AQUACULTURE DRUGS FDA PROSPECTIVE Barbara Montwill FDA/CFSAN Office of Seafood Shrimp School 2005...
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Transcript of AQUACULTURE DRUGS FDA PROSPECTIVE Barbara Montwill FDA/CFSAN Office of Seafood Shrimp School 2005...
AQUACULTURE DRUGS
FDA PROSPECTIVE
Barbara MontwillFDA/CFSAN
Office of Seafood
Shrimp School 2005University of Florida
Aquaculture• Aquaculture – the fastest growing
business (10% per year)• Global aquaculture production
Estimated for 35 million metric tons (~30% of total seafood production)
Estimated production of farm-raised shrimp 2 million metric tons
• U.S. shrimp import: ~75% of total supply
7 countries account for about 70%(Thailand, China, Ecuador, Vietnam, India, Indonesia and Brazil)
AquacultureAquaculture production more intensive larger number of animals per
production unit higher farms density in an
area
Risk of rapid expansion poor water quality disease outbreaks environmental impact
Chemicals in Aquaculture Purpose and use
Sediment and water management Enhancement of aquatic productivity Feed formulation Manipulation and enhancement of
reproduction Growth promotion Health management Improvement of survival rates Transport of live organisms
Chemicals in Aquaculture Benefits (if carried out properly):
control of infection disease prophylactic measure against infections growth and productivity promoters
Concerns (over use or misuse): residue in edible portion developing bacterial resistance human health implications environmental implications
Pesticides Register and regulated by EPA
Federal Insecticide, Fugicide and Rodenticide Act (FIFRA)
Title 40 of the Code of Federal Regulations (CFR)
Use and condition specified on label
Aquaculture DrugsAs defined by the Federal Food, DrugAnd Cosmetic Act (FFDCA) a drug is:
articles recognized in the official United States Pharmacopeia
articles intended to use in diagnosis, cure, mitigation, treatment, or prevention of disease
articles intended to affect the structure or function of the body of man or animal
articles intended to be a component of above
Aquaculture Drugs
Intended use of a compound determines if a compound is a drug.
Antibiotics are drugs: they treat or mitigate disease or affect structure or function
Aquaculture Drugs ALL aquaculture drugs whether for direct
medication or for addition to feed must be approved for use in the US
As mandated by the Federal Food, Drug and Cosmetic Act, a new animal drug may not be sold in interstate commerce unless it is the subject of a New Animal Drug Application (NADA).
Use of unapproved drugs or misuse is a violation, product is adulterated under 21 U.S.C. Section 342 (a)(1) and Section 342 (a)(2)(C)
Aquaculture DrugsNew Animal Drug must be: Effective for the intended use Safe for the target animal Safe for human food (no harmful
residues) determine if the drug has potential to cause
adverse effects (e.g. cancer) determine a tolerance/ safety level
Safe for environment Safe for users
Aquaculture DrugsDrugs are approved: dosage route of administration species limitation of use/ indication for use frequency
Aquaculture DrugsAny deviation from the label is considered:
Extra-label use prohibited except under the provisions
of Animal Drug Use Clarification Act (AMDUCA), Title 21 Code of Federal Regulations Part 530 (21CFR530)
Aquaculture Drugs Only by a licensed veterinarian or under
his/her supervision The animal must be very sick or will die
w/out treatment The veterinary must be familiar w/ the
producers animals No new animal drug is approved for this
illness For food animals there can’t be harmful
residues
Aquaculture DrugsDrugs banned for extra-label use in foodanimals: Chloramphenicol; Clenbuterol; Diethylstilbestrol (DES); Dimetridazole; Ipronidazole (and other
nitroimidazoles); Furazolidone, Nitrofurazone (and other
nitrofurans) Sulfonamide drugs in lactating dairy cattle
(except approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine);
Fluoroquinolones; Glycopeptides.
Aquaculture DrugsApproved
Current Drugs Approved for Current Drugs Approved for
Aquaculture in USA (Total 6)Aquaculture in USA (Total 6)
Chorionic gonadotropin (HCG) Formalin Oxytetracycline Sulfadimethoxine-ormetoprim Sulfamerazine Tricaine methanesulfonate (MS-222)
Aquaculture DrugsApproved
Drugs approved for use in shrimp in Drugs approved for use in shrimp in
the U.S.:the U.S.:
Formalin (control external protozoan parasites)
Some drug use under an Investigational New Animal Drug (INAD)
Aquaculture Drugs FDA do not object use of drugs
determined to be new animal drugs of low regulatory priority if the following conditions are met: The substances are used for prescribed
indications, levels The substances used according to GMPs The substances are appropriate grade for use
in food animals There is not likely to be adverse effect on the
environment
Aquaculture DrugsLow Regulatory Priority
Acetic Acid Calcium Chloride Calcium Oxide Carbon Dioxide Gas Fuller’s Earth Garlic (whole form) Hydrogen Peroxide Ice Magnesium Sulfate
Onion (whole form) Papain Potassium Chloride Povidone Iodine Sodium Bicarbonate Sodium Chloride Sodium Sulfite Thiamine
Hydrochloride Urea and Tannic Acid
Aquaculture Drugs Classification of these substances as
new animal drugs of low regulatory priority are based on current knowledge and should not be considered as an approval
nor an affirmation of their safety and effectiveness
does not exempt facilities from complying with other environmental requirements (e.g. with National Discharge Elimination System requirements)
Aquaculture Drugs Details information on the approved
products available at CVM’s Website:
www.fda.gov/cvm
FDA testing program
FDA testing program Unapproved drugs
administered to aquaculture fish pose a potential human health hazard.
These substances may be carcinogenic, allergenic and/or may cause antibiotic resistance in man
?
FDA testing program Shrimp
Chloramphenicol Nitrofurans Fluoroquinolones Oxytetracycline Quinolones: Qxolinic Acid and Flumequine
Catfish Fluoroquinolones Malachite green Quinolones: Oxolinic Acid and Flumequine
FDA testing program Salmon
Quinolones: Flumequine Ivermectin Oxolinic Acid Malachite green
Crab Chloramphenicol
FDA testing program Seafood products tested
Domestic Import
FDA testing programCountries sampled based on where product is imported from:
Shrimp Brazil Ecuador Indonesia Thailand Vietnam China India
FDA testing programChloramphenicol
Chloramphenicol has never been Chloramphenicol has never been approved for use in food producing approved for use in food producing animals animals
Causes aplastic anemia in humansCauses aplastic anemia in humans
Adverse reactions not dose dependent Adverse reactions not dose dependent and safe level of exposure had not and safe level of exposure had not been determinedbeen determined
Oral solution withdrawn because of Oral solution withdrawn because of documented history of misuse in food documented history of misuse in food animalsanimals
FDA testing programNitrofurans
Nitrofurans (except topical Nitrofurans (except topical applications) were banned for use in applications) were banned for use in food animals in 1991. food animals in 1991.
Considered carcinogen Considered carcinogen Recently have banning topical uses for Recently have banning topical uses for
food animals due to residues concernsfood animals due to residues concerns
FDA testing program Because tested compounds are not
approved, presence of any residues is a violation
Only limitation is sensitivity of the analytical method, a limit of detection (LOD)
FDA testing programFDA determination of violation is
based on drug residues findings with approved regulatory method
Determinative Method Confirmatory Method
FDA testing programAnalytical methods
Analytical methods recommended by FDA
Chloramphenicol: Determiantion of Chloramphenicol Residues
in Shrimp and Crab Tissues by Electrospray Triple Quadrupole LC/MS/MS
LC/MS/MS Analysis of Chloramphenicol in Shrimp
Nitrofurans: Determination of Nitrofurans Metabolites in
Shrimp using LC/MS/MS Both methods are available at CFSAN’s
Website:www.cfsan.fda.gov/seafood1.html
REQUIRMENTS FOR IMPORTED PRODUCTS
Imported Products (21 CFR Part 123.12)
HACCP for all imported fish and fishery products
Under the US FDA Seafood HACCP regulation, aquaculture processors will be expected to reject fish from producers who use drugs illegally.
Importer Verification: Written Verification Procedures
Product specifications to ensure that the product is not injurious to health and not processed under insanitary conditions, and
Affirmative steps
Importer Verification: Written Verification Procedures
Obtaining the processor’s HACCP plan and sanitation records for the lot being entered
Obtaining either a continuing or lot-by-lot certification of proper drug usage
Regularly inspecting the foreign processor’s facilities
Importer Verification: Written Verification Procedures Maintaining the processor’s HACCP
plan and written guarantee that the product is processed in accordance with the U.S. requirements
Periodically end-product testing and written guarantee that the product is processed in accordance with the U.S. requirements
Detention Procedures for Imported Products
Types of detention DETENTION OF AN INDIVIDUAL ENTRY
- Stopping a shipment of an individual entry (due to sample collection or physical examination)
DETENTION WITHOUT PHYSICAL EXAMINATION (DWPE)- Stopping a shipment without collection of
a physical examination by FDA
Procedures for detention of individual entry
Appear violative after initial review of entry or exam
FDA samples and analyzes lot Lot released if no violation found Non-violation does not affect future shipment
Violative product not allowed entry
Procedures for Detention without Physical Examination (DWPE)
Detention based on past violative history (individual processors, countries or geographical area)
Import Alerts has been issued that may cover one or more firms or country
Detention requirements for individual shipmentsIndividual shipments may be released from detention if: The importer submit to FDA an Application for
Authorization to Reconditioning Each shipment is sampled and analyzed Analysis performed by a competent private
laboratory Lab results reported to FDA for review If not violative the shipment is released
Detention requirements –removal from DWPEFirms, countries or products may be removed from DWPE if: Minimum 5 consecutive non-violative
shipments in a 6 month period (can be multiple ports) FDA must be assured that firms are compliant
over a reasonable period to remove from DWPE At least one shipment audited by FDA to
ensure analytical validity Shipments are individual, routine,
commercial entries and represent separate production operations
Detention requirements –removal from DWPE
FDA may request additional documentation to ensure compliance with other provisions of U.S. laws and regulations
FDA may require an establishment inspection
Firms or countries must request removal in writing after 5 non-violative shipments in a 6 month period
Private Laboratories Private labs are employed for two
purposes: Testing of detained imports under FDA review Manufacturer/processor testing for quality
control, HACCP purposes FDA ORA Laboratory Manual provides
a guidance for private laboratories(section 7) This guidance applies only to laboratories
performing testing of product under DWPE
Private Laboratories FDA does not have authority to regulate a
private laboratory, but has legal authority over regulated import products tested and can based its decision on analysis performed by private laboratory
Good relationship is necessary FDA has option to audit Laboratory must be:
Credible Competent Uses standards Uniform Recognized current methods Practices quality assurance and quality control activities
Private Laboratories Submission to FDA Submit the private laboratory complete analytical
package to the servicing Laboratory for the Compliance Branch of your local FDA office.
A complete analytical package should include: Importer’s Certification Notice of FDA Action Form with Commercial Invoice Collection and Analysis Reports Analytical Results Summary Sheet Private Laboratory Certification Analytical Worksheet: including method reference,
validation of the method, instrumentation and operating parameters, all computer printouts, information on blank/fortification samples, certification of standard purity, quality controls applied and all other information necessary to determine the technical validity of the analysis
Private laboratories The Private Laboratory Guidance is
available through the FDA website:
www.fda.gov/ora/science_ref/lm/vol3/section/07.pdf
NOTE: While the guidance is written in reference to private laboratory, it is really the importer that is responsible for the entry’s compliance with applicable laws and regulations.
Private laboratories
FDA does not accept results of testing of product not under DWPE for the purpose of speeding entry reviews
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