© Copyright 2014 by K&L Gates LLP. All rights reserved. FDA UPDATE: Essential Knowledge...

© Copyright 2014 by K&L Gates LLP. All rights reserved.

FDA UPDATE: Essential Knowledge Pharmaceutical and Medical Device Companies Need for 2015

All Hands Meeting - November 6-7, 2014

Presenters:

Ellen Darling

+1.949.623.3540

[email protected]

Carol Pratt

+1.503.226.5762

[email protected]

Agenda FDA Guidance on Social Media/Advertisements New Preemption Implications Proposed Regulation of Software Used in

Healthcare IT Mobile medical applications, medical device

data systems, medical image storage/communication devices

Proposed Regulation of Laboratory Developed Tests

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FDA Guidance on Social Media/Advertisements

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FDA Guidance on Social Media/Advertisements

Evolution of Direct-to-Consumer (“DTC”) Advertising

Before 1906, there were no regulations relating to the marketing of drugs.

A drug company, or really anyone, could concoct crazy formulas, patent them and say anything they

wanted about their invention.

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Evolution of DTC Advertising

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By the mid-1980’s, the FDA declared that it had regulatory jurisdiction over DTC ads and required, among other things:

A fair and balanced account of risks and benefits

A summary of potential side effects

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Meeting these requirements in print ads was do-able, but accomplishing this in radio and TV ads posed problems for the industry.

As a result, companies started relying more on other types of ads as a way to get around the rules:

Reminder Ad Help-Seeking Ad

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Traditional DTC advertising is expensive. In 2007, industry spent $5 billion on DTC ads.

DTC advertising is controversial. Opponents argue:

Leaves patients misinformed and sometimes overwhelmed

Overemphasizes the benefits of the drug Leads to over-utilization of drugs Short-circuits important discussions between a

patient and a physician

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Proponents argue: Helps educate patients about different medical

conditions and drug therapies Causes them to do more research about a

potential condition or drug option More likely to reach out to their doctors with

questions

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Our research indicates that only two countries, the U.S. and New Zealand, allow DTC advertising.

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DTC Ads Via Social Media

Our industry has been relatively slow to utilize social media despite statistics about the number of:

People with multiple devices using social media every day

Facebook comments every minute Tweets generated weekly

This form of advertising is inexpensive compared to traditional, DTC advertising.

So why the delay?

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November 2009 - FDA held a hearing entitled “Promotion of Food and Drug Administration - Regulated Medical Products Using the Internet and Social Media Tools” to discuss, among other things:

What online communications are manufacturers, packers and distributors accountable for?

How can manufacturers, packers and/or distributors fulfill regulatory requirements (e.g., fair balance, disclosure information, and post-marketing submission requirements) in their internet and social media promotion?

When is the use of links appropriate?

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What happened after the FDA hearing in 2009?

The FDA initially received over 70 comments to the docket

In 2009 alone, FDA issued over a dozen warning letters relating to promotion on social media

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June 2014 Notice of Draft Guidance

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The FDA states:

“This draft guidance is intended to describe FDA’s current thinking about how manufacturers, packers, and distributors . . . of prescription human and animal drugs . . . and medical devices for human use . . . that choose to present benefit information should present both benefit and risk information within advertising and promotional labeling . . . of their FDA-regulated medical products on

electronic/digital platforms that are associated with character space limitations—specifically on the

Internet and through social media or other technological venues (Internet/social media)….”

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The FDA continues:

“..Examples of Internet/social media platforms with character space limitations include online microblog messaging (e.g., messages on Twitter or “tweets,” which are currently limited to 140 character spaces per tweet) and online paid search (e.g., “sponsored links” on search engines such as Google and Yahoo, which have limited character spaces as well as other platform-imposed considerations.”

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The FDA stated that the general factors that should be considered in communicating benefit information on Internet/social media with character space limitations are:

“Benefit information should be accurate and non-misleading and reveal material facts within each individual character-space-limited communication (e.g., each individual message or tweet).” Reveal material facts about the use of a

product, such as limitations to an indication or the relevant patient population

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“Benefit information should be accompanied by risk information within each individual character-space-limited communication.”

A company must assess whether, once benefit information is conveyed, there is enough room to “adequately convey required risk information” and any other required information

Should communicate the most serious risks Provide a mechanism (i.e., a hyperlink) to allow direct

and exclusive access to a complete discussion of only the risks of the product

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What does the FDA say a company should do if it cannot fit all of this information in 140 characters?

Do not do it - consider some other mode of advertising

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What Did Industry Think About The Draft Guidance?

FDA’s guidance is contrary to its own conduct Does not take into consideration certain search

engines, such as Google, that state that there is no guarantee that links will be displayed

Precludes, as written, manufacturers, etc… of complex drugs with multiple indications and serious risks, or certainly boxed warnings, from using this form of advertising

FDA should consider following a guideline similar to the FTC’s social media guideline

Violates the First Amendment

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September 2014 Notice of Draft Guidance

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DTC Ads Via Social Media – Risks and Benefits

Managing decisions relating to whether to advertise via the Internet/social media Risks of advertising on social media:

Warning letters Lack of control over re-tweets etc… Litigation with competitors Loss of control of messaging and brand image Costs associated with monitoring and other

regulatory issues

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DTC Ads Via Social Media – Risks and Benefits

Potential benefits of advertising on social media:

Statistics about social media’s effect on buying/decision making

Increase market share? Reminder ads are not as impactful as product

claim ads Sheer increase in the number of your potential

audience Less expensive than traditional DTC ads

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New Preemption Implications

Impact of Preemption Decisions and the FDA’s 2013 Proposal

Wyeth v. Levine, 555 U.S. 555 (2009)

A state-law failure to warn tort action against a brand name drug manufacturer is not preempted.

PLIVA Inc. v. Mensing, 131 S. Ct. 2567 (2011)

FDA’s regulations preventing generic drug manufacturers from changing their labeling except to mirror the label of the brand-name manufacturer preempt state-law failure-to-warn claims against generic drug manufacturers because it is impossible for generic drug manufacturers to comply with both federal and state duties to warn.

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Mutual Pharm. Co., Inc. v. Barlett, 133 S. Ct. 2466 (2013)

State-law design defect claims that turn on the adequacy of a drug’s warnings are preempted by the FDC Act and under Mensing.

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FDA’s Proposal – The Aftermath

FDA’s proposal spawned numerous comments and criticisms:

Several Republican members of Congress expressed “grave concerns” in a letter to FDA Commissioner Hamburg, M.D.:

Proposal conflicts directly with the statuteThwarts the law’s purpose and objectivesImposes significant costs on the drug industry and consumersGeneric Pharmaceutical Association’s concerns:The proposal is unjustified and unwarrantedThe proposal, if allowed, would result in an estimated $4 billion in U.S. health care costs annuallyUnintended consequences affecting patient’s access to drug therapies

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FDA’s Proposal – The Aftermath

Views of the supporters of the proposal:Will allow the public to be informed as soon as possible when new safety information becomes availableAssure labeling for a prescription drug remains up-to-date when the branded drug is no longer being marketedHelps incentivize generic drug manufacturers concerns about tort liability

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The Dolin Decision

Can a brand manufacturer be held liable to a plaintiff for injuries and/or death allegedly caused by ingestion of a drug manufactured and sold by a generic company. Yes.

Dolin v. Smithkline Beecham Corp., 2013 U.S. Dist. LEXIS 3211 | 2013 WL 120279

Patient only ingested generic versionNegligence causes of action allowed to standCauses of action that could not standCourt’s reasoning

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Impact on the Generic and Brand Industry

Safety department’s evolving role

Monitoring adverse events of other companies

Management of new labeling issues

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Proposed Regulation of Software Used in Healthcare IT

Congressional Mandate to FDAExplosion of Health IT

Lack of coherent FDA regulatory framework uncertainty in industry (interferes with innovation)

Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012

Required FDA to develop and post on its website a proposed strategy and recommendations on: An appropriate, risk-based regulatory framework

for healthcare information technology that:

Promotes innovation Protects patient safety, and Avoids regulatory duplication

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Congressional Mandate - FDASIA

FDA required to develop strategy and recommendations with federal partners:

Office of the National Coordinator for Health Information Technology (ONC)

Federal Communications Commission (FCC)

April 2014 – FDASIA Health IT Report “Proposed Strategy and Recommendations

for a Risk-Based Framework” Authored by FDA, ONC and FCC

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April 2014 – FDASIA Health IT Report

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FDASIA Health IT Report – April 2014

Three Categories of Health IT Functionality

1. Administrative Health IT Billing, claims processing, scheduling, etc.

2. Health Management Health IT Health information and data management, data

capture and encounter documentation, electronic access to clinical results, most clinical decision support software

3. Health IT with Medical Device Functionality An instrument, apparatus, implement, machine …

including any component, part, or accessory, which is … intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease”

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Health IT with Medical Device Functionality Current focus of FDA oversightRegulate under FDA’s current regulatory framework for medical devices

If Health IT meets statutory definition of a “medical device,” then subject to FDA oversight

No need for new statutory category or regulations – can regulated under existing medical device framework

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Principles for Regulatory Framework Narrowly tailored approach to FDA regulation of Health IT

Recognizes limited FDA resources Oversight driven by patient risk

Employ a risk-based approach to appropriately mitigate patient safety risks while avoiding unnecessary regulatory oversight

Medical devices: Class I, II, IIILeverage industry standards and best practicesFacilitate innovation

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September 2013 Notice of Draft Guidance

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What’s New? FDA Regulation of Healthcare IT

Mobile Medical Applications – DRAFT Guidance (6/25/13)

“Mobile application” Software that runs on a mobile platform, or Web-based software executed on a server but

tailored to a mobile platform FDA will focus regulatory oversight on mobile

medical apps that are “medical devices” and could pose risk to patient safety if the mobile

app did not function as intended

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FDA Regulation of Medical Devices Class I devices: General Controls

Establishment registration and medical device listing

Quality System (QS) regulation Labeling requirements Medical Device Reporting Premarket notification - 510(k) (unless exempt) Reporting Corrections and Removals

Class II devices: General Controls + Special Controls + (usually) Premarket Notification (510(k))

Class III devices: General Controls + Premarket Approval (PMA)

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FDA Regulation of Mobile Medical AppsFDA intends to exercise enforcement discretion on

low risk software intended to: Help patients self-manage their disease or conditions without

providing specific treatment or treatment suggestions Provide patients with simple tools to organize and track their

health information Provide easy access to information related to patients’ health

conditions or treatments Help patients document, show, or communicate potential

medical conditions to health care providers Automate simple tasks for health care providers Enable patients or providers to interact with Personal Health

Record (PHR) or Electronic Health Record (EHR) systems.

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FDA Regulation of Mobile Medical AppsExamples of apps for which FDA intends to exercise Enforcement

Discretion Allow asthmatics to track inhaler usage, asthma attacks, location of user at

the time of an attack, or environmental triggers of attacks Provide periodic educational information, reminders, or motivational

guidance to smokers trying to quit, patients recovering from addiction, or pregnant women

Enable a patient or caregiver to create and send an alert or general emergency notification to first responders

Allow a user to collect (electronically or manually entered) blood pressure data and share this data through e-mail, track and trend it, or upload it to a personal or electronic health record

Allow user to log, record, track, evaluate, or make decisions or behavioral suggestions related to developing or maintaining general fitness, health or wellness

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FDA Regulation of Mobile Medical Apps

FDA will enforce compliance on mobile medical apps that: Connect to one or more medical devices for the purpose of

controlling the device(s) or displaying, storing, analyzing, or transmitting patient-specific medical device data

Transform the mobile platform (hand held) into a regulated medical device by using attachments, display screens, or sensors or by including functionalities similar to those of currently regulated medical devices

Perform patient-specific analysis and providing patient-specific diagnosis, or treatment recommendations

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Examples of Mobile Medical Apps That Must Meet Regulatory Requirements

Mobile medical apps that connect to existing medical devices to control the device(s) or display, store, analyze, or transmit patient-specific, including apps that:

alter the function/settings of an infusion pump control or change settings of an implantable

neuromuscular stimulator calibrate, control, or change settings of a cochlear

implant act as wireless remote controls or synchronization

devices for computed tomography (CT) or X-Ray machines

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Mobile medical apps that transform a mobile platform into a medical device, including apps that:

use a sensor or lead connected to a mobile platform to measure and display the electrical signal produced by the heart (electrocardiograph or ECG) or blood glucose levels

use tools within the mobile platform (e.g., speaker) to produce controlled levels of test tones and signals intended for use in conducting diagnostic hearing evaluations

use an attachment to the mobile platform (e.g., light source, laser) to treat acne, reduce wrinkles, or remove hair

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Mobile medical apps that perform patient-specific analysis and providing patient-specific diagnosis, or treatment recommendations, including apps that:

connect to a nursing central station and display medical device data to a physician’s mobile platform for review (e.g., a medical device data system)

connect to a perinatal monitoring system and transfer uterine contraction and fetal heart rate data to another display to allow for remote monitoring of labor progress

connect to bedside (or cardiac) monitors and transfer the data to a central viewing station for display and active patient monitoring

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June 2014 – FDA Expands Enforcement Discretion of Health IT

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June 2014 DRAFT Guidance

FDA expanded scope of Health IT devices subject to FDA’s enforcement discretionThree categories of medical devices

Medical device data systems (MDDS) [21 CFR 880.6310]

Medical image storage device [21 CFR 892.2010]

Medical image communications device [21 CFR 892.2020]

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Medical Image Devices

Medical image storage device Provides electronic storage and retrieval

functions for medical images

Medical image communications device Provides electronic transfer of medical image

data between medical devices

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Medical Device Data Systems (MDDS)

MDDS are:

Hardware or software products That transfer, store, convert formats, and

display medical device data Do not modify the data Do not control the functions or parameters of

any connected medical device Are not intended to be used in connection with

active patient monitoring

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Medical Device Data Systems (MDDS) February 2011 – FDA down-classified from

class III (PMA) to class I (general controls) June 2014 – FDA does not intend to enforce

any regulatory requirements “This means that for [these] devices …, the

FDA does not intend to enforce compliance with the regulatory controls, including registration and listing, premarket review, postmarket reporting and quality system regulation for manufacturers of these types of devices.”

Applies also to mobile medical apps that are MDDS

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FDA Regulation of Health IT – Practice Tips

Know whether your software is/is not a medical device Subject to FDA’s enforcement discretion? Subject to FDA’s medical device requirements?

Set limits on functionality Even class I medical devices require more time and $$ to

develop Monitor upgrades & improvements

Ensure marketing claims/strategy are consistent with intended regulatory category Monitor ‘claims creep’

Watch for FDA to finalize guidances FDA is regulating by guidances, not formal rulemaking

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Proposed Regulation of Laboratory Developed Tests

Proposed Regulation of Laboratory Developed Tests (LDTs)

What is an LDT? An in vitro diagnostic (IVD) that is intended for

clinical use and designed, manufactured and used within a single laboratory Made and used by the same lab Device is not sold; test results are sold

Also known as “home brew” assays or devicesIVDs are included in the FDA definition of medical device

FDA has exercised enforcement discretion for LDTs since 1976

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Proposed Regulation of LDTs LDTs have been regulated by CLIA since 1988

CLIA requirements focus on testing process – ability to perform test in an accurate and reliable manner

FDA has been asserting the need for more FDA regulation of LDTs for several years LDTs have evolved from “traditional” LDTs

Typically manufactured in small volumes by local labs

Used commercially available components, legally marketed for clinical use

Were interpreted by physicians and pathologists at treating facility

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Proposed Regulation of LDTs

Modern LDTs are: manufactured with components that are not legally

marketed for clinical use and/or not made by the testing lab offered beyond local populations and manufactured in high

volume used widely to screen for common diseases rather than

rare diseases used to direct critical treatment decisions (e.g., prediction of

drug response) highly complex (e.g., automated interpretation, multi-signal

devices, use of non-transparent algorithms and/or complex software to generate device results)

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October 3, 2014 FDA Proposed Regulation of LDTs

2 Draft Guidances

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LDT Framework Guidance

Rationale for FDA regulation of LDTs FDA regulation of safety and efficacy needed to fill

gaps in CLIA oversight Clinical validity

Accuracy of test to measure or detect the clinical condition for which it is intended

Analytical validity Analytical specificity and sensitivity,

accuracy and precision Not evaluated by CLIA before test is used

Post-market surveillance Adverse event reporting

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LDT Framework Guidance – Proposed Regulation

Continued full enforcement discretion

LDTs for forensic use LDTs used in CLIA-certified, high-

complexity histocompatibility laboratories for organ, stem cell, and tissue transplantation

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Partial enforcement discretion Regulatory requirements

Yes - General controls, registration & listing, AE reporting

No - premarket review, QS Applies to:

Low-risk (class I) LDTs LDTs for rare diseases “Traditional” LDTs LDTs for Unmet Needs” when no FDA-

approved or cleared equivalent device is available

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No enforcement discretion Requirements: premarket review, QS,

registration & listing, AE reporting Moderate risk (class II) LDTs

510(k) FDA aims to use third party review for

premarket review High risk (class III) LDTs

PMA FDA will do premarket review

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Classification of LDTs Risk based FDA will use expert advisory panels Factors (not exclusive list)

Level of risk of disease/condition or patient population

Screening or diagnosis use Nature of the clinical decision based on the test result Other data available to MD (in addition to the LDT

result), Potential consequences/impact of erroneous results

FDA will issue draft guidance within 18 months of finalizing Framework Guidance

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LDT Framework Guidance – Timelines

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Requirement Class After Final Guidance

Registration & Listing

All (except exempt)

6 months

Premarket Review

III Begin - 12 monthsComplete - within 5 years

II Begin – 5 years (after completion of class III reviews)

Complete - within 9 years

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LDT Notification Guidance

Notification to FDA Who: manufacturer of any LDT – no exceptions What: must notify FDA and provide basic

information about LDT Data will be used to classify LDTs Will be made publically available on FDA

website Enforcement discretion depends on notification

When: Within 6 months of final Framework Guidance Prior to significant changes to notified LDTs

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Proposed Regulation of LDTs – Practice Tips

Increased FDA regulation of LDTs is coming Question is when and how much

Comment period on draft guidances ends 1/30/15 Will take FDA time to review and address

comments In 2015, prepare for:

Notification to FDA Registration and listing (unless exempt) Look for draft classification guidance

In 2016, prepare for: Premarket review of prioritized class III LDTs

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Ellen L. Darling

Orange County Office

+1.949.623.3540

[email protected]

Carol Pratt

Portland Office

+1.503.226.5762

[email protected]

Questions?

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© Copyright 2014 by K&L Gates LLP. All rights reserved. FDA UPDATE: Essential Knowledge...

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Transcript of © Copyright 2014 by K&L Gates LLP. All rights reserved. FDA UPDATE: Essential Knowledge...