Expanded Access Programs

Transcript 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 Washington, D.C.

1 (202) 383-8937 [email protected]

Michael Petty Washington, D.C.

1 (202) 626-2951 [email protected]

Preeya Noronha Pinto Washington, D.C.

1 (202) 626-5527 [email protected]

Kim H. Roeder Atlanta 1 (404) 572-4695 [email protected]

Beverly Lorell, MD 1 (202) 383-8937 [email protected]

Michael Petty 1 (202) 626-2959 [email protected]

Preeya Noronha Pinto 1 (202) 626-5547 [email protected]

Kim H. Roeder 1 (404) 572-4675 [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 3

•

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) 5

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 6

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 life threatening 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 8

Expanded Access Programs

• Definitions matter!

“Immediately Life-Threatening Disease or Condition”

― “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 effects Monitoring not generally required 12

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 13

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 14

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, including ― ― ― Institutional Review Board (review and approval, including emergency use) – 21 CFR Part 56 Protection of Human Subjects (informed consent) – 21 CFR Part 50 FDA authority to issue Clinical Holds, based on safety and reporting requirements (adverse event reports, annual reports) – 21 CFR Part 312 15

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 research

…” ― 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? 16

•

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. 18

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 312.8 • 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 sponsor investigator, 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. 19

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 20

Sequence – Expanded Access Programs for Individual Patients

Physician and Patient

• Patient meets regulatory criteria • Patient educated about process

Manufacturer

• Agreement to provide drug • Permission to refer to its IND

FDA

• Physician submits Individual Patient IND • Approval

IRB

• Review and approval • Informed consent

Considerations

• 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 Manufacturers

• 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) ― Effort/burden ― Costs, including whether to charge for the investigational drug 25

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 26

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? 27

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” 28

EAP Communications - Challenges

• Important programs for potentially beneficial patient access • Appropriate to inform of program information ― Company website ― Communiques with patient advocacy organizations ― Press releases ― Many patients today involved with internet research; patient forums, etc. ― FDA websites 29

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 communications ― Questions from HCPs ― Questions from PAOs ― Questions from patients ― Separation of venues, other information on the product & program 30

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 education ― Clinicaltrials.gov

― Other indicia of promotional context/tone 31

Summary

• 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 32

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 distribution.

•

Consideration of CMS National Coverage Determination on Clinical Trials

•

Does Medicare Cover Investigational

•

Drugs?

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 member Medicare typically does not cover: ― Unapproved drugs • ― Approved drugs for investigational uses (

i.e.

, uses that are off label 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 36

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) 37

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 service ―

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 38

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 39

•

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 40

• •

What Is Covered in Expanded Access

•

Programs?

Medicare coverage policies do not specifically address the situation where unapproved/investigational drugs are used for treatment purposes 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 41

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 42

•

Anticipating and Navigating Hidden Risks for Healthcare Providers

Provider Responsibilities -- Expanded

•

Access

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: ― ― ― ― Costs Resources available for patient in event of harm Indemnification Regulatory compliance 45

Expanded Access – Challenges for

•

Hospitals

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 46

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): Expanded Access Consent:

• 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 experimental.

• A description of any benefits to the subject

or to others

which may reasonably be expected from the

research

•

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. 49

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 options:  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/life threatening 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 context • • • Low evidentiary burden when considering use of an investigational drug for a patient with an immediate, life threatening 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 51

Expanded Access – Emergency Situation:

•

Challenges for Hospitals

FDA may authorize Expanded Access for an • Appropriate “when treatment … must occur individual patient without a written submission if an emergency requires the patient to be treated before a written submission can be made

. 21 CFR § 312.310(d).

― Access may begin on verbal authorization (telephone) by the reviewing FDA official.

Draft Guidance, Q17.

within a very limited number of hours or days.” “FDA intends to scrutinize emergency requests and to authorize access for such requests only when the situation is a

true emergency

.”

Draft Guidance, Q11.

― Written submission to be made within 15 working days 52

Expanded Access – Emergency Situation:

• • •

Challenges for Hospitals

Typically, for Expanded Access • “Once an investigational drug is authorized under emergency procedures, there will not be time to obtain prior IRB review.

The emergency use must be reported to the IRB within 5 working days of initiation of treatment

. 21 CFR § 56.104(c) (exemption from IRB review for emergency use of test article).

There can be more than one Expanded Access emergency use of the same drug at the same institution.

Draft Guidance, Q11.

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 …” but FDA will not deny further emergency access if prior IRB review is not feasible.

Draft Guidance, Q11.

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 – Any information provided to FDA to obtain verbal authorization flexibility in the meeting schedule and resources to act quickly) – – Details of telephone/verbal authorization by FDA Treatment protocol (including dosing, frequency, administration) • Consider IRB retrospective review of emergency access: Compliant? – – Informed consent form used or justification for exception Expanded Access submission made to FDA within 15 days 54

Expanded Access – Hospital/IRB

•

Resources to Manage Uncertainties

Policies and Procedures ― Explanation and sequence of • Training for IRB, other staff, physicians who may ― Expanded Access regulatory process (web-based) Checklists for review of • seek Expanded Access Templates: ― Request forms, IRB review Expanded Access requests, particularly for individual ― Consent forms and review patients and emergency process: Adapt for treatment situations scenario of Expanded Access ― ― IRB process for review of Expanded Access requests and documentation of emergency use Identified (and trained) contact persons 55

Healthcare & FDA Life Sciences Roundtable Thank you!

Q & A

•

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 312.8

― ― 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 approval; 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.