As I’ve previously reported in several blog posts over the years, many modified microorganisms that are being developed for use in the manufacture of fuels or chemicals are potentially subject to regulation under the U.S. EPA’s biotechnology regulations (40 CFR Part 725) under the Toxic Substances Control Act (TSCA). TSCA has been in the news in recent weeks because, after many years of hearings and negotiations, the U.S. Congress has passed new legislation that would revise TSCA to substantially overhaul the way chemicals are regulated in the U.S.. This bill, H.R. 2576, formally entitled “The Frank R. Lautenberg Chemical Safety for the 21st Century Act”, was passed by the Senate on June 7, 2016, and at this writing is awaiting signature by President Obama, who is expected to sign it within days.
Passage of this bill is quite significant, not only because it passed with strong bipartisan majorities in Congress and was supported by the chemical industry, but also because TSCA has been the subject of criticism from environmental groups for years. These groups have maintained that the law gave EPA very limited ability to review the safety of chemicals already on the market, and this aspect of the law has been significantly strengthened in “new TSCA”. In fact, this was the driving force behind TSCA reform, and is its major impact.
There are already a number of excellent, detailed summaries of H.R. 2576 posted online by several Washington law firms (e.g. from Bergeson & Campbell; Keller & Heckman; and Beveridge & Diamond). So I won’t provide a general summary of the law, except to note that some of the key provisions of the bill are requirements for EPA to conduct reviews of existing chemicals on the market, provisions governing when state chemical safety laws can or cannot be pre-empted by federal law, and some revisions to the way confidential information must be claimed in submissions under TSCA and to what information may not be claimed as confidential. I’ll summarize the few provisions of H.R. 2576 that might affect EPA review of modified microorganisms that are the subject of Microbial Commercial Activity Notices (MCANs) or other TSCA notices.
It is important to note that there is nothing in H.R. 2576 that explicitly mentions microorganisms or biotechnology. The provisions of H.R. 2576 most likely to affect EPA’s biotechnology program are those which amend Section 5 of TSCA, “Manufacturing and Processing Notices”. This is the section on which the regulations requiring premanufacture notification (PMN) of new chemicals and MCAN notifications of new microorganisms are based. H.R. 2576 made only minor changes to TSCA Section 5, and none of these changes would affect the authority for EPA’s 1997 decision to create MCANs, TERAs, and the other parts of the biotech regulatory program. But some of these changes may affect the way EPA reviews MCANs and PMNs, as follows.
Consideration of affected populations. First, the bill says that, when evaluating the risk of a substance covered in a notification, EPA cannot consider costs or other nonrisk factors, but is required to consider the potential impact of the substance on populations that may potentially be exposed to the substance. EPA arguably had this authority under existing law, but H.R. 2576 would make it a requirement. For biotechnology notices, this would likely require the agency to explicitly review whether the proposed uses of the microorganism might affect specific populations found near the anticipated locations where the organism would be used, and it might therefore be desirable for applicants to consider whether any such populations exist near their production sites and whether any additional measures would be needed to inform local communities about the intended activities. (As an aside, it would be interesting to consider how this requirement would affect EPA’s review of a microorganism that might someday be intended for use in a consumer product or non-centralized manufacturing).
Provision for fee refunds. Second, the bill provides that, if EPA does not make a definitive decision and/or take action within 180 days of the submission of the notice (i.e. the statutory 90 days for review plus the additional 90 days EPA can unilaterally impose), EPA must refund all applicable fees to the submitter, but the agency would still be required to complete its review and render a determination. This is of course favorable to industry, but may have little practical impact, particularly on the biotech program, since EPA’s usual procedure when it needs more time for the review is to ask the submitter to voluntarily agree to suspend the review period (thus stopping the 180-day clock), making it less likely that decisions would not be reached within the stated deadline (unless a submitter refused to agree to a voluntary suspension, for whatever reason).
EPA determinations of risk. Of more importance, the bill requires EPA to 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.
In the case of the first two determinations, EPA must then restrict the use of the substance through a consent order or a Significant New Use Rule.
Although this formulation is quite similar to what has previously been found in TSCA, the statement is potentially broader through the use of the word “or” to delineate all three options under the second determination. At least one law firm has cautioned that this might provide EPA broader authority to reject a notice based on insufficient data or information, and this firm is advising applicants to be sure that their PMNs and other notices contain enough information to avoid this possibility. The firm has also speculated on whether any notifications pending at the time H.R. 2576 takes effect would be assessed under the new standards or those originally found in TSCA.
In my opinion, this change will have a very limited impact on the biotechnology program. In its “Points to Consider” document, EPA provides ample guidance on the data it wants to see in MCANs and other biotech submissions like TERAs, and the agency encourages presubmission consultation, so it is rare for a biotech submission to be rejected solely on account of missing important data. Most MCANs are reviewed and cleared by EPA with very few concerns over the safety of the microorganism, and receive the “no unreasonable risk” finding, but even where the agency had substantive questions, the process to request and obtain additional data from the submitter is straightforward. In the rare case where a submitter is unable to provide any requested information, it would be more common for the submitter to withdraw the MCAN or place it on indefinite hold, rather than to force the agency to issue a finding of insufficient information.
There have been a handful of situations under the biotech program where EPA felt it had sufficient information only to allow certain limited industrial uses of an MCAN microorganism, and in those cases, the agency has used its existing authority to determine that it lacked sufficient information to allow unrestricted commercial use of a microorganism, and instead asked the submitter to enter into a consent order limiting the allowed uses of the microorganism. For example, because the MCANs from Joule and Algenol both proposed the use of photobioreactors to culture modified cyanobacteria, which had never been the subject of any prior MCANs, EPA used the “insufficient information” finding to ask each company to voluntarily enter into consent orders, initially limiting the use of the MCAN strain to the specific facility and photobioreactor described in the MCAN. So, the new language under H.R. 2576 may come into play for a small number of MCAN submissions, but would not substantially change current practice.
Biotechnology exemptions. Unlike some of the earlier versions of TSCA reform bills that Congress has considered, H.R. 2576 makes no significant changes to Section 5(h)(4) of TSCA. This is the section under which EPA created the tiered exemptions and other exemptions from MCAN reporting, and in reviewing one of the earlier Congressional drafts a few years ago, I had some concerns that an unintended consequence of modifications to this section would have been to place the basis for the biotech exemptions in doubt. As far as I can tell, the one change that H.R. 2576 makes to Section 5(h)(4) is minor and does not affect the portion of this section allowing EPA to grant exemptions, so this is not a concern.
Confidential business information. As mentioned above, H.R. 2576 makes changes to the process of claiming confidential protection for certain information in chemical substance notifications. It establishes by statute the requirement that confidential business information (CBI) claims be substantiated at the time the notification is submitted (with certain exceptions such as marketing and sales data); but this has been required under the biotech regulations for MCANs and TERAs (and I believe also for chemical PMNs), so this will have little practical impact on the biotech program. However, the bill carries forward the provision, as under original TSCA, that health and safety information cannot be claimed as CBI, but it clarifies that process information, explicitly including molecular formulas and structures, contained in health and safety information (e.g. test results) can be claimed as CBI. Such CBI claims have been common in MCANs, and this is likely to continue unless EPA makes a shift in its policies. There are other provisions relating to CBI that have been changed – see some of the law firm general summaries referenced above for more information.
EPA biotech website updated. Finally, I’d note that EPA’s biotech program has recently updated its website listing of MCANs it has received and reviewed. The website had previously listed only those MCANs received through the end of the federal government’s fiscal year 2014 (i.e. September 30, 3014). The site now lists the MCANs received in fiscal year 2015 (there were at least 36 MCANs received that year, not all of which were reviewed favorably and cleared) and six additional MCANs received in the first six months of fiscal year 2016 (trough March 31, 2016). Many of the new MCANs covered modified strains of S. cerevisiae, and as always there were a number of MCANs where the identity of the company and the microorganism were claimed as confidential. There were also listings of three new TERAs received and approved by EPA during FY15. I hope to review and comment on these new MCANs and TERAs in a future blog post.
In summary, although H.R. 2576 represents a significant event that may substantially change many aspects of chemical regulation in the U.S., its impact on the biotechnology program will be minimal. After all, the biotech program is a minor component of EPA’s regulatory programs under TSCA — the agency receives about 1,000 chemical notices a year, but received only 36 MCANs in its busiest year (FY15). I don’t expect any major procedural changes or policy shifts in the biotech program as a result of TSCA reform, although I do see the chance for an unintended consequence: because the biotech staff in EPA’s Office of Pollution Prevention and Toxics also have responsibilities in the New Chemicals Review program, it is possible that new regulatory requirements in the chemical review program might result in less staff time for review of biotech submissions. Otherwise, I expect it will be “business as usual” for the biotech program under TSCA.
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/djglass99and 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. Please visit our other blog, Biofuel Policy Watch.