In October of this year, EPA posted on its website, apparently with little fanfare or public notice, an updated and presumably final document entitled the “Algae Supplement to the Guidance Document Points to Consider in the Preparation of TSCA Biotechnology Submissions for Microorganisms.” The website indicates that this document supplements the original 1997 TSCA “Points to Consider” document for biotechnology notices under TSCA by addressing submissions involving R&D or commercial use of genetically engineered algae.
This guidance document is the culmination of a process that EPA first began in 2015. When the Agency issued its biotechnology regulations in 1997, it finalized an earlier-prepared document called “Points to Consider in the Preparation of TSCA Biotechnology Submissions for Microorganisms“, and this document has remained unchanged since that year, and has been used by submitters of Microbial Commercial Activities Notices (MCANs), TSCA Environmental Release Applications (TERAs) and other biotechnology filings under TSCA. Its guidance largely remains relevant, although it was written well before the advent of advanced genetic technologies now in widespread use such as synthetic biology and gene-editing tools, as well as before advances in nucleic acid sequencing technology made it routine to be able to provide detailed sequence information for all the introduced genetic modifications. I believe EPA has for some time been planning a general update of this document, but to my knowledge the “Algae” supplement is the only effort where proposed new guidance has been made available to the public.
The Points to Consider document, while applicable to all biotech submissions under TSCA, was heavily biased towards information needs for applications involving the most common industrially-used heterotrophic microorganisms, primarily including bacteria, yeast and other fungal species. In 2015, EPA first announced its intention to provide a companion document that would provide additional guidance for submissions involving genetically modified algae and cyanobacteria, which, as photosynthetic organisms, were anticipated to be used in ways different from traditional microbial fermentation. Earlier blog posts described the initial public meeting on this topic that EPA held in September 2015 and the follow-up meeting in October 2016. EPA issued a draft algae guidance document in conjunction with the 2016 public meeting, and the present document is an update to the 2016 version, and incorporates the information and feedback EPA received at that open meeting and from the public records docket that was open for comment at that time.
After some introductory sections, the main body of the guidance document is a detailed, comprehensive list of the types of data that EPA would potentially like to see in submissions for uses of algae or cyanobacteria under TSCA. It follows the framework of the 1997 Points to Consider document, in providing lists of the types of data that might be required in EPA submissions, within a series of broad categories. The algae document first asks for information about the recipient microorganism (i.e. the strain that is the starting point for the genetic manipulations) and the genetic changes introduced, information about the potential health and environmental effects (including the environmental fate) of the alga, and information about the proposed use of the modified alga, whether a small-scale field test proposed in a TERA or a manufacturing use proposed in an MCAN. The document provides additional details about information specific for algae or cyanobacteria that would be important for EPA’s risk assessment of proposed use of modified algae in manufacturing, whether in open ponds, enclosed photobioreactors, or heterotrophic fermentation, as well as proposed open pond R&D activities. As with the original Points to Consider document, the algae guidance document provides a comprehensive list of issues to be considered, with the expectation that not every topic identified would be applicable to every submission. In addition, it should be noted that TSCA itself does not impose specific testing requirements on applicants, but only that notices under the Act include all data relevant to health and safety that is known to the applicants.
After brief review of the final document, it appears that EPA made only some minor revisions to the detailed information section as it appeared in the 2016 draft. I found only about 3 or 4 places where the 2020 version included a bullet point for a new topic of information or data not found in the 2016 draft, which were presumably added in response to specific comments from interested parties. This speaks to the thorough job EPA did in creating the original draft, which was so comprehensive in listing potential data needs that there really wasn’t much that needed to be added.
To date, EPA has received very few TSCA submissions for uses of algae or cyanobacteria, some of which I have described in previous blog posts. For example, discussion of MCANs from Joule and Solazyme (now known as TerraVia) posted in 2014, a brief mention of Algenol’s Consolidated MCAN for cyanobacteria posted in 2015, and discussion of the TERA submitted by Sapphire posted in 2013. Presumably this new guidance document will be of value to companies and academic groups planning MCAN or TERA submissions for modified algae or cyanobacteria species in the months and years to come.
D. Glass Associates, Inc. is a consulting company specializing in government and regulatory affairs support for renewable fuels and industrial biotechnology. David Glass, Ph.D. is a veteran of over thirty-five years in the biotechnology industry, with expertise in industrial biotechnology regulatory affairs, U.S. and international renewable fuels regulation, patents, technology licensing, and market and technology assessments. More information on D. Glass Associates’ regulatory affairs consulting capabilities, and links to some of Dr. Glass’s prior presentations on biofuels and biotechnology regulation, are available at www.dglassassociates.com. The views expressed in this blog are those of Dr. Glass and D. Glass Associates and do not represent the views of any other organization with which Dr. Glass is affiliated.