Transcript Slides
CBER
Compliance Update
FDLI Enforcement, Litigation and Compliance Conference
December 8, 2014
Mary Malarkey, Director
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
Office of Compliance and
Biologics Quality
OCBQ – Director, Mary Malarkey
OCBQ - Deputy Director – Mark Schwartz
Division of Case Management
DCM Director, Bob Sausville
Division of Inspections and Surveillance
DIS Director, Gill Conley
Division of Manufacturing and Product Quality
DMPQ Director, Jay Eltermann
DMPQ Deputy Director – Laurie Norwood
Division of Biological Standards and Quality Control
DBSQC Director - Dr. Bill McCormick
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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/GuidanceCom
plianceRegulatoryInformation/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 CBER
CBER 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: [email protected]
Phone: 301-827-3821
Manufacturers Assistance and Technical Training Branch
(MATTB)
Email: [email protected]
Phone: 301-827-4081
Follow us on Twitter
https://www.twitter.com/fdacber
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Compliance Central with
FDA Center Compliance
Directors (Part II)
Steve Silverman, Director
CDRH Office of Compliance
December 8, 2014
The Office of Compliance has
reorganized.
From:
Office of
Compliance
Division of Risk
Management
Operations
Division of
Enforcement A
Division of
Enforcement B
Division of
Bioresearch
Monitoring
The Office of Compliance has
reorganized.
To:
Office of
Compliance
Division of
Analysis and
Program
Operations
Division of
Manufacturing and
Quality
Division of
Premarket and
Labeling
Compliance
Division of
International
Compliance
Operations
Division of
Bioresearch
Monitoring
The Case for Quality
• Support and ownership of quality go beyond
quality/compliance units
• A culture of quality yields benefits.
• Recent trends highlight the importance of quality.
• “Understanding Barriers to Medical Device Quality”
http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTo
bacco/CDRH/CDRHReports/UCM277323.pdf
• 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
Implementation Plan
Initiative 1: Focus on Quality
Initiative 2: Enhanced Transparency
Initiative 3: Stakeholder Engagement
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2013-2014 Case for Quality Activities
Sub-Initiative
Focus on Quality
Data Transparency
Stakeholder
Engagement
Activities
Develop, implement, and assess a pilot that changes engagement
during an inspection
Assess internal/external incentives and measures
Benchmark with other quality performance models
Provide relevant device quality data
Gather and assess stakeholder data needs
Develop a framework for delivering releasable information
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
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Case for Quality:
Implantable Device Pilot
• Implantable battery-containing devices
• Inspections focused on factors that
affect device quality
• Prioritized Form FDA-483s
• Does the pilot improve quality and
resource allocation?
Successful pilots can be
expanded.
Spin
Off
Analyze
Interview/
Assess
Industry
Engagement
Process
Update Program
Pilot
Evaluate/
Modify
Case for Quality: Maturity
Model
FDLI’s Enforcement, Compliance, and
Litigation Conference
Center for Tobacco Products
Office of Compliance and Enforcement
2014 Update
Ann Simoneau, Director
CTP Office of Compliance and Enforcement
December 8, 2014
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
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Regulations and Guidances
Final Rule Tobacco Products, User Fees, Requirements for the Submission of Data Needed to Calculate User Fees
for Domestic Manufacturers and Importers of Tobacco Products
07/10/14
Proposed Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by 04/25/14
Rule
the Family Smoking Prevention and Tobacco Control Act
Proposed National Environmental Policy Act; Environmental Assessments for Tobacco Products; Categorical
Rule
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
Substantial Equivalence Reports: Manufacturer Requests for Extensions or to Change the Predicate
Guidance 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
Enforcement Policy for Certain (Provisional) Tobacco Products that FDA Finds Not Substantially
Guidance 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
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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 Webinars
Title
Date
Other Media Notifications
9/23/2014
Draft Guidance – Substantial Equivalence Reports: Manufacturer 8/6/2014
Requests for Extensions or to Change the Predicate Tobacco
Product
FDA’s Proposed Regulation – “Deeming Tobacco Products To Be
5/29/2014
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”
Electronic Establishment Registration and Product Listing
4/7/2014
Guidance for Industry on Compliance with Regulations
12/9/13
Restricting the Sale and Distribution of Cigarettes and Smokeless
Tobacco To Protect Children and Adolescents