[Federal Register Volume 63, Number 128 (Monday, July 6, 1998)]
[Rules and Regulations]
[Pages 36362-36365]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-17701]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 172
[Docket No. 93F-0286]
Food Additives Permitted for Direct Addition to Foods for Human
Consumption; Acesulfame Potassium
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule; response to objection, confirmation of effective
date.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is overruling the
objection that it has received on the final rule that amended the food
additive regulations to provide for the safe use of acesulfame
potassium (ACK) as a nonnutritive sweetener in alcoholic beverages.
After reviewing the objection to the final rule, the agency has
concluded that the objection does not provide a basis for revoking the
amendment to the regulation. Therefore, FDA is confirming the effective
date for the final rule. The final rule was issued in response to a
food additive petition filed by Hoechst Celanese Corp.
DATES: The effective date of the final rule published at 60 FR 21700
is confirmed as May 3, 1995.
FOR FURTHER INFORMATION CONTACT: Patricia A. Hansen, Center for Food
Safety and Applied Nutrition (HFS-206), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-418-3093.
SUPPLEMENTARY INFORMATION:
I. Introduction
In the Federal Register of May 3, 1995 (60 FR 21700), FDA issued a
final rule amending its regulations to permit the use of acesulfame
potassium (ACK) as a nonnutritive sweetener in alcoholic beverages (the
``alcoholic beverages final rule''). This amendment of the regulation,
codified at 21 CFR 172.800(c)(12), was issued in response to a food
additive petition (FAP No. 3A4391) filed by Hoechst Celanese Corp. FDA
based its decision to permit the use of ACK in alcoholic beverages on
the data in this petition and other relevant information in its files,
including data and information from
[[Page 36363]]
previous petitions for various uses of ACK.\1\
---------------------------------------------------------------------------
\1\ Acesulfame potassium, the potassium salt of 6-methyl-1,2,3-
oxathiazine-4(3H)-one-2,2-dioxide, was first approved for a variety
of uses as a nonnutritive sweetener on July 28, 1988 (53 FR 28379).
Subsequent to its initial approval decision on the use of ACK, FDA
approved the following additional uses for ACK in response to
petitions in: Baked goods and baking mixes, including frostings,
icings, and fillings for baked goods; yogurt and yogurt-type
products; frozen and refrigerated desserts; sweet sauces, toppings,
and syrups; and alcoholic beverages on December 1, 1994 (59 FR
61538, 61540, 61543) and on May 3, 1995 (60 FR 21700).
---------------------------------------------------------------------------
II. Summary of Objection
Following the publication of the alcoholic beverages final rule,
the Center for Science in the Public Interest (CSPI) filed a timely
submission objecting to the approval of ACK for use in alcoholic
beverages. CSPI's submission consisted of a letter, dated June 1, 1995,
and a copy of CSPI's objections to FDA's original approval decision on
ACK (the ``dry uses final rule'') (July 28, 1988, 53 FR 28379).\2\ CSPI
specifically requests that FDA ``withdraw this approval, and, instead,
require that acesulfame potassium (including its breakdown products) be
evaluated for carcinogenicity in properly conducted long-term animal
feeding tests.'' CSPI also requests that FDA reconsider and act
favorably on its previous objections to the dry uses final rule,
alleging that FDA has not addressed these previous objections in a
substantive manner. CSPI does not request a hearing on its objection to
the alcoholic beverages final rule, nor does it request a stay of the
rule.\3\
---------------------------------------------------------------------------
\2\ In its 1988 objections to the dry uses final rule, CSPI
objected to the agency conclusions drawn from each of the three
long-term safety studies of ACK conducted in rodents and sought
revocation of the rule. CSPI asked FDA to consider four separate
objections to the rule and to hold a public evidentiary hearing on
the issues raised in each of its objections. FDA considered the
issues raised by CSPI and responded to them, in detail, in the
Federal Register of February 27, 1992 (57 FR 6667, ``1992 response
to objections''). The agency concluded, after reviewing the
objections, that no genuine issues of material fact had been raised
that would justify a hearing and, accordingly, denied CSPI's
requests for a hearing.
\3\ In its 1988 objections to the dry uses final rule, CSPI
requested a stay of the rule until the hearing it had also requested
could be held. FDA denied both the requests for a hearing and a
stay.
---------------------------------------------------------------------------
III. Provisions for Objections and Hearing Requests
The agency's regulations regarding food additive petitions (21 CFR
171.110) provide that objections and hearings relating to food additive
regulations are to be governed by part 12 (21 CFR part 12). Under
Sec. 12.24(a), the Commissioner of Food and Drugs is to review all
objections and hearing requests and make three determinations: (1)
Whether the regulation at issue should be modified or revoked, (2)
whether a hearing has been justified, and (3) whether an alternative
form of hearing (e.g., before a Public Board of Inquiry under 21 CFR
part 13), if requested, has been justified. As provided for in
Sec. 12.30(a), a person may submit objections and waive the right to a
hearing; such waiver may be express or may result from the failure to
request a hearing (see Sec. 12.22(a)). Even when no hearing has been
requested, the Commissioner has the discretion to order a hearing under
Sec. 12.30(b) and should exercise such discretion when it is in the
public interest to do so. Because issuance of a final rule constitutes
a finding that such action is in the public interest, a substantial
showing is required to justify the Commissioner's exercise of his
discretion to order a hearing to reconsider a final rule.
The objector to the alcoholic beverages final rule for ACK, CSPI,
has waived its right to a hearing by failing to request a hearing (see
Sec. 12.22(a)(4)). Thus, the only remaining question under
Sec. 12.24(a) is whether CSPI's objection, and the information
submitted in support of the objection, establish that the food additive
regulation for ACK should be revoked or modified. If revocation or
modification has not been justified, FDA must then evaluate the record
to determine whether there is a reason for the Commissioner to exercise
his discretion to order a hearing.
As discussed in detail in section IV of this document, FDA has
concluded that CSPI has not established a basis for revocation or
modification of the food additive regulation for ACK. Thus, the agency
is overruling CSPI's objection. Likewise, because CSPI has not
identified new relevant information or articulated an interpretation of
existing information not previously addressed by FDA, there is no
factual dispute to be resolved. Further, there has been no showing that
such a hearing would otherwise be in the public interest. Accordingly,
there is no reason for the Commissioner to exercise his discretion and
order a hearing.
IV. Analysis of the Objection
In order to justify a revocation or modification of the food
additive regulation authorizing the use of ACK in alcoholic beverages,
CSPI must establish that FDA failed to conduct a fair evaluation of the
evidence in the record and thus erroneously concluded that there is a
reasonable certainty of no harm from the use of ACK in alcoholic
beverages. As shown in section IV of this document, CSPI's objections
cite no new data or information and simply reiterate issues that FDA
has previously considered and resolved. Thus, FDA has concluded that
there is no basis to modify or revoke the food additive regulation for
ACK.
A. FDA's Determination of Safety
In its June 1, 1995 letter, objecting to the alcoholic beverages
final rule, CSPI quotes from an FDA memorandum\4\ ``* * * The use of
acesulfame potassium in alcoholic beverages contributes only a very
small percentage of acesulfame potassium intake to the total because of
the limited number of users of these products and their low intakes.''
CSPI indicates its agreement with FDA's assessment of the dietary
intake of ACK, but also goes on to state: ``* * * we expect minimal
public exposure to acesulfame potassium in the alcoholic beverages
covered in the approval. However, de minimis exposure of the public
does not solve the safety problems associated with acesulfame potassium
* * *.''
---------------------------------------------------------------------------
\4\ Memorandum from M. DiNovi, Chemistry Review Branch, CFSAN,
FDA to P. Hansen, Biotechnology Policy Branch, CFSAN, FDA, April 28,
1994 (Ref. 1 in the alcoholic beverages final rule).
---------------------------------------------------------------------------
Although CSPI implies that FDA's decision on the safe use of ACK in
alcoholic beverages was based on intake data alone, this is not the
case. In concluding that the use of ACK in alcoholic beverages was
safe, FDA reviewed data and information in the petition as well as
other relevant information from its files, including data and
information contained in previous petitions for various uses of ACK. As
discussed in the alcoholic beverages final rule (60 FR 21700 at 21701),
FDA made its determination based on an analysis of the safety data and
a consideration of conditions relevant to the proposed use in alcoholic
beverages, including the estimated low increase in dietary exposure to
ACK from its use in alcoholic beverages.\5\
---------------------------------------------------------------------------
\5\ Specifically, in its original review of the safety of ACK,
FDA concluded that a review of animal feeding studies showed that
there is no association between neoplastic disease (cancer) and
consumption of this additive (53 FR 28379 at 28380 and 28381, July
28, 1988). FDA also established an acceptable daily intake (ADI) for
ACK, based on the information from the animal feeding studies. Based
on all of the information before it, FDA concluded that ACK was safe
for the uses proposed in the original petition.
In its evaluation of the safety of ACK for use in alcoholic
beverages, FDA considered, among other things, various conditions
relevant to the proposed use. One consideration was whether an
individual's estimated daily intake (EDI) of ACK would be less than
the ADI that had been previously established from toxicological
information. The agency concluded that the EDI for ACK resulting
from its use in alcoholic beverages, as well as all uses listed at
that time and other uses in a pending petition, was well below the
ADI. On the basis of all the information before it, FDA concluded
that the proposed use in alcoholic beverages was safe.
---------------------------------------------------------------------------
[[Page 36364]]
CSPI's objection to the alcoholic beverages final rule does not
provide any new evidence or identify any evidence that FDA overlooked
in previous evaluations that would call into question FDA's
determination of safety. Moreover, CSPI has not provided a basis for
concluding that the information FDA has evaluated is inadequate to
support a finding that the use of ACK in alcoholic beverages is safe.
Thus, with respect to this issue, CSPI has not provided any basis for
FDA to revoke the alcoholic beverages final rule.
B. Long-Term Testing; Breakdown Products of ACK
As previously noted, in CSPI's objection to the alcoholic beverages
final rule, the organization requests that FDA require long-term animal
testing of the breakdown products of ACK.\6\ CSPI's submission does
not, however, provide any information to support its view that such
testing is necessary to establish the safety of ACK for use in
alcoholic beverages. Because CSPI's submission provides no information
to support its request, it provides no basis for FDA to reconsider its
decision to issue the alcoholic beverages final rule. Thus, the agency
is overruling this aspect of CSPI's objection and is denying the
request that FDA require additional testing of the breakdown products
of ACK.
---------------------------------------------------------------------------
\6\ These products are acetoacetamide-N-sulfonic acid (AAS) and
acetoacetamide (AAA).
---------------------------------------------------------------------------
C. Long-Term Testing; ACK
In its objection to the alcoholic beverages final rule, CSPI also
asks that FDA require additional long-term testing of ACK.\7\ CSPI
alleges that ``* * * technical flaws render several key safety studies
inadequate, and * * * available evidence suggests that acesulfame
potassium may pose a cancer risk'' and mentions four specific issues
with respect to the existing long-term animal testing of ACK, quoting
directly from its objections to the dry uses final rule. In support of
this aspect of its objection to the alcoholic beverages final rule,
CSPI submitted a copy of its objections to the dry uses final rule.
CSPI asked FDA to ``* * * reconsider and act favorably on our 1988
objections.''
---------------------------------------------------------------------------
\7\ As discussed in detail in the dry uses final rule (53 FR
28379 at 28380), the safety data originally submitted by the
petitioner included a feeding study performed in mice and a feeding
study performed in rats. FDA concluded that the mouse study was
adequate for the safety evaluation of ACK, but that the rat study
(``the first rat study'') was inadequate for a safety evaluation of
ACK. The petitioner then conducted a second feeding study in rats
(``the second rat study''); the agency concluded that this second
rat study was adequate to assess the safety of ACK. The agency also
concluded that the results of the second rat study, together with
the results of the mouse study, established that there was no
association between neoplastic disease (cancer) and consumption of
ACK.
---------------------------------------------------------------------------
One of the issues raised by CSPI in its June 1, 1995, letter
concerns the adequacy of one of the long-term studies of ACK that was
conducted in rats: ``* * * the doses of acesulfame potassium given in
the petitioner's second long-term rat study were too low to make that
study adequate to show that the chemical does not cause cancer in rats
* * *.'' CSPI raised exactly the same issue in its objections to the
dry uses final rule, and FDA responded, in detail, to this issue in the
agency's 1992 response to objections.\8\ In its objection to the
alcoholic beverages final rule, CSPI provides no additional evidence or
analysis to support its assertion regarding dosing. Thus, the agency
incorporates its 1992 discussion of the dosing in the second rat study,
in full, into the present response. Specifically, FDA reaffirms its
earlier determination that the dosing levels in this study were
appropriate to evaluate the safe use of ACK, and that this study
demonstrated the safety of ACK (57 FR 6667 at 6669, see also 53 FR
28379, 28380).
---------------------------------------------------------------------------
\8\ In the 1992 response to objections (57 FR 6667 at 6669) FDA
denied CSPI's request for a hearing on this issue because the data
and information identified by CSPI in support of this objection,
even if established at a hearing, would not have been adequate to
justify resolution, in CSPI's favor, of the factual questions about
adequacy of dosing. Because the information cited was not sufficient
to establish CSPI's factual assertion, a hearing was not granted on
this issue (see Sec. 12.24(b)(3)).
---------------------------------------------------------------------------
Once an issue has been considered in a prior proceeding, a party is
estopped from raising that same issue in a subsequent proceeding in the
absence of new evidence.\9\ Because CSPI's objection to the alcoholic
beverages final rule neither identifies nor contains any new evidence
or new analysis to support its assertion that the dosing in the second
rat study was inadequate, it provides no basis for reconsideration of
this issue by FDA. Moreover, CSPI's objection does not provide any
information that links this issue to FDA's determination that the use
of ACK in alcoholic beverages is safe and, thus, provides no basis for
FDA to revoke the alcoholic beverages final rule.
---------------------------------------------------------------------------
\9\ Even if the objections raise material issues of fact, FDA
need not grant a hearing if those same issues were adequately raised
and considered in an earlier proceeding. Once an issue has been so
raised and considered, a party is estopped from raising that same
issue in a later proceeding without new evidence. The various
judicial doctrines dealing with finality are validly applied to the
administrative process. In explaining why these principles ``self-
evidently'' ought to apply to an agency proceeding, the D.C. Circuit
wrote: ``The underlying concept is as simple as this: Justice
requires that a party have a fair chance to present his position.
But overall interests of administration do not require or generally
contemplate that he will be given more than a fair opportunity.''
(Retail Clerks Union, Local 1401, R.C.I.A. v. National Labor
Relations Board, 463 F.2d 316, 322 (D.C. Cir. 1972). (See Costle v.
Pacific Legal Foundation, 445 U.S. 198, 214-215 (1980), reh. den.,
445 U.S. 947 (1980). See also Pacific Seafarers, Inc. v. Pacific Far
East Line, Inc., 404 F.2d 804 (D.C. Cir. 1966))).
---------------------------------------------------------------------------
Another issue raised by CSPI in its June 1, 1995, letter concerns
the adequacy of the long-term study of ACK that was conducted in mice:
``* * * the petitioner's long-term mouse study fell short of FDA
guidelines and standards because: (1) A subchronic study needed to set
the proper high dose was not done, and the high dose used was too low,
and (2) the chronic study lasted only 80 weeks, not the minimum 104
weeks * * *.'' CSPI made precisely the same claims in its objections to
the dry uses final rule, and FDA responded, in detail, to this issue in
the agency's 1992 response to objections.\10\ In its objection to the
alcoholic beverages final rule, CSPI provides no additional evidence or
analysis to support its assertions regarding dosing and study length.
Thus, the agency incorporates its 1992 discussion of the mouse study,
in full, into the present response. Specifically, FDA reaffirms its
earlier determination that both the length of, and the dosing in, the
mouse study were adequate for an assessment of ACK's carcinogenic
potential and that the mouse study demonstrated the safety of ACK (57
FR 6667 at 6669, see also 53 FR 28379, 28380).
---------------------------------------------------------------------------
\10\ In the 1992 response to objections (57 FR 6667 at 6669
through 6670) FDA denied CSPI's request for a hearing on this
objection because the data and information identified by CSPI in
support of this objection, even if established at a hearing, would
not have been adequate to justify resolution, in CSPI's favor, of
the factual questions about the duration of, and dosing used in,
this study. Because the information cited was not sufficient to
establish CSPI's factual assertion, a hearing was not granted on
this issue (see Sec. 12.24(b)(3)).
---------------------------------------------------------------------------
As noted, once an issue has been considered in a prior proceeding,
a party is estopped from raising that same issue in a subsequent
proceeding in the absence of new evidence. Because CSPI's objection to
the alcoholic beverages final rule neither identifies nor contains any
new evidence or new analysis to support its assertion that the mouse
study was inadequate, it provides no basis for reconsideration of
[[Page 36365]]
this issue by FDA. Moreover, CSPI's objection does not provide any
information that would link this issue to FDA's determination that the
use of ACK in alcoholic beverages is safe and, thus, provides no basis
for FDA to revoke the alcoholic beverages final rule.
A third issue raised by CSPI in its June 1, 1995, letter concerns
the results of the first rat study: ``* * * the petitioner's first
long-term rat study shows that acesulfame potassium induced tumors in
rats, even though design flaws biased this study against finding
carcinogenicity* * *.'' CSPI has raised this particular issue twice
before, once as a comment on the petition that supported the dry uses
final rule and once as an objection to the dry uses final rule. FDA
considered this issue and addressed it in the dry uses final rule; FDA
also responded, in detail, to this issue in the agency's 1992 response
to objections.\11\ In its objection to the alcoholic beverages final
rule, CSPI provides no additional evidence or analysis to support its
claim that ACK induced tumors in the animals used in the first rat
study. Thus, the agency incorporates both of its earlier discussions of
this issue (from both the dry uses final rule and the agency's 1992
response to objections), in full, into the present response.
Specifically, the agency reaffirms its earlier determination that the
data and information from the first rat study do not establish a
carcinogenic effect of ACK (57 FR 6667 at 6670).\12\
---------------------------------------------------------------------------
\11\ CSPI claimed that there were increased incidences in
lymphoreticular tumors and several types of other tumors; CSPI also
disputed FDA's reasons for concluding that this study was inadequate
for a safety evaluation of ACK. FDA considered and addressed all of
the points in this objection in the 1992 response to objections (57
FR 6667 at 6670 to 6677). FDA denied CSPI's request for a hearing on
this objection on several different grounds, specifically, a
threshold burden of identifying specific evidence was not met (see
Sec. 12.24(b)(2)), the data and information identified were
insufficient to justify the factual determination in CSPI's favor
(see Sec. 12.24(b)(3)), and the factual issues identified were not
determinative with respect to the action requested (see
Sec. 12.24(b)(4)).
\12\ Because of deficiencies and confounding factors in the
first rat study, FDA further concluded that this study is
``inadequate for assessing the carcinogenic potential of the test
compound or for any other purposes of a safety evaluation'' (53 FR
28379 at 28381). As noted, the petitioner subsequently performed a
second study in a different strain of rat.
---------------------------------------------------------------------------
Again, because this particular issue has been considered in a prior
proceeding, CSPI is estopped from raising that same issue subsequently
in the absence of new evidence. Because CSPI's objection to the
alcoholic beverages final rule neither identifies nor contains any new
evidence or new analysis to support its assertion that the first rat
study shows that ACK induces tumors in rats, it provides no basis for
reconsideration of this issue by FDA. Moreover, CSPI's objection does
not provide any information that would undermine FDA's determination
that the use of ACK in alcoholic beverages is safe and, thus, provides
no basis for FDA to revoke the alcoholic beverages final rule.
A fourth issue raised by CSPI in its June 1, 1995, letter concerns
the results of the second rat study: ``* * * the second long-term rat
study shows that acesulfame potassium induces tumors in rats * * *.''
CSPI raised precisely this same issue in its objections to the dry uses
final rule, and FDA responded, in detail, to this issue in the agency's
1992 response to objections.\13\ In its objection to the alcoholic
beverages final rule, CSPI provides no additional evidence or analysis
to support its assertion regarding the results of the second rat study.
Thus, the agency incorporates its 1992 discussion of the results of the
second rat study, in full, into the present response. Specifically, FDA
reaffirms its earlier determination that the second rat study did not
demonstrate an association between the occurrence of tumors and
treatment with ACK (57 FR 6667 at 6674, see also 53 FR 28379 at 28380
and 28381).
---------------------------------------------------------------------------
\13\ CSPI identified two issues in this objection: (1) The
incidence of rare tumors and (2) the incidence of mammary gland
tumors. CSPI also raised four separate points with regard to the
occurrence of mammary tumors. FDA considered and addressed all of
the points in this objection in the 1992 response to objections (57
FR 6667 at 6674 through 6675). FDA denied CSPI's request for a
hearing on this objection on several different grounds: (1) A
threshold burden of identifying specific evidence was not met (see
Sec. 12.24(b)(2)), (2) the data and information identified were
insufficient to justify the factual determination in CSPI's favor
(see Sec. 12.24(b)(3)), and (3) the factual issues identified were
not determinative with respect to the action requested (see
Sec. 12.24(b)(4)).
---------------------------------------------------------------------------
Once an issue has been considered in a prior proceeding, a party is
estopped from raising that same issue in a subsequent proceeding in the
absence of new evidence. Because CSPI's objection to the alcoholic
beverages final rule neither identifies nor contains any new evidence
or new analysis to support its assertion that the second rat study
shows that ACK induces tumors in rats, it provides no basis for
reconsideration of this issue by FDA. Moreover, CSPI's objection
provides no information that would call into question FDA's
determination that the use of ACK in alcoholic beverages is safe and,
thus, provides no basis for FDA to revoke the alcoholic beverages final
rule.
V. Conclusions
The safety of ACK has been thoroughly tested and the data have been
reviewed by the agency. As discussed previously, FDA concluded that the
available data and information establish the safety of ACK as a
nonnutritive sweetener in alcoholic beverages.
The petitioner has the burden to demonstrate safety before FDA can
approve a particular use of a food additive. Nevertheless, once the
agency makes a finding of safety in an approval document, the burden
shifts to an objector, who must come forward with evidence that calls
into question FDA's conclusion (American Cyanamid Co. v. FDA, 606 F2d.
1307, 1314-1315 (D.C. Cir. 1979)).
CSPI has not identified any information in the record to support
its claim that the FDA incorrectly concluded that the use of ACK in
alcoholic beverages is safe. Nor has CSPI established that the agency
overlooked significant information in reaching its conclusion. Indeed,
the objection has not presented any information or analysis that has
not already been carefully reviewed and weighed by the agency. FDA has
determined that the objection provides no basis for FDA to revoke the
alcoholic beverages final rule or to require additional safety testing.
Accordingly, FDA is overruling the objection.
FDA is confirming May 3, 1995, as the effective date of the
amendment to the regulation.
Dated: June 29, 1998.
Michael A. Friedman,
Acting Commissioner of Food and Drugs.
[FR Doc. 98-17701 Filed 6-30-98; 10:34 am]
BILLING CODE 4160-01-F