I was updating a chapter I am writing about the regulations around genetically engineered (GE) animals, and both supporters and detractors of GE animals have criticisms of the US regulatory approach.
Criticisms from the biotech industry include:
• the approach is process-triggered rather than being based on the actual, relative risks (if any) associated with the novel phenotype or product as compared to those associated with conventional comparators.
• the process is prohibitively time consuming and expensive to complete all of the mandatory testing. AquaBounty has expended over $60 million in attempting to bring the AquAdvantage® salmon through the regulatory approval process thus far (David Frank, AquaBounty, pers. comm.), and still does not have authorization to market in the US.
• some tests are not based on unique risks (e.g. endogenous allergens), and the absence of a known tolerance level or natural levels of variability means regulatory studies are problematic to design and the results are ambiguous to interpret.
• unpredictable timeline.
• focus is only on risks, no consideration is given to potential benefits of the novel phenotype or product, nor are the risks associated with existing alternative approaches to genetic modification and breeding, or regulatory inaction, considered.
The following table outlines the key events in the timeline of the regulatory process for the AquAdvantage® salmon since its genesis over a quarter of a century ago in 1989. No other GE food animal has been approved anywhere else in the world.
|1989||The founder animal from which the AquAdvantage® line was derived was created by microinjection of the transgene into fertilized eggs of wild Atlantic salmon in Canada|
|1992||The AquAdvantage® line was created from the F1-progeny of the EO-1α line.|
|1995||AquaBounty technologies established an Investigational New Animal Drug (INAD) file with the Center of Veterinary Medicine (CVM) of the U.S. FDA to pursue the development of AquAdvantage® salmon.|
|2001||First regulatory study submitted by Aqua Bounty Technologies to U.S. FDA for a New Animal Drug Applications (NADA)|
|2008||U.S. FDA approves Aqua Bounty Canada as a manufacturing site for production of AquAdvantage® salmon eggs|
|2009||FDA guidance on how GE animals will be regulated
FDA approval of first GE animal pharmaceutical
Final AquAdvantage® regulatory study submitted to U.S. FDA.
U.S. FDA inspected and approved Aqua Bounty Panamá as an authorized site for the commercial production of AquAdvantage® salmon for purposes of export to the U.S.
|2010||September: FDA VMAC meeting on AquAdvantage® salmon|
|2011||Political efforts to prevent FDA from regulating GE salmon, ban GE salmon, delay regulatory approval|
|2012||FDA released finding of no significant impact “FONSI” environmental assessment|
|2015||November: US FDA AquAdvantage® Approval
AquaBounty expended over $60 million to bring the AquAdvantage® salmon through the regulatory approval process
|2016||January: US FDA issued a ban on the import and sale of GE salmon until FDA “publishes final labeling guidelines for informing consumers of such content”. The ban was the result of language Alaska Sen. Lisa Murkowski introduced into the 2016 fiscal budget, or omnibus, bill. It also authorizes “an independent scientific review” of the effects of GE salmon on wild salmon stocks and for human consumption.” Fact check investigated some of her claims about the salmon
March: a coalition of environmental, consumer, commercial and recreational fishing organizations sues US FDA over approval of GE salmon approval
May: Canadian Approval of AquAdvantage® for sale in Canada
December: FDA bills AquaBounty for $113,000 “Animal Drug” User Fee for their “approved” animal drug product despite continued FDA ban on the import and commercial sale of AquAdvantage® fillets
Criticisms from the activist industry include:
- lack of public participation and transparency – although the entire AquAdvantage data package was made publicly available.
- no consideration of socio-economic issues including ethics and moral concerns.
- concern about impartiality of the data because the regulatory review studies are being conducted by the company seeking approval of the GE animal.
- environmental risk is not given appropriate consideration as the National Environmental Policy Act is procedural in nature and does not give the FDA the authority to deny an application on environmental grounds.
- lack of mandatory process-based labels on food derived from GE animals, although the passage of the 2016 National Bioengineering Food Disclosure Law may pre-empt that concern.
The AquAdvantage® Atlantic salmon carries an “all fish” growth hormone chimeric gene. The rDNA construct consists of an antifreeze protein gene promoter from ocean pout linked to a chinook salmon growth hormone cDNA. It was envisioned that this construct would raise less public concern because of the “all-fish” nature of the rDNA construct and the fact that does not include any viral or selection marker sequences. Given the founder of this transgenic line was generated in 1989 and that the commercial product was first approved in December 2015, it is hard to argue that the mandatory process-based regulatory process encountered by the GE AquAdvantage® salmon created “an environment of certainty and confidence for researchers, industry and consumers” . It may even have convinced consumers that, since mandatory regulation is required, it must mean that this fast growing fish is somehow more intrinsically risky than conventionally bred fast growing salmon.
One thing is for certain – no small company or university can afford to try to get a GE animal application through regulatory given the unpredictability of the timeline and costs. The protracted regulatory evaluation of this fast-growing Atlantic salmon and uncertainty associated with the process and the timeline has had a chilling effect on investment and development of GE animals for food applications in the US.