Transcript Slide 1
Two Worlds Converge
Pharma/Device
Opportunities
Challenges
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The Code of Federal Regulations
– The Rules –
Title 21 defines FDA’s responsibilities
Online at www.gpoaccess.gov
Regulations multiply quickly… (1971 vs. 2004)
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FDA Centers Organized by Commodity
• Food & Cosmetics (CFSAN - Center for Food Safety &
Nutrition)
• Veterinary Drugs & Devices (CVM - Center for Veterinary
Medicine
• Biologics (CBER - Center for Biologics Evaluation &
Research)
• Drugs (CDER - Center for Drug Evaluation & Research)
• Medical Devices, Diagnostics & Radiological Health
Products (CDRH - Center for Devices & Radiological
Health)
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Definition of a Biologic
(See 21 CFR Part 600 for formal definition)
An agent intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of a
disease or condition.
-ANDIs derived from a living organism such as a
therapeutic serum, toxin, antitoxin, or
analogous product.
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Definition of a Device
(See 21 CFR Part 800 for formal definition)
An instrument, in-vitro reagent, implant,
component part or a similar article, which is
intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of a
disease or condition.
-ANDDoes not achieve its primary intended purpose
through chemical action within the body.
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Definition of a Drug
(See 21 CFR Part 201 for formal definition)
An agent intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of a
disease or condition.
-ANDAchieves its intended purpose by a biochemical/
physiological mechanism by which the agent
produces a response.
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Confused? You’re Not Alone.
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FDA Office of Combination Products
Established in 2002
Reports to the Office of the Commissioner
Assigns primary Center for review
FY2003: Handled 12 products
FY2009: Handled 377 products
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What am I?
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Stent
Drug Eluting Stent
Implant
Implant with Silver Coating
Glucose Monitor with Insulin Pump
A.
B.
C.
Device
Combination Product: Device and Pharma
Combination Product: Device, Diagnostic and Pharma
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Convergent Technologies
An Abbreviated History
• Injections
• Drug eluting stents
• Antimicrobial implants
• Bandaid – Class 1
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Combination Devices
Benefits
• Extend Patent Life – New Dose Forms
• Personal Medicine
– Improve Patient Care
– Eliminate Potential Law Suits
• Reduce Infections and HAIs
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Device needs Pharma
• Within 24 hours implants begin to develop
colonies of bacteria or fungus - biofilms form
• 70% of HAIs are linked to implants
• 10% of catheters, UTI’s develop serious
complications due to the development of
biofilms
• 50% of LVAD recipients develop infections and
die
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WHAT IS A BIOFILM
Staphylococcus Biofilm
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Definition of a Biofilm
An aggregate of microbes with a distinct architecture
Like a tiny city in which microbial cells form towers that
other microbes attach to. These microbes derive
nutrients and protection from this biofilm
community and become highly resistant to treatment
Bacteria growing in a biofilm are up to 1,000 times
more resistant to antibiotics than the same bacteria
not growing in a biofilm and often lead to lifethreatening systemic infections
Does anyone in attendance have a biofilm trying to
develop in their body right now?
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Reducing the Growth of Biofilm
Antibiotics or antifungals can’t reach biofilm that is
growing on an implant when taken by mouth or via
the bloodstream
Pharma: Drug-eluting or infused devices to prevent
biofilms from forming
FDA – Safety and Efficacy
Will the slowly released anti-microbial affect the body’s
natural flora?
Will we build up a tolerance to anti-microbials used?
Tridosan’s overuse has caused it to be banned in
Europe
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What defines a drug?
Drug resistance is increasing while new antibiotics are
decreasing
Approved New Antibiotics
1989: 16
2009: 1
Any product claiming to reduce infection or inflammation must
be classified as a drug
Rediscover materials that have anti-microbial properties – Silver
Silver has natural anti-microbial properties
Devices that contain silver must be approved as a drug; silver is a
drug?
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FDA
• Clinical trials are required for any device that
claims to be capable of causing infection
reduction, biofilm reduction or adhesion
prevention
• Trials require clinical trial candidates
• Is the medical device industry future ready
– stringent FDA requirements including clinical trials
– lengthened time to market
– additional financing required
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Right now
• Drug firms: Facing patent expirations,
shrinking pipelines.
• Wall Street wants GROWTH.
• Device firms: Small, entrepreneurial.
• Device path to market changing quickly.
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Device Paths to Market
Premarket Approval (PMA)
o Used for new, life-supporting, or other high-risk devices
o Staged clinical trials for evidence of safety & efficacy
o Formal FDA review and approval
Premarket Notification [PMN or 510(k)]
o For relatively low-risk devices as defined in CFR
o Submit evidence to FDA that the device is “substantially
equivalent” (SE) to a device already on the market
o Product can be marketed if FDA doesn’t disagree it’s SE
o Results in marketing clearance, not approval
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Compare to Drug Paths to Market
New Drug Application (NDA)
o Well-established path to market
o Modeling, literature, animal studies submitted to FDA
o Staged clinical trials for evidence of safety & efficacy
o Formal FDA review and approval
Abbreviated New Drug Application (ANDA)
o Generic products allowed once patent, exclusivity
expired
o Submit evidence to FDA that generic is bioequivalent
o FDA reviews to ensure equivalence to the safe, effective
innovator drug
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A Closer Look at Device Regulation
• Device regulation began when Amendments to the Food Drug &
Cosmetic Act took effect on May 28, 1976; unregulated prior to
1976
• Most devices allowed onto the market under 510(k) have no safety
and effectiveness testing
• From May 28, 1976 through 2009:
127,239 510(k)s were cleared
o 1,125 PMAs were approved
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• “Equivalence creep” = “Predicate creep”
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1977 device B equivalent to 1975 device A
1982 device C equivalent to device B
1990 device D equivalent to device C
2001 device E equivalent to device D
Is the 2001 device E equivalent to the 1975 device A?
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Problems Evident
• Device recalls, literature, press attention, anecdotal
reports, malfunctions hit critical mass
– e.g., Archives of Internal Medicine reports that the most
commonly recalled device since 2005 is the automated
external defibrillator (AED)
– AEDs were cleared under 510(k)
• GAO report results: Congress orders FDA to study
510(k) process
• FDA forms a Task Force & a Working Group
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Changes to 510(k)s Begin
• Recommendations of Task Force and Working Group
evaluated by FDA
• Early 2011: FDA targets 55 recommendations
• Recommendations draw heavily from pharmaceutical
experience
• FDA makes up ambitious 2011 calendar
• Schedules new guidances beginning in March
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Some Expected Changes
• Identify standards from various agencies & professional
organizations FDA can adopt (mostly engineering)
• Define a new class of 510(k) requiring clinical trials (IIb
designation)
• Require additional information in adverse event reports
(AERs) as seen in drug AERs
• Establish a postmarketing safety database
• Identify safety signals (as in pharmacovigilance)
• Enhance device reviews with medical officers (clinical
practitioners) to evaluate effects on patients
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More Changes
• Establish database of device modifications (similar to
supplemental NDAs)
• Develop a system of universal product identifiers similar
to National Drug Codes (NDCs)
• Establish a consistent vocabulary to describe devices and
their therapeutic categories
• Work with other Centers to establish a Science Council to
advise industry & FDA staff
• Look at submission and formatting of electronic labels (as
in the Structured Product Labeling requirements for
drugs)
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Bottom Line?
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Drug firms: Patent cliff, limited pipeline
Device firms: Small, edible
Combination products a logical extension
Regulations now converging
Information needs expand
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Information Needs
Business Start-Up;
Venture Capital; IPO
Engineering
Small Firm Challenges
Device Manufacture
& Regulation
Established Life Science
Firm; SEC; Shareholders
Chemistry, Biology
Large Firm Challenges
Drug Manufacture &
Regulation
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Speculation
FDA’s current organization by commodity is blurring; emphasis is
moving to therapeutics by system.
As information professionals, will we support a pharmaceutical or
device firm or a health science company developing
all manner of therapies for specific conditions or
particular body systems?
This shift will require we understand, mine and
integrate more cross-disciplinary information to
support complex emerging health care products.
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Truth or Fiction?
Pacemaker the size of a tic tac
Inserted via a small plastic tube into a vein or
artery and placed next to the heart
No lead wires required
Uses renewable energy
Contains an oscillator for storing and
dispensing an electrical charge when needed
Includes memory and a telemetry system for
transferring data
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Truth or Fiction?
Diabetic Contact Lenses
Nano particles in lenses react with glucose
molecules in patients’ tears causing a chemical
reaction that changes the lens color and alerts
the wearer to adjust their glucose
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Truth or Fiction?
Synthetic compounds that stimulate a body’s
own immune response
Delivers broad spectrum activity against
bacteria, fungi and certain viruses
Kills pathogens on contact by attacking the outer
shell of the microbe, destroying it’s outer
membrane.
Microbes are highly unlikely to evolve new outer
membranes and therefore, cannot adapt to this
synthetic microbial agent
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Truth or Fiction?
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Artificial Pancreas
Artificial Heart
Implantable Artificial Kidney
Artificial Liver
Artificial Blood Vessels from Salmon Skin
Artificial Bones using Citric Acid
Artificial Skin that is able to bleed, heal, tan,
sweat and fight off infection
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Future Ready
• Device firms have the engineers to design these
products
• Drugs firms have the resources and the experience
needed to conduct trials, develop, and bring these
products to the market
• Is it logical to conclude that device and pharma will
remain separate?
• Conclusion is identical even when derived from an
entirely unique path.
• Where will our focus be in the next few years, on
devices, pharmaceuticals, or both?
Are you Future Ready?
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Free Information Sources
• CDRH Medical Device Innovation Initiative
at http://www.fda.gov/deviceinnovation
• http://wwwmddionline.com/categories/conve
rgent-technologies
• http://www.ivdtechnology.com
• http://medtechinsider.com
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QUESTIONS?
Marlene Bobka, FOI Services
[email protected]
301-975-9400
Sandra Baker, UBM Canon
[email protected]
215-944-9836
Thank You!
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