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: JSKAHAN@HHLAW.COM
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Presentation Overview
Legal Framework for Regulation of Combination Products FDAs 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
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) 7

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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 Products 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
FDAs Regulatory Structure for Dealing With Drug Delivery Devices
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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FDAs Historical Regulation of Drug Delivery Devices

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
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 industrys 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 FDAs 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 22

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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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