THE POTENTIAL IMPORTANT CONSIDERATIONS A PREVIEW OF CPHI

OF MACHINE INTELLIGENCE IN SERIALISATION WORLDWIDE 2018

September 2018

PATH OF LEAST RESISTANCE

Colorcon highlights how tablet coating can help with swallowability
and inevitably patient compliance.
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 Contents
September 2018 | Volume 18 Issue 6

REGULARS
5 EDITOR’S DESK
Some of the latest Brexit developments as we draw closer to the UK’s exit from the EU…

6 A SMALL DOSE
A brief round-up of some of the developments in the industry including a warning of a
serious side effect and the landmark deal for NHS patients to access CAR-T therapy.

11 OPINION
Looking at patents and their role in the pharma industry, asking the question whether
they are complicating business or enhancing opportunities?

14 COVER STORY
In this feature, Jason Teckoe, from Colorcon, examines tablet design aspects in more
detail, paying particular attention to swallowability.

58 TECH TALK
This time in Tech Talk, Dr Neil Polwart, Novarum founder and BBI Group head
of mobile, looks at blockchain technology in mHealth.

FEATURES
16 ARTIFICIAL INTELLIGENCE
Assessing the opportunities of artificial intelligence, how to get the best value
out of big data and the uses of augmented reality in pharma.

23 SERIALISATION SUPPLEMENT
Within this special supplement, various aspects of serialisation are considered
such as benefits of blockchain and how companies can drive a return
on their serialisation investment.

34 FORMULATION
Insights into important considerations to ensure success in GLP toxicology studies
and uses of modelling to minimise development risks.

38 ANALYTICAL LAB TECHNIQUES

Here, Thermo Fisher Scientific reveals how the latest tools are taking the complexity
out of peptide mapping workflows.

41 APIS/HPAPIS
Examining the intricacies of risk assessment and the importance
of a realistic approach.

44 CLEANROOMS
Discussing design strategies for more energy efficient cleanrooms and outsourcing
of microbiological growth media.

50 CPHI PREVIEW
Previewing this year’s exciting CPhI Worldwide, taking place in Madrid, Spain.

53 DIGITAL HEALTH
Highlighting how technology is a major resource in various aspects of healthcare
and how community is needed to make it all work.
Making Science Work
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 5
HEAD OFFICE
Carlton House, Sandpiper Way,
Chester Business Park,
SO LONG, FAREWELL…
Chester, CH4 9QE.

Tel. +44 (0)1244 680222

Fax. +44 (0)1244 671074
It is fair to say that Brexit
has offered a substantial
amount of ‘editorial fodder’
In light of this, the UK
government issued an initial
series of technical notices,
Web: www.epmmagazine.com
since I started my tenure which set out to inform
EDITORIAL here as editor of European businesses and the public
editor felicity thomas
[email protected] Pharmaceutical Manufacturer. about what steps they should
Even just over the past couple be taking to prepare for a
deputy group editor dave gray of months, we have seen some ‘no deal’ scenario. These
[email protected]
huge stories emerge around preliminary documents have
head of content, life sciences lu rahman, this topic. been welcomed by the industry.
[email protected]

reporter reece armstrong Most recently, there have been “By agreeing to recognise and
[email protected] reports about the government use medicines and vaccines
discussing the issue of funding licensed and manufactured in
publisher duncan wood
the extra costs of stockpiling the EU, the UK government
PRODUCTION vital medicines with drug has taken an important
haed of studio and production companies just in case a step to protect patients. We
sam hamlyn
‘no-deal’ Brexit transpires, urge the EU Commission to
design robert wood including the potential viability do the same,” stated Mike
of flying in medicines. Thompson, chief executive of
ADVERTISING
robert anderton the Association of the British
tel: +44 (0)1244 952359, Major pharmaceutical Pharmaceutical Industry (ABPI).
[email protected] companies have already
shona newton confirmed preparative works Additionally, we have witnessed
tel: +44 (0)1244 952519, are underway for a hard Brexit the shock that the MHRA
[email protected] outcome and the Medicines will no longer be allocated
A look over some
and Healthcare products any centralised marketing
head of media sales, plastics & life sciences of the latest Brexit
lisa montgomery Regulatory Agency (MHRA) authorisation applications as
[email protected] developments as we
has ratified that the issue of a result of the UK potentially
draw closer to the UK’s a medicines’ supply has its becoming a ‘third country’
SUBSCRIPTIONS exit from the EU…
[email protected] highest attention. come March 2019.

EDITOR’S
qualifying readers
Europe - Free, ROW - £249 “The news that EMA has
outside qualifying criteria announced it will discontinue
UK - FREE, ROW - £249 awarding contracts to the
please subscribe online at MHRA, is no surprise. It is,

DESK
www.epmmagazine.com
nonetheless, a shocking
Address changes should be emailed to blow to MHRA,” stated Martin
[email protected] MacLean, life sciences partner
European Pharmaceutical Manufacturer at intellectual property firm,
is published by Rapid Life Sciences Ltd. Mathys & Squire.
European Pharmaceutical Manufacturer
is distributed in electronic and print formats to a
combined readership of 14,000 pharmaceutical Sanofi UK’s MD, Hugo Fry, So, as the UK and the EU
manufacturing professionals.
and the chief executive of prepare their ultimate farewells,
Volume 18 Issue 6 © September2018 AstraZeneca, Pascal Soirot, I too must say my goodbyes
While every attempt has been made to ensure that the
information contained within European Pharmaceutical
have both stressed that their as I close on my last edition
Manufacturer is accurate, the publisher accepts no liability respective companies are as editor of EPM magazine.
for information published in error, or for views expressed.
All rights for European Pharmaceutical Manufacturer
doing all they can to maintain a Thanks for your support
are reserved and reproduction in part or whole continuous supply of medicines, and engagement with this
without written permission is strictly prohibited.
although an overwhelming esteemed publication, it has
sentiment coming from industry truly been an honour.
is that clarification from both
sides of the Brexit negotiating
table is urgently needed.
BPA Worldwide Membership
ISSN No - 2052-4811
6 A small dose

This rare and serious

infection, necrotizing

WARNING!
fasciitis of the perineum
— also referred to as
Fournier’s gangrene
— is considered a

Serious
urological emergency
and has a mortality rate
of more than 20%.

side effect The flesh-eating

disease is caused by
bacteria that enter the
body through a cut or
An important warning was communicated by break in the skin and
the US Food and Drug Administration (FDA) then start to destroy
recently regarding potential infections around tissue. It spreads
the genitals and surrounding area occurring in quickly and requires
patients taking sodium-glucose cotransporter-2 antibiotic treatment as
(SGLT2) inhibitors for type 2 diabetes. well as surgical removal
of any dead tissue.

Landmark deal — it’s CAR-Ty time!

A landmark deal was benefit,” asserted Simon ‘FIRST OF ITS KIND’ DEAL
revealed that will Stevens during the first The cost-effectiveness of
see the first chimeric day of the Health and personalised treatments
antigen receptor T-cell Care Innovation Expo in has previously been
(CAR-T therapy) — Manchester when officially highlighted as an issue
Kymriah from Novartis announcing the deal. by the National Institute
— made available for for Health and Care
children and young “CAR-T cell therapy Excellence (NICE), which
people via the NHS. is the most exciting recommended against
advances in treatment for the use of Yescarta (Kite
WHY IS THIS BIG NEWS? childhood leukaemia for Pharma) in England
Personalised therapies decades,” commented for the treatment of
are an exciting Dr Alasdair Rankin, aggressive subtypes of
development that director of Research at non-Hodgkin lymphoma,
may potentially cure the blood cancer charity earlier in the year.
some patients, in Bloodwise. “Intensive
particular those that chemotherapy can now Kymriah costs around
are unresponsive to cure the vast majority of £282,000 per patient
standard therapies. children but a significant at its full list price.
However, they are also number still tragically It has not been disclosed
extremely complex and die every year because what reduction in price
expensive to produce. they do not respond has been negotiated
to treatment. CAR-T between Novartis and
“CAR-T therapy is a true cell therapy offers the NHS England, however.
game changer, and NHS genuine chance of
cancer patients are now a long-term cure for This is the very first time
going to be amongst children who otherwise within Europe that a
the first in the world to would have no other hope.” commercial deal of this
 www.epmmagazine.com
7

“We are requiring a

new warning about this
risk to be added to the
prescribing information
of all SGLT2 inhibitors
and to the patient
Medication Guide,”
the FDA specified
on its website.

Approved medicines
containing SGLT2
inhibitors include
canagliflozin,
dapagliflozin,
empagliflozin and
ertugliflozin. These
drugs work by causing
the kidneys to remove
sugar from the body
via urine.

kind has been made.

“This constructive fast-
track negotiation also
shows how responsible
and flexible life sciences
companies can succeed
— in partnership with ASTHMA BREAKTHROUGH IN US FOR AZ
the NHS — to make
revolutionary treatments A breakthrough Amgen) significantly HOW DOES IT WORK? inflammation cascade,
available to patients,” therapy designation reduced asthma Tezepelumab is a it is hoped that
added Stevens. has been granted by exacerbations when potential first-in-class tezepelumab may be
the US Food and Drug compared with placebo. new medicine that works suitable for a broad
‘FANTASTIC NEWS’ Administration (FDA) by blocking thymic range of patients.
“It’s fantastic news for for AstraZeneca’s SEVERE ASTHMA stromal lymphopoietin
children and young tezepelumab in patients Severe asthma, which (TSLP), which is involved EXCITING POTENTIAL
people with this form of with severe asthma, is reported to account in the initiation and “Tezepelumab is
leukaemia that CAR-T representing the first for around 10% of persistence of airway exciting because it has
cell therapy will be made for the company for a asthma sufferers, may inflammation. the potential to treat
available on the NHS, respiratory medicine. be uncontrolled despite a broad population of
making them the first in high doses of medicines It is believed that by severe asthma patients,
Europe to have routine This designation, and can require the blocking the epithelial including those ineligible
access to this exciting new which is intended use of chronic oral cytokine (TSLP) it may for currently-approved
type of immunotherapy,” to accelerate the corticosteroids. be possible to stop pro- biologic therapies,”
added Professor Charles development and inflammatory cytokines explained Sean Bohen,
Swanton, Cancer regulatory review of The pathogenesis of being released by executive vice president,
Research UK’s chief medicines intended the condition involves immune cells and as Global Medicines
clinician. “We applaud to treat a serious multiple inflammatory such should prevent Development and
NHS England, NICE and condition, was based pathways, one of which asthma exacerbations chief medical officer
the company for working on clinical study data is T2 inflammation driven and improve control of at AstraZeneca. “The
together to make this demonstrating that asthma. This is found the condition. Breakthrough Therapy
immensely complex tezepelumab (which in more than two-thirds Designation will help us
treatment available to is being developed of patients with severe As this blocking bring tezepelumab to
patients quickly, through by AstraZeneca in asthma, according to mechanism happens patients as quickly
the Cancer Drugs Fund.” collaboration with AstraZeneca’s website. early on in the as possible.”
8 A small dose

Going Pulling
the plug
viral… Pfizer has terminated
two clinical
studies evaluating
domagrozumab for
the treatment of
Duchenne muscular
dystrophy (DMD).

The Phase II study,

which was evaluating
New research has only do virus therapies expanded in future,” virus therapy, the the safety and efficacy
shown that viruses kill cancer cells directly, added one of the researchers neutralised of the treatment, was
may have potential in they do so with only mild study’s lead authors viruses and added them stopped as it did
treating cancer as they side effects compared Dr Elizabeth Ilett, from to melanoma cells in not meet its primary
retain their cancer- to traditional cancer the Leeds Institute of the laboratory, which on efficacy endpoint.
killing ability even treatments and they Cancer and Pathology at its own had no effect. After further evaluation
after injection into the attract the immune the University. “We are But adding white blood of all the evidence
bloodstream. system to the site of only just beginning to cells, called monocytes, it was deemed
the tumour — which understand how viruses meant the virus became that there was no
Oncolytic viruses are means they can work can help us tackle reactivated, allowing it to significant treatment
known to preferentially well when combined cancer, but it is exciting destroy the cancer cells. effect. The open-label
infect and kill cancer with other types of to learn that our bodies extension study was
cells, however, when immunotherapy.” are actually capable of “Our study shows aimed at evaluating
injected into the helping them to destroy that, crucially, viruses the long-term safety
bloodstream it was T-vec is a type of virus cancer tumours.” retain their cancer- and efficacy of
believed that the already approved for killing ability even domagrozumab was
human’s normal immune use on the NHS to treat Three different viruses in the bloodstream,” also concluded.
response neutralised advanced melanoma — currently being explained Melcher. “This
them. skin cancers. However, used in clinical trials — research has profound “We are disappointed
it is only suitable for the were evaluated in the implications for how we by these results and
In this latest study, treatment of tumours study. After they had might use viruses to treat while we are not
which was published that can be reached with been neutralised the cancer in future, opening progressing with the
in the journal Cancer a needle. researchers found that in up virus therapy to studies, the data will
Immunology Research, two of the three viruses many more patients with contribute to a greater
the researchers found In looking at a work white blood cells were hard-to-reach tumours of understanding of this
that cells in the blood around in which viruses able to reactivate them different cancer types.” disease and we will
can actually reactivate injected into the and they were able to evaluate the total data
the virus as it travels to bloodstream could be destroy melanoma cells A number of viruses are set to see if there is a
the tumour site, where it useful as a therapeutic in a lab setting. currently being looked at place for this medicine
was then able to retain option, the researchers in a clinical trial setting, in muscular diseases,”
its ability to destroy the determined that white As a result of their but only one has been said Seng Cheng, PhD,
cancerous cells. blood cells could not findings the study approved for general senior vice president
only carry the virus to authors believe that use via injection directly and chief scientific
“Viruses are a hugely the tumour site, but other viruses might to the tumour. It is hoped officer, Pfizer Rare
exciting new type of were also capable also be effective after that with this latest work, Disease Research
treatment for cancer,” of reactivating the being neutralised by it will be possible to gain Unit. “We are
stressed co-lead author deactivated viruses. the immune system via a better understanding extremely grateful to
Alan Melcher, professor reactivation with white of how virus therapies all those involved with
of Translational “This discovery suggests blood cells. work and will enable this trial, especially the
Immunotherapy at The that cancer treatments their future use in boys who participated,
Institute of Cancer using virus therapy Using antibodies from combination with other and their families.”
Research, London. “Not could be significantly patients undergoing immunotherapies.
 www.epmmagazine.com
9

DRUG PRICE
HIKES… NEE,
DANK U WEL!
A group of doctors and This specific case relates
health advocates from to the price hike of
the Netherlands (the the orphan medicine
Dutch Pharmaceutical Chenodeoxycholic
Accountability acid Leadiant (CDCA),
Foundation) are used in the treatment
taking an Italian of cerebrotendinous
pharmaceutical xanthomatosis (CTX).
company to task after Shortly after the
it raised the price of European Medicines
a life-saving drug Agency approved the
500-fold. market authorisation
for CDCA with an
The Financial Times,1 indication for CTX, the
which reported manufacturer — Leadiant
the news in early Biosciences — increased
September, spoke the annual price from
with the head of the €30,000 to around
foundation, Wilbert €170,000 per patient.
Bannenberg about the
claim they were filing. One can’t help but
“Some companies are reminisce on the actions
misusing the system to of the ‘bad boy’ of
get higher profits, and pharma, Martin Shkreli,
patients are being are
being affected when
cheap, affordable old
who became infamous
for hiking the price of
Daraprim by 5,000%.
Dangerous loophole
products are no longer Although, according to
available. This may be Stat, which reviewed With ongoing efforts to orders are going to the Guardian. “This includes
legal but it’s not socially financial documents, tackle opioid addiction same address, regulators identifying multiple
acceptable,” he said. the drug’s manufacturer, happening on a global are questioning whether orders to the same
formerly known as Turing scale, why is it still opioid medications address or using the
Pharmaceuticals now as possible for patients should be allowed to same payment details.”
Vyera Pharmaceuticals, to buy drugs online be supplied by online
is now suffering from so easily? pharmacies at all. The ability to buy so
dwindling profits, in part many of these high
believed to be due to The Guardian revealed “We have set out actions strength pain killers
the pricing scandal that in a dangerous we’re proposing that is potentially very
loophole for those online pharmacy owners dangerous and with
with an addiction to would be expected increasing numbers
the strong painkillers, to take to meet our of deaths related to
opioids, it is possible to standards and make prescription drugs is in
buy hundreds of drugs sure that people obtain need of safeguarding
that are all delivered to medicines safely online,” imminently…
the same address.1 said Duncan Rudkin, the
1. https://www.theguardian.
chief executive of the com/society/2018/jul/25/
With no alert system General Pharmaceutical online-pharmacies-fail-spot-
in place flagging up Council (GPhC) when multiple-opiate-orders-
addiction?CMP=Share_iOSApp_
1. https://www.ft.com content/e394d54e-ae16-11e8-8d14-6f049d06439c whether or not multiple speaking to The Other
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 11
Opinion

Proper evaluation
of the relevant IP
landscape is crucial
if you wish to be one
step ahead of your
competitors.

EXPERT ADVICE
Here, Dr Natasha Varvogli, intellectual property consultant, and Maria Andrielou, marketing & communication
at VIO Chemicals, look at patents and their role in the pharma industry, asking the question whether they
are complicating business or enhancing opportunities?

W ith pharma’s portfolio shifting substantially toward new product types

and personalised treatments, process technology needs to overcome
multiple challenges across the supply chain. Competition is fierce and the
need for new and revolutionary solutions for drug development starts as early
as the selection of the optimal route of synthesis and starting material, often
calling for ‘out-of-the-box’ thinking.

Breakthrough solutions, as small as they may be, can drive your business
forward. Nevertheless, if you have not considered the intellectual property (IP)
landscape, then, you have only developed half a solution, which can drive your
business right into the ground.

STAY A STEP AHEAD

Proper evaluation of the relevant IP landscape is crucial if you wish to be
one step ahead of your competitors. In today’s era of abundant knowledge
and technological advancements, where businesses grow across borders
and continents, the intangible assets of human intellectuality cannot be
underestimated.
12 www.epmmagazine.com

Analysing the IP landscape will give be regarded as an invention, depends infringement of IP rights is called ‘freedom-
you a competitive advantage to avoid on a number of factors determined to-operate (FTO) search’. To perform an
roadblocks and see hidden opportunities. by patent offices. Then the expert will FTO search properly, one not only needs
It will also draw your attention to issues guide you through all available options, to know and understand patent language
that require frequent monitoring and, why analyse the cost, the markets you and but must also be up-to-date with key
not, lead to an unforeseeable opportunity your competitors are active in and the patent issues across major markets.
for the near future, upon change of facts. relevant timelines.
Through this search, you can identify
Just think of the multiple questions you are Why do you want an expert? and retrieve patents or patent
faced with when you are about to design, applications that are or could potentially
develop and manufacture a new product: For many reasons. Firstly, a novelty search become roadblocks in your commercial
• Are there any IP restrictions related to requires solid experience in process activities. The evaluation of the search
the specific product or activity you are development to become effective. A results requires specialised knowledge
planning to commercialise? single search is almost never enough and to assess:
• If there is room for innovation, can you professional patent searchers perform in- • the scope of the claims;
create an IP asset and use it to become depth bibliographical research in multiple • the legal status of the patent: that is, if
competitive? databases, driven by multiple strategies. the patent is still active and where, or
• How can you overcome any IP if it is under some kind of invalidation
restrictions? Secondly, an expert can file a patent procedure;
• Are there any possible IP rights (IPRs) application in a proper manner. Preparing • and the validity of the claims of a pending
that a competitor might obtain? And a patent application is a highly meticulous patent application: meaning, if it is likely
how can you work around them? task. If it is not done properly from the to get granted and with what scope.
• And, last but not least, how can you beginning and the patent application
ensure that you won’t stumble upon goes public, there is no turning back, and All those issues need to be considered by
any legal bottlenecks if you plan to filing another patent application for the taking into account the technical language
manufacture or commercialise your same invention is not possible. of the claims and any special rules that a
product in a country other than in specific country or region may enforce.
Europe? Thirdly, an expert understands the
implications caused by the differences in IN OR OUT OF EUROPE?
The breakdown before the breakthrough procedural law across borders and can save Europe differs from other major markets
In a hypothetical scenario you and your you from embarrassing and irreversible in an important aspect: the European
R&D team have come up with a solution situations. Every patent office operates and Patent Office. This common route
for a manufacturing process, which examines patents under its own rules. chosen for commercial activities within
is easier, cheaper or faster in a novel the European territory has the task of
manner. Do you need a patent to employ SAILING IN SAFE WATERS issuing patents effective across the
it in your business? Does a patent give Maybe your business is not driven majority of the European countries,
you the right to manufacture and/or sell by innovation and you are offering a but it is not entitled to decide on the
your product? well-established product. You still need infringement of a patent. This is a matter
to ensure that it is IP free in the place resolved, for the moment, only within
What is a patent good for? of manufacturing. And what about the national jurisdictions.
manufacturing process itself or the
The short answer is: to prevent starting materials? If you manufacture and/or plan to
competition. A patent does not give you commercialise your product outside
the right to commercialise your invention, A successful product or manufacturing Europe, you need to be extra cautious
but it will stop others from doing so. This process may be patent-protected by when you analyse the IP landscape and
is an intangible asset that can provide the same token it would make sense file a patent. Take the case of China:
your business with a unique opportunity for you to own IP rights for something European firms have long complained
to grow. useful and innovative. Taking into account that patents in China are often misused
that a patent may last for 20 years, your and enforcing their IP rights in the country
What steps should you take to obtain a business might relate to something well- stumbles upon local judicial protectionism
patent? established, but you may not be ‘off the and ill-fitting law enforcement rules.
hook’ for a critical time span of two to Despite efforts for progress and reform,
Seeking expert support is your only three years. you still need an expert to cope with
option. At first, the expert will perform China’s IPR regime, avoid future violation
a novelty search to ensure that what LAUNCHING A NEW PRODUCT of your IP rights and get a fair share in
you are seeking protection for is indeed The procedure by which your business China’s market and courts.
something new. Whether or not this can activities are checked for possible
 DIGITAL intelligence
MEDIAMORPHOSIS.it

The growing commitment towards digitalisation of production systems

is leading us to Industry 4.0, the new industrial revolution that will change
the way we work and live.

Thanks to this evolution, we will be more and more connected:

collaboration will become a new form of intelligence.

At IMA, the work we do and the way that we think about the future
have always combined to create one big collective brain.
With digital systems, even more so.

www.ima.it
14 COVER STORY

Path of least resistance

Safety by design is fast becoming recognised as an integral part of tablet manufacture,
where it can be used to improve medication adherence. In this feature, Jason Teckoe,
Technical Director, EMEA at Colorcon, examines tablet design aspects in more detail,
paying particular attention to swallowability…

In an environment where the

senior population is on the rise
and more people are taking
the importance of ‘safety by
design’, drawing attention to
tablet dimension, coating and
damage or dusting issues often
associated with uncoated tablets.
The recent focus on medication
multiple medications and dietary appearance.2,3 errors has led regulatory bodies
supplements (some of which to consider tablet differentiation
are large tablets and capsules), TABLETS AS PREFERRED ORAL more prominently, encouraging
swallowability is a growing concern. DOSAGE FORMS manufacturers to think more about
Regulatory agencies around the Tablets remain the most common the patient’s perspective and
world provide guidance regarding solid oral dosage form for whether they are likely to follow
the importance of tablet coating to many reasons, including ease the recommended dosing regimen
not only address differentiation but of manufacture, convenience outlined in their prescription.
to ease the swallowing of tablets for the patient, accurate dose
and capsules to improve patient administration and good stability. The FDA, for example, has released
safety and compliance. two industry guidance documents
Good tablet design can be used on this topic4,5 intended to champion
SAFETY BY DESIGN TO TARGET to provide product differentiation, the patient’s perspective, improve
PATIENT ADHERENCE avoid medication mix-ups and patient compliance and medication
Medication errors are reported to deter counterfeiting. The regulatory outcomes. Adding a coating to a
harm 1.5 million people every year, agencies consider ease of previously uncoated tablet would
some of which result in sickness, swallowing and patient compliance improve patient compliance and
injury and death. It is estimated that important issues for manufacturers bring the tablet in line with the FDA’s
between two to 14% of patients to address, taking into consideration: recent recommendations.
are admitted to hospitals due to • Tablet size and shape
medication errors, and around one • Tablet coating and colour SIZE AND FINISH MATTER
to two percent of those patients are differentiation Now, more than ever, it’s
harmed as a result.1 increasingly important to create
The number and variety of easily distinguishable tablets.
These numbers are alarming medicines available increases and Similar looking tablets — especially
considering most, if not all patients are now taking multiple plain white ones — can be readily
medication errors could be medications and living longer. confused by patients, pharmacists,
prevented. Further, these statistics Administration of medicines may be caregivers and even manufacturers.
only include those medication errors carried out by several healthcare
that have actually been reported. professionals and communication Smaller is also better. An FDA
failures can lead to mistakes. guidance on tablet design reports
The World Health Organisation By creating your dosage form with that complaints from patients about
(WHO) also reports that poor patient the patient in mind, you can make a swallowing increase when tablets
compliance can lead to additional tablet easier to swallow, both literally have diameters exceeding eight
medical costs and adverse health and figuratively. millimetres. And the agency states that
outcomes, which is why regulators the largest dimension of a tablet or
around the world have decided to From the patient’s perspective, capsule should never exceed 22 mm.5
step in. coating makes the tablet appear
easier to swallow and aids in visual In practice, formulators can address
Recent guidance from both the differentiation, thus reducing size by selecting ingredients and
US Food and Drug Administration the potential risk of medication process to effectively minimise
(FDA) and the European Medicines errors. The coating also reduces overall tablet weight and size.
Agency (EMA) highlights tablet friability and overcomes any Even so, we know that dose
 www.epmmagazine.com
15

strength, compressibility and

other factors make it a challenge
to keep tablet size down.
…coating makes the tablet
CHOOSING THE PATH
OF LEAST RESISTANCE easier to swallow and aids
Coating makes tablets easier in visual differentiation,
to swallow and improves tablet
mobility; this is recognised as even
thus reducing the potential
more important for elderly people risk of medication errors.
(recent EMA guidance).3 And as far
as coating goes, the glossier the
finish and more slip it can provide,
the better.

Through extensive research REFERENCES:

and development, Colorcon has 1. United States Institute of Medicine, 2006.
created a unique coating system 2. FDA Guidance: Safety Considerations for Product Design to
to address this recognised and Minimize Medication Errors. https://www.fda.gov/downloads/drugs/
guidancecomplianceregulatoryinformation/guidances/ucm331810.pdf)
growing patient problem. This new
3. EMA Guidance; Good practice guide on risk minimisation and
Opadry EZ, Easy Swallow Film prevention of medication errors. http://www.ema.europa.eu/docs/en_GB/
Coating has been found to provide document_library/Regulatory_and_procedural_guideline/2015/11/
WC500196981.pdf)
increased motility during the
4. https://www.fda.gov/downloads/drugs/
swallowing process, satisfying both guidancecomplianceregulatoryinformation/guidances/ucm331810.pdf
the perception and reality of easier 5. https://www.fda.gov/downloads/drugs/guidances/ucm377938.pdf
swallowing, in a recent study.

The swallowability study, conducted

by the University of Birmingham
(2018, in preparation for
submission), aimed to assess the
potential for coatings to improve
swallowability and to evaluate
the mouthfeel of coated versus
uncoated tablets. Participants
evaluated the swallowability of
tablets along with their mouthfeel,
described as roughness,
adhesiveness, slipperiness, and
palatability. The study results
confirmed that presence of coating
improved the ease of swallowing
and that uncoated tablets are
clearly different to the coated
tablets, being more difficult to
swallow with poor mouthfeel.
Tablets coated with Opadry EZ
coatings were found to be most
palatable from all the samples.
Uncoated tablets rated as the least
acceptable for the participants.

So, remember, when designing a

tablet to ease swallowing, make it
small, oval or a shape with more
rounded edges, and don’t forget
the coating.
16 ARTIFICIAL INTELLIGENCE

Unify and conquer

According to Frank Austin Nothaft, GTM lead for Genomics, Databricks, a unified approach
to big data is the best way to get the most value. Here, he tells us more…

W ith the cost of sequencing

dropping dramatically
over the last decade, genomic
profile provides insight into
their biology, genomic data is
most powerful when viewed at
Cloud computing allows elasticity
around data infrastructure. Large
public cloud companies have all
data volumes have grown a population scale and with the made huge strides in readying
exponentially. By 2020, genomic added context of phenotypic their services for enterprises.
data is expected to be reaching datasets like EMR and imaging These public cloud platforms
upwards of 40 exabytes per year.1 studies. now have more security and
Pharmaceutical companies are controls implemented around
rushing to tap into this genomic While bioinformatics tools have data that is being stored in them,
data goldmine in hopes of traditionally been designed for essential when managing highly
accelerating the costly long-tail of on-premises High Performance sensitive data.
drug development. Computing (HPC) architectures, it
is difficult to scale these storage GENOMIC DATA NEEDS UNIFIED
Early population sequencing systems to petabyte/exabyte ANALYTICS
efforts, such as the Geisenger/ volumes of data in a cost- As commoditised sequencing
Regeneron DiscovEHR effective manner. allows more organisations to
collaboration,2 have demonstrated gain access to massive -omic
the ability to identify novel links For a pharmaceutical R&D team, datasets, success will be
between genomic variants the real value in advanced determined by an organisation’s
and phenotypes of interest. analytics is obtained once these ability to rapidly turn raw genomic
By using information gleaned techniques can be made easily data into actionable biological
by integrating genomic data accessible to domain scientists. insight. A disjointed approach
along with phenotypic sources, Following the example of the to data forces bioinformaticians,
pharmaceutical development Regeneron Genetics Center, computational biologists and
organisations can more precisely advanced analytics can provide bench scientists to work in silos,
target treatments to the underlying tremendous value when deployed which hampers the discovery and
biology driving a disease. through a web portal that allows analytics process.
bench scientists to rapidly drill
This can result in more effective down on the data that supports Building a homegrown
drugs with reduced side effects a link between a gene and a patchwork solution of tools and
and accelerate time to market. phenotype.3,4 technologies pulls valuable
However, a number of technology cycles from domain scientists
hurdles must be overcome for ACHIEVING AGILITY AND SCALE whose expertise is in the biology
REFERENCES:
organisations to fully draw value IN THE CLOUD rather than large-scale data.
1. http://journals.plos.
org/plosbiology/ from their genomics data with One approach that By leveraging cloud computing
article?id=10.1371/journal. advanced analytics and machine pharmaceutical manufacturers technologies to rapidly analyse
pbio.1002195
learning. have traditionally leveraged for genomic data along with
2. http://www.
discovehrshare.com/
large-scale bioinformatics is bioinformatics platforms that
3. https://databricks.com/ THE CHALLENGES OF LARGE- on-premises HPC architectures. bring together large-scale
session/building-the-future- SCALE GENOMIC ANALYSIS Unfortunately, the financial model data processing and advanced
of-drug-discovery
The sheer scale of genomic for managing an HPC installation analytics in one connected
4. https://databricks.com/
session/insights-from-
data is daunting, as a whole requires a significant up-front toolset, disparate teams across
building-the-future-of-drug- genome study can have CapEx investment, which does bioinformatics, computational
discovery-with-apache- upwards of 100GB of data not eliminate OpEx. An alternative biology, and bench science can
spark
per individual. While the data approach is to use cloud be unified to accelerate R&D.
5. https://datascience.nih.
gov/blog/cloud from one individual’s genomic computing.
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18 ARTIFICIAL INTELLIGENCE

BRAVE NEW WORLD

Machine learning offers considerable potential for streamlining and transforming routine
information processes in life sciences — but could more creative applications of artificial
intelligence take things further still? AMPLEXOR’s Siniša Belina assesses the opportunities…

T he scope for artificial

intelligence in life sciences
is potentially significant —
THE HUMAN-MACHINE
CONTINUUM
Although countless articles have
bolder hypotheses and deeper
and more targeted work, to
accelerate discoveries and the
enabling accelerated scientific been written about the threat to development of treatments.
breakthrough, thanks to new people’s jobs presented by AI, if
potential to identify the minutest machines can get to grips with SCALING DATA MOUNTAINS
anomalies in unwieldy global data routine knowledge work and do Machine intelligence at scale also
masses, and facilitating greater it more rapidly than humans ever offers a viable means to track
drug personalisation. could, why wouldn’t companies global patient trends, concerns,
want to take advantage — experiences, behaviour and needs,
Far from hovering on some especially if it allows them to free enabling the life sciences industry
futuristic horizon, the technology up experts for more advanced, to understand what is happening
is already available too — which value-added work? in the real world — to a degree that
means pharma companies need hasn’t been possible previously.
to build it into their agendas and AI technology offers to transform This offers potential not only for
plans now, if they don’t want to risk patient outcomes — as is already more proactive and thorough
sacrificing competitive advantage. being seen in frontline patient monitoring of adverse events
From intelligent internet and diagnostics. UK researchers in and other safety signals as drugs
content searches that adapt to Oxford recently announced the move into markets, but also for
user preferences, to automated availability of AI technology that identifying emerging requirements,
personal assistants like Alexa and can diagnose heart disease and triggering new innovation.
Siri, and customer care channels lung cancer at a much earlier stage
such as web chat, AI is already in from analysis of patient scans.1 Where the life sciences industry
common use as part of people’s Meanwhile, connected devices are has traditionally been one step
routine activities. being used increasingly to transmit removed from patients, public
patients’ data to those managing internet forums and social
One of the great appeals of AI is their care — to enable earlier networks offer an opportunity to
the scope for process automation interventions. understand evolving demands and
and acceleration, using clever engage with patients in new ways.
algorithms that can complete In pharma, machine intelligence AI is already proven for social
complex tasks previously limited to has substantial potential for media monitoring in other markets,
human capacity. The technology enhancing R&D, through the whose best practices could be
is also highly adaptive — machine ability to analyse large volumes carried across to life sciences with
learning tools can be guided to of data leading to richer insights. a few adjustments.
respond to the conditions they To this end, applications, systems,
are exposed to and the results and platforms have already been For all the excitement around AI,
they find, so that they get better developed to transform clinical though, the life sciences industry
REFERENCE:
and better at the job they’ve been trial innovation. This isn’t just is not exactly known as an early
1. AI early diagnosis could
tasked with. So over time they are about distilling subtler patterns adopter of new technology. So,
save heart and cancer able to absorb more and more from once unmanageable volumes there are a number of things that
patients, BBC News, human tasks, to the point that the of disparate data either. It is also need to happen if companies
January 2nd 2018: http://
www.bbc.co.uk/news/ only intervention needed is in the about modelling and extrapolating are to adapt to and exploit the
health-42357257 form of supervisory quality checks. from such findings to arrive at potential ahead of them.
 www.epmmagazine.com
19

TESTING AI’S POTENTIAL speed to market. (Using machine responsive and patient centric.
Once firms have accepted that learning, systems could ‘learn’ how But this relies on a strong sense
change is coming, the next step to produce better output, or the of purpose and a foundation of
is to prepare an IT and data conditions most likely to result in a rich, ready-to-exploit data. So,
environment which allows for new new marketing submission being if companies are going to start
experimentation and insights — accepted first time.) anywhere, this is as good a place
within the restrictions of regulatory If data preparation work has to be as any.
control and privacy protection. done to fulfil regulatory demands,
why not exploit this — laying the
This isn’t just about developing foundations for future innovation,
‘big data’ strategies, but rather and testing just how powerful AI
preparing that data so it can be can be in transforming everyday
analysed efficiently, accurately and processes?
holistically using AI platforms — to
spot emerging trends, anomalies, The critical enabler for maximising
concerns and opportunities in a the potential of data is the creation
very efficient and granular way. of a comprehensive master data
model — one that also includes
For now, regulatory pressures are inter-dependencies between One of the great appeals of AI is
driving most data-related initiatives the data, in a way that can drive
in life sciences. So, this is a good new efficiencies and increased
the scope for process automation
place to start with AI — even if impact through proactive process and acceleration, using clever
just for taking over some of the automation, boosted by AI/ algorithms that can complete
more repetitive or preparatory machine learning. Today, just
stages of submission creation, or about every life sciences business complex tasks previously
content checking, to accelerate is striving to be more agile, limited to human capacity.
 MED-TECH INNOVATION EXPO
15 - 16 MAY 2019 NEC | BIRMINGHAM | UK
medtech | digital healthtech | medical plastics | manufacturing
software | inspection and metrology | regulation | design
early stage innovations | pharmaceutical manufacturing

MAKE
SALES
AT #MEDTECHEXPO

of exhibitors surveyed said they made

sales at Med-Tech Innovation Expo or
would as a result of exhibiting.

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 ARTIFICIAL INTELLIGENCE
21

The next
dimension
As we go further down ‘the rabbit hole’ in terms of
technological advancements, we discuss augmented reality
and its uses for pharma manufacturers with Jean-Yves Balfin,
product manager at Korsch, which has recently launched
PharmaView* — a mixed reality environment.

M ore and more we are

witnessing increasing
applications of technology across
The control that can be gained
from this sort of assistance
has massive potential from a
all areas of life. Augmented manufacturing perspective.
and virtual reality has found Any potential faults or
use in many sectors and, as maintenance that may be
can be viewed when walking required to the machinery can operators and companies should
the vast exhibition halls of any be caught much earlier and consider? “When using a mixed/
pharmaceutical event nowadays, help to streamline processes. augmented reality environment,
is securing its position within the operator is not immersed
healthcare too. Another important function in a completely virtual reality,”
that can be gained through said Balfin. “This means that the
But how can this advancement augmented reality is training. operator doesn’t lose contact
truly help pharmaceutical “Realistic three-dimensional with the real environment but
manufacturers? “The sort of training at scale in the presence simply has holograms and
mixed reality environment that of the machine provides the additional information beamed
we can now create can raise opportunity to instil the best in around them to combine
both efficiency and safety practices for machine operation with the real surroundings.
in machine operation to a and service,” added Balfin.
totally new level,” explained However, it was noted that care
Balfin. “We have based the As augmented reality can delve should be taken in some areas,
PharmaView on the Microsoft deeper into the subassemblies of such as defining the safety
HoloLens-technology, which the machine through holograms distance for machine remote
beams holograms and additional it is possible to train operators control as well as the duration of
information into the user’s actual with virtual tutorials in a way time the operator wears the smart
visual axis, enabling hands-free, that is not really possible in the glasses, which obviously should
interactive capabilities.” real-world. “We have also looked comply with health regulations.
at training prior to delivery of
These interactive capabilities machines and will aim to do this “Augmented reality, such
include operational assistance with PharmaView,” he continued. as the PharmaView, is the
through holograms to assist in “In this way, downtime can be first step towards enhanced
setup, operation or maintenance, reduced and it also gives the communication between operator
multimedia support that can be companies more flexible options and machine,” concluded Balfin.
directly beamed into the smart for training.” “Artificial intelligence will lead
glasses, machine control and to further steps in this exciting
operation as well as a virtual But what of safety, are there technological journey.”
service via secure video any potential safety issues when
call function. using augmented reality that *PharmaView is a registered trademark of Korsch.
 FROM THE EDI TOR

The final countdown

As we close in on the date for companies to be serialisation compliant vast gaps in industry preparedness
have become apparent. The final countdown is on and it’s time to get serious about serialisation…

E arly on in August we passed

the six-month marker before
pharmaceutical companies will
the final hours of serialisation in
both the US and EU, the industry-
wide lag in full serialisation
be required to comply with the implementations remains a concern
European Falsified Medicines and emphasizes the criticality of
Directive (FMD). For some, who trade partner connectivity within
have gotten their preparations the supply chain.”
underway, this milestone will go
without much notice but for others In this special section of our
it may be a wholly different story. September issue, we are focusing
on serialisation, looking at the
The Falsified Medicines Directive potential challenges and benefits
(FMD) 2011/62/EU, which is due that being compliant with the
for adoption in February 2019, will upcoming legislation may bring in
require pharmaceutical companies more detail. Also, we discuss the
to apply serialisation codes to every potential of blockchain and how to
applicable pack. The impending drive value beyond compliance.
legislation will affect all prescription
medicines for the European market But, it is important to remember that
and as underlined by Gill Wright the final countdown is now on and
from Cirrus, it is here to stay overwhelmingly key opinion leaders
irrespective of Brexit!1 in the industry are all advocating the
same thing, there is no one-size-
In a recent survey performed by fits-all solution and if you haven’t
TraceLink a large gap in industry already done so, take action now!
readiness for drug serialisation
was highlighted.2 Only a third of
respondents of this survey stated
they are ‘very prepared’ for the
upcoming deadlines in both Europe
and the US and none reported CONTENTS
completion of all of the fundamental
steps for serialisation compliance.
24 THE MISSING LINK?
Looking at the significance of blockchain in closing the supply
chain trust gap.
“These survey results are startling,”
commented Shabbir Dahod,
26 THINKING LONG-TERM
president and CEO of TraceLink.
Here, David Carpentier, Adents, reveals how tech solutions may add
“Despite goodwill efforts by
serialisation return on investment.
industry and regulators to meet
compliance on time, the industry is 28 GO THE EXTRA MILE…
extremely behind in being ready for
Evaluating the value of serialisation beyond compliance and outsourcing with
serialisation. In 2018, as we reach
six leading solutions’ providers.

30 MEETING SERIALISATION HEAD ON

Discussing how best to meet the serialisation interoperability challenges
head on and drive return on investment.
REFERENCES:
1. https://www.epmmagazine.com/opinion/the-clock-is-
ticking-for-fmd-compliance/
32 THE KEY TO SUCCESS
2. https://www.epmmagazine.com/analysis/serialisation-
In this interview, Simon Cole, Atlantic Zeiser UK, points out why blockchain is
survey-highlights-large-gap-in-readiness/ gaining importance and what effects can be expected from Brexit.
24 SERIALISATION SUPPLEMENT | SYSTECH

The missing link?

In this article, Joseph L Lipari, director, Cloud Implementation Services, Systech International,
reveals the importance of blockchain in closing the supply chain trust gap.

E xperts agree that there exists

a fundamental gap in the
supply chain today. That gap is
This ecosystem is missing a layer
of trust, a layer which will protect
that critical data and will provide
CONNECT THE PHYSICAL
TO THE DIGITAL FOR
COMPLETE TRUST
trust. Manufacturers, distributors, an attestation of ownership If your supply chain challenge
importers, exporters, logistics and integrity. demands comprehensive
providers, health systems and   visibility and trust, consider this:
many other trade partners BUT HOW? connecting the physical product
have had their sights set on Blockchain relies on cryptography, itself with a trusted digital identity,
compliance as deadlines rapidly distributed ledgers and ensuring authenticity when an
approach. I would argue that consensus to provide trust. event is recorded and managing
as regulations come online, the The cryptographically hashed all the transactions by a
need for a secure, interoperable transactions are distributed to blockchain network is the closed
system becomes all the all trusted participants creating a loop required for complete,
more critical. decentralised ledger. There is no absolute trust. This blockchain
dispute regarding transactions would likely be private, with
Enter blockchain, a technology because all participants agree to known, subscribed entities.
which touts values such as the same version of the ledger, When an entity joins the
immutability, security and trust. thereby achieving consensus. permissioned blockchain network
A technology that has captured they will be granted a private key,
the attention of global companies What emerges is a secure representing them on the network
across all verticals and which infrastructure for trusted companies for posting and unlocking
promises to change the way to safely exchange data backed transactions.
business is done. by an immutable platform. Will we
  look back at this period as the time This provides an additional barrier
THE TRUST GAP when blockchain revolutionised for grey market infiltration or
Let’s get in our time machine and the way not only businesses, diversion, as all the players and
rewind to the mid-1990s when but consumers transacted with assets are known in the blockchain.
a little-known company called each other? However, that link is only as strong
Amazon was just starting to sell as the established trust. Serial
books online. This time period Let's face it, as human beings numbers can be copied and the
signified the pendulum swing from the main reason we transact with blockchain would be unaware.
brick and mortar to the genesis another person is based on the
of online retail. trust we have that the other party Truly linking the physical to the
will respond as expected. digital and creating that immutable
Fast forward to today... We see That type of gut instinct trust trust requires a different approach,
more and more companies does not exist in the same manner an approach that can uniquely
close their physical doors and in the digital world. Blockchain identify two identical items.
expand their online presence. technologies have the potential to An approach that absolutely
That fundamental shift changed fill that trust gap, with one caveat. creates that trusted link.
the face of global business and
pointed consumers to websites
and portals and apps where digital
information reigns supreme.
The life sciences supply chain
is no different. With the advent Will we look back at this period as the
of serialisation regulations, time when blockchain revolutionised the
detailed digital information must
accompany physical product as it way not only businesses, but consumers
transverses the global landscape. transacted with each other?
 MED-TECH INNOVATION EXPO
15 - 16 MAY 2019 NEC | BIRMINGHAM | UK
medtech | digital healthtech | medical plastics | manufacturing
software | inspection and metrology | regulation | design
early stage innovations | pharmaceutical manufacturing

MEET
BUYERS
AT #MEDTECHEXPO

of Med-Tech Innovation Expo visitors

said they held purchasing authority
within their organisation.

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DECISION MAKERS
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26 SERIALISATION SUPPLEMENT

Thinking long-term
As the EU Falsified Medicines Directive deadline nears, CMOs & CPOs should embrace tech
solutions that add serialisation return on investment. David Carpentier, founding partner &
CTO for Adents, tell us more…

E nsuring the safety of the

pharmaceutical supply chain
has become a worldwide priority,
technologies will give CMOs and
CPOs a critical competitive edge as
the industry moves toward Industry
overstated. Similarly, the necessity
of protecting cloud storage
and securing data transmission
and two important deadlines are 4.0 connectivity. between trading partners must
about to close in on the global be emphasized.
market. With Europe’s Falsified GOING BEYOND BASIC
Medicines Directive (FMD) set REQUIREMENTS Communication standardisation
to come into full force in less Smart pharma companies are is another important issue.
than six months (February 2019), seeking out partnerships with Part of the EU FMD is the formation
and the US Drug Supply Chain CMOs and CPOs whose solutions of the European Medicines
Security Act’s deadline to be go beyond basic requirements. Verification System (EMVS), a
imposed November 2018, it Success lies in the implementation pan-European system designed
behoves all players in the pharma of systems that offer elevated so that medicines can be verified
manufacturing sector to make capability, scalability and flexibility at the point of dispensation. Upon
intelligent decisions about the — and, in turn, a high level of the FMD enactment, Marketing
systems they employ to ensure integration in terms of data Authorisation Holders (MAHs)
serialisation compliance. exchange and process alignment. that commercialise drug products
distributed in the FMD’s jurisdiction
At this critical juncture, it’s The key is to find hardware- will be required to upload their
important for manufacturers agnostic serialisation solutions product serialisation data to the
to think long-term and to seek that can adapt or scale up to meet European Hub.
ways to maximise opportunities future track & trace mandates,
for growth. Forward-thinking as well as help improve business Reporting to the European Hub will
pharma companies need to look practices. The objective is to entail generating and managing
beyond the need to print unique integrate tools that can better serialisation data compliant with
product identification codes on utilise the reams of data generated each target market. This involves
all Rx units of sale. That’s easy by the serialisation process. certification as an official OBP
enough to achieve… but what This data can be mined and (On-Boarding Partner) Gateway
comes afterward? And how can analysed to produce worth Provider — a designation
manufacturers benefit from the that goes well beyond its initial European pharma manufacturers
changes they’ll need to implement purpose of tracking and storing for would be wise to seek in
to comply with the more complex brand owner regulatory reporting. serialisation partners and vendors.
serialisation requirements? Cyber-security poses another
threat. As we move toward THE POTENTIAL OF
With an overabundance of supply enterprise-level serialisation, INTEGRATING TECH
chain data at their fingertips, it’s solutions will need to be According to the Organisation
vital for manufacturers to figure interconnected in a way that, for Economic Co-operation
out a way to harness and use this in the age of ‘Internet of Things’, and Development (OECD), an
information. Those companies can expose vulnerabilities. estimated 10% of pharmaceutical
that embrace regulatory changes products sold worldwide and 2.5%
and use them as an opportunity For those pharma companies of global imports are counterfeit.
to optimise their supply chains are considering forgoing a previously With trust and transparency of
likely to be the ones left standing planned transactional-only (Level significant concern for businesses,
amid continued consolidation. 2) serialisation system in favour government agencies and
of a more flexible enterprise- consumers around the globe,
And the same is true for their level solution (Level 4), the tighter control of supply
hired contract manufacturers importance of proper encryption chains is crucial.
and packagers. Embracing new and virus protection cannot be
 ADENTS
27

While blockchain presents obsolete, and lend themselves QUESTIONS TO PONDER

unprecedented opportunities to making adjustments as As companies move toward
to secure entire supply chains, production needs change or implementing more comprehensive,
comprehensive end-to-end evolve. A process as intricate as beyond-compliance serialisation
security means more than just serialisation requires an outsized systems, they should ask themselves
documenting transactions on number of components to ‘play several questions.
a shared ledger. nicely’ with each other, and these
ongoing transactional relationships Will my long-term needs be met
In collaboration with Microsoft, are best mediated by software. by my overall strategy?
my company recently developed
Adents NovaTrack, a platform Beyond-compliance ROI and the The most common flaw with many
that lends itself to the building creation of true business value current serialisation solutions is that
of traceability applications using requires utilising the massive they are inherently short-sighted
such technologies as blockchain, amounts of data generated by and likely to be obsolete sooner
Artificial Intelligence (AI), etc. This serialisation efforts to improve rather than later. It’s important to
marriage of technologies brings business practices. Solutions keep in mind that more stringent
comprehensive visibility throughout now exist that open new horizons serialisation regulations will be
product distribution chains and beyond regulatory compliance in phased in eventually, as the ultimate
life cycles and addresses not only terms of data analysis and machine goal is full supply chain traceability.
performance and security, but also learning tools.
governance and scalability. Why invest in a technology that
The bottom line: Smart pharma will need to be replaced in the
CONCLUSION companies, CMOs and CPOs near future?
The need to find creative solutions require comprehensive solutions
to address both current and to help meet the challenges of Serialisation solutions should not
emerging serialisation and track current and future serialisation be approached as one-time, single-
& trace regulations is clear. deadlines. To meet this need, new use drop-ins; rather, they should be
tools to strengthen and future- scalable systems that can address
Hardware-agnostic solutions proof supply chains continue to rolling deadlines with phased-in
are part of the answer, as they be developed — of which Adents requirements.
are much less likely to become NovaTrack is one example.
What knowledge have we gained
since starting the serialisation
implementation process?

Having come to a greater

understanding of the serialisation
process, we need to look back and
consider what we have learned.
What have we done correctly?
What might we have done
differently? What improvements
can be made going forward?

it’s important for

manufacturers to think long-
term, rather than short-term,
and to seek ways to maximise
opportunities for growth.
28 SERIALISATION SUPPLEMENT | ROUNDTABLE

GO THE EXTRA MILE…

As we draw ever nearer to the time that compliance with the European Falsified Medicines
Directive (FMD) is required, we discuss the value of serialisation beyond compliance and
outsourcing with six leading solutions’ providers…

VALUE BEYOND COMPLIANCE OUTSOURCING: BEFORE IT’S TOO LATE

While investment in serialisation is being driven by compliance — The FMD is likely to push many CDMOs away from packaging
businesses should look to add value to their operations altogether, as some don’t have adequate resources to continue
by implementing hardware and software solutions that offer this while also delivering serialisation. The outcome of this will likely
multiple processes. be CDMOs partnering with CPOs, which should be better prepared
Aggregation may not be a condition of FMD but most global for the new regulations. This will allow them to deliver the services
regulations require it, and many pharmaceutical businesses desire that their clients require while meeting FMD compliance.
it of their partners. Adding aggregation capabilities to a packing line For CDMOs large enough to operate from multiple sites,
after, instead of in conjunction with a serialisation solution will centres of excellence for the implementation of serialisation
be costly. may become necessary.
Paolo Landriani, technical department director — SEA Vision Staffan Widengran, director corporate projects, Recipharm

As the legal landscape for drug serialisation continues to evolve, Time is simply too tight to be able to tackle the challenge of
companies must look beyond short-term compliance requirements serialisation independently. Many companies are now considering
and the next major deadline to consider how this will adapt to future external serialisation solutions simply because they have
legislation, both in the markets they currently cater for, markets they underestimated the scale of the challenge. Many are either still
intend to enter in the future and relevant markets that are not struggling to understand what is required, do not have the in-house
yet regulated. expertise or have misjudged the time and resource requirements,
Future-proofing solutions can be more easily achieved when not to mention the upfront investment involved.
outsourcing as a partner contract packaging organisation (CPO) Engaging the support of a CPO can help to minimise these hurdles,
can look beyond the day-to-day and will be more versed in the with tried and tested lines, as well as access to expert knowledge
potential future requirements. making the process more straightforward, efficient and stress-free.
Colin Newbould, director of regulatory affairs and QP services Dexter Tjoa, director corporate strategy, Tjoapack
at The Wasdell Group
Serialisation is far more complex than just placing a barcode
At FutureLink 2018, industry leaders from across the sector on a package. To ensure that all the dynamics of the equipment,
discussed the ways they plan to drive increased business value the data, and the processes work as they should, implementation
from their serialisation solution in a series of polls. cannot be treated as a project for just one or a few functional
When asked in which areas they would use predictive analytics areas. It requires changes and adoption of new technology and
to inform their decision making: processes in almost all areas of an organisation and the supply
chain. Collaboration with each functional area can help to avoid
63% of respondents said supply and demand forecasting,
challenges and missed opportunities. Organisations should partner
16% said inventory management, and leverage product solutions that are proven in serialisation and
and 13% said it will influence decision around operating costs. can help aid in not only meeting the minimum requirements but
Attendees were also asked what areas of the supply chain would can be scalable to provide additional functionality and services.
most benefit from serialisation data, 35% said supply chain services Being innovative and flexible by making smart investments early
including recall management. on can help set the stage for moving beyond compliance.
Dan Walles, VP Solution Marketing, TraceLink Lauren Catalano, technical services manager at Sharp
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30 SERIALISATION SUPPLEMENT

Meeting serialisation
As we get closer to the deadline for the European Falsified Medicines Directive and the need
for companies to be fully ready for serialisation, Markus Rosenkranz, leader Serialisation
Solutions, Rockwell Automation EMEA, discusses how best to meet the interoperability
challenges head on and drive return on investment.

T he need for pharmaceutical

companies to introduce
serialisation technologies into
are on course for forthcoming
EU (February 2019) legislation.
Many more however, are faced
drugs manufacture and distribution with a steep learning curve or
to meet existing, incoming and implementation challenges to
future compliance requirements remaining compliant; not least
is well documented. overcoming the significant
interoperability challenges
It’s difficult to overstate the scale of an extensive supply chain.
of damage caused by drugs
counterfeiting; the human cost MEETING THE SERIALISATION
in lives lost and the suffering CHALLENGE
associated is incalculable. While the regulations make it
Widely reported cases blaming clear that serialisation is the
counterfeits include contaminated solution to protect the supply
blood-thinner medication, home chain from rogue elements
Botox kits, erectile dysfunction and counterfeit products, it is
pills, and medicines used to battle not prescriptive about how the
malaria, tuberculosis and other life- requisite technology should be
threatening diseases. implemented. Moreover, there is
no universally adopted data format
Trusted pharmaceutical brands for capturing the aggregated track-
have suffered in public perception, and-trace information produced by
and the combined financial effect serialisation to make it available to
on the industry is estimated at partners along the supply chain.
around $75 billion per year.
At the manufacturing level, the
A reliable method to prove the new regulations require that
authenticity of drugs sold around every stage of the end-of-line
the world has been a priority for packaging process has tracking
governments and international capability. This includes machines,
regulatory bodies for several years, printers, labellers and associated
and although there is some way vision systems, including barcode
to go before a harmonised global scanners. Every stage in the
standard is possible, many regions finished goods packaging process
are well on the way to requiring must provide a unique serial
pharmaceutical companies to number to the product barcode
provide track-and-trace coding on or RFID tag.
packaging in order to be licensed.
For some products, this might
A number of companies that include five levels of what is known
operate internationally have as parent-child aggregation, with
advanced strategies and are serial numbers applied from the unit
compliant in regions already or dose level all the way up to the
requiring various levels of track- pallet level. For example, the pallet
and-trace labelling, such as the serial number is a ‘parent’ and must
US (since November 2017) or be paired to the unique case serial
 ROCKWELL AUTOMATION
31

head on numbers it contains — the ‘children’.

Similarly, the case serial number is
a ‘parent’ of the cartons (‘children’)
it contains and so on.
RETURN ON INVESTMENT
Serialisation legislation requires
investment from up and down the
supply chain, and a significant
investment from manufacturers.
INTEROPERABILITY Importantly though, as with any
One problem for many such investment, manufacturers
pharmaceutical producers at should also seek a return on
the manufacturing stage is that, investment (ROI) — beyond
historically, many have installed the indirect contribution to
‘black-box’ automation solutions a beneficial reduction in
for their packaging lines. Black-box counterfeiting. The latest
solutions often contain unique or serialisation methods can help
customised machines, customised achieve a rapid ROI by making
software drivers, proprietary the interoperability between
networks and unique application device-level machines and
software. enterprise level information
and business systems. This in
Applying such complex individual turn offers manufacturers the
identifiers retrospectively is a huge opportunity to harvest data that
undertaking that requires high can help increase throughput, aid
speed data handling capability. long-term profitability and further
Moreover, the re-engineering (and adapt their solutions to future
potentially reverse-engineering) regulation changes.
required to re-programme and
update such a system to the new A serialisation solution that
requirements, where it is even includes an integration gateway
possible to do so, often involves with preconfigured channels for
a prohibitive amount of downtime. order creation and the export
of EPCIS data that is simple to
The resulting system, if it reached integrate into the existing system
the required compliances of today can greatly reduce the up-front
would still be very difficult to engineering cost and reduce the
adapt again for new regulations time to achieving ROI.
in the future, and may struggle to
manage any regional variations to Sustainability for pharmaceutical
requirements to produce drugs for manufacturers in the face of
different markets. changing regulations now
hinges upon not just meeting
In addition to all of this, such the serialisation challenge
systems are unlikely to be able but leveraging the required
to take advantage of some of the improvement in data handling
benefits and potential return on capabilities to safeguard their
investment (ROI) of moving to a business in the digital era.
serialisation solution, such as the The good news is that through
kind of the Industrial Internet of serialisation adoption, and
Things (IIoT) gains in productivity particularly when coupled with
and efficiency possible in a the best MES technology now
modern, connected enterprise. available to manufacturers, this
is entirely possible. Moreover,
Serialisation legislation requires by partnering with the right
vendor to implement the right
investment from up and down the supply solution and lean on the recent
chain, and a significant investment from and relevant experience they
manufacturers. Importantly though, as with can bring to the factory, drugs
producers can benefit from
any such investment, manufacturers should the advantages already being
also seek a return on investment (ROI) enjoyed by early adopters.
32 SERIALISATION SUPPLEMENT | ATLANTIC ZEISER

The key to success

More and more markets require certain drugs to be serialised. Pharmaceutical manufacturers
should not lose sight of the opportunities arising from this obligation. In this interview,
Simon Cole, sales executive at Atlantic Zeiser UK, also points out why blockchain is gaining
importance in track & trace systems, and what effects can be expected from Brexit.

Q. What are the benefits of In particular, the introduction of Q. Is Brexit having an impact
Track & Trace systems to pharma additional counterfeit-proof coding on pharma serialisation?
companies and their customers? will increase security and facilitate A. Brexit is making very little
A. First of all, they fulfil legal checks for product authenticity. difference to pharmaceutical
requirements which aim to trading in the UK at present
protect the consumers against Also, these systems will although there is a noticeable
counterfeiting. Yet, these systems increasingly offer further analysis reluctance by companies to
can also do much more. For options, with a specific focus on make certain Capex purchases.
example, they can monitor process optimisation and market It is, however, unlikely that any
packaging systems as well as analysis. But customer loyalty and significant changes will be made
internal and external logistics advertising are also becoming to UK law, once the EU divorce
processes. Based on this, more important with track & trace deal becomes final. As the UK
processes can be optimised, systems, not least because of the remains a significant player
and components with best versus convenient communication options in the pharmaceutical sector,
worst performance and/or quality via smart Internet-based portal it is extremely likely that pack
can be identified throughout the systems. serialisation will have to be
entire supply chain. The overall adopted, in order to maintain
picture can also provide valuable Q. Can we expect to see a rise global reputation and access
market information for different in the use of blockchain? to worldwide markets.
regions. A. Blockchain will be the
appropriate means to ensure Q. How will the pharma industry
Last but not least, serialisation and data integrity and validity. This is regard track & trace technology
track & trace codes can be used already being implemented within in the future?
to establish direct communication some track & trace systems, e.g., A. The pharmaceutical industry
to the consumer, which opens to secure audit trail messages in will recognise that the big
the door for generating customer databases. Increasingly, however, investment in track & trace
loyalty and gaining valuable this technology will also be used technology will make our lives
customer insight. in external communications. It safer as counterfeiting will become
typically manages a peer-to-peer progressively more difficult.
Q. In the next 10 years, what network, collectively adhering This will also be beneficial for
technological developments to a protocol for validating new pharmaceutical manufacturers,
can we expect in the field? blocks. Once recorded, the data in as counterfeited products will no
A. Track & trace systems are any given block cannot be altered longer detrimentally affect their
becoming ever more retroactively without the alteration image, reputation and turnover.
powerful and of all subsequent blocks, which
secure. requires collusion of the network In 10 years from now the
majority. In this respect blockchain pharmaceutical industry will also
is secure by design. recognise additional benefits of
this technology, which will result
in optimised processes, deeper
market insight and better access
to their customers.

Finally, track & trace will become

one of the key technologies which
is essential for being successful
in the pharmaceutical sector.
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34 FORMULATION

RUN TO FORM?
GLP toxicology studies are designed to provide an insight into a drug’s safety profile,
however, formulations need to be carefully developed before these studies can be effectively
performed. In this article, Stephie Lee, scientist, Oral Drug Delivery at Catalent Pharma
Solutions, goes through the important considerations for a successful study outcome.

G LP toxicology studies are

designed to give an insight
into a drug’s safety profile. As the
crystalline form of the drug will give
sufficient exposure, based on the
efficacy and toxicity observed in
FORMULATION DEVELOPMENT
When the native form of a molecule
exhibits dose proportionality in
aim is to predict at what level a dose range-finding and escalation early pharmacokinetic studies
drug becomes toxic, the doses or exploratory toxicology studies; (often DSC Class 1 molecules)
administered are likely to be how exposure can be increased and is anticipated to give sufficient
substantially greater than those that if the drug has low solubility; and exposure, a solution or suspension
will ultimately be given to patients. what role permeability, metabolism, should suffice. It allows for great
If exposure increases with dose in transporters and efflux have dose flexibility and is suitable
a linear fashion, development is on exposure. for both non-rodent species and
likely to be simpler and responses rodents. Solubility can often be
become more predictable. FORMULATION CHOICE maximised and maintained by
A successful study outcome is optimising the pH, or adding
However, this is frequently not more probable if the approach surfactants, co-solvents, or
the case, particularly if the drug is to formulation is based on a complexing agents to the mix.
poorly soluble or permeable, where sound knowledge of a molecule’s If a solution is not possible, then
its exposure may plateau before properties. Therefore, a good a suspension may be developed
toxicity is achieved, or may not even starting point is to determine instead. Typical suspension media
reach the minimum effective level. where in the developability include surfactants like sodium
Because the exposure is neither classification system (DCS) lauryl sulphate and suspending
linear nor proportional for these it falls. (Figure 1) agents such as methylcellulose.
drugs, the lack of predictability may Appropriate suspensions should be
lead to unforeseen safety concerns Class 1 molecules, with good easy to administer at the desired
as increasing numbers of subjects solubility and permeability, are concentration, homogeneous upon
are dosed. the easiest to work with, as it is preparation, and easy to
normally appropriate to dose re-homogenise after storage.
It is therefore important to design them to animals as a solution
studies very carefully, with the first or suspension. For molecules If a solution or suspension is not
step to identify a formulation that in Class 2, poor solubility must practical, potential alternatives
can provide the exposure needs. be overcome, and some form include tablets, or capsules filled
Several factors are to be considered: of enhanced formulation should with the neat drug substance or
the toxicology dose needed to be used to increase solubility a simple blend. While these can
achieve exposure goals; which and, therefore, exposure. Those be given to non-rodent species,
animal species are being used, in Class 3 and Class 4 have low the dosage size may be too large
and what the expected translatable permeability, which can make them for rodents. The final clinical
results to humans will be; whether tricky to use as drugs. formulation is often a capsule
 www.epmmagazine.com
35

or tablet for a DCS Class 1 extrusion technologies. However, dosage form, but if the toxicology
molecule, whether the GLP physical and chemical stability formulation is, say, crystalline
toxicology studies are done with challenges are common, and they or amorphous, then the clinical
a solution, a suspension, or a solid are more expensive and difficult formulation should be too. The
dosage form. to develop than the traditional exception would be, if the predicted
dosage forms. Therefore, an human dose is much lower, then it
IMPROVING SOLUBILITY amorphous dispersion should only could be that an amorphous form
DCS 2 molecules have good be considered as a last resort. will not be necessary.
permeability but poor solubility,
and therefore a simple solution or ADDRESSING PERMEABILITY It takes time to develop a
suspension is unlikely to provide Any molecule that falls into DCS formulation for GLP toxicology
dose proportionality or sufficient Class 3 or 4 has permeability studies, and to carry out the
exposure to achieve toxicity. challenges, which makes necessary analytical work to
Bioavailability enhancement will be formulation for a GLP toxicology support development and testing
required to improve the molecule’s study more complicated. It may of the formulation. Typically, this
kinetic solubility, and possibly also be possible to promote alternative will require two to four months.
retard or prevent precipitation. uptake pathways, such as via the It can, however, save both time
However, development strategy lymphatic system or inhibit active and money in the long run, as
is not usually as straightforward efflux pumps, by using certain some of the critical questions
as for molecules in DCS 3 and 4, excipients. around solubility, permeability and
where permeability is poor. exposure for the drug will already
EXCIPIENT CONSIDERATIONS have been answered.
For those DCS 2 molecules Careful consideration of excipients
where absorption is limited by is also important: they can affect
dissolution rate, micronisation, or costs, regulatory pathway and
co-micronisation with a surfactant, timeline. If a novel excipient is
may suffice. For those that are employed to increase exposure,
solubility-limited but lipophilic, it must always be remembered that It takes time to develop a
the answer may lie in using a extensive supporting safety data
lipid-based delivery system. will be required. Others, while safe
formulation for GLP toxicology
These formulations are usually for humans, may have adverse studies, and to carry out the
straightforward to develop, effects in the animal species used necessary analytical work to
cost-efficient to make and can to conduct the study.
be adapted to give a clinical support development and testing
formulation. The formulation used in the GLP of the formulation. It can, however,
toxicology study should, ideally,
For those where solubility is a be related to the formulation that save both time and money in the
result of its stable crystalline will be used in the clinic, albeit at long run…
structure, an amorphous a higher dose than will be given to
dispersion may be necessary, human subjects. It does not have to
using spray drying or hot melt be exactly the same formulation or
36 FORMULATION

A model future
Here, Rob Harris, chief technical officer, and Matt Ling, technical
director, Juniper Pharma Services (now a part of Catalent Pharma
Solutions), explains why modelling can help to minimise the risks
associated with the development of poorly soluble drugs.

W hether it’s quickly checking

the weather forecast or using
a travel app to choose the fastest
various formulation types is both
time consuming and costly. An
approach that is being adopted
must account for the physiological
differences compared with adults
(such as rate of absorption and
route home, the use of predictive by pharmaceutical scientists is metabolism), which can impact on
technology is fast becoming a the use of modelling software to the pharmacokinetics of the drug,
prominent feature of our lives. simulate the behaviour of drugs. influencing its oral bioavailability
These can predict the stability of and overall efficacy.
In the pharmaceutical industry the drugs in formulations,2,3 in addition
use of predictive applications is to predicting drug absorption and While software modelling is
also starting to change the way we clearance from the body.4,5,6 proving to be a valuable tool
develop medicines. For instance, for assisting drug developers in
predictive technologies are now By inputting the known or streamlining drug development
helping to improve the speed and calculated pharmacokinetic programmes, the accuracy of the
accuracy of decision-making in characteristics and physicochemical simulations generated will always
formulation strategy. properties of a compound into a depend on the quality of the data
computer model that simulates the applied to the model. Insufficient
A promising orally administered human body, the virtual system can or inaccurate data will result in a
drug candidate must be sufficiently predict the uptake and clearance of model that does not reflect the
soluble within the aqueous the drug. This predictive software actual in vivo activity of the drug.
environment of the gastro-intestinal can enable drug developers to It is therefore imperative that
(GI) tract to be absorbed into the assess the merits of different drug developers are armed with
body. However, it is estimated that formulation types, narrowing the sufficient and accurate information
as many as 90% of new drug scope of required experimental to input into the model.
compounds have poor water assessment. The information
solubility,1 presenting a significant obtained can then feed into the The high proportion of
challenge for producing an formulation development strategy practically insoluble drugs
effective medicine. and help assess the overall risk of emerging from drug discovery
development. Moreover, modelling pipelines is showing no signs
Fortunately, this problem can be helps identify information gaps in of slowing anytime soon. The
addressed through the use of preclinical studies, informing the developmental hurdles created
solubility-enhancing techniques, drug developer about what further by these poorly soluble drugs will
which can improve the solubility experimental work needs to place a burden on those involved
REFERENCES: of even the most challenging be undertaken. in the process and increases
1. Am. Pharm. Rev., April drugs. Dosage forms such as risk of extended timelines and
2013, 16(3). amorphous solid dispersions, Another important area of drug extra costs. Modelling systems
2. AAPS Pharm. Sci. Tech., lipid-based self-emulsifying development where modelling are useful tools that generate
2011:12(3):932–937.
systems and nanoparticle systems software can assist is in designing meaningful data to alleviate the
3. Mol. Pharmaceutics.,
2018:15(5):1826–1841. can all provide a much-needed and developing formulations for time-consuming in vivo R&D
4. Mol. Pharmaceutics., boost to solubility. specific patient populations, which required for understanding
2016:13:3206–3215. may have different physiological and improving drug efficacy,
5. Acta Pharm. Sin B. But which solubility-enhancing characteristics. For example, mitigating the risks associated
2016:6(5):430–440.
technique is best suited for your a formulation specifically for with drug development.
6. Drug Metab. Dispos.,
2015:43:1823–1837.
drug? Rigorous in vivo testing of the treatment of young children
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38 ANALYTICAL LAB TECHNIQUES

Putting biotech on the map

Large molecule drugs are valuable for both the clinic and biotech companies, however, they
present a number of additional manufacturing challenges over small molecule therapeutics.
Here, Amy Farrell and Jonathan Bones of The National Institute for Bioprocessing Research
and Training, and Ken Cook, Suraj Patel, Alexander Schwahn and Jon Bardsley from
Thermo Fisher Scientific, reveal how the latest tools are taking the complexity out
of peptide mapping workflows.

T he biopharmaceutical industry
continues to develop protein-
based therapeutics on an ever
mapping is commonly used to
confirm the molecular structure of
peptide therapeutics and determine
used to piece together the overall
structure. Trypsin is most commonly
used for proteolytic digestion due
greater scale. From cytokines post-translational modifications and to its high enzymatic specificity.
to growth factors, hormones to sequence variants. This technique However, despite being well-
monoclonal antibodies, the growth is also used to understand how established in peptide mapping
in protein biotherapeutics has these products interact within workflows, the in-solution trypsin
been driven by their value in the biological systems and identify digestion protocols commonly used
clinic and to biotech companies. signature peptides for quantitation. for sample preparation are often
Liquid chromatography coupled labour intensive and prone to errors
However, these large molecule with mass spectrometry (LC–MS) that can compromise reliability.
drugs present a number of has established itself as a powerful With accurate characterisation
additional manufacturing tool for these purpose, and ongoing fundamental to patient safety,
challenges over conventional advances in technology mean especially in workflows that only
small molecule therapeutics. that the technique is capable of employ ultraviolet (UV) detection
Their greater structural complexity delivering powerful insights into without confirmation by MS,
and the requirement for more protein structure. robust sample preparation and
extensive manufacturing separation methods are essential.
processes mean that robust Despite this uptake in peptide Digestion protocols must therefore
quality control and assurance are mapping, the numerous, manual be reproducible and separation
essential to ensure products are steps required as part of workflows steps must be stable to allow
safe and effective. As a result, have proven time-consuming unambiguous peptide identification
regulatory bodies such as the and vulnerable to human error. based on chromatographic
US Food and Drug Administration In response, the latest advances retention time.
(FDA) and European Medicines in sample preparation, automation,
Agency (EMA) have established separation and detection are Given the importance of peptide
rigorous guidelines around simplifying peptide mapping digestion for many biotech
the control of biotherapeutic workflows and accelerating the workflows, equipment and reagent
Figure 1: Overlaid peptide maps
production protocols. collection of reliable and robust suppliers have responded by
obtained for manual digestion characterisation data. Here, we look developing kits containing all the
of the monoclonal antibody Comprehensive product at how the latest approaches are relevant solutions required for the
rituximab performed by five
people. Measurements were characterisation is essential to cutting complexity and redefining robust and reliable digestion of
obtained using a Thermo ensure these complex products what’s possible from peptide biotherapeutics. These proteolysis
Scientific Vanquish
Horizon UHPLC system,
function as intended and are mapping workflows. kits are capable of providing rapid
with UV detection. safe for patients to use. Peptide protein digestion with exceptional
ENHANCED MANUAL reproducibility and sensitivity to
PROTEOLYSIS PROTOCOLS deliver high-quality characterisation
USING DIGESTION KITS data. While traditional in-solution
Proteolytic digestion plays a key digests could often take days
role in peptide mapping. It is to perform proteolysis, some
used to break up the complex of the latest protein digestion
architecture of protein therapeutics reagents, such as Thermo Fisher
into bitesize fragments that can be Scientific’s SMART Digest kit,
 www.epmmagazine.com
39

typically take around 60 minutes Automated systems based on TOWARDS RELIABLE PEPTIDE
to reach completion. When used magnetic bead technology MAPPING, EVERY TIME
in combination with the high minimise the manual handling To ensure innovative protein
measurement consistency offered required for protein digestion therapeutics are effective and safe
by ultra-high performance liquid and ensure that the reactions to use, and reach patients in the
chromatography instruments, these involved in these workflows are shortest possible timeframe,
workflows provide exceptional levels timed to perfection to reduce the the quality assurance protocols
of measurement reproducibility. possibility of post-translational involved in their manufacture must
In fact, the resilience of the latest modifications. As a result, these be robust, reliable and efficient.
systems even allows individuals automated systems can reach The latest tools for peptide mapping
with no prior experience of levels of reproducibility that are helping biotech companies
protein digestion techniques to extend even beyond the high optimise their manufacturing
achieve accurate and reliable levels achieved using manual workflows by taking the complexity
results. Figure 1 highlights the digestion kit protocols. out of protein characterisation.
peptide map obtained through the Automated systems such as the
manual digestion of rituximab, a Thermo Scientific KingFisher Duo Thanks to powerful proteolysis
large monoclonal antibody. The Prime platform, for example, digestion kits and automated
digestions were performed by five can achieve 1.5 times less LC–MS systems, these modern
individuals, several of whom had variance in results compared techniques are accelerating output
not conducted a protein digestion to those obtained by manual and delivering more accurate
previously. In each case, 5 µL of digestion. This high level results. And because these resilient
digest solution was injected for of performance can make a protocols can be operated by
LC–MS without further purification, considerable difference when individuals of any experience level,
and the peptides were separated more complex proteins human error is minimised and more
using the gradient method. The are involved. consistent results can be achieved.
average relative standard deviation
(RSD), across all 20 peaks was 2.74.
These impressive findings highlight
the measurement robustness that
can be achieved using the latest The latest tools for peptide mapping are
workflow solutions.
helping biotech companies optimise their
AUTOMATED DIGESTION manufacturing workflows by taking the
PROTOCOLS USING
MAGNETIC BEADS
complexity out of protein characterisation.
Novel digestion technologies
are helping to further reduce the
complexity of peptide mapping
workflows by minimising the level
of human involvement required.
Magnetic beads are a proven
support medium for many sample
preparation and purification
processes in life science research,
and many of the latest automated
systems use this technology to
boost the productivity of high-
throughput workflows.
 Pharma contract services

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on market news and trends during the CPhI “CPhI is a big event with participation of
Pharma Innovation Awards and Pharma almost all pharma companies across the
Insight Briefings globe”
Shailesh Shinde
 Free access: 1 ticket, 6 shows, 150 free
seminars, innovation tours, innovation gallery Head of Business Development
and matchmaking Callidus Research Laboratories

Organised by
Join the conversation
@cphiww
 APIs/HPAPIs
41

Curb your enthusiasm…

…not all highly potent compounds require extreme containment! In this
article, Jeff Pavlovich, senior process safety engineer at Cambrex Charles
City, examines the intricacies of risk assessment and the importance
of a realistic approach.

T here is a growing demand for

capacity for the manufacture
of highly potent active
DEFINING POTENCY
If a compound has an eight-hour
time-weighted average
including the OEL. A large amount
of safety data will already have been
compiled for any molecule that is
pharmaceutical ingredients occupational exposure limit (OEL) heading into large scale manufacture.
(HPAPIs). This is partly due to the of 10 µg/m3 or less, it is deemed As well as pre-clinical toxicology and
growing number of molecules in ‘potent’. In the absence of a formal animal studies, this may also include
drug development pipelines that definition of ‘highly potent’, insights gleaned from Phase I clinical
are thought of as highly potent, however, different risk assessors trials. This is used to inform the OELs
but it also reflects the fact that may define the hazards posed by and Occupational Exposure Bands
some of these drugs are now an individual compound differently. (OEBs) determined by risk assessors,
reaching patent expiry, and are Some take a very conservative and then to select the appropriate
now subject to generic competition. view, and may decide that most containment and personal
potent molecules are in fact highly protective equipment, as well
HPAPIs need to be carefully handled potent; whereas others will deem as the engineering strategies
in a contained environment and very few to be highly potent. that will be applied.
before a synthesis is begun, a full
assessment of the potential hazards It is important to remember that However, toxicity data from
of manufacturing and handling of potency is not the same as toxicity. preclinical and clinical work do
the products must be carried out. A drug may be both highly potent not directly translate into the
As well as the HPAPI itself, every and toxic, but this is not necessarily process of determining an OEL:
reagent and intermediate requires the case. A highly potent drug is they are designed to discover
assessment, and for a contract one for which only a very small at what level the drug should be
development and manufacturing dose is required to give a dosed to humans, bearing in mind
company (CDMO) or plant manager, therapeutic effect, but by no means its therapeutic effect and the
there is a careful interplay of is it a given that it will also be highly side-effects it may cause. There is
ensuring the appropriate potency toxic. Both have an impact on the a huge difference between orally
strategy for the safety of operators way it will need to be handled in imbibed or intravenous exposure,
and the local environment, and the the manufacturing facility. and the route by which operators
avoidance of overlaying excessive might be exposed in the facility,
operating costs to customers by The first step for any risk assessment which is far more likely to be
over-specifying the containment is to gather known information about inhalation or topical
required. the safety properties of the molecule, contamination.
42 www.epmmagazine.com

It does, however, give insight to When calculating a molecule’s OEL, useful to inform containment
what effects might occur with both various uncertainty factors will be requirements. A compound in
acute and chronic exposure. included to compensate for the fact OEB1, the lowest level, is non-toxic,
Acute problems might include that not everything is known about and an OEL of 500 µg/m3 is
respiratory or lachrymatory the compound. Components that appropriate. Moving up, an OEB2
problems, whereas chronic effects can affect it include the duration compound will be more hazardous,
could be that the compound is of the study, inter-subject variation, and so the OEL has to be lower;
carcinogenic, mutagenic or a the severity of the effect, and and similarly, OEB3 chemicals
sensitizer on prolonged exposure. factors such as bioavailability, have greater hazards. The highest
bioaccumulation and banding, OEB4, represents those
THE SPECTRUM OF EFFECTS pharmacokinetics. molecules where the hazards
The dose–response curve gives are extreme, and containment
an insight into effects. At the no Some risk assessors will also must be at the forefront of
observed effect level (NOEL), include modifying factors. engineering design.
a compound has no biological These might be the slope of the
effect. Next is the no adverse dose–response curve, the clinical It is at the OEB3 level where
event level (NOAEL), which is often significance of a critical effect significant savings can be made
mentioned in risk assessments. and whether it is reversible, by taking a real-world view.
Continuing up the curve, there is and whether this is relevant A theoretical OEL is based on
the low effect level (LOEL), and the to operators within the plant. an eight-hour exposure, but if
low adverse effect level (LOAEL), the operator could only ever be
then well-tolerated doses. After the With so many uncertainty and exposed for a few minutes, then
maximum tolerated dose has been modifying factors that might be containment and protection
reached, any higher doses are included, there is little wonder that requirements are not so great.
likely to prove hazardous. In animal there is so much variability from It may be that containment within
models, ED50 represents the dose one risk assessor to the next — a normal plant will already be
at which half the test subjects will it is not unheard of for the OEL from acceptable; otherwise relatively
experience an effect, whereas at one assessor being 100 million low-cost options such as HEPA
TD50 half will experience toxicity, times greater than the OEL filters or additional soft-sided
and LD50, half of test subjects will established by another. isolators could be sufficient.
experience a lethal dose. Surrogate testing should be
LOOKING AT THE REAL WORLD used to prove that this approach
Getting around this variability will be successful.
in risk assessments involves the
application of real world context, By taking a realistic approach,
notably a consideration of what it is clear that some compounds
level of exposure risk is acceptable that might be considered highly
for an operator. A starting point potent do not, in reality, require
of one-in-a-thousand, is probably extreme containment. Isolators
more true than one-in-a-million. should be reserved for those
projects for which they are truly
Taking a more realistic view can necessary. HPAPI capacity can
have a huge impact on cost, and easily be maximised and costs
this is why the use of categorisation minimised by not using an
of molecules into OEBs is more isolator where it is not needed.

By taking a realistic approach, it is clear that some compounds

that might be considered highly potent do not, in reality, require
extreme containment.
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44 CLEANROOMS

TIME FOR A CLEAN OUT

Here, Andrew Ramage, microbiology product specialist, Cherwell Laboratories,
puts outsourcing of microbiological growth media under the microscope revealing
the benefits and what makes an ideal media manufacturer.

A nyone who manages or

works in a microbiology
laboratory will know how
factored in the cost of employing
and training staff to make the media?
The cost of running the autoclaves
of contamination and cross-
contamination. All the equipment
will be calibrated regularly
time consuming and resource daily? Equipment calibration and with a planned preventative
hungry making microbiological maintenance; balances and pH maintenance regime to ensure
growth media is. Speaking from meters as well as autoclaves? The reliable operation. The water used,
experience, during the early days cost of validating autoclave cycles? whether WFI (water for injection) or
of my career as a microbiologist Maintaining a clean environment to demineralised, will be of the highest
working in a small food testing manufacture media to avoid cross quality, so should have a low
lab, the making of media and the contamination with other media? microbial count and conductivity.
subsequent growth promotion Investigating media quality issues?
testing took up a significant Not as cheap now, is it? The raw materials will be sourced
portion of the day. Valuable time from trusted suppliers who have
when there were hundreds of Outsourcing of microbiological been vetted by the manufacturer,
samples to test and report. growth media removes all the both for quality and reliability
above from your workload. A high- of delivery. Such materials will
The autoclaves had to be cleaned quality media manufacturer will include media dehydrates,
regularly, as well as maintained do all that for you, freeing up your supplementary additives, petri
and calibrated. Any problems with valuable time and resources. The dishes, glass containers, even the
the autoclave would bring testing media manufacturer is also able labels and packaging. Combined,
to a grinding halt, especially if you to buy raw materials in bulk, which the media will be manufactured
did not have an adequate stock of reduces the unit cost compared via a validated, consistent, fully
media. The same could be said if to the relatively small usage of an documented process.
the media failed growth promotion individual laboratory.
and pH testing. After manufacture comes
ENSURING QUALITY the quality control checks
If all the above seems familiar, As a customer, you will expect the and inspection. The media
maybe it is time to consider highest quality product. To do so manufacturing process is not
outsourcing your microbiological internally is a drain on resources. perfect, so it is vital you can have
growth media? What makes a good media confidence that the media performs
manufacturer and what does a media to your expectations. There should
SHORT-TERM VERSUS LONG- manufacturer do to ensure quality? be no particulates or air bubbles
TERM SAVINGS in agar plates that may give false
You may think that making media Starting at the top level, the results, and no excess moisture on
in-house is a lot cheaper than manufacturer should have a the agar surfaces before packing.
purchasing media externally. defined, robust quality system in A good manufacturer will have a
However, that depends on how you place, in all areas of the company. thorough inspection process of the
do your calculations. At the most This will encompass sales, media before packing, employing a
basic level, you may only be looking accounts, quality, production, well-trained team able to spot the
at the cost of the media dehydrate, maintenance and warehouse. smallest imperfections.
supplements, water and containers You should expect a minimum
(petri dishes and bottles). of ISO 9001 accreditation. The quality control testing in the
laboratory should conform to the
Compared to pre-prepared media, The manufacturer will make media prescribed methods depending on
that is true. To get a more accurate in dedicated facilities of cleanroom the regulatory requirements that
reflection of the cost have you grade to reduce the chances medium will be used in. These will
 www.epmmagazine.com
45

include numerous ISO standards, OPEN AND HONEST

or GMP regulations as set out in The final point to make is that
the European Pharmacopoeia, or your manufacturer should be
US Pharmacopeia. Testing of the open and honest. It may be a A good manufacturer will always
product does not end at release, regulatory expectation you audit
the manufacturer should be able to your suppliers on a regular basis. see an audit as an opportunity to
guarantee performance throughout, Your supplier should be ready make improvements, not as a box
if not beyond, the stated shelf life and willing to host customer audits
of the product. with the appropriate personnel ticking exercise.
on hand to answer your questions.
BESPOKE SOLUTIONS They should also take on board
Does your media supplier only any issues you may find.
sell catalogue items, or can they
be flexible to meet your needs? A good manufacturer will always
To ensure minimal disruption and see an audit as an opportunity to
smooth validation of outsourced make improvements, not as a box
media you may want a product in ticking exercise.
a packaging format that is close
to what you are making in-house.
There is enormous variation in the
types of products being tested,
off-the-shelf products may not meet
your exact requirements (which
is why you are probably making
media/buffers/diluents in-house).
An exact or close match will make
validation far easier. You should
be able to talk to the supplier or
manufacturer to have media that is
manufactured to your specifications
at a sensible price.

DELIVERY AND RELIABILITY

The one thing a media
manufacturer cannot replicate
is being able to make media
immediately there and then. Even
I admit that is one of the great
attractions of making media in-
house. The manufacturer however
should be able to guarantee a
reasonable lead time on your order.
The product that arrives should also
have the maximum possible shelf
life remaining. There is nothing
more annoying than ordering an
item with a six-month shelf life, only
to find it has two to three months
remaining when you receive it.

Part of that reliability should be having

a proven track record at processing
orders efficiently. If you know of other
customers of that manufacturer, it will
be good to get their opinion on the
service they supply.
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 CLEANROOMS
47

Fresh thinking
John Rush subject matter expert — HVAC, from specialist cleanroom design
and construction provider BES, discusses strategies for designing more energy
efficient cleanrooms.

T he environmental footprint and

operational cost of a cleanroom
facility is usually secondary to
of a similar size, where air flows
are likely to be around five times
less. Consequently, part of the
pressure regimes are maintained
during these periods, much less
cooling (for humidity control) and
considerations of functionality cleanroom specialist’s remit re-heat energy (for temperature
and performance. However, the is to fully interrogate the brief balancing) is required.
aims of environmental efficiency and understand the immediate
and technical compliance are needs of the organisation, DESIGNING ENERGY EFFICIENCY
not mutually exclusive. In fact, which may result in a reduction INTO THE SPEC
a holistic approach to designing of the proposed space or a It is commonly assumed that
energy efficiency into the modification of the layout aligned cleanrooms do not need to
requirements of a cleanroom can to the equipment, processes and comply with Part L building
result in a working environment designated staff numbers, when regulations, but all cleanrooms
that meets good manufacturing preparing the user requirement can comply with Part L and it is
practice (GMP) requirements, brief (URB). often possible for them to meet
while complementing the wider the requirements for a RICS’ SKA
energy management strategy The impulse to over-specify rating for sustainable fit out too.
of the site or organisation. is often underpinned by the
lack of clarity offered by To achieve this, the cleanroom
CAUSES OF CLEANROOM current guidance, which does specialist must evolve the
INEFFICIENCY not stipulate how air change specification in line with the
Depending on the specific class requirements should be developing brief from the end
or application of the cleanroom, achieved. Moreover, common user, while using best practice
up to 60% of the facility’s energy specification practice does not data and modelling from previous
consumption is usually accounted take sufficient note of advances installations to demonstrate how
for by its HVAC system. in calculation methodology and high standards can be achieved
Ostensibly, this is unavoidable filtration technology that could using less energy. The design
because of the need to maintain enable reduced flow rates — team must also consider ancillary
a controlled environment through and enhanced energy efficiency accommodation — such as
heating, cooling, humidity — while achieving the required change areas, stores and access
control, air changes and pressure cleanroom standard. routes — to ensure the pressure
regimes. However, innovative regime strategy supports an
design approaches and bespoke Energy consumption is also energy efficient approach.
specification can reduce energy increased by the assumed
demand of HVAC systems by need to ensure an operational As the cleanroom requires more
as much as 50% by avoiding environment within the cooling energy than heating,
common assumptions and over- cleanroom at all times, despite cooling system efficiency should
specification. the disparity in particles entering be prioritised. Where possible
the space when it is unoccupied. latent (moisture) and sensible
Generic commercial thinking By altering the temperature, (heat) cooling systems should
often pervades specification humidity and air change be separated to enable the use
of the HVAC system with a parameters for non-operational of high efficiency chillers and
tendency to over-specify on a hours, energy consumption free cooling.
‘just in case’ basis. This can have can be reduced by up to two
a significant and unnecessary thirds, without de-validating For higher ISO classes (with
impact on the facility’s energy the cleanroom’s classification lower cleanliness standards),
consumption, far beyond the status. If a wider temperature where the clean air requirement
negligible additional energy and relative humidity band is is similar to the cooling demand,
loads involved in futureproofing set for non-operational hours a traditional air conditioning
a centrally air-conditioned office during initial validation, and system may be sufficient, with
48 www.epmmagazine.com

heat recovery contributing to ground source heat pumps are ACHIEVABLE CHALLENGE
the re-heat requirements of ideal for the lower temperature The core principles of energy
humidity control. For facilities outputs required by heating coils efficient building services still
with a lower ISO classification in air handling units and CHP is apply to cleanroom facilities; they
(higher cleanliness standards), an energy efficient solution for simply require a more sector-
where air change rates exceed larger sites. specific, innovation-led design
those required for cooling, partial approach. As the pharmaceutical
conditioning with separate latent Low energy plant and equipment, industry continues to be
and sensible cooling units will such as efficient boilers, chillers held to account on matters
reduce the fan, cooling and and fans can all contribute of environmental impact and
re-heat energy load. to more energy efficient sustainability, while addressing
cleanrooms, along with LED the challenges of operational
Outdoor air conditioning is lighting and presence-detection cost management, designing
the most appropriate option controls, which can enhance the energy efficiency into cleanrooms
for larger or multi-cleanroom lighting scheme while reducing is an achievable challenge that
high standard facilities, where energy waste. should and can be met.
air change rates exceed those
required for cooling. Here,
sensible cooling is provided by
a separate, primary air handling
unit (AHU), removing the need
for re-heat and enabling the …a holistic approach to designing energy efficiency
use of high temperature chilled into the requirements of a cleanroom can result in a
water from very efficient chillers,
combined with free cooling, to working environment that meets GMP requirements,
serve the primary AHU. while complementing the wider energy management
In cleanrooms requiring very low
strategy of the site or organisation
space relative humidity, desiccant
dehumidification may be
specified for use in combination
with the most appropriate HVAC.

Selection of the most suitable

HVAC approach is pivotal to an
energy efficient specification,
but it is the detail of the HVAC
design that will provide the most
substantial and sustainable
energy reduction gains.
Innovative design methodologies
for reducing air moisture content
before the air reaches the
cooling system can significantly
cut the cooling energy load, for
example, and a more complex,
multi-layered HVAC system will
use substantially less energy
over all.

HOLISTIC THINKING
An expertly-designed HVAC
should be specified in
combination with a thermally-
efficient building envelope.
The use of renewable energy
sources can also enhance
sustainability and drive down
operational costs. For example,
 So much more
than a clean surface

Research & Development

Technical Specialists
Quality Built In
Global Presence
Complete Range
Industry Experts
Validation
Innovation
Experienced
Collaborative
It’s not just about the products. It’s more than just a clean
surface. Contec prides itself on its longstanding technical
expertise, innovation and commitment to quality. Continued
improvements in lean manufacturing, safety initiatives, vertical
global integration as well as Research and Development, drive
our critical environments product range forward.
To get to know Contec’s hidden depths, give us call on
www.contecinc.com +33 (0) 2 97 4376 98 or drop us a line at [email protected]
50 CPHI PREVIEW

A CAPITAL IDEA!
As we look towards this year’s exciting CPhI Worldwide, taking place in Madrid, Spain, the
organisers detail the multitude of opportunities event attendees can profit from during their
stay in the Spanish capital.

C PhI Worldwide is back, and

this time in one of the worlds
burgeoning biotech and pharma
contract services, packaging,
machinery and more.
Focused on examining the
intersections between business
and biotech, bioLIVE will present
hubs, Madrid. The city is perfectly Away from the pharmaceutical special sessions on the emerging
placed in the centre of Europe ingredients hall, attendees will role of AI, tackling the workforce
to serve as the ideal location for also have access to co-located shortage, and the technical
following pharma trends, finding events, allowing them to easily and scientific innovations that
pharma products and meeting locate exhibitors ready to meet are shaping the industry today.
pharma people. CPhI Worldwide their business needs: Industry thought-leaders will
will be held 9–11 October at • ICSE connects the exhibit their ground-breaking
IFEMA, Feria de Madrid, Spain. pharmaceutical community ideas and technologies, ready
with contract service providers to grow partnerships in the most
A TIME FOR INNOVATION — with representatives from efficient way.
The event returns in what has clinical trials services, logistics
been a particularly stellar year for providers, data management, BEYOND THE EXHIBITION
new drugs, with an outstanding CROs and CDMOs. A series of Pharma Insight
46 FDA and 92 EU approvals Briefings provide the go-to space
• InnoPack allows buyers
made in 2017. Not only this but for pharmaceutical professionals
to investigate the newest
innovation is finally reaching looking to explore emerging
innovations in pharma
the market with the approval of therapeutic areas and new
packaging solutions, including
Luxturna heralding a new age business opportunities. In these
anti-tempering devices, drug-
of fast-tracked gene therapies. in-depth, high value seminars,
stable barrier solutions and
With over 1000 biologics under unbiased information on trends,
single dose applicator systems.
development and artificial industry developments and the
intelligence (AI) and 3D printing • P-MEC Europe features latest regulatory insights will be
technologies advancing, the international exhibitors shared — encouraging attendees
pharmaceutical market is and manufacturers from to develop strategies that will
currently a hotbed of innovation. pharmaceutical equipment grow their business.
companies focused on
In this dynamic time for the global instrumental analysis, Meanwhile a snapshot of the
pharma industry, CPhI Worldwide measuring and testing most interesting, innovative and
provides an opportunity to come technologies, materials testing, game-changing products coming
together and focus on the latest laboratory and quality control. to the market can be found in the
trends, technologies and insights. • Finished Dose Formulation Innovation Gallery. For a more
Above all else, it is a platform for (FDF) brings together every in-depth look, register for an
the industry to drive forward new aspect of the finished dosage Innovation Tour, where the CPhI
partnerships, do business supply chain, from big pharma exhibition floor will be explained
and grow. and CMO to in/out licensing with inside information on API
and dossier specialists. selection and successful generic
WHAT TO EXPECT formulation development.
AT THE EVENT? INTRODUCING…
Building on last year’s success, In a year that has seen rapid CPhI’s Women in Leadership
which saw a record 45,000 advancement in the biologics Forum (Wednesday, 10
senior pharma professionals in field, CPhI Worldwide will host October) will return for the
attendance, CPhI Worldwide 2018 pioneers from the bio-industry fifth year, in what has been
will host 2500+ exhibitors in 20 — including top industry execs, described by attendees as
easy-to-find zones covering the R&D’s innovative thinkers and a ‘wonderful opportunity to
end-to-end supply chain — from bio-service providers — at new think outside of the box, in an
ingredients, APIs, excipients, event, bioLIVE. industry dominated by men’.
 www.epmmagazine.com
51

Serving as an exceptional visitors and exhibitors to pre- commendations will be awarded

networking opportunity, the arrange their meetings. The to celebrate the innovation
forum allows women to share system automatically finds the and skill shown in the pharma
their experiences, expertise and best matches — ensuring key industry today.
leadership techniques. For the contacts are made by all.
first time this year, men will be AND FINALLY…
welcomed to join their female Additional event planning tools Hosted in the landscape of one
colleagues at this event to available online can be utilised of Europe’s burgeoning biotech
facilitate conversation around for a smoother experience. and pharma hubs, Madrid,
how men and women can work Remember to download the CPhI CPhI Worldwide promises to
together to diversify pharma. Worldwide App which provides be an unmissable opportunity
exhibitors and attendees with to discover the latest and most
Additionally, CPhI will this year a timetable of the day’s activities, innovative advancements, catch
play host to the Big Data & a list of exhibitors and their up with old contacts and form
Machine Learning Summit — hall location. vital new partnerships that will
Europe (Wednesday, 10 October) push the industry to the
in collaboration with The AWARDING EXCELLENCE next level.
Innovation Enterprise. Covering Following the incredible success
key topics such as the role of and popularity of last year’s
big data in the supply chain and awards, a greatly expanded
analytics in drug development CPhI Pharma Awards Gala
and discovery, this conference Dinner (Tuesday, 9 October) will
will bring together forward- take place at the Eurostar
thinking researchers and data Madrid Tower, with 500 influential Hosted in the landscape of one
scientists to discuss their pharma guests expected. of Europe’s burgeoning biotech
latest findings. Among the most famed
accolades in the pharma
and pharma hubs, Madrid,
STAY CONNECTED industry, former winners of the CPhI Worldwide promises to
Attendees are invited to login CPhI Awards feature a ‘who’s be an unmissable opportunity
online and use the Live Pharma who’ of pharma executives.
Connect one-to-one business Last year, over 200 applications to discover the latest and most
match making tool which allows were received, and a total of 17 innovative advancements…
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 DIGITAL HEALTH
53

Tech on trial
Recruitment into clinical trials can be a testing task, leading
to a push more recently into patient-centric approaches.
Technology is a major resource in this respect but there
are some important aspects to consider as Mike Novotny,
founder and CEO of Medrio, discusses further.

A great deal of recent research organisations utilise advancing

has looked into the top technology to mitigate these
challenges the clinical research challenges.
industry faces today, and the
conclusion always seems to be As patient reported outcomes,
for example, go electronic,
the same: Patient recruitment is
researchers are empowered to
among the greatest obstacles,
better demonstrate an investment
if not the number one, that
in the patient experience and
researchers say stands in the way ensure patient safety and comfort.
of clinical trial success. As a result, And as conversation continues
the industry has seen a great to swirl around mHealth and
push, in recent years, to make wearables in clinical trials, one
clinical research more patient- can’t help but wonder about the WHAT DO REGULATORS
centric, expand eligibility criteria, patient-centricity value of these HAVE TO SAY?
and thereby shore up enrolment methods of remote data collection: Then, of course, there’s the
numbers enough to keep their The ability to collect data regulatory question. During
studies moving. remotely, without a site visit, could technological boom times, the
significantly reduce the burden creation of innovative solutions
Technology has been a major of clinical trial participation. can outpace the evolution of
as resource for organisations the regulatory frameworks that
conversation who have embarked on these It’s necessary, however, to keep govern their use. In an industry
endeavours. How does technology any optimism cautious. For the use as sensitive to regulations as
continues to play a role in patient centricity, of next-generation technology to clinical research, this is an
swirl around and what do organisations need truly be feasible, there are some essential consideration.
to consider as they begin to take important considerations. For
mHealth and advantage of it? one, any technological platform The good news, however,
wearables in use for remote data collection is that major regulatory bodies
in clinical MEETING THE NEEDS OF will need to be able to transmit have recognised the promise
PATIENTS that data to the central EDC or of innovative clinical trial
trials, one Among the greatest factors other eClinical system in use in technology, and have moved
can’t help but behind the recruitment and the study; APIs will need to be in to announce their encouragement
retention struggles the industry place to streamline integration, and develop guidance around
wonder about faces are a wariness of unproven so that manual data transfer it. Since 2013, the FDA has been
the patient- treatments (often referred to as doesn’t slow down study timelines. officially in favour of eSource; just
the ‘guinea pig fear’) and the fact It’s not enough for a wealth of in the last year or so, institutions
centricity that, for many potential clinical trial technological solutions simply to ranging from government, non-
value of these subjects, committing to regular exist; they need to be able to work profits and the private sector
methods of site visits over a period of months with one another, as well — and have collaborated to hash out
or years is inconvenient or simply until they do, it won’t be feasible guidance and recommendations
remote data unfeasible. In this light, it will be to harness them for patient for the use of mHealth technology
collection interesting to see to what extent centricity or any other purpose. in clinical trials.
 DIGITAL HEALTH
55

Get connected!
John Rush subject matter expert — HVAC, from specialist cleanroom design
and construction provider BES, discusses strategies for designing more energy
efficient cleanrooms.

P harmaceutical makers have a

patient engagement problem.
Wearable makers have a user
Pharma companies also want
access to patient data in as many
forms as are available, beyond
Gray Matter Analytics announced
the launch of its CoreTechs
Analytics as a Service solution for
engagement problem. Each could clinical trials. But therapy makers providers. It leverages advanced
be the other’s solution. But first have historically been the furthest machine learning to continuously
they need to understand exactly away from patients and their data, improve data quality and allow
what they need to offer patients. trying to peer over the heads of providers to work with clean, dirty,
It may be heresy, but clinical providers and payers in the front structured and unstructured data
outcomes may not be the top row seats. Roche’s $2 billion — accelerating innovation.
priority. Studying employer driven acquisition of Flatiron Health takes
programmes suggests wearable this on, acquiring a sophisticated ….AND THEN THE PAYERS
adoption today is not necessarily data team working with 265 cancer Most important are carriers.
driven by clinical results, but clinics and six research centres. Insurtech startup Zipari has
rather for engagement. And the launched an insurance member
foundation of engagement Connected devices are of special Mobile App to enhance the health
is community. interest. In clinical trials Adherium’s plan onboarding experience with
Hailie asthma and COPD solution biometric login verification, reduce
Adherence software company — based around a sensor and administrative costs with chat-
Adherium’s vice president of nudges that integrate with inhalers bots that guide members through
marketing, Vik Panda recently — was found to support improved a rich self-service user interface,
noted: “Combining community adherence by children by 180%. help members find doctors and
and technology to support health Overall an 80% reduction of acute hospitals with integrated geo-
goals is not a new discovery, as asthma attacks was achieved. location, and drive wellness
the combination deserves credit initiatives. The core of Zipari’s
for the massive success of fitness This can represent a boon for drug software uses predictive analytics
companies like Strava, Aaptiv and companies, but wearables have to provide customer profiles based
Peloton. Data about your health is many suiters. on consumer interactions including
good, but you need a community through wearables.
to put it to work.” PROVIDERS ENTER THE
WEARABLES MARKET Spurring this along is an effort to
New or not, community needs Klue, a software company focused build a standard data ecosystem
to be central. on behaviour tracking and change, for insurance — including for
recently announced a partnership formularies and potentially
PHARMA HUNGERS FOR with Crossover Health in the latter’s extending out to wearables data.
WEARABLES’ ENGAGEMENT clinics. Klue’s new Mindful Eating Vericred is a healthcare data
AND DATA Messenger shows the power of services company serving as a
For drugmakers wearables are artificial intelligence by recognising data translation layer between
a tantalising option to address when, how fast and how much insurance carriers and insurtech
adherence. In industrialised a person consumes through the companies. Today, they deliver
countries therapy adherence nuanced movements of their plan design, rate, provider network
can average at about 50%. wrist. Personalised, actionable and key formulary data for medical
Nonadherence represents an micro-nudges to adopt specific insurance product lines. As health
estimated $100 to $300 billion consumption behaviour can be insurance formularies become
annual burden on the US healthcare offered to empower users to create more restrictive, knowing if a
system alone and according to and hold onto new habits. drug is covered and how much
REFERENCE: the Pharmaceutical Group of the a consumer will pay for that drug,
1. https://www.pgeu.eu/en/
European Union it is estimated to The ability of hospitals to manage is critical when shopping for
policy/5-adherence.html cost the EU €125 billion per year.1 this kind of data is turning a corner. a health plan.
56 www.epmmagazine.com

Pharma companies have to work it’s believed US employers will launch and 95% said they would
to collaborate from a position integrate more than 13 million continue offering wearables.
of strength. Wearables are the wearable devices into wellness
The shifts are unique thread through it all with programmes and even in light of On demand like this, the
their ability to provide live streams, updated privacy laws in Europe smartwatch market is expected
dramatic. But sitting on the wrist throughout there is still growth in workplace- to hit nearly $18 billion in 2020,
in the end if the day. But wearable makers are based fitness tracking. When according to IDC. Fitbit recently
having some difficulty keeping employers prioritise goals for unveiled health-focused features
drugmakers, wearables on wrists, and they are wearables, 77% said they want to with a heart-rate monitor and
wearables looking to health. increase employee engagement a sensor to estimate blood
makers, with their health, a close second oxygen levels. It is launching
WEARABLE MAKERS SEE is the lower bar of wanting to audio coaching sessions and
providers HEALTH AS THE SOLUTION add a fun element to a wellness virtual trainers that can organise
and payers Wearables businesses are working programme, coming in at 74%. personalised fitness routines.
to be more than providers of After that 62% said they want to The company has also
are to novelties that are used for a see improvements in employee expanded toward guided wellness
succeed, as few months and then end up in health, which is a higher programmes that counsel users to
the employer the gadget drawer. Some have expectation with the potential eat and sleep healthier. Apple and
seemed nervous about health, for clinical measures. Xiaomi, plus Alphabet’s Android are
data shows, Nokia sold its digital health making aggressive moves in
community business back to its founder. The problem of wearables’ health as well.
But many more are noting the waning novelty seems to recede
will be key. enthusiasm of employers for when integrated into a community The shifts are dramatic. But in
building wellness programmes like that of a workplace. Fifty-four the end if drugmakers, wearables
around wearables. percent of employers said the makers, providers and payers are
majority of employees were using to succeed, as the employer data
According to consultancy the wearables they were provided shows, community will be key.
Endeavors Partners, this year six months after programme
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58 TECH TALK

Trustworthy transactions
This time in Tech Talk, Dr Neil Polwart, Novarum founder and BBI Group head of mobile,
looks at blockchain technology in mHealth.

T here can be few people working on

a mobile health (mHealth) concept
who haven’t been asked: ‘Are you using
If the list of transactions (often referred to
as a ledger) is stored in multiple locations
(a distributed ledger) and rules are in place
One of the main benefits of blockchain
is the ability to move away from a single
trusted central authority. That benefit is
blockchain?’ to resolve conflicts between the multiple primarily of importance where there is a risk
copies, it becomes possible to authenticate that a central authority might intentionally
Blockchain technology is the underlying a transaction without relying on a central manipulate data.
principle behind virtual currencies such trustworthy source.
as Bitcoin. The idea is simple, elegant However, if we have lost faith in our medical
and solves a key problem with currency The downside of blockchain is inherent providers not to modify our data then we
transactions — yet, how can you trust the within its design. The computational effort have a trust issue, which seems way more
transaction without relying on a central and complexity in generating blockchains fundamental than data storage.
authority to authenticate it? are what brings the inherent robustness,
but also uses huge amounts of electrical It is clear society and its lawmakers still
So, does blockchain have a role to play in power and so their green credentials are poor. trust medical professionals with extremely
mHealth? Possibly. However, it certainly sensitive data, with the recent GDPR
isn’t a panacea and, likely in many Moreover, the concept that transactions regulations having special carve outs for
implementations, does little to actually can be checked implies that their contents data where doctor-patient confidentiality
solve security or privacy issues. must be visible or accessible to others. could be assumed for example.
One solution is a ‘private blockchain’ held
The idea behind blockchain is simple, each by the institution — however, that brings The greatest vulnerabilities to medical data
time a transaction is performed it is passed little benefit over a classic secure database. security come from two completely different
through an algorithm which generates a extremes — firstly, poor user compliance
seemingly random string of letters and Conceptually, some medical records and secondly, in system-wide security
numbers — known as a cryptographic hash. could be held by and only decrypted by vulnerability that enables hackers to
the individuals involved, in some ways access data.
Change any of the inputs to the algorithm, mimicking how people ‘hold’ Bitcoins.
even slightly, and a totally different hash is Rather than jumping on the blockchain
returned, but if you enter exactly the same However, if you lose your credentials you bandwagon as a marketing stunt to suggest
inputs, you will receive exactly the same lose the value of the coins — a mistake we have unparalleled security, we would
output and so it is easy to verify whether some people have found very expensive. be better investing our efforts in good user-
content has been altered. Not many of us can say that we have never experience to help avoid people using bad
forgotten a password or lost a file which we practice, adding features such as two-factor
One of the inputs to the algorithm is the forgot to back-up. authentication and designing infrastructure
hash from the previous transaction in the and software that is robust to attack and
chain and this continues all the way to the Now, what if the consequences of that kept up-to-date.
original transaction. As a result, it becomes were the loss of medical records? Given
impossible to alter any individual record that many patients are the most vulnerable So, I suggest if you are asked; ‘Are you
without also updating every other record in in society — expecting them to manage a using blockchain?’, ask yourself what
the chain. technological solution may be impossible. problem you are trying to solve first.
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