Form GnRH IIA- (W, 1, 2 GnRH IIA- (W, 1, 2 STUDY PROTOCOL FOR A COMPASSIONATE AQUACULTURE INVESTIGA
Administration of U.S. Fish and Wildlife Service Investigational New Animal Drug (INAD) Program
GnRHIIa INAD Protocol update Dec 2021
GnRH IIa Chicken Gonadotropin – Releasing Hormone II analog INAD #13–345 - Government
OMB:
OMB Control No. 1018-####
Expires ##/##/20##
STUDY PROTOCOL FOR A COMPASSIONATE AQUACULTURE INVESTIGATIONAL NEW ANIMAL DRUG (INAD) EXEMPTION FOR CHICKEN GONADOTROPIN-RELEASING HORMONE II ANALOG (GnRH IIa) (INAD 13-345)
U.S. Fish and Wildlife Service, Fish and Aquatic Conservation
__________________________ ____________________
Sponsor Signature Date Approved
Manufacturer:
DelTaq Fish Health LLC
PO Box 343
Stoneville, MS 38776
Office for Coordination of GnRH IIa INAD:
Aquatic Animal Drug Approval Partnership
4050 Bridger Canyon Road Bozeman, Mt 59715
Proposed Starting Date: April 1, 2020
Proposed Ending Date: July 30, 2028
Study Director: Bonnie Johnson
Clinical Field Trial Location:
Facility:________________________________________________________
Investigator:____________________________________________________
Table of Contents
I. STUDY IDENTIFICATION AND TITLE 3
III. INVESTIGATORS/FACILITIES 3
IV. PROPOSED STARTING AND COMPLETION DATES 3
XII. TREATMENT RESPONSE PARAMETERS 12
XIII. FORMS FOR DATA COLLECTION 13
XIV. RECORD KEEPING PROCEDURES 13
XV. DISPOSITION OF INVESTIGATIONAL ANIMALS 13
XVI. DISPOSITION OF INVESTIGATIONAL DRUG 14
XVII. DATA HANDLING, QUALITY CONTROL, MONITORING, ADMINISTRATIVE RESPONSIBILITIES 14
XVIII. PLANS FOR DATA ANALYSIS 15
XIX. PROTOCOL AND PROTOCOL AMENDMENTS 15
All data must be entered through the online INAD database: 33
Form GnRH IIa-1: Report on Receipt of Drug 36
Form GnRH IIa-2: Drug Inventory Form 37
STUDY PROTOCOL FOR A COMPASSIONATE AQUACULTURE INVESTIGATIONAL NEW ANIMAL DRUG (INAD) EXEMPTION FOR CHICKEN GONADOTROPIN-RELEASING HORMONE II ANALOG (GnRH IIa) UNDER INAD #13-345
Clinical field trials to determine the efficacy of gonadotropin releasing hormone II analogue (GnRH IIa) proposed for use as a spawning aid for female ictalurids under INAD 13-345.
Dr. Marilyn Blair, U.S. Fish and Wildlife Service, Branch Chief, Aquatic Animal Drug Approval Partnership Program, 4050 Bridger Canyon Road, Bozeman, MT 59715; Phone: 406-994-9904; Fax: 406-582-0242; Email: [email protected]
Manufacturer: DelTaq Fish Health LLC
PO Box 343
Stoneville, MS 38776
Email: [email protected]
Study Director: Ms. Bonnie Johnson, U.S. Fish and Wildlife Service, Aquatic Animal Drug Approval Partnership (AADAP) Program, 4050 Bridger Canyon Road, Bozeman, MT 59715; Phone: 406-994-9905; Email: [email protected]
Principal Clinical Ms. Paige Maskill, USFWS – AADAP Program
Field Trial Coordinator: 4050 Bridger Canyon Road, Bozeman, MT 59715;
Phone: 406-994-9911; Email: [email protected]
INAD Study Monitors: See Appendix II for names and addresses.
See Appendix IIIa for names and addresses.
Proposed Starting Date: March 13, 2020
Proposed Completion Date: July 30, 2028
Background Information:
Aquaculture presents an opportunity to sustainability increase production of fish, both for conservation purposes and to satisfy the global fish consumption of a growing human population. However, one of the most serious limitations in the advancement of commercial aquaculture of teleost fish species is the control and management of reproductive processes in captivity (Zohar and Mylonas, 2001). Though many advances have been made in husbandry and captive rearing of finfish species, many still exhibit reproductive dysfunctions when captive spawning is attempted. Most commonly, females fail to undergo final oocyte maturation and thus ovulation and spawning. Therefore, the ability to manipulate and control teleost fish reproduction in captivity will not only significantly improve the industry’s ability to provide a steady supply of fish, both in on and off-season spawning, but also allow selective genetic manipulations to further enhance the growth, survival, and flesh quality characteristics of teleost fish reared in captivity. The outcome is increased quantity and quality of fish, both for human consumption and conservation measures.
In general, finfish fail to reproduce in captivity due to reproductive dysfunction caused by stressors associated with the captive environment. As reviewed in Zohar and Mylonas (2001), in females, this is frequently the result of three types of dysfunction:
Failure to mature at all (i.e. vitellogenesis does not occur);
Absence of final oocyte maturation (i.e. vitellogenesis occurs, but does not progress through final oocyte maturation, ovulation, and spawning);
Maturation occurs but spawning does not.
While these reproductive dysfunctions may be addressed through environmental manipulations (i.e. temperature, photoperiod), such efforts alone are often not sufficient to fully overcome the physiological impacts captivity has on limiting sexual maturation and thus reproductive success. Peptides such as Gonadotropin Releasing Hormone analogs (GnRHa, which include GnRH IIa), provide a safe, effective approach to overcome these physiological dysfunction(s) and enhance sexual maturity and spawning of female finfish in captivity.
Benefits of GnRHa (reviewed in Zohar and Mylonas 2001) are that these peptides induce the release of endogenous hormones (e.g. LH/FSH) and repair the endocrine disruption that is causing the reproductive dysfunction. Further, GnRHa act at an elevated level on the Hypothalamus-Pituitary-Gonad (HPG) axis and provide stimulation directly to the pituitary to induce sexual maturation. In addition, unlike other spawning aids (e.g. Carp Pituitary), GnRHa can easily be synthesized and purified, thus presenting no risk of pathogen transmission. Finally, GnRH IIa display a unique structure present in all teleost fish species, and thus the use of GnRH IIa can be successfully applied with success to a wide range of teleost fish species.
B. Purpose of INAD:
The purpose of this INAD for GnRH IIa in a liquid form (saline) for a two phase injection is to develop clinical field trial data that will be used to determine the efficacy and appropriate treatment regimens for use as a spawning aid for female ictalurids. These data will be used to support a new animal drug application (NADA) for “GnRH IIa”.
The U. S. Fish and Wildlife Service (USFWS) and Aquatactics anticipate that it may take several years to complete all the technical section data for a NADA for GnRH IIa. The USFWS and Aquatactics believe it is likely that data from 5-7 treatment seasons will be required in order to adequately assess the efficacy of GnRH IIa as a spawning aid for female ictalurids to support a NADA.
The two major objectives of this study protocol are as follows:
Collect scientific data necessary to establish the efficacy of GnRH IIa as a spawning aid in cultured female ictalurids under typical hatchery situations.
Provide the opportunity for fish culturists and fisheries managers to legally use GnRH IIa to maintain the genetic integrity and improve the reproductive potential of hatchery broodstocks during the period of time necessary for collection of efficacy, safety, and residue data required for an NADA for GnRH IIa use in female ictalurids.
Test and Control Articles:
Drug Identity
Active ingredient
Common Name: GnRH IIa or cGNRH IIa
Chemical Name: (Des-Gly10, D-Arg6, Pro-NHEt9)-LHRH II
(CHICKEN)
CAS Number: 145940-57-4
Amino Acid Profile: pGlu-His-Trp-Ser-His-D-Arg-Trp-Tyr-Pro-NHEt
Appearance: White lyophilized powder
Clear liquid when resuspended in saline
Strength and dosage form
GnRH IIa is a synthetic peptide analogue of gonadotropin releasing hormone II (GnRH II). It is presented as a dry powder to be resuspended in physiological saline solution right before use for an intraperitoneal injection. Dilution rate is dependent upon fish size and intended dosage.
Manufacturer, source of supply
DelTaq Fish Health LLC
PO Box 343
Stoneville, MS 38776
Contact
Person: Tom
Goodrich/Rebecca Goyt
Phone: 425-629-8099
Fax:
425-629-8095: email: [email protected]
or [email protected]
website: www.deltaqfishhealth.com
Verification of Drug Integrity/Strength:
The Manufacturer will provide the analytical data necessary to establish the purity of each lot of GnRH IIa supplied. The lot number and date of manufacture for each batch of GnRH IIa will be placed on the label of each container. The form "Report on Receipt of Drug - Guide for Reporting Investigational New Animal Drug Shipments for Poikilothermic Food Animals" (Form GnRH IIa-1) will clearly identify the lot number for all GnRH IIa shipments. If the integrity of the GnRH IIa is compromised (i.e., by spilling or contamination of the stock container) the event will be carefully recorded, dated, and signed in the Chemical Use Log (Form GnRH IIa-2). All un-usable GnRH IIa must be destroyed by following the disposal methods described in the SDS. The Study Monitor assigned to the Investigator involved will be immediately notified.
Storage Conditions
GnRH IIa will be stored in the original container supplied by the Manufacturer with the appropriate investigational label attached. The container will be stored frozen (-20oC) and out of direct sunlight. The storage unit (i.e. most likely a manual defrost freezer) must be labeled to indicate that it contains hazardous material and that "NO Food or Drink is to be Stored in this Freezer". GnRH IIa should be stored in a secure location.
Handling Procedures
Each Study Monitor and Investigator will be required to have a current copy of the Safety Data Sheet (SDS) for GnRH IIa (see Appendix IV). Each person involved with the study and each person who may be present during the use of GnRH IIa shall be required to read the SDS. Safety precautions as outlined in the SDS will be followed at all times when working with GnRH IIa.
Investigational Labeling
A copy of the label to be attached to each container of GnRH IIa are provided in Appendix V. Although investigational labels will be affixed to GnRH IIa containers by the supplier, it is the responsibility of the Investigator to ensure proper labeling of all containers of GnRH IIa.
Accountability
AquaTactics will be the sole supplier of GnRH IIa to all Investigators under this INAD.
The Online INAD Database must be used by Investigators for ALL INAD reporting. The online INAD database has a built-in system of checks, balances, and email notifications to ensure that all information/data reporting and accountability follows established INAD Study Protocol guidelines. Unless data is entered directly into the online INAD database (i.e., not captured elsewhere at the time of observation or measurement and transcribed into the online INAD database) investigators must archive hard copies of all raw data.
1. All facilities Using GnRH IIa:
Immediately upon receiving an order/shipment of GnRH IIa, the Investigator will complete Form GnRH IIa-1 “Report on Receipt of Drug - Guide for Reporting Investigational New Animal Drug Shipments for Poikilothermic Food Animals" (located in the “Manage/View Drug Inventory” section of the investigator account). The Study Director will forward a copy of this form to the FDA. Arrangements should be made between Investigators and Study Monitors to insure completed Form GnRH IIa-1s are received by the Study Director within 10 days of drug receipt.
All Investigators are also responsible for maintaining an accurate inventory of GnRH IIa on-hand. A Chemical Use Log (Form GnRH IIa-2) must be completed and maintained by each Investigator. Each time GnRH IIa is used, it must be recorded by the Investigator on Form GnRH IIa-2.
At the conclusion of field trials, all remaining GnRH IIa will be disposed of by following the disposal methods in the Safety Data Sheet (note: unless medicated feed is planned for use in another approved field trial, and planned usage is within the storage guidelines established by the manufacturer). Disposition of all GnRH IIa must be properly recorded and accounted for on the Chemical Use Log (Form GnRH IIa-2). The Study Monitor will be responsible for verifying the quantity of GnRH IIa remaining on hand versus the amount indicated on Form GnRH IIa-2. Note: GnRH IIa can be transferred to other facilities that are participating under INAD 13-345. Transfers must be shown in the Drug Inventory section of the database (formerly Form GnRH IIa-2).
7. Preparation Procedures
GnRH IIa for injection will be supplied in vials of 25 mg of a lyophilized white powder. Based on the relatively small amount of hormone per vial, investigators should not attempt to divide GnRH IIa into additional aliquots (unless a high quality analytical balance and a Good Laboratory Practice laboratory are available). Immediately prior to injection, GnRH IIa should be diluted using a sterile, physiological saline solution. Dilution volume is dependent upon dosage and desired injection volume.
10mL of sterile physiological saline solution can be added to the 25mg vial to obtain a Stock Solution concentration of 2500 µg/mL.
To obtain 50mL at 20 µg/mL, dilute 0.4mL of Stock Solution into 49.6mL of sterile physiological saline solution.
To obtain 50mL at 80 µg/mL, dilute 1.6mL of Stock Solution into 48.4mL of sterile physiological saline solution.
Inject 1mL per kg of body weight
Recommended dose of 100 µg/kg as two injections (20% then 80%) is sufficient to act as a spawning aid in female ictalurids. Administer to fish as an intraperitoneal (IP) injection using a sterile syringe and needle (18-20 g needle recommended).
B. Items Needed for Treatment, Data Collection, Etc.:
Treatment equipment should include a scale to determine fish weight and appropriate size sterile needle and syringe (18-20 g needle recommended).
When the Study Protocol has been approved and treatments are scheduled, the Investigator at each facility covered by the GnRH IIa INAD will need to complete several forms. These forms are described in Section XIII. Copies of these forms are attached to this Study Protocol and will be used as a guide only for collecting the data that will be entered into the online INAD database.
The experimental unit in this clinical field trial may consist of a contained or isolated group of fish. This will generally be a group of fish contained in a tank, raceway, or pond. However, it is strongly encouraged that whenever possible, the experimental unit in clinical field trials is individual animals. Whenever individual animals are considered to be the experimental unit, treatment response parameters for each animal must be evaluated separately.
Facilities/Investigators
The proposed facility and the Investigator must be listed in Appendix IIIa of this Study Protocol for the current calendar year before GnRH IIa can be ordered and dispensed under this INAD. Last minute deviations can be requested by the Sponsor or by an Investigator to address emergency-use situations (See Section XX). However, poor planning and/or a lack of preparation will not be considered an emergency situation.
The characteristics of the study animals (species, size, number, etc.) is presented in Appendix VIb.
Period of use
GnRH IIa treatment has been shown to be most effective when administered during the final stages of gamete maturation. In most cases, GnRH IIa will be used within 4 weeks of the time fish are normally expected to spawn.
Environmental conditions
Since GnRH IIa will be injected directly into the peritoneal cavity, there will be no drug discharge from participating facilities. Therefore, GnRH IIa qualifies for a categorical exclusion from the requirement to prepare an environmental assessment under 21 CFR 25.33(e).
Environmental conditions will be variable and include a spectrum of water temperatures and water quality parameters. Environmental conditions will be reported on Form GnRH IIa-3. Drug discharge must be in compliance with local NPDES permitting requirements.
Ability of investigator to fulfill all the requirements of the Study Protocol
See Appendix IIIb for example of knowledge required of hatchery managers (i.e., Investigators).
Prior to initiating each treatment event, the Investigator must first complete Form GnRH IIa-W: “Worksheet for Designing Individual Field Trials” (located under the “New Study Request” tab in the investigator account) that pertains to each specific treatment event. The worksheet should be filled out and forwarded to the Study Monitor through the online INAD database. The Study Monitor will review the planned treatment (worksheet) and forward it to the Study Director at the AADAP Office. The Study Director will then review the worksheet, assign the approved treatment a Study Number, and then the online INAD database will notify both the Investigator and the Study Monitor of the assigned number and approval to proceed. In most cases, this entire process should be able to be accomplished within a single working day. After initiation of the field trial, the Investigator should also record the assigned study number on any paper forms that are being used as a guide to collect the data to enter in the online database (i.e., Form GnRH IIa -2 and GnRH IIa -3), as well as on any additional correspondence regarding that specific treatment event. If for some reason the Investigator is unable to reach the Study Monitor with regards to Worksheet approval and the need for treatment is immediate, the Investigator should contact the AADAP Office for permission to proceed.
Note: The online INAD database, which must be used by Investigators for all INAD reporting, has a built-in system of checks, balances, and email notifications to ensure that all information/data reporting follows established INAD Study Protocol guidelines.
A treatment group or experimental unit may be an entire tank, pond, raceway, or group of fish. However, the experimental unit should be considered individual fish whenever possible.
Control groups will not be a requirement for clinical field trials evaluating the efficacy of GnRH IIa treatment. In some cases the number of broodfish available at a given time for GnRH IIa treatment may be extremely limited. It is likely that some facilities may need to initiate treatment on groups of ten or fewer brood fish. To establish meaningful control groups with such a limited number of animals would be difficult.
Although untreated control groups are not a required element of treatment under this INAD exemption and are at the discretion of the Investigator, control groups are strongly encouraged whenever circumstances permit. Control groups are extremely important to not only document response to treatment, but also to validate potential adverse effects in treated animals. Assignment to control and treatment groups should be random and designed to avoid bias. It is important that all fish are treated in a similar fashion. If fish are physically moved into separate test groups or different rearing units, caution should be used so that handling and rearing conditions are as similar as possible. Control fish should be kept under conditions as similar as possible to treated fish for valid comparison. Use of control groups will ensure that results of efficacy studies provide useful information that will support a NADA.
Although as stated above untreated control groups are not a required element of treatment under this INAD exemption, it is important for all investigators to note that field trials conducted under a more stringent study protocol (i.e including requirements for non-treated controls groups, replication, blinding, dose verification, etc) will ultimately be required in order to support a NADA for GnRH IIa. It is also important to note that the INAD sponsor fully expects that a limited number of facilities/investigators listed under this INAD exemption will agree to participate in such “pivotal” efficacy studies. These studies will be initiated only after direct consultation between facilities/investigators and the sponsor. These studies will be conducted under a separate FDA-approved study protocol (i.e. not the INAD study protocol), and will also be conducted with assistance from, and under the direct supervision of, the sponsor. If for any reason it becomes apparent to the sponsor that facilities/investigators listed under this INAD are not willing to participate in such “pivotal” studies, the sponsor will request that FDA terminate the INAD.
Route of administration
GnRH IIa should be brought to room temperature and injected into the coelomic cavity using an appropriately sized sterile needle and syringe (18-20g). Injections should be administered in the peritoneal cavity. Dilutions of hormones are calculated so each fish receives 1mL per Kg. Insert the GnRH IIa needle, while holding the fish firmly, inject cavity laterally to the uro-genital area under the pelvic fins. Discharge the contents of the syringe and remove the needle. It is strongly encouraged that all fish be anesthetized prior to injection.
Dose to be administered
Standard hormone dosage rates will be no more than 100 ug/kg body weight.
Dosing interval and repetition
GnRH IIa will be administered in a 2 steps manner, 20% of the dose during the first injection and 80% of the dose during the second injection at 12-24h interval.
Drug preparation procedures
GnRH IIa will be supplied by DelTaq Fish Health LLC as a sterile, lyophilized powder in a multi-use container. GnRH IIa will be supplied in 25mg/vial.
10mL of sterile physiological saline solution can be added to the 25mg vial to obtain a Stock Solution concentration of 2500 µg/mL.
To obtain 50mL at 20 µg/mL, dilute 0.4mL of Stock Solution into 49.6mL of sterile physiological saline solution.
To obtain 50mL at 80 µg/mL, dilute 1.6mL of Stock Solution into 48.4mL of sterile physiological saline solution.
Permissible concomitant therapy
Since efficacy data are being collected during the INAD process, there should be little or no concomitant therapy. Preferably, there should be no other therapy during a period extending from 2 weeks prior to treatment to 2 weeks after treatment. Investigators must be prepared to make no changes in fish cultural procedures or environmental conditions, and apply no other hormone therapy once a decision has been made to conduct GnRH IIa treatment. However, if concomitant therapy is required in order to protect/propagate valuable fish stocks, it should be fully documented and the efficacy data from the GnRH IIa treatment involved should be appropriately labeled.
An exception to this concomitant therapy is that the MS222 and Aqui-S 20E anesthetics may be used to sedate fish prior to GnRH IIa treatment. If an anesthetic is used please note which one was used in Form GnRH IIa-3 under the description of results section. Note: the withdrawal time must be followed for whichever anesthetic was used.
XII. TREATMENT RESPONSE PARAMETERS
The collection and reporting of source data begin with the decision to treat valuable fish based on hatchery records or other pertinent species information indicating treatment is warranted. Daily morbidity and mortality records, case history records, as well as any extenuating or mitigating circumstances that may affect treatment response need to be documented. All pertinent treatment response parameters should be reported on Form GnRH IIa-3. Treatment response parameters that should be addressed include the following:
Primary Parameters
The primary response parameter for evaluating the effect of GnRH IIa on fish will be whether a fish is “ripe” or “non-ripe” following treatment. In the case of females, ripe fish are those that have released their eggs in response to normal artificial spawning procedures. Non-ripe fish have not released eggs. With respect to data reporting under this INAD, eggs will only be collected one time from individual fish.
Secondary Parameters
Secondary response parameters for females will include percent hatch.
Secondary parameters may also include general observations on fish behavior and response to routine culture/handling activities. This would include such responses as apparent level of stress, negative fish behavior, etc.
Adverse Reactions
Any adverse reaction that occurs during the study period (whether considered/suspected to be treatment-related or not) should be reported immediately to the Study Monitor, who will in turn notify the Study Director. Such responses might include extremely negative responses/behavior by the fish or hazards to the applicator. Although GnRHIIa has been used with beneficial effect in fish culture and a preliminary TAS has been conducted showing no effects of 5x the dose, it is possible adverse reactions may occur under certain environmental conditions or with respect to specific species/strains of fish. Carefully observe all treated fish for any signs of any adverse reaction to treatment. The Investigator should carefully document all observations of adverse reactions. If any signs of drug toxicity are detected, they should also be documented and immediately reported to the Study Monitor, who will in turn notify the Study Director.
Note: Investigators are strongly encouraged to record observations/comments with respect to all phases of treatment. This may include a description of events before, during, and post-treatment. All extenuating or mitigating treatment circumstances need to be described in detail. Such information is imperative so that accurate study/data analysis can be performed.
Mortalities and Moribund Fish
Any fish that die or are euthanized during the study period should undergo a complete necropsy. Necropsy should include examination of the implant site. Necropsy results should be recorded on Form GnRH IIa-4N: Necropsy Report Form. If it appears that fish died due to handling stress that needs to be reported in the GnRH IIa Form 3: Results Report.
XIII. FORMS FOR DATA COLLECTION
When the Study Protocol has been approved and treatments are scheduled, the Investigator at each facility covered by the GnRH IIa INAD will need to complete the following forms:
Form GnRH IIa-W. Worksheet for Designing Clinical Field Trials under INAD
13-345 - located in the New Study Request tab
Form GnRH IIa-1. Report on Receipt of Drug - Guide for Reporting
Investigational New Animal Drug Shipments for Poikilothermic Food Animals - located in the Manage/View Drug Inventory tab
Form GnRH IIa-2. Drug Inventory Form for use of GnRH IIa under
INAD 13-345 - located in the Manage/View Drug Inventory tab and filled out in Form GnRH IIa - 3 to show use
Form GnRH IIa-3. Results Report Form for use of GnRH IIa under INAD 13-345 –
located in the Active Studies table on the home page
Form GnRH IIa-4N. Necropsy Report - located in Form GnRH IIa - 3
Copies of these forms are attached to this Study Protocol. Actual reporting is
accomplished on forms located in the online INAD database.
XIV. RECORD KEEPING PROCEDURES
As stated immediately above, all data reporting are accomplished via forms located in the online INAD database. All current and completed studies conducted under the investigator account will be stored and available in the online INAD database to the current study monitor, study investigator, and AADAP.
Animals that die during treatment should be disposed of by burial or incineration. Fish will be able to be released 1 day after last injection; follow the MS222 or Aqui-S 20E withdrawal time if it is used to sedate fish at time of injection.
GnRH IIa will be used only in the manner and by the individuals specified in the Study Protocol. If any unused or outdated GnRH IIa remains at the end of the study period, Investigators should contact Study Monitors for instructions regarding drug disposal. Drug disposal information is available in the Safety Data Sheet (SDS) located in Appendix IV of this protocol. Disposition of all GnRH IIa must be properly recorded and accounted for on the Chemical Use Log (Form GnRH IIa -2). The Study Monitor will be responsible for verifying the quantity of GnRH IIa remaining on hand versus the amount indicated on Form GnRH IIa-2. The investigational drug may not be redistributed to others not specified by the protocol and should not be retained by the Investigator after completion of the study (note: unless GnRH IIa is planned for use in another approved field trial, and planned usage is within the storage guidelines established by the manufacturer).
Drug distribution
See Section VII.A.6. Accountability for information and details.
Study Monitors
Study Monitors are generally fish health professionals with experience in diagnosing and treating fish diseases, and the ability to monitor overall fish health with respect to ongoing fish culture practices. A study monitor will be selected by each facility that is authorized to treat fish with GnRH IIa. A list of Study Monitors, along with addresses and phone numbers, can be found in Appendix II. Study Monitors are responsible for supervision of the trials, adherence of the Investigator to the Study Protocol, and inspection of the site.
Special equipment and materials
Most of the equipment and materials required for this study (with the exception of the GnRH IIa itself) are already available at each participating fish hatchery. In recent years, induced final gamete maturation has become a fairly common occurrence at many broodstock facilities. Fish hatchery managers (i.e., Investigators) are well trained and well equipped to handle these situations (see Appendix IIIb). If any additional equipment or materials are required, they will be provided by the Study Monitors (See Section VII.B. Items needed for sample collection, observations, etc.).
Administrator of the drug
GnRH IIa will be administered directly by the assigned Investigator (fish hatchery manager) or under the Investigator's direct supervision (see Appendix IIIa for names). GnRH IIa will be maintained in a secure location, and only the Investigator or a person under his/her direct supervision will have access.
Drug accountability records
See protocol Section VII.A.6. Accountability for details and the following forms will be used as guides for data collection: Forms GnRH IIa-W, GnRH IIa-1, GnRH IIa-2, GnRH IIa-3, and GnRH IIa- 4N.
Recording observations
The Investigator or a person under his/her direct supervision will be responsible for implementing the Study Protocol, making observations, collecting samples, and recording data during the clinical field trials. After the data have been collected and recorded on the forms, the Investigator will send the data to the Study Monitors who will ensure that all required information is provided. The Study Monitors will in turn send the data to the Study Director. The Study Director will analyze and summarize the data and prepare a report that will be submitted to the FDA. Note: If the Study Monitor does not think all required information has been provided, or forms have not been satisfactorily completed, he/she should contact the Investigator and rectify the situation before forwarding the package to the Study Director.
Data storage
The Investigator is responsible for complete and accurate data collection, and must complete all required data forms (see Section XIII). The Investigator should forward all completed forms to the Study Monitor for review. Study Monitors should carefully check each set of data for accuracy and completeness. If a form is incomplete or inaccurate, it should be returned to the Investigator. If a form is complete and accurate, it should be forwarded to the Study Director at the AADAP Office. Note: data that is entered through the online INAD database will be archived in the database. These archived forms will be available as long as the study participant accounts remain open.
Data analysis will be completed by the Study Director located at the AADAP Office. Data from the treatment year will be summarized through tabulation and appropriate statistical analysis. INAD reports will be prepared and submitted to the FDA as required. This submission may include a request for an extension of the INAD based on the data collected during that year. When sufficient data are collected, the entire INAD data set will be summarized in a final report for submission to support a full NADA.
A signed copy of the Study Protocol must be retained by each Investigator. At any time before the study begins, desired changes in the Study Protocol should be brought to the attention of the Study Director. The desired changes will be fully described in the form of an amendment along with the reason for the change. The amendment will be signed by the Sponsor (or its representative) and forwarded to FDA for review. Copies of the signed amendment will be attached to each copy of the Study Protocol. Investigators will be liable for non-compliance violation if drugs are used without a Study Protocol or in a manner different than specified in the Study Protocol, if forms are not filed on time, or if the study data are not properly collected, maintained, and reported. The Study Monitor is responsible for ensuring that all INAD procedures are being followed as defined by the Study Protocol.
Deviations from the established Study Protocol occasionally cannot be avoided. If deviations occur, the Study Monitor should be notified immediately. Protocol deviations should be fully documented and should be accompanied by a written explanation of what happened, why, and what steps were taken to mitigate the deviation. Deviation statements should be documented on Form GnRH IIa-3 in the Description of Results section and in the Study Deviation field.
The contents of this document do not have the force and effect of law and are not meant to bind the public in any way. This document is intended only to provide clarity to the public regarding existing requirements under the law or agency policies.
Zohar, Yonathan & Mylonas, Constantinos. (2001). Endocrine manipulations of spawning in cultured fish: From hormones to genes. Aquaculture. 197. 99-136. 10.1016/S0044-8486(01)00584-1.
Appendix I. Sponsor Contact Information for GnRH IIa INAD #13-345
Sponsor: Dr. Marilyn Blair, U.S. Fish and Wildlife Service, Aquatic Animal Drug Approval Partnership (AADAP) Program
Phone: (406) 994-9904
Fax: (406) 582-0242
Email: [email protected]
Sponsor Address: 4050 Bridger Canyon Road, Bozeman, MT 59715
Study Director: Ms. Bonnie Johnson
Aquatic Animal Drug Approval Partnership
(AADAP) Program
Phone: (406) 994-9905
Fax: (406) 582-0242
Email: [email protected]
Principal Clinical Field
Trial Coordinator: Ms. Paige Maskill
Aquatic Animal Drug Approval Partnership
(AADAP) Program
Phone: (406) 994-9911
Fax: (406) 582-0242
Email: [email protected]
Appendix II. Study Monitors for GnRH IIa INAD #13-345
Note: This information will be provided directly to CVM
Appendix IIIa. Facilities and Names of Investigators
Participating under GnRH IIa INAD #13-345
Note: This information will be provided directly to CVM and DelTaq Fish Health LLC
Appendix IIIb. Sample of Knowledge Required for Position of Hatchery Manager (i.e. Investigators)
Professional knowledge of all facets of fishery biology as well as the ability to apply new scientific findings, developments, and advances toward the resolution of critical propagation problems involving the rearing a variety of fish species under a variety of water quality conditions, water temperatures, water chemistry, etc.
Knowledge of general bacteriology, parasitology, and water chemistry sufficient to treat fish for various diseases.
Skill in interpreting biological observations and ability to draw sound conclusions from available data.
Skill in developing and coordinating available resources to ensure effective management and utilization of manpower, equipment, and funds relative to established priorities and needs.
Skill in coordination of sometimes divergent resource issues to obtain common objectives, including interaction with other Federal, State, Tribal, and private agencies/facilities.
Knowledge of and skill in the use of effective management and supervisory techniques to provide support, guidance, and motivation to hatchery staff.
Appendix IV. Safety Data Sheet (SDS) for GnRH IIa INAD #13-345
See the following 8 pages for the SDS from the supplier.
SAFETY
DATA
SHEET
SECTION 1: Identification of the substance
Product identifiers
Product name : GnRHIIa (Gonadotropin Releasing Hormone II Analogue)
(Des-Gly10, D-Arg6, Pro-NHEt9)-GnRHII
Product Number : 013060
Brand : DelTaq Fish Health
CAS-No. : 145940-57-4
Identified uses : For Use as Spawning Aid in Female Ictalurid Catfish
Company : DelTaq Fish Health LLC
Telephone : +1 425 629 8099
Fax : +1 425 629 8095
Emergency Phone # : CHEMTREC 24 HOUR EMERGENCY NUMBER:
1-800-424-9300
SECTION 2: Hazards identification
Classification of the substance or mixture
GHS Classification in accordance with 29 CFR 1910 (OSHA HCS)
Reproductive toxicity (Category 2), H361
For the full text of the H-Statements mentioned in this Section, see Section 16.
Pictogram
Signal word Warning Hazard statement(s)
H361 Suspected of damaging fertility or the unborn child.
Precautionary statement(s)
P201 Obtain special instructions before use.
P202 Do not handle until all safety precautions have been read and understood.
P281 Use personal protective equipment as required.
P308 + P313 IF exposed or concerned: Get medical advice/ attention.
P405 Store locked up.
P501 Dispose of contents/ container to an approved waste disposal plant.
SECTION 3: Composition/information on ingredients
3.1 Substances
Formula : C64H79N19O12 . xC2H4O2 . yH2O
Molecular weight : 1,306.44 g/mol
CAS-No. : 145940-57-4
-
Component
Classification
Concentration
(Des-Gly10, D-Arg6, Pro-NHEt9)-GnRHII
Repr. 2; H361
<= 100 %
For the full text of the H-Statements mentioned in this Section, see Section 16.
SECTION 4: First aid measures
Description of first aid measures General Advice
Consult a physician. Show this safety data sheet to the doctor in attendance. Move out of dangerous area.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in section 11
No data available
SECTION 5: Firefighting measures
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Carbon oxides, Nitrogen oxides (NOx)
Wear self-contained breathing apparatus for firefighting if necessary.
No data available
SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
For personal protection see section 8.
Prevent further leakage or spillage if safe to do so. Do not let product enter drains.
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.
For disposal see section 13.
SECTION 7: Handling and storage
Precautions for safe handling
Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.
For precautions see section 2.2.
Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature -20 °C
Storage class (TRGS 510): 6.1D: Non-combustible, acute toxic Cat.3 / toxic hazardous materials or hazardous materials causing chronic effects
Apart from the uses mentioned in section 1.2 no other specific uses are stipulated
SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Contains no substances with occupational exposure limit values.
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.
Personal protective equipment Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye
protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Body Protection
Impervious clothing, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Where risk assessment shows air-purifying respirators are appropriate use a full- face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. Do not let product enter drains.
SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
Appearance Form: solid
Odor No data available
Odor Threshold No data available
pH No data available
Melting
point/freezing point
Initial boiling point and boiling range
No data available No data available
Flash point No data available
Evaporation rate No data available
Flammability (solid, gas)
Upper/lower flammability or explosive limits
No data available No data available
Vapor pressure No data available
Vapor density No data available
Relative density No data available
Water solubility No data available
Partition coefficient: n-octanol/water
Auto-ignition temperature
Decomposition temperature
No data available No data available No data available
No data available
SECTION 10: Stability and reactivity
Reactivity
No data available
Stable under recommended storage conditions.
No data available
No data available
Strong oxidizing agents
Hazardous decomposition products formed under fire conditions. - Carbon oxides, Nitrogen oxides (NOx)
Other decomposition products - No data available. In the event of fire: see section 5
SECTION 11: Toxicological information
11.1 Information on toxicological effects
Acute toxicity: No data available
Inhalation: No data available Dermal: No data available
Skin corrosion/irritation
No data available
Serious eye damage/eye irritation
No data available
Respiratory or skin sensitization
No data available
Germ cell mutagenicity
No data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.
ACGIH: No component of this product present at levels greater than or equal to 0.1% is identified as a carcinogen or potential carcinogen by ACGIH.
NTP: No component of this product present at levels greater than or equal to 0.1% is identified as a known or anticipated carcinogen by NTP.
OSHA: No component of this product present at levels greater than or equal to 0.1% is on OSHA’s list of regulated carcinogens.
Reproductive toxicity
Presumed human reproductive toxicant May cause reproductive disorders.
No data available
Specific target organ toxicity - single exposure
No data available
Specific target organ toxicity - repeated exposure
No data available
Aspiration hazard
No data available
Additional Information
SECTION 12: Ecological information
Toxicity
No data available
No data available
No data available
No data available
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
No data available
SECTION 13: Disposal considerations
13.1 Waste treatment methods Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material.
Contaminated packaging
Dispose of as unused product.
SECTION
14: Transport information DOT (US)
Not dangerous goods
IMDG
Not dangerous goods
IATA
Not dangerous goods
SECTION
15: Regulatory information SARA 302 Components
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.
SARA 313 Components
This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.
SARA 311/312 Hazards
Chronic Health Hazard
SECTION
16: Other information Further information
The above information is believed to be correct but does not claim to be all inclusive and shall be used only as a guide. The information in this document is based on the present state of our knowledge and is applicable to the product with regard to appropriate safety precautions. It does not represent any guarantee of the properties of the product. DelTaq Fish Health shall not be held liable for any damage resulting from handling or from contact with the above product.
Version: 1.0 Revision Date: 03/19/2020 Print Date: 03/19/2020
Appendix V. Investigational Label for GnRH IIa INAD #13-345
1. Investigational label for tests in vitro and in laboratory research animals [511.1(a)]:
"Caution. Contains a new animal drug for investigational use only in laboratory animals or for tests in vitro. Not for use in humans."
2. Investigational label for use in clinical field trials [511.1(b)]:
"Caution. Contains a new animal drug for use only in investigational animals in clinical field trials. Not for use in humans. Edible products of investigational animals are not to be used for food unless authorization has been granted by the U.S. Food and Drug Administration or by the U.S. Department of Agriculture."
Appendix VIa. Fish Species Treated under GnRH IIa INAD #13-345
Female Ictalurids (catfish)
Appendix VIb. Table of Facilities and Fish Stocks Treated under GnRH IIa INAD #13-345
Note: This information will be provided directly to CVM
All data must be entered through the online INAD database:
The following forms are to be used as a guide for collecting data that will be entered
into the online INAD database. Any paper forms that are submitted to AADAP will be
sent back to the study participants.
Form GnRH IIa-W: Worksheet for Designing Clinical Field Trials under GnRH IIa INAD 13-345
INSTRUCTIONS
1. Investigator must fill out Form GnRH IIa-W for each trial conducted under this INAD before actual use of GnRH IIa.
2. Investigator should forward a copy of GnRH IIa-W to the Study Monitor for review.
3. After review, the Study Monitor should forward a copy to the AADAP Office for review and assignment of a Study Number.
SITE INFORMATION
Facility |
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Address |
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Investigator |
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Reporting Individual (if not Investigator) |
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Phone |
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Fax |
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FISH CULTURE AND DRUG TREATMENT INFORMATION
Fish species to be treated |
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Average fish size (in) |
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Average fish weight (gm) |
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Number of treated females |
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Number of control females |
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Anticipated date of treatment |
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Estimated total amount of drug for proposed treatments (mg) |
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Intended GnRH IIa dosage (µg/kg) |
Females |
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Method of administration |
IP Injection |
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Number of injections per fish |
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Injection Interval (hrs) |
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Drug manufacturer |
DelTaq Fish Health LLC |
Drug lot number |
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STUDY DESIGN: Provide a brief description of your planned study. The description should include the reason you feel fish should be treated, the treatment dates, the number of fish that will be treated, and if the fish are a threatened or endangered species.
Study designed by |
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DISPOSITION OF TREATED FISH (Human Food Safety Considerations):
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Estimated time (days) from last treatment day to first possible harvest for human consumption. |
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Investigator should initial here to indicate awareness that fish disposition must be in compliance with FDA-mandated withdrawal times as described in Section XV of the Study Protocol. |
WORKER SAFETY CONSIDERATIONS:
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Investigator should initial here to indicate that all personnel handling drug have read the Safety Data Sheet for GnRH II analog and have been provided protective equipment, in good working condition, as described in the SDS. |
Date Prepared: |
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Investigator: |
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Date Reviewed: |
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Study Monitor: |
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Form GnRH IIa-1: Report on Receipt of Drug - Guide for Reporting
Investigational New Animal Drug Shipments for Poikilothermic Food
Animals
INSTRUCTIONS
1. Investigator must fill out Form GnRH IIa-1 immediately upon receipt of GnRH IIa.
2. Investigator should forward a copy of Form GnRH IIa-1 to the Study Director at the AADAP Office
The sponsor, U.S. Fish and Wildlife Service, submits a notice of claimed investigational exemption for the shipment or delivery of a new animal drug under the provisions of Section 512 of the Federal Food, Drug, and Cosmetics Act. The following information is submitted to FDA:
|
Name of Drug |
GnRH IIa |
INAD Number |
13-345 |
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Proposed Use of Drug |
To act as a spawning aid in a variety of fish species. |
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Date of CVM Authorization Letter |
03/12/2020 |
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Source of Drug |
DelTaq Fish Health LLC |
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Date of Drug Receipt |
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Amount of Drug Received (mg) |
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Drug Lot Number |
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Study Worksheet Number |
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Name of Investigator |
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Address of Investigator |
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Location of Trial |
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Approximate Number of Treated Animals |
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Study Protocol Number |
13-345 |
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Approximate dates of trial (start/end) |
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Species, Size, and Type of Animals |
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Maximum total dose |
100 g/Kg body weight |
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Methods of Administration |
IP Injection |
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Withdrawal Period |
1 day after last injection; follow MS222 or Aqui-S 20E withdrawal time if it is used to sedate fish at time of injection |
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Date Prepared: |
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Investigator: |
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Date Reviewed: |
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Study Monitor: |
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Date Reviewed: |
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Sponsor: |
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Form GnRH IIa-2: Drug Inventory Form
For Use in GnRH IIa Clinical Field Trials Conducted under GnRH IIa INAD 13-345
INSTRUCTIONS
1. Investigator should initiate a new form GnRH IIa-2 immediately upon receipt of each shipment of GnRH II analog.
Each lot number of GnRH IIa may be used for multiple treatment regimens.
Qty of GnRH IIa from Reporting
previous page (MG) Facility individual
Date |
Amount of new GnRH IIa received (mg) |
Lot number of GnRH IIa received |
Study Number |
Amount of GnRH IIa used in treatment (mg) |
GnRH IIa transferred (mg) |
GnRH IIa discarded (mg) |
GnRH IIa remaining on hand (mg) |
Inventory by (Initials) |
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xxxx |
xxxx |
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xxxx |
xxxx |
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xxxx |
xxxx |
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xxxx |
xxxx |
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xxxx |
xxxx |
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xxxx |
xxxx |
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xxxx |
xxxx |
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xxxx |
xxxx |
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xxxx |
xxxx |
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xxxx |
xxxx |
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Date Prepared: |
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Investigator: |
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Date Reviewed: |
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Study Monitor: |
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STUDY NUMBER |
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Form GnRH IIa-3: Results Report Form
For Use in GnRH IIa Clinical Field Trials Conducted under GnRH IIa INAD 13-345
INSTRUCTIONS
1. Investigator must fill out Form GnRH IIa-3 no later than 10 days after completion of the study period. Attach lab reports and other information.
2. If GnRH IIa was not used under the assigned Study Number, contact the Study Director at the AADAP Office to close-out the study.
3. Investigator should forward a copy of Form GnRH IIa-3 to the Study Monitor. Within 10 days of receipt, the Study Monitor should forward a copy to the Study Director at the AADAP Office.
SITE INFORMATION
Facility |
|
Reporting Individual |
|
FISH CULTURE AND DRUG TREATMENT INFORMATION
Drug lot number |
|
Total amount drug used (mg) |
|
Fish species treated |
|
Water temperature (oF) |
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Drug dosage - females (µg/kg body wt) |
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Treatment date(s) |
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Average fish weight (gm) |
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Average fish length (in) |
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Number of treated females |
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Number of control females |
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Method of administration |
IP Injection |
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Number of injections per fish |
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Injection Interval (hrs) |
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Spawning/evaluation interval (time from treatment until spawning) |
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Spawning/evaluation date(s) |
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Hormone Results Record
INSTRUCTIONS
“Ripe” females are those fish that have released their eggs in response to normal artificial spawning procedures. “Non-ripe” fish have not released eggs.
Use Additional copies of this form for additional treatment days
Be sure the facility name is written here:
-
GnRH IIa TREATED FISH - Females
CONTROL FISH - Females
Date Treated
Date Evaluated
Ripe
Non-ripe
% Hatch
Date Evaluated
Ripe
Non-ripe
% Hatch
RESULTS: Describe in detail treatment results. Was treatment successful? If treatment did not appear to be successful, explain why not? Were there any mitigating environmental conditions that may have impacted treatment results? Were there any deviations from the Study Protocol? Attach pathology reports; Both Pre-and Post-Treatment.
Toxicity observations: Report any apparent drug toxicity including a description of unusual fish behavior.
OBSERVED WITHDRAWAL PERIOD OF TREATED FISH:
|
Number of days before human consumption. Ensure this time period meets the withdrawal period described in Section XV of the Study Protocol. |
NEGATIVE REPORT GnRH IIa analog was not used at this facility under this Study Number during the reporting period. (The study will be closed out in the online INAD database.)
Date Prepared: |
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Investigator: |
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Date Reviewed: |
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Study Monitor: |
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Study Number:____________________ Page 1 of 1
Form GnRH IIa-4N: Necropsy Report Form
For Use in GnRH IIa Clinical Field Trials Conducted under INAD 13-345
INSTRUCTIONS
1. Investigator must fill out Form GnRH IIa-4N for all fish that die or are euthanized during the study period. Use a new copy of Form GnRH IIa-4N for each individual fish.
2. Submit all Form GnRH IIa-4Ns with appropriate Form GnRH IIa-3s.
Date _____________ Fish Species/ID ________________________ Fish Length (cm) ________
Evaluator(s): __________________________________
Body surface: normal excess mucus irregular color other ____________________
Dermal lesion: none hemorrhagic other _________________________________
closed open
Location: dorsal caudal ventral lateral cranial
base of fin - Pectoral (right), Pectoral (left), Adipose, Dorsal, Anal, or Caudal
Gills: normal pale hemorrhagic other ____________________________
Liver: normal pale mottled other _________________________________
Spleen: normal pale enlarged other _______________________________
Kidney: normal pale swollen other _________________________________
____________________________________________________________________________________
Notes and comments of gross pathologies on other organs and tissues.
eyes ________________________________ stomach _______________________________
body cavity ___________________________ gastrointestinal tract ______________________
gall bladder ___________________________ gas bladder _____________________________
adipose tissue ___________________________ musculature ____________________________
implant site___________________________________________________________________________
other________________________________________________________________________________
____________________________________________________________________________________
Investigator: ____________________________ Date: _______________
NOTICES
Paperwork Reduction Act
In accordance with the Paperwork Reduction Act (44 U.S.C. 3501 et seq.), the U.S. Fish and Wildlife Service collects information necessary to permit the use of an investigational new animal drug to generate data to support a new animal drug approval (NADA) as part of the Fish and Aquatic Conservation fish health network. Your response is voluntary, but is required to obtain or retain a benefit. According to the Paperwork Reduction Act of 1995, an agency may not conduct or sponsor and a person is not required to respond to a collection of information unless it displays a currently valid OMB control number. OMB has approved this collection of information and assigned Control No. 1018-####.
ESTIMATED BURDEN STATEMENT
We estimate public reporting for this collection of information to average 4 hours, including time for reviewing instructions, gathering and maintaining data, and completing and reviewing the form. Direct comments regarding the burden estimate or any other aspect of the form to the Service Information Clearance Officer, Fish and Wildlife Service, U.S. Department of the Interior, 5275 Leesburg Pike, MS: PRB (JAO/3W), Falls Church, VA 22041-3803, or via email at [email protected]. Please do not send your completed form to this address.
FREEDOM OF INFORMATION ACT STATEMENT
Information provided to the Service is generally subject to release to the public under the Freedom of Information Act (FOIA). Certain information, however, may be subject to withholding if the Service determines that the information is a trade secret and/or commercial or financial information that is privileged or confidential. To the extent you are submitting business information that falls into one of these categories, you must clearly mark this information as "Business Confidential" in order for the Service to assess the applicability of FOIA Exemption 4. Any information provided by you that is not marked as “Business Confidential” will be considered releasable to the public under the FOIA [43 CFR 2.26 – 2.33].
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