EXPANDED ACCESS

WORKSHOP

Take a Deep Dive into the New Laws and Regulations to Prepare for Expanded Access Disclosures

March 9, 2017

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David J. Farber

Partner

King & Spalding LLP

Preeya Noronha Pinto

Partner

King & Spalding LLP

CBI Expanded Access Programs 2017

Expanded Access – The Basics

What’s Driving Policy Change?

What’s New from HHS/FDA, Congress and the States

Where Do We Go From Here?

Today’s Agenda

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What is Expanded Access?

Program established by Congress and

regulated by FDA

Goal is to improve access to

investigational drugs by certain

patients for treatment purposes

Differs from a clinical

investigation where the primary

purpose is research(i.e., systematic

collection of data to determine safety

and/or effectiveness)

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Authority for Expanded Access

1997 FDA Modernization Act (amended Section 561 of the FDCA)

21 C.F.R Part 312, Subpart I (FDA regulations have

permitted Expanded Access since 1987)

“Guidance for Industry, Expanded

Access to Investigational

Drugs for Treatment Use—Qs and As.”

FDA Guidance, June 2016

“Charging for Investigational Drugs Under an

IND—Qs and As.” FDA Guidance, June

2016

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General Criteria for FDA Authorization

Patient must have a serious or immediately life-threatening

disease or condition

No comparable or satisfactory alternative therapy exists

Potential patient benefit justifies the potential risks, and those

risks are not unreasonable in the context of the disease or

condition

Providing the investigational drug will not interfere with or

compromise clinical investigations that could support

marketing approval

FDA must determine that:

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Three Categories of Expanded Access

Individual Patients (including for

emergency use)

• 21 C.F.R. § 312.310

Intermediate-Size Patient Populations

• 21 C.F.R. § 312.315

Large Patient Populations

(Treatment IND or Treatment Protocol)

• 21 C.F.R. § 312.320

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Individual Patient Expanded Access

Physician must determine that the probable risk is not greater than that of the disease

Manufacturer must agree to provide the investigational drug

FDA must determine that (1) the general criteria are met and (2) the patient cannot obtain the drug under another type of IND or protocol

IRB must review and approve

EXPANDED ACCESS

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Submission/Request to FDA

Sponsor can submit an “individual patient access protocol” to its existing IND

• Physician is the investigator

Sponsor can submit an “individual patient access IND” and cross-reference information in existing IND

• Physician is the investigator

Physician can submit an “individual patient access IND” and cross-reference information in existing IND with permission from sponsor

• Physician is the sponsor and investigator

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Individual Patient Emergency Use

Emergency use verbally approved by

FDA

All applicable criteria must be met

Physician or sponsor must agree to provide a written submission to FDA within 15 working

days of FDA authorization

IRB must be notified within 5 working days of

initiation of treatment

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FDA Statistics – All Requests

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FDA Statistics – Single Patient Requests

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FDA Authorization of Expanded Access

99% authorization

rate

FDA has authorized more than 99% of requests between 2010 and 2015

FDA has authorized 7110 out of 7176

single patient requests between 2010 and 2015

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Statement of Peter Lurie, MD, MPH, FDA Associate Commissioner for Public Health Strategy and Analysis, to the U.S. Senate Committee on Homeland

Security and Government Affairs, September 22, 2016

So What Is Driving Policy Change?

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Josh Hardy Media Firestorm

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Chimerix CEO Takes the Fall

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Ongoing Media Focus

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CNNSeptember 28, 2013 ·

Andrea Sloan is dying of ovarian cancer. She's

seeking "compassionate use" of a new drug that's

not FDA-approved, but a drug maker says it's too

risky. http://on.cnn.com/1fQkaEs

Ebola Raises More Questions

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Trump Highlights the Issue

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January 31, 2017 POTUS Meeting with Pharmaceutical Executives

“One thing that’s always disturbed me, they come up with a new drug for a

patient who’s terminal, and the FDA says, ‘We can’t have this drug used on the

patient,’ but they say that the patient within four weeks will be dead. They say,

‘Well, we still can’t approve the drug. And we don’t know if the drug works or it

doesn’t work, but we can’t approve the drug because we don’t want to hurt the

patient.’ But the patient is not gonna live more than four weeks.

So we’re gonna be changing a lot of – a lot of the rules.”

Pence Weighs in on “Right to Try”

February 7, 2017:

VP Pence meets with Right to Try advocates in the White House

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Navigating the Issues

Clinical Data

Cost

Liability Protection &

Other Business Considerations

Population vs. Individual

Health

FDA

Ethics

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Policy Changes and New Requirements

• State Right to Try Legislation

• 21st Century Cures Act

• Federal Right to Try Legislation pending

• ClinicalTrials.Govdisclosure requirements

• Revised request form for physicians

• Finalized draft guidances

• User-friendly website

FDA HHS

StatesCongress

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FDA Reduces the Paperwork

• In February 2015, FDA issued Draft Guidance containing a new form (Form FDA 3926) for physicians to make expanded access requests for individual patients

• Form FDA 3926 streamlines the process for making such requests, which would otherwise need to be made on the general IND submission form (Form FDA 1571)

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FDA Reduces the Paperwork

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New Patient-Targeted “How To” Information

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FDA’s New Final Guidances (June 2016)

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“Expanded Access to Investigational Drugs for Treatment Use–Questions

and Answers”

Implementation of FDA’s regulations on expanded access to investigational drugs for

treatment use under an IND

How expanded access is defined, types of expanded access, when and how to request

expanded access, and what information should be included in requests

IRB review

The role of Form FDA 3926

“Charging for Investigational Drugs

Under an IND–Questions and Answers”

Criteria for charging for an investigational drug for expanded access for treatment use

Which costs can be recovered (i.e., direct costs such as cost of drug and shipping/handling, but

not indirect and administrative costs)

Circumstances under which FDA authorizes charging for an investigational drug in a clinical

trial

2008-2015: Recent Federal Policy Efforts2007-08

110th Congress

• H.R. 6270 and S. 3046 (June 2008)

• Bi-partisan, Democratic-led effort (Rep. Watson, D-CA)

• Required FDA to create new expanded access regime

• Permitted manufacturers, following Phase I, to apply for expanded access authority and to charge for drugs

• Provided manufacturer liability protection

2009-10

111th Congress

• H.R. 4732

• Same as previous bill, but no Senate counterpart

2011-12

112th Congress

• H.R. 6342

• Rep. Ron Paul (R-TX)

• Permitted expanded access upon informed consent of patient

• Prohibited FDA from regulating access, or even collecting information

• No Phase I requirement

2013-14

113th Congress

• H.R. 4475 – Rep. Morgan Griffith (R-VA) introduces updated version of Rep. Paul’s bill, with liability protection for manufacturers

• H.R. 5805 – Rep. Michael McCaul(R-TX) introduces Andrea Sloan CURE Act, requiring manufacturers to post contacts for requests and provide denials in writing, and requiring GAO and Task Force Reports to Congress

2015-16

114th Congress

• H.R. 790 – Rep. Griffith bill reintroduced

• H.R. 909 –Andrea Sloan CURE Act reintroduced

• H.R. 3102 –Right to Try Act of 2015

• 21st Century Cures Act (P.L. 114-255)

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Overview of 21st Century Cures

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CURES: Origins in the House

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May 2014: House Energy & Commerce Committee “Call to Action”

• Focus on discovery, development and delivery

• Comments, ideas, 11 roundtables and hearings

January 2015: The first White Paper

April/May 2015: First drafts of House legislation

• Becomes H.R. 6

July 2015: Full House approves the bill

• Significantly modified from original proposals

• The politics – NIH Funding, FDA changes, and the Strategic Petroleum Reserve “pay-for”

CURES: The Senate’s Approach

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• Individual sections move as stand-alone bills through HELP Committee, but don’t reach the Senate Floor

• Many ideas don’t even make it through Committee

• No consideration of NIH funding or the “pay-fors,” particularly the SPR, which has now been used for other legislation

CURES: It All Comes Together

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Sept-Nov 2016: E&C, Ways & Means, and HELP Committees (with little input from Senate Finance) bring together a comprehensive bill

•Combines revised CURES, mental health, hospital outpatient, home infusion and numerous other provisions

•Addresses NIH funding with $4 billion authorization

November 30, 2016: H.R. 34 passes House

•Senator Grassley objects to “Sunshine” changes

December 7, 2016: Passed by Senate (and back through House)

December 13, 2016: Signed by President

Obama

Cures Section 3032

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Section 3032: A Policy is Mandatory!

Manufacturer or distributor of investigational drugs “shall make available” an expanded access policy

• Mandatory requirement to have an expanded access policy, whether or not manufacturer permits expanded access for its products

Expanded access policy “shall be made public and readily available”

• Publicly available Internet posting is sufficient

• Policy may be generally applicable to all manufacturer’s products

Policy may be revised at any time

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Section 3032: Content of Policy

Contact information to facilitate communication about expanded access requests

Procedures for making such requests

General criteria the manufacturer will use to evaluate requests for individual patients, and responses to requests

Length of time the manufacturer anticipates will be necessary to acknowledge receipt of requests

Hyperlink or other reference to the Expanded Access Record in ClinicalTrials.Gov

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Section 3032: Effective Date

The later of:

February 11, 2017 (60 calendar days after

enactment of CURES)

The first initiation of a phase 2 or phase 3

study with respect to an investigational drug

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New ClinicalTrials.gov Regulation

April 18, 2017: Deadline for

responsible parties to achieve

compliance

January 18, 2017: Final Rule

effective date

September 21, 2016: HHS issued

a Final Rule

November 19, 2014: HHS issued a Proposed Rule

on ClinicalTrials.gov

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The statutory authority for the expanded access disclosure

requirements in the rule is Public Health Service Act § 402(j),

which requires the submission of information regarding

whether, for an applicable drug clinical trial of an unapproved

drug/biological product, expanded access is available under

FDCA § 561

General Requirements

• If the responsible party for an “applicable clinical trial” is both the sponsor and the manufacturer, and expanded access is available, there must be a separate Expanded Access Record containing details about how to obtain access to the investigational product

― Applies to all types of expanded access (individual, intermediate or large size)

― Expanded Access Record is assigned a unique NCT number that is linked to the clinical study record for the investigational product

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What Information Is Required?

Brief Title Official Title Brief Summary

Study Type (which is “expanded

access” for this type of record)

Primary Disease or Condition

Intervention Name(s)

Other Intervention Names(s)

Intervention Description

Intervention Type (which is typically

“drug”)

Expanded Access Type

Eligibility Criteria Sex/Gender Age LimitsExpanded Access

StatusName of the

Sponsor

Responsible Party, by Official Title

Contact Information

Unique Protocol Identification

NumberSecondary ID

U.S. Food and Drug

Administration IND Number

Record Verification Date

Responsible Party Contact

Information

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Only bolded data elements are

required for individual patient

expanded access records

When Must Information Be Submitted?

Expanded Access Record must be created no later

than 30 days after expanded access

becomes available

NCT number for Expanded Access Record must be

linked to the clinical trial record

no later than 30 days after the NCT number is assigned

Data elements must be updated within 30 days of

the change

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Areas for Further Clarification…

Does CURES require a hyperlink to the clinical trial record or the

Expanded Access Record?

What if a manufacturer has not yet made a decision about whether

expanded access is available for an investigational product?

What if expanded access is available for an investigational product that is

not part of an “applicable clinical trial”?

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More Transparency for Expanded Access

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Status of State “Right to Try” Laws

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Source: Goldwater Institute (righttotry.org/in-your-state/)

33 states

have adopted

Right to Try

laws, and 14

have pending

bills

Green = Passed Law

Blue = Introduced Legislation

Red = Vetoed

Do’s and Don’t’s of “Right to Try” Laws

What They DO:

• Generally, they aim to grant patient access to investigational treatments if:

• Patient is terminally ill

• Physician recommends treatment

• Patient provides informed consent, and

• Treatment has completed Phase I clinical safety/dose limitation trial

• They grant physicians and manufacturers liability protection against claims arising from adverse events caused by investigational treatments

What They DON’T DO:

• They don’t create a right for terminally ill patients to access life-saving treatments exempted from FDA rules

• State laws do not permit manufacturers to provide patients with access to unapproved drugs, when the federal law mandates “no person shall introduce or deliver for introduction into interstate commerce any new drug”

• They don’t address questions of patient welfare and public health

• They don’t provide free access to experimental treatments

• They don’t compel anyone or any company to fulfill a patient request

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Some in Congress Trying to Build on State “Right to Try” Laws

Bills propose to federalize state RTT laws by

prohibiting FDA from blocking access if: (1)

intended to treat a patient who has been diagnosed

with a terminal illness; (2) is authorized by, and in

accordance with, State law; (3) drug is past Phase I

clinical trials

S.204 - TrickettWendler Right to Try Act of 2017

(Sen. Ron Johnson) - 44 co-sponsors

H.R.878 – Right to Try Act of 2017

(Rep. Andy Biggs) - 36 co-sponsors

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What’s Next?

Social media may overtake planning and procedure

FDA will continue to authorize the vast majority of the Expanded Access requests it receives

Patients will have access to more information about the availability of expanded access

Congress is engaging, forcing policy change

States, driven by the Goldwater Institute, will continue to enact “Right to Try” laws

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Where Do We Go From Here?

How will patients and physician utilize the increased information that will be available from

manufacturers?

This is not a simple issue – there is as much opportunity to do harm than to do good

Is social media the best tool for such a nuanced issue? And how does one become a responsible

voice in the debate?

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QUESTIONS?

THANK YOU!

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David J. Farber

(202) 626-2941

dfarber@kslaw.com

Preeya Noronha Pinto

(202) 626-5547

ppinto@kslaw.com