Many were curious, as I speculated in an earlier blog post, whether EPA’s procedures for reviewing Microbial Commercial Activity Notices (MCANs) and chemical Premanufacture Notices (PMNs) under the Toxic Substances Control Act (TSCA) would be changed by the landmark TSCA reforms enacted in the June 2016 passage of the Frank R. Lautenberg Chemical Safety for the 21st Century Act. Although the Lautenberg Act had no provisions specifically affecting EPA’s biotechnology program under TSCA, some portions of the bill have caused EPA to change the way it reviews MCANs, the determinations it makes regarding each MCAN, and the way in which it publicizes the results of its review. But would this lead to any appreciable changes in EPA’s biotechnology program?
Specifically, the Lautenberg Act required EPA to affirmatively reach one of the following three determinations for each notice submitted:
- A finding that the substance presents an unreasonable risk.
- A finding that either the information is insufficient to permit a reasoned evaluation of the substance; or in the absence of sufficient information and evaluation, the substance may present an unreasonable risk; or the substance may be produced in substantial quantities or may enter the environment in substantial quantities, which may lead to substantial human exposure.
- A finding that the substance is not likely to present an unreasonable risk.
Although largely conforming to prior practice regarding EPA’s risk assessment procedures, the key difference was that EPA now needs to affirm one of these determinations for each MCAN or PMN it reviews, whereas previously if the Agency took no action within the 90 day review period, the Notice was deemed to be accepted (“Dropped from Review”), and the chemical or the microorganism covered in the Notice could proceed to be commercialized.
EPA began following this procedure for all MCANs filed after the June 22, 2016 signing of the Lautenberg Act. For almost all of these MCANs, EPA was able to reach the finding that the microorganism “is not likely to present an unreasonable risk”, and to adopt the necessary paperwork as now required under the amended TSCA. At this time, the Agency also changed the way it had been reporting the filing and disposition of MCANs, and although the new procedures are in conformance with the requirements of the law, the new publication procedures have made it somewhat harder to track MCANs and to easily obtain information on the organism and its intended use covered in each reviewed MCAN.
EPA previously maintained a page entitled “TSCA Biotechnology Notifications Status” (now accessible here), where it chronologically listed all the MCANs (as well as TSCA Experimental Release Applications and Biotechnology Test Marketing Exemption Applications) reviewed by the Agency since 1998 (i.e. since the adoption of the current MCAN regulations). The tables on this page conveniently listed, for each MCAN, the name of the organism, the name of the submitter, and the intended use (except when any such information was claimed as confidential by the submitter), and more importantly each entry also had a link to a page with a 1-2 paragraph description of the organism and its intended use, and an explanation of the basis for EPA’s finding of no unreasonable risk. These tables can still be found at this site, although the links to the decision documents seem to be gone. But this page was convenient because it listed all biotech notices on a single page, separately from chemical PMNs, and it was easy to find and review the most recently-filed notices. In the past, I’ve posted periodic summaries of recently-filed MCANs, using information drawn from this page.
Since the passage of the Lautenberg Act, however, EPA has begun to use a new page where it publicizes all TSCA Section 5 Notices for which it has made the “no unreasonable risk” determination. This page, called “Chemicals Determined Not Likely to Present an Unreasonable Risk Following Pre-Manufacture Notification Review“, lists both MCANs and PMNs in the chronological order in which the determination has been made (additions to this page are announced from time to time in the Federal Register). From this page, you can follow links to a page entitled “Microbial Commercial Activity Notices (MCANs) Table” which indeed lists only reviewed MCANs, but the”No Unreasonable Risk” page is difficult to review and search because it intermingles PMNs and MCANs (note that PMNs and MCANs can be distinguished because PMNs are identified with a prefix of “P” followed by the fiscal year of submission, while MCANs are identified with a “J” and the fiscal year) The”No Unreasonable Risk” page does include links to EPA’s decision documents for each Notice (for example, this one here), but these documents are highly formulaic to meet the requirements of the law, and include little if any detail about the specific organism in question.
So, it is harder now to conveniently and quickly get an overview of recent MCAN activity, and so I’ve done the hard work for you. The table below shows all MCANs received by EPA since June 22, 2016 for which the Agency’s review has concluded. This table shows the MCAN number, the species of the microorganism, and the dates on which EPA review began, the date of EPA’s decision, and the effective date of the decision (i.e. the end of the review period, usually 90 days after submission). Each entry has a link to EPA’s decision document, although the link will first take you to an intermediate page, from which the actual decision document can be accessed.
|Case Number||Chemical Identify||Final Disposition||Review Start Date||Decision Date||Effective Date|
|J-16-0006||Generic: Trichoderma reesei modified||Not likely to present an unreasonable risk||6/22/16||9/2/16||9/7/16|
|J-16-0010||Generic: Saccharomyces cerevisiae modified||Not likely to present an unreasonable risk||6/22/16||9/14/16||9/15/16|
|J-16-0011 through 0016||Generic: Biofuel Producing Organism||Not likely to present an unreasonable risk||6/22/16||9/14/16||9/15/16|
|J-16-0017||Generic: Saccharomyces cerevisiae modified||Not likely to present an unreasonable risk||6/22/16||9/14/16||9/15/16|
|J-16-0018||Generic: Saccharomyces cerevisiae modified||Not likely to present an unreasonable risk||6/22/16||9/14/16||9/15/16|
|J-16-0019||Generic: Trichoderma reesei modified||Not likely to present an unreasonable risk||6/29/16||10/4/16||10/11/16|
|J-16-0020||Generic: Trichoderma reesei modified||Not likely to present an unreasonable risk||6/29/16||10/4/16||10/11/16|
|J-16-0021||Generic: Trichoderma reesei modified||Not likely to present an unreasonable risk||7/15/16||10/19/16||10/25/16|
|J-16-0022||Generic: Trichoderma reesei modified||Not likely to present an unreasonable risk||7/15/16||10/19/16||10/25/16|
|J-16-0023||Generic: Trichoderma reesei modified||Not likely to present an unreasonable risk||7/16/16||10/19/16||10/25/16|
|J-16-0024||Generic: Trichoderma reesei modified||Not likely to present an unreasonable risk||7/28/16||11/14/16||11/21/16|
|J-16-0025||Generic: Trichoderma reesei modified||Not likely to present an unreasonable risk||7/29/16||11/14/16||11/21/16|
|J-16-0026||Section 5(e) Consent Order – May present an unreasonable risk of injury to health and the environment||4/10/17|
|J-16-0033||Generic: Saccharomyces cerevisiae modified to express glucoamylase activity||Not likely to present an unreasonable risk||8/22/16||12/1/16||12/7/16|
|J-16-0034||Generic: Saccharomyces cerevisiae modified||Not likely to present an unreasonable risk||8/23/16||12/1/16||12/7/16|
|J-16-0035||Generic: Saccharomyces cerevisiae modified||Not likely to present an unreasonable risk||8/23/16||12/1/16||12/7/16|
|J-16-0036 through 0041||Generic: Biofuel producing modified microorganism(s), with chromosomally-borne modifications||Not likely to present an unreasonable risk||9/7/16||12/1/16||12/7/16|
|J-17-0001 through 0005||Generic: Saccharomyces cerevisiae modified||Not likely to present an unreasonable risk||10/24/16||1/18/17||1/25/17|
|J-17-0006||Generic: Saccharomyces cerevisiae modified||Not likely to present an unreasonable risk||11/23/16||2/13/17||2/13/16|
|J-17-0007||Generic: Biofuel producing Saccharomyces cerevisiae modified, genetically stable||Not likely to present an unreasonable risk||2/1/17||4/27/17||4/27/17|
|J-17-0008 through 0013||Generic: Modified microorganism||Not likely to present an unreasonable risk||5/8/17||7/27/17||7/27/17|
|J-17-0014||Generic: organic acid producing yeast, modified, genetically stable||Not likely to present an unreasonable risk
There is considerably less information now available about filed MCANs on these pages, and all the company names have either been claimed as confidential or simply omitted, but it is clear that the bulk of the activity is for familiar species of microorganisms. Specifically, there are 8 MCANs for modified strains of Trichoderma reesei, all of which are for enzyme production (some specified as “cellulose-degrading” enzymes) and thirteen MCANs for strains of Saccharomyces cerevisiae, all for production of ethanol. All but one of the T. reesei MCANs were filed in the span of a month in the summer of 2016 and thus may have come from the same company. There were a total of 12 MCANs for “generic biofuel producing organisms”, filed as two separate consolidated MCANs in June and September 2016, and one MCAN for an “organic acid producing yeast” of an unnamed species. There was also one MCAN that became the subject of a consent order, although details of this case do not seem to be available online.
There appear to have been as many as 41 MCANs submitted during Fiscal Year 2016 (October 2015 through September 2016), but only about 14 submitted through the first 10 months of Fiscal Year 2017 (i.e. through July 2017), although the full number received during FY17 has not yet been publicized. It would be interesting to see if the overall numbers for FY17 are indeed down from prior years, and whether this might represent a trend from the prior several years where MCAN numbers increased from year to year. This would not necessarily be surprising, in view of the financial difficulties that many in the biofuel sector have experienced in recent years.
It is somewhat surprising, and perhaps ironic, that the new procedures put in place under the Lautenberg Act have caused EPA’s MCAN listings to be less informative than the old practice. Many observers expected the Lautenberg Act to make EPA’s review of chemical substances more transparent than under existing practices, but these new websites are harder to use to extract useful information. Not only is it beneficial for the general public and environmental group watchdogs for EPA’s MCAN review process to accessible to the public, but these listings have also been useful to industry as a source of competitive information. On the other hand, EPA’s old listings page was notoriously slow to be updated, often no more than once a year, so at least the new listings pages seem to be reasonably up to date in listing decisions: at this writing in January 2018, the “No Unreasonable Risk” page lists PMN decisions made as recently as December 2017, although the most recent MCAN determination was from October of last year.
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 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 copies of some of Dr. Glass’s prior presentations on biofuels and biotechnology regulation, are available at www.slideshare.net/djglass99 and 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.