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Item: 31 54
REGULATORY IMPACT ANALYSIS OF
REGULATIONS ON MICROBIAL PRODUCTS OF
BIOTECHNOLOGY
VOLUME I: TECHNICAL REPORT
Prepared by
Economics, Exposure and Technology Division
Office of Pollution Prevention and Toxics
U.S. Environmental Protection Agency
January 21, 1997
Note: This entire document is available on EPA's World
Wide Web site at http://www.epa.gov/fedrgstr/EPA-TOX/ For paper copies,
contact the TSCA Hotline: e-mail: TSCA-Hotline@epamail.epa.gov; telephone:
202-554-1404; fax: 202-554-5603.

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EXECUTIVE SUMMARY
This Regulatory Impact Analysis (RIA) examines the potential costs, benefits, and
impacts of regulation of microbial products of biotechnology under the Toxic Substances Control
Act (TSCA). The analysis is presented in eight chapters: Introduction; The Regulated
Community; Benefits of the Rule; Industry Costs; Government Costs; Effects of the Rule on
Innovative Activity; International Considerations; and Effects of the Rule on Small Businesses.
A. Introduction
The U.S. Environmental Protection Agency is modifying its current policy under TSCA (as
set forth in its 1986 Policy Statement) regarding oversight of "new" microorganisms. Changes to
the Agency's current policy include the use of section 5(h)(4) of TSCA to limit reporting for certain
categories of "new" microorganisms and revised notification rules for microorganisms intended
for use in research and development (R&D) activities.
The requirements contained in the provisions of the rule, which include notification,
recordkeeping/documentation, and consent agreements, vary depending on the type and stage
of development of a "new" microorganism intended for commercial purposes. For example,
organizations manufacturing, importing, or processing "new" microorganisms that are subject to
oversight and intended for use in certain commercial R&D applications involving environmental
release could choose to submit a TSCA Experimental Release Application (TERA) in lieu of the
notice required at the commercial level, the Microbial Commercial Activity Notice (MCAN).
Notification in connection with the intended general commercial use (GCU) of a "new"
microorganism, that is, use for commercial purposes other than R&D, would be via the Microbial
Commercial Activities Notice (MCAN).
Like the notification formats, the various exemption mechanisms incorporated into the
provisions of the rule also vary by type and stage of development of the microorganism. An
example of two exemption provisions specifically for the R&D stage included in the rule are the

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"contained structure" exemption and the exemption termed "TERA Exempt." The former applies
in cases where microorganisms intended for use in commercial R&D are to be confined in a
contained structure. In contrast, the latter applies in cases where specifically listed
microorganisms intended for commercial R&D are to be used outside of contained structures.
B.	The Regulated Community
The microorganisms potentially affected by the rule are those for which the corresponding
chemical use would be subject to TSCA jurisdiction. By statute, TSCA regulates all chemical
applications not specifically excluded in the Act. Statutorily excluded application areas include
medical, food and beverage, and pesticide applications.
Although unable to quantify the exact magnitude of activity in the biotechnology industry
that is subject to TSCA, the Agency believes that activities involving "new" microorganisms
covered by the rule comprise a modest share of overall activity. According to one estimate, there
are over 1,000 companies pursuing biotechnology activities in the U.S.; of these, however, the
Agency has identified about 130 firms as being involved in commercial R&D or general
commercial use of microorganisms in applications that fall under TSCA jurisdiction. EPA
estimates the share of total R&D spending in biotechnology activities subject to TSCA to be
roughly 7 to 13 percent.
In annual sales, the portion of the biotechnology industry active in areas subject to TSCA
appears to be divided sharply between large and small firms. EPA estimates that roughly half of
the companies potentially affected by the rule have sales of $40 million or more, while most of
those remaining are estimated to have sales of under $10 million.
With the expanding role of universities in the field of biotechnology and the increasing
number of financial relationships developing between industry and universities, it is likely that
some portion of R&D conducted at universities would be subject to the rule (if the work were
determined to be conducted for commercial purposes, as defined in the rule).
C.	Benefits

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Possible adverse impacts associated with the use of "new" microorganisms could
include health effects on humans, animals, and plants, increased costs or decreased productivity
in farming and other areas of the economy, and ecological impacts whose long run health or
economic effects may not be immediately apparent. To avoid these potential impacts, the
provisions of the rule have been designed to reduce risks associated with the introduction of
"new" microorganisms into the environment.
The risk reduction potential of the rule may be realized through a number of different
actions taken by both EPA and the regulated community. The mechanism used by the Agency to
obtain a given industry action depends on the type of activity intended to be undertaken and on
the willingness of the submitter to cooperate voluntarily.
The benefits associated with the requirements contained in the rule arise in connection
with the rule's risk reduction potential. By reducing risk, social costs associated with remediation
of damages to health and the environment, including costs associated with partially or totally
irreversible effects, can be avoided. The rule also contributes to greater regulatory efficiency, as
it is estimated that the notification rules contained in the rule will provide the public with more risk
reduction per dollar expended as compared to current policy. Finally, the pace of
commercialization is also expected to be enhanced, as uncertainty regarding EPA's development
of regulatory requirements and public concern in connection with perceived risks of
environmental introductions of "new" microorganisms would be addressed. Exemptions could
also reduce regulatory burdens for whole groups of products, relative to current policy.
D. Industry Costs
Industry costs are estimated for "Year 1" and "Year 5" in this analysis. Year 1 costs
represent the expected costs for regulation of biotechnology products in the early stages of
oversight while Year 5 costs, estimated by projecting industry growth forward for a period of 5
years beyond the time of the rule, represent an estimate of cost impacts associated with a more
mature industry. Costs are reported in incremental terms, or in terms of costs in excess of the
costs associated with the current regulatory requirements.
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The incremental quantified costs to industry resulting from the rule in 1987 and adjusted
values for 1995 are presented in Tables ES-1a and ES-1b. As is shown in the tables,
incremental costs for Year 1 are estimated to fall within the range of $894,343 to $2,239,734 in
1987 dollars and between $1,212,729 and $3,037,039 for 1995 dollars. Values in Year 5 fall
within the range of $69,696 to $510,722 for 1987 and $94,508 to $562,539 for 1995. These
estimates reflect only direct, quantified costs of regulation under TSCA. Because there are many
costs that could not be quantified, the results should be viewed as conservative estimates of
overall costs.
The first two categories on the chart depend on the number of filings received by the
Agency. The first category, total reporting or submission costs, includes the costs of developing,
submitting, and certifying scientific
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Table ES-1a. Industry Costs Resulting from Final Rule
(1987 Dollars)
Cost Element
Average Expected Costs
Low Cost
Case
High Cost
Case
Year 1
Reporting or Submission Costs
Post Review Monitoring Costs
CBI Substantiation Costs
Recordkeeping Costs
Rule Familiarization Costs
$
$
$
$
-34,845
142,500
-3,776
4,224
786.240
$ 70,390
$ 585,000
$ -5,076
$ 16,940
$1.572.480
Total Costs to Industry in Year 1
$ 894,343
$2,239,734
Year 5
Reporting or Submission Costs	$ -66,960	$	-80,402
Post Review Monitoring Costs	$ 142,500	$ 585,000
CBI Substantiation Costs	$ -10,728	$	-13,632
Recordkeeping Costs	$ 4,884	$ 19,756
Rule Familiarization Costs	$	0	$	0
Total Quantified Costs to Industry in Year 5	$ 69,696	$	510,722
Note: Negative costs represent cost savings of the final rule as compared to current policy.
Source: Appendix D.
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Table ES-1b. Industry Costs Resulting from Final Rule
(1995 Dollars)
Cost Element
Average Expected Costs
Low Cost
Case
High Cost
Case
Year 1
Reporting or Submission Costs
Post Review Monitoring Costs
CBI Substantiation Costs
Recordkeeping Costs
Rule Familiarization Costs
$ -47,250
$ 193,230
$ -5,120
$ 5,728
$1.066.141
$ 95,449
$ 793,260
$ -6.883
$ 22,971
$2.132.282
Total Costs to Industry in Year 1
$1,212,729
$3,037,039
Year 5
Reporting or Submission Costs
Post Review Monitoring Costs
CBI Substantiation Costs
Recordkeeping Costs
Rule Familiarization Costs
-90,798
193,230
-14,547
6,623
	0
$-109,025
$ 793,260
$ -18,485
$ 26,789
$	0
Total Quantified Costs to Industry in Year 5
$ 94,507
$ 692,539
Note: The Regulatory Impact Analysis of Regulations on Microbial Products of Biotechnology prepared on January
14,1994 presented costs in terms of 1987 wage rates. These values have been revised to reflect current
wage rates. Specifically, industry costs for selected regulatory options were updated based on estimated
increases in labor category cost estimates between March 1987 and June 1995.
According to the Bureau of Labor Statistics Employment Cost index, the average percent rate of increase in
total compensation between March 1987 and June 1995 was 35.6% (BLS 1995). This value was used to
inflate values for Year 1 and 5 of the quantified industry costs of selected regulatory options in this table.
Negative costs represent cost savings of the final rule as compared to current policy.
Source: Appendix D.
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and other information for EPA. The second category, total post-review monitoring costs, results
from certain restrictions placed on R&D or industrial activity following Agency review of a
submission. The third item, recordkeeping costs, reflects the costs of maintaining records in
connection with microorganisms intended for R&D use in contained structures. Total
recordkeeping costs depend on the number of research facilities involved in activities subject to
the rule, as well as the number of research projects conducted. Total costs associated with CBI
(or confidential business information) substantiation are also filing-dependent; whereas the final
item, rule familiarization costs, reflects the one-time familiarization costs incurred by affected
facilities.
Other factors may affect potential costs but were not quantified. These factors include
potential delays in product marketing, product withdrawal, or product rejection (these factors are
addressed in Chapter VI - Effects of the Rule on Innovative Activity). Also, some businesses
may be subject to state rules, and may have already developed regulatory compliance programs
for activities not regulated by current EPA policy; cost impacts in connection with this rulemaking
initiative could thus be mitigated in such areas.
E. Government Costs
Costs to the U.S. Government, attributable to the review of materials submitted by the
regulated community under the rule are also estimated for Year 1 and Year 5. These costs are
calculated in incremental terms, or as costs resulting from the rule compared to the cost of
current regulatory requirements. These costs fall into two categories: operating costs associated
with subcommittee meetings of external peer review panels; and annual costs associated with
the review of submission materials performed by EPA staff.
Tables ES-2a and ES-2b present incremental costs to the government for 1987 and
adjusted values for 1995. As shown in the tables, total costs to the government in Year 1 were
estimated to fall between $114,896 to $121,584 in 1987 dollars and between $155,799 to
$164,868 for 1995 dollars. Total government savings expected in Year 5 were estimated to reach
a maximum of $105,344 in 1987 dollars or $142,846 in 1995 dollars.
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F. Effects of the Final Rule on Innovative Activity
As a result of the rule, members of the regulated community may find product development
strategies in connection with certain products to require reassessment. Since potential impacts
of this nature could influence the degree of emphasis a firm places on innovative activity, a
qualitative discussion of the potential impacts the rule may have on innovation has been
developed and incorporated into this analysis.
The high degree of uncertainty surrounding both the potential for commercial success of a
biotechnology product in a particular market area and the regulatory costs associated with its
development make it impossible to estimate innovation impacts quantitatively. Members of the
regulated community themselves may find weighing the financial risk of product
development against potential returns to be difficult in many cases. Potential products for which
regulatory costs constitute significant portions of overall development costs may be candidates
for reassessment, although firms may need to ensure that other factors are adequately
considered prior to making any decisions regarding product development.
Tailoring the regulatory process to shift burdens toward those microorganisms associated
with the greatest uncertainties regarding risk can minimize negative impacts on innovation. Also,
it should be noted that
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Table ES-2a. Total Government Costs Resulting from the Final Rule
(1987 Dollars)
Type of Cost
Year 1
Low
High
Year 5
Low
High
External peer review
Final Rule
Baseline
Incremental Costs
Agency Review
Final Rule
Baseline
Incremental Costs
Total Net Cost to EPA
User Fees Paid to US Treasury
Final Rule
Baseline
Incremental Costs3
Net Government Cost
24,840
0
789,884
738,140
$ 51,744
$ 76,584
10,000
55,000
(45,000)
$121,584
33,900
0
$ 24,840 $ 33,900
1,453,728
1,417,732
$ 35,996
$ 69,896
10,000
55,000
(45,000)
$114,896
Sources: Tables V-2, V-5, V-6, and V-7, Appendix D.
20,700
0
668,118
752,388
(84,270)
(63,570)
15,000
82,500
(67,500)
3,930
28,250
0
$ 20,700 $ 28,250
1,222062
1,423,156
(201094)
(172844)
15,000
82,500
(67,500)
(105,344)
a User fee costs represent a net cost to the Government because the current policy would generate higher user fee revenue
than the final rule.
Note: Because the relative difference for the high cost case is smaller than for the low cost case, high and low cost estimates
are reversed.
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Table ES-2b. Total Government Costs Resulting from the Final Rule
(1995 Dollars)
Year 1
Year 5
Type of Cost
Low
High
Low
High
External peer review
Final Rule	33,683	45,968	28,069	38,307
Baseline	0	0	0	0
Incremental Costs	$ 33,683 $ 45,968	$ 28,069	$ 38,307
Agency Review
Final Rule	1,071,083	1,971,255	905,968	1,657,116
Baseline	1,000,918	1,922,445	1,020,238	1,929,799
Incremental Costs	$ 70,165	$ 48,811	(114,270)	(272,683)
Total Net Cost to EPA	$ 103,848	$ 94,779	(86,201)	(234376)
User Fees Paid to US Treasury
Final Rule	13,560	13,560	20,340	20,340
Baseline	74,580	74,580	111,870	111,870
Incremental Costs3	(61,020) (61,020)	(91,530) (91,530)
Net Government Cost	$164,868 $155,799	5,329 (142,846)
Sources: Tables V-2, V-5, V-6, and V-7, Appendix D.
a User fee costs represent a net cost to the Government because the current policy would generate higher user fee revenue
than the final rule.
Note: The Regulatory Impact Analysis of Regulations on Microbial Products of Biotechnology prepared on January 14,
1994 presented costs in terms of 1987 wage rates. These values have been revised to reflect current wage rates.
Specifically, government costs for selected regulatory options were updated based on estimated increases in labor
category cost estimates between March 1987 and June 1995.
According to the Bureau of Labor Statistics Employment Cost index, the average percent rate of increase in total
compensation between March 1987 and June 1995 was 35.6% (BLS 1995). This value was used to inflate values
for Year 1 and 5 of the quantified government costs of selected regulatory options in this table.
Because the relative difference for the high cost case is smaller than for the low cost case, high and low cost
estimates are reversed.
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impacts on innovation are not necessarily harmful in all cases because not all innovations will be
valuable enough to outweigh the costs and risks they impose. In cases where public opposition to
products beneficial to society is based on misperceptions regarding risk, a regulatory review
process that addresses public concerns could spur innovation.
G. International Considerations
The regulatory requirements of the rule are examined in the context of progress made in
the development of regulatory initiatives in foreign countries. The foreign countries considered
include European Community (EC) nations, Japan, and Canada.
A considerable amount of additional research would be required to determine fully the
impacts of the rule on the international competitiveness of U.S. biotechnology firms. However,
several preliminary observations have been made for this analysis. First, any moderate effects of
the rule on industry cost - positive or negative - could be overwhelmed by other technical,
economic and legal forces affecting international competitiveness.
Second, while it was not possible to project impacts of the rule on U.S. research and
innovation, in theory, any negative impacts on innovation at home could also affect the U.S.
international position. Any such negative impacts might be partly mitigated by gains in other
biotechnology fields (e.g., medical or animal health), if company or university resources were
diverted away from TSCA applications and into other areas of biotechnology research.
Conversely, any encouragement of innovation due to the rule would tend to help the U.S.
competitive position.
Third, it is difficult to draw precise conclusions concerning the relative stringency of various
national regulations, both because the regulatory frameworks in leading biotechnology countries
are in a state of transition and because previous regulatory language did not fully capture the
actual stringency of requirements when put into practice. Actual requirements may depend, to
some extent, on local social, economic, and political factors as well as the actual regulatory
language and scientific considerations. Overall, the similarities among stated national regulatory
approaches examined for this RIA were more striking than the differences. Truly significant
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differences may not become apparent until there have been several years of experience with the
various regulatory schemes.
H. Effects of the Final Rule on Small Businesses
For the purposes of this analysis, EPA defines a small business to be a company with
annual sales of $40 million or less. Based on this definition, EPA found in its Initial Regulatory
Flexibility Analysis (IRFA) that a substantial portion of the regulated community could be classified
as small businesses.
Although data were not available that would allow standard criteria developed by the
Agency to assess the magnitude of small business impacts to be employed, the Agency's finding
of a substantial portion of small businesses in the regulated community prompted EPA to propose
flexibility options to provide relief to small businesses potentially affected by the rule.
In developing flexibility options, two major issues were considered. First, the flexibility
options should not result in an unreasonable risk. Second, regulatory burden for small businesses
should be reduced.
Therefore, one proposed flexibility option would reduce up-front CBI substantiation
requirements for small businesses. This alternative would reduce compliance costs, since some
CBI claims may never require substantiation (typically, substantiation would be required at the time
of a Freedom of Information Act request), while at the same time having little effect on level of risk.
A second alternative would be to eliminate the $100 notification filing fee charged to small
businesses. In the preamble to the rule, EPA requested comment on its IRFA.
While comments specifically addressing the Agency's Initial Regulatory Flexibility Analysis
(IRFA) were not received, comments were submitted indicating concern for impacts on products of
low-value or limited use. Comments were also received on the Agency's proposed alternatives for
substantiation of confidential business information (CBI) claims in connection with TERA
submissions.
With regard to comments regarding smaller-scale products development, EPA finds that,
because smaller scale projects of limited use would most likely be exempt or involve a relatively
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limited set of use and exposure scenarios, burdens due to regulatory review would be expected to
be minimal; thus, the impacts of greatest concern to smaller institutions or organizations could be
frequently mitigated. In considering comments regarding CBI substantiation, EPA has decided not
to require up-front CBI substantiation in connection with TERA submissions. The Agency
considered reducing up-front CBI substantiation requirements for small businesses submitting
TERAs in its IRFA; thus, EPA views the CBI substantiation requirements contained in the final rule
as providing maximum flexibility to small businesses (or any business) conducting R&D.
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