SKIN DRUG DELIVERY: P10 - P22 - ONdrugDelivery
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P10 P22 P26
MICRONEEDLE A SMART PATCH FOR AIRLESS DISPENSERS
ARRAY CHALLENGES PAINLESS DRUG DELIVERY FOR DERMAL DRUG DELIVERY
ARE DISSOLVING FAST
SKIN DRUG
DELIVERY:
DERMAL, TRANSDERMAL & MICRONEEDLES
JANUARY 25TH 2021 • ISSUE NO 116
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EDITORIAL CALENDAR
Publication Month Issue Topic Materials Deadline
February Prefilled Syringes & Injection Devices Feb 1, 2021
March Ophthalmic Drug Delivery Feb 25, 2021
March/April Drug Delivery & Environmental Sustainability Mar 11, 2021
April Pulmonary & Nasal Drug Delivery Mar 25, 2021
May Delivering Injectables: Devices & Formulations Apr 8, 2021
June Connecting Drug Delivery May 6, 2021
July Novel Oral Delivery Systems Jun 3, 2021
August Industrialising Drug Delivery Jul 1, 2021
September Wearable Injectors Aug 5, 2021
September/October Drug Delivery & Environmental Sustainability Aug 19, 2021
October Prefilled Syringes & Injection Devices Sep 9, 2021
November Pulmonary & Nasal Drug Delivery Oct 7, 2021
December Connecting Drug Delivery Nov 5, 2021
January 2022 Skin Drug Delivery: Dermal, Transdermal & Microneedles Dec 2, 2021
2 www.ondrugdelivery.com Copyright © 2021 Frederick Furness Publishing Ltd
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Contents
ONdrugDelivery Issue No 116, January 25th, 2021 Microneedles for Intradermal Delivery of Cancer Vaccines
SKIN DRUG DELIVERY: DERMAL, 05 -09 John Vasilakos, Global Head of MTS Business Development
and Senior Research Immunologist
TRANSDERMAL & MICRONEEDLES Kindeva Drug Delivery
This edition is one in the ONdrugDelivery series Why the Consistent Challenges Surrounding MAPs are Dissolving Fast
of publications from Frederick Furness Publishing.
Each issue focuses on a specific topic within the 10 - 14 Sebastian Braun, Head of Formulation Development
and Manufacturing for Innovative Injection Systems
LTS Lohmann
field of drug delivery, and is supported by industry
leaders in that field.
Pharma Latch Angled Microneedle Patch
EDITORIAL CALENDAR for Enhanced Drug and Vaccine Delivery
Feb 2021 Prefilled Syringes & Injection Devices
Mar Ophthalmic Drug Delivery
16 - 20 Nicky Bertollo, Co-Founder and Chief Technology Lead
Ronan Byrne, Co-Founder; and
Andrew Muddle, Advisory Board Member
Mar/Apr Drug Delivery & Environmental Sustainability Latch Medical
Apr Pulmonary & Nasal Drug Delivery
May Injectable Drug Delivery Medicsen: Needle-Free Smartpatch for Painless Drug Delivery
Jun Connecting Drug Delivery Eduardo W Jørgensen, Chief Executive Officer;
Jul Novel Oral Delivery Systems 22 - 25 Juan César de Mercado, Chief Operations Officer; and
José Carlos Montesinos, Chief Technology Officer
Aug Industrialising Drug Delivery Medicsen
Sep Wearable Injectors
Sep/Oct Drug Delivery & Environmental Sustainability Ensuring Formulation Protection and Patient Care With Airless Dispensers
Oct Prefilled Syringes & Injection Devices Audrey Chandra, Category Project Manager;
Nov
Dec
Pulmonary & Nasal Drug Delivery
Connecting Drug Delivery
26 - 28 Manuela Basso, Communications Manager; and
Raphaële Audibert, Global Category Manager, Inhalation and Dermal
Nemera
Jan 2022 Skin Drug Delivery:
Dermal, Transdermal & Microneedles Product Showcase: Logan Instruments’ Transdermal Testing Portfolio
EDITORIAL: 30 - 31 Jensen Lee, Vice-President of Operations
Logan Instruments
Guy Furness, Proprietor & Publisher
E: guy.furness@ondrugdelivery.com Airless Drug Delivery: Widely Accepted, Accessible and Available
CREATIVE DESIGN:
32 - 36 Stefan Hellbardt, Vice-President Business Development and Scientific Affairs
Aptar Pharma
Simon Smith, Creative Director (Freelance)
E: simon.smith@ondrugdelivery.com
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The views and opinions expressed in this issue are those of the authors.
Due care has been used in producing this publication, but the publisher
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Front cover image, credit GustoImages/Science Photo Library.
Reproduced with permission. www.ondrugdelivery.com
Kindeva
MICRONEEDLES FOR INTRADERMAL
DELIVERY OF CANCER VACCINES
In this article, John Vasilakos, PhD, Global Head of MTS Business Development
and Senior Research Immunologist at Kindeva Drug Delivery, discusses the
immuno-oncology market. He examines the role of cancer vaccines in
supplementing other immuno-oncology therapies, as well as the value of delivering
cancer vaccines intradermally.
Throughout 2020, the
pharmaceutical industry
received ample public
“A series of studies suggests that
scrutiny around its search patients treated with checkpoint
for covid-19 vaccines and inhibitors are more than twice as likely
therapeutics. However, even
with so much focus rightfully
to experience a durable response.”
centred on the race to develop
therapies that address
the pandemic, covid has not diminished immuno-oncology therapies and the value
oncology drugs’ colossal importance in the of delivering cancer vaccines intradermally.
industry. This importance can be measured Kindeva Drug Delivery’s microneedle-based
both in research and development spend and drug delivery platform will be used as an
in drug sales. Clinical development spend on example of how to address many of the
oncology therapies in the US is estimated to industry’s unmet needs with respect to
be more than US$80 billion (£59 billion), intradermal delivery.
which is more than a third of total pharma
development spend.1 Meanwhile, drug THE CURRENT LANDSCAPE OF
sales for oncology are expected to exceed IMMUNO-ONCOLOGY THERAPEUTICS
$300 billion by 2026, representing roughly
a fifth of the total pharma market.1 In the last decade, immune checkpoint
The sustained investment and inhibitors, such as pembrolizumab
opportunity in oncology matters because (Keytruda, PD-1 antagonist) and ipilimumab
cancer remains a public health crisis. Existing (Yervoy, CTLA-4 antagonist), have emerged
drugs and treatment regimens still have many as a dominant class of immuno-oncology
gaps and much room for improvement. therapeutics. There is a strong case to be
These gaps should be addressed by not only made in favour of checkpoint inhibitors
Dr John Vasilakos
optimising the drugs that are used to treat based on the durability of the patient Global Head of MTS Business
cancer, but also optimising the devices that response. In essence, this means that a Development and Senior Research
deliver these drugs. patient can meaningfully extend their life Immunologist
This article focuses on the sizable expectancy when these drugs work. E: john.vasilakos@kindevadd.com
immuno-oncology subsegment, which is A series of studies suggests that patients
expected to grow to nearly $100 billion by treated with checkpoint inhibitors are Kindeva Drug Delivery
2026 – growth of over 20% per annum.1 more than twice as likely to experience a 42 West Water Street
It discusses a dominant immuno-oncology durable response – and roughly 30% of St Paul
MN 55107
drug class (checkpoint inhibitors) and these patients experienced overall survival
United States
their shortcomings, considers the role of (OS) that was more than twice the patient
cancer vaccines in supplementing other population’s median OS.2 Moreover, www.kindevadd.com
Copyright © 2021 Frederick Furness Publishing Ltd www.ondrugdelivery.com 5
Kindeva
combination therapies, in which the patient
is treated with two or more checkpoint
“The number of T-cell targeted immunomodulators in the
inhibitors, have had an even more promising
impact on patient survival.3 pipeline has more than doubled since 2017, with over 200
Among the most prevalent of the programmes targeting either PD-1 or PD-L1.”
checkpoint inhibitors are programmed cell
death protein 1 (PD-1) and programmed
cell death ligand 1 (PD-L1) inhibitors. immune system, which could result in As evidence for their durability
PD-1 is a T-cell receptor that helps deleterious effects on healthy tissues. Cancer grows, checkpoint inhibitors have
downregulate or inhibit immune responses. has found a way to take advantage of been commercially successful for many
In the normal course of events, PD-1 this normal regulatory system. Cancer cells types of cancer, and their popularity in
engages with PD-L1 on antigen-presenting can produce PD-L1, which downregulates clinical trials has continued to grow.
cells – resulting in the inhibition of T-cell T-cell function following PD-1 engagement. Specifically, the number of T-cell targeted
function, such as cytotoxicity. Therefore, Therefore, tumour cells that express the immunomodulators in the pipeline has
PD-1 functions as a brake on T-cell activity, ligand PD-L1 block the tumour-killing more than doubled since 2017 (Figure 1),
thereby preventing overactivation of the function of T-cells by engaging T-cell PD-1. with over 200 programmes targeting either
PD-1 or PD-L1 (Figure 2).4 However,
despite the promise, there is still a clear
need for improvement. The approximately
30% of patients who experience higher
OS represent a significant achievement,
but approximately 70% of patients require
additional therapy.5 Indeed, combination
therapy has become the norm for
oncology patients.
Moreover, checkpoint blockade therapies
have recently been approved for use for
several cancers. For example, the US FDA has
approved Keytruda (Merck, Kenilworth, NJ,
US) for use with chemotherapy (carboplatin)
to treat metastatic head and neck cancer.
In addition to chemotherapeutics, other
combination strategies are being evaluated
with checkpoint blockade therapies, such
as kinase inhibitors, anti angiogenics,
immune-stimulating cytokines and multiple
combinations of checkpoint blockade
Figure 1: Number of T-cell targeted immunomodulators and cancer vaccines in therapies and vaccines.
development globally.
THE ROLE OF CANCER VACCINES
AND COMBINATION THERAPY
WITH CHECKPOINT BLOCKADE
Within the immuno-oncology space, there
is lots of energy around cancer vaccines.
There are an estimated 840 cancer vaccines
currently in development (Figure 1),4 with
up to 600 companies developing them.
In most situations, these vaccines are
being developed as combination therapies,
intended to be delivered to patients in
conjunction with checkpoint inhibitors.
Cancer vaccines are compelling because
checkpoint blockade therapies are not
successful at eliminating all tumours
in all patients, especially when used in
isolation. These immunotherapeutics
are most effective when the tumour
microenvironment (TME) contains tumour-
Figure 2: Number of immunomodulators targeting PD-1/PD-L1 in development globally. infiltrating T-cells (TILs).6 The TME can be
6 www.ondrugdelivery.com Copyright © 2021 Frederick Furness Publishing Ltd
Kindeva
characterised as cold (non-T-cell inflamed) seems ideal, its biggest limitation is
or hot (T-cell inflamed). Hot tumours are a practical one: it is difficult to achieve
“The question of how and
characterised by T-cell infiltration and precise and reproducible delivery to the
molecular signatures associated with immune where cancer vaccines are intradermal layer using traditional delivery
activation, whereas cold tumours exhibit delivered to the body should devices. One challenge is that the dermis is
T-cell absence or exclusion. In general, hot thin – approximately 1,800 μm in depth.
not be overlooked. The
tumours present higher response rates to To achieve this, the delivery device would
checkpoint blockade therapies. Therefore, route of administration may need to deliver the vaccine to a depth of
various efforts have focused on converting impact the ultimate success 500–1,500 μm and do so reliably. The lack
non-inflamed cold tumours into hot tumours of a reliable delivery method has limited the
rates of these vaccines.”
to achieve a better clinical response. use of intradermal vaccination.9
To solve the problem of converting cold Kindeva has advanced the development
tumours to hot ones, numerous strategies of delivery devices that help overcome
have been employed, such as targeting question of how and where cancer vaccines the challenge of intradermal delivery.
tumours with immune stimulators or are delivered to the body should not be With microneedles, Kindeva’s hollow
inhibitors of immune suppressor cells. overlooked. The route of administration microstructured transdermal system (hMTS)
Another approach currently being evaluated may impact the ultimate success rates of facilitates the reliable and reproducible
is cancer vaccination in combination with these vaccines. delivery to the dermis. Kindeva’s hMTS
checkpoint blockade. Vaccination makes device is an injector that includes a drug
sense in the context where the patient INTRADERMAL DRUG DELIVERY cartridge to contain the liquid formulation
exhibits minimal cancer-specific T-cell OF CANCER VACCINES and an array comprised of 12 hollow
immunity. The idea is to increase the microneedles (Figure 3). The cartridge
number of tumour-specific T-cells with As previously discussed, cancer vaccines can be loaded up-front or at the time of
the vaccine and prevent or inhibit their induce tumour-specific immunity. In an use, depending on the drug’s requirement.
inactivation, or enhance their proliferation, ideal world, cancer vaccines would be At the time of use, the applicator delivers
using checkpoint blockade therapies. delivered directly into immune organs such the microneedle array into the skin; the
In other words, cancer vaccines can induce as the lymph nodes, the spleen or the liquid formulation will then move through
tumour-specific T-cells in those patients skin itself. When delivered subcutaneously the hollow microneedles and deliver the
that lack anti-tumour T-cells. or intramuscularly, cancer vaccines are drug into the dermis. The drug delivery
Some of the earliest cancer vaccines deposited into parts of the body where system is intended for the intradermal
available on the market proved to be only immune cells do not normally reside. By space, which makes the injection time
marginally effective. Now, the industry has contrast, intradermal delivery would deliver longer than is typically experienced with
become much wiser about cancer vaccines the vaccine directly into the dermis, where standard vaccine injections. Depending on
with respect to antigen selection, patient immune cells do reside. There is evidence the formulation, the patient and the delivery
selection and combination therapies to use that demonstrates a comparative advantage site, total hMTS injection time is typically
with vaccines, which adds to their promise. of intradermal delivery over intramuscular less than two minutes per mL.
Regarding patient selection or targeting, delivery.7 Of salience to cancer vaccines, The two main features that make
a better understanding of the patient’s intradermal vaccinations have led to Kindeva’s hMTS platform well suited
tumour burden and immune status help enhanced immune responses in many cases.8 to deliver cancer vaccines are the depth
define which patients may benefit from While intradermal delivery of of delivery and the volume of delivery.
vaccination. Conducting vaccine trials only cancer vaccines For depth, Kindeva has refined the device
on patients with late-stage cancer is not design to achieve reproducible intradermal
ideal, because those patients often have
severely compromised immune systems.
For cancer vaccines to work, the patient
needs to have a functional immune
system. Therefore, cancer vaccines should
be delivered to and tested on patients in
earlier stages of the disease.
Other improvements in the development
of cancer vaccines have resulted from the
use of more optimal adjuvants or viral
vectors that enhance cytotoxic T-cells and
interferon-gamma producing T-helper cells,
and the use of cancer antigens that are more
commonly expressed on multiple tumour
Figure 3:
types or antigens that are unique to the
Kindeva’s hollow
patient (neoantigens). microstructured
Continued innovation in cancer vaccines transdermal
and their formulations is essential – but the system (hMTS).
Copyright © 2021 Frederick Furness Publishing Ltd www.ondrugdelivery.com 7
Kindeva
“Devices that enable reproducible intradermal
delivery should be seriously considered by
biopharma companies developing cancer vaccines.”
delivery, using microneedles with a been used in partners’ Phase I and IIa
length of either 1,000 μm or 1,500 drug clinical studies in the US,10-13 and
μm. Cancer vaccines administered via the development of a device suitable for
hMTS will be delivered to a shallower Phase III/commercial use is progressing.
part of the skin compared with Moreover, Kindeva’s manufacturing
vaccines delivered subcutaneously capabilities are in place to meet preclinical
(Figure 4), thus delivering the vaccine and clinical needs.
to the immune-cell-rich dermis and
elicit a more robust immune response. CONCLUSION
In terms of volume, hMTS
can deliver up to 2 mL. This is Immuno-oncology therapies, such as
a meaningful increase in capacity checkpoint inhibitors, are designed
compared with other intradermal to facilitate the ability of the patient’s
and non-intradermal delivery devices immune system to effectively attack and
currently used to deliver vaccines. kill tumours. Over the last decade, there
While the hMTS device is currently has been demonstrable success, with
in development, it is already well blockbuster therapies achieving significant
positioned to be the device-of-choice increases in patient survival rates. Cancer
for biopharma companies developing vaccines can be used in combination with
Figure 4: Anatomy of the skin. cancer vaccines. Kindeva’s device has these checkpoint inhibitors to make cold
8 www.ondrugdelivery.com Copyright © 2021 Frederick Furness Publishing Ltd
Kindeva
tumours hot, thereby increasing the overall COVID-19.” Nat Rev Drug Discov, Label, Multi-Center Trial of SNS-301
success rate. New oncology drug classes 2020, Vol 19, pp 751–752. Added to Pembrolizumab in Patients
continue to crop up and gain momentum, 5. Haslam A, Prasad V, “Estimation of with Advanced Squamous Cell
which provides a reason for optimism. the Percentage of US Patients with Carcinoma of the Head & Neck.”
However, innovation in the Cancer Who Are Eligible for and Poster Presentation,
pharmaceutical industry is not exclusive to Respond to Checkpoint Inhibitor 2020 SITC Annual Meeting.
the discovery of novel drugs and vaccines. Immunotherapy Drugs.” JAMA Netw 11. Algazi A et al, “Early Safety and
Innovation in drug delivery devices can Open, 2019, Vol 2(5), e192535. Efficacy of a Phase 1/2 Open-Label,
also play a meaningful role in improving 6. Duan Q et al, “Turning cold into Multi-Center Trial of SNS-301
how the medical industry treats cancer. For hot: firing up the tumor.” Trends in Added to Pembrolizumab in Patients
example, devices that enable reproducible Cancer, 2020, Vol 6(7), pp 605–618. with ASPH+ Locally Advanced
intradermal delivery should be seriously 7. Teunissen MB, Haniffa M et al, Unresectable or Metastatic/Recurrent
considered by biopharma companies “Insight into the immunobiology Squamous Cell Carcinoma of the
developing cancer vaccines. Devices like of human skin and functional Head and Neck.” Poster Presentation,
Kindeva’s hMTS platform are capable specialization of skin dendritic cell 2020 EMSO Annual Meeting.
of delivering cancer vaccines directly to subsets to innovate intradermal 12. Block MS et al, “Th17-inducing
the dermis, with its relative abundance of vaccination design.” Curr Top autologous dendritic cell vaccination
immune cells, increasing the potential that Microbiol Immunol, 2012, Vol 351, promotes antigen-specific cellular and
the drug is effective in improving patient pp 25–76. humoral immunity in ovarian cancer
survival rates. 8. Ogai N, Nonaka I et al, patients.” Nature Communications,
“Enhanced immunity in intradermal 2020, Vol 11(1), Article 5173.
REFERENCES vaccination by novel hollow 13. Gustafson MP et al, “Preliminary
microneedles.” Skin Res Technol, manufacturing, safety, and immune
1. “World Preview 2020, Outlook to 2018, Vol 24(4) pp 630–635. monitoring results of an allogeneic
2026.” EvaluatePharma, 2020. 9. Kim YC, Jarrahian C et al, “Delivery tumor lysate-pulsed dendritic
2. Pons-Tostivint E et al, “Comparative systems for intradermal vaccination.” cell vaccine for patients with
Analysis of Durable Responses on Curr Top Microbiol Immunol, 2012, newly diagnosed glioblastoma.”
Immune Checkpoint Inhibitors Vol 351, pp 77–112. Poster Presentation, 2016 SITC
Versus Other Systemic Therapies: 10. Gramza A et al, “Phase 1/2 Open- Annual Meeting.
A Pooled Analysis of Phase III
Trials.” JCO Precision Oncology,
2019, Vol 3, pp 1–10. ABOUT THE AUTHOR
3. Larkin J et al, “Five-Year Survival John Vasilakos is the Global Head of MTS Business Development and Senior Research
with Combined Nivolumab and Immunologist at Kindeva Drug Delivery. His previous industry roles include Senior
Ipilimumab in Advanced Melanoma.” Research Immunologist and Business Development of TLR Ligands at 3M Drug
N Engl J Med, 2019, Vol 381, Delivery Solutions Division and Vice-President of Immunology at Biothera. He has
pp 1535–1546. spent more than 25 years in the biopharmaceutical industry, focusing on vaccines and
4. Upadhaya S, Hubbard-Lucey VM, immunotherapy for cancer and chronic viral diseases. He holds a PhD from the University
Yu JX, “Immuno-oncology drug of Cincinnati School of Medicine (OH, US).
development forges on despite
We
know
drug delivery
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Copyright © 2021 Frederick Furness Publishing Ltd www.ondrugdelivery.com 9
LTS Lohmann
WHY THE CONSISTENT
CHALLENGES SURROUNDING
MAPS ARE DISSOLVING FAST
In this article, Sebastian Braun, PhD, Head of Formulation Development and
Manufacturing for Innovative Injection Systems at LTS, discusses the current state
of microneedle-based transdermal drug delivery, covering available microneedle
delivery methods, the US FDA’s current stance on microneedle technologies and LTS’s
microarray patch system and the possibilities it represents.
INTRODUCTION This article will cover the relative merits
in each form of microneedle technology;
For the past decade, innovation in review the specific requirements set out
microneedles has been a focus within the by the FDA in October 2020; present the
pharmaceutical world. Today, microneedles case for the specification of dissolvable
are seen as a viable option for the delivery microarray patch (MAP) technology
of drugs such as biologicals, vaccines and (Figure 1), which uniquely addresses the
difficult-to-deliver small molecules through FDA’s requirements; and finally evaluate
the skin, in both immediate-release and the benefits of MAP technology to each
long-acting products. The widely recognised stakeholder group, including pharma
benefits of transdermal administration in partners, payers, healthcare professionals
terms of pain-free delivery, convenience and (HCPs) and patients.
patient compliance, make microneedles an The skin is an important protective
ideal platform for an increasing number of barrier with an innate reactive capability
therapeutic areas. (Figure 2). Its protective, inflammatory
However, the journey has not been pain- and immunological properties make it an
free. The US FDA has clearly struggled with attractive target for efficient drug delivery.
the quality of submissions received from It has been well documented over the
combination products using microneedles, years that, for various drugs, there are
specifically around stability testing, content many advantages to intradermal delivery
uniformity, risk analysis, sterility validation compared with the intramuscular and
and manufacturing. subcutaneous routes. However, the use
of a traditional needle mostly requires a
relatively sophisticated cold chain supply,
Dr Sebastian Braun
as well as the time and effort of an HCP. Head of Formulation Development
It also presents issues for the patient and Manufacturing for Innovative
as it is quite invasive, particularly Injection Systems
T: +49 2632 99 2770
E: sebastian.braun@ltslohmann.de
Figure 1: LTS’s
MAP system. LTS Lohmann Therapie-Systeme AG
Lohmannstraße 2
56626 Adernach
Germany
www.ltslohmann.de/en
10 www.ondrugdelivery.com Copyright © 2021 Frederick Furness Publishing LtdLTS Lohmann
Figure 2: Skin composition.
for the large portion of patients who suffer NEED FOR A LESS PAINFUL mechanism of choice for many therapies.
from needle phobia. WAY THROUGH THE SKIN The challenge is, of course, that at present
As an alternative approach, MAPs the choice of API is limited to small
can reproducibly deliver APIs into the The pharmaceutical industry is very much molecules, with today less than 30 APIs
dermal and epidermal layers of the skin, aware of the benefits of drug delivery by having been successfully commercialised for
which contain high densities of immune injection in terms of its capability to deliver transdermal therapeutic systems (TTSs).
cells.1 Microneedle technology was first to the dermis, subcutaneous tissue and These limitations have been addressed
conceptualised, and subsequently patented, muscle layers under the skin. For a number by several microneedle technologies which
in the 1950s,2 but it took some time for of drugs, it is, in many ways, an ideal enable the drug to overcome the skin barrier
the benefits of microneedles to be fully delivery route. However, there are evident (Figure 3). Here, the currently available
recognised. It was not until 1998 that a issues too, specifically related to patient transdermal microneedle options are:
paper was published exploring the compliance, usability and safety for HCPs.
possibility of using microneedles for Aversion to needles, pain and needle size • Solid removable microneedles dispense
vaccination in the future.3 Since that early are all very real concerns for many patients. only a limited drug load and deliver a
work, the WHO has identified microneedles Needlestick injuries are a source of great short, sustained release of drug due to the
as a potential game-changer for vaccine concern for HCPs, indeed the WHO stated speed of the skin healing.
distribution and coverage in low-to-middle- in its World Health Report 2002 that of • Coated microneedles deliver an immediate
income countries (LMICs).4 35 million HCPs, two million experience release of API and require only a short
percutaneous exposure to infectious diseases application time on the skin. They do,
each year. The WHO further noted that however, only carry a very limited drug load.
37.6% of Hepatitis B, 39% of Hepatitis C • Hollow microneedles can carry a higher
“The pharmaceutical
and 4.4% of HIV/AIDS in HCPs globally drug load and be used for immediate or
industry is very much are due to needlestick injuries.5 As well as sustained release, but there are limitations
aware of the benefits of the human cost, there is a financial cost too, in the types of API solution that can be
with each needlestick injury case costing delivered this way.
drug delivery by injection
the local healthcare system around US$350 • Dissolvable microneedles offer very little in
in terms of its capability (£259).6 Although MAPs do not entirely terms of compromise, and a great deal in
to deliver to the dermis, eradicate the potential for needlestick terms of benefit. Dissolvable microneedles
injuries, they are certainly a big step in the will be returned to later in this article.
subcutaneous tissue and
right direction towards protecting HCPs. Hydrogel-forming microneedles have the
•
muscle layers under the capacity to carry a higher drug load to
skin. For a number of THE EVOLUTION OF MICRONEEDLES be delivered over a sustained period.
Although they present no sharp-edge
drugs, it is, in many ways,
Transdermal patches offer a demonstrable waste issues, they are limited by diffusion
an ideal delivery route.” improvement in patient compliance, safety of the API in the polymer matrix and by
and usability, and represent the delivery the number of polymers that can be used.
Copyright © 2021 Frederick Furness Publishing Ltd www.ondrugdelivery.com 11LTS Lohmann
the required specification limits and then
adequately demonstrate compliance. Some
submissions showed that verification and
validation testing was not using the final
finished combination product in bench-top,
clinical or human factors studies, and there
was a lack of risk analysis to ensure leaving
the system in place longer than prescribed
would not result in injury or overdose.
The guidance from the FDA in this
regard is clear. Submissions must deliver:
• A comprehensive design control package
that identifies risks and hazards
• A clearly defined control strategy for
EPR, design verification and validation
• A risk management plan
• An iterative guide to risk management
activities throughout the entire product
lifecycle.
Common Manufacturing Deficiencies
One particular area of weakness has been
incomplete facility responsibility listings on
the 356h form. Process parameters and
in-process controls are not supported by
process development knowledge in the
Figure 3: Overview of microneedle technologies. application. There have been significant
failures with submitted batches, with no
All these options offer tangible benefits the criteria for a successful submission.7 root cause analysis provided. In terms
in terms of patient compliance and HCP In it, the FDA stated: “Regulation of of biologics, there have been incomplete
safety compared with injection-based combination products must take into process performance qualifications
administration. It is also worth noting account the safety and effectiveness questions (PPQs) submitted; the product not being
that solid removable, coated and hollow associated with each constituent part and the manufactured within the review cycle and
microneedles all result in sharps waste, product as a whole.” inspection times; the sterilisation validation
whereas dissolvable and hydrogel-forming The FDA’s presentation sought to data delivered has been insufficient; and
microneedles do not. clarify the common product, product-use there have been failures with equipment
and manufacturing deficiencies, as well qualification, process simulation and
MICRONEEDLES AND THE FDA as setting out what it needs to see from sterility testing methods.
future applications. In terms of the common The FDA’s unequivocal requirement
The FDA’s experience of submissions product and product-use deficiencies, the is for evidence of process development
relating to microneedles to date could perhaps headlines related to stability testing in terms and the bridge to commercial scale.
be described as disappointing, with quite of formulation/API migration and continued Submission documentation must deliver
basic failures evident in many fundamental testing of mechanical attributes. commercial process descriptions, process
aspects of submission. This increasing level Content uniformity is fundamental, and flow diagrams, master batch records (MBRs)
of disappointment manifested itself in an there is some work to do for delivery and a sterilisation validation package for
October 2020 presentation from the FDA device designers and the pharmaceutical sterile products.
which sought to set out in very clear terms industry more broadly in order to establish The presentation also highlighted
three clear objectives for prior approval
inspection (PAI):
“The requirements set out by the FDA are nothing more • Readiness for commercial manufacturing
• Conformance to application
than would be expected for any regulated drug delivery
• Data integrity.
device, and it is alarming that the quality of some
submissions has been poor enough to necessitate such In LTS’s opinion, the requirements
set out by the FDA are nothing more
regulatory guidance, given the immediate and unparalleled
than would be expected for any regulated
opportunities this kind of technology presents.” drug delivery device, and it is alarming
that the quality of some submissions has
12 www.ondrugdelivery.com Copyright © 2021 Frederick Furness Publishing LtdLTS Lohmann
per administration – via reducing the dose administered after months one and three.
(“dose sparing”) – and the removal of cold The results demonstrated that the recombinant
“LTS’s goal was to develop
chain distribution challenges. vaccine MAP system is safe and well tolerated,
a transdermal delivery The LTS MAP system is based on and saw mild and moderate reactions in the
method where, if the uncoated dissolvable microneedles, which subjects, comparable with those who received
enables optimal API load without relying the vaccine via IM injection.
API can be delivered
on liquid reservoirs. There are three key
via an injection, it can processing requirements for a homogeneous WHERE NEXT?
be delivered by LTS’s microneedle product:
MAPs are a novel vaccine delivery
transdermal device. LTS has
• Homogeneity of dispensing solution methodology that has the potential to
developed such a device • Dosing precision become a game-changer for immunisation
with its MAP system.” • Precise mould dimensions and geometry. programmes, especially in LMICs, which
mostly rely on vaccine storage and
LTS’s MAP technology can provide transportation at 2–8°C and trained HCPs
been poor enough to necessitate such for improved stability because the API is to administer injectable vaccines by needle
regulatory guidance, given the immediate embedded homogenously in the polymer, and syringe. Whilst the benefits are most
and unparalleled opportunities this kind of ensuring 100% of the drug content obvious for programmes in LMICs, that
technology presents. is dispensed. The API and polymer are does not mean they are irrelevant for the
mixed with a solvent, dispensed into the rest of the world. Indeed, much of the
Meeting FDA Guidance mould and then dried to remove the solvent development work LTS is undertaking right
For 40 years, LTS has been regarded as (Figure 4). The dispensing heads deliver a now is for high-value APIs.
a trusted partner and market leader in precise, reproducible volume of solution. Microneedle technology is considered
innovative transdermal drug delivery Indeed, the dispensing heads are so precise an advantageous delivery route for existing
systems. The company’s mission is to find that pharmaceutical partners can even vaccines, including influenza, tetanus
alternatives for patients where conventional switch formulations and volumes within toxoid, measles-rubella, Hepatitis B and
drug delivery presents challenges. As such, each MAP. Configured for the API to inactivated poliomyelitis vaccine (IPV),
LTS constantly creates new technologies be delivered and desired release option,
that support pharmaceutical development each MAP can feature up to 1,000 needles
and improve patient outcomes. While LTS per cm2, with needle lengths ranging from
is clear about the efficacious benefits of 200 μm to more than 1,000 μm – 900 μm “MAPs are a novel vaccine
TTSs, it is also aware of their limitations being the threshold for pain sensation.
delivery methodology
in terms of API fit, and so is committed to
research and development towards finding a RECOMBINANT VACCINE that has the potential
technology where the compromises inherent HUMAN STUDY RESULTS to become a game-
in current TTSs were reduced.
changer for immunisation
Essentially, LTS’s goal was to develop In this study, LTS aimed to investigate the
a transdermal delivery method where, if safety and the general and local tolerability programmes, especially in
the API can be delivered via an injection, of the recombinant vaccine delivered by a LMICs, which mostly rely
it can be delivered by LTS’s transdermal microneedle system, as well as the efficacy of
on vaccine storage and
device. LTS has developed such a device vaccination. Four cohorts were established
with its MAP system. This system delivers with 12 subjects in each. Three doses of the transportation at 2–8°C and
a range of benefits to the entire healthcare recombinant vaccine were delivered with the trained HCPs to administer
ecosystem in terms of increased patient LTS MAP system, according the standard
injectable vaccines by
comfort and better compliance, a faster “prime-boost-boost” scheme. One dose level
onset, lower overall healthcare costs of recombinant vaccination via intramuscular needle and syringe.”
through self-administration, lower costs (IM) injection was delivered, with boosts
Figure 4: The MAP manufacturing process.
Copyright © 2021 Frederick Furness Publishing Ltd www.ondrugdelivery.com 13LTS Lohmann
as well as vaccines still in development, such • For patients, the reduced pain and lower 3,964,482, 1976.
as inactivated rotavirus and dengue. Given psychological challenge of administering 3. Henry S et al, “Microfabricated
the challenges currently surrounding the microneedle technologies creates the microneedles: a novel approach to
cold-chain distribution of covid vaccines, a potential for increased patient compliance transdermal drug delivery”. J Pharm
great deal of consideration should be given and adherence. Sci, 1998, Vol 87(8), pp 922–925.
to MAPs as an efficient method to mass- 4. “WHO Microarray Patch (MAP)
immunise populations. ABOUT THE COMPANY Product Development Workshop”.
Geneva, Switzerland, 2015.
CONCLUSION LTS Lohmann Therapie-Systeme AG 5. “Needlestick injuries. Protecting
is a leading pharmaceutical technology health-care workers – preventing
MAPs have great potential, but it has been company that develops and manufactures needlestick injuries”. WHO website.
untapped to date. The technology has innovative drug delivery systems such as 6. Mannocci A et al, “How Much
accrued advocates since the 1970s, and transdermal therapeutic systems (TTSs) do Needlestick Injuries Cost? A
today there is a growing weight of evidential and oral thin films (OTFs) for the Systematic Review of the Economic
data to show the concerns around content pharmaceutical industry. The company’s Evaluations of Needlestick and Sharps
uniformity have been largely eradicated. commercial offering encompasses more than Injuries Among Healthcare Personnel”.
This is now a real and present opportunity 20 marketed products and a diverse pipeline Infect Control Hosp Epidemiol, 2016,
for pharma partners to benefit and deliver of more than 30 development projects Vol 37(6), pp 635–646.
real value across the healthcare ecosystem. targeting multiple disease indications. 7. Strasinger C, “Product Development
The technology overcomes the various LTS’s innovation pipeline contains both and Quality Considerations
challenges associated with conventional partner-funded and proprietary LTS- for Transdermal Systems and
formulations and offers tangible benefits funded projects. LTS maintains its leading Microneedle Systems: A Regulatory
for pharma partners, payers, HCPs and, of position through the continuous refinement Perspective”. PharmaEd Resources,
course, patients: of its core TTS and OTF technologies Microneedle Drug Delivery Systems
and by advancing emerging drug delivery Virtual Conference, Oct 27–28, 2020.
• For pharma partners, there is now the technologies, including microarray patches
necessary evidence to demonstrate that (MAPs) for the intradermal delivery of large
MAPs are a safe and reliable dosage form molecule, biological actives. LTS has an ABOUT THE
and that adequate patient dosing can be
achieved. There are several advantages
established dedicated state-of-the-art R&D
centre for its parenteral and sterile MAP
AUTHOR
in terms of custom design too, with both technology platform, including a GMP area Sebastian Braun has worked in the field
sustained and immediate release options for manufacturing of clinical supplies. of transdermal and dermal drug delivery
available, as well as flexibility in needle Founded in 1984, LTS operates today for 15 years. A molecular biologist
design, length, width and composition. from two sites in Andernach (Germany) and with a PhD in analytical chemistry
There are also real options for patent West Caldwell (NJ, US), and a representative and molecular biology, he started his
protection and brand differentiation, office in Shanghai (China). career at a transdermal drug delivery
as well as lifecycle management and company, building a fundamental
product extension opportunities. There REFERENCES understanding of the biological
is also a very clear option to repurpose workings of the skin. Spending the
existing products into a more patient- 1. Fernando GJP et al, “Safety, last 15 years at different transdermal
friendly delivery mechanism. tolerability, acceptability and and dermal drug delivery companies
• For payers, there is a real benefit to immunogenicity of an influenza in various positions, including head
MAPs in that they can enable patient vaccine delivered to human skin by of formulation development, head of
self-administration, creating the potential a novel high-density microprojection manufacturing and head of science
for lower healthcare costs. array patch (Nanopatch™)”. Vaccine, and technology, he is now focused
• For HCPs, they help to reduce the 2018, Vol 36(26), pp 3779–3788. on microneedle development and
challenges and threats associated with 2. Gerstel MS, Place VA, “Drug manufacturing.
needlestick injuries. Delivery Device”. US Patent No
IN WHICH ISSUE SHOULD
YOUR COMPANY APPEAR?
www.ondrugdelivery.com/participate
14 www.ondrugdelivery.com Copyright © 2021 Frederick Furness Publishing LtdPROMISE
TRANSDERMAL “NEXT BIG THING”
MAP
MICRO ARRAY PATCH
Pain-free and easy to use
For biologics, vaccines,
and small molecules
Reduced side effects due
to transdermal application
www.ltslohmann.comEarly Insight
PHARMA LATCH ANGLED
MICRONEEDLE PATCH
FOR ENHANCED DRUG
AND VACCINE DELIVERY
Nicky Bertollo, PhD, Co-Founder and Chief Technology Lead, Ronan Byrne,
Co-Founder, and Andrew Muddle, PhD, Advisory Board Member, all of Latch Medical,
introduce Pharma Latch – a user-centric angled microneedle patch technology.
They discuss its key benefits, such as dramatically increased payload potential,
precision, low cost and variable patch-wear times, and highlight how Pharma
Latch has the potential to overcome many of the limitations of existing routes of
administration for therapeutics and vaccines.
Intradermal delivery holds great a result. Invasive intradermal injections
promise as an attractive alternative to using hypodermic needles, pen injectors
traditional oral and parenteral routes of and even needle-free injectors are associated
administration for the delivery of vaccines with the potential for discomfort and Dr Nicky Bertollo
and therapeutics, including biologics. distress for the patient; have significant Co-Founder and Chief Technology Lead
Systemic uptake of therapeutics via the requirements around infrastructure, training T: +353 1 716 3770
dermal blood capillaries has a host of of personnel and sterile settings; and have E: nicky.bertollo@latch-medical.com
benefits, including avoiding the deleterious the ever-present risk of needlestick injuries.
effects of first-pass metabolism, rapid Transdermal patches overcome some of
drug onset and improved bioavailability these limitations but are confined to a
of APIs, such as biologics, that are not relatively small number of compounds
readily absorbed across the mucosal layers which are known to be able to successfully
of the gastrointestinal tract. Furthermore, permeate the intact outer layer of skin – the
the skin is replete with antigen presenting stratum corneum – either passively or in
cells (APCs) and therefore represents an combination with permeation enhancers.
optimal location for the delivery of vaccines These and other restrictions have
Ronan Byrne
(both traditional and novel DNA- and motivated the development of minimally Co-Founder
mRNA-based vaccines) in order to elicit an invasive microneedle patch (MNP) T: +353 1 716 3770
enhanced immune response. technologies which not only overcome E: ronan.byrne@latch-medical.com
Methods employed to deliver or diffuse many of these limitations but – as noted
drugs into the dermis must compete against by the World Economic Forum in its list of
the skin’s excellent barrier function – and Top 10 Emerging Technologies of 20201
are associated with known limitations as – have the potential to play a role in
transforming healthcare. The enhanced
intradermal delivery attributes offered
by MNPs have the potential to cater for
“Pharma Latch is a existing, repurposed or new ranges of
revolutionary MNP compounds not suited to the established
routes of administration. Dr Andrew Muddle
technology that unlocks Advisory Board Member
Pharma Latch is a revolutionary MNP
a delivery solution that technology that unlocks a delivery solution
addresses a wide variety of that addresses a wide variety of drug and
vaccine delivery challenges faced by both
drug and vaccine delivery
conventional routes of administration and Latch Medical
challenges faced by both current MNP technologies. NovaUCD
conventional routes of Belfield Innovation Park
INTRODUCING PHARMA LATCH University College Dublin
administration and current Dublin
Ireland
MNP technologies.” Pharma Latch is an easily self-administered,
self-anchoring, solid-coated MNP optimised www.pharmalatch.com
16 www.ondrugdelivery.com Copyright © 2021 Frederick Furness Publishing LtdEarly Insight
Figure 1: Pharma Latch microneedle patch
technology. (Image courtesy Latch Medical.
Reproduced with kind permission.)
for therapeutic and vaccine delivery
(Figure 1). Pharma Latch technology
“The proprietary coating technology produces coatings
exhibits opposing arrays of angled stainless-
steel microneedles (MNs) coated using a at room temperature and without the need for linkers
proprietary process performed at room or binders, meaning that APIs may be formulated and
temperature which dries instantaneously and
deposited at relatively higher concentrations.”
is compatible with a range of compounds,
including biologics.
Pharma Latch is applied to the skin
using a simple and intuitive clicking action. for linkers or binders, meaning that Highly user-centric design and ease of
•
This manual clicking moves the opposing APIs may be formulated and deposited use. The Pharma Latch is applied to the
angled MNs towards one another, at relatively higher concentrations. skin using a simple and intuitive manual
penetrating the outer skin layers and The process deposits API-containing clicking action and is easily removed.
drawing the skin onto the MNs in a formulations in uniformly even and Built-in safety mechanisms prevent
controlled, repeatable fashion. Robust, thin layers, which preserves MN accidental deployments, whilst visual,
adhesive-free and instantly reversible tip geometry to a greater extent than tactile and audible feedback is provided
attachment to skin can be achieved. traditional dip-coating techniques.. to the user on successful attachment.
This, coupled with inherent tailorability • Increased payload potential. The The user-centric and intuitive design
in both design and coating, means that combination of these geometry and has no training requirements, allowing
Pharma Latch can facilitate both short- and coating factors can elevate the payload for administration by minimally trained
longer-term patch wear and drug elution potential of the Pharma Latch far beyond medical personnel or self-administration
times (seconds/minutes/days/weeks) across what is currently achieved by solid-coated by patients.
a range of compound types at much higher and dissolvable MNP technologies. Repeatable, reliable penetration and
•
payloads than are currently achieved • Stable coatings. The proprietary coatings depth targeting. Uncontrolled and
by existing solid-coated and dissolvable can potentially be stable at room variable skin deformation occurs during
MNP technologies. temperature, which removes cold-chain the application of conventional MNPs
Key features and benefits of Pharma and logistics requirements, facilitating to skin, resulting in partial, incomplete
Latch’s technology include: global, remote distribution. Pharma and highly variable embedding of the
Latch has demonstrated with a number full MN height.2,3 In some cases, only
• Increased MN surface area available of biological APIs that the coating a small proportion (up to 30%) of MN
for coating. When compared with the process does not affect its stability. height is routinely exposed to skin.4
conventional vertical approach taken by • Robust, adhesive-free attachment. The Variable, incomplete MN penetration
MNPs, the angling of the Pharma Latch unique manner in which the angled MNs may potentially reduce payload delivery
MNs – specified for a given depth target interdigitate with and anchor to the efficiency for both conventional solid-
in the skin – results in greater surface skin removes the need for chemical- coated MNPs and dissolvable MNP
area available for coating with the API. based adhesives. This also opens up the technologies.3,5 The unique method of
• Superior coating concentration across a possibility of long-term patch wear from engagement applies subtle traction to
range of compound types. The proprietary hours and days up to several weeks – skin during deployment, drastically
coating technology produces coatings at a possibility not achievable using existing reducing deformation and ensuring near
room temperature and without the need solid-coated MNP technologies. full-length (>95%) exposure of the angled
Copyright © 2021 Frederick Furness Publishing Ltd www.ondrugdelivery.com 17Early Insight MNs to skin.6 The superior penetration ENGINEERING THE PHARMA LATCH variability in MN penetration across efficiency of Pharma Latch’s angled MNs existing MNPs is well reported in the could result in reduced dosing variability, The Pharma Latch is optimised for skin scientific literature. Importantly, the extent which will be observed in drug absorption penetration and adhesive-free attachment. of this deformation can be exacerbated measured in the pharmacokinetic data of The unique solution ensures that each by the anatomical location and integrity its products. individual angled MN is repeatably inserted of the skin, as well as by subdermal fat.7 No • reliance on pre-energised to the same depth in the skin every time in The combination of these patient-related applicators. Many MNP solutions every patient. and skin biomechanics factors can be looking to deliver higher payloads need expected to give rise to dosing variability a high-density MN configuration. These Mechanism across repeated applications on the same need a high-velocity impact onto the Subtle traction is applied to the skin by the patient (i.e. intra-subject variability) and/ skin to aid penetration – requiring a opposing arrays of angled MNs keeping or between patients across a population pre-energised applicator. This also limits the skin taut and dramatically reducing (i.e. inter-subject variability) when treated potential patch size. Pharma Latch’s skin deformation during insertion. This using conventional MNP technologies. controlled mechanism of engagement novel mechanism of insertion is illustrated with skin removes the reliance on in Figure 2. Conceptually, the net effect Repeatability pre-energised applicators and increases of these attributes results in skin being The Pharma Latch deployment mechanism the range of permissible patch sizes from drawn up onto the Pharm Latch MNs in a is designed to produce repeatable MN 4 cm2 upwards. controlled, repeatable fashion. insertion, independent of skin type or C onfigurable to meet treatment • The mechanism of insertion differs anatomical location. This substantially objectives. The Pharma Latch platform fundamentally from many existing MNP reduces intra-subject and inter-subject can be readily adapted to meet varied technologies and application techniques dosing variability risks, which may be treatment objectives, including human (including both manual pressing and observed in pharmacokinetic data. The factors considerations, with one- or two- high-speed impact using pre-energised increased penetration efficiency achieved part configuration options to facilitate applicators) which effectively act to push by the Pharma Latch MNs, derived from a both short- and long-term wear and the skin away from the patch as it is combination of the angled MN geometry and delivering low-to-high payloads. being applied. As mentioned prior, the skin insertion mechanics, ensures repeatable, Figure 2: Schematic depicting Pharma Latch’s mechanism of engagement, the subsequent release of the API from the fully embedded angled microneedles and the method of removal. 18 www.ondrugdelivery.com Copyright © 2021 Frederick Furness Publishing Ltd
Early Insight
The scalable approach to MN fabrication FUTURE OUTLOOK
ensures that the Pharma Latch design
“The Pharma Latch
(i.e. MN geometry, tip height, number The Pharma Latch technology is technically
deployment mechanism and density) is readily customisable to validated and currently moving towards a
is designed to produce accommodate the desired payload and number of pre-clinical studies with a range
intended release kinetics of the deposited of different compounds and vaccines. The
repeatable MN insertion,
coating. MN density can be tuned to simplicity of Pharma Latch, combined with
independent of skin type or meet the payload objectives of the specific its payload potential, opens up a variety
anatomical location.” application, which gives rise to a range of new possibilities – both in the MN
of potential Pharma Latch configurations. drug delivery sphere and also in a broader
Pharma Latch makes use of a two-part consideration of drug delivery opportunities
near-full-length coated MN exposure and system (with reloading capabilities) for previously considered out of reach for
release of API into the interstitial fluid of the high-density MN patch configurations MNP technologies.
skin for systemic uptake. supporting high payloads, with the second The company is actively seeking
part increasing the mechanical advantage collaborations with companies looking
Manufacturing and promoting usability. A one-part system to develop novel products which meet
The increased MN insertion efficiency of is available for lower payload, low-MN- currently unmet patient needs – be they
Pharma Latch, coupled with a controlled, density applications. existing compounds or vaccines, generic
manual application action, removes the APIs looking to differentiate through the
need to employ costly, high-strength Coating 505(b)(2) route of registration in the US
metal alloys. Pharma Latch uses low- Pharma Latch’s solid MNs coated with or new compounds or vaccines looking to
cost, surgical-grade stainless steel and API offer an advantage over dissolvable be delivered intradermally, be they small
can be produced using scalable, low-cost MNP technologies in that the solid MNs molecules, vaccines or biologics.
production methods leveraging standard themselves provide the mechanical backbone
pharmaceutical packaging materials and and requisite strength. This potentially ABOUT THE COMPANY
processes. Coating of the MNs relies on a simplifies the mechanical considerations
highly automated process with established around – and specific requirements of – Latch Medical is a venture-funded company
high-volume, low-cost techniques. excipients in a given formulation. This with a platform microneedle technology.
approach, coupled with the method of The technology is centred on opposing
Tailorability coating, can simplify the formulation arrays of angled microneedles that can
Pharma Latch is highly configurable and both process, whilst simultaneously increasing penetrate the outer layers of the skin
the core MN platform and coating process the range of compound types that can be in a manner ensuring consistent needle
can be readily tailored to meet the treatment readily incorporated into the platform. penetration and without the use of any
objectives, in terms of desired payload, release adhesive. The platform can be used in a
kinetics and wear times. Pharma Latch offers Payload number of different applications, including
an unsurpassed ability to target specific depths The tailorability in the proprietary coating drug delivery, biosensing and wearables.
in the skin, owing to its superior penetration process allows the delivery of payloads In 2019, Pharma Latch was awarded a
efficiency (>95% length penetration),6 which far in excess of what is currently being substantial grant by the Irish government.
may be important when treating certain achieved by solid-coated and dissolvable A rapid development plan ensued, allowing
dermatological conditions or administering MNP technologies. Combined with the the Pharma Latch technology to progress.
vaccines. The direct implication of a highly self-anchoring angled MN geometry, this
efficient MN insertion is that vertical potentially allows Pharma Latch to rival the REFERENCES
penetration depth is ultimately governed by the dosages currently being delivered through
MN geometric parameters and, specifically, more traditional means. As a result, Pharma 1. “Top 10 Emerging Technologies of
the vertical MN tip height from the substrate, Latch has the potential to offer a step 2020”. World Economic Forum,
which can typically be engineered to be in the change in MN-mediated therapeutic and November 10, 2020.
range of 250–600 μm or beyond. vaccine delivery. 2. Römgens AM et al, “Monitoring
the penetration process of single
microneedles with varying tip
diameters”. J Mech Behav Biomed
“Pharma Latch has the potential to offer a step change in
Mater, 2014, Vol 40, pp 397–405.
MN-mediated therapeutic and vaccine delivery.” 3. Donnelly RF et al, “Optical
coherence tomography is a valuable
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