1 Two Worlds Converge Pharma/Device Opportunities Challenges.

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Two Worlds ConvergePharma/Device

OpportunitiesChallenges

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The Code of Federal Regulations – The Rules –

Title 21 defines FDA’s responsibilitiesOnline 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.

-AND-Is 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.

-AND-Does 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.

-AND-Achieves its intended purpose by a biochemical/physiological mechanism by which the agent produces a response.

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Confused? You’re Not Alone.

• 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?

• Stent• Drug Eluting Stent• Implant• Implant with Silver Coating• Glucose Monitor with Insulin Pump

A. DeviceB. Combination Product: Device and PharmaC. 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 BiofilmAn aggregate of microbes with a distinct architectureLike 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 life-threatening 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 EfficacyWill 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

decreasingApproved New Antibiotics

1989: 16 2009: 1Any product claiming to reduce infection or inflammation must

be classified as a drug

Rediscover materials that have anti-microbial properties – SilverSilver 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 deviceso Staged clinical trials for evidence of safety & efficacyo Formal FDA review and approval

Premarket Notification [PMN or 510(k)]o For relatively low-risk devices as defined in CFRo Submit evidence to FDA that the device is “substantially

equivalent” (SE) to a device already on the marketo Product can be marketed if FDA doesn’t disagree it’s SEo Results in marketing clearance, not approval

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Compare to Drug Paths to MarketNew Drug Application (NDA)o Well-established path to marketo Modeling, literature, animal studies submitted to FDAo Staged clinical trials for evidence of safety & efficacyo 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 bioequivalento 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:o 127,239 510(k)s were clearedo 1,125 PMAs were approved

• “Equivalence creep” = “Predicate creep”o 1977 device B equivalent to 1975 device Ao 1982 device C equivalent to device Bo 1990 device D equivalent to device Co 2001 device E equivalent to device Do 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?

• 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

Drug Manufacture & Regulation

Established Life Science Firm; SEC; Shareholders

Business Start-Up; Venture Capital; IPO

Engineering Chemistry, Biology

Small Firm Challenges Large Firm Challenges

Device 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 tacInserted via a small plastic tube into a vein or artery and placed next to the heartNo lead wires requiredUses renewable energyContains an oscillator for storing and dispensing an electrical charge when neededIncludes 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?

• 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/convergent-technologies

• http://www.ivdtechnology.com• http://medtechinsider.com

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QUESTIONS?Marlene Bobka, FOI Services Sandra Baker, UBM [email protected] [email protected]

301-975-9400 215-944-9836

Thank You!