Posted: December 16th, 2022

REGULATION OF INTENTIONALLY ALTERED GENOMIC DNA ANIMALS

Please follow the instructions, the format is very important. attached is:
1. instructions paper
2. grading
3. a sample paper from the lecture
4. the rule

Message from the teacher:
To talk briefly but in greater detail about assignment 4, I just want to emphasize the position from which you will be writing (mid-level staffer). Remember that this requires you to be objective; there should be no bias nor any preference shown towards “for” or “against” prior to your final recc. Your final recc. is the only place where you should demonstrate your inclination for one side over the other. Keep in mind that saying a rule is beneficial or conversely, detrimental, is not biased so long as you support your statement with relevant information from the comments that you choose.

Some of you will find that you will have some comments that are ultimately for the regulation, but suggest revision. The same goes for comments that are against the given regulation, but likewise recommend certain changes to be made. It is best that you find comments that are very clearly for or against. This is not to say that you cannot use a comment that makes such suggestions; you can, but you’ll need to think critically about why the commenter is making these suggestions. Be careful not to allow discussion of the suggested revision to potentially undermine your for/against argument.

Needless to say, it’s extremely important that you choose only comments from credible sources, and those that are relevant to your rule. You will use these comments in your final group paper, so you’ll want to make sure to invest the time to mine for these legitimate comments now.

Just to reiterate how to find comments for those of you who are unsure: go onto Dr. Beales’ Blackboard website and download the file labeled “potential rules” in the Syllabus section. There is a link for each rule. Clicking this link will take you to the federal regulation website, and for most of you, if you move your mouse along the toolbar on the left hand side, you’ll see a comment symbol with the option to read public comments. This is what you’ll want to click to be able to access these comments. Some of you might have to look up the comments for your rule on the website by copying and pasting either the Document Number or the RIN Number into the search bar. Try this out, and if you find you still have problems finding your comments, just shoot me an emai
115TH CONGRESS SENATE REPORT
2nd Session 104-341

REGULATION OF INTENTIONALLY ALTERED GENOMIC DNA ANIMALS ___________________________________________________________________________

APRIL 4, 2018 – Ordered to be printed
___________________________________________________________________________

[Insert full name], from the Senate Committee on [Insert Committee],
Submitted the following

REPORT ON COMMENTS

[To accompany, S. 1043]
The Senate Committee on FDA has looked at the guidelines by the FDA as well as the comments by various organizations and academia. The recommendation of the committee is that the regulation does not pass. This is because of evidence that questions its legality. Hence there is need for it to be reviewed.

PURPOSE OF PROPOSED RULE
The FDA released the Regulation of Intentionally Altered Genomic DNA animals on January 19, 2017. The draft was to clarify their stand on regulation of these animals. The methods used to modify their genome include random or targeted Change in their DNA sequence through methods such as Insertions, substitutions, deletions and nucleotide insertions (FDA, 2017). The regulations apply to both the parent animal in which the alteration is done initially as well as the lineage of these animals which contain the genomic alteration.
The regulations on genetically modified animals apply to domesticated pets, livestock that will be later consumed or for use in drug factories. These laws are not binding. However industry is expected to follow them closely in order to gain market approvals. The laws encompass details that the FDA will require to know about the identity of the animal, its characteristics, the biological process as well as their labelling(FDA, 2017). The Agency would also wish to know the safety and efficiency of use for the intended use of the animals. Consequently, the areas that will be studied include the environmental impacts that these animals will pose, the risks of these animals on animals and human health as well as safety questions that the producers may not have adequately addressed.
The rules are based on the Food, Drug and Cosmetic Act that is established under the Federal government. The law states that the DNA that is inserted on animals can be regulated as a new animal drug as documented in the 1938 law. Interpretation of this law envisions that when a single gene is inserted into two different animals that are of the same species(FDA, 2017). The result is the creation of two different forms of the same species. This is because DNA integrates itself randomly. The law is also of the case that the animal’s offspring needs to be subjected to regulations because it bears a resemblance to its parent.
ESTABLISHING THE DEBATE
Regulation of Intentionally Altered Genomic DNA animals is a topic that is of great interest to many Americans. Consequently, the issue has attracted a lot of comments both from individuals especially academia and organizations.
This review aims at looking at the comments on the proposed regulation. Certain quarters of society are for the proposed regulation while others are against it. Robert M. Califf M.D., and Ritu Nalubola, Ph.D. in their article FDA’s Science-based Approach to Genome Edited Products are for government intervention. Their opinion is that such a broad move is a step in the right direction to alter the genome of animals, plants and microorganisms to produce desired characteristics. The Consumer Union is in support of these regulations. They believe that genetically engineered animals need to go through rigorous assessments. While at the same time treating these animals as “New animal drugs.” Consequently, genetically modified animals should be treated just like other animals whose genetic has been engineered. The third comment which is in support of intervention is one by Alison Van Eenennaam. In his comment titled Will – And Should – Gene Edited Animals Be Regulated?

Other organizations are more informed about the issue and they feel it is not a step in the right direction. Those against intervention on these regulations include The Biotechnology Innovation Organization (BIO). The organization is tasked with carrying out research and development in the field of agriculture, healthcare, environmental and industrial biotechnology products. The second body is the Information Technology and Innovation Foundation (ITIF). The organization is of the opinion that the proposal is counterproductive and ill-considered because it doesn’t comply with principles enshrined in the U.S regulation for biotechnology products that was laid down back in 1986. The third body that is seeking intervention is the George Washington University (GWU). The body is of the opinion that the regulator’s approach that they are trying to mimic is also a failure.
COMMENTS FOR INTERVENTION
The Consumer Union is in agreement with the provisions of the FDA regulation. Their stand is that animals whose genomic DNA has been intentionally altered should be treated as a new drug (Hansen, 2017, p. 2). Consequently, there are established laws that should be used to address this issue. Where the animals are treated just like genetically engineered animals. These animals pose as new animal drugs because a safety assessment is necessary which is associated with new animal drugs.
One of the issues they raise in their argument is the use of recombinant DNA constructs. It implies therefore that genetic materials are gotten from different sources using the most modern technologies such as genome editing. The method introduces inheritable changes in the animals (Hansen, 2017, p. 3). The genetic material changes are however not covered by GFI #187. The FDA regulations however come out broadly on this issue whereby they propose covers already existing technology, emerging technology as well as future in road that may be made to alter the genome of animals.
The effects of gene editing techniques for example CRISPR-Cas9 remain unknown. Consequently, all gene-edited animals should be analysed via whole genome sequencing as well as incorporating epigenetic profiling so that off-target effects are established (Hansen, 2017, p. 5). There after several tests should follow such as proteomics, metabolomics and transcriptomics to determine the effects of modification of the animals. Furthermore, all genetically engineered animals need to be labelled. Such a move would ensure that there is transparency in addressing concerns by consumers as well as establishing post market health effects.
Robert M. Califf M.D., and Ritu Nalubola are biotechnologists who have weighed on the debate. Their take on the issues is that animals produced via genome editing, is in line with the views of the FDA (Robert, Califf, & Ritu 2017). The genome of animals that has been altered intentionally using modern genome editing techniques or via rDNA results in a drug. This is because the intention is to alter the function and structure of the animal. Hence there is need to regulate this move under the FDA regulations that are being proposed. Through research on industry they have established that industry is responsible in ensuring that products are safe and meet all requirements of law. Consequently, the regulations by FDA are not countering existing law but rather they are complementing them to ensure safe practices reign supreme.
The arguments by Alison Van Eenennaam are centred on his research on Dairy cows. The breeds include the Holstein which naturally grows horns. These animals are dehorned because they pose a threat to other cows or their care givers. Consequently, he has done research in this field whereby he has established that it is possible to produce cows that are genetically dehorned. This is by using horn free alleles from the Angus breed which is hornless (Eenennaam, 2018). The researchers take on the issue is that regulation on this science will be a step in the right direction more so the regulations that FDA want to establish.
This is because it would be unhealthy and illegal to sell an animal which is classified as being unsafe. In scenarios whereby the genetic of the breeding method remain unknown or are unclear. Gene editing introduces different transgenic and foreign rDNA that cannot be distinguished from natural variations and alleles (Eenennaam, 2018). If these changes remain unmonitored, the benefits that would have resulted from genetic engineering are likely not to be achieved.
COMMENTS AGAINST INTERVENTION
The Biotechnology Innovation Organization (BIO is of the opinion that FDA did not adhere to principles set forth by the White House Office of Science and Technology Policy of 1986. The policy states that the risk of a product is based is the nature of the product rather than the process used to produce it (BIO 2017, p. 4). Secondly, regulation should be commensurate to degree of risk. Consequently, the findings of the Coordinated Framework of 1986 should be the only basis on which analysis is to be done. Furthermore, it is on this basis that all future oversights of biology based products should be done.
Government intervention would therefore offer regulations based on certain fundamental principles. For instance, oversight should be done using a scope of discretion based on statutes and based on the evidence that risks presented is reasonable. Secondly, the characteristics of the organism should be used to determine whether the organism offers risks to the environment rather than relying on the technique used (BIO 2017, p. 7). The comment is of the view that new technologies in molecular modification increases the likelihood of producing better breeds. This is because the method utilises techniques that are more precise and efficient as compared to traditional cross breeds. The new breeds introduced have new phenotypic traits that do not offer risks to the environment just like their parent species. Furthermore if oversight were to be skewed on such technology it would lead to hindrance on development of a technology that was promising.
The organization is also against the intervention because they are not in line with the principles presented in the Organization of Economic Cooperation and Development (OECD) of 1995. Its main principles are that government intervention should only be carried out when the issue is of a high magnitude and such an issue can only by solved via government intervention. (BIO 2017, p. 15) In this case the problem can be solved via an understanding between academia and professionals in the field. Secondly, government intervention should only be carried out by first articulating the problem so that the problem is solved cost effectively without impeding innovation as the new regulation is doing. The issue at hand would be impeding on the milestones that have been achieved in the area of genome editing.
The regulation is of the view that there is a taxonomic relationship between the recipient animal and the gene that is introduced. But according to the comment by BIO, this is far from the truth. Since time immemorial there has been no evidence in this view (BIO 2017, p. 20). Scientists globally have strongly affirmed that risk relates to attributes of the product rather than the genetic modification.
ITIF has also weighed in on the issue. Their take is that the regulations are ill considered and are likely to be counterproductive. Furthermore, they feel that the regulations are non-compliant with the U.S regulation for biotechnology that was laid down back in 1986 (ITIF, 2017, p. 2). The FDA regulations, exempts inconsumable animals as well as other animals based on the Assessment of their risk factors from regulation. Despite this, the FDA is establishing laws for review and approvals of animals whose genomes have been altered using new technologies which were important in advancing the frontiers of research. This seems not to be reasonable.
The FDA has also done little to establish the relationship between hazards and their relationship to the environment or human health. If FDA is to exercise such authority over such a pertinent issue. Such a move is a takeover from longstanding U.S policy where authorities are required to provide persuasive case that clearly shows that there are associated hazards that would result because of failure to regulate (ITIF, 2017, p. 2). In the regulations there is no evidence for such an effort. For example the issue of gene edited mosquitoes is a case in point. The mosquito has been used to address diseases such as Dengue, Zika and Chikungunya.
In addressing this issue, FDA has been reluctant in regulating it and has consistently deferred with the Environmental Protection Agency (EPA). This is because the species does not play any role in any ecosystem on earth. In doing so, they by passed consultations that would have necessitated further regulatory action (ITIF, 2017, p. 3). Such a move would have been reasonable and consistent with existing practices especially in the field of molecular biology. Under number 187 in its guidance document, FDA has made it clear that the mosquitoes meet the definition of an “animal drug.” Despite this fact, FDA is defiant to regulate the gene edited variant used to suppress transmission of human disease. Consequently, credit for this should go to Congress.
The third organization that is against the intervention by government is the George Washington University (GWU). The argument that they rise is that the argument is a departure from the Coordinated Framework for regulation of Biotech of 1987 (GWU 2017, p. 3). The regulation aimed at regulating the product gotten from biotechnology based on the risks they pose rather than on how they are created. The regulation proposes modern technologies that exclude mutagenesis and phenotypic selection. Which would result in genome alterations that are random. Such a move would be a takeover from modern technologies which the guidance aimed at regulating.
FDA’s approach is widely seen to be imposing strict regulations on emerging technologies which were seen to offer new frontiers in the field of research. It would have led to many genetic combinations and more phenotypic outcomes. This is then combined with the fact that the guidance’s assertion of drugs in the FD&C Act under section 201 (g) is not identifiable (GWU 2017, p. 6). Furthermore, in most instances the alteration of the genome can result from other conventional practices of breeding.
Genome editing allows faster growth of animal breeds as compared to conventional animal breeding methods. The challenge that arises is that it would be difficult to scientifically distinguish between animals developed via genome editing and animals from conventional breeding practices (GWU 2017, p. 7). This is because the animals are identical except the method that was used to create them and might have been used several generation earlier. Intervention should therefore be on the basis of the method used to come up with the new strain or breed.
The GWU is also of the opinion that the Regulations come with additional costs that are not necessary. For instance the guidance has listed certain requirements that need to be applied before market approval. They include labelling and shipping of animals, disposition of animals and environmental considerations. In addition, there are other responsibilities such as information on source, identity and functionality of the edited genome (GWU 2017, p. 8). As well as post approval requirements such as drug registration, keeping of records and reports that are concerned with approval of products. All these factors have an associated cost which might be detrimental in research and diminish possibilities of propelling research.
Further observations by GWU show that the guidance is a departure from already existing federal policies in the field of biotechnology regulation which is not consistent with established policies. The comment takes references of President Clinton’s executive order number 12866 that was effected in 1993. The order states that agencies such as FDA should propose or adopt regulations only based on the intended benefits which also justify the cost (GWU 2017, p. 11). In the case of the FDA guidance, there is no evidence of such a determination.
The analysis of the economic viability has also been a key issue. The guidance, does not address risk reduction while at the same time justifying the cost. Moreover, the FDA has not done an economic viability study of the benefits as well as the costs of the guidance (GWU 2017, p. 13). Yet the Bill Clinton executive order 12866 requires such an analysis. The analysis would involve determining the negative effect of the regulation that it might have on development, marketing as well as use of the genome edited animals and hence address issues in environmental protection, health, nutrition and agriculture.
FINAL RECOMMENDATION
Based on the comments by the various organizations and academia it would be prudent and advisable for government not to intervene. The comments by BIO, ITIF and GWU analyse key areas of the Regulation of Intentionally Altered Genomic DNA animals. The take based on the three comments is that due procedure was not followed in coming up with the regulations such as President Clinton’s executive order number 12866, defers with the guidelines of EPA, the U.S regulation for biotechnology of 1986 as well as the principles of the Organization of Economic Cooperation and Development (OECD) of 1995. Consequently, the laws do not have a strong legal backing.
The regulations could water down the achievements of biotechnology. The regulations propose limitation of genome editing methods which would have expanded the frontiers of research. Furthermore, research on the adverse effects of genome edited animals are not known to have any adverse effects on the health of human beings, animals or have adverse effects on the environment. The move would be retrogressive in nature and may spell doom on a good technology that is biotechnology. The three organizations offer diversified viewpoints that have a solid backing of evidence against what the FDA is proposing. Consequently, the FDA needs to look into some of the comments that have been discussed along with those of other organizations and academia before these legislations are passed. So that the concerns of organizations, academia and consumers are addressed.

References
BIO. (2017, June 19). Docket Number: FDA-2008-D-0394: Regulation of Intentionally Altered Genomic DNA in Animals; Draft Guidance for Industry; Notice of Availability. Retrieved from https://www.bio.org/sites/default/files/2017%20BIO%20comments%20FDA%20CVM%20GFI%20%23187.pdf

Eenennaam, A. V. (2018, January 12). Will – And Should – Gene Edited Animals Be Regulated?. Retrieved from https://geneticliteracyproject.org/2017/02/08/will-gene-edited-animals-regulated/
FDA. (2017). Guidance for Industry Regulation of Intentionally Altered Genomic DNA in Animals
GWU. (2017, June 19). How to Regulate Genome-Edited Animals? A Comment on FDA’s Proposed Guidance | Regulatory Studies Center | The George Washington University. Retrieved from https://regulatorystudies.columbian.gwu.edu/how-regulate-genome-edited-animals-comment-fda%E2%80%99s-proposed-guidance

Hansen, M. (2017). Comments of Consumers Union to the Food and Drug Administration on the Notice of Availability: Regulation of Intentionally Altered Genomic DNA in Animals; Draft Guidance for Industry Docket No. FDA 2008-D-0394.
ITIF. (2017). FDA Must Revise Current Regulatory Proposal for Gene-Edited Animals.

Robert, M., Califf, M. D., & Ritu, N. (2017, January 18). FDA’s Science-based Approach to Genome Edited Products | FDA Voice. Retrieved from https://blogs.fda.gov/fdavoice/index.php/2017/01/fdas-science-based-approach-to-genome-edited-products/

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