Lecture 3: Drug Regulation & Adverse Drug Reactions

What organization is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation's food supply, cosmetics, and products that emit radiation?

FDA

What organization regulates veterinary biologics (vaccines, bacterins, antisera, diagnostic kits, and other products of biological origin) to ensure that the veterinary biologics available for the diagnosis, prevention, and treatment of animal diseases are pure, safe, potent, and effective?

APHIS

What organization is responsible for the protection of human health and the environment?

EPA

Who is involved in the drug approval process?

• FDA – Food and Drug Administration

• CVM – Center for Veterinary Medicine (FDA)

• FFDCA – Federal Food, Drug, and Cosmetic Act (Gives FDA legal authority to regulate)

• NADA – New Animal Drug Application

• OMUMS – Office of Minor Use and Minor Species Animal Drug Development

• ONADE – Office of New Animal Drug Evaluation

How does the drug approval process start?

with an idea from a sponsor: entity or individual responsible for collecting and submitting info to the FDA

What process do the CVM and sponsor guide a drug through?

the new animal drug application process (NADA)

What does the NADA process insure?

• Safety to the animal
• Safety to the products made from the treated animal
• Effectiveness of the drug
• The drug does not have an adverse environmental impact
• The drug is safe to the people administering or coming into contact with the drug

What are the 5 major sections of NADA?

• Target Animal Safety: Identifies harmful side effects, Establishes margin of safety

• Effectiveness: Demonstrates drug works as suggested (dose, route, etc)

• Human Food Safety: Toxicology, residue chemistry, microbial food safety, analytical method

• Chemistry, Manufacturing, and Controls: Ingredients, facility, packaging, storage

• Environmental Impact:Environmental impact, sometimes excluded

The sponsor presents NADA packet to _____ who approves if the information submitted by the sponsor meets the requirements for approval. After approval → notice published in federal register and sponsor can now sell drug.

FDA

How determines if veterinary oversight is necessary for safe and effective use of a drug (OTC or Rx/VFD)?

FDA

What is ANADA?

abbreviated new animal drug application for generic animal drugs: sponsor proves to the CVM that the generic copy is the same as the approved brand name animal drug with respect to: active ingredient, strength, dosage form, and dosage regimen and route of admin

What is conditional approval?

reasonable expectation of effectiveness, but not substantial evidence allowing company to sell drug while gathering more evidence

What are type A ADRs?

expected but exaggerated pharmacologic or toxicologic responses to a drug

What are type B ADRs?

reactions are unexpected responses that are unrelated to the drug's normal pharmacological effects

• They are dose-independent, unpredictable and idiosyncratic.

• Type B ADRs include allergic and pseudoallergic (non-immunological) reactions

What are type C ADRs?

occur from prolonged drug administration (ex. iatrogenic hyperadrenocorticism seen in dogs from chronic prednisone use)

What are type D ADRs?

occur sometime after treatment with the causative drug and therefore may be difficult to diagnose

What are type E ADRs?

• Type E for (End of Treatment) ADRs occur when drug treatment is discontinued abruptly.

• This is usually related to the development of pharmacodynamic tolerance and the oppositional process that suddenly go unopposed

What are type F ADRs?

Type F or (Failure) ADRs occur with lack of expected efficacy

(ex. lack of antimicrobial efficacy due to the emergence of antimicrobial resistance in previously susceptible pathogens)

What are type G ADRs?

Type G (Gaffes) ADRs result from human error and mostly involve outright overdose

How do you submit AER?

FDA Approved or Indexed Product: Contact the company and directly report Or FDA Form 1932a

Unnapproved Drug: FDA Form 1932a

What should an AER include?

• Health of the animal before the event, including pre-existing medical problems

• Names and doses of drugs, vitamins, and supplements the animal has been given

• Veterinary examination findings, including specialist exams Test results (bloodwork, urinalysis, fecal exam, imaging, etc.)

• Current type and/or brand of food/feed and treats

• Follow-up information can be submitted if your animal’s health changes as a result of the event after your initial report

• Note: The identities of all persons and animals are held in strict confidence by FDA and are protected to the fullest extent of the law.

What is OTC status dependent on?

whether it is possible for “adequate directions for use” to be included with the drug, as interpreted by a layperson

Safe use for OTC includes:
• Safety to the animal
• Safety to the people administering the drug

• Safety of food products from the animal
• Safety to the environment

How are veterinary OTC drugs different than human OTC drugs?

• they undergo a full approval by the FDA

• human OTC drugs are not legal to give to an animal without the involvement of a veterinarian in a VCPR

What is mandated for Rx drug use at the federal level?

VCPR

What did the veterinary feed directive do?

• This affects medications used in feed and water

• Non-therapeutic indications, such as for growth promotion or feed efficiency, are eliminated

• Use of VFDs for growth promotion or feed efficiency would be extralabel and thus prohibited

What drugs are not affected by the VFD?

• Ionophores

• Bacitracins
• Coccidiostats

What is the FDA guidance for industry #263?

• In place in June 11, 2023

• OTC antimicrobials for veterinary species → RX label

  • Vendors can sell old stock until inventories are gone

  • No more OTC antimicrobials of medically important status

• Goal:

  • Improve risk of antimicrobial resistance

  • Ensure better animal health outcomes

  • Increase veterinary oversight