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Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, 5, 132-144
REVIEW ARTICLE
ISSN: 2213-476X
eISSN: 2213-4778

Recent Updates on Nanomedicine Based Products: Current Sce-

nario and Future Opportunities

Ajmer Singh Grewal1, Viney Lather2,*, Neelam Sharma1, Sukhbir Singh1, R.S.
Narang3, Jasjeet Kaur Narang4 and Deepti Pandita2

1
Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India; 2Jan Nayak Ch. Devi
Lal Memorial College of Pharmacy, Sirsa, 125055, Haryana, India; 3Sri Guru Ram Das Institute of Dental
Applied Clinical Research, Clinical Trials and Regulatory Affairs

Sciences and Research, Amritsar, Punjab, India; 4 Khalsa College of Pharmacy, Amritsar, Punjab, India

Abstract: Background: Nanomedicine, defined as the application of nanotechnology for the pre-
vention, cure and diagnosis of diseases, has emerged as one of the most exciting tools in the medi-
cal field for direct benefit to human health. Nanomedicine aims to engineer the materials at nano-
scale to develop new drugs, delivery systems in a way to mimic or understand the cellular proc-
esses at molecular level for therapeutics of diseases. Based on their applications, nanomedicines
include nano drug delivery systems, nano-diagnostics, nano-theranostics, and nano-medical im-
ARTICLE HISTORY
plants.

Received: March 09, 2018

Revised: March 29, 2018
Accepted: May 19, 2018
DOI:
10.2174/2213476X05666180611115135
Objectives: The current manuscript will provide a global scenario about different nanomedicines
and their applications, the overall market, and the ongoing developments in their regulation by dif-
ferent regulatory bodies.
Discussion: The different properties displayed by materials at nano-scale in terms of size, chemi-
cal reactivity, solubility, mobility, magnetic and optical properties open the ways for their utiliza-
tion in the field of medicine. The Food and Drug Administration (FDA) has approved products us-
ing nanotechnology under different product categories. The last two decades have seen a tremen-
dous growth in the development of nanomedicine-based products in global regulatory markets
particularly in the area of drug delivery systems and diagnosis.

Keywords: Nano-drug delivery systems, nanomedicine, nanotechnology, nanotheranostics, quality and

safety, regulatory aspects.

1. INTRODUCTION diagnosis, drug targeting, cancer therapy, and re-

Nanotechnology works at the atomic, molecu-
lar, and supra-molecular levels of approximately
1-100 nm scale and is a promising field of science
implicated for a range of consumer goods to health
products. It has the potential to open up new pos-
sibilities for improvement of drug properties i.e.
solubility and stability, development of additional
proficient methodology in drug delivery systems
and offers great prospective in medical imaging,
*Address correspondence to this author at the Jan Nayak Ch.
Devi Lal Memorial College of Pharmacy, Sirsa, 125055, Haryana,
India; Tel: +91-1666-238114; Fax: +91-1666-238100;
E-mail: vinnylather@gmail.com
generative medicine [1-5]. Nanomedicines inte-
grate nanoparticles to attain improved targeting,
reduced toxicity, and enhanced efficacy of thera-
peutic, biological or diagnostic agents in vivo [6].
Incorporation of existing drugs in nanoparticles
facilitates superior pharmacodynamic and/or
pharmacokinetic parameters. Global regulatory
trends for nanomedicines are undefined so far and
therefore, there is a need of closer collaboration
amongst regulatory agencies. Alternatively, con-
ventional strategies have been adopted for the
development of nanomedicines as well as for their
safety and toxicity evaluation [7]. Nevertheless,
numerous nanomedicines have received regulatory
approval, however, approval of ‘nanosimilars’

2213-4778/18 $58.00+.00 © 2018 Bentham Science Publishers

Recent Updates on Nanomedicines Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2
may require different guidelines. Biologics based
nanoparticles encountered complexity in replica-
tion of products because little alteration in
nanoparticle properties might transform the bio-
logical impact [8, 9]. According to a research re-
port from the Business Communications Company
Research, despite the catastrophic consequences of
the 2008-2009 crisis on capital markets, the global
nanomedicine sector had grown tremendously
[10]. The BCC Research firm has estimated the
global nanopharmaceutical market at $209 billion
in 2014 and anticipated to expand to $412 billion
by 2019. In this context, the term “global market”
is defined as the sum of the markets in the USA,
Europe (France, Germany, United Kingdom, Bel-
gium, Netherland, Italy, and Spain) and Japan.
Further, the market share of nanopharmaceuticals
was 15% of the total pharmaceutical market in
2014 and is estimated to grow to 22% in 2019. In
addition, the average compound annual growth
rate (CAGR) for this class of products is estimated
to be 14.5% as opposed to 5.5% for non-nano
pharmaceuticals. The oncology sector is the most
dominant one amongst the nanopharmaceuticals,
representing approximately 35% of the global
market [11, 12]. Various key points like applica-
tions of nanomedicines, global authorities for their
regulation and the recent updates on the nano-
medicine based products in the global market will
be highlighted in this review.
2. APPLICATIONS OF NANOMEDICINE IN
MEDICAL FIELD
Nanomedicine simply means the medical appli-
cation of nanotechnology. The size of nanoparti-
cles is comparable to that of nearly all bio-
molecules and cellular structures; thus, nanoparti-
cles can be useful for both in vivo and in vitro re-
search and applications in biomedical research.
Applications of medical nanotechnology span
across a variety of areas such as in drug develop-
ment, drug delivery technologies, medical devices,
medicines, therapeutics (in disease’s diagnostics,
abnormal conditions), surgery, medical robotics,
enhanced gene therapy, tissue engineering proce-
dures and in the general sake of increasing knowl-
edge of the human body [13, 14]. Nanotechnology
is providing innovative therapeutic opportunities
for various therapeutic agents which cannot be
used efficiently as conventional oral formulations,
133
owing to their bioavailability problems. Nanotech-
nology offers amazing prospects to improve mate-
rials and medical devices and also to construct
novel “smart” technologies and devices where cur-
rent and more conventional tools may be reaching
their limits [15]. Nanomedicine is used for early
detection, diagnosis, treatment and prevention of
diseases like diabetes, infections, cancer, infec-
tious diseases, eye diseases, Alzheimer’s disease,
arthritis, cardiovascular diseases like atherosclero-
sis, musculoskeletal dysfunctions, and many more
[16-22]. Nanomedicine based products can result
in noninvasive nano-devices that can enter the
body to detect blood glucose levels, differentiate
among normal and cancerous cells, and offer ge-
netic screening for numerous disorders. Applica-
tions of nanomedicine in cardiovascular disorders
include early detection and treatment of athero-
sclerosis and decreasing re-stenosis rates after
stenting. The term “nano-theranostics” may be de-
fined as a methodology that combines simultane-
ously the modalities of the therapeutic and diagno-
sis in a nano-carrier. The nano-theranostics based
nanomedicines can reach systemic circulation,
evade host defense system and deliver the medi-
cine as well as diagnostic agents at the targeted
location to detect and treat the disorder at the
cellular and molecular level. The various applica-
tions of nanotechnology in medicine (including
both therapy and diagnosis of diseases) are pre-
sented in Fig. (1) [13-22].
3. SAFETY, QUALITY AND REGULATORY
ASPECTS OF NANOMEDICINES
Despite the tremendous advancements in the
field of nanotechnology, it poses several potential
risks which can be broadly classified as: the risk to
health and environment from nanoparticles and
nanomaterials; the risk posed by molecular manu-
facturing; and the risk to society. Nanotechnology
relates to distinctive properties of materials on a
nano-scale leading to greater risk for major insta-
bility at atomic and molecular levels resulting in
increased risk of damage at cellular level [23]. De-
spite the many proposed advantages of nanoparti-
cles, growing concerns have been expressed on
their potential adverse effects on human health. As
nanoparticles have different physicochemical
characteristics than their fine-sized analogues due
to their extremely small particle size and more sur-
face area, they need to be evaluated separately for
134 Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2 Grewal et al.




 
 
 
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Fig. (1). State of the art applications of nanotechnology based products in medicine.
toxicity and adverse effects on health. In addition,
in the field of nanomedicine, subcutaneous and
intravenous injections of nanomedicine based car-
rier systems deliver exogenous nanoparticles di-
rectly into the human body exclusive of passing
through the usual absorption route. These nano-
medicine based carrier systems themselves could
be liable for the toxicity and interaction with the
biological macromolecules. Next, insoluble
nanomedicine based carrier systems may perhaps
accumulate in cells, tissues or organs. Therefore, it
is mandatory to deal with the potential health and
safety implications of nanomaterials used in
nanomedicine [24]. Subsequently, the manufactur-
ing and application of nano-materials are growing
extensively resulting in increased production and
consumption of nanomaterials. Human beings can
be exposed through various ways including breath-
ing, ingestion, and penetration across the skin. An
important challenge for scientists, industries, and
regulatory agencies is how to categorize the novel
materials and what further analysis regarding tox-
icity and safety is mandatory before these products
become available in the market [25].
Applications of nanotechnologies and incorpo-
ration of nanomaterials in medicines are growing
and several novel products, currently in develop-
ment are expected to enter the market in the near
future. Therefore, it is becoming increasingly im-
portant to have regulatory frameworks that prop-
erly address and specifically manage the potential
risks of nanotechnology. Pharmaceutical regula-
tory agencies and organizations around the world
for technical and regulatory perspectives/guidance
for nanomedicines are United States Food and
Drug Administration (USFDA), Center for Drug
Evaluation and Research (CDER) nanotechnology
programs, American Society for Testing and Mate-
rials (ASTM) committee E56 on nanotechnology
in the United States [1]; European Medicines
Evaluation Agency (EMEA) in European Union;
Therapeutic Goods Administration (TGA) in Aus-
tralia; Pharmaceuticals and Medical Devices
Agency (PMDA) in Japan; Health Canada [Public
Health Agency of Canada (PHAC) and Canadian
Institutes of Health Research (CIHR)] in Canada;
Taiwan’s Food and Drug Administration (Taiwan
FDA) in Taiwan; the Agência Nacional de
Vigilância Sanitária or National Sanitary Surveil-
lance Agency (ANVISA); Central Drug Standard
Control Organization (CDSCO) in India; China
Food and Drug Administration (CFDA) in China
Medicines; the Ministry of Food and Drug Safety
(MFDS) in South Korea; and Healthcare Products
Regulatory Agency (MHRA) in United Kingdom
[26] https://www.pharmatutor.org/articles/phar-
maceutical-regulatory-agencies-and-organizations-
around-world-scope-challenges-in-drug-develop-
ment. Nanotechnology standardization for electri-
cal and electronic products and systems has initi-
ated a line of activities through working groups
towards harmonizing standards that focus on the
WG1 Terminology and nomenclature led by Can-
ada; WG 2 Measurement and characterization led
by Japan; WG 3 HSE led by the USA; and WG 4
Material Specifications led by China [27]. The
most important aspects regarding safety, quality
and regulation of nanotechnology-based products
used in medicine for different parts of the world
are represented in Table 1.
Recent Updates on Nanomedicines Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2 135

Table 1. Safety, quality and regulatory aspects of nanomedicine-based products in different parts of the world.

S. Regulatory
Country Description Ref.
No. Authority

USFDA guidelines have made it crucial for technical assessments to designate

product-specific characteristics, taking into account the effects of nanomaterials
in the specific biological and mechanical context of all products and their pro-
posed application.

CDER research on nanomaterials development includes identification of the limi-
US-FDA,
United tations of current test methods to assess the quality and safety of nanomedicines;
1 CDER and [28-34]

States and evaluation of the application of nanotechnology on product characteristics,
ASTM
including stability and content uniformity.

ASTM Committee E56 on nanotechnology was formed in 2005 which addresses
issues related to standards and guidance materials for nanotechnology and
nanomaterials, as well as the coordination of existing ASTM standardization re-
lated to nanotechnology needs.


Nanomedicine products marketed in the European Union are covered by compre-
hensive EU legislation: Regulation No 726/2004, Directive 2001/83/EC, Direc-
tive 2003/94/EC, Directive 2003/63/EC.

EMEA in 2006 published the first regulatory reflection paper on nanotechnology-
based medicinal products for human use and launched a webpage dedicated to
nanotechnology.
European
EMEA’s task, according to its mission statement is “to contribute to the protec-
2 EMEA tion and promotion of public and animal health by mobilizing scientific re- [35-37]

Union
sources from throughout the European Union to provide high-quality evaluation
of medicinal products, to advise on research and development programmes and
to provide useful and clear information to users and health care professionals de-
veloping efficient and transparent procedures, to allow timely access by users to
innovative medicines through a single European marketing authorization, and in
particular through a pharmacovigilance network and the establishment of safe
limits for residues in food producing animals”.


TGA regulates therapeutic goods (including supplements and sunscreen) and
medical devices. Decisions on household chemicals are made by the Secretary to
the Department of Health who is advised by a committee formed under the
Therapeutic Goods Regulations.

According to the TGA, if nanomaterials are added to existing therapeutic goods,
3 Australia TGA [38-41]

they will require reassessment, and manufacturers must submit or hold safety
data on new products. However that requirement does not appear to be reflected
in the TGA Regulations, nor do any sunscreens or other therapeutic goods
known to contain nanomaterials appear to be listed in the register of Therapeutic
Goods.


PMDA is an independent administrative legal authority which is the entry portal
for the approval of drugs and medical devices and collaborates with the Ministry
of Health, Labour and Welfare (MHLW).

Various laws and regulations provide the basis for pharmaceutical administration
in Japan; among them are the Pharmaceutical Affairs Law (PAL), the Law Con-
4 Japan PMDA cerning the Establishment for Pharmaceuticals and Medical Devices Organiza- [42]

tion, and the Law Concerning Securing Stable Supply of Blood Products.

The Pharmaceutical and Medical Device Act has been launched in Nov 2014
which is entitled as “Act on Securing Quality, Efficacy and Safety of Pharma-
ceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene
Therapy Products and Cosmetics”.

Table 1. contd…
136 Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2 Grewal et al.

S. Regulatory
Country Description Ref.
No. Authority

PHAC and CIHR are two health Canada agencies for regulations of nanomedici-
nes prospective. Health Canada encourages sponsors and other stakeholders to
communicate with the responsible regulatory authority early in the development
process, especially for combination products that are, contain or make use of
nanomaterials.

The Department encourages manufacturers to request a pre-submission meeting
PHAC and
5 Canada with the responsible regulatory authority to discuss the type of information that [43]

CIHR
may be required for their product's safety assessment.

As part of its international collaborative work on nanotechnology and nanomate-
rials, health Canada is engaged with Environment Canada. Its goal is to share in-
formation and develop joint approaches on regulatory aspects of nanomaterials
including terminology and nomenclature as well as risk assessment and man-
agement.

Taiwan FDA does not have yet established specific nanotechnology-based drug-
related regulations. The abbreviated review process for new drug registration
was established in 2010 and drafting of the guidance for technical review of
Chemistry, Manufacturing, and Controls (CMC) of the nanomedicines was done
in 2013.
6 Taiwan Taiwan FDA [1]


Draft include the CMC review checklist for nano-pharmaceuticals and guidance
for technical review of CMC of the liposomal drug products with an attachment
of the current regulations for liposomal drug products including new chemical
entities, new administration routes, new indications, new combinations, new
dosage forms, new doses, new dose units and generic formulations.

ANVISA generated in 1999 is an independently administered and financially

autonomous regulatory body of the Brazilian government managed by a colle-
giate board of directors and linked to the Ministry of Health and is the entry por-
7 Brazil ANVISA tal for the regulation and approval of drugs and medical devices. [44]


In view of this situation, Brazil has started to reform and improve its system such
as by means of allowing manufacturers to commence their application process
before the Goods Manufacturing Practices (GMP) certificate has been obtained.

CDSCO is the national regulatory body and entry portal for regulation and ap-
proval of pharmaceuticals and medical devices in India and is linked to the Min-
istry of Health and Family Welfare and holds six zonal offices, four sub-zonal
offices, several port offices and laboratories.
8 India CDSCO [45]


Within the CDSCO, the Drug Controller General of India is the main licensing
authority which directly issues permission for new drugs and specific medical
devices and for the manufacturing of certain drugs (vaccines, blood-products, r-
DNA derived).

CFDA, earlier called as State Food Drug Administration is responsible for phar-
maceutical legislation and the regulation, approval and inspection of drugs and
medical devices in China.

Relevant approval procedures are conducted by the CFDA Department of Drug
and Cosmetics Registration and accordingly by the CFDA Department of Medi-
9 China CFDA cal Device Registration. [46]

In this field, China is in a backlog in comparison with international compliance

guidelines and in slow processing of numerous approval applications.

A new classification of pharmaceuticals is being envisaged and Innovative drugs
covering an urgent medical need shall be approved by means of “Fast Track”.

Table 1. contd…
Recent Updates on Nanomedicines Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2 137

S. Regulatory
Country Description Ref.
No. Authority

MFDS previously known as Korea Food and Drug Administration is the entry
South portal for the approval of drugs and medical devices.
10 MFDS [47]

Korea
It cooperates with the Ministry of Health and Welfare (MoHW) which takes the
final decision of covering, coding and pricing of medical devices.

According to MHRA judgments on safety, quality and performance will be in-

formed by all available, relevant and reliable evidence, with the burden of proof
often resting on companies.
United
11
Kingdom
MHRA
Important regulatory checkpoints for any novel medicine include the moment at [48]

which permission is given to enter into first-in-man studies, the time of market
authorization and not least review of information captured by post-market sur-
veillance.

Table 2. List of nanomedicine based products approved by different authorities for their medicinal applications [49-
53].

Delivery Year of Approval

Name of Product Active Molecule Indication (Use) Route
System Approval Authority

USFDA and Systemic fungal infec-

AmBisome® Amphotericin B Liposomes 1997 Intravenous
EMEA tions

1996 USFDA and AIDS-related Kaposi's

DaunoXome® Daunorubicin citrate Liposomes Intravenous
EMEA sarcoma

1996 USFDA and Lymphomatous men-

DepoCyt® Cytarabine Liposomes Intrathecal
EMEA ingitis

USFDA and
DepoDur® Morphine sulfate Liposomes 2004 Pain relief Epidural
EMEA

Doxorubicin hydro- PEGylated USFDA and

Doxil® 1995 Karposi's sarcoma Intravenous
chloride liposomes EMEA

Doxorubicin hydro- PEGylated USFDA and

Caelyx™ 2005 Ovarian cancer Intravenous
chloride liposomes EMEA

Doxorubicin hydro- PEGylated USFDA and

LipoDox® 2008 Multiple myeloma Intravenous
chloride liposomes EMEA

Influenza virus anti-

Inflexal® V gens (hemagglutinin, Liposomes 1997 EMEA Influenza vaccine Intravenous
neuraminidase)

Respiratory distress
Curosurf® Poractant alpha Liposomes 1999 USFDA Intratracheal
syndrome

Post-surgical Local/
Exparel® Bupivacaine Liposomes 2011 USFDA
analgesia Depofoam

Acute lymphoid
Marqibo® Vincristine sulfate Liposomes 2012 USFDA Intravenous
leukemia

Copaxone® Glatiramer Polymeric drugs 1996 EMEA Multiple sclerosis Subcutaneous

Table 2. contd…
138 Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2 Grewal et al.

Delivery Year of Approval

Name of Product Active Molecule Indication (Use) Route
System Approval Authority

Non-metastasizing
Mepact™ Mifamurtide Liposomes 2009 EMEA resectable osteosar- Intravenous
coma

Metastatic breast
Myocet® Doxorubicin Liposomes 2000 EMEA Intravenous
cancer

Photodynamic therapy
USFDA and
Visudyne® Verteporfin Liposomes 2000 for eye neo- Intravenous
EMEA
vascularization

Lipid-based USFDA and Systemic fungal

Abelcet® Amphotericin B 1995 Intravenous
(non-liposomal) EMEA infections

Metastatic adenocar-
MM-398 Iritonecan Liposomes 2015 USFDA cinoma of the Intravenous
pancreas

Lipid-based USFDA and Systemic fungal

Amphotec® Amphotericin B 1996 Intravenous
(non-liposomal) EMEA infections

PEGylated
® Adenosine adenosine Adenosine deaminase
Adagen 1990 USFDA Intravenous
deaminase deaminase deficiency disease
enzyme

2008
Fab’ fragment of a 2009 Crohn’s disease,
PEGylated anti- USFDA
Cimzia® humanized anti- rheumatoid arthritis, Subcutaneous
body fragment 2013 and EMEA
TNF-alpha antibody psoriatic arthritis
2013

Febrile neutropenia,
PEGylated USFDA
Neulasta® Filgrastim 2002 nonmyeloid malig- Subcutaneous
filgrastim and EMEA
nancies

PEGylated L- Acute lymphoblastic

Oncaspar® L-asparaginase 1994 USFDA Intramuscular
asparaginase leukemia

PEGylated in- USFDA and

Pegasys® Interferon alfa-2b 2002 Hepatitis B and C Subcutaneous
terferon alfa-2b EMEA

PEGylated in-
USFDA and
PegIntron® Interferon alfa-2b terferon alfa-2b 2001 Hepatitis C Subcutaneous
EMEA
protein

PEGylated in-
Plegridy® Interferon beta-1a 2014 USFDA Multiple sclerosis Intravenous
terferon beta-1a

Polymer-protein
conjugate Improved sta-
Adynovate® bility of protein 2015 USFDA Hemophilia Intravenous
(PEGylated factor via PEGylation
VIII)

Human growth hor- PEGylated hGH

USFDA and Acromegaly, second-
Somavert® mone (hGH) receptor receptor an- 2003 Subcutaneous
EU line therapy
antagonist tagonist

Table 2. contd…
Recent Updates on Nanomedicines Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2 139

Delivery Year of Approval

Name of Product Active Molecule Indication (Use) Route
System Approval Authority

Anti- vascular endo- PEGylated Neovascular age-

Macugen® thelial growth factor anti-VEGF 2004 USFDA related macular de- Intravitreal
(VEGF) aptamer aptamer generation

Anemia associated
PEGylated USFDA and Intravenous
Mircera® Epoetin beta 2007 with chronic renal
epoetin beta EMEA /Subcutaneous
failure in adults

Krys- Polymer-protein
Porcine-like uricase 2010 USFDA Chronic gout Intravenous
texxa®/pegloticase conjugate
Nanocrystals in USFDA and
Emend® Aprepitant 2003 Emesis, antiemetic Oral
capsules EMEA

Megace ES® Megestrol acetate Nanocrystals 2001 USFDA Anorexia, cachexia Oral

Nanocrystals in USFDA and

Rapamune® Sirolimus 2000 Immunosuppressant Oral
tablets EMEA
USFDAand Hypercholesterolemia,
Tricor® Fenofibrate Nanocrystals 2004 Oral
EMEA hypertriglyceridemia

Zypadhera® Olanzapine Nanocrystals 2008 EMEA Schizophrenia Intravenous

Xeplion® Paliperidone Nanocrystals 2009 USFDA Schizophrenia Intramuscular

Prophylaxis of organ
Nanoemulsions
Neoral® Cyclosporine 2000 EMEA rejection following Oral
in soft capsules
organ transplant

Nanoemulsions
Norvir® Ritonavir 1999 EMEA HIV infections Oral
in soft capsules
Polymeric drugs Hyper-phosphatemia,
Renagel® Sevelamer 1998 EMEA Oral
in tablets Renal dialysis

Polymeric Advanced prostate

Eligard® Leuprolide acetate 2002 US-FDA Subcutaneous
nanoparticles cancer
Polymeric Metastatic breast can-
Genexol® Paclitaxel 2001 South Korea Intravenous
micelles cer, pancreatic cancer
Polymeric
Opaxio® Paclitaxel 2012 USFDA Glioblastoma Oral
nanoparticles

2005 Metastatic breast can-

® Protein-drug USFDA and cer, non-small-cell
Abraxan Paclitaxel 2012 Intravenous
conjugate EMEA lung cancer, pancre-
2013 atic cancer
Monoclonal antibody
(against human epi- Protein-drug Metastatic breast
Kadcyla® 2013 USFDA Intravenous
dermal growth factor conjugate cancer
receptor-2) and DM1
Recombinant fusion
Primary cutaneous T-
protein of fragment
cell lymphoma,
A of diphtheria toxin Protein-drug
Ontak® 1999 USFDA CD25-positive, Intravenous
and subunit binding conjugate
persistent or recurrent
to interleukin-2
disease
receptor

Table 2. contd…
140 Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2 Grewal et al.

Delivery Year of Approval

Name of Product Active Molecule Indication (Use) Route
System Approval Authority

Surfactant-
Systemic fungal infec-
Fungizone® Amphotericin B based nano- 1966 USFDA Intravenous
tions
formulation

Sedative-hypnotic for
USFDA and
Diprivan® Propofol Nanoemulsion 1989 induction and mainte- Intravenous
EMEA
nance of anesthesia

Eye inflammation,
Durezol® Difluprednate Nanoemulsion 2008 USFDA Ocular
uveitis

Restasis® Cyclosporine A Nanoemulsion 2003 USFDA Dry eye syndrome Ocular

Ikervis® Cyclosporine A Nanoemulsion 2015 EMEA Dry eye syndrome Ocular

Hormone replacement
Estrasorb™ Estradiol Nanoemulsion 2003 USFDA therapy during meno- Transdermal
pause

Liver/spleen lesion
Metal oxide
Feridex® Iron oxide 1996 USFDA Magnetic resonance Intravenous
nanoparticles
imaging

Silicone-coated,
GastroMARK™/ Silicone coated iron
superparamag- 2001 USFDA Imaging agent Oral
Lumirem® oxide nanoparticles
netic iron oxide

Feraheme™ Iron deficiency ane-

Metal oxide
Iron oxide 2009 USFDA mia in chronic kidney Intravenous
/Ferumoxytol nanoparticles
disease in adults

Iron deficiency in
USFDA and
Venofer® Iron sucrose Nanocomplex 2000 chronic kidney dis- Intravenous
EMEA
ease

Ferric carboxymal-
Ferinject® Nanocomplex 2007 EMEA Iron deficiency Intravenous
tose

Iron-hydroxide dex-
Cosmofer® Nanocomplex 2014 EMEA Iron deficiency Intravenous
tran complex

Iron-hydroxide dex-
Ferrisat® Nanocomplex 2008 EMEA Iron deficiency Intravenous
tran complex

Iron deficiency in
Sodium ferric gluco- USFDA and
Ferrlecit® Nanocomplex 1999 chronic kidney dis- Intravenous
nate EMEA
ease

Iron deficiency in
INFeD® Iron dextran Nanocomplex 1957 USFDA chronic kidney dis- Intravenous
ease

Anemia, kidney fail-

Rienso® Ferumoxytol Nanocomplex 2012 EMEA Intravenous
ure, chronic

Local ablation in
Metal oxide
NanoTherm® Iron oxide 2013 EMEA glioblastoma, prostate, Intratumoral
nanoparticles
and pancreatic cancer

Table 2. contd…
Recent Updates on Nanomedicines Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2 141

Delivery Year of Approval

Name of Product Active Molecule Indication (Use) Route
System Approval Authority

Recombinant adeno- Head and neck

Gendicine® virus expressing Virosomes 2003 China squamous cell Intratumoral
wildtype-p53 carcinoma

Gene for dominant-

Rexin-G® negative mutant form Virosomes 2007 Philippines All solid tumors Intrahepatic
of human cycline G1

Inactivated hepatitis Vaccine against

Epaxal® Virosomes 2008 EMEA Intravenous
A virus hepatitis A

90Y-ibritumomab
Zevalin® Nanoparticles 2002 EMEA Lymphoma, follicular Intravenous
tiuxetan

Onivyde® Irinotecan Liposomes 2015 USFDA Pancreatic Cancer Intravenous

Psychostimulant,
Avinza® Morphine sulfate Nanocomplex 2002 USFDA Oral
analgesic

Dexamethyl-
Focalin XR® Nanocomplex 2005 USFDA Psychostimulant Oral
phenidate HCl

Metyhlphenidate
Ritalin LA® Nanocomplex 2002 USFDA Psychostimulant Oral
HCl

Zanaflex® Tizanidine HCl Nanocomplex 2002 USFDA Muscle relaxant Oral

Vitoss® Calcium phosphate Nanocrystal 2003 USFDA Bone substitute Bone graft
®
Ostim Hydroxyapatite Nanocrystal 2004 USFDA Bone substitute Bone graft

NanOss® Hydroxyapatite Nanocrystal 2005 USFDA Bone substitute Bone graft

EquivaBone® Hydroxyapatite Nanocrystal 2009 USFDA Bone substitute Bone graft

®
Invega Paliperidone Nanocomplex 2009 USFDA Schizophrenia Oral

Sustenna® Palmitate Nanocomplex 2014 USFDA Schizophrenia Intramuscular

Malignant
Ryanodex® Dantrolene sodium Nanocomplex 2014 USFDA Intravenous
hypothermia

4. OVERVIEW OF THE NANOMEDICINE CONCLUSION

BASED PRODUCTS APPROVED WORLD-
WIDE
Nanomedicine is a relatively new and rapidly
evolving field combining nanotechnology with the
biomedical and pharmaceutical sciences. The
adoption of nanoscience terminology by pharma-
ceutical scientists resulted in the advent of nano-
pharmaceuticals (nanomedicine based products).
An overview of various nanotechnology-based
products (nanopharmaceuticals or nanomedicine
products) approved recently by various regulatory
authorities has been presented in Table 2 along
with their active molecules, delivery system, ap-
plications and route of administration [49-53].
This review article outlines that nanotechnol-
ogy is considered to be an innovative industrial
reformation and also proved to be helpful in vari-
ous diseases by improving efficiency and safety in
nanomedicines and nanodevices. In medicine, it
bestows therapeutics, diagnosis, early detection as
well as a preventive indication for a wide range of
disorders. The agencies like USFDA and EMEA
should initiate to prepare currently for the upcom-
ing revolution in nanomedicine. Nanomedicine is
one of the chief tools of the 21st century with de-
sired prospects for both the researchers and phar-
maceutical industry. A strategic approach for
evaluation of the toxicity and safety of nano-
142 Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2018, Vol. 5, No. 2
medicine-based products within the standard set of
framework will encourage further research on the
technology and stir up the conventional systems
for drug delivery. Collaboration among countries
around the world is required in order to exchange
information and to ensure a high level of protec-
tion for humans and the environment, while not
hampering the development of new beneficial
products and their global marketing. In the interest
of all manufacturers, regulatory authorities and
consumers, there is a mandatory requirement for
an international harmonization for the evaluation
of the toxicity and safety of nanomedicine based
products.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The authors declare no conflict of interest, fi-
nancial or otherwise.
ACKNOWLEDGEMENTS
Declared none.
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