), the hearing is informal and the rules of 
evidence do not apply. No participant may interrupt the presentation of 
another participant. Only the presiding officer and panel members may 
question any person during or at the conclusion of each presentation. 
Public hearings under part 15 are subject to FDA's policy and 
procedures for electronic media coverage of FDA's public administrative 
proceedings (part 10, subpart C (21 CFR part 10, subpart C)). Under 
Sec.  10.205, representatives of the electronic media may be permitted, 
subject to certain limitations, to videotape, film, or otherwise record 
FDA's public administrative proceedings, including presentations by 
participants. The hearing will be transcribed as stipulated in Sec.  
15.30(b) (see section VII of this document). To the extent that the 
conditions for the hearing, as described in this notice, conflict with 
any provisions set out in part 15, this notice acts as a waiver of 
those provisions as specified in Sec.  15.30(h).

VI. Request for Comments

    Regardless of attendance at the public hearing, interested persons 
may submit either electronic or written comments to the Division of 
Dockets Management (see ADDRESSES). It is only necessary to send one 
set of comments. Identify comments with the docket number found in 
brackets in the heading of this document. Received comments may be seen 
in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.

VII. Transcripts

    Transcripts of the public hearing will be available for review at 
the Division of Dockets Management (see ADDRESSES) and on the Internet 
at http://www.regulations.gov approximately 30 days after the public 
hearing. A transcript will also be made available in either hard copy 
or on CD-ROM, upon submission of a Freedom of Information request. 
Written requests are to be sent to the Division of Freedom of 
Information (ELEM-1029), Food and Drug Administration, 12420 Parklawn 
Dr., Element Bldg., Rockville, MD 20857.

    Dated: March 1, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-5476 Filed 3-6-12; 8:45 am]
BILLING CODE 4160-01-P