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MAKING DRUG DELIVERY NEEDLES NEED-LESS

A Painless Revolution

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 TABLE OF CONTENTS

Abstract......................................................................................................................3

Introducti.on.............................................................................................................3

Where, When and How Do Injuries Occur?....................................................5

What Devices Are Involved in Percutaneous Injuries?...............................5

What is a Needle-Free Injection Device and How Does it Work?...........6

Mechanism Based on Type of Injection..........................................................7

Needle-Free Injection Devices Can Be Divided

into 2 Types Based on the Source of Power...................................................8

Past and Present Needle-Free Injection Devices Manufacturers...........9

Few Examples of Currently Marketed Devices.............................................10

Conclusion.................................................................................................................11

References.................................................................................................................12

Authors Info ..........................................................................................................13

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 ABSTRACT

Conventional hypodermic needles introduced during the 1800s

are majorly used for drug delivery. This system involves piercing
the skin followed by delivering the drug into the subcutaneous
region of the skin. Although being majorly used, hypodermic
needles bring along several challenges such as needle stick
injuries and obvious painful administration with associated Challenges of
problems. Needle free injection, as a cullter-breaking idea could Hypodermic needles
hugely impact this
landscape. Introduction of
Needle-free Devices
This narrative review aims to discuss the import of needle free
drug delivery - about the introduction of needle-less injections,
their applications, and advantages over needle-based injections.
A comprehensive literature review was also done about
needle-free injections technologies and devices used. An
overview of the currently available marketed products and
recent trends are clearly
mentioned in this article.

HYPODERMIC NEEDLES VS NEEDLE-FREE DRUG DELIVERY

LEGACY TECHNOLOGY NEW INNOVATION

INTRODUCTION

Needle-Free Injection Technology (NFIT) offers the very obvious

benefit of reducing patient concern about the use of a needle.
The aim of the modern needle-free injection is to enhance the
prescribing and adoption of important drugs that require
self-injection, such as biologics. The intention of needle-free
injection technologies is to achieve this by improving the
patient experience and removing the barriers to self-injection,
such as the fear of needles.

Clearly the impacts of needle free injection are

multi-faceted.

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 Occupational exposure to blood-borne pathogens from
needlesticks and other sharps injuries is a serious problem, but it
is often preventable. The Centers for Disease Control and
Prevention (CDC) estimates that each year 385,000 needlesticks
and other sharps-related injuries are sustained by hospital-based
healthcare personnel. Similar injuries occur in other healthcare
settings, such as nursing homes, clinics, emergency care
services, and private homes. Sharps injuries are primarily
associated with occupational transmission of hepatitis B virus
(HBV), hepatitis C virus (HCV), and human immunodeficiency
virus (HIV), but they may be implicated in the transmission of
more than 20 other pathogens. WHO reports in the World Health
Report 2002, that of the 35 million health-care workers, 2 million
experience percutaneous exposure to infectious diseases each
year. It further notes that 37.6% of Hepatitis B, 39% of Hepatitis C
and 4.4% of HIV/AIDS in Health-Care Workers around the world
are due to needle-stick injuries. Although the cost of
Needle-stick Injuries through occupational HIV and hepatitis
seroconversion is relatively rare, the risks and costs associated
with a blood exposure are serious and real. Costs include the
direct costs associated with the initial and follow-up treatment
of exposed healthcare personnel, which are estimated to range
from $500 to $3,000 depending on the treatment provided.
Costs that are harder to quantify include the emotional cost
associated with fear and anxiety from worrying about the
possible consequences of an exposure, direct and indirect costs
associated with drug toxicities and lost time from work, and the
societal cost associated with an HIV or HCV
seroconversion; the latter includes the possible loss of a workers
services in patient care, the economicburden of medical care,
and the cost of any associated litigation.

Needle free drug delivery could therefore, have massive

implications.

Procedures during
PROCEDURES DURING WHICH NEEDLE STICK which needle stick
INJURIES OCCUR injuries occur

Work locations of
needle injuries

16

Venepuncture Handling clinical waste

12
Injection administration Clearing working area
8
Operating/Assisting Other
3 21
4 Aspiration

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 Where, When and How Do Injuries Occur?

Sharp devices can cause injuries anywhere within the healthcare

environment, data from Center for Disease Control and
Prevention (CDC) states that the majority (40%) of injuries occur
on inpatient units, particularly medical floors and intensive care
units, and in operating rooms (Figure 2). Injuries most often
occur after use and before disposal of a sharp device (41%),
during use of a sharp device on a patient (39%), and during or
after disposal (16%). There are many possible mechanisms of
injury during each of these periods as shown in CDC data on
hollow-bore needle injuries

WORK LOCATIONS WHERE INJURIES OCCUR

Access Transfer/Process
specimens(5%)
Circumstances
Recap IV line(6%)
needle(6%)
Manipulate needle in associated with
Patient(26%)
needle injuries
Collision worker
of sharp(10%)
Devices involved
Other(4%) in percutaneous
Handle/Pass
equipment(5%) injuries
During
clean-up(10%) In Transit to
Improper
During sharps disposal(4%) Benefits of needle
disposal(10%)
disposal(13%) free injections

CIRCUMSTANCES ASSOCIATED WITH HOLLOW BORE

NEEDLE INJURIES
Waste/laundry/
central supply(1%) Other(4%)
Labs(5%) ER(8%)
Outpatient(9%) OR(25%)

Inpatient(40%)

Procedure
room(25%) OB/GYN
Intensive care
Pediatrics ward
Medical surgical ward unit
21% 2% 2% Jail unit - less than 1%
*Missing values are not included in the total n. Nursery 1%
Psychiatry ward 1%
What Devices Are Involved in Percutaneous Injuries?

Although many types of sharps injure healthcare personnel,

aggregate data from CDC indicates that six devices are
responsible for nearly eighty percent of all injuries
(Figure 4). These are:

Disposable syringes (32%)

Suture needles (19%)
Winged steel needles (12%)
Scalpel blades (7%)
Intravenous (IV) catheter stylets (6%)
Phlebotomy needles (3%)

Overall, hollow-bore needles are responsible for 59% of all

sharps injuries.

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 .With the use of needle-free technology, a variety of
problems associated with the hypodermic needles are Needle-free Injection
eliminated. One of the most significant drawbacks which can be device
eliminated by needle-free technology is avoiding the use of
needles and thus cutting off the high cost of the needles which Classification of Needl
includes need for sharps management, disposal costs, and e-Free device under
needle stick injury testing and treatment costs. Another problem FDA
with traditional needles is the lack of reusability. If a needle
syringe is not sterilized, reusing it can lead to the spread of Classification of
disease (as discussed earlier). Additionally, the pitfalls of Needle-Free device
needle-based injections are psychological resistances to under ISO
self-injection or needle-phobia, awareness of serious problems
has caused physicians and their patients to either delay therapy
initiation or seek out less-invasive alternatives, even at a cost to
clinical effectiveness. When a needle is inserted through the skin, Solid sharp (34%)
the vaccine or drug it carries provides systemic immunity. This is
Other/unknown(6%) Suture needle (19%)
because the vaccine gets into the bloodstream and provokes the
Glass(2%)
body to create antibodies that are carried throughout the entire Scalpel (7%)
body. Needle-free systems are designed to solve these problems Hollow-bore needle
(59%)
making them safer, less expensive, and more convenient.

What is a Needle-Free Injection Device and How Does it

Work?
Other(8%)

Hypodermic needle Winged-steel needle

According to Food and Drug Administration [FDA], a needle-less
or needle-free injection is a device used for the parenteral 21% 13% 6% 3% 6%

administration of a medicament. Needle-free injectors are IV stylet

classified as Class II devices under FDAs code of federal Phlebotomy needle
regulations 21CFR880.5430 (Non-electrically powered fluid Other hollow - bore needle

injector). A non-electrically powered fluid injector is a *Vacuum tube holder/phebotomy needle assembly
non-electrically powered device used by a health care provider
to give a hypodermic injection by means of a narrow, high
velocity jet of fluid which can penetrate the surface of the skin
and deliver the fluid to the body.

There are several other kinds of needle free injection device

types - Other types of jet injectors have been defined by their
design features. Gas-powered jet injectors are defined in section
872.4465 as a syringe device intended to administer a local
anaesthetic. The needle free injection device is powered by a Mechanism of drug
cartridge containing pressurized carbon dioxide which provides flow
the pressure to force the anaesthetic out of the syringe.
Spring-powered jet injectors are defined in section 872.4475 as a
syringe device intended to administer a local anaesthetic. The
syringe is powered by a spring mechanism which provides the
pressure to force the anaesthetic out of the syringe.

Needle-free injectors are classified under ISO 21649:2006.

"Needle-free injectors for medical use - Requirements and test
methods.

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 In general, a Needle-Free Injection Device (NFID) is a drug Needle-free injection mechanism of drug flow
delivery system which works on a mechanism where liquid or
powder medication is forced into a tiny jet stream at high
pressure through a tiny orifice that is held against the skin. The
medication injects itself at high speed directly through the skin
without a physical instrument such as a needle needing to
physically pierce the skin. The jet stream of the medication is
small and fast enough to break through the skin, creating a more
comfortable experience. The design of the device has a major
influence on the accuracy of subcutaneous delivery and the
stresses imposed on the product to be delivered. However, it
also supports to a great extent for intramuscular and intradermal
drug delivery.

Over the next couple of sections we will explore the intricate

details of a needle free injection system. Needle-free injection mechanism comparison
with hypodermic needles

In this needle free injection system, a tube-shaped device is held

against the skin and a burst of air forces the molecules of
medicine into the body. The device is designed to force the
medicine far enough through the skin so it enters the
bloodstream.

Mechanism Based on Type of Injection

a) Powder Injection:
A closer look to needle free injection mechanism
These injections consist of a chamber filled with solid drug
content and a nozzle for firing drug particles into the skin. The
particles exit from the nozzle along with a gas stream and
impinge the skin surface leading to formation of a hole into the
skin with the progression of the injection. Drug particles get
deposited in a spherical pattern at the end of the hole and
penetrate across the stratum corneum.

Needle-free powder injection mechanism

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 b) Liquid Injection: Classification of
Needle-free injection
The basic principle of this injection is if a high enough pressure devices based on
can be generated by a fluid in intimate contact with the skin, power
then the liquid will punch a hole into the skin and be delivered Spring Powered
into the tissues in and under the skin. Although the same Compressed-Gas
principle is applied as in powder, there is a difference in the Powered device
actual design and operation of the powder injection devices.
These systems use gas or spring, pistons, drug loaded
compartments and nozzles. Typically, the nozzle has an orifice
size of about 150 to 300 m. The effect of the jet on the skin Needle-free liquid injection mechanism
surface starts the formation of a hole in the skin through
erosion, fracture, or other skin failure mechanisms. Further
impingement of the jet increases the depth of the hole in the
skin. If the volumetric rate of hole formation is less than the
volumetric rate of jet impinging the skin, then some of the liquid
splashes back towards the injector. This way the liquid is
delivered to the intended area for injection.

Needle-Free Injection Devices Can Be Divided into 2 Types

Based on the Source of Power

Spring-Powered: Spring powered needle-free injection

Spring-powered devices are compact and lower cost, but suffer

from a limited range of force and reduced versatility.
Spring-powered devices have been primarily used for
subcutaneous administration and self-administration of drugs.
This method works on a spring mechanism which is drawn back.
The spring is released by hitting a trigger, thus leading to the
generation of jet stream of the drug for subcutaneous,
intramuscular or transdermal delivery of a drug. Examples of
available devices are Dermojet, Medi-jector, etc.

Compressed Gas-Powered:

This system consists of an air/gas cartridge which is attached to

the gun through a tubing system that delivers power to the
piston after trigger actuation; it releases the piston and creates a
jet stream of the drug. It is suitable for subcutaneous,
intramuscular or transdermal use. Examples of available devices
are Biojector, Pulse, Needle-Free - Felton, Lenexa, Ks. Agro-Jet Manufactures of
/Med-Jet - Mit, Montreal. Gas-powered devices (jet injectors) Needle-free
have been primarily used for vaccine delivery, they have been injection devices
designed to deliver larger volumes, and their main disadvantage
is its reliance on an exhaustible energy source, likelihood to
bruise and mechanical failure.

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 Studies have shown that most needle needle-free injection
systems can deliver the target molecule at a variety of tissue
Compressed gas-powered needle-free injection
depths ranging from the dermis to the muscle depending on the
force generated by the jet. The method utilizes a high-pressure
stream of liquid able to penetrate the skin. This method is not
commonly used for some reasons, among them the pain and
bruises caused by the liquids deep penetration. The new
strategy developed uses micro-jets to deal with this issue.

Micro-jets are small jet injectors, with about half the nozzle
diameter of conventional jet injectors (50-100 micrometers
compared to 75-200 micrometers). Micro-jet injectors also
contain much less liquid 215 nanolitres (compared to
30,000-100,000 nanolitrers). This small amount of liquid allows
the injector to control the depth of penetration, a parameter
that had not been controlled until now. With a micro-jet injector,
the depth of penetration can be as small as 200 micrometeres,
compared to 2-20 millimeters in the conventional jet injector.

Past and Present Needle-Free Injection Devices

Manufacturers

More than a dozen companies have developed alternatives to

needle injections, which includes:

Antares Pharma Inc

PharmaJet
Injex Pharma
Weston medical
Pen Jet Corporation
Evans Enterprise
Advantaget Health Services
Health for Personal Care
National medical products, Inc

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 Currently marketed
Currently marketed
devices
devices

Few Examples of Currently Marketed Devices

Department
Product Type of Actuation Drug Drug
Company of Comments
Name system mechanism Types Volumes
penetration

Liquid --- Compatible with

Medi-jector Antares Subcutaneous Insulin all types of
based needle Spring
vision Pharma Inc. U-100 insulin
free injection

Liquid Used to deliver

Biojector Bioject Compressed Subcutaneous,
based needle Liquid 1 vaccines
2000 gas Intramuscular
free injection

Liquid Can be used for

Vitajet3 Bioject based needle Spring Subcutaneous Insulin 0.02-0.5 self-administartion
free injection

Liquid Subcutaneous Available for

Iject Bioject based needle Compressed Variable
intradermal, Liquid single use or
free injection gas
Intramuscular multiple users.

Weston Liquid Delivers drug in

Intraject Compressed Subcutaneous Liquid 0.5
medical based needle less than
gas
free injection 60 milli sec.
Liquid Subcutaneous Low cost, e
Penjet Compressed Liquid 0.1-0.5
Penject based needle intradermal, asy to operate
coporation gas
free injection Intramuscular

Liquid
Dual safety
Injex30 Injex based needle Spring Subcutaneous Insulin 0.05-0.3 system is present
free injection

Liquid Deliver largest

Injex150 Injex based needle Spring Subcutaneous Insulin 0.8-1.5 dose among
free injection injex products
Liquid Subcutaneous Operating is
Crossject Crossject based needle Spring intradermal, Liquid 0.2-1 based on novel
free injection Intramuscular gas tech

Depixol Liquid Operates by

Lundbeck Compressed Liquid 2-3
depo based needle Intramuscular using
limited gas
injection free injection compressed gas

Powderject Liquid Uses helium gas

Powderject Compressed Powder ---
pharmacue based needle Intradermal for delivery of
system gas
ticals free injection drug particles

Liquid Subcutaneous
Liquid 0.1-0.3 Can deliver wide
Miniject Bio valves based needle Spring intradermal, range of drugs
free injection Intramuscular

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 Conclusion

Needle-free technology offers the very obvious benefit of

reducing patient concern about the use of a needle.
Additional benefits include the very fast injection compared
with conventional needles, and no needle disposal issues. Concluding
Needle-free Injectors are more reliable, easier to use, more description and
efficient, much safer, and have no disposal problems. Accep- benefits of using
tance by patients, continuing development,s and lowering costs, needle-free injection
all make needle-free systems the best method for vaccinations, devices
or insulin self-treatments. The future of needle-free injection
systems looks bright, with a steady growth due to increasing Work locations of
demand for prevention of needle stick injuries and painless needle injuries
delivery of medication and this fact is further strengthened by
the strong clinical trial data available. Some of the applications
expected to be key to the success of needle-free technologies
include vaccines, biotechnology drugs - protein and peptide
delivery, gene delivery, and insulin. Needle-free devices have
come a long way to the present state and are expected to play
an increasingly important role in the novel drug delivery
technologies markets in the coming years. However, it brings
along very few challenges such as, the method is complex and
expensive, all systems are not fitted into one size, the need for
personnel training and maintenance, and at present current
non-applicability it is not applicable forthe Intravenous route.
Needle free injection technology also faces There are alsoseveral
challenges in terms of controlling the speed of the coil or
pressure of the effect produced by the compressed gas and the
velocity imparted to the drug since various skin types may
require different waveforms to deliver adequate volumes of
drugs to the desired depth. Although tailoring the pressure
profile gives a negligible drawback when compared to the
advantages of Needleneedle-free technology but with the rapid
advancement in technology, actuators are being introduced to
control the pressure of injection.

HCL believes in innovation and customer satisfaction, and has

the ability to support on needle-free injection
technology and regulation processes through its vast experience
in supporting global organizations through international
standards, directives, and regulations. HCL can provide product
compliance including R&D support that helps in regulatory
approval, for healthcare product
manufacturers.

Needle free injection technology is a breakthrough approach in

terms of nuanced care-giving, and could have an immense
humanizing impact on this segment of medicine.

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 References

http://www.who.int/occupational_health/topics/needinjuries

https://www.cdc.gov/sharpssafety

http://www.bd.com/europe/safety/en/facts.asp

http://www.nursingworld.org/

https://www.ncbi.nlm.nih.gov/

https://www.researchgate.net/

https://www.ijppsjournal.com

www.wjpps.com

www.pharmatutor.org

http://pubs.lib.umn.edu

https://www.fda.gov/MedicalDevices/DeviceRegulationand-
Guidance/GuidanceDocuments/ucm071663.htm

https://www.iso.org/standard/35954.html

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Author Info

Amit is a skilled engineering professional with nearly3 years of experi-

ence in blendingDesign, Development, Manufacturing, and Quality
experience encompassing the entire product life cycle of Medical
Devices andConsumer Plastic Products. He also holds an experience in
Tool & Die making industry and as a Certified CAD trainer. He has a
bachelors degree in Mechanical Engineering.

AMIT PAUL

Chakransh is an IRCA certified Lead Auditor for an EN ISO 13485:2012 &

ISO 13485:2003 with an expertise in the field of Quality Assurance &
Regulatory Affairs. He has Master degree in Biotechnology with 9 years
of experience in Medical Devices, Biopharmaceuticals & APIs. His roles
majorly include handling a Design and Development team for remedia-
tion as well as sustainability activities of medical devices as per the
Quality norms.He is also an internal PQA for HCL Medical DU Bangalore
Projects.
CHAKRANSH DIXIT
CHAKRANSH DIXIT
Nerissa DSouza

Karthi is a highly experienced engineering professional holding an

experience of nearly 14 years. He has expertise in New Product Develop-
ment, Design Transfer, Manufacturing Engineering, and Lean Six Sigma.
He has a Masters degree in Business Administration and a Bachelors
degree in Mechanical Engineering. Karthi is currently pursuing his PhD
and research works.

KARTHI MANI

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