[Federal Register: August 5, 2003 (Volume 68, Number 150)]
[Rules and Regulations]
[Page 46403-46410]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05au03-15]
 
 
[[Page 46403]]
 
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
 
Food and Drug Administration
 
21 CFR Part 172
 
[Docket No. 1987F-0179]
 
 
Food Additives Permitted for Direct Addition to Food for Human
Consumption; Olestra
 
AGENCY: Food and Drug Administration, HHS.
 
ACTION: Final rule; denial of requests for a hearing and response to
objections.
 
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SUMMARY: The Food and Drug Administration (FDA) is denying the requests
for a hearing it has received on the final rule that amended the food
additive regulations to provide for the safe use of sucrose esterified
with medium and long chain fatty acids (olestra) as a replacement for
fats and oils in savory snacks. After reviewing the objections to the
final rule and the requests for a hearing, FDA has concluded that the
objections do not raise any issue of material fact that justifies a
hearing or otherwise provides a basis for revoking the regulation.
 
FOR FURTHER INFORMATION CONTACT: Mary Ditto, Center for Food Safety and
Applied Nutrition (HFS-255), Food and Drug Administration, 5100 Paint
Branch Pkwy., College Park, MD 20740, 202-418-3102.
 
SUPPLEMENTARY INFORMATION:
 
Table of Contents
 
I. Background and Procedural History
II. Standard for Granting a Hearing
III. Objections and Supporting Documents Submitted by Center for
Science in the Public Interest (CSPI)
IV. Analysis of Objections and Response to Hearing Requests
    A. Carotenoids
    1. Are Carotenoids Beneficial to Health?
    2. Does Consumption of Olestra Cause a Harmful Depletion of
Carotenoids?
    B. Vitamin K
    C. Gastrointestinal (GI) Effects
    1. Are the Observed GI Symptoms Adverse Health Effects?
    2. Did FDA Err in Pooling Certain GI Data for Analysis?
    D. Adequacy of Olestra's Label Statement
    1. Label Statement Regarding GI Effects
    2. Label Statement Regarding Absorption of Nutrients
    E. Alleged Procedural Problems in the Olestra Proceeding
    F. Alleged Absence of Reasonable Certainty of No Harm
V. Summary and Conclusion
 
I. Background and Procedural History
 
    In a notice published in the Federal Register of June 23, 1987 (52
FR 23606), FDA announced that a food additive petition (FAP 7A3997) had
been filed by the Procter & Gamble Co., 6071 Center Hill Rd.,
Cincinnati, OH 45224-1703 (P&G, the petitioner), proposing the issuance
of a food additive regulation providing for the safe use of sucrose
esterified with medium and long chain fatty acids as a replacement for
fats and oils. The common name for this additive is olestra.
Subsequently, the petitioner amended the petition to limit the intended
use of the additive to a 100 percent replacement for conventional fats
in the preparation of savory snacks (i.e., snacks that are salty or
piquant but not sweet, such as potato chips, cheese puffs, and
crackers).
    FDA reviewed the data and information in the olestra food additive
petition to determine whether the additive is safe (see section
409(c)(3) of the Federal Food, Drug, and Cosmetic Act (the act) (21
U.S.C. 348(c)(3)), for use in savory snacks. As part of this review
process, FDA held public meetings of the agency's Food Advisory
Committee (the FAC) and a working group of the FAC, the Olestra Working
Group (the OWG) to provide for a scientific discussion of FDA's
evaluation of the safety data in the petition.
    On January 30, 1996, FDA issued a final rule in the Federal
Register authorizing the use of olestra in place of fats and oils in
prepackaged ready-to-eat savory snacks (61 FR 3118, January 30, 1996)
(Sec.  172.867 (21 CFR 172.867)). In the preamble to the final rule,
FDA concluded that all safety issues regarding olestra had been
addressed adequately and that there is a reasonable certainty that no
harm will result from the use of olestra in savory snacks. The 1996
olestra regulation requires that the fat-soluble vitamins A, D, E, and
K be added to olestra-containing foods to compensate for any inhibition
of absorption of these vitamins caused by olestra. The 1996 regulation
also requires that foods containing olestra be labeled with the
following information statement:
    THIS PRODUCT CONTAINS OLESTRA. Olestra may cause abdominal
cramping and loose stools. Olestra inhibits the absorption of some
vitamins and other nutrients. Vitamins A, D, E, and K have been
added.
(Sec.  172.867(e)(1)).
    Consistent with section 409(f) of the act (21 U.S.C. 348(f)), the
preamble to the final rule advised that objections to the final rule
and requests for a hearing were due within 30 days of the publication
date (i.e., by February 29, 1996)\1\ (Sec.  171.110 (21 CFR 171.110)
and 21 CFR 12.22(a).) On February 29, 1996, CSPI filed six objections
to the final rule and requested a hearing on all six objections.\2\
CSPI had substantially participated in the November 1995 OWG/FAC
meeting and had also filed multiple sets of comments with FDA prior to
issuance of the final rule.
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    \1\ In addition to notifying the public of the opportunity to
submit objections and hearing requests, FDA requested comments on
the olestra label requirement on such issues as the need for such a
label, the adequacy of its content, the agency's word choice, and
the configuration of the label. In the Federal Register of March 3,
2000 (65 FR 11585), FDA announced that a food additive petition (FAP
0A4708) had been filed by P&G proposing to amend Sec.  172.867 by
removing the requirement for the label statement prescribed in Sec.
172.867(e). Elsewhere in this issue of the Federal Register, FDA is
issuing a final rule that responds to FAP 0A4708. In that final
rule, the agency responds to comments received regarding the label
statement.
    \2\ In addition, FDA received several letters within the 30 day
objection period, all of which expressed general opposition to
olestra, identified no substantive question to which the agency can
respond, and did not request a hearing. These letters will not be
discussed further.
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    In the preamble to the 1996 final rule (61 FR 3118 at 3169), FDA
advised that it would publish in the Federal Register notice of the
objections that it received or lack thereof.\3\ This document fulfills
the agency's obligation to publish such a notice. The only timely,
substantive objections FDA received were from CSPI.
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    \3\ The January 30, 1996, final rule includes a more detailed
background statement.
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II. Standard for Granting a Hearing
 
    Under Sec.  171.110 of the food additive regulations, objections
and requests for a hearing are governed by part 12 (21 CFR part 12) of
FDA's regulations. Specific criteria for determining whether a hearing
has been justified are set forth in Sec.  12.24(b). Under the
regulation, a hearing will be granted if the material submitted by the
requester shows, among other things, that: (1) There is a genuine and
substantial issue of fact for resolution at a hearing; a hearing will
not be granted on issues of policy or law; (2) the factual issue can be
resolved by available and specifically identified reliable evidence; a
hearing will not be granted on the basis of mere allegations or denials
or general descriptions of positions and contentions; (3) the data and
information submitted, if established at a hearing, would be adequate
to justify resolution of the factual issue in the way sought by the
requestor; a hearing will be denied if the data and information
 
[[Page 46404]]
 
submitted are insufficient to justify the factual determination urged,
even if accurate; and (4) resolution of the factual issue in the way
sought by the requestor is adequate to justify the action requested; a
hearing will not be granted on factual issues that are not
determinative with respect to the action requested, (e.g., if the
action would be the same even if the factual issue were resolved in the
way sought).
    A party seeking a hearing is required to meet a ``threshold burden
of tendering evidence suggesting the need for a hearing.'' (See Costle
v. Pacific Legal Foundation, 445 U.S. 198, 214-215 (1980), reh. den.,
446 U.S. 947 (1980), citing Weinberger v. Hynson, Westcott & Dunning,
Inc., 412 U.S. 609, 620-621 (1973).) An allegation that a hearing is
necessary to ``sharpen the issues'' or to ``fully develop the facts''
does not meet this test. (See Georgia-Pacific Corp. v. U.S. EPA, 671
F.2d 1235, 1241 (9th Cir. 1982).) If a hearing request fails to
identify any evidence that would be the subject of a hearing, there is
no point in holding one. In judicial proceedings, a court is authorized
to issue summary judgment without an evidentiary hearing whenever it
finds that there is no genuine issue of material fact, and a party is
entitled to judgment as a matter of law (see Rule 56, Federal Rules of
Civil Procedure). The same principle applies in administrative
proceedings (Sec.  12.28).
    A hearing request must not only contain evidence, but that evidence
must raise a material issue of fact concerning which a meaningful
hearing might be held. (See Pineapple Growers Association v. FDA, 673
F.2d 1083, 1085 (9th Cir. 1982).) Where the issues raised in the
objection are, even if true, legally insufficient to alter the
decision, the agency need not grant a hearing. (See Dyestuffs and
Chemicals, Inc. v. Flemming, 271 F.2d 281 (8th Cir. 1959), cert.
denied, 362 U.S. 911 (1960).) FDA need not grant a hearing in each case
where an objector submits additional information or posits a novel
interpretation of existing information. (See United States v.
Consolidated Mines & Smelting Co., 455 F.2d 432 (9th Cir. 1971).) In
other words, a hearing is justified only if the objections are made in
good faith, and if they ``draw in question in a material way the
underpinnings of the regulation at issue.'' (See Pactra Industries v.
CPSC, 555 F.2d 677 (9th Cir. 1977).) Finally, courts have uniformly
recognized that a hearing need not be held to resolve questions of law
or policy. (See Citizens for Allegan County, Inc. v. FPC, 414 F.2d 1125
(D.C. Cir. 1969); Sun Oil Co. v. FPC, 256 F.2d 233, 240 (5th Cir.),
cert. denied, 358 U.S. 872 (1958).)
    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 can be 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, RCIA v. NLRB, 463 F.2d 316, 322 (D.C.
Cir. 1972).) (See also Costle v. Pacific Legal Foundation, supra at
1106, and Pacific Seafarers, Inc. v. Pacific Far East Line, Inc. 404
F.2d 804 (D.C. Cir. 1968).)
    In summary, a hearing request must present sufficient credible
evidence to raise a material issue of fact and the evidence presented
must be adequate to resolve the issue as requested and to justify the
action requested.
 
III. Objections and Supporting Documents Submitted by CSPI
 
    In a document dated February 29, 1996, entitled ``Objections and
Request for Hearing'' (CSPI obj.), CSPI submitted to the Division of
Dockets Management, its objections to the approval of the use of
olestra as a food additive in savory snacks. CSPI submitted six
objections to the 1996 final rule, and requested a hearing on issues
raised by each objection. CSPI raised one general objection to the 1996
final rule, asserting that FDA improperly concluded that the use of
olestra in savory snacks meets the safety standard of reasonable
certainty of no harm. CSPI also raised five specific objections,
asserting that: (1) Olestra's potential to deplete carotenoids may
present a risk of harm to health, which precludes a finding of
reasonable certainty of no harm; (2) FDA's decision to require
compensation with vitamin K may not solve health problems that
depletion of vitamin K may cause; (3) the potential GI disturbances
that olestra may cause are adverse health effects that preclude a
finding of reasonable certainty of no harm; (4) the label statement
required on an interim basis by the 1996 final rule is insufficient to
protect the public against adverse effects associated with consumption
of olestra; and (5) problems with procedure and process tainted FDA's
review of, and decision-making process for, the food additive petition
for olestra to the detriment of FDA's consideration of the public
health concerns raised by CSPI and others. In support of its objections
and hearing requests, CSPI filed 18 exhibits (CSPI exh. 1 through
18.)\4\
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    \4\ In a letter dated August 26, 1996 (Docket No. 1987F-0179),
CSPI requested that certain documents submitted to the agency after
February 29, 1996, be considered part of their objections. As noted
previously, February 29, 1996, was the final day allowed under
section 409(f)(1) of the act for submission of objections and
hearing requests, including supporting material. Accordingly, the
material submitted in August 1996 was not timely filed and thus, has
not been considered in evaluating the CSPI objections and hearing
requests.
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IV. Analysis of Objections and Response to Hearing Requests
 
    As noted in section III of this document, CSPI raised one general
objection and five specific objections to the 1996 final rule. In this
document, FDA addresses each of CSPI's objections, as well as the data
and information filed in support of each, comparing each to the
standards for granting a hearing in Sec.  12.24(b). Because several of
the issues in the general objection overlap with the five more specific
objections, FDA addresses CSPI's five specific objections first (CSPI
obj. 2 through 6), followed by the general objection (CSPI obj. 1).
 
A. Carotenoids
 
    In its second objection and request for a hearing, CSPI states that
there are two questions central to a discussion of the depletion of
carotenoids by consumption of olestra. First, are carotenoids
beneficial to health? Second, if carotenoids are beneficial to health,
does consumption of olestra cause depletion of carotenoids such that
there would be an absence of a reasonable certainty of no harm? CSPI
claims that FDA did not answer either of these questions accurately and
requests a hearing on both factual issues.
1. Are Carotenoids Beneficial to Health?
    In its objection and request for a hearing, CSPI asserts that FDA
erroneously concluded that there is no demonstrated health benefit of
carotenoids except the provitamin A function of beta-carotene.
    In analyzing this objection, it is important to recognize that
FDA's position on carotenoids (as articulated in the 1996 final rule)
has two parts. First, although FDA concluded that there is no
demonstrated association between carotenoids per se and health
 
[[Page 46405]]
 
benefits, the agency agrees that epidemiological studies show an
association between diets rich in fruits and vegetables and decreased
cancer risk (61 FR 3118 at 3149).\5\ As shown in this section, all of
the evidence and opinions cited by CSPI to support this objection is
consistent with an association between fruit and vegetable consumption
and health benefits. Second, FDA concluded that the variation in serum
levels of carotenoids associated with olestra consumption is within the
normal range, given diet variations and the bioavailability of
carotenoids. CSPI's objection does not directly address this second
issue.\6\
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    \5\ Indeed, CSPI itself concedes that there may be ``substances
in fruits and vegetables for which carotenoids are markers'' that
are beneficial to health (CSPI obj. at 19).
    \6\ Although not strictly relevant to the objections lodged by
CSPI, it is important to note that in its 1996 final rule, FDA
acknowledged the growing body of data and information regarding
carotenoids and committed to reviewing such information within 30
months of olestra's initial approval (61 FR 3118 at 3168 and
footnote 94). In June 1998, FDA presented the accumulated data and
information to the FAC.
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    CSPI offers essentially two arguments to support its view that FDA
erroneously concluded that there is no demonstrated health benefit of
carotenoids except the provitamin A function of beta-carotene. First,
CSPI asserts that FDA's position on carotenoids is a minority view.\7\
To support this challenge, CSPI relies on statements of Drs. Regina
Ziegler (CSPI exh. 10), Walter Willet (CSPI exh. 13), and Jerianne
Heimendinger (CSPI exh. 8) to demonstrate that FDA's position is not
well-founded. Importantly, Drs. Ziegler and Willet both state that
fruits and vegetables, not carotenoids per se, are associated with
reduction of the risk of cancer. (CSPI exh. 13, p. 1; CSPI exh. 10,
letter dated October 23, 1995, p. 1, and letter dated January 21, 1996,
p. 2.) Similarly, Dr. Heimendinger asserts merely that evidence is
``increasing that * * * carotenoids may play important roles'' in
reducing cancer risk (emphasis added). (CSPI exh. 8, Heimendinger
letter, p. 2). Thus, none of these statements support CSPI's claim that
carotenoids have been demonstrated to have a significant beneficial
health role.\8\ Accordingly, FDA is denying CSPI's request for a
hearing on this issue because the information identified in the
objection is insufficient to justify the factual determination urged by
CSPI (Sec.  12.24(b)(3)).\9\
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    \7\ Although CSPI asserts that FDA's view is a minority view,
the final rule noted that five different conferences or reviewing
groups have examined the relationship between carotenoids and
disease and concluded that there was insufficient evidence to
recommend specifically the consumption of carotenoids, except to
encourage the consumption of fruits and vegetables (61 FR 3118 at
3148). CSPI does not challenge this fact..
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    CSPI also relies on the dietary guidelines issued by the Department
of Health and Human Services (DHHS), 4th edition, to support its
assertion that FDA's position on carotenoids is a minority view.
Careful reading of the guidelines establishes that, once again, the
evidence identified in the objection does not support the position
urged by CSPI because the guidelines do not identify carotenoids per se
as beneficial to human health.
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    \8\ CSPI's objection and hearing request on this point also
refer to an article published by Dr. Edward Giovannucci addressing
the association between high intake of tomato products and reduced
incidence of prostate cancer and claims that Dr. Giovannucci opposes
the approval of olestra because of the additive's potential to
deplete carotenoids, citing CSPI exh. 8. Although CSPI exh. 8
contains numerous letters from individuals opposing olestra's
approval, there is no identifiable communication from Dr.
Giovannucci in that exhibit. In the absence of specifically
identified evidence demonstrating Dr. Giovannucci's position, FDA is
denying CSPI's objection and hearing on this point (Sec.  12.24
(b)(2)). In addition, CSPI's reliance on the Giovannucci article is
misplaced because, even as described by CSPI, the paper does not
support CSPI's claim that carotenoids themselves have been shown to
have distinct health benefits. Accordingly, FDA is denying CSPI's
claim on this point (Sec.  12.24(b)(2) and (b)(4)).
    \9\ CSPI also relies on its White Paper (CSPI exh. 1) and
exhibits 3 through 7 to the White Paper. Although this reference is
quite lengthy (approximately 230 pages total), CSPI fails to specify
the information or data in these documents that support its
assertion that FDA's position on carotenoids is a minority view. In
such circumstances, reliance on the White Paper (CSPI exh. 1) and
exhibits 3 through 7 cannot justify a hearing because a hearing will
not be granted in the absence of available and specifically
identified reliable evidence to support the factual issue asserted
(Sec.  12.24(b)(2)).
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    Consumption of these foods [fruits and vegetables] is associated
with a substantially lower risk of many chronic diseases, including
certain types of cancers. (CSPI exh. 11, p. 13.)\10\
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    \10\ CSPI's exh. 11 is a photocopy of the complete dietary
guidelines pamphlet. However, at the time of olestra's approval,
only an excerpt (the cover and pp. 22-23 of the pamphlet) was in the
record.
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Elsewhere the guidelines describe the role of carotenoids in health as
yet-to-be established.
    The antioxidant nutrients found in plant foods (e.g., vitamin C,
carotenoids, vitamin E, and certain minerals) are presently of great
interest to scientists and the public because of their potentially
beneficial role in reducing the risk for cancer and certain other
chronic diseases. Scientists are also trying to determine if other
substances in plant foods protect against cancer. (CSPI exh. 11, p.
13, emphasis added.)
Because the information regarding the DHHS dietary guidelines is
insufficient to establish CSPI's claim regarding the role of
carotenoids in human health, FDA is denying a hearing on this issue
(Sec.  12.24(b)(3)).
    As a third basis to show that FDA's position regarding carotenoids
is a minority view, CSPI cites correspondence between FDA and two
different institutes of the National Institutes of Health (NIH).\11\
CSPI challenges FDA's reliance on the letter from the NEI because it
only addresses the role of beta-carotene, not lutein or lycopene. Even
if CSPI's claims on this issue are correct, FDA is denying its request
for a hearing because the assertion that lutein and lycopene have a
beneficial role in eye health is not supported by specifically
identified factual evidence. Accordingly, CSPI's allegations are mere
speculation, which is not an adequate basis for a hearing request
(Sec.  12.24(b)(2)).
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    \11\ Following the November 1995 meeting of the FAC, FDA
exchanged letters with experts at the National Eye Institute (NEI)
and the National Cancer Institute (NCI). CSPI claims that the fact
FDA consulted with experts at NCI and NEI demonstrates that FDA was
uncertain of its position on carotenoids, an assertion unsupported
in the record.
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    With respect to the NCI, CSPI claims that there are conflicting
views in the record from NCI and that FDA should determine, on the
record, the ``official'' NIH position. Specifically, CSPI believes that
Dr. Ziegler's views are significantly different from the views
expressed by the then Director of the Division of Cancer Prevention and
Control, NCI, NIH, Dr. Peter Greenwald.\12\ CSPI does not demonstrate
why such a determination is necessary, the authority under which it
would be done, or how it would alter the outcome of this proceeding.
Accordingly, FDA is denying CSPI's request for a hearing on this issue
(Sec.  12.24(b)(2) and (b)(4)).
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    \12\ In fact, CSPI's own documents demonstrate that there is no
conflict as to the official statements of the NCI regarding
carotenoids because Dr. Ziegler acknowledges that she does not speak
on behalf of the NCI (even though her two letters are written on NCI
letterhead). (CSPI exh. 10, letter dated January 21, 1996, p. 1).
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    Finally, CSPI asserts that FDA staff, the OWG, and the FAC failed
to acknowledge and accept data from in vitro, animal, and epidemiologic
studies that all point to a protective role for carotenoids. In support
of this portion of its second objection, CSPI cites two articles (CSPI
obj. at p. 20, footnote 19).\13\ This portion of CSPI's objection is
without foundation because the information specifically cited is not
adequate to establish the factual issue urged by CSPI\14\ (Sec.
12.24(b)(3)). In particular, the first article cited (Garewal, H.,
``Antioxidants in Oral Cancer Prevention,'' American Journal of
Clinical Nutrition, 62:1410S-1416S, 1995, at 1413S.) concludes that the
reported results do not themselves demonstrate a reduction in human
 
[[Page 46406]]
 
cancer risk,\15\ and CSPI does not identify any other potential health
benefit of carotenoids established by this article. Similarly, the
second publication (Bertram, J. S. and H. Bortkiewicz, ``Dietary
Carotenoids Inhibit Neoplastic Transformation and Modulate Gene
Expression in Mouse and Human Cells,'' American Journal of Clinical
Nutrition, 62:1327S-1336S, 1995, at 1328S.), notes that the
investigators' results simply provide ``a possible mechanistic basis
for the activity of carotenoids as chemopreventive agents (emphasis
added).'' Moreover, citing this second publication, CSPI asserts that
``carotenoids affect intercellular communications'' (CSPI obj. at p.
20, footnote 19). However, CSPI does not demonstrate how the effect of
carotenoids on intercellular communications supports its assertion that
carotenoids are beneficial to health.\16\ Accordingly, FDA is denying
CSPI's hearing request on this issue (Sec.  12.24(b)(3)).\17\
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    \13\ These articles are the only specific data identified by
CSPI to support its second objection.
    \14\ CSPI claims that FDA, the OWG, and the FAC ignored certain
data on carotenoids. Importantly, however, the two journal articles
cited by CSPI were published in a supplement to the December 1,
1995, issue of the American Journal of Clinical Nutrition. The FAC/
OWG meeting was held November 14 through 17, 1995, and CSPI presents
no evidence that these articles were even available at the time of
the meeting. In fact, these two articles were not submitted to FDA
until December 22, 1995.
    \15\ CSPI states that ``carotenoids reverse oral leukoplakia in
rats.'' (CSPI obj. at p. 20, footnote 19.) However, the Garewal
article cited by CSPI in support of this statement presents no data
on the reversal of oral leukoplakia in rats.
    \16\ As noted previously, in the 1996 final rule, FDA concluded
that the variation in serum levels of carotenoids associated with
olestra consumption is within the normal range, given diet
variations and the bioavailability of carotenoids, a conclusion not
addressed directly by CSPI. In view of this unchallenged conclusion,
the Bertram and Bortkiewicz paper, id. at 1333S-1334S, appears to
support a finding of no harm from olestra's effects on carotenoid
levels of consumers of olestra-containing food. ``Our demonstration
that dietary carotenoids can inhibit neoplastic transformation and
modulate the expression of gene products in both human and mouse
cells implies that these ubiquitous compounds have hitherto unknown
properties. Moreover, these effects were produced at micromolar
concentrations that are within the physiologic range * * * ''
    \17\ Indeed, the paper by Bertram and Bortkiewicz is consistent
with FDA's conclusion that the available evidence demonstrates an
association between a diet rich in fruits and vegetables and
reduction in the risk of certain diseases. ``Many epidemiologic
studies have shown a consistent inverse correlation between
consumption of foods rich in carotenoids * * * and future risk of
cancer.'' (Id. at 1327S.)
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    CSPI's second argument to support its position that FDA erroneously
concluded that there is no demonstrated health benefit of carotenoids,
except the provitamin A function of beta-carotene, is that the agency
wrongly insisted on randomized trials to establish the role of
carotenoids in health. CSPI bases this allegation on the fact that FDA
quoted Dr. Alvan Feinstein in the preamble to the 1996 final rule. CSPI
implies that FDA relied on Dr. Feinstein and thus, ignored evidence in
the record that establishes a beneficial role of carotenoids in human
health. In addition, CSPI claims that Dr. Feinstein is a ``debunker''
and he, and his views, lack credibility.
    These allegations are not adequate to justify a hearing on this
issue for three reasons. First, CSPI quotes Dr. Feinstein out of
context. Contrary to CSPI's claim, Dr. Feinstein did not ``insist'' on
randomized trials. Instead, Dr. Feinstein described certain limitations
of epidemiologic studies (studies such as those cited by another
witness, Dr. Meir Stampfer), including the fact that it is difficult to
draw conclusions about cause and effect relationships from such studies
(61 FR 3118 at 3147 to 3148), a conclusion not directly challenged by
CSPI. Thus, FDA is denying CSPI's hearing request on this point because
a hearing will not be granted where the information to support the
factual conclusion urged is unreliable (Sec.  12.24(b)(2)). Second,
CSPI asserts that Dr. Feinstein failed to acknowledge that the test
methods he advocated might not be meaningful for dietary carotenoids.
Because CSPI offers no evidence to suggest that these methods are not
appropriate and does not show how, if at all, prevailing on this
factual issue would change the outcome of the rulemaking, FDA is
denying a hearing on this issue (Sec.  12.24(b)(2) and (b)(4)).
Finally, in reaching its position on carotenoids, FDA considered all
the comments, data, and information that the agency had received on
carotenoids, including information from epidemiological studies (61 FR
3118 at 3149). FDA's position on the carotenoids issue is not
inconsistent with the findings of the epidemiological studies relied
upon by CSPI (61 FR 3118 at 3149). Thus, even if Dr. Feinstein's views
were shown to be incorrect and CSPI prevailed on this issue, the
outcome of the ruling would not be altered. Therefore, FDA is denying
CSPI's request for a hearing on this issue (Sec.  12.24(b)(4)).
2. Does Consumption of Olestra Cause a Harmful Depletion of
Carotenoids?
    In its second objection and request for a hearing, CSPI asserts
that consumption of olestra likely would cause major depletions of
serum levels of carotenoids and that this depletion could be harmful
because carotenoids have beneficial properties.\18\ CSPI also asserts
that even a 5 to 10 percent reduction in serum levels of carotenoids
could be harmful. CSPI offers several arguments to support this portion
of its objection.\19\
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    \18\ To the extent that CSPI contends that there is a lack of
reasonable certainty of no harm from olestra's depletion effect on
carotenoids, CSPI's hearing request is denied because whether a food
additive is safe for its intended use (i.e., whether there is a
reasonable certainty of no harm) is a question of law to be decided
based on the facts established in the record. Under Sec.
12.24(b)(1), a hearing will not be granted on issues of policy or
law.
    \19\ It is important to note that depletion of serum carotenoid
levels is relevant only if carotenoids themselves are shown to have
human health benefits. As discussed in the previous section, CSPI's
objection and hearing request fails to establish any genuine issue
of material fact regarding FDA's conclusion that there is no
demonstrated health benefit of any carotenoid except the provitamin
A function of beta-carotene. Thus, this portion of CSPI's objection
and hearing request is also denied because resolution of this issue
in CSPI's favor would not alter the outcome of this proceeding
(Sec.  12.24(b)(4)).
---------------------------------------------------------------------------
 
    First, CSPI asserts generally that the amounts of olestra consumed
are sufficient to cause major depletions of carotenoids, referring to
``the section [above] on consumption estimates.'' (CSPI obj. at p. 24.)
However, there is no such section in CSPI's submission.\20\ Moreover,
CSPI's objection did not offer any facts to contradict FDA's conclusion
in the final rule that the magnitude of olestra's effects on carotenoid
absorption are likely to be within the range of normal variation (61 FR
3118 at 3149). Accordingly, FDA is denying CSPI's challenge to the
agency's determination that any depletion of carotenoids by olestra
consumption would be minor because a hearing on a factual issue will
not be granted in the absence of specifically identified, available
evidence to support the requestor's position (Sec.  12.24(b)(2)).
---------------------------------------------------------------------------
 
    \20\ It is possible that CSPI intended to reference the
discussion in its White Paper (CSPI exh. 1) on consumption
estimates, but no such reference was given (Sec.  12.24(b)(2)).
---------------------------------------------------------------------------
 
    CSPI also challenges FDA's conclusion on the magnitude of
carotenoid depletion by asserting that patterns of consumption of
olestra will not prevent such depletion. In particular, CSPI asserts
that P&G's depletion studies only measured the status of beta-carotene
and thus, the full impact of olestra consumption on carotenoids was not
assessed. However, CSPI did not submit or otherwise specifically
identify evidence to establish that olestra's effect on beta-carotene
was not representative of the additive's effect on carotenoids
generally. Moreover, CSPI does not demonstrate how resolving this
particular issue in its favor will alter the outcome of this
proceeding. Accordingly, FDA is denying CSPI's objection and hearing
request (Sec.  12.24(b)(2) and (b)(4)).
    CSPI also claims that FDA erroneously relied on data presented by
P&G on patterns of consumption when the agency concluded that olestra's
effects on carotenoid absorption would not be harmful. CSPI did not
present
 
[[Page 46407]]
 
any specific information to dispute P&G's consumption pattern data;
instead, CSPI simply asserted that other consumption patterns were
likely.\21\ Mere allegations of this type do not require that a hearing
request be granted (Sec.  12.24(b)(2)). Moreover, although the
petitioner did present information on snack consumption patterns and
their effects on carotenoid depletion, FDA did not rely on this
information in its safety determination (61 FR 3118 at 3149 at footnote
51). Accordingly, even if CSPI were to prevail on this factual issue,
the outcome of this rulemaking would not be altered and thus, FDA is
denying this portion of CSPI's objection and hearing request (Sec.
12.24(b)(4)).\22\
---------------------------------------------------------------------------
 
    \21\ For example, CSPI claims that the ``great popularity of
tomato-based salsa in recent years suggests that many consumers
would consume tortilla, corn, or potato chips with this carotenoid-
rich dip, with or between meals.'' (CSPI obj. at p. 24.) Similarly,
CSPI asserts that ``consumption of savory snacks is likely to
increase if olestra snacks become generally available.'' (CSPI obj.
at p. 25.) CSPI does not identify any particular information or
evidence in the record to support either assertion (Sec.
12.24(b)(2)).
    \22\ In questioning the petitioner's evidence on consumption
patterns, CSPI also challenges the hypothesis of Dr. Penny Kris-
Etherton, a P&G consultant, that consumption of olestra-containing
foods between meals has no effect on carotenoid depletion.
Importantly, however, CSPI fails to identify any credible data or
information to support its assertion that this hypothesis is
``unproven and doubtful.'' (CSPI obj. at p. 25.) Thus, FDA is
denying CSPI's request for a hearing on this point (Sec.
12.24(b)(2)).
---------------------------------------------------------------------------
 
    Finally, CSPI relies on the proceedings of a January 1996 workshop
at the Harvard School of Public Health to support its view that
olestra's depletion of carotenoids will be harmful.\23\ In particular,
CSPI cites estimates of the possible impact on the public health that
would allegedly result from the wide-spread use of olestra in snack
foods, which estimates were presented at the Harvard meeting (CSPI exh.
13). CSPI contends that if FDA had correctly understood the Harvard
meeting estimates regarding carotenoid depletion, it is doubtful that
olestra would have been approved\24\ (CSPI obj. at 28).
---------------------------------------------------------------------------
 
    \23\ CSPI raises two spurious arguments regarding carotenoids,
neither of which is adequate to justify a hearing on this issue.
Specifically, CSPI criticizes the agency because no one from FDA's
``senior level'' attended the meeting, and faults the summary
prepared by the FDA staffer who did attend the meeting. In addition,
CSPI claims that Dr. Stampfer was given only a limited period to
speak during the November 1995 FAC meeting and that his schedule
precluded him from staying for the afternoon session when he could
have expanded his comments. Neither of these arguments raises a
material question of fact that requires a hearing (Sec.
12.24(b)(1)).
    \24\ CSPI also asserts that at the Harvard meeting, P&G employee
Dr. Keith Triebwasser ``stated that he could not assume that
depletion of carotenoids was harmless,'' citing a letter from Dr.
Alberto Ascherio (CSPI exh. 15). Importantly, however, Dr. Ascherio
does not directly quote or even paraphrase Dr. Triebwasser; instead,
the letter contains Dr. Ascherio's characterization of what Dr.
Triebwasser said. (Dr. Ascherio stated: ``The responses of the
gentleman from Procter & Gamble made it clear that there is no
scientific evidence to support [a conclusion that depletion of
carotenoids will not harm people's health.]'' Again, the information
tendered by CSPI is insufficient to justify the factual conclusion
urged and thus, FDA is denying CSPI's request for a hearing on this
issue (Sec.  12.24(b)(3)).
---------------------------------------------------------------------------
 
    FDA is denying CSPI's request for a hearing on this point because
the data and information submitted are insufficient to establish that
olestra's depletion of carotenoids will be harmful (Sec.  12.24(b)(3)).
First, the comments of those preparing the estimates undermine their
validity. In particular, in their letter transmitting the estimates,
Drs. Willett and Stampfer readily acknowledge that the estimates are
not based on an established cause and effect relationship and are
speculative in that they are based on a number of assumptions (CSPI
exh. 13, pp. 1, 3, and 4). Moreover, in the preamble to the final rule,
FDA outlined several considerations to be addressed in determining
whether olestra's effect on carotenoids will be harmful, including the
other factors that influence carotenoid utilization (carotenoid
stability, bioavailability, and absorption) and whether serum
carotenoid levels are an adequate indicator of carotenoid availability
(61 FR 3118 at 3148 to 3149). Neither CSPI nor the scientists who
prepared the Harvard estimates addressed these considerations.
Accordingly, the Harvard estimates in and of themselves are not
adequate to demonstrate that olestra's effect on carotenoid levels will
be harmful.
 
B. Vitamin K
 
    In its third objection and request for a hearing, CSPI challenges
FDA's conclusion that supplementation of olestra with vitamin K will
offset the additive's effect on vitamin K and thereby prevent adverse
health effects associated with vitamin K depletion in olestra
consumers. CSPI claims that FDA's decision on this point is erroneous
for two reasons. First, CSPI asserts that a decision on olestra's
safety should not have been made in the absence of a study of the
interaction between Coumadin (a widely used anti-coagulant) and
olestra. Importantly, however, CSPI did not specifically identify any
available data or information in the record to demonstrate why data
from a study of olestra's effects on Coumadin therapy are
necessary.\25\ Accordingly, FDA is denying CSPI's request for a hearing
on this question because it is merely an unsupported allegation (Sec.
12.24(b)(2)). Second, CSPI asserts that olestra supplemented with
vitamin K may have adverse effects on bone formation. Once again, CSPI
fails to specifically identify any data or information that could be
used to resolve this question. Accordingly, FDA is denying CSPI's
objection and hearing request on this point (Sec.  12.24(b)(2)).
---------------------------------------------------------------------------
 
    \25\ In fact, this concern was raised at the November 1995 FAC
meeting and addressed in the preamble to the final rule. One
witness, Dr. John Suttie, testified that vitamin K intake can vary
from day-to-day by three or four-fold and that diet is not usually a
primary factor of concern with anti-coagulation therapy.
Accordingly, he concluded that changes due to consumption of
vitamin-K compensated olestra would likely be within the normal
range of dietary variation (61 FR 3118 at 3147).
---------------------------------------------------------------------------
 
C. GI Effects
 
    In its fourth objection and request for a hearing, CSPI asserts
that in a significant proportion of individuals olestra causes GI
disturbances, including diarrhea, that these disturbances are adverse
health effects, and that these GI disturbances are of sufficient
concern to warrant a finding that there is no ``reasonable certainty of
no harm.'' CSPI also asserts that FDA's analysis of the data from two
8-week studies obscured the detection of trends between olestra
consumption and GI symptoms reported.
1. Are the Observed GI Symptoms Adverse Health Effects?
    In its objection and request for a hearing, CSPI asserts that FDA
erred by concluding that certain GI effects of olestra (such as anal
leakage, underwear staining, and oil-in-the-toilet) are not relevant to
the question of the safety of olestra.\26\ In particular, CSPI asserts
that these olestra-related effects can have an ``adverse effect on
people's lives and interfere with their daily activities'' and thus
implies that FDA should have considered them in determining olestra's
safety. In support of this objection, CSPI relies heavily on the
proceedings before the OWG and the FAC (such as the testimony of Dr.
Ian Greaves and Ms. Rosie Schwartz.)\27\
---------------------------------------------------------------------------
 
    \26\ In its fourth objection, CSPI also claims that consumption
of olestra causes diarrhea, which CSPI claims is an adverse health
effect. However, CSPI does not further address diarrhea in this
objection.
    \27\ As part of their objections, CSPI criticizes a P&G market
research study, and the OWG's alleged reliance on it. FDA told the
OWG that the agency had not used data from the market research study
in its analysis. Moreover, FDA did not rely on the study in
determining that olestra is safe. CSPI concedes as much (CSPI obj.
at p. 33).
---------------------------------------------------------------------------
 
    At its core, CSPI's fourth objection concerns the meaning of the
statutory standard of ``safe,'' section 409(c)(3)(A) of the act, and,
specifically, what is
 
[[Page 46408]]
 
``harm'' for purposes of that standard.\28\ CSPI has not demonstrated
that FDA wrongly decided any genuine and substantial issue of fact
concerning the GI effects of olestra. Rather, CSPI disagrees with FDA's
application of the statutory safety standard, alleging that FDA ignored
certain effects of olestra consumption that CSPI claims preclude a
finding of safety.\29\ In the absence of a genuine and substantial
issue of fact, a hearing need not be granted because a hearing is not
needed to settle issues of law (Sec.  12.24(b)(1)).
---------------------------------------------------------------------------
 
    \28\ As noted in the preamble to the final rule, ``safe'' means
``proof of a reasonable certainty of no harm,'' a standard drawn
from the legislative history of section 409 of the act; harm in this
context means ``hazardous to the health of man or animal.'' (61 FR
3118 at 3119 to 3120.) FDA concluded that ``an effect is harmful if
it affects health, not if it is simply an undesirable or unexpected
effect that has no adverse health consequences.'' (61 FR 3118 at
3120.)
    \29\ Contrary to CSPI's assertions, FDA's evaluation of the
evidence in the record did address a broad range of GI symptoms,
including loose stools, cramping and bloating, fecal urgency, oil-
in-the toilet, and anal leakage (61 FR 3118 at 3152 to 3159). In
applying the statutory standard of ``safe,'' FDA concluded that none
of these effects is harmful to health (61 FR 3118 at 3159). CSPI's
objection identifies no factual evidence to contradict this
conclusion.
---------------------------------------------------------------------------
 
2. Did FDA Err in Pooling Certain GI Data for Analysis?
    In its objection and request for a hearing, CSPI asserts that FDA's
analysis of two 8-week studies was inappropriate because the analysis
pooled the data from both studies.\30\ CSPI asserts that pooling these
data was inappropriate because different formulations of olestra were
used in the two studies. CSPI also objects to pooling the data because
it would allegedly diminish the ability to detect trends in one
study.\31\
---------------------------------------------------------------------------
 
    \30\ FDA explained that pooling the data from the two studies
increased the number of study subjects, thereby increasing the power
of the data to detect trends (61 FR 3118 at 3153).
---------------------------------------------------------------------------
 
    FDA is denying CSPI's request for a hearing on this issue because
the organization failed to identify specifically any reliable evidence
to support either of its factual allegations. That is, CSPI did not
identify any data or information to support its claim that different
olestra formulations precluded the pooling of the data from the two 8-
week studies\32\ (Sec.  12.24(b)(2)). Moreover, even if the data from
the two studies should have been analyzed separately, as asserted by
CSPI, that analysis would not have changed the outcome of this
proceeding because the results would be the same whether analyzed
separately or pooled (61 FR 3118 at 3153 to 3154). Accordingly, FDA is
denying CSPI's hearing request on this point (Sec.  12.24(b)(4)).
---------------------------------------------------------------------------
 
    \31\ In its first objection, CSPI alludes to the pooling issue
but does not elaborate on or support its challenge to pooling data
(CSPI obj. 1 at p. 16).
    \32\ In fact, although the two formulations of olestra differed
in the degree of stiffness, each was within the range of stiffness
permitted by the 1996 final rule (Sec.  172.867(b)(14)).
---------------------------------------------------------------------------
 
D. Adequacy of Olestra's Label Statement\33\
---------------------------------------------------------------------------
 
    \33\ Elsewhere in this issue of the Federal Register, FDA has
concluded, based upon a subsequent food additive petition submitted
by P&G containing new data and information, that olestra-containing
foods need not bear the information statement required by the
original final rule. FDA has concluded that most of the information
statement is no longer required to ensure that olestra-containing
products are not misbranded. The olestra regulation, Sec.  172.867,
as revised in response to P&G's petition, requires that an asterisk
appear in the ingredient list beside the added vitamins A, D, E, and
K. The asterisk will reference the statement, ``Dietarily
insignificant.'' The purpose of such labeling is to inform consumers
that their vitamin status will not change as a result of consuming
olestra-containing products. Accordingly, CSPI's objections to the
olestra label statement imposed by the 1996 final rule are arguably
moot.
---------------------------------------------------------------------------
 
    In its fourth objection and request for a hearing, CSPI challenges
the label statement required by the 1996 final rule, claiming that it
is not sufficient to protect the public from adverse effects associated
with consumption of olestra. CSPI also claims that the portion of the
label statement regarding the nutritional effects of olestra
consumption is inadequate. CSPI offers several specific criticisms in
support of these general allegations. As shown in the following
sections D.1 and D.2, none of CSPI's specific allegations raises a
question of material fact that requires a hearing. In analyzing CSPI's
objection regarding the olestra label statement, it is critical to
recognize that FDA did not require the statement to ensure olestra's
safe use (61 FR 3118 at 3160). Instead, the label statement was
designed to prevent olestra-containing foods from being misbranded.
1. Label Statement Regarding GI Effects
    CSPI alleges that the GI effects portion of the olestra label
statement is not adequate for three reasons. First, CSPI claims that
the word ``laxative'' should be used to describe olestra's GI effects.
Second, CSPI asserts that all GI effects of olestra should be
disclosed, including diarrhea, underwear staining, oil-in-toilet, and
anal leakage because they ``might distress'' consumers of olestra-
containing snacks. Third, CSPI claims that the GI portion of the
olestra label statement ought to advise consumers to seek medical
treatment if the effects of olestra consumption do not subside within
48 hours of consumption. Importantly, CSPI does not dispute any facts
that underlie FDA's decision regarding the label statement.
Fundamentally, CSPI's allegation in this instance is that olestra-
containing foods are misbranded in the absence of these three pieces of
information. Whether foods that bear the olestra label statement set
out in Sec.  172.867 are misbranded is a question of law. Thus, FDA is
denying CSPI's hearing request on this point because a hearing will not
be granted on issues of law (Sec.  12.24(b)(1)). Moreover, even if such
questions are questions of fact, CSPI did not specifically identify any
data or other information to support its position. Thus, on this basis,
FDA is denying this hearing request (Sec.  12.24(b)(2)).
2. Label Statement Regarding Absorption of Nutrients
    CSPI also challenges that portion of the olestra label statement
that relates to absorption of nutrients. CSPI asserts that this portion
of the olestra label statement has several deficiencies. Specifically,
CSPI claims that the word ``compensation'' should be substituted for
``added,'' that carotenoid depletion resulting from olestra consumption
should be disclosed, that consumers should be advised that there are
``no data'' about the vitamin K repletion, and that the statement
should begin with the word ``warning'' and appear on the front of the
package. Again, in presenting this portion of the fifth objection, CSPI
fails to identify specifically any underlying factual dispute that
could be resolved by a hearing. The question of whether olestra-
containing foods that bear the required label statement are misbranded
is a question of law. Accordingly, FDA is denying CSPI's request for a
hearing on this point because a hearing will not be granted on issues
of law (Sec.  12.24(b)(1)).
 
E. Alleged Procedural Problems in the Olestra Proceeding
 
    In its fifth objection and hearing request, CSPI claims that there
were a number of problems with the procedures utilized by FDA to reach
a decision about the safety of olestra. CSPI raises the following six
complaints: (1) Its White Paper was not provided promptly enough to the
members of OWG and FAC, (2) the presentation by FDA's staff to OWG did
not adequately address carotenoids, (3) the 1996 final rule unfairly
described support for olestra and discounted letters from CSPI members
opposing olestra's approval, (4) the petitioner engaged in a letter
writing campaign to gain olestra's approval, (5) FDA discounted the
opinions of CSPI's experts and ignored the ``scientific information''
in the letters from these experts, and (6) members of OWG and FAC were
biased. As is the case with its fourth objection and hearing request,
CSPI specifically identifies no factual issue underlying any of its six
procedural complaints. In such circumstances, a hearing is not
 
[[Page 46409]]
 
required (Sec.  12.24(b)(1)). Accordingly, FDA is denying CSPI's fifth
objection.\34\
---------------------------------------------------------------------------
 
    \34\ In fact, CSPI raised most of these complaints in comments
to FDA prior to olestra's approval, and the agency addressed each
such complaint in the preamble to the final rule (61 FR 3118 at 3163
to 3165). CSPI's fifth objection and hearing request does not
dispute FDA's resolution of these challenges in the final rule.
---------------------------------------------------------------------------
 
F. Alleged Absence of Reasonable Certainty of No Harm
 
    As noted, CSPI filed six objections to FDA's decision to approve
olestra, including a general objection (CSPI obj. 1) that asserts that
the additive does not meet the statutory standard of ``reasonable
certainty of no harm.''\35\ Many of the assertions of CSPI's general
objection mirror the allegations of the more specific objections (CSPI
obj. 2 through 5), which FDA has considered previously and denied.\36\
Even standing alone, however, CSPI's first objection must be denied for
several reasons.
---------------------------------------------------------------------------
 
    \35\ The act prohibits FDA from approving a food additive if it
has not been shown to be ``safe'' for its intended use, section
409(c)(3) of the act; FDA's regulation, relying on the legislative
history of the Food Additives Amendment of 1958, defines ``safe'' as
``a reasonable certainty in the minds of competent scientists that
the substance is not harmful under the intended conditions of use.
It is impossible in the present state of scientific knowledge to
establish with complete certainty the absolute harmlessness of the
use of any substance.'' (Sec.  170.3(i) (21 CFR 170.3(i)).)
    First, CSPI's first objection challenges FDA's finding that
olestra is safe for use in savory snacks.\37\As noted, resolving the
question of olestra's safety requires the application of the legal
standard (``safe'') as defined by FDA's regulations (``reasonable
certainty of no harm'') to a set of facts. As such, the question of
whether olestra is safe for its intended use is a question of law,
not fact. Accordingly, FDA is denying CSPI's first objection because
a hearing will not be granted on issues of policy or law (Sec.
12.24(b)(1)).
    \36\ In these circumstances and for reasons of economy, FDA does
not restate its analysis and basis for denial of the specific
objections.
    \37\ CSPI asserts that FDA's approval of olestra is ``artibrary
and capricious'' and thus erroneous (CSPI obj. at p. 12). In fact,
the standard of review for a food additive approval is ``a fair
evaluation of the entire record * * *'' (section 409(g)(2) of the
act). CSPI provides no evidence that FDA did not conduct a fair
evaluation of the entire record.
---------------------------------------------------------------------------
 
    Second, although CSPI's first objection is the longest of the six,
it is almost exclusively a series of allegations\38\ without any
specifically identified and available evidence to support them.\39\
That is, CSPI did not cite specific data or other factual information
in the record to demonstrate the validity of its challenges to FDA's
conclusions (CSPI obj. at pp. 8 through 18). Thus, CSPI's first
objection is denied for a second, separate reason because a hearing
will not be granted on the basis of mere allegations (Sec.
12.24(b)(2)).\40\
---------------------------------------------------------------------------
 
    \38\ For example, in its discussion of the ``Inadequate Safety
Base'' for olestra, CSPI notes Dr. Klish, a witness at OWG,
testified that at 1 year, children's GI tracts are the same as
adults and therefore, data from adults can be extrapolated to
children. On this subject CSPI simply asserts, ``Life experience,
however, does not support that view. After all, why do one- and two-
year-olds experience `toddlers' diarrhea' * * * ?'' (CSPI obj. at p.
8.)
    \39\ In the carotenoids portion of its first objection, for
example, CSPI refers to a ``selection of letters from noted
scientists opposing the approval of olestra'' (CSPI exh. 8.)
Notably, however, CSPI does no more to identify the specific facts
these experts dispute or to specify the data and other information
on which these experts rely (Sec.  12.24(b)(2)).
    \40\ It is not surprising that CSPI's allegations are
unsupported because, in some cases, the allegations are clearly
false. For example, CSPI claims that ``the FDA staff declined to
consider'' certain data regarding carontenoids (CSPI obj. at p. 6).
In fact, FDA devoted a significant amount of attention to the
carotenoids issue (61 FR 3118 at 3147 to 3149 and 3161), but
ultimately reached a different conclusion than that urged by CSPI.
---------------------------------------------------------------------------
 
    Third, CSPI asserts that the quality of certain studies relied upon
by FDA is ``spotty at best,'' and claims that these tests were
``critical'' to the safety evaluation of olestra (CSPI obj. at p. 13).
In support of this claim, CSPI cites parts of the 1996 final rule and
supporting memoranda discussing the limitations of certain studies.\41\
(CSPI obj. at p. 12, footnote 8). Importantly, however, CSPI does not
demonstrate how the outcome of this proceeding would have been
different if, due to these alleged quality problems, FDA had not been
able to rely on these ``certain studies'' in determining the safety of
olestra. Thus, FDA is denying CSPI's first objection because a hearing
will not be granted on factual issues that are not determinative of the
action requested\42\ (Sec.  12.24(b)(4)).
---------------------------------------------------------------------------
 
    \41\ In particular, CSPI quotes excerpts from the 1996 final
rule in which FDA identified certain limitations of these studies of
olestra. Identifying such limitations is consistent with FDA's
obligation to make a ``fair evaluation of the data'' in the record
when determining olestra's safety (section 409(c)(4) of the act).
    \42\ For example, CSPI offers several criticisms of a P&G
 
marketing study which the company presented to illustrate
consumption patterns for savory snacks (CSPI obj. at p. 13, footnote
10). In fact, as CSPI noted (CSPI obj. at p. 33), FDA told OWG that
FDA had not relied on data from this study in its safety evaluation
(Transcript of the FAC meeting, November 16, 1995, at p. 55).
---------------------------------------------------------------------------
 
    Fourth, CSPI challenges FDA's conclusion that the GI effects seen
in P&G's 8-week studies are not harmful health effects. As part of this
challenge, CSPI criticizes the size of the two 8-week studies and
asserts that a larger study would likely have shown statistical
significance at the 8 grams/day (g/d) dose, citing the comments of
David Allison, Ph.D., a statistician and consultant to FAC (CSPI obj.
at pp. 13 through 14 and footnote 11). CSPI fails to note that Dr.
Allison concluded his statement by saying that whether ``to make a
great deal of argument on is there or isn't there an effect at the 8 g
dose is really a misleading kind of argument because it seems almost
certain that there is but, rather, is it an important effect, an effect
that is clinically meaningful * * *'' (transcript of FAC meeting,
November 16, 1995, at p. 52). In the same footnote, CSPI claims that
Dr. Marvin Schneiderman performed a trend test which demonstrated an
increase in incidence of ``gastrointestinal disturbances above the
placebo level at 8 g/day.'' In fact, Dr. Schneiderman's analysis
concerned only anal leakage, not all GI effects (CSPI exh. 14 at p. 2).
FDA found that anal leakage is not a health hazard (61 FR 3118 at
3154), a fact not disputed by CSPI in its objections and hearing
requests. Accordingly, FDA is denying CSPI's objection on this point
because a hearing will be denied where the data and information
submitted are insufficient to justify the factual determination urged
(Sec.  12.24(b)(3)).
    Finally, CSPI disputes FDA's conclusion that the ``diarrhea''
experienced by olestra consumers is not clinical diarrhea and thus, not
an adverse health effect.\43\ In particular, CSPI asserts that ``weight
and water content of diarrheal stools was increased over those of loose
and normal stools in subjects eating 20 g/day of olestra.'' (CSPI obj.
at p. 16). Importantly, however, CSPI does not cite a reference to
support this conclusion. In the absence of specifically identified and
available evidence to support a disputed fact, a hearing must be denied
(Sec.  12.24(b)(2)). Moreover, CSPI does not explain how a finding of
increased stool weight among olestra consumers would alter FDA's
conclusion that olestra's GI effects are not harmful to health.\44\
Thus, FDA is denying a hearing on this issue because it is not
determinative of the question at issue (Sec.  12.24(b)(4)). Likewise,
although FDA concluded that increased water content of stools could be
an indicator of true diarrhea (61 FR 3118 at 3158), FDA concluded that
in the study in question, the data ``regarding stool water
concentration--expressed as a percent of stools by weight--suggests
that the stool water concentration of subjects having diarrhea during
the olestra 20 g/d period did not differ from that of their
nondiarrheal stools during the placebo period'' (61 FR 3118 at 3171;
Ref. 88). Thus, even if CSPI intended to rely on Ref. 88 to support
this allegation, the memorandum does not establish that
 
[[Page 46410]]
 
the subjects' stool water content increased when they consumed olestra.
Thus, FDA is denying CSPI's hearing on this point (Sec.  12.24(b)(3)).
---------------------------------------------------------------------------
 
    \43\ CSPI refers to a December 26, 1995, memorandum of Karl
Klontz, M.D., erroneously describing it as Ref. 87 to the final rule
(CSPI obj. at p. 16, footnote 14). In fact, Dr. Klontz's December
26, 1995, memorandum is Ref. 88 of the final rule (61 FR 3118 at
3171).
    \44\ Olestra is not digested and thus will add to the weight of
the stools of olestra consumers (61 FR 3118 at 3158). Thus, mere
increase in stool weight of olestra consumers is not itself evidence
of harm.
---------------------------------------------------------------------------
 
V. Summary and Conclusion
 
    The act requires that a food additive be shown to be safe prior to
marketing under section 409 of the act. Under Sec.  170.3(i), a food
additive is ``safe'' if there is a reasonable certainty in the minds of
competent scientists that the substance is not harmful under the
intended conditions of use. In the agency's January 30, 1996, final
rule approving olestra, FDA concluded that the studies conducted to
establish the safety of this additive demonstrate that olestra is safe
for its intended use in savory snacks.
    The petitioner has the burden to demonstrate the safety of the
additive in order to gain FDA approval. Nevertheless, once FDA 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)).
    Despite its many allegations, CSPI has not established that FDA
overlooked significant information in the record in reaching its
conclusion that olestra is safe. In such circumstances, FDA has
determined that the objections do not raise any genuine and substantial
issue of fact that would justify an evidentiary hearing on any of the
objections raised (Sec.  12.24(b)). Accordingly, FDA is overruling
CSPI's objections and is denying CSPI's requests for a hearing in their
entirety.
 
    Dated: July 23, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-19509 Filed 8-1-03; 4:00 pm]
 
BILLING CODE 4160-01-S