Investigational Drugs

Compounding

Most journals will not accept an article advocating the use of a drug clinically when it is made from bulk ingredients (i.e., raw chemical).  When a drug is made commercially, the researcher should use the commercial preparation (e.g., tab, cap, oral solution, etc) to do the investigation.  Yes, it is more expensive; however, you don't want a journal to reject your publication because of the source of the drug!

See the American Veterinary Medical Association (AVMA)'s viewpoint on Compounding: "Compounding: Are you following the rules?" (PPT).

Drugs Administered at the Owner's Home

California Department of Consumer Affairs
Board of Pharmacy
2013 Lawbook for Pharmacy (PDF)
Business and Professions Code
Chapter 9, Division 2 
Article 4: Requirements for Prescriptions 

Prescription Container - Requirements for Labeling

Section 4076

(a) A pharmacist shall not dispense any prescription except in a container that meets the requirements of state and federal law and is correctly labeled with all of the following:

  1. Except where the prescriber or the certified nurse-midwife who functions pursuant to a standardized procedure or protocol described in Section 2746.51, the nurse practitioner who functions pursuant to a standardized procedure described in Section 2836.1, or protocol, the physician assistant who functions pursuant to Section 3502.1, the naturopathic doctor who functions pursuant to a standardized procedure or protocol described in Section 3640.5, or the pharmacist who functions pursuant to a policy, procedure, or protocol pursuant to either Section 4052.1 or 4052.2 orders otherwise, either the manufacturer's trade name of the drug or the generic name and the name of the manufacturer. Commonly used abbreviations may be used. Preparations containing two or more active ingredients may be identified by the manufacturer's trade name or the commonly used name or the principal active ingredients.
  2. The directions for the use of the drug.
  3. The name of the patient or patients.
  4. The name of the prescriber or, if applicable, the name of the certified nurse-midwife who functions pursuant to a standardized procedure or protocol described in Section 2746.51, the nurse practitioner who functions pursuant to a standardized procedure described in Section 2836.1, or protocol, the physician assistant who functions pursuant to Section 3502.1, the naturopathic doctor who functions pursuant to a standardized procedure or protocol described in Section 3640.5, or the pharmacist who functions pursuant to a policy, procedure, or protocol pursuant to either Section 4052.1 or 4052.2.
  5. The date of issue.
  6. The name and address of the pharmacy, and prescription number or other means of identifying the prescription.
  7. The strength of the drug or drugs dispensed.
  8. The quantity of the drug or drugs dispensed.
  9. The expiration date of the effectiveness of the drug dispensed.
  10. The condition or purpose for which the drug was prescribed if the condition or purpose is indicated on the prescription.
    1. Commencing January 1, 2006, the physical description of the dispensed medication, including its color, shape, and any identification code that appears on the tablets or capsules, except as follows:
      1. Prescriptions dispensed by a veterinarian.
      2. An exemption from the requirements of this paragraph shall be granted to a new drug for the first 120 days that the drug is on the market and for the 90 days during which the national reference file has no description on file.
      3. Dispensed medications for which no physical description exists in any commercially available database.
    2. This paragraph applies to outpatient pharmacies only.
    3. The information required by this paragraph may be printed on an auxiliary label that is affixed to the prescription container.
    4. This paragraph shall not become operative if the board, prior to January 1, 2006, adopts regulations that mandate the same labeling requirements set forth in this paragraph.

(b) If a pharmacist dispenses a prescribed drug by means of a unit dose medication system, as defined by administrative regulation, for a patient in a skilled nursing, intermediate care, or other health care facility, the requirements of this section will be satisfied if the unit dose medication system contains the aforementioned information or the information is otherwise readily available at the time of drug administration.

(c) If a pharmacist dispenses a dangerous drug or device in a facility licensed pursuant to Section 1250 of the Health and Safety Code, it is not necessary to include on individual unit dose containers for a specific patient, the name of the certified nurse-midwife who functions pursuant to a standardized procedure or protocol described in Section 2746.51, the nurse practitioner who functions pursuant to a standardized procedure described in Section 2836.1, or protocol, the physician assistant who functions pursuant to Section 3502.1, the naturopathic doctor who functions pursuant to a standardized procedure or protocol described in Section 3640.5, or the pharmacist who functions pursuant to a policy, procedure, or protocol pursuant to either Section 4052.1 or 4052.2.

(d) If a pharmacist dispenses a prescription drug for use in a facility licensed pursuant to Section 1250 of the Health and Safety Code, it is not necessary to include the information required in paragraph (11) of subdivision (a) when the prescription drug is administered to a patient by a person licensed under the Medical Practice Act (Chapter 5 (commencing with Section 2000)), the Nursing Practice Act (Chapter 6 (commencing with Section 2700)), or the Vocational Nursing Practice Act (Chapter 6.5 (commencing with Section 2840)), who is acting within his or her scope of practice.

Dispensing Dangerous Drug in Incorrectly Labeled Container

Section 4077

(a) Except as provided in subdivisions (b) and (c), no person shall dispense any dangerous drug upon prescription except in a container correctly labeled with the information required by Section 4076.

(b) Physicians, dentists, podiatrists, and veterinarians may personally furnish any dangerous drug prescribed by them to the patient for whom prescribed, provided that the drug is properly labeled to show all information required in Section 4076 except the prescription number.

(c) Devices that bear the legend "Caution: federal law restricts this device to sale by or on the order of a _____," or words of similar meaning, are exempt from the requirements of Section 4076, and Section 111480 of the Health and Safety Code, when provided to patients in skilled nursing facilities or intermediate care facilities licensed pursuant to Chapter 2 (commencing with Section 1250) of Division 2 of the Health and Safety Code.

(d) The following notification shall be affixed to all quantities of dimethyl sulfoxide (DMSO) prescribed by a physician, or dispensed by a pharmacy pursuant to the order of a physician in California: "Warning: DMSO may be hazardous to your health. Follow the directions of the physician who prescribed the DMSO for you."

(e) The label of any retail package of DMSO shall include appropriate precautionary measures for proper handling and first aid treatment and a warning statement to keep the product out of reach of children.

False or Misleading Label on Prescription

Section 4078

(a)

  1. No person shall place a false or misleading label on a prescription.
  2. No prescriber shall direct that a prescription be labeled with any information that is false or misleading.

(b) Notwithstanding subdivision (a), a person may label a prescription, or a prescriber may direct that a prescription be labeled, with information about the drug that is false under either of the following circumstances:

  1. If the labeling is a necessary part of a clinical or investigational drug program approved by the federal Food and Drug Administration or a legitimate investigational drug project involving a drug previously approved by the federal Food and Drug Administration.
  2. If, in the medical judgment of the prescriber, the labeling is appropriate for the proper treatment of the patient.

(c) The furnisher of a prescription labeled pursuant to subdivision (b) shall make, and retain for three years from the date of making, a record stating the manner in which the information on the prescription label varies from the actual drug in the container and documenting the order of the prescriber to so label the container. The prescriber shall make, and retain for at least three years, a record of his or her order to so label the container.

California Department of Consumer Affairs
Board of Pharmacy
2013 Lawbook for Pharmacy (PDF)
Division 2, Chapter 9: Business and Professions Code
Article 12: Prescriber Dispensing

Veterinarian in Teaching Hospital May Dispense and Administer Dangerous Drugs and Devices; Requirements

Section 4170.5

(a) Veterinarians in a veterinary teaching hospital operated by an accredited veterinary medical school may dispense and administer dangerous drugs and devices and controlled substances from a common stock.

(b) The veterinary teaching hospital shall designate a pharmacist to be responsible for ordering the drugs for the common stock and the designated pharmacist-in-charge shall be professionally responsible to insure that inventories, security procedures, training, protocol development, recordkeeping, packaging, labeling, and dispensing occur in a manner that is consistent with the promotion and protection of the health and safety of the public.

(c) The veterinary teaching hospital's pharmacist-in-charge shall develop policies, procedures, and guidelines that recognize the unique relationship between the institution's pharmacists and veterinarians in the control, management, dispensation, and administration of drugs.

(d) The board may inspect a veterinary teaching hospital dispensing or administering drugs pursuant to this section.

Exceptions to Section 4170: Samples; Clinics; Veterinarians; Narcotic Treatment Programs; Certain Cancer Medications

Section 4171

(a) Section 4170 shall not prohibit the furnishing of a limited quantity of samples by a prescriber, if the prescriber dispenses the samples to the patient in the package provided by the manufacturer, no charge is made to the patient therefor, and an appropriate record is entered in the patient's chart.

(b) Section 4170 shall not apply to clinics, as defined in subdivision (a) of Section 1204 or subdivision (b) or (c) of Section 1206 of the Health and Safety Code, to programs licensed pursuant to Sections 11876, 11877, and 11877.5 of the Health and Safety Code, or to a prescriber dispensing parenteral chemotherapeutic agents, biologicals, or delivery systems used in the treatment of cancer.

Storage Requirements

Section 4172

A prescriber who dispenses drugs pursuant to Section 4170 shall store all drugs to be dispensed in an area that is secure. The Medical Board of California shall, by regulation, define the term "secure" for purposes of this section.

California Department of Consumer Affairs
Board of Pharmacy
2013 Lawbook for Pharmacy (PDF)
Division 10: Uniform Controlled Substances Act 
Chapter 5: Use of Controlled Substances
Article 1: Lawful Medical Use Other than Treatment of Addicts

Issuing Prescription: By Whom; For What Purpose; Quantity to Be Prescribed

Section 11210

A physician, surgeon, dentist, veterinarian, naturopathic doctor acting pursuant to Section 3640.7 of the Business and Professions Code, or podiatrist, or pharmacist acting within the scope of a project authorized under Article 1 (commencing with Section 128125) of Chapter 3 of Part 3 of Division 107, or registered nurse acting within the scope of a project authorized under Article 1 (commencing with Section 128125) of Chapter 3 of Part 3 of Division 107, or physician assistant acting within the scope of a project authorized under Article 1 (commencing with Section 128125) of Chapter 3 of Part 3 of Division 107, or naturopathic doctor acting within the scope of Section 3640.5 of the Business and Professions Code, or an optometrist acting within the scope of Section 3041 of the Business and Professions Code may prescribe for, furnish to, or administer controlled substances to his or her patient when the patient is suffering from a disease, ailment, injury, or infirmities attendant upon old age, other than addiction to a controlled substance.

The physician, surgeon, dentist, veterinarian, naturopathic doctor acting pursuant to Section 3640.7 of the Business and Professions Code, or podiatrist, or pharmacist acting within the scope of a project authorized under Article 1 (commencing with Section 128125) of Chapter 3 of Part 3 of Division 107, or registered nurse acting within the scope of a project authorized under Article 1 (commencing with Section 128125) of Chapter 3 of Part 3 of Division 107, or physician assistant acting within the scope of a project authorized under Article 1 (commencing with Section 128125) of Chapter 3 of Part 3 of Division 107, or naturopathic doctor acting within the scope of Section 3640.5 of the Business and Professions Code, or an optometrist acting within the scope of Section 3041 of the Business and Professions Code shall prescribe, furnish, or administer controlled substances only when in good faith he or she believes the disease, ailment, injury, or infirmity requires the treatment.

The physician, surgeon, dentist, veterinarian, or naturopathic doctor acting pursuant to Section 3640.7 of the Business and Professions Code, or podiatrist, or pharmacist acting within the scope of a project authorized under Article 1 (commencing with Section 128125) of Chapter 3 of Part 3 of Division 107, or registered nurse acting within the scope of a project authorized under Article 1 (commencing with Section 128125) of Chapter 3 of Part 3 of Division 107, or physician assistant acting within the scope of a project authorized under Article 1 (commencing with Section 128125) of Chapter 3 of Part 3 of Division 107, or a naturopathic doctor acting within the scope of Section 3640.5 of the Business and Professions Code, or an optometrist acting within the scope of Section 3041 of the Business and Professions Code shall prescribe, furnish, or administer controlled substances only in the quantity and for the length of time as are reasonably necessary.

Purchase of Controlled Substances by Hospital Without a Pharmacist for Emergencies; Conditions on Providing to Patients

Section 11211

In order to provide a supply of controlled substances as may be necessary to handle emergency cases, any hospital which does not employ a resident pharmacist and which is under the supervision of a licensed physician, may purchase controlled substances on federal order forms for such institution, under the name of such hospital, such supply to be made available to a registered nurse for administration to patients in emergency cases, upon direction of a licensed physician.

Obtaining and Using Controlled Substance for Research, Instruction, or Analysis; Conditions

Section 11212

Persons who, under applicable federal laws or regulations, are lawfully entitled to use controlled substances for the purpose of research, instruction, or analysis, may lawfully obtain and use for such purposes those substances classified in paragraphs (45) and (46) of subdivision (b) of Section 11054 of the Health and Safety Code, upon registration with and approval by the California Department of Justice for use of those substances in bona fide research, instruction, or analysis.

That research, instruction, or analysis shall be carried on only under the auspices of the individual identified by the registrant as responsible for the research. Complete records of receipts, stocks at hand, and use of these controlled substances shall be kept.

The Department of Justice may withdraw approval of the use of such substances at any time. The department may obtain and inspect at any time the records required to be maintained by this section.

Research Approval by a Research Advisory Panel

Section 11213

Persons who, under applicable federal laws or regulations, are lawfully entitled to use controlled substances for the purpose of research, instruction, or analysis, may lawfully obtain and use for such purposes such substances as are defined as controlled substances in this division, upon approval for use of such controlled substances in bona fide research, instruction, or analysis by the Research Advisory Panel established pursuant to Section 11480 and 11481.

Such research, instruction, or analysis shall be carried on only under the auspices of the head of a research project which has been approved by the Research Advisory Panel pursuant to Section 11480 or Section 11481. Complete records of receipts, stocks at hand, and use of these controlled substances shall be kept.

New Drugs for Investigational Use in Animals

Code of Federal Regulations (CFR)
Title 21: Food and Drugs
Part 500, Subpart C: Animal Drug Labeling Requirements

Labeling of animal drugs; misbranding

Section 500.51

(a) Among the representations on the label or labeling of an animal drug which will render the drug misbranded are any broad statements suggesting or implying that the drug is not safe and effective for use when used in accordance with labeling direction, or suggesting or implying that the labeling does not contain adequate warnings or adequate directions for use. Such statements include, but are not limited to:

  1. Any statement that disclaims liability when the drug is used in accordance with directions for use contained on the label or labeling.
  2. Any statement that disclaims liability when the drug is used under "abnormal" or "unforeseeable" conditions.
  3. Any statement limiting the warranty for the products to a warranty that the drug in the package contains the ingredients listed on the label.

(b) This regulation is not intended to prohibit any liability disclaimer that purports to limit the amount of damages or that sets forth the legal theory under which damages are to be recovered.

Any person wishing to obtain an evaluation of an animal drug liability disclaimer under this regulation may submit it to Division of Compliance, (HFV-230), Center for Veterinary Medicine, Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855. A supplemental NADA providing appropriately revised labeling shall be submitted for any approved new animal drug the labeling of which is not in compliance with this regulation.

Use of terms such as "tonic", "tone", "toner", or "conditioner" in the labeling of preparations intended for use in or on animals

Section 500.52

(a) The use of terms such astonic, tone, toner, and similar terms in the labeling of a product intended for use in or on animals implies that such product is capable of a therapeutic effect(s) and causes such a product to be a drug within the meaning of section 201(g) of the Federal Food, Drug, and Cosmetic Act. The unqualified use of such terms in a product's labeling fails to provide adequate directions and indications for use of such product and causes it to be misbranded within the meaning of section 502(a) and (f)(1) of the act. The termstonic, tone, toner, and similar terms may be used in labeling only when appropriately qualified so as to fully inform the user regarding the intended use(s) of the product.

(b) The unqualified use of the termconditioner and similar terms in the labeling of a product intended for use in or on animals implies that such product is capable of a therapeutic effect(s) and causes such a product to be a drug within the meaning of section 201(g) of the act. The unqualified use of such terms in a product's labeling fails to provide adequate directions and indications for use of such product and causes it to be misbranded within the meaning of section 502(a) and (f)(1) of the act. The termconditioner and similar terms may be used in labeling only when appropriately qualified so as to fully inform the user regarding the intended use(s) of the product. A product labeled as a "conditioner" or with a similar term can be either a food or drug depending upon the manner in which the term is qualified in the labeling to reflect the product's intended use.

(c) An article so qualified as to be represented as a drug must be the subject of an approved new animal drug application unless the use of the article under the conditions set forth in its labeling is generally recognized as safe and effective among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs.

Exemption from certain drug-labeling requirements

Section 500.55

(a) Section 201.105(c) of this chapter provides that in the case of certain drugs for which directions, hazards, warnings, and use information are commonly known to practitioners licensed by law, such information may be omitted from the dispensing package. Under this proviso, the Commissioner of Food and Drugs will offer an opinion, upon written request, stating reasonable grounds therefore on a proposal to omit such information from the dispensing package.

(b) The Commissioner of Food and Drugs has considered submitted material covering a number of drug products and has offered the opinion that the following drugs when intended for those veterinary uses for which they are now generally employed by the veterinary medical profession, should be exempt from the requirements of 201.105(c) of this chapter, provided that they meet the conditions prescribed in this paragraph. Preparations that are not in dosage unit form (for example, solutions) will be regarded as meeting the conditions with respect to the maximum quantity of drug per dosage unit if they are prepared in a manner that enables accurate and ready administration of a quantity of drug not in excess of the stated maximum per dosage unit:

  • Atropine sulfate. As an injectable for cattle, goats, horses, pigs, and sheep, not in excess of 15 milligrams per dosage unit; as an injectable for cats and dogs, not in excess of 0.6 milligram per dosage unit.
  • Barbital sodium. For oral use in cats and dogs, not in excess of 300 milligrams per dosage unit.
  • Epinephrine injection. 1:1,000. For cats, dogs, cattle, goats, horses, pigs, and sheep (except as provided in 500.65).
  • Morphine sulfate. As an injectable for dogs, not in excess of 15 milligrams per dosage unit.
  • Pentobarbital sodium. For oral use in cats and dogs, not in excess of 100 milligrams per dosage unit.
  • Phenobarbital sodium. For oral use in cats and dogs, not in excess of 100 milligrams per dosage unit.
  • Procaine hydrochloride injection. Containing not in excess of 2 percent procaine hydrochloride, with or without epinephrine up to a concentration of 1:50,000. For use in cats, dogs, cattle, goats, horses, pigs, and sheep.
  • Thyroid. For oral use in dogs, not in excess of 60 milligrams per dosage unit.

Code of Federal Regulations (CFR)
Title 21: Food and Drugs
Part 511: New Animal Drugs for Investigational Use

New animal drugs for investigational use exempt from Section 512(a) of the act

Section 511.1b: New animal drugs for clinical investigations in animals

(b) New animal drugs for clinical investigation in animals. A shipment or other delivery of a new animal drug or an animal feed containing a new animal drug intended for clinical investigational use in animals shall be exempt from section 512(a) and (m) of the act if all the following conditions are met:

  1. The label shall bear the statements: [Caution. Contains a new animal drug for use only in investigational animals in clinical 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. In the case of containers too small or otherwise unable to accommodate a label with sufficient space to bear the caution statements required by paragraph (a) or (b) of this section, the statements may be included on the carton label and other labeling on or within the package from which the new animal drug is to be dispensed.
  2. The person or firm distributing or causing the distribution of the new animal drug or animal feed containing a new animal drug shall use due diligence to assure that the new animal drug or animal feed containing a new animal drug will actually be used for tests in animals and is not used in humans.
  3. The person who introduced such shipment or who delivered the new animal drug or animal feed containing a new animal drug for introduction into interstate commerce shall maintain adequate records showing the name and post office address of the investigator to whom the new animal drug or animal feed containing a new animal drug is shipped and the date, quantity, and batch or code mark of each shipment and delivery for a period of 2 years after such shipment and delivery. Upon the request of a properly authorized employee of the Department at reasonable times, such records shall be made available for inspection and copying.
  4. Prior to shipment of the new animal drug for clinical tests in animals, the sponsor of the investigation shall submit in triplicate to FDA a "Notice of Claimed Investigational Exemption for a New Animal Drug" including a signed statement containing the following information:
    1. The identity of the new animal drug.
    2. All labeling and other pertinent information to be supplied to the investigators. When such pertinent information includes nonclinical laboratory studies, the information shall include, with respect to each nonclinical study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
    3. The name and address of each clinical investigator.
    4. The approximate number of animals to be treated (or if not available, the amount of new animal drug to be shipped).
    5. If the new animal drug is given to food-producing animals, the statement shall contain the following additional information:
      1. A commitment that the edible products from such animals shall not be used for food without prior authorization in accordance with the provisions prescribed in this section.
      2. Approximate dates of the beginning and end of the experiment or series of experiments.
      3. The maximum daily dose(s) to be administered to a given species, the size of animal, maximum duration of administration, method(s) of administration, and proposed withdrawal time, if any.
    6. If a sponsor has transferred any obligations for the conduct of any clinical study to a contract research organization, a statement containing the name and address of the contract research organization, identification of the clinical study, and a listing of the obligations transferred. If all obligations governing the conduct of the study have been transferred, a general statement of this transfer--in lieu of a listing of the specific obligations transferred--may be submitted.
  5. Authorization for use of edible products derived from a treated food-producing animal may be granted under the provisions of this section and when the following specified conditions are met, except that in the case of an animal administered any unlicensed experimental veterinary biological product regulated under the viruses, serums, toxins statute (21 U.S.C., chapter V, sec. 151et seq. ) the product shall be exempt from the requirements of this section when U.S. Department of Agriculture approval has been obtained as provided in 9 CFR 103.2. Conditional authorization may be granted in advance of identification of the name(s) and address(es) of the clinical investigator(s) as required by paragraph (b)(4)(iii) of this section. Information required for authorization shall include, in addition to all other requirements of this section, the following:
    1. Data to show that consumption of food derived from animals treated at the maximum levels with the minimum withdrawal periods, if any, specified in accordance with paragraph (b)(4)(v)(c ) of this section, will not be inconsistent with the public health; or
    2. Data to show that food derived from animals treated at the maximum levels and with the minimum withdrawal periods, if any, specified in accordance with paragraph (b)(4)(v)(c ) of this section, does not contain drug residues or metabolites.
    3. The name and location of the packing plant where the animals will be processed, except that this requirement may be waived, on request, by the terms of the authorization.[Authorizations granted under this paragraph do not exempt investigational animals and their products from compliance with other applicable inspection requirements. Any person who contests a refusal to grant such authorization shall have an opportunity for a regulatory hearing before FDA pursuant to part 16 of this chapter.]
  6. On written request of FDA, the sponsor shall submit any additional information reported to or otherwise received by him with respect to the investigation deemed necessary to facilitate a determination whether there are grounds in the interest of public health for terminating the exemption.
  7. The sponsor shall assure himself that the new animal drug is shipped only to investigators who:
    1. Are qualified by scientific training and/experience to evaluate the safety and/or effectiveness of the new animal drug.
    2. Shall maintain complete records of the investigations, including complete records of the receipt and disposition of each shipment or delivery of the new animal drug under investigation. Copies of all records of the investigation shall be retained by the investigator for 2 years after the termination of the investigation or approval of a new animal drug application.
    3. Shall furnish adequate and timely reports of the investigation to the sponsor.
  8. The sponsor:
    1. Shall retain all reports received from investigators for 2 years after the termination of the investigation or approval of a new animal drug application and make such reports available to a duly authorized employee of the Department for inspection at all reasonable times.
    2. Shall provide for current monitoring of the investigation by a person qualified by scientific training and experience to evaluate information obtained from the investigation, and shall promptly investigate and report to FDA and to all investigators any findings associated with use of the new animal drug that may suggest significant hazards pertinent to the safety of the new animal drug.
    3. Shall not unduly prolong distribution of the new animal drug for investigational use.
    4. Shall not, nor shall any person acting for or on behalf of the sponsor, represent that the new animal drug is safe or effective for the purposes for which it is under investigation. This requirement is not intended to restrict the full exchange of scientific information.
    5. Shall not commercially distribute nor test-market the new animal drug until a new animal drug application is approved pursuant to section 512(c) of the act.
  9. If the shipment or other delivery of the new animal drug is imported or offered for importation into the United States for clinical investigational use in animals, it shall also meet the following conditions:
    1. The importer of all such shipments or deliveries is an agent of the foreign exporter residing in the United States or the ultimate consignee, which person has, prior to such shipments and deliveries, informed FDA of his intention to import the new animal drug as sponsor in compliance with the conditions prescribed in this subdivision; or
    2. The new animal drug is shipped directly to a scientific institution with adequate facilities and qualified personnel to conduct laboratory or clinical investigations and is intended solely for use in such institutions and which institution has submitted a statement as sponsor of the investigation.
  10. The sponsor shall submit either a claim for categorical exclusion under 25.30 or 25.33 of this chapter or an environmental assessment under 25.40 of this chapter.

Food and Drug Administration (FDA)
Center for Veterinary Medicine
Program Policy & Procedure Manual (PPM)
Office of New Animal Drug Evaluation Reviewers Chapter: Requirements for Investigational New Animal Drug Exemptions

What is an Investigational New Animal Drug Exemption?

Section II

Statutory authority to exempt unapproved investigational new animal drugs from the requirements of an approved new animal drug application (NADA) or abbreviated new animal drug application (ANADA) is in section 512(j) of the Federal Food, Drug, and Cosmetic Act (the act). We often refer to this as an investigational exemption. This exemption makes it possible for unapproved new animal drugs to be shipped in interstate commerce for use by experts, qualified by scientific training and experience, to investigate their safety and effectiveness.

There are two sets of requirements for investigational exemptions. The regulations at 21 CFR part 511 include a set of requirements for exempting unapproved new animal drugs for tests in vitro and in laboratory research animals (21 CFR 511.1(a)) and a different set of requirements for unapproved new animal drugs used in clinical investigations (21 CFR 511.1(b)). These regulations allow sponsors to collect safety and effectiveness data needed to support the approval of new animal drug applications while at the same time protecting the public from unsafe residues of investigational new animal drugs in food.

Exemption Requirements for New Animal Drugs for Clinical Investigation

Section IV

For new animal drugs used in clinical investigations, the sponsor must establish an investigational new animal drug file ((J)INAD) and meet the requirements for an investigational exemption before shipping the drug in interstate commerce. An original (J)INAD will generally be established for each new chemical entity, species, combination, and dosage form.

The sponsor of a (J)INAD may be an individual or entity who plans to submit an application for approval (i.e., (A)NADA) following the completion of the investigation. The NCIE form submitted to the (J)INAD file must be signed by the sponsor or by an agent acting on behalf of the sponsor. Sometimes a sponsor will ask to establish a (J)INAD file for their investigational new animal drug without including an NCIE form with the submission. The exemption does not apply until an NCIE form is submitted.

In order to exempt a new animal drug for clinical investigational use from sections 512(a) and 512(m) of the act, we must have from the sponsor of the investigation the signed NCIE form in triplicate, or a signed statement containing the following information listed below. Note that we must have this information from the sponsor before each shipment of the new animal drug.

  1. The identity of the new animal drug.
  2. Copies of all labeling and other pertinent information to be supplied to the investigators.
  3. The name and address of each investigator.
  4. The approximate number of animals to be treated and the number of control animals. If this information is not available, the amount of new animal drug to be shipped must be provided.
  5. If the new animal drug is given to food-producing animals, also include:
    • A commitment that edible products from investigational animals will not be used for food without prior authorization from us;
    • Approximate dates of the beginning and end of the experiment or series of experiments; and
    • The maximum daily dose(s) to be administered to a given species, the size of animal, maximum duration of administration, method(s) of administration, and proposed withdrawal time, if any.
  6. A statement containing the name and address of the contract research organization (CRO) (if any) to which the sponsor has transferred any obligation(s) for the conduct of the clinical investigation, identification of the study or studies involved, and a listing of the obligation(s) transferred.

Furthermore, the requirements below must also be met for an investigational new animal drug to qualify for the exemption:

  1. The label of the new animal drug must bear the statements:
  2. CAUTION: Contains a new animal drug for use only in investigational animals in clinical 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.

    If it is a bulk substance for use in the manufacture of a new animal drug for investigational use, it must bear the following labeling statement:

    CAUTION: For manufacturing, processing, or repacking in preparation of a new animal drug limited by Federal law to investigational use.

  3. If the product container is too small to accommodate a label with sufficient space to bear the caution statements, the statements may be included on the carton label and other labeling on or within the package from which the new animal drug will be dispensed.
  4. The person distributing the new animal drug will use due diligence to assure that it will actually be used for tests in animals and is not used in humans.
  5. The person distributing the new animal drug will maintain adequate records for each shipment of the new animal drug for a period of two years after such shipments and make such records available to us, upon request.

Food and Drug Administration (FDA)
Center for Veterinary Medicine
Program Policy & Procedure Manual (PPM)
Section 4000 - Labeling
PPM Number 1240

Identification/Promotion of Product Approval

Section 301(l) of the Federal Food, Drug, and Cosmetic Act prohibits the use in labeling or advertising of any human drug or device "any representation or suggestion that approval of an application with respect to such drug or device is in effect." There is no such prohibition regarding animal drugs. The Center for Veterinary Medicine (CVM) is not opposed, in principle, to the appearance of such information on labels or labeling of, or in advertisements for, approved new animal drugs. However, all such additions to labels and package labeling must be submitted to CVM as a special DER to the approved new animal drug application. Promotional labeling for all approved products must be submitted for review at the time of initial dissemination. Prescription animal drug advertising must be submitted at the time of initial publication as currently required by 21 CFR 510.300.

Purpose: This document established CVM policy and provides guidance for reviewing submissions of sponsors interested in voluntarily placing the Food and Drug Administration (FDA) approval information on labels or package labeling or in using it in advertising or other promotional material for approved new animal drugs.

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Procedure for Center Recommended Labeling Changes

Purpose: The purpose of this guide is to provide information on labeling changes made through the supplemental approval process.

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Antibacterials Labeled for Secondary Infections

In the early 1950s, apparent success in reducing mortality in an unfamiliar turkey disease referred to as mud fever, blue comb, or transmissible enteritis, led researchers to believe that antibiotics and other drugs had a beneficial effect on the causative agent. Several drug products were subsequently approved with claims for prevention and treatment of the disease. Studies on the etiology of the disease extended over a 20-year period. In the early 1970s, the cause of the disease was determined to be a virus which is now generally recognized as a coronavirus.

Because of the above information and the fact that antibacterials are not known generally to affect virus infections, any beneficial effect is believed to result from reducing death loss from secondary bacterial infections caused by bacteria sensitive to the drug. Generally, there is little or no effect on the morbidity of the primary infection. This principle can be applied to all drug products labeled with the indications for use against viral infections or "associated" secondary infections.

Purpose: The purpose of this guide is to provide guidance for review of products intended to control secondary bacterial infections.

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Uniformity in Labeling

The basic purpose of labeling is to enable drugs to be used safely and effectively by lay persons in the case of OTC products, or by veterinarians in the case of prescription items. The user has a right to expect that the same sort of information will be given for all drugs with similar activities. For this reason, uniformity goes beyond the mere physical layout of the labeling. The approved labeling establishes the limits for journal advertising, promotional material, mailing pieces, and verbal representations by the drug firm's detail person. Because of this, a uniform approach to labeling is required.

Purpose: This guide provides criteria to facilitate the consistent and uniform application of policies relating to the review and evaluation of drug labels and labeling.

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General Policies for Animal Drug Label Review

Although the review of labels for compliance with certain mandatory requirements may appear to be somewhat mechanical, a knowledge of policy, precedent animal drugs, the Act and Regulations, currently accepted good veterinary medical procedures and the application of good judgment are all essential. Consultation with others within the Center/Agency and in other agencies is appropriate and necessary in some situations. (See CVM Guide 1240.2320, "Communication and Liaison with Other Centers and Agencies".)

Purpose: This guide sets forth the general policies to be used in the review and evaluation of labels for animal drug products.

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Therapeutic Use Directions for Medicated Feed and Drinking Water

Purpose: This guide establishes the Center's policy on therapeutic use directions for medicated feed and drinking water.

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Established Names

Drugs are often times known by various names which may be code names, chemical names, acronyms, innovator's names, trivial names, official names, compendial names and United States Adopted Names (USAN). Because of the number of drugs available, it is important that we establish a name which is familiar to everyone so we can have a common denominator when discussing a drug. The need for designating a single name for each drug is specified in Section 508 of the Federal Food, Drug, and Cosmetic Act. 21 CFR Part 299 provides regulations that interpret Section 508 of the Act.

Use of an established name, if there is one for a drug, is required by Section 502(e)(1) of the Act as information of the identity of a drug which may be distributed in different dosage forms under different brand or proprietary names by manufacturers or distributors.

Physicians and veterinarians may use or prescribe drugs by an established name instead of a brand name.

Purpose: This guide establishes the Center's policy on therapeutic use directions for medicated feed and drinking water.

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Food and Drug Administration (FDA)
Center for Veterinary Medicine
Program Policy & Procedure Manual (PPM)
Section 4100 - Drugs
PPM Number 1240

Sterility of Ophthalmic Products

In a statement of policy issued on September 1, 1964, the Food and Drug Administration ruled that liquid preparations offered or intended for ophthalmic use that are not sterile may be regarded as adulterated within the meaning of section 501(c) of the FFDCA, and, further, may be deemed misbranded within the meaning of section 502(j) of the Act. On October 28, 1972, this ruling was extended to affect all preparations for ophthalmic use.

Purpose: The purpose of this guide is to clarify the Center's position regarding the sterility of ophthalmic products.

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Sterility and Pyrogen Requirements for Injectable Drug Products

Purpose: This guide describes CVM policy regarding sterility and pyrogenicity requirements of veterinary injectable drug products. All injectable veterinary drug products are sterile except euthanasia products and natural and synthetic steroid hormonal ear implants intended for use in bovine and ovine species. Pyrogen levels in sterile, injectable veterinary drug products are within established limits.

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Overformulation in Animal

Purpose: This guide establishes the policy and criteria for permitting overformulation of active drug ingredients in animal drug products.

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Policy on Sterilization of New Animal Drug Products and Containers by Irradiation

Sterilization by irradiation, in general, is permitted for use with drug products. The administration policy with regard to irradiated drugs is stated in 21 CFR 310.502(a)(11). This regulation addresses only human drug products. However, the policy is also applicable to drugs subject to Section 512 of the Federal Food, Drug, and Cosmetic Act (FFDCA) which includes drugs for animal use. There are no other specific regulatory requirements at this time for using this procedure.

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Extralabel Drug Use in Animals

Code of Federal Regulations (CFR)
Title 21: Food and Drugs
Part 530: Extralabel Drug Use in Animals

Veterinary records

Subpart A, Section 530.05

(a) As a condition of extralabel use permitted under this part, to permit FDA to ascertain any extralabel use or intended extralabel use of drugs that the agency has determined may present a risk to the public health, veterinarians shall maintain the following records of extralabel uses. Such records shall be legible, documented in an accurate and timely manner, and be readily accessible to permit prompt retrieval of information. Such records shall be adequate to substantiate the identification of the animals and shall be maintained either as individual records or, in food animal practices, on a group, herd, flock, or per-client basis. Records shall be adequate to provide the following information:

  1. The established name of the drug and its active ingredient, or if formulated from more than one ingredient, the established name of each ingredient;
  2. The condition treated;
  3. The species of the treated animal(s);
  4. The dosage administered;
  5. The duration of treatment;
  6. The numbers of animals treated; and
  7. The specified withdrawal, withholding, or discard time(s), if applicable, for meat, milk, eggs, or any food which might be derived from any food animals treated.

(b) A veterinarian shall keep all required records for 2 years or as otherwise required by Federal or State law, whichever is greater.

(c) Any person who is in charge, control, or custody of such records shall, upon request of a person designated by FDA, permit such person designated by FDA to, at all reasonable times, have access to, permit copying, and verify such records.

Limitations

Subpart B, Section 530.11

In addition to uses which do not comply with the provision set forth in 530.10, the following specific extralabel uses are not permitted and result in the drug being deemed unsafe within the meaning of section 512 of the act:

  1. Extralabel use in an animal of an approved new animal drug or human drug by a lay person (except when under the supervision of a licensed veterinarian);
  2. Extralabel use of an approved new animal drug or human drug in or on an animal feed;
  3. Extralabel use resulting in any residue which may present a risk to the public health; and
  4. Extralabel use resulting in any residue above an established safe level, safe concentration or tolerance.
Labeling

Subpart B, Section 530.12

Any human or animal drug prescribed and dispensed for extralabel use by a veterinarian or dispensed by a pharmacist on the order of a veterinarian shall bear or be accompanied by labeling information adequate to assure the safe and proper use of the product. Such information shall include the following:

  1. The name and address of the prescribing veterinarian. If the drug is dispensed by a pharmacy on the order of a veterinarian, the labeling shall include the name of the prescribing veterinarian and the name and address of the dispensing pharmacy, and may include the address of the prescribing veterinarian;
  2. The established name of the drug or, if formulated from more than one active ingredient, the established name of each ingredient;
  3. Any directions for use specified by the veterinarian, including the class/species or identification of the animal or herd, flock, pen, lot, or other group of animals being treated, in which the drug is intended to be used; the dosage, frequency, and route of administration; and the duration of therapy
  4. Any cautionary statements; and
  5. The veterinarian's specified withdrawal, withholding, or discard time for meat, milk, eggs, or any other food which might be derived from the treated animal or animals.
Extralabel use from compounding of approved new animal and approved human drugs

Subpart B, Section 530.13

  1. This part applies to compounding of a product from approved animal or human drugs by a veterinarian or a pharmacist on the order of a veterinarian within the practice of veterinary medicine. Nothing in this part shall be construed as permitting compounding from bulk drugs.
  2. Extralabel use from compounding of approved new animal or human drugs is permitted if:
    1. All relevant portions of this part have been complied with;
    2. There is no approved new animal or approved new human drug that, when used as labeled or in conformity with criteria established in this part, will, in the available dosage form and concentration, appropriately treat the condition diagnosed. Compounding from a human drug for use in food-producing animals will not be permitted if an approved animal drug can be used for the compounding;
    3. The compounding is performed by a licensed pharmacist or veterinarian within the scope of a professional practice;
    4. Adequate procedures and processes are followed that ensure the safety and effectiveness of the compounded product;
    5. The scale of the compounding operation is commensurate with the established need for compounded products (e.g., similar to that of comparable practices); and
    6. All relevant State laws relating to the compounding of drugs for use in animals are followed.
      
  3. Guidance on the subject of compounding may be found in guidance documents issued by FDA.
Extralabel drug use in nonfood animals

Subpart D, Section 530.30

(a) Because extralabel use of animal and human drugs in nonfood-producing animals does not ordinarily pose a threat to the public health, extralabel use of animal and human drugs is permitted in nonfood-producing animal practice except when the public health is threatened. In addition, the provisions of 530.20(a)(1) will apply to the use of an approved animal drug.

(b) If FDA determines that an extralabel drug use in animals not intended for human consumption presents a risk to the public health, the agency may publish in the Federal Register a notice prohibiting such use following the procedures in 530.25. The prohibited extralabel drug use will be codified in 530.41.

Drugs prohibited for extra label use in animals

Subpart E, Section 530.41

  1. The following drugs, families of drugs, and substances are prohibited for extralabel animal and human drug uses in food-producing animals
    1. Chloramphenicol;
    2. Clenbuterol;
    3. Diethylstilbestrol (DES);
    4. Dimetridazole;
    5. Ipronidazole;
    6. Other nitroimidazoles;
    7. Furazolidone;
    8. Nitrofurazone;
    9. Sulfonamide drugs in lactating dairy cattle (except approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine);
    10. Fluoroquinolones; and
    11. Glycopeptides
    12. Phenylbutazone in female dairy cattle 20 months of age or older
    13. Cephalosporins (not including cephapirin) in cattle, swine, chickens, or turkeys:
      1. For disease prevention purposes;
      2. At unapproved doses, frequencies, durations, or routes of administration; or
      3. If the drug is not approved for that species and production class.
  2. The following drugs, families of drugs, and substances are prohibited for extralabel animal and human drug uses in nonfood-producing animals: [Reserved]
  3. [Reserved]
  4. The following drugs, or classes of drugs, that are approved for treating or preventing influenza A, are prohibited from extralabel use in chickens, turkeys, and ducks:
    1. Adamantanes
    2. Neuraminidase inhibitors.