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Annual Meeting & ExpositionSeattle, Washington | March 22-25
Your Annual FDA Update
Ilisa B.G. Bernstein, PharmD, JD, FAPhADeputy DirectorOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration
CAPT Mary Kremzner, PharmD, MPH, BCGPDivision DirectorDivision of Drug InformationCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration
Both speakers are employed by FDA and have nothing to disclose.
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Disclosures
• Target Audience: Pharmacists
• ACPE#: 0202-0000-19-053-L03-P
• Activity Type: Knowledge-based
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CPE Information
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Learning Objectives At the completion of this knowledge-based activity, participants will be able to:• Describe U.S. Food and Drug Administration (FDA) activities
during the last year that affect pharmacy practice.• Describe the FDA’s anticipated direction and focus in the
coming year.• State how changes in FDA regulations and actions will affect
the practice of pharmacy.
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Assessment Question FDA’s Biosimilar Action Plan includes:
A. Improving the efficiency of the biosimilar and interchangeable product development and approval process.
B. Maximizing scientific and regulatory clarity for the biosimilar product development community.
C. Developing effective communications to improve understanding of biosimilars among patients, providers and payors.
D. Supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay market competition to follow-on products.
E. All of the above
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Assessment Question What year did FDA see the highest number of novel drug approvals?
A. 2018
B. 2017
C. 2016
D. 2015
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Overview
Who We AreNew Approvals
And PerformanceDrug Shortages
Compliance And Enforcement
ActionsRecalls
Nitrosamines in ARBs
Drug Safety CompoundingDrug Supply
Chain Security And Integrity
Innovation In Drug
Development
BiosimilarsOpioid Crisis
Update
Updates from CBER, CDRH,
CFSAN, CTP, CVMWhat’s Next?
Resources For Pharmacists
www.fda.gov
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What we do
Promote and protect public health
FDA’s primary responsibility is to protect the American people from unsafe or mislabeled food, drugs, and other medical products and to make sure consumers have access to
accurate, science‐based information about the products they need and rely on every day.
FDA/CDER (Center for Drug Evaluation and Research) ensures that safe, effective and high quality drugs are available for U.S. consumers
www.fda.gov
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Office of Compliance
Center for Drug Evaluation and Research
Office of Compliance
Office of Manufacturing
Quality
Office of Unapproved Drugs
and Labeling Compliance
Office of Scientific Investigation
Office of Drug Security, Integrity,
and Response
Office of Program & Regulatory Operations
www.fda.gov
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Office of Communications
Center for Drug Evaluation and Research
Office of Communications
Division of Online Communications
Division of Health Communications
Division of
Drug Informationwww.fda.gov
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New drug approvals and performance
www.fda.gov
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CDER’s annual novel drug approvals: 2009-2018
www.fda.gov
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Notable first-in-class approvals
• First oral medication approved to treat adults with Fabry disease
Galafold
(migalastat)
• First non-opioid treatment for facilitation of opioid discontinuation in adults – opioid withdrawal symptoms
Lucemyra
(lofexidine HCl)
• First monoclonal antibody to treat adult patients living with multi-drug resistant HIV-1
Trogarzo
(ibalizumab-uiyk)
www.fda.gov
14
Notable rare disease approvals
• First FDA approved drug to treat adults and children ages 1 year and older with a rare, inherited form of rickets
Crysvita
(burosumab-twza)
• First FDA approved drug derived form marijuana for treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and DravetSyndrome
Epidiolex
(cannabidiol)
• Treats adults with a rare and serious genetic disease known as phenylketonuria (PKU)
Palynziq
(pegvalisase-pqpz)
www.fda.gov
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Other notable novel drug approvals
www.fda.gov
• New class of drugs called calcitonin gene-related peptide receptor (CGRP) antagonists
• FDA approved for adults for prevention of migraine
Aimovig (erenumab-aooe)
Ajovy (fremanezumab-vfrm)
Emagality (galcanezumab-gnlm)
• First FDA approved drug with an indication to treat smallpox
• Protect the U.S. from bioterrorismTpoxx (tecovirimat)
• Second FDA approved drug for cancer treatment based on a common biomarker
• Can be used to treat any kind of tumor that has a specific characteristic, as opposed to where in the body the tumor originated
Vitrakvi (larotrectinib)
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Notable non-novel drug approvals
www.fda.gov
• First FDA approved drug to treat multiple sclerosis in childrenGilenya (fingolimod)
• First FDA approved drug for certain patients 12 and older with pheochromocytomaor paragangliomaAzedra (iobenjuane I131)
• New technology to product Tc-99 for a wide range of imaging studies; first non-uranium process to produce Mo-99 to prepare Tc-99m
• First time in 30 years that patients in the U.S. have a domestic source of this important diagnostic agent
RadioGenix System (Technetium Tc-99 sodium pertechnetate generator)
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New drug approvals
www.fda.gov
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Biosimilar approvals
www.fda.gov
• 2018: CDER approved 7 new biosimilars– Pegfilgrastim (2)– Epoetin alfa– Filgrastim– Adalimumab– Rituximab– Trastuzumab
• As of January 2019, there are 17 FDA approved biosimilars
• There are now at least one biosimilar for each of the top selling biological drugs in the U.S.
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Generic drug approvals and performance
www.fda.gov
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Generic drug approvalsTotal generic drug approval actions 2018 generic drugs approved by month
www.fda.gov
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Significant first generic drug approvals
www.fda.gov
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Drug competition action plan
www.fda.gov
Streamline ANDA review process
Enhance scientific and regulatory
clarity
Reduce the “gaming” to delay generic approvals
23www.fda.gov
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Drug shortages: new vs. prevented
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Drug Shortage Task Force
www.fda.gov
What are root causes of drug shortages?
• Economics of drug shortage
• Manufacturing and distribution
What are potential solutions?
• Market-driven actions
• Governmental actions
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Drug shortage stakeholder listening session
www.fda.gov
• The impacts of drug shortages affect every level of the healthcare system, ultimately compromising the standard of care, producing waste, and increasing costs.Theme 1
• Multiple market factors such as buyer and seller consolidation, low margins, and contracting practices contribute to drug shortages. Theme 2
• It is unclear what the right level of transparency is based on manufacturing security concerns, and hospital, pharmacy, and GPO needs. The healthcare community would like more transparency throughout the supply chain.
Theme 3
• Multiple federal agencies such as FDA, DEA, and CMS, have different authorities on drugs – making it hard for industry/hospitals to manage. Ideas have been put forth on how agencies can mitigate but may unintentionally exacerbate the issues
Theme 4
Recalls
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Drug product recalls
www.fda.gov
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Drug product recalls by type
www.fda.gov
tDS= Tainted dietary supplement
Rx= Prescription drug
OTC= Over the counter drug
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Compounding product recalls
www.fda.gov Number of compounding products may be misrepresented since a large number of products were characterized as “all products”.
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Major reasons for drug recalls
www.fda.gov
FY2017
• Lack of assurance of sterility
• Impurities/degradation products
• CGMP deviations
• Failed USP dissolution test requirements
FY2018
• CGMP deviations
• Failed impurities/ degradation specifications
• Subpotent drug
• Lack of assurance of sterility
FY2019 Q1
• CGMP deviations
• Lack of assurance of sterility
• Subpotent drug
• Failed dissolution specifications
Nitrosamine impurities in ARBs
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Nitrosamines
www.fda.gov
NDMA
• probable human carcinogen
• valsartan-containing medicines
NDEA
• probable human carcinogen
• irbesartan-, losartan-, & valsartan-containing medicines
NMBA
• possible human carcinogen
• losartan-containing medicines
34www.fda.gov
ARB recalls due to nitrosamines
July-August 2018
Major, Prinston, Teva, Camber &
Torrent recall valsartan-containing
products d/t NDMA
October 2018
Aurobindo & ScieGen recall irbesartan d/t
NDEA
November 2018
Sandoz recalls losartan/HCTZ d/t NDEA; Mylan and
Teva recall valsartan-containing
products d/t NDEA
December 2018
Mylan & Aurobindo expand valsartan recalls;
Torrent recalls losartan d/t NDEA
January 2019
Torrent recalls losartan-
containing products d/t
NDEA; Prinstonrecalls irbesartan-
containing products d/t NDEA
February 2019
Macleods recalls losartan/HCTZ d/t
NDEA; Camber recalls losartan d/t
NMBA
March 2019
Aurobindo recalls valsartan-containing
products d/t NDEA
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What your patients need to know…
www.fda.gov
Patients should continue to take an ARB that is recalled
until they are able to obtain a replacement
from their pharmacy or an alternative
treatment from their doctor
Patients are more at-risk for a cardiac event
related to abruptly stopping their
treatment
Cancer risk associated with nitrosamines is related to a patient’s
long-term exposure to these compounds
Overall risk of cancer is low
Compliance and
Enforcement Actions
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Compliance and enforcement priorities
www.fda.gov
Opioids CompoundingSupply chain
integrity
Unapproved drugs
Quality safety initiatives
Data integrity assurance
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Enforcement by the numbers
www.fda.gov
Enforcement action CY2018
Seizures 1
Injunctions 6
Warning letters 142
Recalled 1,406
Clinical investigator disqualifications 1
Companies or products added to import alerts 112
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Notable regulatory/enforcement efforts
www.fda.gov
• Warning letters– CanaRx: facilitating the sale of
unapproved drugs
– Illegal sale of opioids online
– McKesson: DSCSA violations
• Recalls– voluntary and mandatory
• Sentencing/fines/forfeiture– TC Medical/SB Medical:
smuggling of unapproved drugs for unlicenced wholesale distribution
– Canada Drugs: illegal sale of misbranded and counterfeit drugs in the U.S.
• Injunctions
• Seizures
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Contaminated kratom products
www.fda.gov
• No FDA approved uses for kratom
• Kratom-containing dietary supplements and bulk dietary ingredients found in unapproved drugs
• Salmonella contamination outbreak
• Heavy metals: unsafe levels of lead and nickel
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Drug Safety
www.fda.gov
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FAERS Public Dashboard Updates
www.fda.gov
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Real World Data and Evidence
www.fda.gov
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Compounding
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FDA Compounding Policy - 2018• Established and advanced strategic policy goals as
described in 2018 Compounding Policy Priorities Plan.
• Issued 11 policy documents in 2018:– one draft guidance document (finalized in March 2019),
– two revised draft guidance documents,
– six final guidance documents,
– one final regulation, and
– one revised draft memorandum of understanding between FDA and states.
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What’s new in compounding?
• Revised Draft Guidance: Insanitary Conditions at Compounding Facilities
• Revised Draft Memorandum of Understanding Addressing Certain Distributions of Compounded Drug Products Between the State of [insert STATE] and the FDA
• Final rule: List of Bulk Drug Substances that can be used to Compound Drug Products under Section 503A of the FD&C Act
www.fda.gov
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Office stock and access – Public meeting• When: May 21, 2019
• Purpose: to hear from health care professionals, outsourcing facilities, and other stakeholders regarding access to office stock from outsourcing facilities considering the policies proposed in the revised draft guidance on CGMP for outsourcing facilities.
• How: Register on FDA’s website for in-person or webcast
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Compounding oversight and inspections
www.fda.gov
Drug Supply Chain
Security and Integrity
52www.fda.gov
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DSCSA goals
www.fda.gov
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“Dispenser” requirements
www.fda.gov
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Product identifiers –now on packages…
www.fda.gov
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Identifying suspect and illegitimate products
Examples of what to look for…
www.fda.gov
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Notify FDA if you findillegitimate products
www.fda.gov
Innovation in Drug Development
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Innovation in digital technologyproposed framework for
Prescription Drug Use Related Software
www.fda.govReference: https://www.fda.gov/NewsEvents/Newsroom/FDAInBrief/ucm626166.htmhttps://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm613692.htm
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Innovation in OTC drugs• Draft guidance: Innovative
Approaches for Nonprescription Drug products
• OTC Naloxone Drug Facts Label
www.fda.gov
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Expanded access
www.fda.gov
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Patient Affairs Staff
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Biosimilars Action Plan: Goals
Product development
Scientific and regulatory
clarity Communications
Market competition
www.fda.gov
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Biosimilars for insulin
www.fda.gov
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Opioids update
www.fda.gov
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Efforts to address the opioid crisis
www.fda.gov
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Efforts to address the opioids crisis
www.fda.gov
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Opioid analgesic REMS
• Goal: reduce serious adverse outcomes due to inappropriate prescribing, misue, and abuse while maintaining access
• Approved September 2018
• Applies to all ER/IR forms intended for outpatient use
• Requires training be available for all health care providers who are involved in the management of patients with pain, including nurses and pharmacists
www.fda.gov
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Addressing the illegal sale of opioids online
• Online Opioid Summit
• Collaboration with internet stakeholders
• Warning letters
• Domain name seizures
• Abuse complaints
• Criminal investigations
www.fda.gov
Center for Tobacco (CTP)
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E-cigarette epidemic
www.fda.gov
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Youth Tobacco Prevention Plan
www.fda.gov
Center for Devices and Radiologic Health (CDRH)
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Novel Device Approvals
www.fda.gov
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Notable novel device approvals
First artificial iris
First blood test to detect traumatic brain injury
First mobile app to help treat substance abuse disorders
World’s smallest heart valve (newborn)
www.fda.gov
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Drug Safety Communication
• FDA alerted patients and healthcare providers of genetic laboratory tests with claims to predict a patient’s response to specific medications
• There are a limited number of cases in which some evidence exists to support correlating a genetic variant and drug levels, and FDA includes that information package prescribing information
www.fda.gov
Center for Food Safety and Applied Nutrition (CFSAN)
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Watch out for false promises about so-called Alzheimer’s cures
www.fda.gov
“You can even reverse mental decline associated with dementia or even Alzheimer’s in just a week;”
“Clinically shown to help disease of the brain such as Alzheimer’s and even dementia;”
“Supplements are used to cure Alzheimer’s disease;”
Center Veterinary Medicine (CVM)
82
CVM update
www.fda.gov
Canine heart disease and certain diets – investigating
potential links
Five year action plan –Antimicrobial stewardship
What’s next?
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CDER 2019 Priorities
Continuing work on all fronts with respect to opioids and opioid addiction
Implementing the legislative framework around drug compounding
Modernization of the Office of New Drugs
Implementation of the 21st Century Cures Act provisions
Implementation of the FDA Reauthorization Act and other user fee goals
Implementation of Track and Trace law (DSCSA)
www.fda.gov
85
Tools to keep you informed
www.fda.gov
Get email updates
from FDAhttps://www.fda.gov/aboutfda/contactfda/stayinformed/getemailupdates/default.htm
• Drug information• Drug safety communications• CDER drug safety labeling
changes• Medication guides• Drug shortages• MedWatch safety alerts: FDA
safety information• Recalls, market withdrawals
and safety alerts
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Tools to keep you informed
www.fda.gov
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Tools to keep you informed
Drug safety communications
REMS – Approved Risk Evaluation and Mitigation Strategies
SrLC – drug Safety-related Labeling Changes
Drug recalls
Medication guides
FAERS public dashboard
Information by drug class
www.fda.gov
88
Tools to keep you informed
www.fda.gov
89
Tools to keep you informed
www.fda.gov
90www.fda.gov
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Assessment Question FDA’s Biosimilar Action Plan includes:
A. Improving the efficiency of the biosimilar and interchangeable product development and approval process.
B. Maximizing scientific and regulatory clarity for the biosimilar product development community.
C. Developing effective communications to improve understanding of biosimilars among patients, providers and payors.
D. Supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay market competition to follow-on products.
E. All of the above
92
Assessment Question What year did FDA see the highest number of novel drug approvals?
A. 2018
B. 2017
C. 2016
D. 2015
