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Drug safety and quality: protecting the patient
Annual 2017
AN
NU
AL
20
17
03
This issue is dedicated to an extremely prevalent and topical issue. In
recent years more and more reports have surfaced in the media about fake
and counterfeit medications – and the trend is growing. The problem is no
longer restricted to developing countries or so-called lifestyle drugs. Unsafe
medications are also being found in the West. Every indication is affected;
some 53% of all counterfeits that are intercepted in the legitimate supply
chain are lifesaving treatments.
For us at Sandoz, where quality and patient safety are the number one
priority, this development is especially worrying. Every year, we supply more
than 500 million patients with Novartis products through Sandoz affiliates as
well as selected partner pharmaceutical companies. Counterfeit medications
are not only an infringement of intellectual property, they also pose a serious
danger to public health. Anti-infectives are particularly affected by this topic,
which aggravates the risk of antimicrobial resistance – our focus field of last
year’s publication. In our cover story, we outline the extent of the problem
(beginning on page 6) and present the latest figures (page 20).
A number of experts and projects from industry, authorities and associations
are working hard to put a stop to this practice. From page 22, you can find
out about the role customs plays in pulling dangerous goods from circulation
and exposing networks. Have you heard of the edible barcode or the mobile
drug scanner? An overview of the multiple possibilities for marking products
or making their composition analyzable – even by laypeople – can be found
starting on page 26. In the future, it will be even more difficult to infiltrate
counterfeits into the legal product chain – every prescription medicine will
be coded with a unique number. We present our comprehensive serialization
project from page 32.
What makes the medications developed by pharmaceutical companies
better? The lengths to which the pharmaceutical industry goes in order to
guarantee the quality of its products never fail to impress me. Starting on
page 42 we provide an insight into this quality assurance process – and
show that it by no means ends with regulatory approval.
I hope you enjoy our magazine and wish you a stimulating read.
All the best,
Michael Kocher
Global Head B2B Business
A life-threatening challenge
04
Contents
Drug safety: the difference within
A lucrative business for some, a
real danger for others. Counterfeit
medicines are on the rise. Sandoz
and the entire Novartis group are
championing the fight against fakes.
The role of customs
Customs plays an important role
in the fight against counterfeits
and smuggling. In order to detect
illegal traffic, data analysis and
collaboration are key.
06 22
LEGAL INFORMATION Publisher: Sandoz GmbH, Biochemiestraße 10, A-6250 Kundl/Tirol (Publication Manager: Markus Schardt) • Corporate Publishing: Egger & Lerch, A-1030 Vienna, www.egger-lerch.at • Photography: Sandoz GmbH (pp. 6, 8, 15, 16, 19, 26), Phearum Xinhua/picturedesk.com (p. 23), FORMA Photography (pp. 32, 38, 39, 40, 41), Reinhard Lang (p. 36), GettyImages (p. 42), Fotostudio Attersee (p. 45) • Translation: CLS Communication, CH-4051 Basel • Printing: Piacek, A-1100 Vienna
05
For the patient’s sake
How far does quality need to go?
Medicines have to continuously
prove themselves, even after
approval – the only way to ensure
that the patient gets the right
treatment.
A question of technology
Counterfeiters are constantly
developing their production.
Sophisticated technologies
make it difficult for them to copy
medicines and packaging.
Falsified medicines in figures
What are the trade routes
of fake pharmaceuticals?
Provenance, destinations and
the amounts around the world
according to statistical data.
Serializing the future
Each unit receives a
unique serial number:
a major project with many
challenges in store.
42
26
20
32
Make access happen: It is the proclaimed purpose of Sandoz to pioneer new ways to help people access high-quality medicine.
06
Drug safety: the difference withinA lucrative business for some, but a real danger for others. In some regions particularly, the trade in counterfeit pharmaceuticals is flourishing – and not just online. With the looming threat of falling confidence in medicines, healthcare providers and health systems, tackling the problem calls for the united effort of every region of the world.
07
08
Myanmar in 2005: More than half a million people were
infected with malaria. So it was not really surprising when,
in February, a young man went to a local hospital with
a high fever. He complained of headaches, chills and
nausea. The doctors diagnosed malaria straight away
and prescribed artesunate. The symptoms should have
disappeared after a few days – but not in this case. The
concentration of the parasites in his blood rose even
further. He went into a coma and suffered kidney failure.
The doctors tried to save him, but it was too late. The
infection was too far advanced.
The course of the disease was highly unusual in this case,
as the compound was considered safe and is generally very
well tolerated by patients. So it was investigated in more
detail, with a shocking result: the administered medication
contained only 20% of the active ingredient; it was a fake.
GLOBAL REACH
Time and again, there are horror stories in the media
about counterfeit pharmaceutical products and their –
sometimes fatal – effects on humans. Recently, the WHO
confirmed that both generic and innovative medicines
are being counterfeited, not only posing a serious danger
to health, but also causing an impact on the economy
and on jobs. It is believed that between 30% and 70% of
medicinal products in developing countries are counterfeit.
Developed countries are also not immune to this trend,
with estimates putting the figure at up to 7%. Anti-malarials
and antibiotics are among the most commonly reported
substandard and falsified medicinal products, but all
types of medicines can be affected. They can be found
in illegal street markets, via unregulated websites, and in
pharmacies, clinics and hospitals. In 2015, the devastating
death toll from malaria was 429,000. Reports estimate that
up to one-third of anti-malarials are fake.
The entire Novartis Group, to which Sandoz belongs, is
taking the fight against illegal counterfeits very seriously.
And with good cause: The low-grade products are in direct
conflict with the company’s purpose. Sandoz is committed
to improve access to high-quality medicines, medical
information and healthcare for patients throughout the
world. Since it was founded in 1996, Novartis has deployed
investigative resources to examine counterfeit, falsified,
illegally diverted and stolen pharmaceuticals worldwide
in close collaboration with law enforcement partners.
Authorities around the world are provided with timely
data and evidence which they can use to launch their
own investigations or mount prosecutions – an essential
tool in the fight against counterfeits. In 2016, the Anti-
Counterfeiting program was re-launched with the active
contribution and support of a special working group, under
the leadership of the Novartis Anti-Counterfeiting Steering
A local hospital in Myanmar: malaria is a
very common infection the HCPs have to deal
with on a regular basis.
09
Definitions by the World Health Organization (WHO)
Substandard: Also called “out of
specification”, these are author-
ized medicinal products that fail to
meet either their quality standards
or specifications, or both.
Unregistered/unlicensed:
Medicinal products that have not
undergone evaluation and/or ap-
proval by the National or Regional
Regulatory Authority (NRRA)
for the market in which they are
marketed/distributed or used,
subject to permitted conditions
under national or regional regula-
tion and legislation.
Falsified: Medicinal products that
deliberately/fraudulently misrep-
resent their identity, composition
or source.
Counterfeit (definition by
Novartis): Medicinal products
which have been deliberately
and fraudulently mislabeled with
respect to identity, source or
history, with IP/TM infringement
implications.
Committee (ECN sponsored). Its core ambition is to protect
patients and, beyond that, the company’s reputation. An
ambitious cross-functional roadmap has been designed
with a set of nearly 50 objectives. Since the beginning of
2017, dozens of successful enforcement cases as well as
training and awareness initiatives have been launched, with
internal and external stakeholders such as local police,
customs and health authorities.
“Customs statistics in recent years have shown an
increase in the number of counterfeit and falsified
medicines seized,” said Stanislas Barro, Global Head
of Anti-Counterfeiting and Chair of the Novartis Anti-
Counterfeiting Working Group, which is a pillar of the
company’s Global Security stra tegy. “Such medical
products represent a serious and growing problem
for patients, public health and other authorities and
pharmaceutical manufacturers alike. For patients who are
generally unable to distinguish between authentic, falsified
and counterfeit products, the health risks are enormous.”
As a global leader in generic pharmaceuticals, Sandoz is
particularly affected by the growing number of counterfeits.
The company is therefore working closely with the
superordinate Novartis Global Security.
Barro and his team continuously monitor and improve the
security of the distribution chain, as well as the security
The entire Novartis Group, to which Sandoz belongs, is taking the fight against illegal counterfeits very seriously. And with good cause: the low-grade products are in direct contradiction to Sandoz’ purpose to improve access to high-quality medicines for patients throughout the world.
10
features on the packaging of Novartis products. All cases
of confirmed falsified and counterfeit Novartis products are
being investigated, regardless of where they were made
available, via the internet or on local markets. “One of the
main challenges lies with identifying the criminals operating
these illegal networks, especially since most of them are
now operating online. This requires substantial investment
and resilience in the intelligence and investigation phase
of the case,” Barro says. “We report confirmed incidents
to local law enforcement and health authorities so
that falsified and counterfeit medicines are seized and
destroyed – and the individuals profiting from these criminal
networks are brought to justice.”
INVESTIGATORS ON SITE
One example of Global Security’s recent work took place
in Burkina Faso. Until then, neither the Anti-Counterfeiting
case history nor the risk map for the region were showing
anything suspicious there. However, at the end of June
2017 this changed. Global Security sent both its Forensic
Expert and Regional Intelligence Officer in charge of the
African market to conduct a survey on Coartem® on local
markets in and around Ouagadougou. After just a few days
on site and several samples collected, one thing became
clear: There was a large presence of counterfeit Coartem®
in circulation. The colleagues issued a detailed forensic
report and immediately informed local health authorities
and law enforcement. The samples had been analysed
by a Novartis Forensic Manager: Not only would the fake
medication fail to cure the disease, it also contained
chemicals that could cause serious side-effects. But
Counterfeit drugs may contain
the original medicine in fake packaging
no active ingredient at all (placebo)
too little active ingredient (underdosed)
too much active ingredient (overdosed)
the wrong active ingredient
toxins, impurities or bacteria
Since the beginning of 2017, Stanislas Barro is Chair of the Novartis Anti-Counterfeiting Working Group.
11
ANTI-INFECTIVE*
21.1 %
CARDIOVASCULAR
11.6 %
CENTRAL NERVOUS SYSTEM
11.0 %
ALIMENTARY
11.0 %
of all counterfeit medicines detected in the legitimate supply chain are lifesaving-related treatments:
52.8%
* including both branded and generic anti-infectives/antibiotics, such as anti-malarial
Every therapeutic
category is affected
Source: Pharmaceutical Security Institute
12
Source: Trustwave Global Security Report, 2016
A web phenomenonEveryone with an email address knows about the phenomenon of spam. According to the Global Security Report by Trustwave, in 2015 around 54% of all incoming messages were spam, the majority of which were about pharma and health issues.
Accounting for 38.7% of spam,
emails on health issues are in
undisputed fi rst place. So-called
lifestyle drugs, such as prod-
ucts for weight loss or erectile
dysfunction, are heavily advertised
– even if you have not subscribed
to this type of newsletter in the
fi rst place.
The internet is the main supply
source of counterfeit medications,
and spam is a proven means of
mass advertising. According to a
2012 report by the European Al-
liance for Access to Safe Medi-
cines (EAASM), the likelihood of a
user who orders pharmaceuticals
online receiving a fake is 63%. The
WHO also cites a fi gure of over
50% for websites that conceal
their corporate address.
Spammers do not generally mar-
ket the products advertised in the
messages themselves. They make
money by signing on to affi liate
marketing programs. In these, they
distribute advertisements for the
vendor’s products or services, and
the vendor pays them a percent-
age of each sale they bring in.
HEALTH DATING ADULT PRODUCTS OTHER
72.8 %
4.0 %
1.2 %
2.1 %19.9%
38.7 % 18.3 % 12.3 % 6.6 % 24.1 %
20142015
Spam CategoriesIn 2014, health-related spam peddling pills, potions, and other miracle cures made up almost three-fourths of spam messages. In 2015, that portion dropped to 39 percent – still the largest share.
One of the biggest trends for
rogue online pharmacies at the
moment is pretending to sell a
genuine branded product online
while, in the end, the buyer will
receive a substandard version of
what he or she ordered – which is
potentially harmful to the patient.
This is an illegal yet highly lucra-
tive acti vity. Mostly prescription
medicines are sold here without
prescription, often for drug abuse.
Omnitrope® from Sandoz, for ex-
ample, is popular with bodybuild-
ers because the growth hormone
helps increase muscle mass.
13
Reasons why people would buy prescription-only medicines online without a prescription
Source: Discounted or Dangerous, EAASM, 2012
39% 35% 33% 16%
Cheaper than a prescription
Avoid visiting a healthcare
professional
Quickest and most convenient
route to purchase
Can’t buy it in their country
there is another possible consequence about falsified
pharmaceuticals which aggravates the situation. “It’s
entirely possible that patients would lose trust in Coartem®
while the genuine product is known to be the only effective
curative anti-malaria treatment available in most situations,”
Barro summarizes.
CONTENT MAT TERS
“Our experience is that falsifications are often difficult to
detect,” Barro explains. It goes without saying that the
tablets should look as similar to the original as possible.
Their contents are surprising, however. Either they contain
none of the active ingredient that they are supposed
to contain, or the dosage is incorrect – both situations
leading to therapeutic failure. In some cases, dangerous
and potentially life-threatening substances are also found,
such as bacteria or harmful materials. This is particularly
the case if the compounds were adulterated under poor
hygiene conditions. Although one might think that counter-
feiters have no interest in causing serious harm to the
consumers of their goods, patient safety is definitely
taking a backseat to their profits. Indeed, there are plenty
of examples of dangerous ingredients, from antifreeze
to bacterial contamination to dangerously high doses of
“There is not the one counterfeiter type, it ranges from the simple retailer to the large scale organization.”Stanislas Barro, Novartis
14
painkillers. The mixtures range from quite accurate to
utterly reckless; compounds of colored clay, sealed with
wax, have even been found.
The people who operate this business cannot be pigeon-
holed either. “There is not only one type of counterfeiter.
They range from the simple retailer on a local flea market
to a large scale and sophisticated criminal organization
owning tens of thousands of rogue online pharmacies
and operating from many countries with very substantial
financial means,” Barro explains. The latter function like
large international firms and have the technology to master
complex manufacturing processes themselves. And
presumably, there is an entire illegal chain of operators
with suppliers of raw materials, manufacturers, exporters,
importers, distributors, and so on in between. Most
counterfeit medicines come from India and China. To
conceal their origins, the manufacturers often choose
complex routes with multiple middlemen. The products
head west through black market channels. Research
suggests that it is not unusual for them to change hands
more than 30 times before reaching the end customer.
THEFTS WITH CONSEQUENCES
When it comes to white-collar crime and illegal supply
chains like this, Michele Riccardi is all ears. For ten years,
he has been investigating this at Transcrime, a research
center of the Catholic University of the Sacred Heart in
Milan. “It struck us that there were more and more media
reports emerging about medicine theft. We wanted to
follow them up,” he explains. Prescription products,
particularly for oncology, were stolen on a large scale from
Italian hospital pharmacies during 2013 and 2014. “In Italy
and many other countries, these are covered by health
insurance. So why steal medicines that cannot be sold on
the black market?” the team of scientists asked. They were
“It’s a really profitable business. The value-volume ratio is higher than for many illegal drugs.”Michele Riccardi, Transcrime
International business crime and illegal markets are Michele Riccardi’s main fields of research at Transcrime.
15
The tablets should look as similar to the original as possible,
which makes them hard to detect.
16
on to something bigger. The cancer treatment appeared
again in the UK, the Netherlands, Spain, Portugal, Finland
and particularly Germany – in the legitimate supply chain. A
complicated network of receivers and bogus corporations
ensured that criminals could smuggle the goods back into
the regular market.
A BRIEFCASE FULL OF VALUABLES
“It’s a highly profitable business. If someone manages to
steal a briefcase full of cancer medicines from a hospital,
the contents may well be worth 150,000 to 200,000 euros,”
Riccardi says. “That is a better value-to-volume ratio than
for many illegal drugs.” The goods were laundered through
wholesalers registered in Italy, Latvia, Hungary, Romania,
Slovenia and Slovakia. With fake documentation, it seemed
as if the packs came from legal sources. In reality, the
Camorra and other organized criminals were involved.
“Actually, stolen genuine medicines fall under the definition
of falsified medicinal products recently proposed by the
WHO. They mislead the patient as to the actual source of the
pharmaceutical purchased and the way it was shipped and
stored,” Barro says. People who illegally steal and distribute
cancer therapies are unlikely to observe the cold chain for
storage and transport. Thus, to secure the distribution chain
is one of the most important tasks in the fight against fakes.
Especially during chemotherapy, the patient’s immune system is weakened. To reduce the risk of infection, the treatments are packed in sterile conditions and often require refrigerated storage.
17
In 2007 and 2008, counterfeit heparin killed 149 Americans. Chinese smugglers had laced the anti-thrombosis product with cheap chondroitin sulfate.
In late November 2016, police arrested a pharmacist from Bottrop in Germany who had been preparing cancer products in his cleanroom laboratory since 2011. He is accused of having underdosed chemotherapies and antibody infusions for years.
In the early 1990s, almost 70 children in Bangladesh died from acute kidney failure. It was found they had drunk paracetamol syrup that had been doctored with diethylene glycol.
In 2008, medicines that were supposed to treat erectile dysfunction led to the hospitalization of 150 men from Singapore. Four of them died and seven suffered severe brain damage.
1.3 milliontablets with fake Androcur, which is used to treat prostate cancer, were circulating in six regions of Brazil during 1997-98.
They only contained flour.
More than 1,000 people were hospitalized in Congo during 2014-15. They were suffering from the toxic effects of adulterated diazepam containing the antipsychotic haloperidol, which triggers involuntary muscular contractions.
Popstar Prince’s demise is probably one of the most famous examples of death from adulterated medicines: counterfeit painkillers containing fentanyl were found in his house; the substance was also in his circulatory system.
Incident with “vaccines” that contained only water. In Niger, over
50,000 people received falsified meningitis vaccine during an epidemic
in 1995. 2,500 people died, many were permanently handicapped.
Newsflash
18
“Fortunately, our supply chain is one of the most secure in
the industry. There have been very few incidents in recent
years,” Barro explains.
SMALL CHANGES, B IG IMPACT
Even if the counterfeit itself is not toxic, substan dard
medicines prevent patients from receiving their required
treatment. Because they are unaware that they are
taking an inferior product, their conditions can worsen
and in critical cases be fatal. Children and older people
are particularly vulnerable to the real danger of cheap
pharmaceutical copies.
As are cancer patients, whose immune system is greatly
weakened, especially during chemotherapy. To reduce the
risk of infection, the medications are packed under sterile
conditions and often require refrigerated storage. The
dosage is also individual – based on the patient’s weight
and the stage of illness. In addition, the dosages for the
same medicine may vary from one country to another,
thereby potentially posing a serious threat to the health
of the patients. Small variations mean that the patient is
not receiving the best treatment. They can lead to serious
health problems and also mean that the treatment does not
prolong life.
THE ECONOMIC IMPACT
The patients pay with their health and in some cases even
their life. But there is also an economic impact. A report by
2,0182,1932,177
3,0023,147
2012
2013
2014
2015
2016
Total number of incidents
Source: Pharmaceutical Security Institute
the European Union Intellectual Property Office (EUIPO)
concludes that counterfeiters cost legitimate pharmaceu-
tical companies around EUR 10 billion a year – in the EU
alone. These losses translate directly into 38,000 jobs that
are lost through lower productivity. If the indirect impact
is also taken into account – interaction with other sectors
such as missing orders for suppliers or lost tax income –
the total loss for the EU economy is around EUR 17 billion
or 91,000 jobs. The authors of the research only take
manufacturing and wholesale into account, not retail trade.
All in all, the economic magnitude is therefore much greater.
JOINT ACTION
Solving the issue requires a sustained commitment not
only from national governments and international health
organizations, but also from the pharmaceutical industry
and other healthcare stakeholders. Companies are joining
forces and working more closely together to address the
counterfeit problem, for example with the Pharmaceutical
Security Institute, a not-for-profit industry body founded
in 2002. Today, it comprises 33 member companies
dedica ted to sharing information on the counterfeiting
of pharmaceuticals and paving the way for enforcement
action, such as raids, product seizures, arrests and
prosecutions by authorities.
Customs have always been and will remain a cornerstone
in the company’s anti-counterfeiting strategy. Still, the
erectile dysfunction category represents the vast majority
19
of counterfeit and falsified products seized by customs.
“We need authorities also to focus on more complex
categories of pharmaceuticals which are harder to detect
yet represent a very high risk for the patients”, Barro
claims. “Our responsibility is to provide them with enough
information about our key products – especially in high
risk countries – to enable them to perform a meaningful
risk analysis on a regular basis.” To further intensify
cooperation and raise awareness, Novartis has recently
launched an ambitious Customs recordal process in key
countries.
Novartis is also actively cooperating with trade associa-
tions such as the Global Fund, the European Federation of
Pharmaceutical Industries and Associations (EFPIA) or the
International Federation of Pharmaceutical Manufacturers
& Associations (IFPMA), which campaigns globally against
counterfeits. With an educational video and the global
awareness campaign “Fight the Fakes” it aims at warning
consumers about the danger from counterfeit medicines.
“Such cooperation between the private sector and trade
associations is absolutely crucial,” says Barro. “It is para-
mount that we can assure patients that products that bear
our name are, in fact, our products, backed by superior,
unwavering standards of quality, safety, and efficacy. Our
responsibility in this respect is a powerful incentive for us to
get better at what we do every day.“
In Ghana, there are approx-imately 2,000 registered pharmacies, most of them in the big cities. To increase access in rural areas, also licensed chemical shops can sell medicines.
“Our supply chain is one of the most secure in the industry.” Stanislas Barro, Novartis
PROVENANCE ECONOMIES FOR COUNTERFEIT PHARMACEUTICALS, % OF GLOBAL SEIZED VALUE , 2011–2013 1
United Arab Emirates
3.9%
Hong Kong
2.6%
Egypt
1%
Other
3.9%
Bulgaria
United Arab Emirates
Hong Kong
Yemen
Niger
United States
Kenya
India
55.3%China
(Mainland)
33.3%
Falsifi ed medicines in fi gures
Hong KongHong Kong
China (Mainland)
Top Countries of Origin
Top Destinations
Cameroon
Democratic Republic of Congo
Angola
India
TR ADE ROUTES FOR FAKE PHARMACEUTICAL PRODUCTS (BY GLOBAL SEIZED VALUE)1
Sources:1 Mapping the Real Routes of Trade
in Fake Goods, OECD, 20172 Keeping it real, International Policy
Network, 20093 Falsifi ed Medicines Costing the
Earth, Alliance for Safe Online Pharmacy EU, 2013
4 Statista 20175 Pharmaceutical Security Institute:
http://www.psi-inc.org/geographicDistributions.cfm
The graph shows the regions in which the most drug counterfeiting has been reported. It also demonstrates that counterfeits often remain undiscovered by the authorities in countries that have no clear legal regulations and/or lack monitoring. An incident involves seizing hundreds or thousands of pharmaceuticals on average, and, occasionally, even greater numbers.
DISTRIBUTION OF PHARMACEUTICAL INCIDENTS 5
ACCORDING TO WHO ESTIMATES,
OF MEDICINES AROUND THE WORLD ARE COUNTERFEITS.3
10%
21
1579690
416347
282189
94
North America
Asia
Latin America
Europe
Eurasia
Near East
Africa
CONVEYANCE METHODS FOR COUNTERFEIT PHARMACEUTICALS, 2011–2013 1
82%
Air
13%
Sea
4%
Road
1%
USD 95 billion.4THE ECONOMIC DAMAGE THEY CAUSED IN 2015 AMOUNTED TO APPROXIMATELY
Falsifi ed medications can result in the emergence of drug resistant strains of diseases ranging from Aids and malaria to tuberculosis and bird fl u.2
22
The role of customsCustoms plays an important role in the fight against counterfeits and smuggling. Authorities have been working together on this for a long time – both at a national level with local companies and organisations and internationally.
About 5.1 tonnes of counterfeit medicines
were seized and destroyed in Phnom
Penh in 2014. Brigadier General Long Sreng,
deputy chief of the anti-economic crimes
department of the Cambodian interior
ministry, shows the fakes to the media.
23
24
The container ship from China was carrying tea. At least,
that’s what the documents claimed when it docked in
Le Havre, the largest container port in France, in February
2014. The customs officers, however, decided to take a
closer look at the cargo and made an astounding disco very.
They found 2.4 million packs of headache pills, erectile
dysfunction tablets, and other pharmaceuticals on board
– all of which were fakes. Until then, the largest seizure of
counterfeit medicines in the European Union. Quite the find
for the officers.
A DANGEROUS SOUVENIR
Every day, customs officers find the most peculiar souve-
nirs at transit areas worldwide. Live or stuffed animals, fake
designer handbags, drugs and weapons: Many goods that
are transported in suitcases or cargo containers are not
allowed to be brought into the country or require special
permits. Medicinal products have already been ranked third
on the list of confiscated items in the EU.
As with illegal drugs, smugglers are becoming ever-more
cunning when it comes to getting their merchandise across
the border. They hide it in teddy bears or label it as animal
feed. But the investigators have a number of tricks up their
sleeves, too.
NOT J UST PAPERWORK
Some 43% of all US imports arrive at the Port of Long
Beach, California. One freight container is processed every
7.8 seconds., which doesn’t leave US Customs and Border
Protection officers with much time to trawl through the
documents for trigger words. Instead, their work begins
before this point – with a little help from digital technology.
Automatic targeting tools identify suspicious containers
using algorithms. With the help of international customs
networks, the containers are often inspected at their port
of departure before they commence their journey.
JOINING FORCES AGAINST ONLINE- CRIME
“Crime is increasingly international,” agrees Cecilia Fant,
Criminal Intelligence Officer at Interpol. Every year, the
Pharmaceutical Crime Department brings together
authorities from various countries to combat the illegal sale
of medications online. The year 2017 was no exception, with
customs and police officers from more than 100 countries
successfully raiding organized counterfeiters: Operation
Pangea X saw more than 25 million units of illicit and
counterfeit pharmaceuticals taken out of circulation. The
goods had an estimated market value of USD 51 million.
Approximately 3,500 dubious pharmacy webshops were
taken offline after the operation took place, and some 400
people were arrested.
Thousands of questionable packages were seized in the
process. Most fake medicines are distributed by mail, which
poses one of the main difficulties: division of the goods into
several individual deliveries hinders access for customs.
Much can be achieved by comparing data, however,
with countries exchanging information. “It is a joint effort
between many different agencies. They send information
about seizures and arrests. We look at all the data and
try to find cases,” Fant explains. When the first Operation
Pangea launched in 2008, ten countries took part; the
operation in 2017 involved more than 120.
A DATABASE AGAINST FAKES
By their very nature, counterfeits are difficult to detect
because they are designed to look as similar as possible
to the originals. Knowing how to spot a fake takes a great
deal of expertise. To facilitate the exchange of information,
the World Customs Organization (WCO) has launched the
Interface Public Member (IPM) database. Officers on the
ground can use it to look up product-specific data in real
time. Novartis joined IPM back in 2012 and feeds facts and
images relating to its medicines into the database. This
makes it easier for customs officers to identify counterfeits
when they are confronted with them.
25
Counterfeit products seized in the EU*
Clothing: 12.3%Other goods: 11.1%Medicines: 10.1%*Transcrime, Estimating the counterfeit markets in Europe, 2015
Detecting the toolWhen it comes to pharmaceuticals, investigators are
not only on the lookout for tablets. Manufacturing
equipment is also of interest.
These days, US customs authorities are seizing 19 times
more tablet presses than in 2011. Tablet presses can
easily be bought online – a small investment to kick-start
a lucrative business.
Importing tablet presses into the US is not a crime in itself,
but the Drug Enforcement Administration (DEA) has to be
informed in advance. Detecting the presses is not always
an easy task for the officers. They range in size from small
table-top devices to those that are larger than a fridge and
can produce 170,000 tablets per minute. Non-registered
presses are reported to the police, but are not always
seized. Sometimes law-enforcement officers have the
machines fitted with tracking devices, which lead them
straight to the counterfeiters.
26
27
Along the supply chain control mechanisms are key to ensuring drug safety. More and more countries are adopting serialization where pharmacists scan the code before handing the product over to the patient.
A question of technologyThe pressure to innovate is high: counterfeiters are only one step behind genuine manufacturers, and are continually refining their production methods. Sophisticated technologies are used to make it as difficult as possible for them to copy medicines and their packaging.
28
Among the items that investigators take out of circulation,
the broad array of smuggled pharmaceuticals is plain to
see – quite literally. Packs with obvious differences from the
original and typos are just as common as boxes that look
almost identical, even to the trained eye. It is only ever a
matter of time until a well-made copy surfaces. On average,
it takes between 12 and 18 months for supposedly counter-
feit-proof technologies to be replicated.
SET TING THE BAR HIGH
Staying one step ahead of the counterfeiters demands
constant change and vigilance. Several measures are
taken to make their job as difficult as possible, including
holograms, special ink, foils and other additions to make
the medicine’s packaging distinctive and hard to copy.
In addition to special materials and visible elements,
concealed markings are also used. Features that are tricky
to manufacture and difficult to forge help to ensure as
great a difference as possible between originals and fakes,
making imitations easier to identify.
The combination is key. Manufacturers rely on more than
one characteristic to make their products as counterfeit-
proof as possible. Special features are combined with less
visible or entirely hidden elements. A transparent, specially
marked strip that shows whether or not the pack has been
Stamp format
Square 2D Data Matrix codes
can contain up to 3,116 figures or
2,335 characters. They are used
to code not only the Pharmacy
Product Number (PPN) which
clearly identifies products at the
international level, the batch name,
and the expiration date, but also
the serial number that makes each
pack unique and traceable. For more
information on serialization, please
see the article starting on page 32.
Technology used on packaging
29
The first-use guarantee
Tamper-evident packaging:
sealing the package with a
sticker provides an additional
layer of security. If someone
tries to open or tamper with the
packaging, the label or sticker is
irreversibly damaged. A special
glue is used so that the seal
cannot just be peeled off. Further
security measures, such as
printed markings, can also be
incorporated. The EU Falsified
Medicines Directive requires
this method for all prescription-
only medications, and it can be
implemented using either a gluing
or a label solution.
Radio waves
Radio frequency identification
(RFID) uses radio waves. Each
pack is fitted with a tiny chip on
which all of the information has
been saved – including the unique
serial number. The products can
be identified and traced from
production to the consumer using
a reader. The US Food and Drug
Administration (FDA) recommends
the use of RFID technology to
combat counterfeits. The costs
are higher than for other methods:
each chip costs between USD 0.05
and USD 0.15.
Tilt and reveal
Holograms can be two- or even
three-dimensional: new images
are revealed when the pack is
tilted. Holograms are worked
into metal or plastic foil and then
applied to the packaging. They
are not reusable: if you try to
remove the sticker, the surface is
damaged.
The edible barcode
Why not put a traceable ID on
the product itself? Silicic acid
microtags make it possible.
They are printed or sprayed
on to the pill and simply
swallowed by the patient.
Information on the medicine’s
origin is therefore available
right on the tablet itself. The
microtags are much smaller
and cost significantly less than
RFID chips at approximately
USD 0.01 per tablet. The
silicic acid is harmless and is
simply excreted by the body.
Simply scratch it off
West African countries, such as
Ghana and Kenya, use mPedigree.
The patient scratches off a panel
on the packaging to reveal a
code and sends it via SMS to
mPedigree. Within seconds, he or
she receives a reply as to whether
or not the product is genuine.
The text messages are free of
charge. This verification system
is now mandatory for malaria
medications in Nigeria.
Differing views
These are also used on bank
notes: color-shift inks are specially
protected colors that change
shade when they are observed
from a different angle. They are
difficult to fake and can therefore
provide additional protection when
applied to medicine packaging.
30
The minilab
The Global Pharma Health Fund
(GPHF) has developed small fi eld
test kits to cheaply test, on site,
which substances a compound
contains. The lab kit can analyze
57 active ingredients, including
those to treat malaria, tubercu-
losis and HIV, and is used in over
80 countries around the world.
The infrastructure in developing
countries in particular can rarely
accommodate the identifi cation
of counterfeit or substandard
medicines. This miniature labora-
tory can be used anywhere, even
by those who have only basic
knowledge of chemistry. A test
costs less than two euros.
The drug scanner
Fast, reliable results: with the
mobile Thermo Scientifi c TruScanTM
device, even non-experts can
check the chemical composition
of a medical product. All of the
components are assessed in a rapid
spectroscopy: active ingredients,
excipients, fi llers and colorings
as well as solid and liquid glazes
can be measured through sealed,
transparent packaging. The device
registers what the substance is
meant to contain when the label
is scanned, making it possible to
clearly diff erentiate between even
very similar chemical compounds.
Analytic technologies
31
opened or print finishing with a UV coating are just two
examples of techniques that are applied to packaging to
make it all the more difficult for counterfeiters to duplicate.
THE DATA WILD CARD
Moving up to the next level of difficulty, some technolo-
gies also incorporate databases. Giving each box its own
unique code and therefore rendering it traceable makes it
more difficult for criminal groups to feed their products into
the legitimate supply chain. An RFID chip or randomized
serial number gives each sales unit a unique identity. When
products are scanned at the pharmacy, the computer tells
the pharmacist whether or not the product is an original. It
displays the path the medicine has followed to that point
– from the production line to dispensing. Track-and-trace
systems are becoming more and more widespread, with
Turkey implementing one in 2011, and China and California
following suit in 2015. The other US states are set to do so
at the end of 2017, and the EU at the beginning of 2019.
Manufacturers rely on more than one characteristic to make medicines as counterfeit-proof as possible.
It is not always enough, however, to make the boxes them-
selves distinctive and give them a serial number. What if
criminal groups get hold of original packaging and fill it with
different contents? Simple test kits can help if this is the
case: Using specially developed mini labs, you can find out
whether or not the contents match the label on the box,
without any high-tech equipment or in-depth know-how.
Technology is advancing, generating useful tools against
counterfeiters.
32
More than 200 million packets of medicinal products leave the production site of Sandoz Kundl, Austria, every year, and go on to be used in over a hundred countries.
33
Serializing the futureEach pack is given a unique serial number, making the medicine supply safer for the patient. It is a major project, and its implementation has many challenges in store.
34
The pharmacist takes the box out of the drawer and scans
the code on the packaging. A green light immediately
appears on her screen. “Have a nice day,” she says, once
she has given the medicine to the patient.
What looks like a simple process at the pharmacy and
is barely noticeable to the customer is, in reality, a major
IT undertaking: The computer at the pharmacy is linked
to the national database system which manages all of
the country’s serial numbers. This in turn is linked to
the central European database, the “European Hub.”
In a matter of seconds, the computer checks whether
the serial number is registered there and may be sold.
10.5 billion packs are provided on prescription in the EU
every year. From February 2019 onwards, 32 countries
will be introducing this verification procedure to check
prescribed medicines before they are dispensed. This
group comprises the 28 EU member states as well as
four others, including Switzerland. A similar system will be
rolled out in the US as early as November 2017.
THE DIGITALIZ ATION OF THE FLOW OF GOODS
“We started with Turkey. This was followed by many other
project launches, including China, South Korea, Saudi
Arabia, India, the EU, and the US. We will soon set to
work in Egypt and Russia, too,” explains Michael Ritter.
As Global Program Manager SPT/TEP, he is responsible
for ensuring that serialization is implemented in good time
at all of the Novartis production sites. He is experienced
at what he does: He has been realizing these processes
since 2009. He submits his budget proposals and
coordinates the necessary steps from Basel. For the
pharmaceutical companies who manufacture medications,
this increased security measure is very labor-intensive.
Not only do they have to upgrade their production
lines in terms of technology, they also need to adapt
their packaging design and rethink and rework their IT
processes. Barely any department is unaffected by the
changes.
“Serialization digitalizes the flow of goods to protect the
supply chain. It has to be done, because counterfeits are
getting in time and again,” Ritter explains. “The US uses a
track-and-trace system which renders the product visible
every step of the way. In the EU, on the other hand, only the
production and dispensing to the patient are tracked. This
is the point-of-dispense verification. If the product is sold in
a pharmacy, the serial number is booked out in the system.”
The folding boxes zoom along the conveyor belt in the
site at a breathtaking speed. But production line L2, which
produces the antibiotic Curam® for the Saudi-Arabian
“Serialization digitalizes the flow of goods to protect the supply chain.”Michael Ritter, Novartis
35
The EU Directive
The EU Falsified Medicines Directive (FMD)
stipulates that all prescription-only medicines
must be serialized and verified in pharmacies
before they are dispensed to patients. Tamper-
evident packaging is also required, so that it
is apparent whether or not the packaging has
previously been opened. This will apply to all
28 EU countries from February 2019 onwards.
Four additional countries will be implementing
the measures voluntarily. Directive 2011/62/
EC was first presented in 2011, and the final
Delegated Act was published in February 2016.
The US Act
Congress passed the US Drug Supply Chain
Security Act (DSCSA) in 2013. It dictates
that manufacturers of prescription-only
pharmaceuticals must equip them with a global
trade identifier number (GTIN), a serial and
batch number, as well as an expiration date.
The roll out starts in November 2017. This
track-and-trace system makes it easier to
identify potentially dangerous substances and
remove them from the supply chain.
pharmaceutical company
wholesalers pharmacy/clinic prescription-holder
End-to-end control system
not dispensed, investigationverification of
each unit right before it is dispensed
optional: spot checks
randomized serial number uploaded
for each unit via data matrix code
pharmaceutical industry database
system
pharmacy database system
delivery dispensed
request1
reply2
booked out3
delivery
36
“Linking multiple and different IT systems is quite a task, but we are up to the challenge.” Jörg Fridgen, Sandoz
Encoded and readable
The product data is encrypted
and stored in the 2D matrix code:
the randomized, unique serial
number (SN), the product code
(GTIN), the batch number (LOT),
the manufacturing (MFG) and
the expiration date (EXP). This
information is additionally written
out in full to the right of the code.
This Curam� package was produced for the
Saudi Arabian market.
37
market, lies idle in the middle of the hall. A technician has
just installed the new printer and is checking the data
transfer and image quality. At the Kundl site alone, one
of the manufacturing sites within the Novartis network,
40 production lines are currently undergoing a technical
upgrade. At Novartis, a total of 39 plants and approximately
300 lines are being upgraded. New printers, scanners and
other devices have to be installed and tested. An intricate
plan ensures that there are no delivery shortages as a
result, since each individual production line is idle for one to
two weeks during the upgrade.
The team at Sandoz has been working intensively on
the serialization processes, and since the beginning of
2016 they have been doing so in collaboration with their
business customers. Because Sandoz not only produces
its own medicines, but also supplies other pharmaceutical
companies globally. Around 50 active B2B customers
currently have a contract with Sandoz, and these products
are dispatched to patients in some 55 different countries.
Keeping track of it all is crucial here, as the regulations
that apply to medical substances differ from country
to country.
READY FOR ON - BOARDING
Although they may be less visible than in production, the
changes required in IT are even more far-reaching. Addi-
tional data has to be generated, transported, and securely
stored and sent. “We aren’t the only ones who need new
systems. Our customers need them so they can manage
product data and compare it with the authorities,” Jörg
Fridgen explains. In his capacity as a project manager in the
B2B department at Sandoz, he coordinates activities with
the partner companies. Multiple and different IT systems
have to be matched with the Novartis cloud. A dedicated
onboarding process enables the companies to link to it. The
colleagues in B2B work closely with their contact partners,
providing advice, discussing the technical prerequisites and
preparing the subsequent end-to-end tests. These tests
check whether the data flow functions smoothly. “It is the
moment of truth after a long and protracted process. We
make sure that the connection works for each customer
and for each site that manufactures products for them,”
Fridgen tells us.
And then you need the serial numbers. They are not
consecutive – that would be too easy to fake. Instead, they
are randomly allocated using an algorithm. “More often than
not, our B2B partners transfer their own serial numbers to
us,” Fridgen explains. They are then saved in the Novartis
cloud and sent to the production facility, where they can be
printed onto the packaging. Then production can resume.
TAMPER- PROOF
The serialization system can only provide protection against
manipulation if the packaging has remained unopened
throughout: so-called tamper-evident packaging. A narrow
sticker has to be adhered to the edge of the folding
box. When the packaging is opened for the first time or
somebody tries to manipulate it, the sticker tears. To
implement this process in production requires special care.
“It is difficult to apply a sticker that tears easily while the
product is moving down the conveyor belt without reducing
the speed,” says Fridgen.
A great deal of time and money was invested in finding
the right label. On one hand, the sticker has to be easy to
apply during production; and on the other, it needs to have
a degree of durability afterwards. Test packaging featuring
different solutions was subjected to extreme temperatures
for extended periods of time. You have to make sure the
sticker doesn’t fall off, even after several months. The
researchers were particularly interested in the way patients
handle the packaging. It was important to ensure that even
the elderly and those physically impaired by certain illnesses
are able to open the packaging. The effort was well worth
it: “We have found the perfect label that meets all of the
criteria. If you try to pull it off, it breaks up into pieces,” Ritter
explains. And so, the sealed packs roll off the conveyor belt
in the production site – soon to be available in the pharmacy.
38
All of the production lines that produce prescription-only medicines must be upgraded to accommodate coding and tamper-evident-packaging technology. This affects a total of 300 lines at 39 Novartis sites.
39
The pick-and-place robot grabs the blister packs and sorts them into folding boxes. A suction arm inserts the patient information leaflet into the box, which is then carefully closed.
40
The monitor indicates any faults and displays the photographs on the right-
hand side. Here, the factory operator can see, for example, if the printer cartridge
has to be replaced and adapt the contrast or make other changes.
The 2D matrix code containing the product information, including the encoded serial number, is printed directly onto the packaging. The printer processes a maximum of 240 folding boxes per minute. A camera photographs each image printed, using special software to check whether the image quality is sufficient and can be read by standard scanners. If everything is in order, the serial number is uploaded to the database. If there are any issues, the corresponding number is registered in the system as faulty and the folding box is rejected. This ensures that only legible packages are dispatched.
41
Reading codes on bottles is more complicated. They speed upright through the production and filling facility, a small tube enters the bottlenecks from above and fills them with the powder or liquid. The process is fully automated and the bottles may also rotate during it. A 360-degree scanner reads the information, irrespective of the direction in which the label is facing.
42
Each year more than half a billion people take Sandoz medications. A great responsibility for the team at Sandoz to monitor quality and ensure safety for the patient.
43
For the patient’s sakeHow far does quality need to go? Strict standards apply particularly where medicines are concerned. Products have to prove themselves continuously, even after regulatory approval has been granted, as this is the only way to ensure that patients get the treatment they deserve.
44
Cytostatics are essential compounds for treating cancer.
They are particularly good at attacking rapidly growing
cells. However, this makes them potentially hazardous for
people who have to handle them. Anyone involved in the
production process, the mixing or dispensing of these me-
dicinal products must protect themselves. “Glass is still the
best packaging material for them,” explains Medical Affairs
Lead Roland Starlinger, who is in charge of the product
range of injectable anticancer agents. But how can the vial
be protected against breakage, and how can we ensure
that doctors and nursing staff will not come into contact
with traces of the toxic substance?
CAREFULLY PACK AGED
The Novartis aseptics production site in Unterach, Austria,
specia lizes in sterile, injectable medicinal products for
treating cancer. It was one of the first companies to develop
a special additional packaging container for the injection
vial in 2000: Onko-Safe®, which has already received two
packaging awards and achieved good test results. “Drop
tests on the original packaging showed that the 100-ml
glass vial only breaks when dropped from a height of more
than 1.80 meters. Once it has shattered, the medication
does not leak out. This further increases protection
against contamination,” says Starlinger. During production,
the vials containing cytostatics are washed to ensure
decontamination.
THE RULE KEEPER
“Our employees in the cleanroom who oversee the auto-
matic filling process have to be specially trained, because
they work with the open product,” says Susanne Kästner.
As the Head of Quality Systems and Compliance, she is
responsible for ensuring that the quality standards are
met at the Unterach site, so that the medicinal products
ultimately reach the patients. Before production can
even start, strict regulatory requirements that apply to
the pharmaceutical industry have to be implemented.
Good Manufacturing Practice (GMP) not only regulates
Better safe than sorry: the additional Onko-Safe® plastic casing protects the
cancer therapy injection vial against breakage and
the environment against contamination.
45
“Everyone has to do their part to ensure that we maintain the highest standard of quality. Only then will patients get the medicinal products they need.”Susanne Kästner, Novartis
parameters related to technology and hygiene parameters,
but also to Quality Assurance oversight, documentation
and employee training.
A CRUCIAL VISIT
Official audits are regularly conducted at all Novartis
Group sites. “We assist with the inspections and present
our processes and quality systems. We have successfully
completed numerous inspections by international
authorities in the past,” says Kästner. “This involves a
degree of preparation. While the requirements from the
various authorities overlap to a great extent, some are
regionally specific.”
In addition to external audits, meticulous internal reviews
are also conducted on an ongoing basis. Novartis has its
own quality manual. Each of the global sites is obliged to
implement this locally. It contains the GMP requirements
from the various regions, includes the information from
the Group-wide inspections and rolls it out to all locations.
“Our aim in this regard is to always be up-to-date and try
to foresee future developments,” says Kästner.
AN ANALY TICAL APPROACH
The Quality Control (QC) department is home to experts
who analyze raw materials, the materials used and the
final products in the laboratory. Only if all results meet the
46
specification the Qualified Person will release the product
for the market. One particularly sensitive area is aseptic
filling, which is subject to strict conditions. The environment
must also be continuously monitored, particularly in the
sterile production area. The experts carry out regular
stability tests for each product to ensure the specifications
are also met over the shelf-life.
BACK TO THE ROOTS
Quality starts with the raw materials, and therefore with
the suppliers. The active substances, excipients and all
required materials, such as the vials and syringes, must
be flawless. To guarantee this, Susanne Kästner and the
auditing team visit the manufacturers and perform audits:
“Novartis has high-quality standards, with which suppliers
also have to comply.”
SERVED CHILLED
Supply Chain Management ensures that the medication
reaches the hospital or the pharmacy undamaged. Many
anticancer agents have to be refrigerated, so temperature
data loggers are enclosed in the shipping crates and are
read out on arrival. The mediactions may only be distributed
if the data comfirms that the cooling chain was unbroken
as planned. Otherwise, they will not be distributed and an
investigation has to be performed.
THE BIG PICTURE
“My commitment to quality is to keep improving,” says
Susanne Kästner. She keeps her eye on the big picture, but
raises awareness of smaller details too, because these can
have serious consequences. “If, for example, a packaging
component from another product remains at the line, this
might lead to a recall. And this can lead to product unavail-
ability and results in patients no longer being treated with a
lifesaving medication – we are dealing with vital anticancer
agents. Ultimately, everyone must do their part every day
to ensure that we meet the requirements and maintain the
highest quality standard. Only then can we make our con-
tribution to ensure that patients get the medicinal products
they need for their treatment.”
Lifecycle of a pharmaceutical product
Research Preclinical study
Causes of illness/ starting points for medicines
Identification and preselection of
substances
Testing of effects and side effects
5 1,5Yea
rsS
ubst
ance
s
up to 100,000 250
GxP
47
Good Clinical Practice (GCP)
Clinical studies must comply
with regulations based
on ethical and scientific
principles. These focus
on patient protection,
their informed consent for
participation, and achieving
good quality study results.
The US was the first country
to introduce formal GCP
regulations in 1977. The
European Community
published theirs in 1989,
although they were not
defined in detail. In 1996,
regulations in the US, Europe
and Japan were harmonized.
The core element of GCP
is quality management.
Any ongoing study has to
be monitored in line with
predefined criteria.
Good Manufacturing Practice (GMP)
Strict manufacturing
requirements as regards
hygiene, premises, machines,
and the required checks are
designed to safeguard the
quality of pharmaceutical
products. The official term
was coined by the US Food
and Drug Administration
(FDA) in 1962. In America,
the regulations are referred
to as Current Good
Manufacturing Practice
(cGMP). The lower-case
“c” differentiates the US
from the EU: in the US, the
regulations are reviewed
every year to ensure they
are up to date and adapted if
necessary.
Good Distribution Practice (GDP)
These regulations aim
to ensure that a product
makes it safely from A to
B. Individual regulations
may differ from country to
country. On 7 March 2013,
the European Commission
published its Guidelines on
Good Distribution Practice
of medicinal products for
human use, which entered
into force on 7 September
2013. In addition to helping
to improve the monitoring
of distribution channels
and therefore safeguarding
the quality and integrity
of medicines, they aim to
prevent counterfeits from
entering the legal supply
chain.
Good Pharmaco-vigilance Practice (GVP)
Pharmacovigilance is the
science and activities relating
to the detection, assessment,
understanding and prevention
of adverse effects or any
other possible drug-related
problem, as defined by the
WHO. The main objective is to
reduce patient safety risks by
monitoring the risk-benefit-
ratio of the substances on
the basis of incoming case
reports. The WHO Uppsala
Monitoring Centre (UMC) in
Sweden has been the center
of the reporting system
since 1978. It operates the
“VigiBase” database. More
than 15 million case reports
from over 100 countries have
been received and evaluated
since 1968.
Clinical study Market launch Distribution
Phase 1Suitability testing
on a small group of healthy individuals
Phase 2Testing on a small group of patients
Phase 3Testing on
several thousands of patients
Application for marketing authorization
Production and market launch
Supply chain
Monitoring and product safety
checks
Use in practice
6 2 2
5 1
GDPGCP GVPGMP
Source: Pro-Test Germany Vfa – German Association of Research-Based Pharmaceutical Companies
48
Providing access to quality medicines
“Sandoz aims at increasing patients’ access to a comprehensive range of high-quality medicines at an affordable cost worldwide.”Michael Kocher, Sandoz
What does quality mean to you personally?
For me, quality means continuous improvement
and making no compromises. It is far more than
an external requirement, like passing audits by
the authorities. At the end of the day, we strive
to ensure that the patients are provided with
highest quality medicines. This is what Sandoz’
philosophy “Quality beyond compliance” is
about: to put patients’ needs first. We believe it
is essential for Sandoz’ success to deliver two
aspects of quality: the measurable quality of our
medicinal products, which includes consistency
of processes, as well as the unique commitment
of quality in all our activities.
The quality of the final product and
how it is manufactured…
These two issues are inseparably linked to each
other. For Sandoz, sustainability means ensur-
ing the high quality of our pharmaceuticals,
while maintaining the highest standards in the
interests of associates, patient safety and the
environment – in everything we do. We imple-
ment the highest environmental standards in all
our business practices and activities worldwide.
These global standards apply equally to our
employees and business partners. We strive
to make efficient use of natural resources and
to minimize the environmental impact of our
activities and products. And we do all of this to
ensure that people around the world have ac-
cess to high-quality medicines.
Why is Access such an important
topic for Sandoz?
Despite all the medical breakthroughs of the
past century, universal access to healthcare
is still the most important medical need that
has not been fulfilled yet. At least 400 million
people worldwide have no access to health-
care at all and more than 2 billion lack access
to basic medicines. Sandoz aims at increasing
patients’ access to a comprehensive range of
high-quality medicines at an affordable cost
worldwide. On the one hand, this happens
through the classic retail channel within the
respective countries. On the other hand, we sell
our products via our B2B organization partner-
ing with selected pharmaceutical companies.
This enables us to reach an enormous number
of patients: an estimated 535 million patients in
2016. Our goal is to reach one billion.
Global Head B2B Business Michael Kocher is responsible for both API and FDF Partner Labels at Sandoz.
In our interview, Michael Kocher talks about the extension of the business, his concept of quality and the motivation he gets from the Sandoz aim of providing high-quality medicines globally.
49
In 1962, the thalidomide tragedy rocked the world of
pharmaceuticals. The sleeping tablet and relaxant
marketed in Germany as Contergan caused thousands of
children to be born with severe malformations. Until then,
the substance was considered harmless and was available
in Germany without prescription. It was even recommended
to pregnant women to alleviate morning sickness.
It took a total of four years before the medicine was
taken off the market. Some 320 million daily doses were
produced during that time, despite the fact that initial signs
of the product causing nerve damage were reported as
early as 1959. The manufacturer did not take Contergan
off the market until the end of November 1962, when
pressure from the media had intensified. The scandal led
to comprehensive regulation of the entire pharmaceutical
market. The very reason the scandal occurred in the
first place was the lack of a Medicinal Products Act in
Germany – and even that would still take some time. Not
until 15 years later did the government pass a law making
the authorization process mandatory, if only for new
compounds. The US reacted more quickly and tightened
its safety regulations just a year after the scandal. Today,
Patient safety revisited535 million patients took Sandoz products in 2016. Sebastian Horn’s team is tasked with making sure that these are as safe as possible. It is a huge responsibility that requires a keen eye.
What does Sandoz Global B2B Business
offer to its clients?
Our B2B Business offers a broad portfolio
of products and services. It also covers
extensive geographic areas. We are not a
traditional CMO: the vast majority of the
products we sell are Novartis developments,
so we own the IP. We offer highest quality
products meeting the outstanding safety
standards of Novartis. This is fairly unique,
particularly in light of our constantly growing
product range, which includes much more
than anti-infectives by the way. Considering
the industry trend towards a consolidated
supply base, it is a major benefit for our
customers, who can get products of several
therapeutic areas from a single source.
What are the greatest challenges when
it comes to quality?
One major challenge is the external sourcing.
Certain components are delivered to us by
our suppliers. To ensure that all materials
meet our standards, we conduct rigorous
examinations upon their arrival. One more
challenge is the reproducibility: all processes
have to comply with the high-level internal and
external requirements all the time. Variable
factors, such as environmental conditions,
outside temperature or the staff matters at the
production lines, are not allowed to affect the
quality of the final product by any means.
What is your motivation at Sandoz?
The pharmaceutical industry is a truly signifi-
cant one – we produce life-saving medicines.
All products I was previously responsible for
were nice to have but not really essential. This
is why I accepted the offer from Sandoz. I said
to myself: this is an experience that I would
really like to make.
50
products not only have to be thoroughly tested before they
are approved, but their effects and potential side effects
also have to be closely documented afterwards as well.
KNOW YOUR MEDICINE
“No medicine, no substance, is safe or unsafe as a
matter of principle – it depends to a great extent on the
individual patient, as well as on how much of it is taken
and when. We have to know exactly what these factors
are and document them to make taking medication as
safe as possible,” says Sabastian Horn, who heads up
the Global Pharmacovigilance department at Sandoz in
Holzkirchen, Germany. Explaining such a broad product
portfolio and the rapid pace of medical progress in a way
that is understandable to non-experts is quite a challenge.
“Medication and knowledge are like hardware and software:
They have to be perfectly coordinated. Our work informs
doctors and patients on how to take each substance and
what it does,” Horn tells us.
AN EYE FOR DETAIL
To this end, the department closely monitors the side
effects of the products – in clinical studies, by consulting
scientific journals, and by drawing upon feedback from
patients and doctors. A computer program statistically
evaluates the cases, but doctors and pharmacists also
assess whether the symptoms are linked to the medicine.
If so, there are various consequences. “We may just
have to update the patient information leaflet to include
a new potential side effect. Or we may have to add a
contraindication, for instance that the substance should not
be taken by children,” Horn explains. Information may also
have to be sent out to doctors. In severe cases, the product
may have to be classified as prescription-only or it may
have to be reserved for administration in a hospital – or it
could be taken out of circulation entirely.
SAFET Y FIRST
“My family takes Sandoz products, too. That is my
motivation. I want them and all other patients to get the
best medicines and be fully informed about what they are
taking,” says Sebastian Horn. As a qualified doctor, he is
“My family and all other patients should get the best medicines and know exactly what they are taking.”Sebastian Horn, Sandoz
aware of the responsibility he shoulders: “Half a billion
people per year take our compounds. There is no point
sweeping risks under the carpet. We have to do the right
thing for patients. We owe it to them and we owe it to our
reputation. Even if we have to exclude a patient group
from taking a substance, at the same time we are able to
say to everyone else with good conscience: You can take
it safely.”
The Contergan case taught the industry a terrible lesson
on how far drug safety has to go. It just so happens that
thalidomide is being prescribed again: It is an effective
leprosy treatment and can also be used to treat cancer.
Pregnant women are still strongly advised against taking it.
