# Presentation: 042677

## Transgenic Fish Developments:Are Transgenic Fish & Shellfish in Our Future?

- John C. Matheson III
- Office of Surveillance and Compliance
- Center for Veterinary Medicine
- US Food & Drug Administration

**Notes:**
Good morning.  I’d like to especially thank Dan McGovern for inviting me to speak with you about transgenic fish.  

Soon, if not already, excited researchers and entrepreneurs will be offering you an array of genetically modified fish with improved production and disease resistance characteristics that they claim will improve your profitability.  How does one evaluate such claims? 

I want to spend a little time: 1) putting transgenic fish in the context of other biotech products that are regulated at FDA, 2) summarize the areas the Center for Vet Medicine considers in approving (or not) transgenic fish with animal drug modifications, 3) summarize what other Federal agencies have to do with aquaculture, and 4) suggest some areas that you, as producers and potential customers for transgenic fish or shellfish, may want to consider in directing these researchers and entrepreneurs towards products that you need and want.

## Biotech Products & CVM

- Modified Plants as Feed Components
- Microbial Products as New Animal Drugs 		& Feed Components
- Non-Heritable Gene Therapies - New 			Animal Drug Products
- Modified Animal Varieties as New Animal 		Drugs

**Notes:**
At CVM, we regulate animal feeds, feed components, and animal drugs. We see biotechnology products in 4 broad areas.

The very successful GM plants, like Round-up Ready cotton, produce animal feed components that are evaluated for safety through a consultation process.

Microbial fermentation products may be either new animal drugs or animal feed ingredients, depending on the indications and claims. This technology is becoming well-established.

Gene therapy is an offshoot of human gene therapy experimentation and is in its infancy for animal uses.

GM animals with heritable expression of chemicals for harvest and also animals that express animal drugs substances for improved animal health or productivity are actively being developed.

## Products not Process

*	*
*	**	**No new statutes are needed.*
*	**	**Products of biotechnology can be accommodated under the same regulatory systems that already exist.*

**Notes:**
FDA and the rest of the federal government regulates by product categories, not by the manufacturing methods. Product regulation is ingrained throughout the US regulatory systems, in their authorizing statutes and regulations.

Products creating using biotechnology fit into existing product categories (sometimes with some effort). For example, new drug products for humans made from biopharm transgenic animals are regulated as human drugs. 

## Products not Process

- FDA Regulates Products
- Animal Drugs Include:
- articles for use in the diagnosis, cure, mitigation, treatment, or prevention of disease (e.g., antibiotics, NSAIDs)

**Notes:**
Animal Drugs are defined by the Food, Drug and Cosmetic Act to include two categories: one dealing with therapeutic uses of drugs and the second:

## Products not Process

- Animal Drugs Include:
- articles (other than food) intended to affect the structure or any function of the body of animals (e.g., production drugs and hormones, anesthetics, contraception)

**Notes:**
Drugs that have to do with increasing the productivity of animals or management aids assist in efficient handling of animals. These are generally referred to as “production drugs”. As a group these have been more controversial than therapeutic categories.  

## What Does CVM Look At?

- For Each Animal Drug or Drug-like GM Agronomic Animal Variety
- Food Safety
- Environmental Safety
- Target Animal Safety
- Effectiveness / Claims
- Quality Controls
- Labeling / Promotion

**Notes:**
CVM approves animal drugs before they may be legally marketed. For each product we look at a number of technical areas:

## Products not Process

- Animal Drugs Do Not Include:
- Vaccines against animal diseases
- Food for animals (except medicated feed)
- Articles added to food to add functionality, e.g, to improve nutrition, to improve color, to improve shelf life - These may be food additives, color additives, GRAS substances, etc.

## Products not Process

- Animal Drugs Do Not Include:
- Clones
- Triploids, Tetraploids
- Intrageneric Crosses
- Genetic Screening Techniques
- GM Laboratory Animals (e.g., mice, 			zebra danios)

## Examples of Approved Animal Drugs

- Recombinant Bacterial Fermentations
-  	rBST for Dairy Cows (1993)
-  Competitive Exclusion Products
-  Preempt (1998)

**Notes:**
Injectable, recombinant bovine somatotropin, AKA bovine growth hormone, was approved by CVM in 1993. It has about a 30% market penetration in the US today.  Canada and Europe have refused to approve the product, even though they can find no food safety reason to support their rejection.

Growth hormone is one of the more prominently mentioned transgenic fish genetic modifications being investigated.  Surprisingly, some parts of the Canadian government are supporting this research. Are there any analogies between BST for dairy cows and transgenic fish with added GH genes?

Competitive exclusion products are cultures of live bacteria that, when established in the gut of farm animals, prevent colonization by pathogenic bacteria. When these products carry disease prevention claims, they are animal drugs.  Expect to see more of these in the future.

## Biotech = New Drug Delivery Methods

- Protein Hormone Growth Promoters Can Be 	Delivered By:
- Injection of the protein, e.g, rbST
- Somatic Cell Therapy = some cells are GM to produce the hormone
- Heritable GM = all cells contain the gene to produce the hormone, including eggs and sperm

**Notes:**
For example adding growth hormone to a cow can be accomplished through use of BST injections, gene therapies, or by germ-line modification (making a transgenic variety).  It all amounts to adding an animal drug, but the conditions are different - dose, areas of the body where the drug is released,  opportunity for a withdrawal time, etc.  People continue to discuss this, but absent a special law for regulating transgenic animals, the Federal government is directed to apply the existing laws.  The animal drug provisions of the FFDCA best fit most of the transgenic fish being investigated now. Others will no doubt come along that could be looked at as containing food additives, vaccines, nutritional supplements. The rule for the Federal government is and has been for over a decade that we regulate the product not the process.

## Transgenic Animals with Agronomic Traits

- None Approved Yet - Many Considered to		Contain Animal Drugs in the US
- Increased Growth Rate, Resistance to 		Diseases - of most interest to researchers
- Fish and Shellfish Most Amenable to 		Current Level of Technology
- Situation Changing Rapidly

**Notes:**
Many of the modifications that are being investigated involve the addition of animal drug substances, under the current US laws. Development of site specific gene insertion and animal genome projects could change the scope of potential genetic modifications to yield more desirable products than currently.

## What Does FDA Do With Aquaculture?

- Drugs for Aquacultured Organisms
- Feed Ingredients, Animal Feed Additives
- Food Additives, Color Additives for Human 	Food Derived from Aquaculture
-  Monitoring for Residues, Intentional and 		Environmental
- Seafood Inspection / HACCP

**Notes:**
Now let’s summarize who regulates what with aquaculture.

## What Does USDA Do With Aquaculture?

- Vaccines
- Research
- Cooperative Extension to Farmers
- Development of Export Markets

## What Does EPA Do With Aquaculture?

- Pesticides for Use Around Aquaculture 		Facilities
- Effluent Quality from Aquaculture Facilities

## What Will You Look At?Some Possibilities Include:

- Types of Modifications Desired
- Management Changes Required for Each
- Costs vs. Other Approaches
- Multiple Modifications?
- Customer Reaction - Market Effects
- Industry-Wide or Each Producer?
- Gene Pool / Breed Registry?

**Notes:**
CVM does not exercise any control over the direction that research may take, its usefulness in the marketplace, its cost efficiency, aesthetic acceptability to consumers, or on whether genetic resources for the future will be preserved.

You, as the customers for biotechnology products and as food producers and marketers, can and do affect the types of biotechnology products developed for your industry.  I encourage you to be an active participant in planning for the future of biotechnology in your industry.  

## END

- CVM’s Website is www.fda.gov/cvm