CDC Drug Service

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CDC Drug Service

• A Novel Approach to Tracking and Treating Rare
  and Exceptional Infectious Diseases

USPHS Scientific Training Symposium Pharmacist
Category Day, 2009
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Objectives

• Discuss history mission of the CDC Drug Service
  and role in providing drugs/biologics otherwise
  unavailable for domestic use
• Provide an overview of the anti-parasitic drugs
  and biologics maintained/provided by the Drug
  Service
• Describe some of the parasitic diseases treated
  and uses of the biologics
• Explain how the Drug Service provides a
  surveillance function
• Describe obstacles encountered in procurement of
  products and obtaining INDs

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History

• Immunobiologics Activity (IA) est. in 1965
• National center for storage/distribution of
  biological products
• Provided vaccines not available from commercial
  sources for immunization
• Intended to protect high-risk groups
• Limited demand for products licensure not
  expected
• Original products botulinum toxoid, anthrax
  vaccine, tularemia vaccine
• Provided surveillance function (pentamidine and
  AIDS)

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History (continued)

• Stocked products for potentially fatal illnesses
  with no other effective therapy available
• Vaccinia immune globulin (VIG), Diphtheria and
  Botulism antitoxin (DAT, BAT)
• Immune globulins against arboviruses (e.g. EEE,
  WEE, SLE)
• In late 1960s began collaboration with several
  of the Quarantine Stations to strategically
  position products
• 1986 first pharmacist hired by CDC to revamp and
  reorganize the program for distribution of drugs
  and biologics for rare diseases
• CDC Drug Service currently staffed by 4
  pharmacists

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Preparedness Activities

• Project management for contracts with Sanofi,
  formerly Acambis, (ACAM2000 smallpox vaccine) and
  Cangene (VIG)
• Contracts provide for license maintenance, dating
  extension, relabeling, post-marketing
  requirements, etc.
• Both products stored in the Strategic National
  Stockpile (SNS)

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CDC Drug Service
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CDC Drug ServiceImmunobiologics
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ImmunobiologicsProphylactic Use

• Products
• Smallpox (vaccinia) vaccine
• Anthrax vaccine
• Botulinum toxoid

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ImmunobiologicsProphylactic Use

• Limited supply or limited demand for products
  not commercially available
• Recommendations for use supported by Advisory
  Committee on Immunization Practices (ACIP)
  guidelines

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ImmunobiologicsProphylactic Use

• Uses
• Routine, non-emergency use
• Intended to protect high-risk groups
• Laboratory personnel
• Animal technicians

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ImmunobiologicsProphylactic Use

• Release procedures
• Site registration
• Research project verification
• Vaccine release
• Post-vaccination safety reporting

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ImmunobiologicsTherapeutic Use

• Products
• Botulism Antitoxin (BAT)
• Diphtheria Antitoxin (DAT)
• Vaccinia Immune Globulin (VIG)

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ImmunobiologicsTherapeutic Use

• Botulism
• Approximately 100 cases in the U.S. annually
• Three primary types of botulism
• Food borne botulism
• Wound botulism
• Infant botulism
• Early intervention and treatment key to reducing
  morbidity

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ImmunobiologicsTherapeutic Use

• Diphtheria
• Respiratory diphtheria cases in the U.S. are few
  due to vaccination coverage.
• Differential diagnosis can be challenging due to
  both rarity and symptomatology

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ImmunobiologicsTherapeutic Use

• Smallpox
• Eradication in the late 1970s through global
  vaccination efforts.
• Vaccinia Immune Globulin (VIG) used to treat
  adverse reactions associated with the smallpox
  (vaccinia) vaccine.

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ImmunobiologicsTherapeutic Use

• Product has no known capacity for domestic
  licensure and commercial support
• Limited supply or limited demand for products
• No other effective alternative therapy available
• Sentinel surveillance capacity profile

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ImmunobiologicsTherapeutic Use

• Central storage repository
• Strategic National Stockpile (SNS)
• CDC Drug Service
• Distribution points
• Strategic National Stockpile (SNS)
• CDC Quarantine Stations

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ImmunobiologicsTherapeutic Use

• Release procedures
• CDC Subject Matter Expert (SME) contacted by
  local treating physician
• Clinical Consultation
• Emergency Release
• SNS
• CDC Quarantine Station

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CDC Quarantine StationDrug distribution network
ME
Seattle
Chicago
VT
NH
WA
MA
ND
MT
RI
NY
MN
CT
CT
MI
WI
NJ
PA
OR
SD
ID
New York
WY
MD
IA
OH
NE
IN
WV
No.CA
IL
NV
VA
San Francisco
UT
KY
CO
MO
KS
NC
TN
SC
OK
So.CA
AR
Atlanta
NM
AZ
Los Angeles
AL
North TX
GA
MS
Honolulu
East TX
LA
West TX
FL
Miami
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Anti-Parasitic Drug Formulary, 2009
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Severe Malaria in U.S.

• Avg. 1,500 cases
• annually (10 severe)
• P. falciparum
• Imported malaria
• Approved drug
• IV Quinidine
• RBC destruction ? vessel organ damage
• ? end-organ failure

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Artesunate (IV)

• 1st line agent for severe malaria,
• WHO Guidelines, SEAQUAMAT trial

• Severe malaria disease
• High parasitemia
• Inability to take oral medications
• Lack of timely access to intravenous quinidine
• Quinidine intolerance or contraindications
• Quinidine failure

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Filariasis

• Larve ? Adult worm ? microfilarea ?
• lymphatic system destruction
• Microfilarema, asymptomatic
• May develop
• Lymphadema, elephantitis
• TPE
• Ocular lesions, blindness

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Diethylcarbamazine (DEC)

• Filariasis drug of choice
• Hetrazan withdrawn in 1998
• Kills microfilaria and some adult worms
• Indications
• Lymphatic filariasis, TPE, Loa Loa
• Loa Loa prophylaxis

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Leishmaniasis

• Transmitted by sandflies
• Leishmania genus
• 3 major clinical types
• cutaneous
• visceral (kala-azar)
• mucosal
• Old World (OWCL)
• New World (NWCL)

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Sodium Stibogluconate(Pentostam)

• Pentavalent antimonial
• 100mg/ml parenteral solution (MDV)
• Dose 20mg/kg/day IV or IM
• cutaneous 20 days
• visceral, mucosal 28 days
• Adjust ? children, ? renal impairment
• Monitoring EKG, SCr, LFTs, CBC
• (pre-, mid-, post-treatment)

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American TrypanosomiasisChagas Disease

• T. cruzi, kissing bugs
• Acute Phase
• asymptomatic/mild
• Chronic (30 symptomatic)
• Dilated cardiomyopathy, enlarged organs
• US transmission
• blood/organ donation
• vectors

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Nifurtimox

• Inhibits DNA synthesis of T. cruzi
• Good efficacy in acute phase chronic?
• GI, CNS, Depression
• Alternative Benznidazole

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CDC Nifurtimox Releases,1997 2009
Clinical patient releases Blood donor releases
Blood donor screening starts

as of April 16, 2009
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Acknowledgements

• CDC Drug Service
• CAPT John Becher (ret., USPHS), RPh
• CDC Division of Parasitic Diseases
• CAPT Barbara Herwaldt, MD
• CAPT Anne Moore, MD, PhD
• CDR (sel.) Sue Montgomery, DVM
• CAPT Paul Arguin, MD
• CDC Division of Global Migration and Quarantine