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13
Regulatory Aspects ofInulin-Based
Pharmaceutical Products
PriyaJindal, SarjanaRaikwar, BalakDasKurmi,
andNikharVishwakarma
Abstract
A fructan-type plant polysaccharide, inulin (IN), is abundantly distributed in the
natural world. The main plant sources of IN are Jerusalem artichokes, chicory,
and dahlia. Its unique and exible structure, stabilizing/protecting qualities, and
organ-targeting ability distinguish it from other biodegradable polysaccharides,
making it a potential carrier for drug delivery. Inulin has three hydroxyl groups
on each fructose unit which serve as platform for chemical modication. This
promotes targeted, prolonged, and regulated release of medications and biomol-
ecules while also enhancing cellular absorption and bioavailability. It provides a
thorough analysis of the preliminary studies required for regulatory approval of
pharmaceuticals based on inulin. It explores the complexities of preclinical
research, encompassing investigations into toxicity, pharmacokinetics, pharma-
codynamics, and formulation development. Determining whether inulin is a
dietary ber or a medication, ensuring safety and effectiveness through clinical
trials, and adhering to international standards for purity and quality are important
factors to be taken into consideration. Regulatory frameworks differ across
regions, requiring thorough compliance strategies for market access. Regulating
agencies have strict standards for the quality and purity of pharmaceuticals, espe-
cially inulin-containing formulations. Good manufacturing practice (GMP) com-
pliance is essential for maintaining the reliability and consistency of
manufacturing processes, which reduces the possibility of contamination or vari-
ances in product quality. It addresses the complicated area of intellectual property
P. Jindal · B. D. Kurmi
Department of Quality Assurance, ISF College of Pharmacy, Moga, Punjab, India
S. Raikwar · N. Vishwakarma (*)
Department of Pharmacy, Gyan Ganga Institute of Technology and Sciences,
Jabalpur, Madhya Pradesh, India
290
protection, highlighting how crucial it is to protect innovation in order to increase
patient access to these valuable medications. This chapter examines the complex
structure of regulations governing these products’ manufacture, labeling, and
distribution.
Keywords
Inulin · Regulatory bodies · Preclinical studies · Clinical trials · Quality control ·
Purity · Intellectual property protection
13.1 Introduction toRegulatory Aspects ofInulin
Inulin is a dietary ber of high solubility present in over 36,000 species of plants
and acts as a spare polysaccharide. Inulin was originally recognized by Thomson in
1817, after Valentine Rose isolated it from the roots of the Compositae plant Inula
helenium in 1804 (Apolinário etal. 2014). It belongs to the fructans class of carbo-
hydrates as a polysaccharide. Fructans consist of fructose molecules linked together
in a chain through a β-(2→1)-D-fructose-fructose bond (Mudannayake etal. 2022).
These compounds are naturally found in various herbs, vegetables, and fruits, such
as onions, artichokes, garlic, wheat, and bananas. Notably, chicory and Jerusalem
artichoke tubers, which are rich in inulin, serve as essential raw materials for the
commercial production of inulin. It can be added to processed goods as a sugar or
fat substitute to affect the desired qualities. Inulin is a highly desirable natural nutri-
ent due to its outstanding biocompatibility, wide range of bioactivities, and excel-
lent chemical characteristics (Rubel et al. 2021). Inulin is versatile in culinary
preparation and very useful in physiological processes. Among these, it helps
decrease blood glucose and lipid proles, such as triglycerides and cholesterol.
Furthermore, inulin serves as an antidiarrheal, laxative, and antidiabetic, and it also
has anticancer properties (Kalyani Nair et al. 2010). European countries have
accorded inulin recognition as a natural food ingredient. Since it is a natural sugar
alternative, inulin has become widely used as an ingredient in many products. As a
result, companies are now able to indicate on the label the higher-quality ber con-
tent. Inulin provides just 25–35% of the energy provided by digestible carbs, yet it
is extensively utilized as sugar substitute in processed foods or to add required qual-
ities. It has a sweetness content of approximately 10% that of sucrose. The micro-
bial fermentation of inulin yields alcohols, including ethanol, and is another
application of inulin’s biochemical qualities in the chemical industry. Nowadays,
the food and pharmaceutical industries are the ones that use inulin (Ahmed and
Rashid 2019). Inulin, a polydisperse β-(2–1) fructan, is held together by glycosidic
bonds that connect its β-D-fructose residues. Interestingly, due to these specic
β-(2–1) bond connections, inulin resists digestion in the small intestine. Instead, it
becomes a feast for the benecial bacteria residing in our large intestine, leading to
fermentation. This unique property not only contributes to gut health but also
reduces the calorie value of inulin (Tawck etal. 2022). Chicory inulin contains a
P. Jindal et al.
291
range of 2–60 fructose units, which indicate an amalgamation of oligomers as well
as polymers. The functioning of inulin is inuenced by the polymerization degree
(DP) as well as branching (Mensink etal. 2015). Plant inulin has a low DP (maxi-
mum <200), but bacterial inulin has a much greater DP (varying from 10,000 to
over 100,000) and is 15% more branched (Carboni etal. 2022). Though Jerusalem
artichokes and dahlia are also considered excellent sources for industrial manufac-
turing, chicory can be used to economically manufacture inulin (Shoaib etal. 2016).
Plant roots are the popular source of inulin among the other parts and are utilized in
inulin extraction processes. Chicory is produced biannually by the plants belonging
to the family Asteraceae (Redondo-Cuenca etal. 2021). Raw syrup is extracted and
initially puried in the rst step of the inulin production process, and processing is
done in the second step. Advanced technologies like pulsed electric eld (PEF),
ultrasonography, and supercritical carbon dioxide have also been explored for use in
the inulin extraction process.
13.2 Overview ofRegulatory Agencies
Across the globe, various regulatory agencies diligently oversee pharmaceutical-
based products. One such governing agency is Food and Drug Administration or
USFDA which plays an important role in the regulation in United States. Its mission
extends beyond safeguarding public health—it also involves promoting it. The FDA
achieves this by conducting inspections, supervising processes, exercising control,
and certifying the effectiveness and safety of food items, human and veterinary
drugs, medical devices, and biological products (Lile 2023).
The Central Drug Standard Organization (CDSCO) serves as India’s regulatory
authority responsible for ensuring the safety of pharmaceuticals, including medical
devices. As the National Regulatory Authority, it operates under the Directorate
General of Health Services, Ministry of Health and Family Welfare belonging to the
Government of India. Its multifaceted responsibilities encompass drug approval,
standardization, oversight of clinical trials, quality control, and coordination with
state drug control agencies. Also, it provides guidance to these state organizations
to ensure uniform implementation of Drugs and Cosmetics Act. Notably, CDSCO
also plays a pivotal role in granting licenses for critical pharmaceutical categories,
such as vaccines, sera, and blood products, in collaboration with state regulatory
bodies (D.S.P and Agarwal 2017).
Health Canada, as a government department, plays a vital role in safeguarding
the well-being of Canadians. Within Health Canada, the Health Products and Food
Branch serves as the national authority responsible for regulating, evaluating, and
closely monitoring the quality, effectiveness, and safety of various health-related
products available in the Canadian market. This oversight extends to drug products,
biologics, gene therapies, and even diagnostic items (Marchildon 2013).
The European Medicines Evaluation Organization (EMA) is the European body
responsible for evaluating medical products. Earlier between 1995 to 2004, it was
recognized as the European Agency for the Evaluation of Medicinal Products. The
13 Regulatory Aspects ofInulin-Based Pharmaceutical Products
292
Table 13.1 Various Regulatory Agencies in Different Countries
Jurisdiction Regulatory body
Ministry of Health, Labour and Welfare
(MHLW)
Japan
Therapeutic Goods Administration Australia
Health Canada Canada
Medicines and Healthcare Products
Regulatory Agency
UK
Food and Drug Administration (FDA) USA
European Medicines Agency (EMA) Europe
Central Drug Standard Control Organisation
(CDSCO)
India
EMA was established with funding from the pharmaceutical sector, the European
Union, and indirect member-state contributions. Its primary objective was to har-
monize the efforts of existing national medicine regulatory authorities. Notably,
within the European consolidated system, pharmaceutical industries apply to the
EMA for authorization permission for marketing. Once issued by European
Commission (EC), this is acceptable across all European Union/member states of
EEA (Pignatti etal. 2011).
In Japan, the Ministry of Health, Labor, and Welfare (MHLW) holds authority
over pharmaceutical laws as well as regulations. As a cabinet-level ministry within
the Japanese government, the MHLW is responsible for delivering health, welfare,
and labor services. Notably, one of its key sectors is the Bureau of food safety along
with Pharmaceuticals (Shinya 2019).
Therapeutic Goods Administration of Australia and Medicines and Healthcare
Products Regulatory Agency of United Kingdom serve as prime examples of
national regulatory bodies overseeing pharmaceuticals and related products. These
organizations verify that pharmaceutical products based on inulin meet strict quality
and efcacy standards, protecting patient welfare and public health by reviewing
applications for marketing authorization, inspecting manufacturing facilities, and
keeping an eye on post-market safety (Aziza 2021). Table 13.1 highlights the
numerous regulatory authorities in different countries.
13.3 Guidelines forDeveloping Inulin-Based
Pharmaceutical Products
Previously, there was no regulatory authority that have approved the health claims
associated with the marketing of inulin. However, in the recent years several regula-
tory bodies are monitoring the use of inulin in humans. Inulin derived from chicory
roots is widely regarded as safe (GRAS) based on independent evaluations conducted
by the expert panel in 1992 and 2002. The safety of Inulin for food products as
dietary bers has already been afrmed by several regulatory agencies such as
USFDA, Food Standards Australia New Zealand (FSANZ), European Food Safety
P. Jindal et al.
293
Authority, Health Canada, Canada and FOSHU Japan. Several recommendations are
required to produce inulin-based pharmaceutical goods, including implementation of
preclinical trials to safeguard the safety of inulin and the development of products for
pharmaceutical use. The guidelines laid down by the regulatory agencies are used to
ensure the quality of any pharmaceutical products based on inulin.
13.4 Clinical Trials forInulin-Based Pharmaceutical Products
Inulin-based pharmaceutical products are gaining popularity due to their distinctive
properties and applications in drug delivery system. Clinical trials for insulin-based
pharmaceutical products lay a crucial foundation to assess its capabilities, effective-
ness, and stability in the biological milieu. Different clinical trials for inulin-based
pharmaceutical products are highlighted in Table13.2.
13.5 Quality Control andQuality Assurance ofInulin-Based
Pharmaceutical Products
Quality assurance (QA) and quality control (QC) are essential for maintaining com-
pliance with current good manufacturing practices (cGMP) and safeguarding the
consistency, quality, and safety of drug products, whether they are protein-based or
nucleic acid-based. QC consists of thoroughly evaluating and testing pharmaceuti-
cal products at various stages of production in order to nd and repair defects or
variations. It assures that each product satises the stipulated quality requirements
before it enters the market, protecting patient safety. QA, on the other hand, is con-
cerned with developing and maintaining a strong system of processes, documenta-
tion, and standards in order to avoid quality concerns in the rst place. It involves
not just product quality but also the overall quality of pharmaceutical manufacturing
and delivery (Geigert 2002).
The aim of QA department in pharmaceutical supply systems is to provide guar-
antee that each medication administered to a patient is effective, completely safe,
and of the requisite quality. The quality system’s technical and managerial activi-
ties, such as assessing the documentation of the pharmaceutical product, completing
quality-control tests in labs, and controlling the performance of the product, warrant
pharmaceutical products’ quality (Ghante et al. 2024). Managerial tasks include
choosing suppliers which are reputable, establishing contract terms, regulating the
supplier performance, and carrying out assessment processes across the network of
the distributors (Fig.13.1).
13.5.1 Pharmaceutical Quality Assurance Framework
A pharmaceutical quality assurance framework guarantees that pharmaceutical
goods are continuously manufactured and controlled in accordance with quality
13 Regulatory Aspects ofInulin-Based Pharmaceutical Products
294
Table 13.2 Clinical trials of inulin-based pharmaceutical products
Study title
NCT number Status Conditions Interventions Sponsor Study type
Reference
Investigating the
mechanism of action
of dietary ber on the
gut microbiota and
metabolites
NCT05906589 Recruiting Psyllium
Inulin
Inulin supplement
Psyllium
supplement
Maltodextrin
supplement
University of Aberdeen Interventional van den
Haak Merel
and Kiltie
(2023)
Treating ibd with
inulin
NCT03653481 Completed Inammatory
bowel
disorders
Oligofructose-
enriched inulin
supplement (OI)
Dietary
supplement:
Maltodextrin
Children’s Hospital of
Philadelphia
Interventional Jessica
(2018)
Effects of inulin on
satiety and food
intake
NCT01025375 Completed Obesity Dietary
supplement: Inulin
Dietary
supplement: Inulin
Dietary
supplement:
Placebo
Maastricht University
Medical Center
Interventional Hiel (2019)
Inulin in burn-
induced insulin
resistance
NCT05532488 Recruitment
not yet
initiated
Burn injury
Resistance to
insulin
Insulin
resistance
after burn
Dietary
supplement: Inulin
20mg
Other: Placebo
University of Belgrade Interventional Clark (2013)
Inulin and S.
salivarius reduce
halitosis
NCT02794766 Completed
with results
Halitosis
Diseases of
the tongue
Inulin + S.
salivarius drug
S. salivarius drug
Placebo drug
Universidade de Passo
Fundo
Interventional Fernando
(2020)
P. Jindal et al.
295
Study title
NCT number Status Conditions Interventions Sponsor Study type
Reference
Hemodialysis and the
gut microbiome with
p-inulin
NCT02572882 Completed
with results
Chronic
kidney
disease
Dysbiosis of
the gut
microbiome
P-inulin as a
dietary
supplement
University of Pennsylvania Interventional Raj etal.
(2021)
Inulin for treating
infections in the
intensive care unit
NCT03865706 Active, not
recruiting
Antibiotic-
resistant
infection
Nosocomial
infection
Pathogen
transmission
Nutrition
disorder,
critical Illness
and sepsis
Inulin oral
suspension
Placebo oral
suspension
Broad-spectrum
antibiotics
Oral suspension: Inulin
Oral suspension: Placebo
Broad-spectrum
antibiotics
Interventional Thomas
(2021)
TarGut CKD study:
p-inulin in CKD and
gut microbiome
NCT03348592 Unknown
status
Chronic
kidney
disorder
Oligofructose-
enriched inulin
(p-inulin): Dietary
supplement
Other: No
treatment
National Institute of
Diabetes and Digestive
and Kidney Diseases
(NIDDK)
Interventional Sohn etal.
(2024)
Obesity, gut
microbiota, and
vegetables high in
fructans of the inulin
type
NCT03852069 Completed Obesity Dietary
supplement: Inulin
Dietary
supplement:
Placebo
Cliniquesuniversitaires
Saint-Luc-Université
Catholique de Louvain
Interventional Leyrolle
etal. (2021)
(continued)
13 Regulatory Aspects ofInulin-Based Pharmaceutical Products
296
Table 13.2 (continued)
Study title
NCT number Status Conditions Interventions Sponsor Study type
Reference
Inulin and acetate
production and
human metabolism of
substrate
NCT03711383 Completed Obesity
Prediabetes
Inulin and
resistant starch as
dietary
supplement
Dietary
supplement: Inulin
Dietary
supplement:
Placebo
Maastricht University
Medical Center
Interventional Canfora
etal. (2022)
Inulin
supplementation for
patients with type 1
diabetes
NCT05795972 Recruiting Diabetes Dietary
supplement: Inulin
Other: Standard
therapy
Fondazione Policlinico
Universitario Agostino
Gemelli IRCCS
Interventional Veronica
(2024)
Impact of inulin on
human iron
absorption
NCT01483092 Completed Absorption of
iron
Bacteria in
the gut
Inulin as a dietary
supplement
Dietary
supplement:
Maltodextrin
Swiss Federal Institute of
Technology
Interventional Petry etal.
(2012)
Effect of food matrix
on inulin-type fructan
prebiotic efcacy
NCT05581615 Completed Healthy Other: Inulin Beneo-Institute Interventional Jackson
etal. (2023)
Effect of delivery rate
on inulin colonic
fermentation (EON)
NCT05619341 Completed Irritable
bowel
Psyllium as
dietary
supplement
Inulin: Dietary
supplement
University of Nottingham Interventional Robin
(2024)
Tolerance and
application of agave
inulin in healthy
adults
NCT01925560 Completed Tolerance Other: Agave
inulin
Other: Placebo
University of Illinois at
Urbana-Champaign
Interventional Holscher
etal. (2015)
P. Jindal et al.