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Title 21 defines FDA’s responsibilities
Online at www.gpoaccess.gov
Regulations multiply quickly… (1971 vs. 2004)
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• 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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(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.
-AND-
Is derived from a living organism such as a therapeutic serum, toxin, antitoxin, or analogous product.
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(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.
-AND-
Does not achieve its primary intended purpose through chemical action within the body.
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(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.
-AND-
Achieves its intended purpose by a biochemical/ physiological mechanism by which the agent produces a response.
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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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• Stent
• Drug Eluting Stent
• Implant
• Implant with Silver Coating
• Glucose Monitor with Insulin Pump
A.
Device
B.
Combination Product: Device and Pharma
C.
Combination Product: Device, Diagnostic and Pharma
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An Abbreviated History
• Injections
• Drug eluting stents
• Antimicrobial implants
• Bandaid – Class 1
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• Extend Patent Life – New Dose Forms
• Personal Medicine
– Improve Patient Care
– Eliminate Potential Law Suits
• Reduce Infections and HAIs
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• 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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Staphylococcus Biofilm
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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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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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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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• 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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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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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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• 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: o 127,239 510(k)s were cleared o 1,125 PMAs were approved
• “Equivalence creep” = “Predicate creep” o 1977 device B equivalent to 1975 device A o 1982 device C equivalent to device B o 1990 device D equivalent to device C o 2001 device E equivalent to device D o Is the 2001 device E equivalent to the 1975 device A?
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• 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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• 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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• 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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• 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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• 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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Business Start-Up;
Venture Capital; IPO
Established Life Science
Firm; SEC; Shareholders
Engineering
Small Firm Challenges
Device Manufacture
& Regulation
Chemistry, Biology
Large Firm Challenges
Drug Manufacture &
Regulation
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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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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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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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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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• 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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• 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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• 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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Marlene Bobka , FOI Services
MBobka@foiservices.com
Sandra Baker , UBM Canon
Sandra.Baker@ubm.com
301-975-9400 215-944-9836
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