
 

 
 
 

 

HHS 
U.S. Department of Health and Human Services
   



U.S. Food and Drug Administration 
  



  A to Z Index


  Follow FDA


  En Español

 



Search FDA  Submit search  

                

 

  Popular Content


  Home


  Food


  Drugs


  Medical Devices


  Radiation-Emitting Products


  Vaccines, Blood & Biologics


  Animal & Veterinary


  Cosmetics


  Tobacco Products

    





Archived Content

The content on this page is provided for reference purposes only. This content 
has not been altered or updated since it was archived.



Search Archive  Submit archive search  
       
 

Vaccines, Blood & Biologics
  
    
  
  Home
   Vaccines, Blood & Biologics
   Blood & Blood Products
   Approved Products
    Licensed Products (BLAs)
  	 Fractionated Plasma Products
    
 
  


Finding of No Significant Impact Text - Atryn




  Share


  Tweet


  Linkedin


  Pin it

  More sharing options 
    Linkedin


    Pin it



  Email


  Print

 
FINDING OF NO SIGNIFICANT IMPACT

for

 the rBc6 rDNA Construct in GTC 155-92 Goats
Expressing Recombinant Human Antithrombin III (ATRYN)

 NADA 141-294

GTC Biotherapeutics, Inc.

 

The Center for Veterinary Medicine has carefully considered the potential 
environmental impact of this action and has concluded that this action will not 
have a significant effect on the quality of the human environment. Therefore, an 
environmental impact statement will not be prepared.

We have prepared the attached Environmental Assessment (EA) dated January 29, 
2009, in support of a new animal drug application (NADA) by GTC Biotherapeutics, 
Inc. (GTC) for the Bc6 rDNA construct in the GTC 155-92 lineage of goats that 
have been genetically engineered (GE) to express recombinant human antithrombin 
III (rhAT; tradename ATryn ® for use in humans or “ATRYN”)1 in the milk of 
lactating does. ATRYN will be manufactured in the form of a sterile, lyophilized 
powder for use in making a solution for intravenous infusion. A formulation of 
this recombinant protein2 is the subject of a biologics license application 
(BLA) that is currently under review by the Food and Drug Administration’s 
(FDA’s) Center for Biologics Evaluation and Research (CBER). This product is 
intended to treat patients with congenital antithrombin III (ATIII) deficiency 
to prevent life- threatening clot formation during high risk situations such as 
surgery and obstetrical procedures.

This EA focuses on the potential environmental effects of the GTC 155-92 GE 
goats and their waste products at, and around, the two sites where they are 
currently housed. The main site is the GTC farm in central Massachusetts where 
these goats are raised and a production herd of several hundred animals is used 
to produce ATRYN for use in humans. A secondary facility is located in central 
Pennsylvania where a small herd of a few dozen GTC 155-92 goats is held in 
reserve.

CBER will separately comply with its NEPA obligations arising from its review of 
the biologic license application submitted by GTC Biotherapeutics, Inc.

GTC has submitted extensive information to the FDA as part of its 
investigational new animal drug (INAD) file, new animal drug application (NADA), 
investigational drug application ( IND), and BLA. In addition, members of FDA’s 
staff inspected or site visited the GTC farm in Massachusetts on at least two 
occasions. Relevant information from all of these sources, as well as FDA’s 
reviews of the data and information provided by GTC were used in the EA.

General risk questions addressed in the EA include the following:
  What are the risks associated with the GE goats while under confinement?
  What is the likelihood that the GE goats will escape from confinement?
  What are the likely consequences should the GE goats escape from confinement?

GTC Massachusetts Farm

As indicated in the EA, the hazards and risks associated with GE animals in 
confinement are highly dependent on the gene expression product and the ability 
of the inserted gene construct to mobilize and spread to other animals. In the 
case of the GTC 155-92 goat production herd at the GTC farm in Massachusetts, 
the following environmental risks were identified and considered for the goats 
while under confinement:
  Risk of gene flow via mobilization of rDNA construct.
  Risk of direct toxicity resulting from increased environmental concentrations 
  of rhAT.
  Risk of disease spread from confined housing of 155-92 goats.
  Risks that may be associated with the disposal of GE animal wastes or 
  carcasses. 

CVM’s review indicates that the Bc6 rDNA construct is not likely to mobilize and 
spread to other organisms, and the gene product (rhAT) does not pose an 
intrinsic hazard; therefore, the GTC 155-92 lineage of goats in confinement is 
not likely to present any significant risk to the environment.

At least five levels of containment are present at the GTC farm to prevent the 
escape of the GTC 155-92 goats. Containment includes physical barriers (two 
separate fences), 24-hour security, daily checks by the farm’s veterinary staff, 
and video surveillance. In addition, all of the GTC 155-92 goats have redundant 
identification systems (ear tattoos, neck tags, and electronic transponders) 
that allow them to be identified easily and quickly. Taken as a whole, the 
containment and security systems insure that escape of any 155-92 GE goats from 
the GTC farm is highly improbable. In the unlikely event of an escape, the 
presence of redundant animal identification systems reduces the possibility that 
any of the goats will remain at large for an extended period of time.

As noted in the EA, assuming that one or more GTC 155-92 goats were able to 
escape the confines of the GTC farm, there is very little reason to believe that 
they would be able to survive, reproduce, or establish a population in the 
nearby environs, or that they would be able to migrate to another nearby habitat 
and do so. First, in order to establish a population, two or more animals would 
need to escape at approximately the same time, or interbreed with surrounding 
feral goats. Given the high value of these animals, and the intensive 
surveillance systems in place, escaped animals would likely be recaptured within 
a very short period of time and returned to the farm. In the unlikely event that 
the escaped animals were not recovered, the likelihood of long-term survival, 
reproduction and establishment is extremely low. First, there are no known 
populations of feral goats in the northeastern United States. Second, the harsh 
winter climate of Massachusetts makes the likelihood of survival after escape 
low. Finally, the presence of potential predator species (e.g., dogs, coyotes) 
makes survival and establishment highly improbable. Further, reproduction in the 
wild is particularly unlikely because adult male and female rhAT goats are 
housed separately on the GTC farm, and thus unlikely to escape at the same time 
should any escapes actually occur. In addition, there is no evidence to 
indicate, and little reason to hypothesize, that the addition of the Bc6 rDNA 
construct to their genome has increased their fitness and made these goats any 
more likely to establish in the wild than normal domesticated goats.

As discussed in the EA, even if one or more 155-92 GE goats were able to escape 
and survive for an extended period of time outside the GTC farm, it is hard to 
postulate any significant adverse effects that they might have on the local 
environment. In addition, there is no reason to believe that the Bc6 rDNA 
construct would spread to other populations of feral goats as there is no 
information available to indicate any feral goat populations exist in 
Massachusetts or nearby states. Interactions with domesticated goats in the 
vicinity of the GTC farm are also not expected because the GTC 155-92 goats 
would be quickly recognized by their ear tattoos and neck tags, captured, and 
returned to the GTC farm. In addition, there are no known livestock farms in the 
area surrounding the GTC farm; therefore, interactions with other domestic goats 
are unlikely.

Because the Bc6 rDNA construct is not mobilizable, even if interactions were to 
occur with domesticated animals or wildlife species in the area, there is no 
realistic pathway for the gene to spread to these animals. Direct transfer to a 
related species, such as sheep, is not expected as the offspring of goat-sheep 
matings are generally stillborn or die as embryos, and goats do not interbreed 
with any other species. Thus, the probability for the Bc6 rDNA construct to 
spread to any animals other than goats is negligible.

Pennsylvania Goat Facility

In almost all respects, conditions that affect the risk analyses described for 
the GTC farm in Massachusetts are similar or identical to those for the 
Pennsylvania goat-holding facility. Major differences between the two are in the 
number of GE goats (several hundred in Massachusetts versus several dozen in 
Pennsylvania) and in the production of milk containing rhAT (none is produced in 
Pennsylvania). The GE goat facility in Pennsylvania has a similar level of 
physical containment to the GTC farm in Massachusetts and the GTC 155-92 goats 
there are never allowed outside of their barn. Procedures for animal husbandry 
and to insure biosecurity are also very similar to those for the Massachusetts 
farm and the animal identification systems are identical for both. Disposal 
procedures for goat wastes are similar to, and generally equivalent, to those 
followed in Massachusetts. One additional major difference between the two 
facilities is in the disposal of animal carcasses. They are incinerated off-site 
in Massachusetts as opposed to being buried 6 feet underground and treated with 
lime in Pennsylvania; however, both are USDA-acceptable means of destruction and 
neither should present a risk to the environment because the gene construct does 
not pose an intrinsic hazard and is not likely to mobilize and spread.

An analysis of the available information indicates that the same conclusions 
should apply for the Pennsylvania facility as for the GTC Massachusetts farm 
with respect to the risks associated with confinement, the likelihood of escape, 
and likelihood of harm in the event that the 155-92 GE goats should in fact 
escape from confinement. The risks associated with confinement in Pennsylvania 
are minimal because the GE animals are identical and conditions of confinement 
are comparable to those at the farm in Massachusetts. Considering the high level 
of containment, the likelihood of escape at the Pennsylvania facility is also 
very low. As for the Massachusetts farm, in the unlikely event of an escape, the 
presence of redundant animal identification systems reduces the possibility that 
any of the goats will remain at large for an extended period of time. The 
environments surrounding both facilities are quite similar, largely wooded and 
semi-rural in nature. As in Massachusetts, coyotes are abundant in Pennsylvania 
and have caused significant losses in sheep/lamb flocks in the state. Therefore, 
should one or more of these animals escape, the likelihood for survival, 
reproduction and establishment of the 155-92 GE goats (or the probability they 
will cause adverse effects on the local environment) is very low and no greater 
in Pennsylvania than in Massachusetts.

Conclusion

There is adequate and substantial information available to conclude that GE 
goats in the GTC 155-92 lineage that contain Bc6 rDNA constructs are not 
expected to have a significant impact on the quality of the human environment 
when held under the current conditions of confinement at locations in 
Massachusetts and Pennsylvania.

 

___________________________                                           
________________________________________
  Date                                                                           
                            Steven D. Vaughn, D.V.M.
                                                                                 
              Director, Office of New Animal Drug Evaluation, HFV-100
 

Attachment:

Environmental Assessment for the Bc6 rDNA construct in GTC 155-92 Goats 
Expressing Recombinant Human Antithrombin III (rhAT or ATRYN); Dated January 29, 
2009

1 The approved international nonproprietary name ( INN) and United States 
Adopted Name (USAN) for this recombinant protein is antithrombin alfa. The FDA 
assigned proper name is antithrombin III (Recombinant).

2 The product tradename for the formulated dosage form of this protein is ATryn 
® for Injection. Per CVM’s convention, all proprietary names of drugs are 
written in upper case letters. In this case ATRYN is equivalent to ATryn ®.
 

 


Return to

  Approval History, Letters, Reviews and Related Documents - ATryn	[ARCHIVED] 
   
 


More inFractionated Plasma Products
   


Resources for You

  Approval History, Letters, Reviews and Related Documents - ATryn	[ARCHIVED] 
  ATryn 
 var maincontentcss = document.getElementById("middle_js"); if(maincontentcss) {
 maincontentcss.style.width = "71%"; }       


   Page Last Updated: 03/27/2015  
 Note: If you need help accessing information in different file formats, see 
Instructions for Downloading Viewers and Players.
 Language Assistance Available: Español | 繁體中文 | Tiếng Việt | 한국어 | Tagalog | 
Русский | العربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | 
Deutsch | 日本語 | فارسی | English	 




FDA


  Accessibility


  Careers


  FDA Basics


  FOIA


  No FEAR Act


  Site Map


  Nondiscrimination


  Website Policies

 




U.S. Food and Drug Administration
 10903 New Hampshire Avenue
 Silver Spring, MD 20993
 1-888-INFO-FDA (1-888-463-6332)
Contact FDA 

Subscribe to FDA RSS feeds Follow FDA on Twitter Follow FDA on Facebook View FDA 
videos on YouTube View FDA photos on Flickr 


   FDA Archive


   Combination Products


   Advisory Committees


   Regulatory Information


   Safety



   Emergency Preparedness


   International Programs


   News & Events


   Training & Continuing Education


   Inspections & Compliance



   Federal, State & Local Officials


   Consumers


   Health Professionals


   Science & Research


   Industry

 

Scroll back to top 
     


Popular Content

  Home

   
  Latest Recalls

   
  Report an Adverse Event

   
  MedWatch Safety Alerts


  News Releases


  Consumer Updates


  About FDA


  Contact FDA


  Browse by Product Area


  Product Areas

  back

    Food


    Drugs


    Medical Devices


    Radiation-Emitting Products


    Vaccines, Blood & Biologics


    Animal & Veterinary


    Cosmetics


    Tobacco Products

