論文 / 著書情報
Article / Book Information
Title

Corporate Characteristics and Adoption of Good Manufacturing
Practice for Dietary Supplements in Japan

Authors

Keigo Sato, Kota Kodama, Shintaro Sengoku

CitationInternational Journal of Environmental Research and Public Health, Vol.
17, Issue 13

Pub. date

2020, 7Creative Commons

Information is in the article.

Powered by T2R2 (Science Tokyo Research Repository)

Article

Corporate Characteristics and Adoption of Good
Manufacturing Practice for Dietary
Supplements in Japan
Keigo Sato 1, Kota Kodama 2 and Shintaro Sengoku 1,3,*
Department of Innovation Science, School of Environment and Society, Tokyo Institute of Technology,
Tokyo 108-0023, Japan; sato.k.bz@m.titech.ac.jp
2 Graduate School of Technology Management, Ritsumeikan University, Osaka 567-8570, Japan;
kkodama@fc.ritsumei.ac.jp
3 Life Style by Design Research Unit, Institute for Future Initiatives, University of Tokyo,
Tokyo 113-0033, Japan* Correspondence: sengoku.s.aa@m.titech.ac.jp
Received: 18 May 2020; Accepted: 27 June 2020; Published: 1 July 2020
1

Abstract: Good manufacturing practice (GMP) is advocated and implemented as a standardized
procedure for manufacturing dietary supplements. However, in Japan as a case, only half of the
manufacturers in this field so far adopt it. To address this issue, the present study aims to explore
the effect of key characteristics of a company on the adoption of and compliance with GMP for
dietary supplements. The focus is on the effect of expertise in the pharmaceutical industry. The
relationships between company characteristics and the adoption of GMP were analyzed for 90
manufacturers in the dietary supplement industry in Japan. A binomial logistic regression analysis
showed that each of the following three factors had a positive and significant effect on thecompany’s adoption of GMP: company size in terms of revenue (odds ratio = 1.04, p = 0.019),
possession of a manufacturing license for pharmaceutical products (13.7, p = 0.003), and number ofown product categories manufactured (3.93, p = 0.00009). These findings strongly suggest that thecompany’s manufacturing capability of pharmaceutical products works as a key driver for the better
adoption of a quality standard in the dietary supplement industry in Japan. Few considerations
were made for conditions of the adoption and implementation of GMP. The present study
empirically contributes by providing key clues for issues in the dietary supplement industry and byforming a theoretical base for policymakers and the regulatory authorities.
Keywords: functional food; quality certification; industry convergence; organizational capability;
GMP; good manufacturing practices

1. Introduction
A dietary supplement is a food shaped as a soft capsule, hard capsule, tablet, granule, or liquidthat differs from regular food and contains functional physiological ingredients. It is expected tocontribute to promoting health and preventing disease in aging societies, and it is considered a wayof self-medication with the potential to reduce the public health burden. The market for dietary
supplements expanded steadily in accordance with expectations and increased food technology
innovation [1–3]. The dietary supplement industry incorporated various business entities:
pharmaceutical and food companies, small and medium-sized enterprises (SMEs), start-up
companies that use novel functional ingredients and/or local specialty foods, new entrants from otherindustries, and original equipment manufacturers (OEMs).

Int. J. Environ. Res. Public Health 2020, 17, 4748; doi:10.3390/ijerph17134748

www.mdpi.com/journal/ijerph

Int. J. Environ. Res. Public Health 2020, 17, 4748

2 of 12The Number of Companies
with GMP

2016

0
2014

0
2012

40

2010

2

2008

80

2006

4

2004

120

2002

6

2000

160

1998

8

1996

200

1994

10

1992

Market Size (billion USD)

In Japan, the size of the dietary supplement market is growing and currently totals $8 billion
United States dollars (USD) (Figure 1), and the industrial ecosystem is developed based on thetransdisciplinary environment described above. Notably, more than 70% of dietary supplement
manufacturers outsource their manufacturing process to OEMs.

Figure 1. Historical transition of the market size of dietary supplements (the line) and number of good
manufacturing practice (GMP)-licensed manufacturers for dietary supplements in Japan (the bars).
Data on the market size and the number of companies were obtained from commercially available
sources [4] and from GMP certification organizations (Japan Health and Nutrition Food Association—
JANFA, and Japanese Institute for Health Food Standards—JIHFS).

As a recent regulatory movement, a unique Food with Function Claims (FFC) system waslaunched in Japan in 2015. This system was introduced with the policy intention to use functional
food and dietary supplements for health promotion and disease prevention, as well as for control of
medical expenses. FFC are foods submitted to the Secretary General of the Consumer Affairs Agency(CAA) as products whose labels bear function claims based on scientific evidence, which is the
responsibility of food business operators [5]. Before the launch of the system, making function claims
on food labels was only allowed for government-approved Foods for Specified Health Uses (FOSHU)
and self-certified Foods with Nutrient Function Claims (FNFC) that complied with the specifications
and standards designated by the government. The system of Foods with Health Claims (FHC) can bedelineated into three categories, as shown in Figure 2.

Foods

Pharmaceuticals

Foods with Health Claims
So-ca lled“hea lth foods”

Foods with
Function Claims(FFC)

Foods with Nutrient
Functi on Claims(FNFC)

Foods for Specified
Hea lth Uses
(FOSHU)

Notification

Self-certification

Approval

Pha rma ceuticalproducts & Quasipha rmaceuticalproducts

Figure 2. Categories ranging from food to pharmaceuticals containing Foods with Health Claims.

In the current FFC system, the government does not evaluate the safety and effectiveness offunction claims. Food business operators submit an appropriate function claim based on scientificevidence for which they are responsible. Scientific evidence for function claims must be obtained
through a clinical trial or systematic review of the literature. To propose function claims under the
FFC system, it is required to submit a premarket notification and to label the package in accordance

Int. J. Environ. Res. Public Health 2020, 17, 4748

3 of 12with the Food Labeling Standards pursuant to the Food Labeling Act, as well as the “Guidelines on
Notification of Foods with Function Claims”. This system provides more information about
functional food products to consumers and helps especially small companies develop functional
foods [6–8]. The FFC system accelerates new entrants and the further growth of the market.
Alongside the growth of the market and industry, quality issues such as inappropriate
manufacturing process management and insufficient ingredient amounts emerged [9]. According to
the Food and Drug Administration (FDA) report about dietary supplements in 2013, 6307 adverse
event reports from 2008 to 2011 resulted in serious outcomes—unspecified important medical eventsof a serious nature (53%), hospitalization (29%), serious injuries or illnesses (20%), resulted in a lifethreatening condition (8%), and death (2%) [10]. In Japan, the Ministry of Health, Labor, and Welfare(MHLW) drew attention to quality issues by presenting examples of health hazards caused by healthfoods [11]. The factors that affect the quality of the product are the quality of the raw materials
themselves, the addition of multiple materials, and impurities. Since raw materials are notstandardized, purity and ingredient amounts vary from manufacturer to manufacturer. In the caseof natural plant extract ingredients, in addition to the fact that the ingredients contained are often not
specified, the ingredients contained in the product vary depending on where it is grown and when it
is harvested. The National Institute of Health and Nutrition disseminates information on safety andhealth damage for health foods through their website [12].
It is problematic that consumers can hardly determine whether a product is sufficiently qualified
when purchasing it, since all products have a similar shape and appearance, for example, tablets or
capsules. Therefore, quality assurance standards were developed and implemented to reduce thisasymmetry of information between manufacturers and consumers. For example, in thepharmaceutical industry, good manufacturing practice (GMP) was adopted as a means of quality
assurance and control. This regulatory standard ensures the compliance of pharmaceuticalmanufacturers with defined manufacturing and packaging procedures.
Several studies reported that the implementation of GMP by a company effectively induces
profound behavioral changes in the organization and individuals and, furthermore, enhances thelevel of knowledge and awareness of the significance of product quality and safety [13]. GMP is used
to manage an appropriate operation under a manufacturing process in accordance with defined
standards to ensure that quality control is properly implemented. Quality risks such as
misidentification or mislabeling of ingredients, adulterations, substitutions, and contaminations in
the production process can be decreased through the GMP system, ultimately decreasing the numberof consumer complaints [14]. In addition, the implementation of GMP reportedly improves theworking environment and promotes employee motivation and productivity [15]. The International
Conference on Harmonization (ICH) provides current good manufacturing practice (cGMP).
GMP is advocated as a standardized regulatory system for the manufacturing process, as in thepharmaceutical industry [3,15]. Some countries including the United States, European Union (EU),
Korea, Taiwan, and China already adopt GMP as a regulatory requirement for product qualification[3,7,16,17]. However, in Japan, GMP for dietary supplements is still voluntary. In Japan, twoorganizations certify the GMP for dietary supplements, namely, the Japan Health and Nutrition Food
Association (JANFA) and the Japanese Institute for Health Food Standards (JIHFS). However, since2005, only around 150 Japanese OEM companies (half of all OEM companies) adopted GMP (Figure1). The GMP system is not mandated, because dietary supplements are not legally defined in Japan[18].
The present study aims to explore the effect of the key characteristics of a company on the
adoption of and compliance with GMP for dietary supplements, with a focus on the effect of expertisein the pharmaceutical industry. This study also explores how to successfully implement GMP tofurther innovate dietary supplements by identifying factors that influence the adoption (or rejection)of GMP. Furthermore, the required organizational capability needed for implementation is discussed.
From the perspective of product characteristics and institutional aspects, dietary supplements
are positioned between food and medicine in the regulatory spectrum [19]. In this regard, several
studies on regulatory science and innovation management discussed the influence of technologicalInt. J. Environ. Res. Public Health 2020, 17, 4748

4 of 12and regulatory trajectories and the path-dependent or creative mechanism of the dietary supplement
industry.
The dietary supplement industry is an emerging one formed by the industrial integration of thepharmaceutical and food industries [20]. The concept of industrial convergence highlights that new
industry sectors form as knowledge, technology, and institutions from various industries fuse [21,22].
In the case of dietary supplements, the pharmaceutical industry introduced technical competences,whereas the food industry focused on marketing competence [23].
Several studies revealed the significance of implementing standards for quality control in the
manufacturing process, such as pursuing operational excellence in improving product quality andproductivity, as well as educational contributions to employees. Others are external effects such asbuilding healthy relationships with customers and the positive effects of product marketing [24–26].
Reportedly, the size of an enterprise affects the adoption of quality control standards. Notably, smallsized companies with relatively undifferentiated product lines tend to be motivated to adopt a quality
control standard for differentiation purposes in the competitive marketplace and as a requirement bycustomers with relatively large buying power [25].
As a negative impact, additional costs for quality assurance, including human resource
development or hiring and investment for GMP-complying facilities and equipment, are obstacles tothe introduction of GMP [27,28]. Therefore, larger enterprises tend to more proactively introduce
quality standards, because of a relatively lower cost burden than small and mid-sized enterprises[29].
As discussed, prior studies revealed the existence of external and internal factors that affect the
adoption and implementation of quality control standards. In the business of contracted
manufacturing organizations (CMOs) for dietary supplements, the cost burden and organizational
capability are considered key internal factors that affect the adoption and implementation of GMP
for dietary supplements. Specifically, the introduction and maintenance of GMP-complying
manufacturing facilities and equipment for inspection are key elements of direct costs, and building
organizational capabilities such as improving operations and employee education may increaseindirect costs. These additional costs are considered relatively lighter for larger enterprises in termsof the economy of scale, resulting in the smoother adoption of GMP.
Hypothesis 1: The adoption rate of GMP for dietary supplements is correlated with the size of the CMO.
Regarding CMOs in the pharmaceutical sector, their organizational capability to manufacture
pharmaceutical products may contribute to dietary supplements, since they operate GMP-level
manufacturing processes and quality controls that are mandatory for pharmaceutical products. Theirpolicy, expertise, and human resources could contribute to improving the level of manufacturing
process and quality control in the dietary supplement sector, promoting the more proactive adoptionof GMP for dietary supplements.
In contrast, as the path-dependency theory points out, non-pharmaceutical manufacturing
companies such as food manufacturers have a lower awareness and absorptive capability to adopt
GMP for dietary supplements, i.e., they may need to spend additional time and cost to acquire andnurture their organizational capability [30]. Based on these considerations, we hypothesize thatbarriers to adopting GMP may differ between pharmaceutical and food manufacturers.
Hypothesis 2: The adoption rate of GMP for dietary supplements is higher among manufacturers ofpharmaceutical products than among food product manufacturers.
Customer relationships are considered key external factors in the adoption of GMP.
Manufacturing under the GMP system standardizes and guarantees a certain level of product quality
and reduces the level of uncertainty on the customer side. It is also expected to reduce transaction
costs between a CMO as an OEM and their clients as end-product manufacturers. Furthermore, in anenvironment wherein information between OEMs and their clients is asymmetrical, acquiring GMP
provides clients with a certificate of quality control in manufacturing, which may contribute tobuilding credibility. In other words, GMP as a certification has a signaling effect that eliminates
asymmetrical information and strengthens the relationship between two manufacturers.

Int. J. Environ. Res. Public Health 2020, 17, 4748

5 of 12In the present study, considering difficulties in measuring the level of a specific customer
relationship, the number of product categories that the CMO can manufacture was employed as aproxy for the strength of the customer relationship. Typical categories of dietary supplements are soft
capsule, hard capsule, tablet, granule, and liquid. CMOs capable of manufacturing various forms of
dietary supplements are considered to sufficiently meet their customers’ requirements. Therefore, thenumber of categories of manufactured dietary supplements at a CMO was set as a surrogate variable
for the strength of the customer relationship.
Hypothesis 3: The adoption rate of GMP for dietary supplements is correlated with number of productcategories a contract manufacturing enterprise can manufacture.
2. Materials and Methods
Data were collected for 90 OEMs in the Japanese dietary supplement industry in 2016 (thecontract manufacturing company guidebook, UBM media; company information database Orbis,
Bureau van Dijk).
We considered the possession of one or more of four types of licenses related to marketing or
manufacturing for pharmaceutical or quasi-pharmaceutical products as a surrogate variable for the
manufacturing capability of pharmaceutical products. We also considered the possession of one ormore of 22 types of licenses related to manufacturing processed food as a surrogate variable for the
manufacturing capability of food products. The shape of the dietary supplement was classified into
five categories (i.e., soft capsule, hard capsule, tablet, granule, and liquid). The number of productcategories ranged from zero (with only a packaging process) to five (with manufacturing processes
for all categories mentioned).
Statistical analyses were performed using R statistical software (version 3.4.1, The R Foundation,
Vienna, Austria, 2017). This article does not contain any studies with human or animal subjects
performed by any of the authors.
3. Results
3.1. Descriptive Satistics
Table 1 provides the descriptive statistics of the sample data. The standard deviations forrevenue and the number of employees were relatively large, suggesting a considerable difference inthe size of these CMOs.
Table 1. Descriptive statistics of the samples (90 original equipment manufacturers (OEMs) in theJapanese dietary supplement industry).

0.51
5.99
160.9

Standard
Deviation
0.50
19.13
291.4

MaximumValue
1
170.46
1837

Minimum
Value
0
0.04
3

0.27

0.44

1

0

0.51

0.50

1

0

1.81

1.41

5

0

Variables

Mean

Compliance of GMP
Revenue (billion yen)
Number of employees
License for manufacturing
pharmaceutical products
License for manufacturing foodproducts
Number of product categories

Int. J. Environ. Res. Public Health 2020, 17, 4748

6 of 123.2. Effect of Company Size
Figure 3 compares the revenue and number of employees of CMOs with and without GMP (n =46 and 44, respectively). To test hypothesis 1, the Mann–Whitney U test was employed to compare
the revenue and number of employees of companies that do or do not comply with GMP for dietary
supplements. The test revealed that companies with GMP have significantly more revenue and alarger number of employees than those without it (p < 0.01 and 0.01, respectively). This supports
hypothesis 1.
p<0.01p<0.01
10000
Number of Employees

Revenue (billion yen)

1000
100
10
1
0.1
0.01

1000
100
10
1

Companies
without GMP(n=44)

Companies
with GMP(n=46)

Companies
without GMP(n=44)

Companies
with GMP(n=46)

Figure 3. Revenue and number of employees of contracted manufacturing organizations (CMOs) for
dietary supplements with and without GMP in Japan.

3.3. Effect of Business Domains
To test hypothesis 2, the samples were divided into four subgroups based on the possession oflicense(s) for both manufacturing food and pharmaceutical products (subgroup A), only for food (B),
only for pharmaceutical (C), or neither (D) (Figure 4). Fisher’s exact test revealed that the adoption
rates of GMP varied across these subgroups (p < 0.01). Furthermore, we examined the difference
between subgroups A (both food and pharmaceutical products) and D (neither) using a t-test (Holmmethod). The results in Figure 4 show that companies with a license for manufacturing
pharmaceutical products tend to have a significantly higher adoption rate of GMP for dietary
supplements. These results support hypothesis 2.

Food manufacturer

Yes

No

Group AGroup C

w/o GMP: 3with GMP: 13
Adoption: 81%

w/o GMP: 1
with GMP: 7
Adoption: 88%
p=0.04No

Pharmaceutical manufacturer

YesGroup B

Group D

w/o GMP: 18
with GMP: 12
Adoption: 40%

w/o GMP: 22
with GMP: 14
Adoption: 39%

Figure 4. Summary of adoption rates of GMP for dietary supplements for possession of license(s) for
manufacturing food and/or pharmaceutical products.

Int. J. Environ. Res. Public Health 2020, 17, 4748

7 of 123.4. Effect of Number of Product Categories
To test hypothesis 3 regarding the effect of the number of product categories, the company
samples were divided into six subgroups according to the number of categories of manufactured
dietary supplement products, ranging from G-0 (no product, i.e., only packaging process) to G-5 (fivecategories, i.e., soft capsule, hard capsule, tablet, granule, and liquid). Fisher’s exact test revealed thatthe adoption rates of GMP for dietary supplements varied across subgroups (p < 0.00001). Then, thedifferences were further examined between subgroups G-0 and G-3, G-0 and G-4, G-1 and G-3, andG-1 and G-4 using a t-test (Holm method). Figure 5 indicates that the adoption rates of GMP for
dietary supplements were significantly correlated with number of product categories manufacturedby the companies (r2 = 0.952). This supports hypothesis 3.

Figure 5. Relationship between the number of product categories and adoption rate of GMP.

3.5. Binomial Logistic Regression Analysis
Based on the above-mentioned results, a binomial logistic regression analysis of the adoption
rate of GMP for dietary supplements was conducted. Table 2 shows the correlation coefficients of
selected variables: revenue size, possession of a license for manufacturing pharmaceutical products,
and the number of categories of manufactured dietary supplement products. Considering
multicollinearity caused by the high correlation between revenue and the number of employees(correlation coefficient = 0.82), a model including revenue without the number of employees was run
based on the lower value of Akaike’s information criterion (AIC).
Table 2. Correlation coefficients of selected variables (revenue size, possession of a license for
manufacturing pharmaceutical products, and the number of categories of manufactured dietary
supplement products).
Variable

GMP

Revenue No. of Employees

Revenue
Number of employees
Pharmaceutical manufacturer
dummy
Food manufacturer dummy
Number of product categories

0.231 *
0.374 **

0.824 **

0.389 **

−0.002

0.098

0.066
0.546 **

−0.1120.121−0.096
0.317

Pharmaceutical Food
Dummy
Dummy

0.188
0.169

0.121

*: p < 0.05; **: p < 0.01.

Table 3 provides the results of a binominal regression analysis of the adoption rate of GMP for
dietary supplements with four independent variables. The odds ratio for revenue size was 1.04 (95%
confidence interval 1.01 to 1.09, p = 0.019), that for the pharmaceuticals dummy was 13.7 (95%

Int. J. Environ. Res. Public Health 2020, 17, 4748

8 of 12

confidence interval 2.85 to 90.8, p = 0.003), and that for the number of product categories was 3.93
(95% confidence interval 2.14 to 8.61, p = 0.00009). This model confirms the three hypotheses of thestudy and provides a consolidated view of the contribution of these factors to the adoption of GMP
for dietary supplements.
Table 3. Binomial logistic regression analysis of the adoption rate of GMP for dietary supplementswith four independent variables.

0.021
1.04

95% ConfidenceInterval
Lower
Upper
0.0025
0.106
1.01
1.09

0.00004 ***0.019 *

2.62

13.7

2.85

90.8

0.003 **

−0.13
1.37

0.88
3.93

0.24
2.14

3.10
8.61

0.84
0.00009 ***Variables

Coefficien t

Odds
Ratio

Constant
Revenue size
Pharmaceutical manufacturer
dummy
Food manufacturer dummy
Number of product categories

−3.86
0.04

p-Value*: p < 0.05; **: p < 0.01; ***: p < 0.001.

4. Discussion
The results obtained in this study suggested that the size of the company in terms of revenue or
the number of employees, license for manufacturing pharmaceutical products, and the number ofcategories of manufactured dietary supplements contributed to the adoption of GMP for dietary
supplements. From a historical viewpoint, the dietary supplement industry emerged through theconvergence of the food and pharmaceutical industries, and it was nurtured by these two streams ofindustrial and organizational capabilities. The present study found that pharmaceutical capability
influences a quality level for manufacturing dietary supplements, accompanied by expertise in
manufacturing a wide range of dietary supplement products.
In the industry convergence model, multiple convergence steps (knowledge convergence,technology convergence, applicational convergence, and industry convergence) were proposed as aroute to industry convergence [23]. Applicational convergence was pointed out as being influenced
by the institution and customer needs. The results of this research suggested that, under theapplication of quality standards such as GMP, it is relatively easy to integrate the pharmaceuticalindustry into the food industry, whereas it is not so for the food industry into the pharmaceuticalindustry, i.e., potential asymmetric process/dynamics of the industry convergence, which is expected
to provide practical implications to revisiting regulatory conditions in Japan.
Since the introduction of GMP is voluntary in Japan, companies are not uniformly affected by
the institution. In the paragraph below, we discuss the reason why Japan’s GMP system is voluntary
in comparison with the United States case.
In the United States, GMP for pharmaceuticals was formalized in 1962 [14]. Until 1994, dietary
supplements were treated in the same way as regular foods. Since 1994, dietary supplements are
regulated under the Dietary Supplement Health Education Act (DSHEA). Dietary supplements aredefined as foods with a shape that was processed for consumption, such as a capsule or tablet. In
2007, the cGMPs for dietary supplements were published by the Food and Drug Administration(FDA). The GMP-based product qualification is mandatory for all firms that manufacture, package,label, or hold dietary supplements in the United States [7,15,31]. While statements of functional
claims can be displayed on the packaging or labels according to the DSHEA, the manufacturing
process is controlled by the GMP.
On the other hand, Japan introduced a legislative framework for FFC in 2015. This system spans
food and dietary supplements. However, dietary supplements under this system account for a smallpart of the Japanese dietary supplement market. In Japan, many dietary supplements are excluded
from the system, and no legal system exists to comprehensively regulate dietary supplements. The

Int. J. Environ. Res. Public Health 2020, 17, 4748

9 of 12

relationship between dietary supplements and related legal systems is shown in Figure 6. Complex
Japanese institutions are attributed to the historical path-dependency of a repeatedly revised system.
It is difficult to redesign the Japanese legislative framework and legally define dietary supplements,
because of the historical path-dependence of the system for dietary supplements and the market
structure, which is dominated by dietary supplements outside the system, as mentioned. These
factors developed a voluntary system without GMP being mandated in Japan.

✓: dietary supplements in market
Shape✓
FHC system

Tablet /capsule etc.

No

✓

Food

Yes

No

Tablet /capsule etc.

Yes

Food
Functional Claim

US

Shape

Functional Claim

Japan

✓
DSHEA system

Figure 6. Comparison of legislative frameworks of functional foods in Japan and the United States.
HC and DSHEA stand for Foods with Health Claim and Dietary Supplement Health Education Act,
respectively.

In Japan, the introduction of GMP was discussed since the 2000s. In 2005, MHLW required thatthe industry work on ensuring the safety of dietary supplements. MHLW published the “GMP
guidelines”, specifying the GMP management process from the acceptance of raw materials topackaging and shipment of final products. In response, two organizations (JANFA and JIHFS)
implemented voluntary GMP certifications. In 2008, a third party-certification system related to GMP
was proposed in a report by the MHLW on the safety assurance of “Health Food”. Thereafter, theHealth Food Certification Council was founded in 2009, and JANFA and JIHFS were designated as
third party-certification organizations in 2014. Under the FFC system in 2015, GMP for dietary
supplements was further promoted. According to the guidelines for notification for FFC by the CAA,
it is strongly recommended that dietary supplements as FFC are manufactured at plants with GMP
certification. Because one of the goals of FFC is safety assurance, manufacturers are required to ensure
an appropriate manufacturing process. As the market for FFC is expanding, the GMP adoption rate
will increase further.
According to the results of this study, food-based SMEs and companies with fewer products
have lower rates of GMP adoption. Since these companies tend to deal with dietary supplements asa means of promoting regional economy and innovation, mitigating such trade-offs could be a key
point of discussion to make the regulation more effective. Large-scale pharmaceutical manufacturers
have the capability of pharmaceuticals. However, in Japan, because the preventive approach is not
built into the healthcare system, few large-scale pharmaceutical companies deal with dietary
supplements. In an effort to achieve disease prevention and health promotion endorsed by the central
and local governments, the design and construction of an industrial/social system that integrates
prevention and treatment would be effective to join more pharmaceutical companies
As for the limitations of the present study, it employed cross-sectional data of 90 CMOs in Japan.
As such, it was limited to a specific period and/or regional context. To obtain a deeper understandingof the adoption process of GMP for dietary supplements, it is necessary to conduct a time-course
observation and analysis of these cases. In addition, some dietary supplement manufacturers keep
the manufacturing process inside their own facilities and highly comply with GMP. Factors regarding
the adoption of GMP in these companies would differ from those regarding the CMOs examined inthis study. Further studies are needed in the future to address these points.

Int. J. Environ. Res. Public Health 2020, 17, 4748

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5. Conclusions
The present study focused on key success factors related to the adoption and implementation of
GMP for dietary supplements in Japan. As a result of the empirical observations of 90 CMOs that are
OEM manufacturers of dietary supplements, three factors were identified as affecting the adoptionof GMP: company size, manufacturing capability of pharmaceutical products, and the number ofcategories of manufactured dietary supplements. Among those, expertise in manufacturing
pharmaceutical products seemed to be the most influential in the dissemination and implementationof quality standards in the regional dietary supplement industry. These results and suggestions are
expected to form a theoretical base for policymakers and regulatory authorities to reconsider thecurrent regulatory framework and need for international harmonization, as well as to provide a cue
for practitioners in industry on how to improve their capability to manufacture dietary supplements
Author Contributions: Conceptualization, K.K. and S.S.; methodology, K.S.; software, K.S.; validation, K.S.;
formal analysis, K.S.; writing—original draft preparation, K.S.; writing—review and editing, K.K. and S.S.;
visualization, K.S.; funding acquisition, K.K. and S.S. All authors have read and agreed to the published versionof the manuscript.
Funding: The present study was supported by JSPS KAKENHI Grant Number 15H05183 (K.K.) and a research
donation from the Life Style by Design Research Unit, Institute for Future Initiatives, of the University of Tokyo(S.S.).
Acknowledgments: The authors acknowledge the support and encouragement of Hideko Ikeda (the chairmanof the Board of the Japanese Institute for Health Food Standards) and the helpful advice of Yoshiaki Nagatome
and Toshiaki Kurazumi (Japan Health and Nutrition Food Association). We thank Prof Dr Hiromichi Kimura
and Prof Hideaki Shiroyama of the Institute for Future Initiatives at the University of Tokyo for providing
advices to the manuscript. We also thank three anonymous reviewers for their contribution to improving themanuscript. Our gratitude is extended to each of the parties listed above.
Conflicts of Interest: The authors hereby declare any personal circumstances or interests that may be perceived
as inappropriately influencing the representation or interpretation of the reported research results. K.S. was an
employee of FUJIFILM Corporation and participated in the case project. The funding bodies had no role in thedesign of the study, the collection, analyses, or interpretation of the data, or in the writing of the manuscript, orin the decision to publish the results.

References
1.

Bigliardi, B.;Galati, F. Innovation trends in the food industry: The case of functional foods. Trends Food Sci.
Tech. 2013, 31, 118–129.

2.

da Costa, J.P. A current look at nutraceuticals—Key concepts and future prospects. Trends Food Sci. Tech.
2013, 62, 68–78.

3.

Starr, R.R. Too Little, too late: Ineffective regulation of dietary supplements in the United States. Am. J.
Public Health 2017, 105, 478–485.

4.

Fuji-keizai. Health & Beauty Foods Marketing Summary, ed. 3; Fuji-keizai: Tokyo, Japan, 2017; pp. 11–15.

5.

Consumer Affairs Agency. (2015). What Are “Foods with Function Claims”? Available online:
https://www.caa.go.jp/policies/policy/food_labeling/information/pamphlets/pdf/151224_1.pdf(accessed

on 21 June 2020
6.

Tanemura, N.; Hamadate, N.; Urushihara, H. The need for consumer science and regulatory science
research on functional foods with health claims—What should we do to harmonize science and technology
with society? Trends Food Sci. Tech. 2017, 67, 280–283.

7.

Farid, M.; Kodama, K.; Arato, T.; Okazaki, T.; Oda, T.; Ikeda, H.; Sengoku, S. Comparative study offunctional food regulations in Japan and globally. Global J. Health Sci. 2019, 11, 132–145.

8.

Yuda, N. Understanding Foods with Function Claims through analytical results of notification status. J.
Nutritional Food 2017, 16, 1–10.

Int. J. Environ. Res. Public Health 2020, 17, 4748

9.

11 of 12Pravst, I.; Žmitek, K. The coenzyme Q10 content of food supplements. J. Fur Verbraucherschutz Und
Lebensmittelsicherheit 2011, 6, 457–463.

10.

United States Government Accountability Office. DIETARY SUPPLEMENTS—FDA May Have
Opportunities to Expand Its Use of Reported Health Problems to Oversee Products. 2013. Available online:
https://www.gao.gov/assets/660/653113.pdf (accessed on 21 June 2020).

11.

Ministry of Health, Labor and Welfare, To Prevent Health Damage from Health Food and Prevent its
Spread.

2013.

Available

online:https://www.mhlw.go.jp/topics/bukyoku/iyaku/syoku-

anzen/dl/pamph_healthfood.pdf (accessed on 21 June 2020).
12.

National Institute of Health and Nutrition. Information System on Safety and Effectiveness for Health
Foods. 2020. Available online: https://hfnet.nibiohn.go.jp/ (accessed on 21 June 2020).

13.

Costa Dias, M.A.; Sant’Ana, A.S.; Cruz, A.G.; de Assis F. Faria, J.; Fernandes de Oliveira, C.A.; Bona, E. On
the implementation of good manufacturing practices in a small processing unity of mozzarella cheese in
Brazil. Food Control 2012, 24, 199–205.

14.

He, T.-T.; Ung, C.O.L.; Hu, H.; Wang, Y.-T. Good manufacturing practice (GMP) regulation of herbal
medicine in comparative research: China GMP, cGMP, WHO-GMP, PIC/S and EU-GMP. Eur. J. Integrative
Med. 2015, 7, 55–66.

15.

da Cruz, A.G.; Cenci, S.A.; Maia, M.C.A. Quality assurance requirements in produce processing. Trends
Food Sci. Tech. 2006, 17, 406–411.

16.

Van Breemen, R.B. Development of Safe and Effective Botanical Dietary Supplements. J. Medicinal Chem.
2015, 58, 8360–8372.

17.

Dickinson, A. History and overview of DSHEA. Fitoterapia 2011, 82, 5–10.

18.

Ohama, H.; Ikeda, H.; Moriyama, H. Health foods and foods with health claims in Japan. Toxicology 2006,
221, 95–111.

19.

Santini, A.; Tenore, G.C.; Novellino, E. Nutraceuticals: A paradigm of proactive medicine. Eur. J. Pharm.
Sci. 2017, 96, 53–61.

20.

Papachristos, G.; Sofianos, A.; Adamides, E. System interactions in socio-technical transitions: Extending
the multi-level perspective. Env. Innov. Soc. Transitions 2013, 7, 53–69.

21.

Curran, C.S.; Leker, J. Patent indicators for monitoring convergence—examples from NFF and ICT. Tech.
Forecast Soc. Change 2011, 78, 256–273.

22.

Hacklin, F.; Marxt, C.; Fahrni, F. Coevolutionary cycles of convergence: An extrapolation from the ICT
industry. Tech. Forecast Soc. Change 2009, 76, 723–736.

23.

Bröring, S.; Cloutier, L.M.; Leker, J. The front end of innovation in an era of industry convergence: Evidence
from nutraceuticals and functional foods. R D Mgt. 2006, 36, 487–498.

24.

Crowley, R.; FitzGerald, L.H. The impact of cGMP compliance on consumer confidence in dietary
supplement products. Toxicology 2006, 221, 9–16.

25.

Holleran, E.; Bredahl, M.E.; Zaibet, L. Private incentives for adopting food safety and quality assurance.
Food Pol. 1999, 24, 669–683.

26.

Sampaio, P.; Saraiva, P.; Rodrigues, A.G. ISO 9001 certification research: Questions, answers andapproaches. Int. J. Qual. Reliability Mgt. 2009, 26, 38–58.

27.

Escanciano, C.; Santos-vijande, M.L. Implementation of ISO-22000 in Spain: Obstacles and key benefits.
British Food J. 2014, 116, 1581–1599.

28.

Tunalioglu, R.; Cobanoglu, F.; Karaman, A.D. Defining economic obstacles to the adoption of food safetysystems in table olive processing firms. British Food J. 2012, 114, 1486–1500.

Int. J. Environ. Res. Public Health 2020, 17, 4748

29.

12 of 12Herath, D.; Hassan, Z.; Henson, S. Adoption of food safety and quality controls: Do firm characteristics
matter? Evidence from the Canadian food processing sector. Canadian J. Agri. Econ. 2007, 55, 299–314.

30.

Cohen, W.M.; Levinthal, D.A. Absorptive Capacity: A New Perspective on Learning and Innovation.
Admin. Sci. Q. 1990, 35, 128.

31.

Shao, A. US dietary supplement cGMPs: Ingredient supplier qualification. Drug Info. J. 2011, 45, 25–35.
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