Expanded Access Programs

King & Spalding
May 22, 2014
Presentation for Clinical and Translational Science
Center ─ University of California, Davis Health System
Expanded Access to Investigational Drugs
for Treatment Use
Beverly Lorell, MD
Michael Petty
Preeya Noronha Pinto
Kim H. Roeder
Washington, D.C.
Washington, D.C.
Washington, D.C.
1 (202) 383-8937
1 (202) 626-2951
1 (202) 626-5527
1 (404) 572-4695
[email protected]
[email protected]
[email protected]
[email protected]
Kim H. Roeder
Preeya Noronha Pinto
Beverly Lorell, MD
Michael Petty
1 (404) 572-4675
1 (202) 626-5547
1 (202) 383-8937
1 (202) 626-2959
[email protected] [email protected]
[email protected] [email protected]
Topics for Discussion
• Expanded Access Programs: A brief primer for clinical
research centers and physician investigators
Access for individual patients, intermediate-size patient
groups, and large patient populations
Roles of the FDA, physician, healthcare institution
(including the IRB), and manufacturer
• What to expect from the pharmaceutical manufacturer
• Consideration of CMS NCD clinical trial policies and
Expanded Access Programs
• Considerations for healthcare providers
Anticipating and navigating challenges
Expanded Access to Investigational Drugs for
Treatment Use
― A Brief Primer of the FDA Expanded Access
Regulations, as amended in 2009
What are Expanded Access Programs?
• Program regulated by FDA
To improve access to investigational drugs for the treatment of
patients with a serious or immediately life-threatening disease or
condition who do not have comparable or satisfactory alternative
therapeutic options and who may benefit from such therapies
• Intent is treatment
Differs from use of an investigational drug in a clinical trial
where the primary purpose is research (i.e., the systematic
collection of data)
• Method of obtaining access
FDA approval of an Expanded Access Submission, which is a
type of an Investigational New Drug (IND) application (i.e., a
new IND or protocol amendment to existing IND)
Key Features of the Amended Regulations
• Consolidated requirements (Subpart I of 21 CFR Part 312)
• Three distinct categories of patient access
Individual patients, including for emergency use
Intermediate-size patient populations
Broad populations
― Treatment IND (a new IND) or Treatment Protocol
(protocol to an existing IND)
• General standards, as well as specific standards based
on the size of population and seriousness of the disease
• Requirements for obtaining access
• Safeguards, including IRB review, informed consent, and
reporting requirements to FDA
FDA’s Recent EAP Track Record
For period of Oct. 13, 2011 – Oct. 12, 2012:
• Total received by CDER: 940. Total approved: 936.
― Individual patients: Received: 908. Approved: 904.
― Emergency use INDs: Received: 289. Approved: 287.
― INDs (not emergency use): Received: 498. Approved: 496.
― Protocols (amendment to existing IND): Received 121. Approved 121.
― Intermediate-size populations (protocols – amendment to
existing IND): Received: 10. Approved: 10.
― Broad populations (Treatment Protocols – amendment to existing
IND): Received: 7. Approved: 7.
• The majority of submissions (87%) were new Expanded Access INDs
for individual patients submitted by physicians.
― Source: Presentation of Richard Klein, Office of Health and Constituent Affairs, FDA. CBI
Expanded Access Conference, Philadelphia, PA, July 17 – 18, 2013.
General Requirements (21 CFR 312.305)
• FDA must determine that:
― Patients to be treated have a serious or immediately lifethreatening illness or condition
― No comparable or satisfactory alternative therapy exists
― Potential patient benefit justifies the potential risks of
the treatment, and those risks are not unreasonable in
the context of the disease or condition being treated
― Providing the drug will not interfere with or
compromise clinical investigations that could support
marketing approval for the Expanded Access indication
Expanded Access Programs
• Definitions matter!
“Immediately Life-Threatening Disease or
― “A stage of disease in which there is a reasonable
likelihood that death will occur within a matter of
months or in which premature death is likely without
early treatment.” (21 CFR 312.300)
“Serious Disease or Condition”
― “A disease or condition associated with morbidity
that has substantial impact on day-to-day functioning.
Short-lived and self-limiting morbidity will usually
not be sufficient, but the morbidity need not be
irreversible, provided it is persistent or recurrent.
Whether a disease of condition is serious is a matter
of clinical judgment, based on its impact on such
factors as survival, day-to-day functioning, or the
likelihood that the disease, if left untreated, will
progress from a less severe condition to a more
serious one.” (21 CFR 312.300)
Individual Patients (21 CFR 312.310)
• Physician must determine that probable risk does not exceed that of
the disease for the individual patient
• FDA must deem that patient cannot obtain access under another type
of IND or protocol, and that “potential risks are reasonable”
• Emergency use
FDA may authorize without written submission, followed by written
submission within 15 working days
• Safeguards
Sponsor is often the physician who submits an IND for treatment
use, in roles of investigator and sponsor
Generally limited to single course of treatment
Submission of end-of-treatment report to FDA, including all adverse
Monitoring not generally required
Intermediate-Size Populations (21 CFR 312.315)
• Generally up to 100 patients
• Demonstration of need for investigational drug
Drug being developed, but patient cannot participate in clinical trial
Drug not being developed (e.g., rare disease)
An approved or related drug is no longer marketed or not available
(e.g., drug shortage with foreign version of drug)
• Sufficient evidence that drug is safe for proposed dose and duration
relative to size of exposed population
• Preliminary clinical evidence of effectiveness or plausible
pharmacologic effect
• Additional safeguards
Explanation of why drug cannot be developed or, if drug is being
developed, why patients cannot be enrolled in a trial for the use
Monitoring, as well as annual report for review by FDA
Large Populations: Treatment IND/Protocol
(21 CFR 312.320)
• Drug is being investigated in clinical trial to support marketing, or
all trials have been completed
• Company is actively pursuing marketing approval
• Sufficient evidence of safety and effectiveness for the use
Serious Disease: Evidence from phase 3 trial or compelling data from
phase 2 clinical trials
Immediately Life-threatening Disease: Available evidence provides
reasonable basis to conclude drug may be effective for the use and
would “not expose patients to an unreasonable and significant risk of
illness or injury” (could consist of evidence more preliminary than
phase 2 or 3 trials)
• Additional safeguards
― 30-day wait period for FDA review, or earlier notification of
FDA approval
― Monitoring, as well as annual report for review by FDA
Role of the IRB
• Drugs used in FDA-approved Expanded Access Programs
are investigational drugs, even though the drugs are being
used for treatment, not research.
• All FDA human subject protections are applicable,
Institutional Review Board (review and approval, including
emergency use) – 21 CFR Part 56
Protection of Human Subjects (informed consent) – 21 CFR Part
FDA authority to issue Clinical Holds, based on safety and
reporting requirements (adverse event reports, annual reports) –
21 CFR Part 312
Expanded Access: Challenges for IRBs
• In compliance with 21 CFR Part 50, how can the 8
Basic Elements of informed consent cited in 21 CFR
50.25(a) be incorporated?
As example, element (1) requires a statement “that the study
requires research, an explanation of the purposes of the
― FDA has not provided guidance or examples of informed consent
templates appropriate for Expanded Access
― To what depth should IRB review what is and isn’t known about
the investigational drug?
― Is it best practice for IRB to have template for informed consent
for Expanded Access Programs? Should templates differ for the
3 categories of Expanded Access?
Emergency Use in Expanded Access:
IRB Review
• Question: Can the same drug be used at the same institution more
than once? If so, is prospective IRB review required for the
subsequent expanded access emergency use of the same drug?
• FDA’s answer (See May 2013 FDA draft guidance):
― “There can be more than one expanded access emergency use of the same drug at the
same institution.
― FDA expects that, for expanded access uses authorized under the emergency
procedures, there typically will not be time to obtain prior IRB approval of the use.
― In such cases, the emergency use must be reported to the responsible IRB within 5
working days of initiation of treatment (21 CFR 56.104(c)). Once an investigational
drug is used in an emergency situation without prior IRB approval, any subsequent
uses of the investigational drug at that same institution would ordinarily require prior
IRB review and approval (21 CFR 56.104(c)).
― However, when prior IRB review and approval is not feasible for a subsequent
expanded access emergency use at a particular institution, FDA does not intend to
deny the subsequent request for emergency use due to lack of time to obtain
prospective IRB review, as long as that use will be reported to the IRB within 5
working days of initiation of treatment.”
Role of the Physician (21 CFR 312.305)
• Responsibilities of licensed physicians who administer or
dispense an investigational drug under Expanded Access
Obligations of an investigator, including
Adverse event reporting to sponsor
Ensuring IRB review and informed consent
Records, including accurate case histories and
drug disposition
An investigator who also submits a new IND
for Expanded Access for an individual patient
is considered a sponsor-investigator and must comply with the
FDA requirements of both sponsors and investigators.
Role of the Manufacturer
• Decide whether to provide the investigational drug under
an Expanded Access Program
• Decide whether to charge for the drug, pursuant to 21 CFR
• Expanded Access for Individual Patients
In response to a physician’s request for expanded access to an
investigational drug as the sponsor-investigator,
Company is not required to provide the drug
If company agrees to provide drug to a physician as sponsorinvestigator, company provides physician with written authorization
for FDA to reference the company’s existing IND
If company decides to provide the EA submission to FDA for the
single patient as the sponsor, company submits a protocol
amendment to an existing IND that it holds.
Role of the Sponsor (21 CFR 312.305)
Manufacturer (or Sponsor-Investigator)
• As sponsor of an FDA-approved IND, obligations include
IND safety reports to FDA
Annual reports to FDA
Ensuring that the licensed physicians are qualified to administer
the investigational drug for Expanded Access use
Monitoring the physicians as investigators (only for Expanded
Access Programs for intermediate-size and broad populations)
Providing information to physicians to minimize risk and
maximize potential benefits (including Investigator Brochure)
Maintaining an effective IND for the Expanded Access use
Records, including drug disposition
Other sponsor responsibilities under 21 CFR 312 may apply
Sequence – Expanded Access Programs for
Individual Patients
Physician and Patient
• Patient meets regulatory criteria
• Patient educated about process
• Agreement to provide drug
• Permission to refer to its IND
• Physician submits Individual Patient IND
• Approval
• Review and approval
• Informed consent
• Patients, physicians and healthcare providers are
often confused about Expanded Access Programs
― Understanding the amended regulations
and providing accurate and transparent
information helps to lower the risks
Key Take-Aways
• Common issues of misunderstanding for patients,
physicians and healthcare providers
― “Compassionate Use” – a potentially misleading term
― Manufacturer is not required to provide investigational drug or
provide it free of charge
― Physician always incurs regulatory obligations as investigator
― Obligations as sponsor-investigator, if the physician is holder of
the Individual Patient IND
― Potential medical costs may be incurred by the patient
― Including costs of the drug and medical expenses for injury
― Use of drug at stage of early and incomplete understanding of
its safety risks: Possible overestimation of benefit and
underestimation of risk
Understanding the Pharmaceutical
Manufacturer Perspective on Expanded Access
Programs (EAPs)
EAP Challenges and Risks for Pharmaceutical
• Inherent Tensions and Need for Balance
Make information on process/requirements available;
process transparent
Update information
Monitoring (required for Intermediate Size and Broad
Population EAP)
Costs, including whether to charge for the
investigational drug
EAP Challenges with Physicians
• Challenges with physicians
Emergency requests
Wanting access outside the program
Wanting full indemnities
Wanting promises of no cost to patients
Wanting funding
Locations; number of sites
Qualified in this role?
Not properly fulfilling investigator role
Not wanting the program to end
Pros/cons of company-sponsored submissions
EAP Challenges regarding FDA
• Challenges with FDA
Tremendous discretion
Evidence of safety
Can get different decisions from FDA
Information on whether drug is being developed for population to
be treated and if not, why/under what circumstances could it be
EAP vs. open-label safety study
Risk of interference with clinical investigations
“Significant number” of similar requests can result in FDA
request for more sponsor involvement.
EAP = less push for FDA to approve?
EAP – Additional Challenges
• Other Challenges
Physician, FDA, and drug sponsor are key
parties, but other stakeholders exist
Distraction from clinical trials/application
Supply issues
How to say “No”
EAP Communications - Challenges
• Important programs for potentially beneficial
patient access
• Appropriate to inform of program information
―Company website
―Communiques with patient advocacy
―Press releases
―Many patients today involved with internet
research; patient forums, etc.
―FDA websites
Communications - Challenges (cont’d)
• Safety and efficacy are not proven
• Drug is unapproved, and may not be approved
• Can technically create “labeling”, although no approved
label exists
• ≠ traditional scientific exchange or investor relations
― Questions from HCPs
― Questions from PAOs
― Questions from patients
― Separation of venues, other information on the
product & program
Pharma Company Communications Challenges (cont’d)
• No promotional context/claims allowed
― Low-keyed factual tone
― Not suggest drug will be approved
― Charging for drug
― Third party administrator experience
― Awareness of program is goal
― Program focus, rather than studies, data, or disease
― Clinicaltrials.gov
― Other indicia of promotional context/tone
• Regulators increasingly cynical of corporate intent
― Commercial role/involvement
― “Prepping the market” concern
― Implied claims; demand creation
― ChemGenex untitled letter for Omapro
• Bottom Line
― Patient access info must remain the “out front”
message versus “promotional” messages
312.6 Labeling of an investigational new drug.
(b) The “label” or “labeling” of an investigational new drug shall
not bear any statement that is false or misleading in any particular
and shall not represent that the investigational new drug is safe or
effective for the purposes for which it is being investigated.
312.7 Promotion of investigational drugs.
(a) Promotion of an investigational new drug. A sponsor or
investigator, or any person acting on behalf of a sponsor or
investigator, shall not represent in a promotional context that an
investigational new drug is safe or effective for the purposes for
which it is under investigation or otherwise promote the drug.
This provision is not intended to restrict the full exchange of
scientific information concerning the drug, including dissemination
of scientific findings in scientific or lay media. Rather, its intent is
to restrict promotional claims of safety or effectiveness of the drug
for a use for which it is under investigation and to preclude
commercialization of the drug before it is approved for commercial
• Consideration of CMS National Coverage
Determination on Clinical Trials
Does Medicare Cover Investigational
• To be covered under Medicare, drugs must be (1) safe and effective
and (2) reasonable and necessary for the diagnosis or treatment of
illness or injury or to improve the functioning of a malformed body
• Medicare typically does not cover:
― Unapproved drugs
― Approved drugs for investigational uses (i.e., uses that are offlabel and not “medically accepted”)
• Limited Exceptions (e.g., Group C cancer drugs, drugs covered
through NCDs, LCDs, or individual coverage decisions)
• Medicare policies regarding coverage of investigational drugs are
typically considered in the context of clinical trials—although these
policies are not directly applicable to Expanded Access Programs,
they are instructive
NCD for Routine Costs in Clinical Trials
• Medicare’s “Clinical Trial Policy”
• Applies to items and services reimbursable under Medicare Part A,
Medicare Part B, and Medicare Advantage (MA)
• In order for routine costs to be covered, a clinical trial must be a
“qualified” trial through one of three pathways:
― Meet certain “qualifying criteria” (not yet established by CMS)
― Automatically qualified
― Funded by NIH, CDC, AHRQ, CMS, DOD, VA directly or
through one of their centers or cooperative groups or
― Conducted under an IND reviewed by FDA or IND-exempt
― Coverage mandated under an NCD (e.g., Coverage with
Evidence Development policy where item/service is covered by
Medicare only in the context of a clinical trial)
NCD: What IS Covered?
• All items and services that are typically covered absent a clinical
trial (in both experimental and control arms)
• Required solely for the provision of the investigational item or
― e.g., investigational drug administration costs such as infusion
supplies and nursing time
• Required solely for the clinically appropriate monitoring of the
effects of the item or service
― e.g., additional lab tests to monitor for side effects of the
investigational drug
• Required solely for the prevention of complications
• Needed for reasonable and necessary care arising from the provision
of an investigational item or service, including for the diagnosis or
treatment of complications
NCD: What IS NOT Covered?
• The investigational item or service itself, unless otherwise covered
outside of the clinical trial
― Is the investigational use of an FDA-approved drug a “medically
accepted” off-label use? If so, it may be covered outside of the
clinical trial
• Items and services provided solely to satisfy data collection and
analysis needs and that are not used in the direct clinical
management of the patient
― e.g., monthly CT scans (solely to collect data) for a condition
usually requiring only one scan
• Items and services customarily provided by the research sponsors
free of charge for any enrollee in the trial
• Coinsurance/deductibles
Outpatient Prescription Drugs under
Medicare Part D
• Part D drugs are not subject to the NCD
• Part D coverage is typically limited to FDA-approved drugs used for
a medically-accepted indication (i.e., supported by compendia)
― In clinical trials, an example of drugs that may be covered under
Part D are FDA-approved drugs used as a control or as part of
combination therapy (unapproved drugs would not be covered)
• Coverage also depends on the formulary of the patient’s Part D plan
What Is Covered in Expanded Access
• Medicare coverage policies do not specifically address the situation
where unapproved/investigational drugs are used for treatment
• Two paradigms: (1) “Reasonable and Necessary” Standard and (2)
Clinical Trial Policy (NCD)
• Under either paradigm, the investigational drug itself is usually not
covered, but other items and services associated with clinical care
and/or treatment of the patient are likely covered
― e.g., costs of infusion of an investigational drug and overnight
observation services to monitor the patient
― e.g., costs of hospital stay to monitor/treat cardiac complications
resulting from use of the investigational drug
― e.g., follow-up visits to physician office for examination of
potential side effects from investigational drug regimen
Key Take-Aways
• Look to Medicare clinical trial policies to determine likely Medicare
coverage of Expanded Access Programs—consult your Medicare
Coverage Analysis document prepared for the clinical trial
• Investigational drugs used in Expanded Access Programs are
typically not covered by Medicare
― Providers/patients may be responsible for costs, depending on
whether a manufacturer charges for the investigational drug
• Other treatment costs associated with the use of investigational drugs
in Expanded Access Programs are typically covered by Medicare
― Includes investigational drug administration costs,
diagnosis/treatment of complications, monitoring of side effects
• Items/services performed solely for data collection or analysis,
provided free of charge, or not ordinarily covered by Medicare are
typically not covered by Medicare in Expanded Access Programs
• Anticipating and Navigating Hidden Risks for
Healthcare Providers
Provider Responsibilities -- Expanded
• According to the FDA, most Expanded
Access requests are individual patient
treatment IND requests, including
emergency requests
• These types of Expanded Access requests present unique
challenges to an institution attempting to apply its regular
investigational drug processes
A physician (not a corporate sponsor) may be acting as the
sponsor-investigator, bearing substantial responsibility for the
entire process (patients can access an investigational drug only
through a licensed physician, regardless of the sponsor).
Expanded Access is focused on treatment, not research; but all
review processes referenced are couched in terms of research.
“Emergency” truncates advance documentation and IRB review.
Expanded Access – Individual Patient:
Challenges for Hospitals
• Patient expectations and
dire medical circumstances
• No clinical research
agreement with corporate
sponsor; how to address:
Resources available for
patient in event of harm
Regulatory compliance
Expanded Access – Challenges for
• The Draft Guidance recognizes that FDA allowing
recovery of a cost does not mean that FDA controls
reimbursement policy for government programs or private
health plans
FDA does not attempt to direct
from whom costs are recovered
(usually, the patient/third party payor)
For purposes of disclosure, the patient
must be informed of responsibility for
these costs in the event they are not
covered by a third party payor
Hospital and IRB must manage expectations
that the institution will absorb these costs (subject to charity care
policies, if applicable); and also protect patients from exploitation
Expanded Access – Hospital/IRB
Resources to Manage Uncertainties
• Will the informed consent process in this context
be adequate to protect the physician and hospital if
the investigational drug provided under Expanded
Access is not effective, or worse yet, is injurious to
the patient?
“ … patients who are candidates to receive investigational drugs
under Expanded Access programs … should be afforded a
rigorous informed consent process that effectively
communicates the risks and potential benefits of any
investigational therapy to be used for treatment use in a way that
does not raise false expectations about a positive outcome
from treatment and makes clear what is unknown about the
drug.” 74 Fed. Reg. 40900, 40920 (Aug. 13, 2009)
Expanded Access – Elements of
Informed Consent (21 CFR § 50.25)
21 CFR § 50.25(a)(1) & (3):
A statement that the study
involves research, an
explanation of the purpose of
the research and the expected
duration of the subject’s
participation, a description of
the procedures to be followed,
and identification of any
procedures which are
A description of any benefits
to the subject or to others
which may reasonably be
expected from the research.
Expanded Access Consent:
Note – Must address duration
of treatment
Note: Treatment under an
Expanded Access mechanism
is not intended primarily to
develop data that could be
used to benefit other patients.
See 74 Fed. Reg. 40900, 40920
(Aug. 13, 2009)
Expanded Access – Duration of Therapy
Per the Draft Guidance,
individual patient access is
generally limited to a single
course of therapy for a specified
duration, unless FDA expressly
approves multiple courses or
chronic therapy.
FDA may authorize multiple
courses or chronic therapy when
the circumstances of the
treatment are well-defined and
reasonable in light of the
available evidence to support
use of the drug. Draft
Guidance, Q9.
“FDA … does not typically
authorize access of unspecified
duration at the discretion of the
treating physician.” Draft
Guidance, Q9.
FDA may require monitoring if
use is for an extended duration.
Expanded Access – Elements of
Informed Consent (21 CFR § 50.25)
21 CFR § 50.25(a)(4):
A disclosure of appropriate
alternative procedures or
courses of treatment, if any,
that might be advantageous.
Expanded Access Consent:
• No other acceptable medical
 There is no FDA-approved
drug available to treat the
patient’s condition
 Approved drugs are not
available, have not worked or
cause intolerable side effects
 The patient is not eligible for a
clinical trial that might help
• Note: What about alternative
unapproved treatments?
Expanded Access – Informed Consent:
Risks and Benefits // FDA Observations
Query: Is there a tendency to
overestimate the benefit or
underestimate the risk of access
to the unapproved drug, for
patients with serious/lifethreatening diseases who have
no alternatives?
Limited information about
safety and effectiveness is
available for Expanded Access
drugs, particularly if still in the
early stage of study
Safety more
important than
efficacy in this
Low evidentiary burden when
considering use of an
investigational drug for a patient
with an immediate, lifethreatening condition
Unknown risks and limited
information: Patient may
experience some benefit, no
effect or harm
But note that toxicity may
worsen patient’s already dire
situation – e.g., increase pain or
accelerate death without offering
an increase in patient’s quality
of life
Expanded Access – Emergency Situation:
Challenges for Hospitals
• FDA may authorize
• Appropriate “when
Expanded Access for an
treatment … must occur
individual patient without a within a very limited
written submission if an
number of hours or days.”
emergency requires the
“FDA intends to scrutinize
patient to be treated before
emergency requests and to
a written submission can be authorize access for such
made. 21 CFR § 312.310(d).
requests only when the
situation is a true
― Access may begin on verbal
authorization (telephone) by
the reviewing FDA official.
Draft Guidance, Q17.
Written submission to be
made within 15 working days
Draft Guidance,
Expanded Access – Emergency Situation:
Challenges for Hospitals
• Typically, for Expanded Access • “Once an investigational drug is
authorized under emergency
used in an emergency situation
procedures, there will not be
without prior IRB approval, any
time to obtain prior IRB review.
subsequent uses of the
investigational drug at that same
• The emergency use must be
institution would ordinarily
reported to the IRB within 5
require prior IRB review and
working days of initiation of
approval …” but FDA will not
treatment. 21 CFR § 56.104(c)
deny further emergency access if
(exemption from IRB review for
prior IRB review is not feasible.
emergency use of test article).
Draft Guidance, Q11.
• There can be more than one
Expanded Access emergency
use of the same drug at the same
institution. Draft Guidance,
Checklist of Information Needed from
Physician: Expanded Access for Individual
• In case of emergency, IRB
should require (5 days) –
• Consider encouraging prior
IRB review (requires some
flexibility in the meeting
Any information provided to
schedule and resources to
FDA to obtain verbal
act quickly)
Details of telephone/verbal
• Consider IRB retrospective
authorization by FDA
review of emergency
Treatment protocol
access: Compliant?
(including dosing, frequency,
Informed consent form used
or justification for exception
Expanded Access submission
made to FDA within 15 days
Expanded Access – Hospital/IRB
Resources to Manage Uncertainties
• Policies and Procedures
• Training for IRB, other
staff, physicians who may
Explanation and sequence of
seek Expanded Access
Expanded Access regulatory
process (web-based)
• Templates:
Checklists for review of
Expanded Access requests,
particularly for individual
patients and emergency
IRB process for review of
Expanded Access requests
and documentation of
emergency use
Identified (and trained)
contact persons
Request forms, IRB review
Consent forms and review
process: Adapt for treatment
scenario of Expanded Access
Healthcare & FDA Life Sciences Roundtable
Thank you!
Additional Information and References
― Useful FDA resources about Expanded Access
Programs (EAP)
― Brief summary: Regulatory history of EAP
― Brief summary: When a
manufacturer may charge
for an investigational drug
in an EAP
Resources for Today’s Discussion
• “Expanded Access to Investigational Drugs for Treatment Use”
74 FR 40900, August 13, 2009.
Amends 21 CFR Parts 312 and 316.
• “Charging for Investigational Drugs under
an Investigational New Drug Application”
74 FR 40872, August 13, 2009.
Amends 21 CFR Part 312.
• “Guidance for Industry. Expanded Access to Investigational Drugs
for Treatment Use–Qs & As. Draft Guidance.” May 2013.
• “Charging for Investigational Drugs Under an IND–Qs & As.
Draft Guidance.” May 2013.
Background of Expanded Access
• 1987 – FDA amends the Investigational New Drug (IND)
regulations at 21 CFR Part 312 to provide access for
broad patient populations under a Treatment IND/Protocol
• 1997 – Congress enacts FDAMA, making Expanded Access part
of the statute and specifying when an individual patient
may obtain an investigational drug for treatment use
• 2006 – FDA issues proposed rule to further amend 21 CFR Part
312 and address limitations
― Only addressed access for large groups of patients
― Did not define levels of evidence required for different categories
― Might have resulted in inequitable patient access
• 2009 – FDA issues final rule amending existing regulations,
effective October 13, 2009
Charging for the Investigational Drug
under Expanded Access
• A manufacturer may charge for an investigational drug under an
IND, including drug provided under Expanded Access. 21 CFR
― Must request authorization from FDA and demonstrate:
Sufficient enrollment in any ongoing clinical trial needed for marketing
approval to assure FDA that it will be successfully completed as planned;
Evidence of adequate progress in drug development for marketing
Information specifying drug development milestones the sponsor plans to
meet in next year; and
Amount to be charged recovers only direct costs of manufacturing,
shipping, and handling; for Expanded Access, may also charge for costs of
monitoring, complying with FDA reporting requirements, and other
administrative costs.
If company is not the sponsor of the Expanded Access IND, it is not
required to obtain authorization from FDA to charge for the
investigational drug.

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