Pharma Report Winter 2021 - Retrospective view of legal developments for the pharmaceutical industry in Norway
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Pharma Report
Winter 2021
Retrospective view of
legal developments
for the pharmaceutical
industry in Norway
5-year
anniversary edition
Introduction
Dear reader As part of our desire to share information with
As the first part of 2020 was an unprecedented our partners and other interested parties, we
and challenging period due to the effects of the have for several years published Pharma Report,
ongoing pandemic, people all over the world a biannual publication on some of the legal
continued to feel the impact of Covid-19 during developments for the pharmaceutical sector in
the second part of the year. With still challenging Norway. The latest edition marks the publication’s
times ahead, it is important to remember the value 5-year anniversary since its initial release in 2016.
of compassion and understanding as we together
take the steps required to ensure the safety of our In this anniversary edition, you can read about
communities and those we hold dear. a supreme court case regarding whether a
university had obtained an invention allegedly
The second part of 2020 demonstrated that the made by a research fellow, as well as the
pharmaceutical and life science industry plays a implications of the landmark decisions by the
pivotal role in overcoming the obstacles caused European Court of Justice on both SPCs and
by this pandemic. During the second half of the whether cannabidiol is a narcotic. You can also
year, Haavind has assisted the industry in several gain insight into EU’s new pharmaceutical strategy
matters directly related to Covid-19. We are well as well as the evaluation of the SPC-system,
aware of the effects on day-to-day business and gain knowledge on the new guidelines for
and the significant contributions by the industry procuring new medicinal products in the specialist
and their staff, which positively affect patients, healthcare.
healthcare personnel and communities. As 2020
demonstrated that access to a well-functioning As a leading law firm on healthcare and life
healthcare system is even more critical to science in Norway, our team continuously and
society than ever, it has also shown that the closely monitors legal developments relevant to
pharmaceutical industry is a key stakeholder of the pharmaceutical sector. If you wish to discuss
the puzzle. how your business can meet the legal challenges
of this innovative and highly regulated sector, you
are always welcome to contact us.
2
About the authors
Håkon Austdal
Senior Lawyer
Håkon is the primary author and editor of Haavind’s Pharma Report. He
specialises in regulatory affairs and intellectual property rights (IP), particularly
focusing on the healthcare and life sciences sector. He assists pharmaceutical
and biotechnology companies with a variety of services, including regulatory
advice, patent litigation, management, licensing and enforcement
of intellectual property rights, complaints on administrative decisions,
pharmaceutical advertising and interaction between healthcare personnel
and healthcare organizations, as well as various commercialization and R&D
agreements
In addition to a law degree, Håkon also holds a bachelor’s degree in
pharmacy, and has work experience from various pharmacies, as well as the
Norwegian Medicines Agency.
Håkon is recognized as a Rising Star by Legal 500 (2020) in the category
Intellectual Property.
Vebjørn Krag Iversen
Partner and Head of IP
Vebjørn is a contributing author of Haavind’s Pharma Report. He is the Head
of Haavind’s IP Practice Area and has substantial expertise with advising the
pharmaceutical and life sciences sectors with all aspects of IP. His practice
includes patent litigation, trademarks and copyright issues, trade secrets,
product imitation and strategic IP advice, IP licensing, commercialization and
R&D agreements.
Vebjørn is recognised as a Next Generation Partner by Legal 500 (2020) as
well as being ranked in Chambers and Partners (2020), both recognitions in
the category Intellectual Property.
3
Content
05 Supreme court case regarding employee’s inventions
09’ The landmark ruling from CJEU on cannabidiol (CBD)
12 The new law on the protection of trade secrets
16 Clinical trials and the use of anonymous expert declarations
20 A brief look at the EU’s New Pharmaceutical Strategy
23 The end of SPCs for new applications for old drugs
27 Evaluation of the SPC-regulation
30 New guidelines for implementing medicinal products in
specialist healthcare in procurement
34 Summary of minor regulatory developments
4
Employee’s
rights
Supreme court case
regarding employee’s
inventions
Collaboration between academia and
industry is often fruitful but requires an
orderly approach to the use of and rights
to project results to avoid pitfalls.
Background
The case concerned a dispute on inventorship and remuneration
between a former employee and the University of Oslo. The
former employee was employed first in a temporary position as an
engineer at one of the university’s faculties, then later as a research
fellow and finally admitted to a doctorate program at the faculty.
As part of her doctorate program, two members of the scientific staff
were appointed as her supervisors.
As part of her doctoral degree thesis, the research fellow had
written a draft of an article describing a discovery made during
her work, which consisted in growing bone cells from mice in a
water-soluble cellulose gel called Histocare, which had been
developed by a Swedish professor. The Swedish company Ascendia
manufactured the gel. In 2004, the university had received several
tubes of the gel from one of the supervisors to discover possible
new methods of use for the gel, including healing of wounds.
No formal material transfer agreement was made between the
university, Ascendia and the supervisor, as this was considered
purely academic cooperation. However, this project was put on
hold for other reasons until the research fellow was employed and
instructed by one of the supervisors to perform research to test the
survival of bone cells in the gel.
5
Employee’s
rights
In the summer of 2006, the research fellow In 2009, the research fellow finished her doctoral
discovered that the bone cells had formed degree. In 2010, she filed a complaint against
three-dimensional growth, which according the university. In the complaint, she stated that
to her was unexpected and a result caused she had found a patent application online and
by deviating from the instructions given by her believed it was based on her work with the
supervisors. Consequently, there was extensive Histocare gel. The university responded that no
contact concerning the discovery between the inventions had been made at the university in
supervisors and the Swedish Professor during her research project. Thus there was no basis for
the summer. The finding resulted in a draft for a the research fellow or her supervisors being co-
scientific publication where the research fellow, inventors.
her supervisors and the Swedish Professor were
co-authors. The findings of this draft article were The case at the District Court and Court of
presented on a Nordic conference during the Appeal
spring of 2007. The draft was not published, In 2015, the former research fellow filed a lawsuit
but further work on the publication resulted in against the university, Ascendia and the Swedish
a second draft made available to the Swedish Professor at Oslo District Court. The lawsuit
Professor in 2008. Neither this draft was published. against Ascendia and the Swedish Professor was
ultimately rejected by the Supreme Court in 2017
Meanwhile, during the autumn of 2006 and due to the lawsuit having to be filed to the courts
spring 2007, there had been extensive contact in the country of their domicile (i.e. Sweden), cf.
between the supervisors and the Swedish the rules of the Lugano Convention. As such, the
Professor, where it inter alia had been discussed remaining party of the lawsuit was her former
whether the publication of the results could be employee, the university. The material aspects
delayed in light of a patent application that was of the case were processed by Oslo District
being prepared by Ascendia. During 2007, one Court. The former research fellow had alleged
of the supervisors had also provided input on the several grounds against the university, including
patent application. This work was performed by a claim on remuneration for inventions claimed
the supervisor via his own company, not formally by an employer. She also claimed damages for
through the university. However, the specific infringement of copyrights.
dealing concerning these questions were not
disclosed by the supervisor to the university until The Norwegian Act respecting the right to
a later stage. A patent application was filed in employees’ inventions (the Act) stipulates that
Sweden in 2007 by Ascendia, which formed the an employer can claim an invention from an
basis for a PCT-application that inter alia has employee in certain circumstances and under
resulted in a granted European Patent. Ascendia certain conditions. Section 7 of the Act stipulates
used parts of the draft articles in the patent that an employee has the right to remuneration
applications. The Swedish Professor was named for inventions, whether the invention is claimed
as the sole inventor in these patent applications. with the basis in the Act itself, or “on other basis”
The patent applications concerned a product – (e.g. an agreement). This, however, presupposes
osteoblastic cell aggregate – which is suitable for that the employee is an inventor, and furthermore
treating wounded bone tissue and a method for that the invention has actually been claimed by
manufacturing such a product. the employer.
6
Employee’s
rights
The District Court issued its decision in February work as a supervisor and that of an independent
2018 and found that the research fellow was not consultant in the same research project, and that
a co-inventor of the patents in questions, and the supervisor’s collaboration with the Swedish
thus did not assess whether the university had Professor and access to the draft article occurred
obtained the inventions described in Ascendia’s in relation to his employment at the university.
patent applications. The court also ruled that Consequently, the Court of Appeal found that
the university was not responsible for any misuse the university was liable for damages due to
of copyrights since there was no identification infringement of copyright. However, in measuring
between the supervisor’s actions in this regard the damages, Court of Appeal found that no
and the university. Consequently, the claim for sufficient evidence had been presented that the
damages for copyright infringement was also research fellow had incurred a financial loss
rejected. such as loss of royalty for the publication or other
financial loss that could be derived from the
The research fellow appealed the case to infringement of copyright.
Borgarting Court of appeal, which heard the
case in November 2019 and rendered its’ decision The case at the Supreme Court
in December 2020. Unlike the District Court, the The research fellow appealed the case to the
Court of Appeal ruled, while expressing some Supreme Court, which only decided to process
doubt, that the research fellow was the co- whether the university had obtained the invention
inventor of the invention described in the patent and thus whether the research fellow was entitled
applications. However, the Court of Appeal to remuneration under the Norwegian Act
also ruled that the university had not obtained respecting the right to employees’ inventions.
the invention, and consequently, the research
fellow had no right to remuneration according To be entitled to such remuneration, the employer
to the Act respecting the right to employees’ must have obtained the invention either based on
inventions. Also, unlike the District Court, the the rules such acquisition described in the Act or
Court of Appeal found that the supervisor had “on other basis”, cf. the wording in section 7 of the
acted as an employee of the university, and Act. It was clear that the procedure described in
that it could not be differentiated between the the Act had not been followed, thus the question
7
Employee’s
rights
for the Supreme Court was whether the university Comments
had obtained the inventions “on other basis”. While the result of this case may seem unfair to
the employee, the Supreme Court’s assessment
The Supreme Court found that if this is the on this matter is hardly surprising. Nevertheless,
case, a condition is that the employee must the case serves as a reminder on the many
have accepted or approved the employer’s challenging aspects that must be considered for
acquisition, and thus have renounced his right to enterprises involved in R&D and collaborate with
the invention. As such, it is not enough that the academia – which pharmaceutical companies
employer has administered the invention as he do extensively. Beyond the legal questions of the
would have such rights. Both parties must have case, the matter also raises several ethical issues,
committed to transfer the rights to the invention where the case has raised extensive criticism of
from the employee to the employer, which is a the university’s conduct relating to this matter.
question which must be evaluated based on
ordinary rules on entering into agreements. The case should thus serve as a reminder for
the pharmaceutical industry of the importance
Otherwise, the employer’s administration and of ensuring proper agreements regulating the
use of the invention is unlawful and may result in performance of R&D activities properly and the
damages, but not in remuneration as stipulated in right to project results from such collaboration,
the Act. as well as including the right to publication of
the results. There are challenges that must be
With regard to whether there existed such “other considered when collaborating with academic
basis” in the case at hand, the Supreme Court institutions, including the need for sufficient and
pointed to the fact that the supervisor had acted tailored IPR-clauses and financial compensation
in relation to the invention without the former in cases where the project results in valuable
research fellow’s knowledge could not commit output such as patentable inventions. Further
her to transfer the invention to the university. awareness should also be raised internally in
The court also pointed out that the supervisor’s academia and among R&D intensive industries
actions could not be deemed to have bound the on the ethical implications that can occur
university to have acquired the invention, which during collaboration process and the need for
also was outside his authority. transparency in these decisions.
Consequently, the Supreme Court ruled that the
university had not obtained the invention based
on “other grounds”.
8
Regulatory
The landmark Is CBD from cannabis sativa
still a narcotic drug? It’s
ruling from CJEU complicated.
on cannabidiol Background
(CBD) The Cannabis sativa plant (also known as
hemp) naturally contains several different
active substances. The two most known are
tetrahydrocannabinol (THC), a psychotropic
substance, and cannabidiol (CBD), which does
not provide such an effect.
Over several years, the emergence of productions
containing CBD has risen significantly in the
EU. Examples of such products are cosmetics,
foodstuffs, and electronic cigarettes. From a
medicinal law perspective, the problematic
aspects concerning CBD is its extraction from the
cannabis plant. Such extracts will contain various
degrees of THC. Several countries allow for the
cultivation of so-called industrial hemp, provided
that the THC content of the cannabis plant does
not exceed 0.2% THC. And while this has allowed
for the emergence of products containing CBD
based on the extract of cannabis sativa, the
regulatory regime for such products is somewhat
challenging.
The Single Convention on Narcotic Drugs of
1961 as amended by the 1972 Protocol defines
cannabis as “the flowering or fruiting tops of
the cannabis plant (excluding the seeds and
leaves when not accompanied by the tops)
from which the resin has not been extracted,
by whatever name they may be designated.” A
“drug” according to the same Convention is any
substance listed in either Schedule 1 or Schedule
2 of the Convention. Listed in Schedule 1 is
“Cannabis and cannabis resin and extracts and
tinctures of cannabis”.
9
Regulatory
In Norway, the narcotics regulation defines the EU, and if the ban violated Article 34 and 36
cannabis as a narcotic substance, which means on the Treaty of the Functioning of the European
that the manufacturing, procurement, sales, Union (TFEU), which prohibits unjustified
import, export, storage, possession and use quantitative restrictions on the free movement of
of cannabis are prohibited. The definition of goods in the internal market.
cannabis is stricter than that of the Convention
since cannabis refers not only to the “flowering First, the CJEU had to interpret whether CBD was
or fruiting tops of the cannabis plant”, but to a narcotic substance. A prohibition on narcotic
all of the parts of the plant above the ground drugs generally exists in all Member States of the
(excluding the seeds). Norway does not have any EU with the exception of strictly controlled trade
rules that allows for a 0.2% limit of THC in the for use for medical and scientific purposes. It may
plant where the CBD is extracted. Consequently, thus not rely on the principle of free movement of
CBD extracted from the cannabis plant (including goods.
the leaves) will be considered a narcotic by the
national narcotics regulation. In this regard, the CJEU found that it was clear
that the CBD at issue was extracted from the
The recent decision from the CJEU on CBD Cannabis plant in its entirety. As such, fell under
On 19 November 2020, the European Court the literal interpretation of the Single Convention
of Justice (CJEU) rendered a decision (case on Narcotic Drugs and would thus constitute a
C‑663/18) on the marketing of CBD products «drug» under this convention.
in the European Union. The background of the
case concerned the marketing and distribution However, the CJEU also found that the purpose
in France of an e-cigarette with CBD-oil, where of the convention had to be taken into account
the CBD-oil cartridges where produced from when interpreting whether CBD was a drug. It
industrial hemp in the Czech Republic, which pointed out that CBD did not appear to have
allows for the use of the entire cannabis sativa any psychotropic effect or any harmful effect on
plant in production. However, in France, national human health based on available scientific data,
legislation prohibited use etc. of cannabis, and that the cannabis variety from which the CBD
cannabis plants and cannabis resin, products was extracted had a THC content not exceeding
containing cannabis or products obtained from 0.2%. In light of these facts, the CJEU found that
cannabis, cannabis plants or cannabis resin. it would be “contrary to the purpose and general
However, an exception was made for commercial spirit” of the convention to include CBD “under
use provided that the plant came from one of the definition of ‘drugs’ within the meaning of that
several specified varieties of cannabis sativa, convention as a cannabis extract.” Consequently,
where only the fibre and seeds of the plants were CBD was not a narcotic drug, and it was lawfully
used, and the plant itself contained less than produced and marketed in the Czech Republic.
0.2% THC. This was not the case of the CBD-oil As such, Articles 34 and 36 TFEU applied.
cartridges in question and import and sales of the
products were thus contrary to French law. The CJEU also found that the French prohibition
constituted as having equivalent effect to
This raised the question of whether the French quantitative restrictions within the meaning of
legislation was in harmony with EU legislation. Article 34 TFEU. However, a measure having
The reference to the CJEU raised two questions: equivalent effect to quantitative restrictions
whether CBD could be considered an agricultural may be justified on one of the grounds of public
product under the Common Agricultural Policy of interest set out in Article 36 TFEU, which includes
10public health. Nevertheless, CJEU pointed Implications for Norway
out case law on Article 36, stating that such Norway is not a member of the European Union,
a national provision must be appropriate for and thus directly affected by the decision of the
securing the attainment of the objective pursued CJEU. However, the EEA agreement does contain
and must not go beyond what is necessary to similar provisions as those of article 34 and article
attain it and can only be considered appropriate 36 of the TFEU (cf. articles 11 and 13 of the EEA
for securing the achievement of the objective Agreement), and the principle laid out by the
pursued if it genuinely reflects a concern to secure CJEU on article 34 and 36 will apply likewise for
the attainment of that objective in a consistent the interpretation of those provisions.
and systematic manner.
However, the matter may not be as
The CJEU ruled that it is up to the national straightforward as it appears by first glance. On
court to determine whether the restriction 2 December, the UN Commission on Narcotic
on the marketing of CBD lawfully produced Drugs (CND) took a number of decisions on
in another Member state was appropriate the international control of cannabis and
and proportionate to protect public health. cannabis-related substances, including voting
Nevertheless, it provided guidance for the court over 1) recommendation to delete extracts and
to make such a determination, in particular, that tinctures of cannabis from Schedule I of the 1961
it was clear that synthetic CBD that would have Convention and 2) recommendation to add a
the same properties would not be affected by footnote to Schedule I of the 1961 Convention,
the prohibition. The CJEU also clarified that it was which would exclude preparations predominantly
not necessary to demonstrate that the property of containing CBD and not more than 0.2% of
CBD is identical to substances that are narcotic THC from international control. Neither of these
drugs, but that the court should assess the recommendations passed, which means that
scientific data available to make sure that the risk products containing CBD based on the extract of
to public health does not appear to be based the cannabis plant appear to still be covered by
on purely hypothetical considerations. While the convention.
not explicitly stated in the judgement, it is clear
that the CJEU is of the opinion that the French As such, it is still unclear how these two seemingly
prohibition as presented before it would likely not contradictory positions will shape Norway’s policy
hold up to scrutiny. and which will prevail. The Ministry of Health and
Care Services has requested that the Norwegian
Medicines Agency evaluate the significance of
the two decisions and their consequences for
Norwegian legislation on narcotics and how it is
to be practiced. The matter will then ultimately be
decided by the Ministry.
11Intellectual
property
The new law on the protection of
trade secrets
With effect from 1 January 2021, the new Norwegian Act on
trade secrets will enter into force. What are the implications for
the pharmaceutical industry?
12Intellectual
property
The pharmaceutical industry is one of the b) has commercial value because they are
most research-intensive industries globally, secret
and intellectual property rights are key to its
competitive edge due to the huge financial sums c) the holder of the information has made
spent on developing a medicinal product from a reasonable steps to keep secret
promising molecule at the lab to a ready-to-use
medicinal product which can be administered The three requirements are cumulative and must
to patients. A common view is that patents are thus all be fulfilled in order to enjoy the protection
the most important IP-tools that pharmaceutical as a trade secret by the Act.
companies have at their disposal to ensure return
on investment for companies and researchers The first requirement is self-explanatory, although
and thus enables new and innovative drugs. And the requirement of “easily available” may involve
while this may still be true, increasing attention is some nuisances regarding what degree of work
paid on data which should be considered and is required to produce the same information. For
protected as trade secrets. instance, a compilation of individual elements
may still be secret even if the individual elements
While the topic on confidentiality vs increased are publicly known, which for instance may be the
transparency and disclosure of clinical trial case with customer databases or formulas.
information is a well-known and challenging
area to manage for the industry, another The second requirement states that the
aspect requires just as much attention. The information has commercial value because it is
extensive interaction in the pharmaceutical secret. The commercial value may be the present
and biotechnology area, either in the form of commercial value, but also potential commercial
outsourcing arrangements with other firms or value. This requirement will be fulfilled where
via collaborations such as consortiums, joint infringement of the information may cause harm
ventures and other forms of collaboration, as to the holder of the information by, for example,
well as increased mobility of employees between undermining its scientific or technical potential,
companies, means that there is an increased commercial or financial interests or the ability to
transfer of sensitive information. It is crucial that compete.
exchange of such information is appropriately
and diligently managed. For the pharmaceutical industry, several forms
of information could thus be considered trade
The new Act on Trade Secrets key provisions. secrets. Examples of such information is strategic
More so will this be the case under the new business plans, data resulting from early-stage
Norwegian Act on trade secrets, which entered research, formulas, proprietary biological
into force with effect from 1 January 2021. The Act databases, clinical trial data (methods, results,
implements EU’s Directive 2016/943/EU on trade etc.) and processes to manufacture biologic or
secrets. biosimilar medicines.
The concept of “trade secrets” is defined in section Particular attention should be paid to the third
2 first paragraph of the Act. “Trade secrets” refer to requirement, that the holder of the information
information which must have made reasonable steps to keep the
information secret. This requires that the holder of
a) is secret in the sense that the information is the information must, based on the circumstances
not as a whole, or as arranged or assembled, and steps taken, have a legitimate expectation
publicly known or easily available
13Intellectual
property
in a start-up company than in a multi-global
business. Businesses should take this into account
when implementing or revising their trade secret
policy.
Steps that should be considered include (but are
not limited to):
− Identification of the business’ trade secrets
Marking documents that describe trade
secrets as “Confidential” or “Contains trade
secrets” etc.
− Ensuring that all employees, contractors
and collaborating partners have signed
and are subject to sufficient confidentiality
clauses (e.g. non-disclosure agreements)
− Implementing physical and electronic
that the information remains a secret. In other restrictions on access to trade secret and
words, it is not sufficient that the holder has not limiting the number of personnel with
spread the information himself. The requirement of access
reasonable steps requires a specific expectation − Educating your employees and personnel on
of the trade secret holder’s circumstances, the company’s policy on the management
considering how the business is organised and of trade secrets, especially regarding travels
which risk factors it is natural to exercise actions and remote working, as well as the need for
against. encryption, password protection and physical
storage in such situations
Such steps can include both physical barriers, for
example, restricted access to facilities, technical Mobility of employees has increased over the last
protection (for instance encryption) and legal decade, and the pharmaceutical industry is no
restrictions (for instance confidentiality clauses in exception in this regard. When an employment
contracts). is discontinued, companies should have good
routines in place to ensure that they contribute
The preparatory works of the Act describes to the protection of trade secrets, including
that the requirement of reasonable steps can requirements to return documents and stored
be considered a “cautious intensification” of information, as well as ensuring restriction of
the holder’s demands compared with the access to both premises and online access.
requirements in previous legislation. As such,
businesses should adopt a wholesome approach The Act naturally prohibits anyone from obtaining
to which steps they use to ensure that trade access to or misappropriation of trade secrets
secrets remain secret. in an unlawful manner. However, it is also
considered an infringement to e.g. obtain, use or
In this requirement lies not only qualitative disseminate a trade secret if one is aware that one
measures, but also a quantitative dimension. It is at the time of obtainment, use or dissemination
easier to demonstrate that reasonable steps have was or should be aware that the trade secret
been implemented for a small group of persons was obtained by an infringement. Furthermore,
14Intellectual
property
the manufacturing, marketing or sales of goods Comments
that infringes a trade secret, and import, export or Several aspects of the Act have previously
storage of such infringing goods is also prohibited. been described in various parts of Norwegian
The Act specifies that goods are considered as legislation, and as such, the Act constitutes a
infringing a trade secret if they are shaped, have continuation of previous legislation in a new form.
a characteristic or function or are manufactured However, as described above, particular attention
or marketed in a way that significantly benefits should be made to the “mild intensification” of
from a trade secret that has been unlawfully reasonable steps that are required for trade
acquired, used or disseminated. secret holders. Businesses should also take into
account that this requirement may be interpreted
and further elaborated upon in case law in the
future, both from national courts and from the
European Court of Justice. In other words, being
too relaxed on implementing steps may cause
problems at a later stage.
For pharmaceutical businesses, maintaining that
certain information is protected as a trade secret
is naturally important. Our experience is that both
major and mid-size pharmaceutical companies
have implemented steps to ensure secrecy and
have a conscious approach regarding their own
secrets. However, pharmaceutical industries
are often collaborating with other parties in the
development of medicinal products, including
SMEs and start-ups, and not only need to
have a conscious approach to their own trade
secrets, but also that of their counterparties.
While it may seem an extreme scenario, the
damages both financially and reputation-wise if
a medicinal product would have to be withdrawn
from the market or a clinical trial due to use of
misappropriated trade secrets from a third-party
cannot be exaggerated.
Preventive measures should thus be double-
edged - pharmaceutical companies should
educate their personnel not only on the
importance of protecting their own trade secrets,
but also on the importance of respecting the
rights of its collaboration partners. For the same
reason, when entering into an agreement where
trade secrets will be shared, it should be stated
precisely what information shared in the project
will constitute such trade secrets.
15Regulatory
Clinical trials
Background
On 19 August 2016, a university hospital (the
sponsor) applied for approval of the use of high-
and the use of
dosed cyclophosphamide in a clinical trial study
concerning breast cancer to the Norwegian
Medicines Agency (the NMA). The study’s
anonymous
primary objective was to prospectively evaluate
the objective response rate of dose dense
cyclophosphamide in patients with TP53 mutated
expert
breast cancer or TP53 wild-type breast cancer.
The NMA initially had objections and comments
declarations.
to the study presented to the sponsor on
26 September 2016. These objections were
addressed by the sponsor on 6 October 2016. The
NMA later approved the study on 10 October 2016
provided that certain amendments were made in
Is “new information” eligible the study protocol. A new protocol was submitted
by the sponsor on 20 October 2016. On 30
to stop a clinical trial if the October 2020, the NMA confirmed in an e-mail
that they did not object to the study being started
information was already based on the latest submitted protocol.
provided in the study
On 17 September 2019, the sponsor applied
protocol? And do anonymous for an amendment of the study protocol and
patient consent, which was made to extend the
expert declarations have study. The NMA then noticed that the patient
any merit in administrative population with locally advanced breast cancer
(LABC) was not consistent with the basis for the
decisions by a government original approval of the NMA. The NMA referred
agency? to that some patients with LABC were not offered
the standard triple treatment before they were
16Regulatory
included in the study, but instead were treated the documentation`s totality, the NMA alleged
solely with a taxane (a cytostatic drug). The NMA the study was performed with a different design
considered the standard treatment to consist of and for another patient group than which was the
taxane monotherapy followed by a combination basis when the study was approved.
of anthracycline and cyclophosphamide.
With regard to the second and third requirements,
After some lengthy correspondence with the the NMA, in essence, alleged that since the
sponsor following the next months, the NMA NMA approved the application on the condition
issued a warning to stop the inclusion of new that the patients should have received standard
patients in the study in February 2020. Following treatment prior to the start of the study, the NMA’s
the sponsor’s comments, an administrative order assessment of the patients’ safety was made
to stop the inclusion of new patients in the study based on other conditions than those present. The
was rendered in March 2020. NMA thus found that there was new information
that caused doubt about the participating
Pursuant to the Norwegian Clinical Trials patients’ security. There was particularly a
Regulation, the NMA has the authority to stop potential loss of prognosis due to the treatment
a pending clinical trial, insofar that either 1) the offered in the study. The NMA also found that
conditions for approval are no longer considered the fact that the patient population was different
fulfilled, 2) new information causes doubt about from the one NMA based for its approval, caused
the security of the trial or 3) new information doubts about the study’s scientific value since the
causes doubt about the scientific value of the trial. clinical relevance was harder to assess.
The NMA alleged that all these requirements
were applicable. In this regard, the sponsor pointed out several
aspects concerning the study`s safety and
Regarding the first requirement, the NMA alleged scientific value and why the assessments
that the study is being conducted on another of the NMA were wrong and based on a
patient group than that approved by the NMA misunderstanding, and that there had been no
on 30 October 2016. The NMA claimed that change of the inclusion criteria in the protocol
the study was approved on the basis that the and thus no change of the patient population.
patients should have tried standard treatment
before the inclusion in the study. However, the A somewhat peculiar aspect of the case was
sponsor referred to that in the study protocol of that the NMA prior to the decision to stop the
the application the inclusion criteria stated that inclusion of patients to the study had obtained
treatment of anthracycline was not mandatory a specialist declaration that was critical to the
for patients with LABC and TP53 mutations, and study. This was done in December 2019, and the
that the reason for this was also present. The specialist declaration was obtained due to the
inclusion criteria of the patient group had not application for amendment made by the sponsor
been amended. in September 2019. The specialist declaration
concluded that the study design offered a
Nevertheless, the NMA argued that it was the treatment which potentially provides loss of
application as a whole, including the sponsor`s prognosis since the treatment choice offered was
correspondence on the receipt of the application not “standard of care”. The sensational aspect of
up to the approval which formed the basis for the this specialist declaration was not named, it was
NMA’s approval of the clinical study. Based on presented anonymously.
17Regulatory
in the application for its view. Unsurprisingly, the
Ministry here referred to the clear statements in
the study protocol of the application referring
to those patients with LABC could be offered
monotherapy, as well as the reasons for not
providing anthracyclines. As such, the first legal
basis for stopping the study was not fulfilled.
On the second and third requirements for
stopping the study, the Ministry again pointed out
that the study protocol stated that patients with
LABC could be treated with taxane monotherapy
prior to inclusion in the study. Consequently,
this was not new information, and thus the
requirements for stopping the study were not
fulfilled in this regard either.
However, the Ministry pointed out that the NMA
had the option to overturn its own decision of 30
October 2016 based on the Norwegian Public
Administration Act section 35, which allows
for overturning the decision if the balance of
interests is significantly in favour of overturning
the decision. The Ministry found that if the risk
for loss of prognosis has been substantiated,
this requirement was fulfilled. The NMA had in
This anonymity was criticised heavily by the this regard referred to the anonymous specialist
sponsor, which also pointed out flaws in the declaration. The Ministry stated that the author
declaration, including that it lacked any reference of this declaration was unknown and chose not
to cited literature on the matter. to place any weight on it. Instead, it obtained a
specialist declaration from a professor in clinical
The Ministry’s decision oncology at the University of Copenhagen. This
Not surprisingly, the sponsor complained about declaration concluded that the study protocol
the decision. The NMA upheld its decision, and was entirely ethically responsible and that
the case was transferred to the Ministry of Health all patient groups included were offered an
and Care Services, which rendered its decision on acceptable treatment that would not cause loss
21 December 2020. of prognosis for the patients participating.
The Ministry first addressed whether the study was Consequently, the Ministry found that the NMA
being performed in a different patient population had no legal basis for its decision to stop the study
than previously approved. The Ministry stated that and revoked the NMA’s decision from March
the NMA outlined individual sentences scattered 2020.
18Regulatory
Comments
The case is somewhat exceptional, and the
correspondence between the sponsor and the
NMA discloses that with regard to the scientific
aspects of the case, there were significant
differences in the view of the sponsor and
the view of the NMA. However, from a legal
perspective, the NMA’s position appears to
completely disregard that it is the study protocol
that forms the basis of the clinical study. In
light of the clear statement in the protocol, the
NMA’s view of a “wholesome approach” of the
application is somewhat surprising.
More problematic is the use of an anonymous
declaration and to use this as a basis for an
administrative decision. If a declaration is to have
any merit in an administrative decision, it must,
of course, be possible for a third-party to assess
the author’s background and qualifications. In
a statement on the case before the media, the
Director of the NMA has justified the decision on
anonymity, stating that the level of conflict was
extremely high at the time of the decision.
19Policy
A brief look at the EU’s
New Pharmaceutical
Strategy
On 25 November 2020, the Commission
presented its new “Pharmaceutical
strategy for Europe”. The overarching
goal is to ensure that patients have
access to innovative and affordable
medicines and support competitiveness,
innovative capacity and sustainability of
EU’s pharmaceutical industry.
Overview of the strategy
The strategy, which is available at the Commission website, has four
main goals:
− Ensuring access to affordable medicines for patients and
addressing unmet medical needs (e.g. in the areas of
antimicrobial resistance, cancer and rare diseases)
− Supporting competitiveness, innovation and sustainability of
the EU’s pharmaceutical industry and the development of high
quality, safe, effective, and greener medicines
− Enhancing crisis preparedness and response mechanisms and
addressing security of supply
− Ensuring a strong EU voice in the world, by promoting a high
level of quality, efficacy, and safety standards
20Policy
The strategy contains several flagship initiatives, − A proposal to revise the variation framework
which in particular address the review and for medicines, through changes in legislation
revision of the pharmaceutical legislation in the and guidelines, to make the lifecycle
EU. This includes: management of medicines more efficient and
adapted to digitalisation
− A proposal to revise the system of incentives
and obligations in the pharmaceutical Many of these proposals are rather non-specific.
legislation considering the relationship Furthermore, some of the initiatives also stem
with intellectual property rights, to support from other strategies and action plans recently
innovation, access, and the affordability of published by the Commission. For instance, one
medicines across the EU of the initiatives mentioned is to optimise the
supplementary protection certificates system, to
− Considering introducing measures to restrict make it more transparent and efficient, which
and optimise the use of antimicrobial also is an initiative mentioned in the Intellectual
medicines, as well as exploring new types of Property Action Plan (which was presented on
incentives for innovative antimicrobials. the same day). An evaluation of supplementary
protection certificates has already been carried
− Review to addressing market competition out and was also published in tandem with the
considerations and thus improving access to pharmaceutical strategy (see separate article in
generic and biosimilar medicines, including this report).
interchangeability and the “Bolar” exemption
The strategy not only proposes legislative
− A proposal to revise the legislation on changes. For instance, a flagship initiative on
medicines for children and rare diseases antimicrobial resistance is to pilot innovative
to improve the therapeutic landscape and approaches to EU R&D and public procurement
address unmet needs through more tailored for antimicrobials and their alternatives aiming to
incentives provide pull incentives for novel antimicrobials.
The strategy also mentions several collaboration
− A proposal to revise the legislation to and support initiatives. Another example which
adapt to cutting-edge products, scientific concerns innovation is to support collaborative
developments (e.g. genomics or personalised projects bringing together stakeholders to take
medicine) and technological transformation forward the use of high-performance computing
(e.g. data analytics and digital tools) and artificial intelligence in combination with EU
health data for pharmaceutical innovation.
− A proposal to revise the pharmaceutical
legislation to provide for simplification, the The strategy also builds on the experiences
streamlining of approval procedures and gained during the COVID-19 pandemic
flexibility for the timely adaptation of technical concerning the vulnerability of supply lines for
requirements to scientific and technological medicinal products. The strategy proposes a
developments, to address the challenges revision of pharmaceutical legislation to enhance
relating to the interplay of medicines and security of supply and address shortages
devices through specific measures including stronger
21Policy
obligations for supply and transparency, earlier Despite the non-specific nature of several of the
notification of shortages and withdrawals, initiatives, the publication of the Pharmaceutical
enhanced transparency of stocks and stronger Strategy indicates that the following years will be
EU coordination and mechanisms to monitor, quite busy for the pharmaceutical industry, both
manage and avoid shortages. A proposal has with regard to regulatory aspects as well as those
been made to establish an EU Health Emergency involving the protection of intellectual property
Response Authority (“HERA”), which is intended to and innovation.
strengthen the coordination of operations across
the whole value chain in health emergencies. For Norway’s part, any amendments in
HERA will monitor and pool production capacity, pharmaceutical legislation in the EU will facilitate
raw material requirements and availability, thus an equivalent amendment in national legislation,
addressing supply chain vulnerabilities. provided that the amendments are included in
the EEA-agreement. Traditionally, Norway has
Comments been quick to adopt amendments that concern
The actions and measures of the Pharmaceutical regulatory changes in the basic pharmaceutical
Strategy will be implemented gradually, as many legislation, whereas other amendments have
initiatives are proposed to be completed within been a more cumbersome process. This is
either 2021 or 2022. The legislative proposals exemplified by the fact that the regulation on
concerning the pharmaceutical legislation will pediatric extensions was not implemented
likely be performed in late 2022 but will depend until 2017 in Norway, and the amendment in
on the progress of evaluation processes. Regulation 469/2009 concerning SPC-waivers
has yet to be implemented.
22Intellectual
property
The end of SPCs for new
applications for old drugs
Several years of divergent opinion on whether SPCs should be
granted for patents protecting new therapeutic application of
previously approved active ingredients has finally been settled
by the Court of Justice of the European Union.
A supplementary protection certificate (SPC) (b) A valid authorisation to place the product
is a sui generis intellectual property right that on the market as a medicinal product has
can extend by up to five years the protection been granted in accordance with Directive
conferred by a patent. However, SPCs only extend 2001/83/EC or Directive 2001/82/EC, as
the protective scope of the underlying patent appropriate
(the basic patent) to the “product” covered by
the authorisation to place the corresponding (c) The product has not already been the
medicinal product on the market and for any use subject of a certificate
of a product that has been authorised before
the expiry of the certificate. The term “product” (d) The authorisation referred to in point (b) is
is important in this regard since it is defined in the first authorisation to place the product
the SPC- regulation as “the active ingredient or on the market as a medicinal product
combination of active ingredients of a medicinal
product”. These four requirements have created numerous
legal challenges during the soon to be 30
SPCs for medicinal products are governed by years of SPC-protection in Europe (including
Regulation 469/2009/EU. In order to be granted the predecessor Regulation 1768/92/EEC), and
an SPC, there are four basic requirements that numerous court cases have been brought before
must be fulfilled at the date of application (which the Court of Justice of the European Union (CJEU)
must be no later than six months after the grant in order to seek clarification. While several of
of the authorisation to place the product on the these cases have established a clarification on
market), cf. Article 3 of the SPC-regulation: the interpretation of these requirements, one issue
that has been quite elusive for several years is
(a) The product is protected by a basic patent whether SPC-protection could be granted for so-
in force called second-medical-use patents.
23Intellectual
property
“Second-medical-use patents” claims that did not cover the use prescribed by
A second-medical-use patent claims the use of Regulin.
an already known substance or combination of
substances for a new therapeutic indication. Such The CJEU ruled that in such a scenario, “the mere
patents have had a renewed interest in the patent existence of an earlier marketing authorisation
area in the recent years, as illustrated by the UK obtained for a veterinary medicinal product
Supreme Court decision Warner-Lambert vs. does not preclude the grant of a supplementary
Actavis in 2019. protection certificate for a different application
of the same product for which a marketing
Whether such patents should be eligible for authorisation has been granted, provided that
SPC-extension when an SPC has previously been the application is within the limits of the protection
granted for the same active ingredient(s) has conferred by the basic patent relied upon for the
been unclear. purposes of the application for the supplementary
protection certificate.” With this ruling, the CJEU
A literal reading of the requirements in the SPC- opened the door for SPCs on second-medical-use
regulation appears to preclude the possibility for patents on previously known active ingredients.
SPCs for second-medical-use since article 3(d) Nevertheless, the scope of the ruling caused
states that the first valid marketing authorisation much debate concerning the interpretation of the
for the product has to be the first marketing term “product” in this context and led to divergent
authorisation to place the product on the market approaches between EU-member states.
as a medicinal product. The SPC-regulation
defines the term “product” as the active ingredient
or combination of active ingredients, and not
different uses of said active ingredient(s). A
restrictive approach to the term “product” would
thus preclude the grant of an SPC based on a
second marketing authorisation for the same
active ingredient(s).
Early case law from the CJEU seemed to favour
such an interpretation, and thus the door seemed
shut for any hope of SPC on newly developed
medicinal products on previously known active
ingredients that had been on the market as
medicinal products for several years. In 2012, the
CJEU nevertheless rendered the famous Neurim
judgement (C-130/11). The facts of the case were,
in a nutshell, that the active ingredient (melatonin)
had been placed on the market originally as a
veterinary medicinal product (Regulin) for the
use of regulating the seasonal breeding activity
of sheep. Neurim had obtained a marketing
authorisation for the medicinal product Circadin,
which is used for the treatment for insomnia in
humans and held a patent with medical use
24Intellectual
property
The Santen case (C-673/18) only one therapeutic application of the product
This divergence ultimately led to a new referral in question. The CJEU stated that if that were the
to the CJEU in 2018, by the Paris Court of Appeal. case, “that therapeutic application might justify the
The facts of the case were somewhat similar – the grant of an SPC notwithstanding the fact that the
Japanese pharmaceutical company held a patent same active ingredient, or the same combination
that protects, inter alia, an ophthalmic emulsion of active ingredients, is covered by a different,
in which the active ingredient is ciclosporin, an already known, therapeutic application which
immunosuppressive agent. gave rise to an earlier MA.”
Santen obtained a marketing authorisation in 2015 However, the CJEU nevertheless stated that «It
for the medicinal product Ikervis, which contains follows that, contrary to what the Court held
the active ingredient ciclosporin. Ikervis is used to in paragraph 27 of the judgment in Neurim, to
treat severe keratitis in adult patients with dry eye define the concept of ‘first [MA for the product]
disease that has not improved despite treatment as a medicinal product’ for the purpose of Article
with tear substitutes, causing inflammation of the 3(d) of Regulation No 469/2009, there is no need
cornea. Upon applying for an SPC with basis in to take into account the limits of the protection of
their patent and the marketing authorization of the basic patent.» While the decision Neurim is
Ikervis, the French industrial property office (INPI) not further mentioned in premises of the decision,
denied the application, stating that there existed it is difficult to interpret this as anything other
an earlier marketing authorisation for ciclosporin, than an overturn of the previous view the Court
namely for the medicinal product Sandimmun, held in Neurim. The Court also pointed out that
which was indicated for preventing the rejection this interpretation is in line with the objectives of
of solid organ and bone marrow grafts and for the SPC-regulation, and referred to statements
other therapeutic indications. in the Explanatory Memorandum, referring to
that in establishing the SPC-regime, the legislator
The refusal ultimately brought the case before intended not to protect all pharmaceutical
the CJEU, which on 9 July 2020 issued its ruling research giving rise to the grant of a patent and
C‑673/18. The CJEU referred to the definition of the marketing of a new medicinal product, but to
“product” in the SPC-regulation, and that this protect research leading to the first placing on the
referred to the active ingredient or combination of market of an active ingredient or a combination of
active ingredients “irrespective of the therapeutic active ingredients as a medicinal product.
application of that active ingredient, or of that
combination of active ingredients, in respect of Consequently, the CJEU ruled that the first
which that MA was obtained.» marketing authorisation in article 3(d) cannot be
the marketing authorisation which covers “a new
With regard to article 3(d), the court referred therapeutic application of an active ingredient,
to the possible view that the concept of first or of a combination of active ingredients, and
marketing authorisation should refer to the first that active ingredient or combination has already
marketing authorisation “would necessarily call been the subject of a marketing authorisation for
into question that strict definition of the term a different therapeutic application.”
‘product’”, since the basic patent could cover
25Intellectual
property
With this decision, it can be argued that the
CJEU has succeeded in reducing some of the
complexity of the interpretation of the SPC-
regulation by avoiding a purpose-driven
interpretation which ultimately would lead to
more uncertainty and divergence between
Member States. On the other hand, critical voices
will argue that the CJEU’s decision also curtails
important incentives for pharmaceutical research,
and that the SPC-regulation is no longer fit for
purpose. However, as is clear from the recent
evaluation of the SPC-regulation by the European
Commission (a subject you can read more about
in a separate article of this publication), the SPC-
regulation is not designed as an incentive for
research models based on incremental innovation
(e.g. repurposing of existing molecules to address
new and challenging therapeutic areas), instead
its purpose is to encourage innovation in novel
active ingredients.
Comments The CJEU’s decision will nevertheless impact the
An interesting aspect in the aftermath of the pharmaceutical industry, and it could also lead to
decision is that a request for ruling (Novartis (C- claims for revocation of many previously granted
354/19)) which also concerned second-medical- SPCs as well as refusing pending and future
use patents and SPC, was withdrawn a few applications. The Norwegian Industrial Property
months after Santen was issued. The withdrawn Office has updated it’s examination guidelines
case concerned whether Article 3(c) makes it with reference to Santen, stating that a marketing
possible for an applicant who has previously authorisation is not the first authorisation if it
been granted an SPC on the basis of a product concerns a new therapeutic application of
which protects the product per se, to be granted an active substance or combination of active
a supplementary protection certificate for a substances if a previous marketing authorization
new use of the product which constitutes a new has been issued for the same active substance(s).
therapeutic indication specifically protected by a
new basic patent. The interpretation of the term
“product” in Santen would indicate that the CJEU’s
answer to this question would likely be negative.
26You can also read
