EAP pres

Ernest Mario School of Pharmacy
Expanded Access
Programs/Compassionate Use
William Jackson, PharmD, RPh
Introduction to Pharmaceutical Industry
2/14/2014

Objectives
• Define Expanded Access Programs (EAPs)
• Define the regulations involved in expanded
access programs
• Describe the physician, patient, and industry
perspective on expanded access programs
• Apply understanding of expanded access
programs by reviewing a case study

IND Submitted
NDA Submitted
Review Decision
Sponsor answers any
questions from review

How is it actually done
• Components
– Budget
– Regulations
– Protocol development
– Investigator/site initiation
– Investigational Review Board (IRB)
– Trial/ study participant enrollment /data
maintenance
– Study closure/statistical analysis/reporting
Initiation of
trial
Maintenance
of trial/data
Reporting of
data

Clinical trial research matrix
Protocol
manager
Clinical
investigators
Medical
oversight
Clinical site
monitors
Drug supply
Advocacy
groups
Data mgt
specialists
Regulatory
agencies
(FDA)

Drug is in
Phase 3 trials,
but isn’t
approved yet

What is Expanded Access?
Peppercorn J et al. Presented at: ASCO University 2010
• An investigational new drug (IND) or biologic
• Treats a patient with serious disease
• Patient has no other treatment options
• Patient does not meet criteria for clinical trials

When EAPs occur
• EAPs can occur in phase 2, during phase 3, or after
phase 3
• They occur before FDA/health authority approval and
marketing of approved agent
• Key criteria: sufficient safety and efficacy
– This criteria is relative to the patient population and need
Phase 2
Phase 3
Expanded Access Programs
FDA
Approval

Expanded Access is a Balance!
IND in clinical trials
have not been proven
safe and effective yet
Patient has exhausted all
Other treatment options AND
Doesn’t meet criteria for clinical
trial

Expanded Access Options
Large Population
Intermediate-size
population
Individual
Patient

Large Population
• Can have hundreds to thousands
• Company sponsored trial
• Incorporated into a Treatment Use Protocol for EAP
– Treatment Use Protocol: Allows physicians to provide
investigational new drugs to patients OUTSIDE of clinical trials.
• Pros :
- Proper conduct : high quality controlled safety data
- Allows all regions to have access
- Increase awareness : pt population / drug
• Cons:
- Resources and costs (drug supply, human capital)
- Low number of requests
1. Peppercorn J et al. Presented at: ASCO University 2010
2. Michener T. Presented at: CBI’s 5th Annual Congress; March 12-13, 2012; Philadelphia, PA

Intermediate-size population
• More than one patient, but does not enough to
constitute a treatment use protocol
• Can have multiple intermediate-size EAPs at once
– FDA can request to consolidate these under a Treatment use
protocol

Individual Patients/Single Patient IND
US Regulatory mechanism under which a pharmaceutical
company can make available to a physician an
investigational drug for the treatment of individual
patients outside of clinical trials.
Pros:
• Less resources
• Could start quickly
• Fits with a low number of request
Cons:
• Limited monitoring of safety
• Spontaneous requests : unpredictable

FDA REGULATIONS
Expanded Access Programs

FDA Final Rule Oct 2009
• Clarifies existing regulations and adds new types of
expanded access for treatment use
• Revises the charging regulation to clarify the
circumstances under which charging for an
investigational drug in a clinical trial is appropriate
• Permits charging for a broader range of
investigational and expanded access uses
1. Michener T. Presented at: CBI’s 5th Annual Congress; March 12-13, 2012; Philadelphia, PA
2. Guidance for Industry. Expanded Access to Investigational Drugs for Treatment Use – Qs & As. May
2013

FDA regulations – Subpart I
• Consolidates treatment use into a separate
subpart of the IND regulations describing:
– Three (3) distinct access categories:
• Individual
• Intermediate-size
• Treatment IND/protocol
– General criteria for each the 3 access
categories
– Requirements for submission
– Safeguards to EAPs (informed consent, IRB
review, reporting)
2013
2. Food and Drug Administration Final Rule 2009

Requirements for all EAPs
21 CFR 312.305
• Serious or immediate life threatening illness or
condition
• Lack of alternative therapies
• Benefit justifies risks
• Providing drug will not interfere with the expanded
use
• All human subject protections apply to all EAPs
2013
2. Food and Drug Administration Final Rule 2009

FDA
Physician
Patient
Industry
IRB (ethical)
Klein R. Presented at: Rare Disease Day; March 1, 2012; FDA
Community
Effort
Perspectives to consider with EAPs

FDA Perspective
• Size of exposed population and seriousness of disease
• Need sufficient evidence of safety and effectiveness
• The needs of individual must be balanced against
society’s
• Contrast this with research which is the systematic
approach to understanding the safety and efficacy of
a drug
• ~20% of drugs entering phase 1 end up approved
• At least 1/3 are withdrawn due to safety concerns

Physician Perspective
• Patient has a serious and life-threatening disease
• No acceptable treatment options, and not eligible for
clinical trials
• Company sponsored vs physician sponsored
• May need to help initiate the process
• Commitment to filing paperwork, ongoing support,
and monitoring of patient
• Potential for not being compensated

Patient Perspective
• May provide patients access to a potentially beneficial
therapy
• Treatment IND may provide a bridge between product
development and approval by making it more widely
available

Industry Perspective
• EAP can be a chargeable program - it is the
company's decision
• Companies may request cost recovery
– Cost recovery may occur if it is a barrier
• May promote development of additional uses of a
drug
• Early access may make enrollment of phase 2 and 3
trials more difficult
• Manufacturing capacity may limit supply for other
trials

Ethical Perspective
• Is there a risk worse than death?
• Investigational Review Board (IRB) involved with all forms
of EAP
• New drugs have many unidentified toxicities and risk that
may not be seen in early clinical development
– Suffering
– Pain
– Acceleration of death
“There are things worse than
death – being made to die faster,
being made to die more miserably,
or having ones dying prolonged…
with no increase in quality of life”
- Arthur Caplan, 2007

Summary of Expanded Access Programs
• EAPs have:
– No research intent
– Investigational agent
– Patients with no other alternatives
• Three (3) EAP types:
– Individual use
– Intermediate size population
– Large population
• FDA, physician, patient, industry, and IRB work
closely together to monitor proper use and safety

Summary
• Clinical research development encompasses many
different forms of research
• Other examples:
– Investigational Sponsored Research (ISR)
– Health Economics Outcomes Research (HEOR)
– Non-clinical intervention research
– Late phase research

Case study continued
• Scarlet Knight fever is a condition estimated to affect
less than 20,000 people in the US
• You work at RU Pharma and lead the EAP
development team
• You get a request from a doctor for access to an
investigational drug for one patient with Scarlet
Knight fever
• What type of EAP is this?
• Who would be responsible for monitoring
the patient for this type of EAP?
• Does this still need to be reviewed
by an IRB?

Where to find access programs
• Healthcare provider
• www.clinicaltrials.gov
• Patient Advocacy Groups
• Online
• Word of mouth (other patients)

References
“Requirements for all expanded access uses.” 21 CFR 312.305. 2013
Food and Drug Administration Final Rule. Expanded access to investigational drugs for
treatment use. Federal Register. Rules and Regulations 2009;74(155):40900-40945.
Accessed at: http://www.gpo.gov/fdsys/pkg/FR-2009-08-13/pdf/E9-19005.pdf
Guidance for Industry. Expanded Access to Investigational Drugs for Treatment
Use – Qs & As. May 2013. Accessed at:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati
on/Guidances/UCM351261.pdf
Klein R. Expanded access programs. Presented at: Rare Disease Day; March 1,
2012; Office of Special Health Issues, Food and Drug Administration. Accessed
at:
http://www.fda.gov/downloads/ForIndustry/DevelopingProductsforRareDiseases
Conditions/OOPDNewsArchive/UCM294794.pdf
Michener T. Presented at: CBI’s 5th Annual Congress; March 12-13, 2012;
Philadelphia, PA
Peppercorn J, et al. Introduction to expanded access rules and regulations. ASCO
University 2010. Accessed at: http://university.asco.org/expanded-access-
introduction

Questions?

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