Sage Publications, Inc. Science, Technology, & Human Values

The Neoliberal Regulatory State, Industry Interests, and the Ideological Penetration of
Scientific Knowledge: Deconstructing the Redefinition of Carcinogens in Pharmaceuticals

Author(s): John Abraham and Rachel Ballinger
Source: Science, Technology, & Human Values, Vol. 37, No. 5 (September 2012), pp. 443-477
Published by: Sage Publications, Inc.
Stable URL: http://www.jstor.org/stable/23474403
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Articles
Science, Technology, & Human Values

37(5) 443-477
The Author(s) 2012
The Neoliberal Reprints and permission:
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Regulatory State, DOI: 10.1177/0162243911424914

http://sthv.sagepub.com
Industry Interests, USAGE
and the Ideological

Penetration of
Scientific Knowledge:
Deconstructing the
Redefinition of
Carcinogens in
Pharmaceuticals
S "2
John Abraham and Rachel Ballinger
Abstract
It is argued that neoliberal political ideology has redefined the regulatory

state to have greater convergence of interests and goals with the phar
maceutical industry than previously, particularly regarding acceleration and
' Department of Sociology, Centre for Research and Health in Medicine (CRHaM), University
of Sussex, Brighton, United Kingdom
2 Cancer Research UK, Sussex Psychological Oncology Group, Brighton and Sussex Medica
School, University of Sussex, Brighton, United Kingdom
Corresponding Author:
John Abraham, Centre for Research and Health in Medicine (CRHaM), Department o
Sociology, University of Sussex, Brighton BNI 9SN, United Kingdom
Email: J.W.Abraham@sussex.ac.uk
444 Science, Technology, & Human Values 37(5)
cost reduction of drug development and regulatory review.

the pharmaceutical industry has been permitted to set the a
how shorter term and cheaper alternative carcinogenicity tes
are investigated for validity. The authors contend that, w
approval of the neoliberal regulatory state, the commercial
the pharmaceutical industry framed the process and inte
validating these new test systems, thereby influencing wha
knowledge about the carcinogenic status of new pharmaceut
such alternative tests were occasioned by "molecularization,"
of their validation was not determined by technoscientific
of standards of validation, but by the sociopolitical goals of t
institutions. Indeed, a different validation process could hav
ducted had the priority been to develop carcinogenicity t
interests of public-health protection. While the resulting va
cated that the short-term alternative tests posed small risk
mercial interests of pharmaceutical firms, they provided litt
that patients would not be exposed to greater risks than
undetected carcinogens.
Keywords
politics, power, governance, expertise
Introduction
Since the 1970s, a core element of science and technology studies (STS) has
been the sociology of scientific knowledge (SSK). Notwithstanding underly
ing debates about relativism, constructivism, and realism, scholars agree on the
fundamental claim of SSK that social, political, and economic factors can
shape the very content of scientific knowledge (Abraham 1995,1-35; Barnes
1974; Bloor 1984; Gieryn 1982; Millstone 1978; Chubin and Restivo 1983;
van Zwanenberg and Millstone 2000; Webster 1991). In particular,
MacKenzie (1981) found that, in late-nineteenth-/early-twentieth-century
Britain, the content of statistical knowledge was influenced by (eugenics)
ideology and the interests and goals of the professional middle class, rather than
inexorably determined by mathematical logic and/or empirical discoveries.
This article follows that SSK tradition, together with STS's long
standing concerns about governance of technological risk and the newly
emerging field of "STS and neoliberal science" (Bal and Halfman 1998;
Abraham and Ballinger 445
Bloomfield and Doolin 2011; Braun

Randalls 2010; van Zwanenberg and
Consistent with Lave, Mirowski, a
scholars to undertake detailed explo
ical-economic forces of neoliberalis
trace the links between neoliberal i
tical industry and drug regulatory
knowledge about pharmaceutical car
the United States and Europe. Spec
counts as knowledge when identify
cals as carcinogenic risks to human
The STS scholars, Gillespie, Eva, and
and Ilgen (1985), Abraham (1993
investigated carcinogenic risk asse
but their emphasis was on internati
regulatory assessments of case-stud
the 1990s. Contradistinctively, and
research on emerging global food
more recent and on cross-national
carcinogenicity testing for all pha
(2002) examined how the direction
to industry demands, his research
micals, rather than pharmaceutica
gical knowledge to the regulator
Shostak (2005, 2007) focused on t
ronmental toxicology, though Sho
of such geneticization on to regula
States.
In the pharmaceutical sector, we argue that neoliberalism as a political
movement and ideology has redefined the regulatory state to have much
greater convergence of interests and goals with the drug industry than pre
viously, particularly regarding acceleration and cost reduction of drug
development and regulatory review. Consequently, drug regulatory agen
cies have accepted and supported the pharmaceutical industry's agenda of
streamlining new drug testing, including carcinogenicity evaluation
requirements. Although pharmaceuticals are the focus of this article, neolib
eral enhancement of industry influence over carcinogenicity evaluation
since the 1980s has been reported in other fields, such as tobacco and envi
ronmental chemicals (Ong and Glantz 2000; Huff and Tomatis 2002). For
example, the tobacco and chemical industries have successfully influenced
that evaluation process at the World Health Organization's e

known as the International Agency for Research on Cancer
ently without any condemnation from Member State regulato
(Cook and Bero 2006). In the United States, neoliberal conser
Supreme Court and Congress curbed the Food and Drug Adm
(FDA's) ambitions to regulate the tobacco industry, while ch
facturers supported by the George W. Bush Administration
halted the Environmental Protection Agency's integrated carc
assessment reports on the grounds that they were too "alarmin
lic (Hilts 2003, 292-94; Furlow 2011).
Unlike many reports of neoliberal and business influence
ulatory sectors, we provide an in-depth analysis of the m
such influence, and how they relate to the techno-scientific
claims in the pharmaceutical sector. The pharmaceutical
been permitted to set the agenda about how shorter term
alternative carcinogenicity testing systems are investigated
In particular, we contend that, with the tacit approval of th
regulatory state, the commercial interests of the pharmaceut
framed the process and interpretation of validating these n
tems, thereby influencing what counts as knowledge about
genic status of new pharmaceuticals. Such framing was not
by the technoscientific logic of toxicology or a lack of prev
sional standards of validation, but rather by the sociopolitical
controlling institutions. Indeed, a different validation proce
been conducted had the priority been to develop carcinogenic
the interests of public health protection, especially because
professional standard among scientists was well advanced wh
dation process was undertaken.
To investigate the development and validation of these alter
term carcinogenicity tests involving genetically engineered
employed documentary and interview research methods. Field
ope and the United States spanned three years from the mid-2
umentary research included an extensive review of the techn
regarding pharmaceutical toxicology since 1950 and the Web s
evant institutions/organizations. For example, PubMed (1
searched electronically using keywords, "carcinogenicity tes
assessment," "transgenic animals," and "genetically altere
els"; and Scrip (1998-2010)the twice-weekly pharmaceutical
letterwas searched manually. E-mail notifications of latest d
took the literature review beyond books and articles
Abraham and Bollinger 447
organizational practices via consul

meetings, newsletters, and press rel
Interviewees were mainly "info
knowledge of, or some involvement
of pharmaceuticals. Fifty-three inte
from the pharmaceutical industry, dr
committees, academic and governm
advocacy groups, and patient organi
semistructured to allow probing and
as preplanned core questions. All
except for three when contemporan
data were coded and analyzed indep
Neoliberal Ideology and Ne

Before new pharmaceuticals are per
must test them for safety according
maceutical companies submit their te
agencies, government scientists revi
des whether to permit the drugs on
pharmaceutical regulation remain, bu
the neoliberal ideological reconstruc
The commercial interests of the ph
alism itself (Abraham 1995, 36-86; B
Liebenau 1981). Concern that indust
government regulatory agencies is as
(Abraham 1995, 36-86; Mitnick 1980
neoliberalism there was a governmen
basic goal, and indeed raison d'etre
protect public health over and abov
ceutical firms, albeit too frequently
the neoliberal shift, which began in,
ged that expectation into enrolment
ever-expanding appetite for increase
owski, and Randalls 2010).
The UK election of Prime Minister
Conservative Party in three subsequ
the neoliberal shift. The Thatcher go
maceutical industry's claims that sta
sive to the needs of business and inn
drugs on to the market fast enough (Abraham and Lewis

Consequently, a reform of the British civil service, includin
ment of Health's state-funded pharmaceutical regulation, wa
This created the UK Medicines Control Agency (MCA), w
be entirely funded by fees paid by pharmaceutical firms for t
work it conducted in exchange for a more "efficient service"
meant "lighter touch" regulation and faster drug approvals
1989a). On arrival, the new director of the MCA, who came f
maceutical industry, stated that his goal was to reduce "proc
for new drugs by 24 percent in the first year, even though he
the scientific quality (regarding safety or efficacy) of the new
tions for that year (Anon. 1989b). With applause and large s
for the MCA's executives from government Ministers, the g
UK drug regulatory agency were reset to emphasize its "dua
ities" to industry and patients (MCA 1991). Between 1989 an
drug processing times fell by more than two-thirds, from 154
to just 44results for which the pharmaceutical firms paid
making the MCA one of the richest regulatory agencies in E
ham and Lewis 2000, 65-66).
Similarly, in Sweden, the Government created the Medical
Agency (MPA) in 1990 in response to industry complain
approval times were too long. This removed pharmaceutic
from the state's National Board of Health and Welfare. Like t
MPA was a semiautonomous drug regulatory agency formed
consultation with industry and accelerate drug approval time
for high fees from industry, which entirely funded the Sw
(Anon. 1990). As in the United Kingdom, between 1989 and 1
times fell sharply, by more than half (Anon. 1994a).
In Germany too, the election of the neoliberal Christian Dem
1980s made the Government more responsive to pharmaceut
complaints about regulation. In 1987, pharmaceutical firms b
thirty court cases against the German drug regulatory agency
gesundheitsamt (BGA), for "failing to act" on drug applic
1989c). The BGA argued that approval rates were not always a
because of the poor quality of new drugs, noting that in 1988
sixty-two new drugs approved were of outstanding therapeuti
(Anon. 1989d). Despite the BGA's protestations, after continui
it was disbanded in 1994 and replaced with the Bundesinstit
mittel und Medizinprodukte (BfArM), another semiautonomou
agency, instructed by the German Ministry of Health that
continue to be so conservative [as

new products" (Anon. 1994b). By 1
were cut in half and regulators ha
consultation with pharmaceutical c
1995).
Thus, these neoliberal changes occurred in three countries with signifi
cant pharmaceutical industries and drug regulatory agencies in Europe. The
shaping of the European Union (EU) supranational drug regulatory system,
which was becoming established during the early and mid 1990s, was
strongly influenced by these neoliberal developments taking place in many
of its most important member states for the pharmaceutical sector (Abra
ham and Lewis 2000). In 1995, the supranational European Medicines Eva
luation Agency (EMEA) and concomitant regulatory systems were put in
place. The EMEA was to be largely funded by fees from pharmaceutical
companiesinitially 28 percent in 1995, but rising to about 70 percent
by 1999 and thereafter (Abraham and Davis 2007b, 397). Moreover, supra
national EU regulators were required to make approval decisions within
strict timelines consistent with the reduction in regulatory review times that
had been introduced in Germany, Sweden, and the United Kingdom (Abra
ham and Lewis 2000). The supranational EU drug regulatory system, there
fore, reflected the neoliberal framework that had come to dominate its most
influential member states in the pharmaceutical sector.
Meanwhile, in the United States, in 1981 probusiness Reagan became
President and the Republicans gained control of the Senate against a back
ground of reported deterioration in the international competitive position of
US industries (NAS 1983). Believing that America's economic and indus
trial decline resulted from excessive government interference with the pri
vate sector, the New Right within the Reagan Administration and Congress
committed to radical deregulatory agendas (Hilts 2003, 210-11). Reagan's
health policy adviser, formerly president of the US Pharmaceutical Manu
facturer's Association, invited the pharmaceutical industry to propose FDA
reforms (Anon. 1981a). Congress convened a Commission to address "reg
ulatory overkill at the FDA" (Anon. 1981b, 10). The Commission recom
mended reforms designed to promote more rapid approval of new drugs,
which the FDA management implemented by narrowing the scope of the
FDA's regulation of industry data and allowing closer and more frequent
contact between industry and FDA officials (Anon. 1982a; FR 1985,
1987). Some FDA scientists expressed concern before a Senate Committee
that such management pressure to expedite approvals might "compromise
the scientific integrity of [new drug] reviews" (Anon. 1981c, 1982b).
Meanwhile, Reagan's Secretary of State for Health praised the

of FDA-industry cooperation (Anon. 1986).
Under Reagan and Bush (senior), the President's Task
Regulatory Relief and the White House Council of Competit
Vice President Quayle exerted continual pressure on the FDA
the 1980s and early 1990s to remove regulatory barriers to
ucts by "streamlining" the drug approval process (Anon.
However, because the FDA had been subject to severe budget
ing the Reagan and Bush (senior) Administrations, it could n
approval times sufficiently to meet industry demands (Hilt
Neither the Bush (senior) Administration nor Congress were
increase its budget, so the pharmaceutical industry was permi
fund the agency via fees under the 1992 Prescription Drug
(PDUFA; Anon. 1992). Conditions of PDUFA included that
fees could only be used to fund/accelerate the FDA's drug r
and that the fee payments would only be reauthorized after ev
if the pharmaceutical industry and Congress could agree on s
mance goals for the FDA in each period (USGAO 2002,7). The
ther accentuated the formation of a neoliberal regulatory stat
the industry de facto influence over the FDA's priorities and
1993 and 2003, the extent of funding for the FDA from indu
from 25 to 50 percent, while the agency cut its drug approval
in the same period (Abraham and Davis 2007b).
It was in this context that the International Conference on Harm
of Technical Requirements for Registration of Pharmaceutica
Use (ICH) was formed in the early 1990s. It comprises the thr
tical industry associations and government regulatory agenc
United States, and Japan. The ICH sought to harmonize, stre
reduce pharmaceutical testing requirements as means of acce
drug development and regulatory review times across the th
which made up about 85 percent of the global market (Abrah
was in the commercial interests of industry because it reduce
opment costs and could accelerate product access to markets
not be in the interests of patients and public health if it compro
checks and increased risks of drug toxicity/injury. Entirely c
the neoliberal drug regulatory states that had emerged in E
United States, regulators from the three agencies willingly p
the ICH project of reducing drug testing, which was to be eno
ential on global technoregulatory standards for pharmaceuti
more, throughout the 1990s, the regulatory agencies p
industry to set the agenda of th

International Federation of Pharma
(Abraham and Reed 2001). Gripped
could be construed by managers of r
their institutions because with fewer
to review and a concomitant reduction in their workload to meet ever
shrinking drug-approval-time goals. A significant target for streamlining
at the ICH was the expensive and time-consuming process of carcinogeni
city testing. Thus, the pharmaceutical sector is highly congruent with Lave
et al.'s (2010, 660) more general observation that, "while varying across
national contexts," "over the past 30 years," there has been a "broad global
movement towards neo-liberalism."
New Ways of Testing Pharmaceuticals for

Carcinogenicity
It is well established that exposure to some chemicals, including pharma
ceuticals, may cause cancer in people. Hence, all newly discovered pharma
ceutical entities could pose some carcinogenic risk. In order to assess that
risk, since the 1960s, government drug regulatory agencies have required
scientists in pharmaceutical firms (or their contract research organizations)
to test their new drugs for carcinogenicity before deciding whether to
approve them on to the market (WHO 1969).
When testing new drugs for carcinogenicity, scientists have had to rely
on the extrapolation of results from nonhuman tests because most carcino
genic risks accelerate over the life spanseventy to ninety years for
humansfar too long for clinical trials (Schou 1992, 210). Two types of
carcinogenicity test have been developed: short-term in vitro mutagenicity
tests, and life span in vivo studies in rodents (Hayashi 1994, 291). The for
mer involves adding the test drug to disembodied mammalian/human cells
or to microorganisms in glass dishes (in vitro) to see if the chemical alters/
damages DNA, causing mutations associated with carcinogenicity (King
1996, 93-94). Pharmaceuticals found to damage DNA are known as geno
toxic carcinogens, However, many carcinogens cause cancer without dama
ging DNA as a primary biological activity (Purchase 1992). They are
known as nongenotoxic carcinogens and are not detected by in vitro muta
genicity tests (Ashby and Tennant 1991).
To screen for nongenotoxic carcinogens, tests in whole live animals (in
vivo) have been deployed. These animal models of human carcinogenesis
have involved feeding rodents the test drug over (most of) their life span,
usually between eighteen and twenty-four months. At the end

the incidence and nature of the tumors found among the rode
test drug are compared with those in a "control group,"
receive the drug. Due to the problem of extrapolating finding
species, and to humans in particular, the WHO (1969) recomm
these "life span" carcinogenicity testing should be conducted
species (typically mice and rats) before government regulator
the grounds that, if a drug caused cancer in more than one
(a trans-species carcinogen), then it would pose a greater carc
to humans. By the late 1970s, the regulatory agencies in Nor
Western Europe, and Japan had all adopted this view (Ab
Exceptionally, such rodent life span testing could be deferre
keting of new drugs intended to treat life-threatening condi
delaying therapy for desperately ill patients (D'Arcy and
258).
During the 1990s, the regulatory requirement of two life span studies in
two rodent species began to be challenged within the ICH agenda. By 1998,
the ICH had decided that two life span carcinogenicity tests (one in rats and
one in mice) should no longer be a necessary regulatory requirement to
screen for nongenotoxic carcinogens. As an alternative, the ICH proposed
that only one life span carcinogenicity study (typically in rats) was neces
sary and that the second life span study (typically in mice) could be replaced
with a much cheaper, smaller scale, and short-term study in genetically
engineered rodents (typically mice), which would last approximately six
months, involve about a third of the number of animals, and incur only a
fifth of the cost of a life span study (Lumley and Van Cauteren 1997).
That these types of alternative tests were available as prominent alterna
tives was due to the "molecularization" of toxicology in the aftermath of
the geneticization of cancer causation, together with the extent to which
some government scientists, especially at the U.S. National Institute of
Environmental Health Sciences (NIEHS) and the FDA, promoted and
"translated" genetically engineered animal models for use in risk assess
ment and regulatory decision making (Dalpe et al. 2003; Frickel 2004;
Shostak 2005,2007). The FDA was able to push this new conceptualization
of carcinogenicity testing through to acceptance at ICH because the agency
is responsible for governing the largest pharmaceutical marketnearly half
the world marketwhich all major drug companies seek to access. That
institutional power within the global political economy of pharmaceuticals
meant that the drug industry at ICH paid attention to the regulatory concepts
preferred by the FDA, as they had done previously regarding the
bioequivalence concept in the Unite

Such was the influence of the ICH th
carcinogenicity study with a short
engineered rodents was transposed
the world, especially in the EU,
1997; Lubiniecki 1997; Pettit 2001).
The short-term in vivo tests prop
carcinogenicity studies involved
rodents, into which genes were i
tumor development (known as on
to suppress tumor development, kn
removed"knocked out" (Tennan
nale for these short-term in vivo
tumor development, known as "i
cally engineered rodents so that ca
in the whole live animal much sooner than in "normal" rodents because
only the later stages of carcinogenesis would need to occur. On this
logic, if a new drug were carcinogenic, then it should be detected fairly
quickly by these short-term tests because the initiated animals should
develop more cancer tumors more rapidly than the control animals
(Schou 1992).
In practice, most genetically engineered rodent test models were mouse
models, and the general expectation was that, under this new regulatory
regime, the life span study would be in rats implying that the "second-spe
cies" short-term in vivo test would need to be in mice, albeit genetically
engineered. Three types of genetically engineered mouse tests were out
lined at the ICH, namely, those involving transgenic mice with the onco
gene, v-Ha-ras, introduced (the tgAC model), "knock-out" mice with the
tumor-suppressor gene, p53, removed (the p53 model), and transgenic mice
with the oncogene, c-Ha-ras, introduced (the rasH2 model). While such
mouse models had certainly been developed by 1998, they had not been
validated. That is to say, their capability to correctly identify carcinogens
and noncarcinogens had not been systematically assessed. Despite this, fol
lowing the ICH, from 1998, regulatory agencies permitted pharmaceutical
firms to conduct life span carcinogenicity studies in just one rodent species
so long as they also employed one of these new short-term in vivo tests
appropriately, even though it was not known whether those new tests could
adequately screen for nongenotoxic carcinogens. Insofar as that new testing
regime took on a life of its own, the FDA's institutional power could be
regarded as having been partly converted into what Carpenter (2010,
394) calls "conceptual power." However, it was neither unchallen

even secure, conceptual power because of lack of validation.
For example, the UK government expert advisory Committee
nogenicity (UKCoC) concluded that this regulatory change "lack
priate scientific rigour to justify its use as a working documen
provision of information to support regulatory decisions" (Dep
Health 1997, 113). One UK regulator asserted that "it was bad sc
include an unvalidated assay as an alternative,"1 while a senior
scientist in the field considered validation to be "absolutely
because "one should never introduce into regulation a completel
procedure of such a major type without validating itboth to
intrinsic worth of the method and to make sure there are enough l
around the world with experience of the procedure."2 Even
experts acknowledged that "conclusions cannot be drawn [about t
of the new short-term tests] until the results of validation stu
obtained" (MacDonald 1998, 272).
The Meaning and Increasing Significance of Va

as a Professional Scientific Standard
After these changes to the regulations for carcinogenicity testing, "valida

tion" studies were conducted during the 2000s, primarily in the United
States with some input from European scientists. Before considering those
"validation" studies, it is necessary to examine the prevailing technoscien
tific and regulatory standards regarding validation processes that were
available in the United States and Europe. This puts in context the signifi
cance attached to validation as both a principle and a process in regulatory
science.
In the United States, efforts to develop professional scientific standards
for validation of regulatory science have taken many forms. For instance,
one well-documented idea is the creation of the Health Effects Institute
(HEI) in 1980, which became responsible for sponsoring research on air
quality standards and the toxicology of air pollutants. The underlying prin
ciple, which guided the formation of the HEI, was that the validity of reg
ulatory science could be achieved by removing the direct funding decisions
for toxicological research from government and industry. Rather, the HEI,
an early "public-private partnership" received half of its funding from the
government's EPA and half from the automobile industry (Jasanoff 1990,
209-16). Hence, the HEI provided a functional separation between the key
stakeholders and research funding decisions affecting the interests
involvedat least that was the claim

received some support from an i
research by the US General Accoun
the GAO also found that the research
tion, suggesting that the quest for n
ment was not the most effective w
regulation that might conflict directl
While the scientific community has
itypertaining to toxicological tests fo
1997, there was no formalized proce
regulatory agencies. The lessons of t
of limiting industry control of regu
malized at the EPA or other federa
icological Research (now known as t
Research) determined the validity o
sensus" involving "review by scienti
ticular field" (ICCVAM 1997, Appen
came under scrutiny after the US Co
Health Revitalisation Act of 1993, w
criteria for the validation and regul
methods, and [to] recommend a pro
dated alternative methods [could]
VAM 1997, preface). Between 1994 and 2000, the Interagency
Coordinating Committee on the Validation of Alternative Methods (ICC
VAM) became established to take on this role for NIEHS with responsibil
ities across many federal regulatory agencies (ICCVAM 2003). Such
institutionalization of scientific validation culminated in the ICCVAM
Authorization Act of 2000, which stated that "each federal agency shall
ensure that any new or revised acute or chronic toxicity test method, includ
ing animal test methods and alternatives, is determined to be valid for its
proposed use prior to requiring, recommending, or encouraging the applica
tion of such test method" (Public Law 106-545, 4C).
In 1998, the US National Toxicology Program's Interagency Center for
the Evaluation of Alternative Toxicological Methods (NICEATM) was
formed to provide operational and scientific support for ICCVAM, whose
efforts were further strengthened by the creation of the Scientific Advisory
Committee on Alternative Toxicological Methods (SACATM) in 2004.
These bodies review evidence and make recommendations, but do not
themselves conduct validation studies (Schechtman 2002). Formally, each
of the federal regulatory agencies, such as the FDA, remain autonomous
in deciding whether they wish to accept and/or implement ICC

ommendations about new tests' "potential usefulness, limit
applicability to federal testing requirements" (Stokes et al.
Throughout the 2000s, the FDA's position was that it would not
withhold approval of a new pharmaceutical on to the market sol
some test methods have not been formally validated (SACATM
tion IX, discussion). Nonetheless, the scientific community's gr
mitment to the principle of validation in carcinogenicity testing is
by the American Chemistry Council's assertions in 2002 tha
National Toxicology Program, through ICCVAM, is obliged to e
transgenic mouse-model test methods in a formal validation pro
intends to routinely evaluate data from such assays as part of its
screening program" (Brozena and Becker 2002).
Meanwhile in Europe, the supranational European Commis
lished the European Centre for the Validation of Alternativ
(ECVAM) in 1991 (Directive 86/609/EEC). Although ECVAM i
ilar to ICCVAM, it differs in its greater emphasis to coordinat
promote, and even develop/research alternative/new test meth
ing those relating to carcinogenicity. ECVAM has looser connec
government regulatory agencies than ICCVAM, working ins
broad networks of laboratories, including the pharmaceutica
(Balls 2002; van Zeller and Combes 1999). It has been more forth
than ICCVAM in stipulating criteria for validation processes, w
concerned about persuading regulators of the legislative imperat
grate the scientific principle of validation into regulatory polic
cally, by the early 2000s, ECVAM had established criteria for v
studies, including "clarity of defined goals," "quality of overall
"independence of management," "independence of selection of t
rials," "independence of data collection and analysis," "number
erties of test materials," and "quality and interpretation of resu
and Balls 2002, 18).
The Process of Validation
It was widely acknowledged, therefore, that the new short-term in vivo ca

cinogenicity tests using genetically engineered mice needed to be validated
in order to have confidence that they could screen for carcinogens, espe
cially nongenotoxic carcinogens. The lessons from the HEI in the United
States combined with heightened professional concerns in both the EU and
United States about validation of regulatory science might have suggeste
the need to separate industry influ

process. However, the dominance of
health protection, permitted by the
the validation process and deeply in
noscience involved, so that the n
potential conceptual power could be
gain. Our investigation reveals that
the validation, and how the data we
were consistent with the pharmaceu
have been different if the primary
tion of public health.
Carcinogenicity Validation as an
The validation studies were conduct
Institute (ILSI) involving in particu
Health and Environmental Science
behind the ILSI validation studies were senior scientists from American
pharmaceutical firms, such as Shering-Plough, Sinofi Sterling Winthrop,
Novartis, Johnson & Johnson, Merck, and Pfizer.3 As one senior scientist
with experience of coordinating pharmaceutical laboratories explained:
[T]hrough HESI, the pharmaceutical industry, especially in the States

HESI membership was international, but it was dominated by either Ameri
can companies or the American base of non-American companiesthey
could see lots of changes coming and they really wanted to evaluate the worth
of the enormous expenditure of time, animals, effort, everything else
[They] could see the potential benefit of the transgenic mouse models in
terms of time if accuracy and validity could be proven.2
ILSI was founded in 1978 as a not-for-profit worldwide foundation with

headquarters in Washington, DC, but it is supported by chemical and phar
maceutical industry funding and membership, while also involving some
scientists from academia and government. Under the auspices of ILSI's
HESI, the validation process became known as the "Alternative to Carcino
genicity Testing (ACT)" programinvolving fifty-five laboratories at a
cost of US$35 million.4 Eighty percent of the program's experimental stud
ies were conducted in the United States.5 The ACT program had a formal
Steering Group, all nine of whose members were from industry, three
quarters of whom were from the United States, including leading figures,
who had argued at the ICH for abandonment of life span car
tests in mice (Robinson and MacDonald 2001).
There were some advisers and members of ACT subcommit
were from academia, government research organizations, an
agencies, including the FDA (Cohen, Robinson, and MacD
However, the core funding for the ACT program came from
nies, mainly in the pharmaceutical sector (Robinson and Mac
3-4).6 Even scientists involved in the ACT program, who
tively of it, acknowledged the industry's central role. As one
[ISLI-HESI] brought together the people who have the bigges
the trans-national pharmaceutical companies, they brought th
people together at the same table."7 Indeed, some of the regula
in recommending and approving the new alternative short-ter
cinogenicity tests at the ICH, subsequently took up employm
pharmaceutical industry either during or after the ACT program
was a public-private partnership, then the ILSI was a private
which appropriate government and academic scientists were i
their advice and support.
The dominant presence of industry in the ACT program had
for the type of expertise welcomed to participate in data collec
and interpretation. For example, one of the leading proponen
program had major reservations about involving the World
zation's IARC, an independent body, which constructs lists of
IARC scientists were not consulted, despite their specialist ex
cinogen identification and categorization. This proponent of
gram, who was influential in shaping its management, j
exclusion of IARC as follows:
I don't have a lot of confidence in the I ARC process. If I ARC calls phnobar
bital a possible human carcinogen ... in my view they are not being scien
tifically honest ... because the compelling data say that it's not a human
carcinogen.9
He further questioned IARC's categorization of dioxin as a carcinogen,

commenting that though "not a nice chemical, we make billion-dollar deci
sions and it's always touted as a carcinogen" when the only incident of
human accidental exposure showed "no evidence of cancer."9 These com
ments indicate that the scientists managing the ACT program were reluctant
to involve experts that were more likely than themselves to interpret phar
maceuticals and other chemicals as posing carcinogenic risk, and hence to
categorize those pharmaceutical indu

This probably reflected a wider con
many cancers are not caused by pha
environment, which is encouraged b
sizing individualized risk factors fo
2004). The ACT program's exclusion
independent of industry and more s
chemicals, together with the domin
in constructing the ACT program, m
gram met ECVAM's criterion of va
dence of management."
Framing the Science as Screening

As Murphy (2001) found in tobacco
bias" in expertise framed the conten
vement of industry scientists and ma
short-term in vivo mouse studies at
nical" approach and design of the A
For example, the basic methodology
prospective. That is to say, the app
engineered mouse models using chem
or noncarcinogens in humans and/o
nant (1997, 240), one of the preemin
genicity testing and transgenics sug
A more objective approach [than the re

programme] is to assay chemicals that
[lifespan] bioassays and to evaluate th
span and short-term in vivo studies] con
the transgenic models of detecting tran
ing to non-carcinogens.
One senior US government scientis

program rejected Tennant's "mor
favor of a retrospective validation m
The consensus amongst particularly t

was that they ... primarily... felt obl
compounds that have had a lot of hum
personal experience and by epidemiologyshould [be] negative

had turned out to be positive in some, if not all long-term [lifesp
studies. Because the fear was that if the short-term [in vivo] stud
be particularly sensitive, and might show up to be positive, and if
happened then they would have lost all confidence in trying to
term [in vivo] study.10
In other words, the primary concern that informed the m

design was that the alternative short-term in vivo tests with ge
neered mice might produce results that would propel scientist
even more pharmaceuticals as presenting carcinogenic risk t
span mouse studies had done. Indeed, according to many scie
academia, industry and government, including some closely i
the ICH process, "the ILSI [ACT] study was an attempt by th
convince themselves that these assays [short-term in vivo t
overly sensitive," that is, they would not produce more results t
scientists believed were false positives by "mis-identifying"
saw it) noncarcinogens as carcinogens.11 The industry's attitu
program was paraphrased by a former senior FDA scien
involved in both the ICH and the ACT program, as: "let's ma
[short-term in vivo] assays don't start popping up findings t
than the two-year mouse and two year rat together."8 Clearl
terization meant "worse" for the commercial interests of the
cal industry, as was made explicit by another expert sc
elaborated on industry's concerns as being that the new alte
term in vivo tests in genetically engineered mice might "th
of false positives, and cause a lot of problems in regulatory de
future pharmaceutical products]."7
A second consequence of industry ascendancy within the A
for methodological design was in the selection of compounds t
the new short-term mouse models. The pervasive industry con
that the short-term in vivo tests did not produce more false pos
rodent life span tests resulted in most of the compounds se
ACT program being noncarcinogens. As one senior scientist
explained why the selection of drugs was "heavily weighted
which would be presumed to have no [carcinogenic] effect."7 I
twenty-one compounds used, only six were human carcinoge
teen were noncarcinogens in humans. Yet, from the perspec
ing for carcinogens in order to protect public health, the prio
test systems that will be able to detect human carcinogens, so th
Table I. Compounds Assessed in the A
Class Compound
(1) Evidence of tumorigenic activity in humans:

Genotoxic human carcinogen Cyclophosphamide,
melphalan, phenacetin
Immunosuppressant human carcinogen Cyclosporin A
Hormonal human carcinogen Diethylstilbestrol, estradiol
(2) Nongenotoxic rodent carcinogens putatively noncarcinogenic in humans:
Rodent carcinogens/putative human Phenobarbital, clofibrate, reserpine,
noncarcinogens (human data) dieldrin, methapyrilene
Rodent carcinogens/putative human Haloperidol, chlorpromazine,
noncarcinogens (by mechanisms) chloroform, metaproterenol,
WY-14643 DEHP, sulfamethoxazole
(3) Noncarcinogens Ampicillin, D-mannitol, sulfisoxazole
agencies can then consider whether that risk is sufficient to prohibit human
exposure to the drug, including the denial of marketing approval. Thus, the
ACT program gave over twice as much attention to checking the validity of
these short-term in vivo tests according to industry interests (not too many false
positives regarding noncarcinogens) compared with the interests of public
health protection (not too many false negatives regarding human carcinogens).
The commercial interests of pharmaceutical companies also affected the
selection of drugs used because firms did not want any products with market
value to be part of the ACT program in case the new mouse models indi
cated that they were carcinogens. According to one US regulator, it would
have been scientifically interesting to investigate some pharmaceutical
products that had been permitted on to the market despite previous positive
carcinogenicity results in rodent lifespan studies, but added that that would
"probably have alienated more people [meaning industry] than was neces
sary."12 Consequently, in the methodological design of the ACT program,
one of the inclusion criteria for the compounds selected was that they
should be "on-proprietary" (Robinson and MacDonald 2001, 18). A for
mer FDA regulator at the ICH, who had subsequently moved to a US phar
maceutical firm surmised that "if the regulatory authorities had had their
freewill about which compounds would be in, there probably would have
been a few different ones," but significantly added that "the FDA went
along with itunderstanding that this was really [to let industry] become
comfortable [with the new mouse models]."8 The compounds finally
selected for the ACT program are listed in Table 1. Even at an ACT
workshop, many participants suggested that, from a scientif

"a different suite of test chemicals from those used might h
informative" (Pettit 2001, 194). More specifically, these find
that the ACT program could scarcely be said to meet the
dard for validation studies regarding "independence of selec
materials."
Maintaining Unscientific Interpretive Flexibility for Scientists

The evident lack of independence of the ACT program's management com
bined with the bias in chemical selection was compounded by the fact that
the analyses of the data were not blinded in accordance with the norms of
scientific trials. In other words, pharmaceutical firms chose which chemi
cals they would test, so the investigating scientists/pathologists examining
the genetically engineered mice (and their tumors) knew the carcinogenicity
status of the compound to which the mouse model had been exposed. As
one scientist reflected, the lack of blinding permitted the power of sugges
tion and concomitant biases, which needed little encouragement given the
extent of industry and ICH involvement:
People from different companies who were contributing to the study had their
pet chemicals that they were interested in. And then they would do retrospec
tive reviews of the literature on the chemical. That's really dangerous. So you
got this chemical, you get some squiffy data in the main [lifespan] animal
studies, you then do a transgenic test and it comes out positive or negative
because you say "of course it was positive, we've got this bit here, this bit
there, that bit there". Or if it came out negative, you'd say, "well, of course
it was negative because these positive things are just artefacts, it was negative
here, here and there". That's what happens [without blinding], it's the way
people behave. So it has to be done blind, they have to not know what the
outcome is going to be, in my view, for a proper study. So as a validation
study, it was very badly flawed.13
The lack of blinding is not only at odds with the scientific principles of
drug trials in general, it would also seem to be inconsistent with ECVAM
criterion of "independence of data analysis."
Transparency of the ACT program was also rather limitedmuch more
so than the FDA's process of drug regulatory review. ILSI made results of
all the ACT studies publicly available, but neither the database nor process
of analysis was open to public or wider scientific scrutiny,14 even though
this validation process had important implications for public health by
determining, in part, how new phar

as posing carcinogenic risk to hum
bases about pharmaceutical testing
sionals and legislators as a scientific
development of clinical trial regist
the limited transparency detracted fr
(Abraham and Sheppard 1997; Per
Interpretation of the Resu

Although the ACT program involve
were tested in more than one short-term in vivo mouse model. Across the
six known human carcinogens, involving thirty-two tests, the mouse models
correctly identified these carcinogens in only seventeen (53 percent), pro
duced nine false negatives (28 percent), and six (19 percent) of the results
were equivocal. Hence, in nearly half of the cases, these animal models
failed to identify human carcinogens, which could hardly inspire confidence
in their capability to screen for the human carcinogenicity of pharmaceuti
cals in drug regulation. By contrast, the mouse models correctly identified
82 percent of compounds that were both human noncarcinogens and rodent
carcinogens, and 100 percent of the compounds that were noncarcinogens
in both humans and rodents (Eastin et al. 2001; Storer et al. 2001; Usui
et al. 2001; van Kreijl et al. 2001).
After completion of the ACT program, the results were discussed by a
panel of its expert scientists chaired by Professor Samuel Cohen, an Amer
ican University Professor of Pathology and Oncology with extensive exper
tise in toxicology, a trustee of HESI, and a former advisor on the ILSI ACT
Steering Committee.4 Downer (2007) has noted that tests of reliability can
contain irreducible ambiguities requiring judgments with real conse
quences. Our analysis of interpretations of the ACT program results shows
how such judgments are structured by the power and goals of the social
interests at stake.
On the whole, the pharmaceutical industry and regulators involved with
the program found the results reassuring and became more comfortable about
the prospect of using the short-term in vivo mouse models.8'15 One regulator,
who had criticized the ICH for recommending use of these short-term mouse
models in 1998 before validation, was similarly reassured:
we've actually looked at all these models, decided which ones we think are
good enough for regulatory acceptance, and put forward how we think these
should be applied, and general recommendations for study desi

guidelines are there now. You couldn't produce the guidelines b
studies were validated because they weren't validated.16
Apparently a method had been found to manage new drugs

carcinogenic-risk-assessment part of the regulatory process t
sen workload for regulators and result in faster and cheaper
ment for industry with no greater risk than before of denial
approval by regulators because of carcinogen identification.
confidence that the new short-term in vivo genetically eng
models did not produce "excessive" false positives, their
became much better aligned than before with the commercia
industry and the political interests of regulators, who, under
had redefined the mission of regulation as the rapid process
development.
Goodman (2001), an academic scientist closely involved wit
strated how these institutional interests could shape the very
entific knowledge about carcinogen identification and d
considered two aspects of the short-term mouse models to o
of comfort," namely, that these models could be used to inc
dence in a negative result [with a compound in a life span rat
vide "the ability to place a positive result [in a life span roden
proper context" (Goodman 2001, 174). In other words, there w
the pharmaceutical industry (and regulators sympathetic to i
comfortable with the new short-term mouse models so long
firmed negative results in rats or made overall negative interpre
likely by prompting reconsideration of positive findings in rats
converse scientific possibilities, namely, the confirmation of p
or the ability to put negative findings in "proper context," w
trary to industry interests, but might increase public health pr
not mentioned within a "level of comfort." As Winickof
(2010) report regarding the internationalization of new stand
risk regulation, judgments about the adequacy of framewor
assessment embody values about public health and the priorit
protection relative to industry interests.
Yet, as a close examination of the technoscience underpinn
program reveals, there was comfort not because of high levels
in scientific validity, but rather because the new short-term
appeared to satisfy the interests of the dominant stakeholders
ceutical industry and the government regulatory agencies. F
scientists, including some within t

evidence that i these new short-term
improvement over, or could even ad
mice as means to screen for potent
the regulatory protection of public
given a mere 53 percent detectio
program Panel could not agree abou
positive carcinogenicity findings fr
disagreed as to whether an unexpect
evidence of irrelevant oversensi
information the test indicating that
(Pettit 2001, 193).
Although the panellists "generally
substitute for the two-year [life sp
ACT program scientists significantly
the new short-term mouse models m
tifying genotoxic compounds," but
individual model presents any part
traditional mouse strains for evalu
genotoxic modes of action" (Pettit
in the ACT program also alluded to t
models regarding screening for non
nogens because the organ specific
appear to correlate well with poten
humans" which "will significantly l
with respect to mechanism of action
chemicals that are not genotoxic" (
18). Particularly sceptical about the
mouse models to nongenotoxic hum
MacDonald (2001, 188) noted that al
deleted in these mice "may have in
esis, [they did] not give a clear ind
carcinogenesis." This is because, as
"experimental evidence shows that
ary to some other biological effect"
Yet from the perspective of patien
new mouse models were to replace l
then the crucial issue was whether the new mouse models could be relied
upon to detect nongenotoxic carcinogens because it was those carcinogens
for which the life span studies were used to screen. As several scientists,
including the UKCoC explained, the new short-term mouse

detected genotoxic carcinogens," but that "in most cases"
gens would be "detected in a standard battery of genotoxicity
have been used alongside life span studies for decades (UKCo
tion 2i; Goodman 2001, 175). As one industry toxicologist ou
program reflected:
With the benefit of hindsight, I don't think the outcome of that

gramme] was worth the effort ... because we are actually prett
where we were before it was done. It hasn't helped me make decis
what we are going to do with our drugs in development. ... There
studies for detecting genotoxicity but we haven't solved the prob
genotoxic carcinogens.17
Despite these major reservations, Cohen, Robinson, an

(2001,189) contended that the new short-term mouse models
"useful information in the overall evaluation of potentia
hazard to humans" and "provide the next step in our ultimate
able to accurately predict human carcinogenesis for a given c
do so without relying on long-term [lifespan] bioassays in an
contradiction inherent in the ACT program experts' optimis
these new mouse tests could match their commercial and poli
in avoiding life span tests is encapsulated in their comment t
they [the ACT program experts] consider the [new genetical
mouse] models scientifically valid, the current data set is not
validate the models" (Pettit 2001, 195). Such optimism infect
ernment regulatory agencies. For example, the EU's supranati
ulatory Committee for Proprietary Medicinal Products (2002)
as the Committee for Human Medicinal Products, considered t
genetically engineered mice "could be used for regulatory p
alternative to the long-term mouse study in conjunction with
[life span] rat study."
Other expert scientists and toxicology bodies outside the A
were often much more forthright in their criticisms. The U
noted "that these mice identify some genotoxic compou
12), but advised that "further development and validation o
in-vivo models to evaluate non-genotoxic carcinogenesis and
ters may be valuable" (section 2iii). Overall, the Committee's v
there was not enough data from the ACT program "to really
questions" about nongenotoxic carcinogenicity.18 Focusin
on whether these new short-term ge

could replace life span mouse studies,
of the models" were suitable in that
gested that most scientists outside th
convinced by the new mouse models
OverallI think the majority of scientis

with the end resultsbecause we really
model, and obviously we haven't got [th
Conclusions and Policy Impl

Frickel (2004) and Shostak (2005, 2007
ican toxicology of environmental
involved the "activism" of scientist
neered animal models as testing system
regulatory sphere, including the FDA
ticals regulation, that, together with
the global pharmaceutical political
genetically engineered mouse models
carcinogenicity testing. However, as
"molecularization" is only one dim
knowledge formation. It does not expl
for alternative tests to translate in the
agement, and interpretation of those a
the international pharmaceutical secto
to understand why the government
the industry's agenda of streamlining
ing, in particular. One also needs to un
latory agencies essentially gave the ph
in designing, managing, and interp
whether the alternative tests were va
gen identification and screening.
We have shown that the precise
occurred resulted from a neoliberal i
goals of drug regulatory agencies and
ceutical industry, culminating in regul
displayed in the ICH project and subse
these reasons that, on the watch of gov
mine the validity of short-term mouse
commercial goals of the industry, rather than the interests of p

logical imperatives internal to toxicological science. Indee
sional scientific standards regarding validation had never be
their stipulations, but had no compelling effects on the ACT
whose interest-driven practices clashed with those scientific
As Lave, Mirowski, and Randalls (2010, 660) have observ
domains, "neoliberalism had shifted methods, organization a
of technoscience."
Moreover, the interpretation of the short-term mouse models as valid
replacements for the life span tests in mice in order to identify and
screen for nongenotoxic human carcinogens is highly questionable, even
by the standards of some of the ACT program scientists themselves.
Yet, such validity is what is needed if the short-term mouse models are
to maintain regulatory levels of public health protection. Nonetheless,
the short-term mouse models have been introduced into pharmaceutical
regulations, thus contributing to the "scientific knowledge" about
whether or not new pharmaceuticals are carcinogens. The industry has
achieved its objective of having the option to jettison life span carcino
genicity studies in mice in favor of cheaper and shorter mouse tests,
which the industry and its allies in regulatory agencies may present
as valid because the ACT program has shown that the short-term mouse
models are not "overly sensitive" to noncarcinogens. Such validation
indicated that the short-term mouse models pose small risks to the com
mercial interests of pharmaceutical firms, but provided little reassurance
that they would not permit patients to be exposed to greater risks than
before from undetected carcinogens that find their way on to clinical
trials or the market.
This raises the question of whether the drug regulatory agencies should
be characterized as "captured" by industry regarding "technoscientific"
standards for carcinogenic risk assessment. Abraham (1995), who studied
pharmaceutical regulation in the United Kingdom and the United States
from the late nineteenth century to the mid-1980s, found that there had been
capture in both countries in that period, though significantly more in the
United Kingdom than the United States. However, overall, he concluded
that UK and US drug regulation should be characterized as "corporate
bias," rather than capture because "industry interests played a key role in
the establishment and evolution of regulation, and the state, under certain
conditions, defined its own interests independently of the industry" (Abra
ham 1995, 85). Capture theory, therefore, tends to glorify the beginnings of
state regulation as adversarial toward industry during "cycles" of
regulatory zeal, while simultaneous

regulatory agencies in "cycles" of "
As we have noted, discussions abou
neoliberalism. It is possible for the f
latter, so clearly they are distinct
change. Neoliberalism advocates tha
jectto the tests of the market, where
conditions of antimarket protectioni
less, neoliberalism can accentuate op
lization and marketization of the
business interests. In this case, it m
permitted the commercial interests
pharmaceutical carcinogenicity testi
interests of public health. They perm
neoliberal political context in which
to make regulatory agencies more r
ever, the regulators have not relinq
matters, only their leadership and po
of public health. In that respect, w
ments in carcinogenicity testing stan
Abraham and Lewis (2000) call "ne
capture, and a neoliberal corporate b
as scientific knowledge in ways hit
Acknowledgments
The authors are grateful to two anonym
vious draft and to the Wellcome Trust f
this article is based.
Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research,
authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research,
authorship, and/or publication of this article: The Wellcome Trust (Grant No.
064051).
Interview Notes
1 Senior scientific officer, UK drug regulatory agency.
2 UK university toxicology professor and industry/regulatory cons

3 UK university toxicology professor involved with ILSI; US toxic
Boehringer Ingelheim.
4 Professor of Pathology and Microbiology, Nebraska University.
5 Scientific Director of an EU company and formerly Toxicology
UK companyboth ILSI companies.
6 Senior Scientist, FDA.
7 Director, National Center for Toxicogenomics, NIEHS.
8 Vice president, Safety Assessment, at a US pharmaceutical comp
FDA scientist).
9 Vice president, Pharmaceutical Safety at a US drug firm, and inv
ACT.
10 Group leader, transgenic carcinogenesis, Laboratory of Molecular Toxicology,

NIEHS, and involved with ILSI ACT.
11 Vice president, Safety Assessment at a US pharmaceutical company; govern
ment scientist, Laboratory of Molecular Toxicology, NIEHS; government
scientist, Laboratory of Toxicology, Pathology and Genetics, Netherlands
National Institute of Public Health and Environment; director, National Center
for Toxicogenomics, NIEHS.
12 FDA scientist, Office of Pharmaceutical Science.
13 Academic scientist and former member, UKCoC.
14 Senior official, ILSI ACT.
15 Dutch regulator and coordinator, CPMP safety group.
16 Senior UK regulator, MCA.
17 Toxicologist and Vice president of a UK pharmaceutical company.
18 Member, UKCoC.
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Bios
John Abraham is a professor of sociology and director of the Centre for Research
in Health and Medicine (CRHaM) at the University of Sussex, where he has been
leading an STS research program on pharmaceuticals and working on carcinogenic
risk assessment of pharmaceuticals fo

adviser to the UK House of Commons
he was centrally involved in its eight-mo
maceutical Industry" (2005). He is the au
politics and sociology of pharmaceutica
European Union, namely, Science, Po
(UCL/St Martins Press, 1995), The The
World's Most Controversial Sleeping P
icines in Europe: Competition Expertis
is the editor of Regulation of the Phar
Rachel Ballinger is a research fellow

cial Oncology Group, Brighton and S
sex. Over the past 13 years her rese
various health-care and policy settin
study on clinical and patient decision
aged 70 and over with breast cancer
in breast cancer surgery decision-m
treated for Hodgkin Lymphoma.

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The Neoliberal Regulatory State, Industry Interests, and the Ideological Penetration of

Scientific Knowledge: Deconstructing the Redefinition of Carcinogens in Pharmaceuticals

Science, Technology, & Human Values

Regulatory State, DOI: 10.1177/0162243911424914

Industry Interests, USAGE

and the Ideological

It is argued that neoliberal political ideology has redefined the regulatory

cost reduction of drug development and regulatory review.

Bloomfield and Doolin 2011; Braun

that evaluation process at the World Health Organization's e

organizational practices via consul

Neoliberal Ideology and Ne

drugs on to the market fast enough (Abraham and Lewis

continue to be so conservative [as

Meanwhile, Reagan's Secretary of State for Health praised the

industry to set the agenda of th

New Ways of Testing Pharmaceuticals for

usually between eighteen and twenty-four months. At the end

bioequivalence concept in the Unite

394) calls "conceptual power." However, it was neither unchallen

The Meaning and Increasing Significance of Va

After these changes to the regulations for carcinogenicity testing, "valida

involvedat least that was the claim

in deciding whether they wish to accept and/or implement ICC

The Process of Validation

It was widely acknowledged, therefore, that the new short-term in vivo ca

the need to separate industry influ

[T]hrough HESI, the pharmaceutical industry, especially in the States

ILSI was founded in 1978 as a not-for-profit worldwide foundation with

He further questioned IARC's categorization of dioxin as a carcinogen,

categorize those pharmaceutical indu

Framing the Science as Screening

A more objective approach [than the re

One senior US government scientis

The consensus amongst particularly t

personal experience and by epidemiologyshould [be] negative

In other words, the primary concern that informed the m

Table I. Compounds Assessed in the A

(1) Evidence of tumorigenic activity in humans:

workshop, many participants suggested that, from a scientif

Maintaining Unscientific Interpretive Flexibility for Scientists

determining, in part, how new phar

Interpretation of the Resu

should be applied, and general recommendations for study desi

Apparently a method had been found to manage new drugs

scientists, including some within t

including the UKCoC explained, the new short-term mouse

With the benefit of hindsight, I don't think the outcome of that

Despite these major reservations, Cohen, Robinson, an

on whether these new short-term ge

OverallI think the majority of scientis

Conclusions and Policy Impl

commercial goals of the industry, rather than the interests of p

regulatory zeal, while simultaneous

Declaration of Conflicting Interests

1 Senior scientific officer, UK drug regulatory agency.

2 UK university toxicology professor and industry/regulatory cons

10 Group leader, transgenic carcinogenesis, Laboratory of Molecular Toxicology,

Abraham, J. 1993. "Scientific Standards and Institutional Interests: Carcinogenic