[Federal Register Volume 87, Number 176 (Tuesday, September 13, 2022)]
[Proposed Rules]
[Pages 55930-55932]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-19430]


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DEPARTMENT OF COMMERCE

Bureau of Industry and Security

15 CFR Part 774

[Docket No. 220826-0174]
RIN 0694-AI84


Request for Comments Concerning the Imposition of Section 1758 
Technology Export Controls on Instruments for the Automated Chemical 
Synthesis of Peptides

AGENCY: Bureau of Industry and Security, Commerce.

ACTION: Advance notice of proposed rulemaking (ANPRM).

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SUMMARY: The Bureau of Industry and Security (BIS), Department of 
Commerce, maintains controls on the export, reexport and transfer (in-
country) of dual-use items and less sensitive military items pursuant 
to the Export Administration Regulations (EAR), including the Commerce 
Control List (CCL). Certain instruments for the automated synthesis of 
peptides (automated peptide synthesizers) have been identified by BIS 
for evaluation according to the criteria in section 1758 of the Export 
Control Reform Act of 2018 (ECRA) pertaining to emerging and 
foundational technologies. BIS is seeking public comments on the 
potential uses of this technology, particularly with respect to its 
impact on U.S. national security (e.g., whether such technology could 
provide the United States, or any of its adversaries, with a 
qualitative military or intelligence advantage). This advance notice of 
proposed rulemaking also requests public comments on how to ensure that 
the scope of any controls that may be imposed on this technology would 
be effective (in terms of protecting U.S. national security interests) 
and appropriate (with respect to minimizing their potential impact on 
legitimate commercial or scientific applications).

DATES: Comments must be received by BIS no later than October 28, 2022.

ADDRESSES: You may submit comments, identified by regulations.gov 
docket number BIS-2022-0023 or by RIN 0694-AI84, through any of the 
following:
     Federal eRulemaking Portal: http://www.regulations.gov. 
You can find this advance notice of proposed rulemaking by searching 
for its regulations.gov docket number, which is BIS-2022-0023.
     Email: [email protected]. Include RIN 0694-AI84 
in the subject line of the message.
    All filers using the portal or email should include the name of the 
person or entity submitting the comments in the name of their file(s), 
in accordance with the instructions below. Anyone submitting business 
confidential information should clearly identify the business 
confidential portion at the time of submission, file a statement 
justifying nondisclosure and referring to the specific legal authority 
claimed, and provide a non-confidential submission to be made publicly 
available.
    For comments submitted electronically containing business 
confidential information, the file name of the business confidential 
version should begin with the characters ``BC.'' Any page containing 
business confidential information must be clearly marked ``BUSINESS 
CONFIDENTIAL'' on the top of that page. The corresponding non-
confidential version of those comments must be clearly marked 
``PUBLIC.'' The file name of the non-confidential version should begin 
with the character ``P.'' The ``BC'' and ``P'' should be followed by 
the name of the person or entity submitting the comments or rebuttal 
comments. Any submissions with file names that do not begin with a 
``P'' or ``BC'' will be assumed to be public and will be made publicly 
available through https://www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: For questions on automated peptide 
synthesizers, contact Dr. Tara Gonzalez, Chemical and Biological 
Controls Division, Office of Nonproliferation and Treaty Compliance, 
Bureau of Industry and Security, Telephone: (202) 482-3343, Email: 
[email protected]. For questions on the submission of comments, 
contact Willard Fisher, Regulatory Policy Division, Office of Exporter 
Services, Bureau of Industry and Security, U.S. Department of Commerce, 
(202) 482-6057, Email: [email protected].

SUPPLEMENTARY INFORMATION: 

Background

Identification of Section 1758 Technologies

    As part of the National Defense Authorization Act (NDAA) for Fiscal 
Year 2019, Public Law 115-232, Congress enacted the Export Control 
Reform Act of 2018 (ECRA), 50 U.S.C. 4801-4852. Section 1758 of ECRA 
(as codified under 50 U.S.C. 4817) authorizes the Bureau of Industry 
and Security (BIS) to establish appropriate controls on the export, 
reexport or transfer (in-country) of emerging and foundational 
technologies essential to the national security of the United States. 
Due to the absence of specific definitions or other guidance in ECRA 
differentiating the terms ``emerging technology'' or ``foundational 
technology,'' and in order to ensure greater efficiency in implementing 
controls for such items, BIS has chosen to characterize such 
technologies as ``Section 1758 technologies'' for purposes of section 
1758 of ECRA, rather than characterizing a specific technology as 
either ``emerging'' or ``foundational.''
    As described in section 1758(a)(2)(B) of ECRA, the identification 
of Section 1758 technologies takes into account: (i) the development of 
these technologies in foreign countries; (ii) the effect export 
controls imposed pursuant to this section may have on the development 
of such technologies in the United States; and (iii) the effectiveness 
of export controls imposed pursuant to this section on limiting the 
proliferation of the emerging and foundational technologies in foreign 
countries.
    The Secretary of Commerce must establish appropriate controls on 
the export, reexport or transfer (in-country) of technology identified 
pursuant to the Section 1758 process. In so doing, the Secretary must 
consider the potential

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end-uses and end-users of Section 1758 technologies, and the countries 
to which exports from the United States are restricted (e.g., embargoed 
countries). While the Secretary has discretion to set the level of 
export controls, at a minimum a license must be required for the export 
of such technologies to countries subject to a U.S. embargo, including 
those countries subject to an arms embargo.
    In addition, section 1758(a)(2)(C) of ECRA (50 U.S.C. 
4817(a)(2)(C)) requires the interagency process for identifying Section 
1758 technologies to include a notice and comment period.

November 19 Advance Notice of Proposed Rulemaking

    On November 19, 2018, BIS published an advance notice of proposed 
rulemaking, ``Review of Controls for Certain Emerging Technologies'' 
(83 FR 58201) (November 19 ANPRM). The November 19 ANPRM identified 
biotechnology in a representative list of fourteen technology 
categories concerning which BIS sought public comment to determine 
whether there are specific emerging technologies that are essential to 
U.S. national security and for which effective controls can be 
implemented. The biotechnology-related comments submitted to BIS in 
response to its November 19 ANPRM are not addressed in this ANPRM, 
because none of the comments specifically addressed the question of 
export controls on automated peptide synthesizers.

Evaluation of Automated Peptide Synthesizers Pursuant to Section 1758 
of ECRA

    Instruments for the automated synthesis of peptides (automated 
peptide synthesizers) have been identified by BIS for evaluation 
according to the criteria in section 1758 of ECRA pertaining to 
emerging and foundational technologies.
    Peptides and polypeptides are polymeric chains of amino acids, 
linked together by peptide bonds. Proteins are three-dimensional (3D) 
macromolecules composed of one or more folded large chains of 
polypeptides. Proteins must fold into the correct 3D shape to be 
functionally active. The first peptide bond was synthesized over 100 
years ago. However, in the last few decades, advances in chemical 
synthesis methods have established automated peptide synthesis as a 
common laboratory technique.\1\ Long-established synthesis methods 
using fluorenylmethyloxycarbonyl (Fmoc) chemistry can reliably and 
routinely produce high quality polypeptides around 50 amino acids in 
length.\2\
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    \1\ R.B. Merrifield, Solid Phase Peptide Synthesis. I. The 
Synthesis of a Tetrapeptide, 85 J. Am. Chemistry Soc'y 2149 (1963).
    \2\ Da'san M.M. Jaradat, Thirteen Decades of Peptide Synthesis: 
Key Developments in Solid Phase Peptide Synthesis and Amide Bond 
Formation Utilized in Peptide Ligation, 50 Amino Acids 39 (2017).
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    Recent advances in peptide synthesis technology and instrumentation 
have increased both the speed of peptide synthesis and the length of 
peptide products, including peptides and proteins greater than 100 
amino acids in length.\3\ Most protein toxins that are controlled under 
Export Control Classification Number (ECCN) 1C351 on the Commerce 
Control List (CCL) (see Supplement No. 1 to part 774 of the EAR) are 
over 100 amino acids in length and have an average length of 300 amino 
acids (with the notable exception of conotoxins, which range between 
10-100 amino acids in length). Consequently, absent the imposition of 
additional controls on the export, reexport or transfer (in-country) of 
certain peptide synthesis technology and instrumentation (e.g., 
automated peptide synthesizers), there would be an increased risk that 
such technology and instrumentation could be used to produce controlled 
toxins for biological weapons purposes.
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    \3\ Sameer S. Kulkarni et al., Rapid and Efficient Protein 
Synthesis Through Expansion of the Native Chemical Ligation Concept, 
Nature Revs. Chemistry, Mar. 29, 2018, at 1.
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Request for Comments

    Consistent with section 1758(a)(2)(C) of ECRA (50 U.S.C. 
4817(a)(2)(C)), BIS welcomes comments on the following questions. If 
specific automated peptide synthesizer instruments are described by 
respondents, BIS requests that this should be done, to the extent 
practicable, within the context of the following questions.
    (1) What is the current state of development of automated peptide 
synthesizers in the United States, including those having primarily 
academic or commercial applications, and how does this compare with 
that of other countries (e.g., is the United States at the forefront of 
such development in the academic and commercial fields)? Where 
possible, please identify any publicly available studies that support 
your position.
    (2) What is the current availability and predominate application(s) 
of automated peptide synthesizers in the United States and how does 
this compare with that of other countries (e.g., how common is the use 
of these instruments in life sciences laboratories/institutions and 
other academic or commercial settings)?
    (3) To what extent are custom peptide synthesis services available 
in the United States and other countries, and would the availability of 
such services (particularly for academic or commercial applications) be 
likely to impact domestic or foreign demand for automated peptide 
synthesizers?
    (4) To what extent are current or near-term developments in peptide 
synthesis technology expected to address the challenges of peptide 
length, sequence fidelity, and protein folding (e.g., are efforts 
currently underway to integrate protein folding into the automation 
process)?
    (5) To what extent would the establishment of Section 1758 
technology export controls on automated peptide synthesizer 
instruments, and related ``software'' and ``technology,'' impact U.S. 
technological leadership in this field (e.g., within the academic or 
commercial spheres) and would this impact be distinctly different if 
controls were placed primarily on ``software'' as opposed to hardware, 
or vice versa?
    (6) To what extent would the imposition of Section 1758 technology 
export controls on automated peptide synthesizer instruments, and 
related ``software'' and ``technology,'' likely be effective in terms 
of limiting the proliferation of these items abroad (including the 
potential use of such items to produce controlled toxins for biological 
weapons purposes)?
    (7) To what extent has the increased availability of lower cost 
coupling reagents, together with recent advances in automated peptide 
synthesizers and related technology, overcome economic or technological 
factors that previously might have limited the availability and use of 
this technology, abroad?
    (8) To what extent should Section 1758 technology export controls 
on peptide synthesizer technology be implemented multilaterally (rather 
than unilaterally), in the interest of increasing their effectiveness 
and minimizing their impact on U.S. industry?
    Several respondents who commented on BIS's November 19 ANPRM 
indicated their preference for multilateral export controls over 
unilateral export controls, because the former typically place U.S. 
industry on a more level playing field with respect to producers/
suppliers in other countries. In this regard, note that section 1758(c) 
of ECRA (as codified under 50 U.S.C. 4817(c)) provides that ``the 
Secretary of State, in consultation

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with the Secretary [of Commerce] and the Secretary of Defense, and the 
heads of other Federal agencies, as appropriate, shall propose that any 
technology identified pursuant to subsection (a) [of ECRA] [which 
addresses the interagency process for identifying Section 1758 
technologies] be added to the list of technologies controlled by the 
relevant multilateral export control regimes.''
    Finally, BIS encourages comments addressing any other automated 
peptide synthesizer technology topics deemed to be relevant to this 
inquiry.
    Comments should be submitted as described in the ADDRESSES section 
of this ANPRM and must be received no later than October 28, 2022.
    This ANPRM has been designated a ``significant regulatory action,'' 
although not economically significant, under Executive Order 12866. 
Accordingly, this ANPRM has been reviewed by the Office of Management 
and Budget (OMB).

Matthew S. Borman,
Deputy Assistant Secretary for Export Administration.
[FR Doc. 2022-19430 Filed 9-12-22; 8:45 am]
BILLING CODE 3510-33-P