CBER Compliance Update

FDLI Enforcement, Litigation and Compliance Conference December 8, 2014Mary Malarkey, DirectorOffice of Compliance and Biologics QualityCenter for Biologics Evaluation and Research

Office of Compliance and Biologics Quality

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OCBQ’s mission is to ensure the quality of products regulated by CBER over their entire

lifecycle through pre-market review and inspection, and post-market review, surveillance,

inspection, outreach and compliance

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Current OCBQ Priorities

• Continued FDASIA and DQSA Implementation – 2nd anniversary of enactment of FDASIA (July 9, 2014)

– FDASIA • PDUFA V – focus on “lessons learned”• Titles VII Drug Supply Chain and Title X Drug Shortages

– DQSA• DSCSA illegitimate and suspect product notification provision

• Engaged with CDER on Quality Metrics

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DSCSA

• Beginning on January 1, 2015, a trading partner who determines that a product in its possession or control is an illegitimate product must notify the Food and Drug Administration (FDA or Agency) and certain immediate trading partners under section 582 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360eee), as added by the Drug Supply Chain Security Act (DSCSA).

• Trading partner - manufacturers, repackagers, wholesale distributors, or dispensers

Current OCBQ Priorities - 2• Program Alignment

– Working with other agency components to address Dr. Hamburg’s decisions for implementation, communicated by memorandum on February 3, 2014.

• Other quality initiatives– Working with other agency components to update quality

guidance and implement standards for quality (e.g., Council on Pharmaceutical Quality)

• Preparedness activities– Centers for Innovation and Advanced Development in

Manufacturing – Ebola

• International – Mutual Reliance Initiative

Current OCBQ Priorities - 3• OCBQ Move to the White Oak Campus.

– OCBQ moved May 16 – August 25, 2014 – lot release laboratories relocated last.

– Pause for lot release sample submission until September 2, 2014; no effect on lot release protocols or release of products

• What’s next?– Increasing filling and lyophilization capacity for

production of reagents and standards for the other Essential Regulatory Laboratories, manufacturers and other global partners.

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ucm345223.htm

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White Oak Campus Map

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United States v. Regenerative Sciences, LLC and Christopher Centeno, et al.

• The complaint for the injunction was filed August 6, 2010, by the Justice Department on behalf of the FDA in the U.S. District Court for the District of Columbia, against Regenerative Sciences and three of its employees, Christopher J. Centeno, M.D., John R. Schultz, M.D., and Michelle R. Cheever. The injunction the government requested would permanently prevent the company and cited individuals from adulterating and misbranding the cultured cell product (or any other drug) while the product, or one or more of its components, is held for sale after shipment in interstate commerce. 

• Regenerative Sciences agreed to cease production of the cultured cell product while the case is pending. 

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US vs Regenerative Sciences LLC - 2

• On July 23, 2012, United States District Judge Rosemary Collyer granted summary judgment for the government and issued a permanent injunction prohibiting the defendants, from distributing adulterated or misbranded drugs or causing them to become adulterated or misbranded after shipment of one or more of their components in interstate commerce.

• The product at issue is an autologous cultured cell product that was subject to more than minimal manipulation during manufacturing and that was promoted as a treatment for a variety of orthopedic conditions. The court held that this product is a “drug” under the Federal Food, Drug, and Cosmetic Act and rejected the defendants' argument that it falls within the "practice of medicine" and thus outside the scope of the Act.

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US vs Regenerative Sciences LLC -3

• The court also held that the Act's interstate commerce requirement was satisfied because its components were shipped in interstate commerce. The court also dismissed the eight counterclaims filed by the defendants, which challenged, under various theories, FDA's authority to regulate the autologous cell products and FDA's regulations for human cellular and tissue based products.

• Regenerative appealed the decision and on February 4, 2014, the DC Federal Circuit Court of Appeals ruled in the Agency’s favor

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Vision for CBERCBER uses sound science and regulatory

expertise to: Protect and improve public and individual

health in the US and, where feasible, globally Facilitate development, approval of and access

to safe and effective products and promising new technologies

Strengthen CBER as a preeminent regulatory organization for biologics

INNOVATIVE TECHNOLOGY ADVANCING PUBLIC HEALTH

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Public Access to CBER

CBER website:http://www.fda.gov/BiologicsBloodVaccines/default.htm

Phone: 1-800-835-4709 or 301-827-1800

Consumer Affairs Branch (CAB) Email: ocod@fda.hhs.gov

Phone: 301-827-3821

Manufacturers Assistance and Technical Training Branch (MATTB)

Email: industry.biologics@fda.govPhone: 301-827-4081

Follow us on Twitter https://www.twitter.com/fdacber

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Compliance Central with Compliance Central with FDA Center Compliance FDA Center Compliance

Directors (Part II)Directors (Part II)

Steve Silverman, DirectorSteve Silverman, Director

CDRH Office of ComplianceCDRH Office of Compliance

December 8, 2014December 8, 2014

The Office of Compliance has The Office of Compliance has reorganized.reorganized.

From:From:

The Office of Compliance has The Office of Compliance has reorganized.reorganized.

To:To:

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The Case for Quality The Case for Quality • Support and ownership of quality go beyond Support and ownership of quality go beyond

quality/compliance unitsquality/compliance units

• A culture of quality yields benefits.A culture of quality yields benefits.

• Recent trends highlight the importance of quality.Recent trends highlight the importance of quality.

• ““Understanding Barriers to Medical Device Quality”Understanding Barriers to Medical Device Quality” http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/UCM277323.pdf

• October 31, 2011 webcast:October 31, 2011 webcast: http://fda.yorkcast.com/webcast/Viewer/?peid=7134123bd5c94d909fdae41fce3469411d

http://fda.yorkcast.com/webcast/Viewer/?peid=7134123bd5c94d909fdae41fce3469411d

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The Case for Quality The Case for Quality Implementation PlanImplementation Plan

Initiative 1: Focus on QualityInitiative 1: Focus on Quality

Initiative 2: Enhanced TransparencyInitiative 2: Enhanced Transparency

Initiative 3: Stakeholder EngagementInitiative 3: Stakeholder Engagement

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2013-2014 Case for Quality Activities2013-2014 Case for Quality Activities

Engage industry and other stakeholders in national venues

Engage industry and FDA districts in local venues

Partner with industry and other stakeholders to develop collaborative forums and

trustful engagements

Stakeholder Stakeholder

EngagementEngagement

Data TransparencyData TransparencyProvide relevant device quality data

Gather and assess stakeholder data needs

Develop a framework for delivering releasable information

Activities Sub-Initiative

Focus on QualityFocus on QualityDevelop, implement, and assess a pilot that changes engagement during an

inspection

Assess internal/external incentives and measures

Benchmark with other quality performance models

Case for Quality:Case for Quality:Implantable Device PilotImplantable Device Pilot

•Implantable battery-containing devicesImplantable battery-containing devices•Inspections focused on factors that Inspections focused on factors that affect device qualityaffect device quality•Prioritized Form FDA-483sPrioritized Form FDA-483s•Does the pilot improve quality and Does the pilot improve quality and resource allocation?resource allocation?

Spin Off

Update Program

Successful pilots can be Successful pilots can be

expanded.expanded.

Case for Quality: Case for Quality: Maturity ModelMaturity Model

FDLI’s Enforcement, Compliance, and Litigation Conference

Center for Tobacco ProductsOffice of Compliance and Enforcement

2014 Update

Ann Simoneau, Director

CTP Office of Compliance and Enforcement

December 8, 2014

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Compliance and Enforcement Report

• Office of Compliance and Enforcement (OCE) created a comprehensive report covering 2009 through September 30, 2013

• Report includes several charts and graphs representing the advisory (WL) and enforcement activities of the office

• Report available on the CTP website

• Plan to update periodically

Regulations and GuidancesFinal Rule Tobacco Products, User Fees, Requirements for the Submission of Data Needed to Calculate User Fees

for Domestic Manufacturers and Importers of Tobacco Products07/10/14

Proposed Rule

Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act

04/25/14

Proposed Rule

National Environmental Policy Act; Environmental Assessments for Tobacco Products; Categorical Exclusions

01/23/14

Guidance Establishing That a Tobacco Product Was Commercially Marketed in the United States as of February 15, 2007

09/29/14

Guidance Requirements for the Submission of Data Needed to Calculate User Fees for Domestic Manufacturers and Importers of Tobacco Products

07/16/14

Draft Guidance

Substantial Equivalence Reports: Manufacturer Requests for Extensions or to Change the Predicate Tobacco Product

07/15/14

Guidance Civil Money Penalties for Tobacco Retailers - Responses to Frequently Asked Questions 06/26/14

Guidance Registration and Product Listing for Owners and Operators of Domestic Tobacco Product Establishments

04/07/14

Draft Guidance

Enforcement Policy for Certain (Provisional) Tobacco Products that FDA Finds Not Substantially Equivalent

02/25/14

Deeming (Proposed Rule)

On April 24, 2014, FDA proposed a new rule that would extend CTP’s authority to cover additional tobacco products.Products that would be “deemed” to be subject to FDA regulation are those that meet the statutory definition of a tobacco product, including:•Electronic Cigarettes (e‐cigarettes)•Cigars•Pipe Tobacco•Nicotine Gels•Waterpipe (Hookah)•Tobacco Dissolvables not already under the FDA’s authority

Retailer Enforcement

FY 14 Results• Contracts with 55 jurisdictions• Contracts with tribes• Over 124,000 inspections completed• Over 8,100 Warning Letters• Over 1,070 CMP’s issued• Sale to minor violation rate for FY 14 was 11.4%

Internet Surveillance

Issued WLs to online retailers– Sale of tobacco products to minors

• Minors were able to purchase regulated tobacco products from their websites

– Modified risk tobacco product violations– Flavored cigarette violations– Smokeless tobacco product warning

statement violations

“Provisional” Tobacco Products Found Not Substantially Equivalent (NSE)

• Misbranded and adulterated NSE tobacco products webpage

• Letters to regulated industry

• Draft Guidance – Enforcement Policy for Retailers

• Ongoing surveillance and inspections

• Notifications to retailers

User Fees

• Domestic manufacturers and importers of regulated tobacco products

• Currently applies to cigarettes, snuff, chewing tobacco, and roll-your-own tobacco

• Warning Letter for failure to pay user fees – King Mountain Tobacco Company, Inc.

• Import Alert – Lit Distributor, Inc. & DK Distributors, Inc.

Compliance WebinarsTitle DateOther Media Notifications 9/23/2014Draft Guidance – Substantial Equivalence Reports: Manufacturer Requests for Extensions or to Change the Predicate Tobacco Product

8/6/2014

FDA’s Proposed Regulation – “Deeming Tobacco Products To Be Subject to the Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Regulations on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products”

5/29/2014

Electronic Establishment Registration and Product Listing 4/7/2014Guidance for Industry on Compliance with Regulations Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco To Protect Children and Adolescents

12/9/13