Transcript Regulatory and Legal Challenges for Developers of Drug Delivery Devices

Regulatory and Legal Challenges for
Developers of Drug Delivery Devices
Public Workshop: Innovative Systems for Delivery of
Drugs and Biologics – Scientific, Clinical, and
Regulatory Challenges
July 8, 2003
Bethesda, Maryland
Jonathan S. Kahan
Partner
Hogan & Hartson L.L.P.
555 Thirteenth Street, NW
Washington, DC 20004-1109
Phone: (202) 637-5794
Fax: (202) 637-5910
E-Mail: [email protected]
Hogan & Hartson L.L.P.
Presentation Overview
• Legal Framework for Regulation of Combination
Products
• FDA’s Historical Approach to the Regulation of
Combination Products and Drug Delivery Devices
• The Obstacles and Challenges to Efficient
Regulation of Drug Delivery Devices
• Consideration of New Policies and Procedures to
Regulate Drug Delivery Devices
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Legal Framework for Regulation
of Combination Products and Drug
Delivery Devices
• Drugs
– Articles Intended to Prevent, Cure, or Treat Disease
– Articles Intended to Affect Structure or Function of the
Body (Section 201(h) of FDCA)
• Devices
– Same Definition As Drugs, but Devices Cannot
Achieve Their Primary Purposes Through Chemical or
Metabolic Action in or on the Body
– Devices Usually Accomplish Their Primary Purpose by
“Mechanical” Means
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Legal Framework
• Biologics (Section 351, PHS Act)
– A Virus, Serum, Toxin, Antitoxin, Vaccine, Blood,
Blood Component or Derivative, Allergenic Product, or
Analogous Product
– Intended for the Prevention, Treatment or Cure of
Diseases or Injuries of Man
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Legal Framework
• Prior to 1990, Combination Products Regulated on
a Case-by-Case Basis
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Condoms With Nonoxynol-9
Biliary Lithotripters Used With Ursodeoxycholic Acid
Transdermal Patches for Drug Delivery
Antimicrobial Coated Catheters
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Legal Framework
• The SMDA of 1990 Sought to Add Structure to
Combination Product Regulation, Including Drug
Delivery Devices
• FDA Promulgated Procedures to Effect SMDA
• Under SMDA, a Lead Center Within FDA To Be
Designated for Review Authority Based On
“Primary Mode of Action”
• Primary Mode of Action Never Defined by
Congress or FDA
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Legal Framework
• Definition of Combination Products (21 C.F.R. §
3.2)
– Comprised of Two or More Regulated Components
That Are Physically, Chemically, or Otherwise
Combined or Mixed and Produced As a Single Entity
(e.g., Prefilled Syringes)
– Two or More Separate Products Packaged Together in a
Single Package or As a Unit (e.g., Lumbar Puncture
Kits)
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Legal Framework
• Definition of Combination Products (21 C.F.R. § 3.2)
– A Product Packaged Separately but Intended for Use With a
Particular Approved Product Where Both Products Are
Required to Achieve the Intended Use, Indication, or Effect,
and the Approved Product’s Labeling Would Need to Be
Changed Upon Approval
– Any Investigational Product Packaged Separately, but
Intended for Use Only With Another Individually Specified
Investigational Product Where Both Products Are Necessary
to Achieve the Intended Use
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Legal Framework
• FDA’s Regulatory Structure for Dealing With
Drug Delivery Devices
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Office of Combination Products
The Center Product Jurisdiction Officers
The Request for Designation
The Pre-IDE/Pre-IND Meetings
Coordination Between CDRH, CBER, CDER
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FDA’s Historical Regulation of
Drug Delivery Devices
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Syringes (Prefilled and Non-Prefilled)
Infusion Pumps
Metered Dose Inhalers
Transdermal Patches
Iontopheresis Devices
The Interface Between the 510(k) Notice, PMA,
ANDA, and NDA Processes
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Historical Regulation
• The Second Generation of Drug Delivery Devices
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Tobacco Products
Laser Activated Drugs
Drug Coated Catheters and Stents
Catheters to Locally Deliver Specific Drugs
Porators and New Patches
The Drug Lollipop or Chewing Gum
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Historical Regulation
• The Evolving Technologies
– Drug Delivery Via Chip Technologies
– The Closed Loop Physiological Monitor Triggering
Drug Delivery
– Inhalation for Drug Delivery
– Needle-free Drug Delivery
– Implantable Encapsulation Technologies
– Nanotechnology Drug Delivery Devices
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The Challenges and Obstacles of
New Drug Delivery Technologies
• Many Drug Delivery Devices Are Developed By
Device Companies for Uses With Approved Drugs or
Biologics
• Creates Challenges if the Device Allows the Drug to
Be Used For:
– New and Different Indications
– Different Mode of Delivery (e.g., I.V. vs. Topical)
– Different Drug Dosage/Schedule
• The Challenge of Modifying the Drug Formulation to
Optimize Delivery With the Device
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Challenges and Obstacles
• Is a New NDA Required for the Drug if You Have a
Different Delivery Mechanism Than the Mechanism
Described in the NDA Approved Labeling?
• Does the PMA Process or the NDA Process Predominate in
Drug Delivery Review?
• Does the Drug Labeling and the Device Labeling Have to
“Mutually Conform?”
– What is the definition of mutually conforming labeling?
– Does the labeling have to be identical or just similar in spirit?
– Who resolves issues of cross-labeling and how?
• What is the Regulatory Path if the Device is Designed to
Deliver a Family of Drugs?
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Challenges and Obstacles
• The Challenge of Pharma/Device Industry Cooperation
– The Regulatory Process Can Be Made Easier If the Pharmaceutical
Manufacturer Authorizes Access to Its NDA and
Clinical/Preclinical Files to the Device Company or Files an NDA
or NDAS to Support the Device Approval
– Often the Device Allows Broadened Uses of the Drug – an
Incentive for Pharma Cooperation
– In Some Cases, the Device May Allow Use of Less Drug Through
More Optimal Delivery – a Disincentive for the Pharma
Cooperation
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Challenges and Obstacles
• The Regulatory Implications of Pharma/Device
Interaction
– Without Pharma Cooperation (NDA, DMF Access and
Research Cooperation), Device Companies Have a
Difficult Time Obtaining NDA Approval
– The Applicability of the Section 505(b)(2) Process in
Approving New Drug Delivery Devices, Where the
Route of Administration Is Outside NDA/ANDA
Approvals
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Challenges and Obstacles
• The Regulatory Pathway Conundrum
– Should a 510(k) or PMA be required along with an
NDA for each new drug delivery device?
• The “pullout PMA” or “pullout NDA” paradigm
– Can a PMA be approved that includes drug component
labeling?
• The Cypher Serolimus Eluting Coronary Stent on Raptor™
Over-the-Wire Delivery System
– The device industry’s historical difficulty in navigating
the NDA/ANDA process
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Challenges and Obstacles
• The Lead Center Conundrum
– Drugs Used With New Drug Delivery Devices Are Often Modified
in:
• Formulation
• Dosage administration
• Dosing schedule
– Should CDER or CBER Always Have Lead Jurisdiction of the
Drug or Biologic?
– Does FDA Routinely Focus on the Last Thing the Product Does to
Define “Primary Mode of Action”?
• Drug delivery catheters
• Transdermal drug delivery
• The photodynamic therapy paradigm
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New Approaches to Drug
Delivery Devices
• Is the FDA’s Interpretation of Primary Mode of
Action Outdated?
• Can the Process Be Streamlined?
• If the Drug to be Delivered Is Already Approved
for Delivery in Similar Doses, Schedule, and
Formulation, Can Jurisdiction be Given to CDRH
With Consultation by CDER/CBER?
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New Approaches
• Should There Always be Preference For One
Approval Submission?
– Is the Idea of the New NDA or NDA Supplement Along
with a PMA or 510(k) for the Drug Delivery Device
Outmoded and Inefficient?
– Does FDA Need New Legislation to Accomplish a
“Unitary Approval Mechanism” for Drug Delivery
Devices?
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New Approaches
• How Best to Define “Primary Mode of Action”?
• Factors to Consider in Defining Primary Mode of Action
What is the Innovative Drive Behind the
Product?
What Role Does Safety and Efficacy Play in
Defining Primary Mode of Action?
How Will the Product be Used?
Who Will Use the Product?
• Should the Primary Mode of Action Standard be
Legislatively Replaced?
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Conclusion
• The Present System of Dual Approvals is Not
Optimal
• The Primary Mode of Action Standard, as
Presently Implemented Without Guidance, is
Difficult to Apply and Interpret
• New FDA Guidance on Classes of Drug Delivery
Devices and the Regulatory Pathways Would Be a
Significant Help
– The Intercenter Agreements are Outdated
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Conclusion
• Move Toward a Unitary Drug Delivery Device
Approval Mechanism with Single Center
Jurisdiction is Needed
• The OCP Should Have the Power to Oversee and
Play a Significant Role in Novel Drug Delivery
Device Approvals
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