Transcript Compounding Misadventures

Compounding Misadventures and
the Legislative Fix (DQSA)
L. Ross Day, R.Ph.
Director, Novation Pharmacy
1
©2012 Novation Confidential.
©2013
L. Ross Day, R.Ph. Disclosure
Financial Relationships
Salaried employee of Novation
No financial relationship with any pharmaceutical company
2
©2012 Novation Confidential.
Pharmacy Education Learning Objectives
At the conclusion of this presentation,
participants will be able to:
3
•
Articulate the number of newly reported drug
shortages through Q2 2014
•
List, by therapeutic category, the types of
newly reported drug shortages most
frequently reported in the last three years
•
List reasons that have been provided for drug
shortages
•
Describe negative economic and clinical
outcomes of drug shortages, including drug
compounding misadventures, and the new
legislation focused on ensuring drug quality
and security
©2012 Novation Confidential.
Current State of Drug Shortages
4
©2012 Novation Confidential.
The State of Drug Shortages…(As of June 30, 2014)
Number of New Drug Shortages Reported by Year
New shortages decreased 24% in 2012 and 31% in 2013 (YOY)
University of Utah Drug Information Service
[email protected]
5
©2012 Novation Confidential.
National Drug Shortages
Active Shortages by Quarter (through Q2 2014)
University of Utah Drug Information Service
[email protected]
6
©2012 Novation Confidential.
Active Shortages (by therapeutic category)
Top 5 Drug Categories through Jun 30, 2014
University of Utah Drug Information Service
[email protected]
7
©2012 Novation Confidential.
Most Drug Shortages are Injectables
and Multi-Sourced Generics
Brand-Generic Type
Form Type
82% are Sterile
Injectables
Source: IMS Institute for Healthcare Informatics, Drug Shortages: A Closer Look, November 2011.
8
©2012 Novation Confidential.
83% are Multi-Sourced
Generics without Patent
Protection or Exclusivity
Causes of Drug Shortages
Drug Shortages Caused by Multiple Reasons
Manufacturing
Issues
Discontinued/
Suspended
Increased
Demand
Raw Material
Issues
Crystallization/
Particulates
Recall
No Reason
Supplied
Import Ban
FDA Review
Source: IMS Institute for Healthcare Informatics, Drug Shortages: A Closer Look, November 2011.
10
©2012 Novation Confidential.
Major Sites with Manufacturing Issues
Consent
Decree
Boehringer
Ingelheim: Ben Venue
Site
Ceasing
Operations
Novartis/Sandoz:
Boucherville Canada
Fresenius Kabi (APP):
Grand Island site under
warning letter. Failed reinspection in January
Boehringer
Ingelheim: API &
FG
Novartis/Sandoz:
EBEWE SITE
Apotex: Richmond Hill &
Toronto
Teva: Hovav Israel API Plant
Teva: Irvine Facility
Strides (Mylan): warning letter
at Facility #2 (not the oncology
site)
FOR SALE!
WL
Wockhardt: Chikalthana
Baxter: Marion North
Cove Site
Baxter: Jayuya site
Fresenius Kabi (APP): at
Kalyani API facility. Known to
make Oncolytic APIs
WL
11
©2012 Novation Confidential.
Wockhardt: Waluj
Implications of Drug Shortages
12
©2012 Novation Confidential.
Drug Shortage Crisis has Profound Implications
Increased labor expenses
2011 survey1 revealed $216 million labor costs and an
average time spent of 9 hours per week for pharmacists
and 8 hours per week for pharmacy technicians
Increased non-labor expenses
Unprecedented generic drug price increases
Billions of remediation mandated re-investments
Potential for patient injury
2010 survey2 revealed current environment of drug
shortages has even resulted in patient deaths
Possibility of delayed patient treatment
Shortages of several oncology medications have resulted
in delayed or deferred chemotherapy treatment regimens
with unknown effects on patient outcomes
1. Kaakeh R, Sweet BV, et al. Impact of Drug Shortages on U.S, Health Systems. Am J Health-Syst Pharm. 2011;68:1811-9.
2. ISMP survey on drug shortages. ISMP Medication Safety Alert! 2010;15(15):4.
13
©2012 Novation Confidential.
Documenting Patient Harm
ISMP Survey Published April 2012
Medications most frequently
involved in reports of patient harm
– Top five medications in short supply
• Doxorubicin liposomal injection
• Morphine (oral concentrate and
injection)
• Fentanyl injection
• Calcium gluconate injection
• Fluorouracil
– Other problematic oncology
medications (Cisplatin, Daunorubicin,
and Paclitaxel)
14
©2012 Novation Confidential.
Problems associated with a drug
shortage that resulted in patient harm
– Alternative medication provided, but
not drug of choice leading to
inadequate treatment (35%)
– Error with an alternative drug or
form/strength of drug (27%)
– Omission of vital medication leading to
non-treatment of patient (27%)
– Error when hospital pharmacy
attempted to compound a product or
drug strength no longer available (6%)
2012 Fungal Meningitis Outbreak (NECC)
15
©2013 Novation Confidential.
Compounding Misadventures in 2012
16
•
Franck’s Compounding Pharmacy
– Adverse events during eye surgeries
• Contaminated triamcinolone ophthalmic solutions
• 47 patients developed serious fungal infections p. surgery
– Recall of all products sold since November 2011
– Franck’s closed and re-opened under another name 4 days later
– Franck’s previously implicated in deaths of 21 polo ponies in 2009
• Federal court ruled FDA lacked jurisdiction for pharmacists
compounding
•
NECC
– Outbreak of fungal meningitis
• Epidural steroid injections (reports began in late August)
• Multi-state outbreak
• Over 750 cases; 64 deaths
• Recall of all products
©2012 Novation Confidential.
©2013
Pharmacy Sterile Compounding Summit
Feb. 6th, 2013, Washington, DC - Convened by ASHP and AHA
Invited Speakers And Stakeholders
Observers
• FDA (Axelrad, Sklamberg, Anderson, Ireland, Riley)
• Pew Charitable Trusts (Coukell,
Cosell, Despres)
• USP (Firschein, Schnatz, Kastango-Clinical IQ)
• ISMP (Cohen)
• CDC (Craig)
• Practitioners (DOP’s from Vanderbilt Univ.,
Cleveland Clinic and Baptist Montgomery)
• GPO’s (Novation, Premier, Cardinal and HPG)
• NABP (Russell)
• Mass Society of Health-System Pharmacists (Kerr)
• State Boards of Pharmacy (Massachusetts and
Minnesota)
• Children’s Hospital Association (Rudisill)
• AMA (Dickinson)
• Compounding Industry- Pharmedium (Kruzynski, Rasnic)
17
©2012 Novation Confidential.
• Federation of American Hospitals
(Chambers)
• APhA (Rowe)
• National Community
Pharmacists Assoc
(Blankenship, Hauser)
• National Patient Advocate
Foundation (Lamarca)
After the Summit, More Misadventures
•
FDA conducts audits of “specialty pharmacy” compounders all over the US
– All four Pharmedium facilities were inspected in 2013
– Observations and 483’s found with all compounders, including Pharmedium
– cGMP standards were used for the first time as the basis of audits
• Likely that FDA was establishing a baseline in order to make new regulations
•
Georgia Compounding Pharmacy widens recall
– Clinical Specialties Compounding Pharmacy of Augusta, GA
– First recall was for Avastin
– Latest recall was for all sterile products compounded at this facility
•
Michigan AG (Mar 27th, 2013) Seeks Grand Jury Investigation (ASHP Daily News)
– Criminal charges being considered for executives of NECC
•
Officers of NECC settle claims with victims
– May 7th, 2014, officers and executives of NECC agree to $100 million settlement for
victims
18
©2012 Novation Confidential.
©2013
HR 3204 Drug Quality & Security Act
Drug Quality and Security Act (Compromised 2 earlier bills)….
HR 3086- Compounding Clarity Act (April 2013- states empowered)
S.959- HELP Committee Bill (August 2013- FDA empowered)
•
180 page bill introduced Sept. 25th, passed Sept. 28th, signed by President
– Compounding Regulations (Title 1 – 30 pages)
– Track and Trace (Title 2 – 150 pages)
•
DQSA (Title 1) Section 503A- “Traditional Compounding”
– 503A – Traditional Compounding (Regs already existed in F.D.C. Act)
– State pharmacy license required and USP <797> Based – Ceiling
– Limited, if any, anticipatory compounding – Primarily patient specific
– State Board of Pharmacy Inspections (Must inform FDA of concerns found)
• Quality issues
• Warnings/Sanctions
• 503A Violators (May need to be registered in 503B)
– Compounding in hospital-based pharmacies will fall under 503A
19
©2012 Novation Confidential.
©2013
HR 3204 Drug Quality & Security Act (cont)
•
DQSA (Title 1) Section 503B- “Outsourced Compounding” (New)
– Entities are defined as “Outsourcing Facilities” (new)
– Federal registration required – “FDA oversight”
– Registrants will be on FDA website (listing whether they start with sterile or start with
API bulk)
– Fees (to cover inspections) will be assessed upon registration
– Inspection frequency determined by risk (higher risk of API bulk to sterile will have
more inspections)
– Reporting requirements (e.g. production activity, ADR’s, compounding for drug
shortages etc.)
– Labeling to include:
• “This is a compounded drug”
• “Not for resale”
• “Office use only”-- (industry and stakeholders hoping to get this modified)
– Can hold RX license if doing traditional 503A activities (CAPS model)
– Limitations: (“Do not compound” list from FDA; Limitations on bulk substances
20
©2012 Novation Confidential.
©2013
Compounding Quality Act (summary)
• Defines 3 distinct classes of producers
– Pharmacy, Outsourcing Facility, Manufacturer
• Explains exemptions
• Requires annual establishment and re-inspection fees
• Places onus on FDA to perform audits for Outsourcing Facilities
• Designates drugs that may not be compounded
• Defines bulk ingredient qualifications
• Places restrictions on wholesaling
• Increases state and FDA communication (two way)
21
©2012 Novation Confidential.
Outlook Beyond 2014
• Fewer new shortages, but number of active shortages will remain high
– Continuing potential to impact patient care, including additional compounding
misadventures
• Comprehensive drug management policies and procedures will remain important
– Effective communication remains critical to drug shortage management strategies
• Shortage crisis will continue to be the subject of government review and advocacy
efforts
• New Compounding/Track and Trace Legislation passed to ensure quality and security of
the pharmaceutical supply chain
• Estimates of 2 to 3 years before substantial improvement due to improved/expanded
manufacturing facilities (following billions of dollars worth of remediation)
• New FDA Guidance to be discussed at second Compounding Summit (July 2014)
– cGMP Standards specific for compounding facilities to be defined
– Do Not Compound List to be expanded (25 new ones→ now total > 75)
22
©2012 Novation Confidential.
Do Not Compound List …(Not safe / ineffective)
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
23
Aminopyrine
Chloramphenicol
Esmolol
Gatifloxacin
Phenylpropanolamine
Propoxyphene
Rapacuronium
Rofecoxib
Adrenal cortex
Dexfenfluramine
Diethylstilbesterol
Fenfluramine
Methamphetamine injection
Trovafloxacin
Bromfenac sodium
Chorionic gonadotropin
Methapyrilene
Phenacetin
©2012 Novation Confidential.
•
•
•
•
•
•
•
•
•
•
Phenformin
Potassium arsenite
Potassium chloride (oral,
>100mg/dose)
Reserpine
Sulfadimethoxine
Sulfathiazole (except vag use)
Temafloxacin
Tetracycline (liq oral for peds >
25mg/ml)
Tribromsalan
Zomepirac
Approximately 50 other compounds
What is your contracting criteria?
Have you established minimum requirements for a contract?
• Registered as FDA outsourcing facility (503-B)- FDA’s
Recommendation
– Comply with cGMP regulations
– Provide procedure for adverse event reporting
– Provide list of all medications compounded
• National provider or regional provider- “compounding scale”
• Will the compounder provide their most recent 483 observation form?
– Will the compounder provide you a satisfactory 483 resolution
document?
• What is your risk appetite? (non-sterile → sterile or sterile → sterile)
• Will your compounder determine BUD for all products at least
annually?
• Will your compounder perform sterility testing on all batches?
• Can your compounder pass a QSR (Quality Site Review)?
– Performed by your facility or a qualified independent auditor
24
©2012 Novation Confidential.
Discussion