Download Therapeutants in Aquaculuture

Therapeutants in Aquaculuture
Agriculture vs. human use and the development of bacterial resistance
Scale: Abx used 100 times more in food animals than in humans.
The problem of aquaculture
Aquatic "pollution" - widespread drug exposures: OTC (Ca chelation, breakdown
times, water vs. sediments)
Pharmaceutical companies view many aquaculture ventures as small potatoes; i.e.,
not worth the risk of development.
BOTTOM LINE: Control versus spread of disease
Currently available applications
FDA-approved drugs - Approved only for specific diseases
MS222
Formalin (fish, fish eggs, shrimp)
Romet-30 (sulfadimethaxine, ormetoprim) (salmon, catfish)
Sulfamerazine – recently removed from list
Oxytetracycline (salmon, catfish, lobster)
FDA-unapproved Low Regulatory Priority Treatments
Primarily topical treatments for fish eggs, simple parasitic treatments
17 products ranging from acetic acid to ice to urea:
Acetic acid, CaO, NaCl for protozoa, monogenes
MgSO4 for monogenes
Garlic, onions against crustaceans
EPA-registered products
Algicides – chelated copper, copper-based compounds
Herbicides – shade control, organic bromides, endothall, fluidone, glyphosate,
2,4-D based compounds (large ##)
Fish toxicants / piscicides – rotenone, antimycin
USDA-licensed biologics
Bactericins – available for Aeromonas, Yersinia, Vibrio, Edwardsiella
Diagnostic kits – available for Renibacterium
Feeds – unregulated? Probiotics, glycans
What is the process for a new drug?
Drug must be effective and safe (GRAE, GRAS)
Approved new animal drug application or
Have an investigational new animal drug exemption (INAD)
INAD Exemptions
Emergency Exemptions
Extra-label use policy for veterinarians (limited basis, not for large scale,
can't be mixed in feed, nor use by public, including fish pathologists
specifically!)
Compassionate Exemption : Allows pharm company to do research on an
unapproved drug prior to approval.
Must collect supporting data for NADA approval
Must have framework: sponsor, monitor, investigators
Sponsor, veterinarian, scientists, aquaculture facility
Sponsor important to guarantee QA/QC of drug! Not all OTC are
alike?!
Must have safety and efficacy information (human and environmental)
Can use FARAD (Food Animal Residue Avoidance Data Bank)
and National Coordinator for Aquaculture NADAs.
Minor Use Animal Drug Program (NRSP-7).
Request a compassionate exemption from FDA
Must have letter of response/approval from FDA's CVM (100 days).
Annual basis only.
Sponsor: aquaculture facility, association or pharmaceutical company, responsible
for all communications with CVM, must develop protocols, notifys CVM
of shipments. Pharm company ultimately sponsors NADA….
Monitor: veterinarian; provides QA/QC of data, does not participate in data
collection, can work on behalf of sponsor.
Investigators: scientists, concerned aquaculture facility; conducts trial, manages
daily aspects, directs administering of drug
Upon approval:
Sponsor and monitor prepare clinical trials
Investigators undertake trials according to protocols.
Sponsors notify FDA/CVM of each drug shipment
Data analysis and submission of data to FDA/CVM.
Sponsor holds the INAD exemption.
Issues to consider
At least 2 adequate and well-controlled efficacy studies are required.
Phase I: Dose-titration studies (3 doses, 1 control, 2 water temps or water quality
conditions), optimal dose
Phase II: Clinical field trial at 3 sites
Sources, batches, lot numbers must all be recorded.
Residue depletion and environmental safety data must be generated.
Treatment Schedules
Initial targeting - efficacy studies, control groups
Types of drug studies
Whole animal
Cell or bacterial culture
Batch vs. individual
Route of administration
Oral, bath, injection (im, ip, subq)
Dosing interval & Duration
Criteria for evaluation: morbidity, mortality, adverse reactions, etc.
Tissue-residue analyses – use highest dose group
Hinton-Mueller agar & Bacillus cereus
HPLC
Delvo-P test kit for OTC
Environmental residues
How much drug is left in the water or sediment
How much remains in the water after filtration (if used)
How much drug is excreted.
Fate and effects data:
Photolysis/hydrolysis
Biodegradation
Adsorption
Sed tox
Fish and invert LC50
Chronic toxicity in fish and invert
NPDES permit (National Pollutant Discharge Elimination System) via EPA.
Integrated Pest Management (Schisto or Onchocerca examples if time permits)
Management at each level
Cultural changes
Breaking the life cycle