View from Washington Hot Topics in Health Care Regulation CMS & FDA

© 2015 Epstein Becker & Green, P.C. | All Rights Reserved. ebglaw.com

View from WashingtonHot Topics in Health Care Regulation

CMS & FDA

October 30, 2015


Hot Topics in CMS

© 2015 Epstein Becker & Green, P.C. | All Rights Reserved. | ebglaw.com 3































Hot Topics in FDA Regulation

© 2015 Epstein Becker & Green, P.C. | All Rights Reserved. | ebglaw.com

Agenda

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I. Diagnostics

A. Laboratory Developed Tests

B. Point of Care Tests

II. Pharmaceuticals

A. Drug Compounding

B. 505(b)(2)s

III. Medical Devices

A. Novel technologies

B. Mobile Health

IV. Combination Products

V. Challenging FDA


Diagnostics


Diagnostic Tests

Characteristics LDT IVD

What are they? Diagnostic Tests Diagnostic Tests

Who regulates right now? CMS (under CLIA) FDA (under FDCA)

Who makes them? Clinical Labs Manufacturers

Path to Market? • Validate internally• Start offering the test

• Spends years dealingwith FDA to get approval

On-going Requirements Limited A real pain

Two Broad Categories of Tests• Laboratory Developed Tests (LDT): Developed for in-house (single lab) use• In Vitro Diagnostics Tests (IVD): Developed to sell to multiple laboratories


LDT Horizon

1. Big differences in IVD and LDT regulation have biased against IVDs

2. FDA says it has authority to regulate LDTs like it regulates IVDs . . . and hasjust chosen not to do so for ~ 40 years, though that may be changing

3. FDA proposed a draft guidance that describes regulations of LDTs (not inuse yet). Key takeaways from draft:

i. Risk-based Regulation

ii. Long phase in of requirements

iii.Retains limited ‘enforcement discretion’ for

a. Tests for unmet needs

b. Tests for rare diseases

c. “Traditional” LDTs


Proposed Phase-In of Regulations


LDT Horizon

1. Billions of dollars at stake

i. Most high value genetic tests, advanced diagnostics for cancer, etc. are LDTs

ii. Many large and small labs rely heavily on LDTs for revenue

2. Congress is very interested

i. Competing proposals on Capitol Hill

ii. If clinical labs and IVD manufacturers can come up with an approach both like, ithas the best chance of becoming law

a. Labs and manufacturers are both big constituents

b. Cogresspersons need to have the support of both

iii.Current best guess – Absent Congressional action, FDA issues final guidance in thespring/summer


Point-of-Care Testing

1. LDTs are tests run in-house by laboratorians

i. Doctors take samples and send them to labs

ii. Results come back days/weeks later

2. With point-of-care testing, on the other hand –

i. Tests are run in an exam room or at the bedside

ii. Results in minutes

3. Most customers for point-of-care testing are “certificate of waiver” sites

i. These are physicians offices, urgent care clinics, minute clinics, etc.

ii. Non-traditional labs

iii.“Waiver” refers to the fact that CLIA lab requirements are waived for certificateof waiver sites

4. FDA decides which tests can be used at certificate of waiver sites

i. Test developers submit an application to get a CLIA waiver from FDA


~70% of all clinical testing

facilities are Certificate of

Waiver (“CoW”) sites

CoW sites represent the vast

majority of POCT sites

By law, CoW sites can only

perform CLIA-waived tests

Conclusion: The CLIA Waiver

Process Is Essential to Patients

Receiving the Full Benefits of

POCT

Promise of Point of Care Testing

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The current FDA process is stacked against CLIA waivers

• FDA created regulatory barriers that slowed development of POCT

There is increasing recognition this is bad for innovation and bad for patients

Reform is being pushed from all quarters, e.g.,

• Coalition for CLIA Waiver Reform

o Launched by EBG in May 2014

o Includes IVD manufacturers and public interest groups

• AdvaMed

• STD/AIDS Advocacy Groups

Real traction – hope to see major reforms in the next two years

• Secured bills in the House and Senate to require revision of FDA standards

• Ongoing discussions with FDA on ways to improve regulation

CLIA Waivers and Point-of-Care Testing

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Pharmaceuticals


Pharmaceuticals

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Characetistics Compounded Drugs FDA-approved Drugs

What are they? Drugs Drugs

Who regulates right now? FDA, States FDA, States

Who makes them? • Pharmacies• Outsourcing Facilities

Manufacturers

Path to Market? Make and sell (nopremarket review)

FDA review and approvalrequired

On-going Requirements Increasingly a real pain A real pain

Two Broad Categories of Drugs• Compounded Drugs: Historically, drugs made based on patient specific prescription

• Less individualized drugs have become more common in recent years• FDA-approved Drugs: Made for the masses


Compounding Quality Act of 2013 (applies to human drugs)

• Increases FDA oversight of small, traditional compounders (“503A” pharmacies)

• Creates a new kind of compounding entity: FDA-licensed compounders for steriledrugs (“503B” outsourcing facilities)

• Compounders chose which kind of compounder they want to be

Pharmacy Compounding

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503A 503B

Prescriptions Must have a patient-specific prescription

Call sell to doctors before receivingprescriptions

Products that youcan make

Can compound withmany activeingredients

Soon to be ltd. to compounding with:- Shortage drugs ingredient (~250)- A list of ingredients FDA is developing

Quality Standards State/USP FDA/cGMP

Interstate limits Soon (5%/30%) No limits


FDA is revamping its animal drug compounding guidelines

FDA has an “anti-503A” campaign

• They don’t want these compounders making sterile drugs

• They are rigorously enforcing the specific prescription requirement

• They are frequently inspecting 503As, finding problems, and pressing them tobecome 503Bs subject to FDA cGMPs if they sterile compound

It’s unclear how limited the menu of active ingredients will be for 503Bs

• FDA is making its list now

• The final list will constrain what 503Bs can make

It’s unclear how the 503A interstate shipment limits will shake out

• Currently proposed a 30% limit

• May not be as bad as it seems….

Pharmacy CompoundingOther important points

46


There are three basic kinds of new drug applications

• “Stand-alone” applications that contain all data to support approval (“505(b)(1)”)

• Applications that rely on previous FDA approvals (“ANDA” and “505(b)(2)”)

oThese applications rely on approvals of “Reference Listed Drugs” or “RLDs”

505(b)(2)s are a pathway for lower cost innovation

• You rely on previous approval to cut down work substantially

• You can introduce new, market differentiating feature through the path, e.g.,

oNew dosage forms (e.g., from immediate release to extended release)

oNew delivery systems (e.g., from syringes to transdermal patches)

oNew combinations (e.g., combining two+ active ingredients in a single pill)

With exponentially increasing costs to bring entirely new active ingredientsto market under 505(b)(1), teaching old drugs new tricks through the505(b)(2) path holds increasing appeal for small/mid-sized pharma

505(b)(2)s

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Devices


Devices, Generally

1. The FDA Center for Devices and Radiological Health (CDRH)

i. Regulates medical devices (and IVDs)

2. Different processes from bringing products to market

i. Pre-market Approval (“PMA”) for high risk devices

ii. 510(k)s for moderate risk devices

iii.De Novo Applications (used to bring new technologies to the 510(k) path whenthey don’t initially qualify for 510(k) review)

iv.Low risk devices = no FDA premarket review

3. Regulation of different device types is laid out in various FDA device“classifications,” e.g.,

§870.3545 Ventricular bypass (assist) device.(a) Identification. A ventricular bypass (assist) device is a device that assists the left or rightventricle in maintaining circulatory blood flow. The device is either totally or partially implanted in the body.

(b) Classification. Class III (premarket approval).


Novel Devices = Tremendous Potential

1. Newer implants for hip, knee, etc.

i. Better materials

ii. Embedded monitoring technologies

2. 3-D printing for customized devices (and drugs)

3. Robotics (assisted surgery, orthotics, etc.)

4. Software

i. Clinical Decision Support

ii. Mobile Health Applications (Apps)

iii.Telemedicine


Mobile Health

1. New FDA Guidances

i. Mobile Medical Applications (Feb. 2015)

ii. Clinical Decision Support Guidance (Scheduled for this year)

iii.Taking a more innovator-friendly approach

a. CDRH recognizes potential public health value of products

b. Taking a hands-off approach to low-risk apps

2. Still a lot of work being done on the policy development and applicationside

i. EBG Coalitions

a. mHealth Coalition

b. Clinical Decision Support Coalition

ii. Activity on Capitol Hill


CombinationProducts


Combo Product: A combination of a drug/biologic and device

The Lead Review Center is based on the “Primary Mode of Action” of theproduct, but Centers must work together too

• Deciding PMOA is not always easy

• FDA has been defaulting to finding drug PMOAs for products

oAdds lots of time/expense relative to device pathways

oFDA is getting fought on these decisions by innovators

Various problems on policy side that are being addressed by many players

• Combination Products Coalition (EBG managed Coalition of industry leaders)

• AdvaMed/PhARMA/BIO

• Capitol Hill (Reform Bills in Congress)

Combination Products

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Do Burdensome Combination Products Policies Hold a Key to Extending theProfitable Life of Drugs?

Example: Drug delivery systems

• Novel drug delivery systems are being developed to add assurance of safe andeffective use

• The standards being applied to assessment of these systems are increasing

oWhat was previously more of an engineering / human factors evaluationexercise is now transforming into actual use studies with products

Example: Mobile devices

• Interest in new technologies to monitor patients, assure compliance, adjust dose

• If embedded in pivotal trials, they may be part of the conditions for approval

Could patents on these ancillary products provide additional, indirect, avenuesof protection for drug products from generic competition?

Problems May Create Opportunities

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Challenging FDA


Policy challenges can be successful

• FDA Guidance for Industry: New Chemical Entity Exclusivity Determinations forCertain Fixed-Combination Drug Products (Oct. 2014)

• Responded to 2013 citizen petition, and driven by public health needs

• Changed longstanding interpretation of 5-year exclusivity to extend it tocombination drug products with old active moieties

o Intended top motivate development of combination antibiotics

Product-specific challenges

• Formal Dispute Resolution (Appeals)

• Provide persuasive public health arguments based in science and law

• Always consider this as an option when you are struggling with FDA

oBe respectful and practical in appeals

oDon’t let concerns about ‘retribution’ from reviewers keep you from trying it

Challenging FDAChallenging FDA at the Agency Level

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Court challenges

• Law is the dominant consideration

• Courts will not overrule FDA public health or scientific conclusions

• Focus on –

oDecision-making process

oDeviations from precedent

oDeviations from words or intent of the law

oDisparate treatment (Bracco Diagnostics v. Shalala arguments)

Challenging FDAChallenging FDA in Court

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Healthcare

View from Washington Hot Topics in Health Care Regulation CMS & FDA