Friday December 13, 2013 (SW50 2013)

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NEWS
WORLDWIDE
EUROPEAN UNION
FRANCE
EUROPE
RUSSIA & RELATED COUNTRIES
NORTH AMERICA
LATIN AMERICA
AFRICA
AUSTRALIA & NEW ZELAND
INDIA, PAKISTAN & ASIA
DISCOVERY AND BUSINESS DEVELOPMENT

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Parmi les sujets slectionns dans ce numro :

Do Drugmaker plans to release trial data go far enough?
Le mythe du vaccin qui rend autiste

p.2
p.4

Can expert gatekeepers ensure clinical trial transparency?

Oral contraceptives linked to glaucoma
Could the Mini-tablet get kids to take their Medicine?

p.5
p.7
p.8

EU Commission formally invites medtech, pharma to early multipartyHTA pilot

p.10
EMA: Fee reductions for designated orphan medicinal products

p.12

HMA : Active Substance Master File (ASMF) worksharing procedure

p.14
European Pharmacopoeia and traditional Chinese Medicines
p.15

ANSM: Nouveau format de rapport dinspection: phase pilote

p.16
HAS : Rappel dinformation sur la vaccination contre les papillomavirus
humains par le Gardasil
p.18
UK PPRS published, but industry discord remains
p.19
FDA implementation of the Compouding Quality Act
p.27
FDA: Good review practice: Clinical review of investigational new drug
applications
p.28
FDA: Guidance for industry Bioequivalence studies with
pharmacokinetic endpoints for drugs submitted under an ANDA Draft
guidance
p.28
TGA: Australian statistics on medicines and vaccines 2012
p.37
Supply chain solution in China

p.39

India will require videotaped evidence of clinical trial consent

p.41

Beyond words, the world

 Adrien Tillet

NEWS
Do Drugmaker Plans To Release Trial Data Go Far Enough?
What weve learned from people in other industries, such as people who drill holes in the Gulf of Mexico,
is that the more trust there is for their products, they more leeway they have with regulation, said Hans
Eichler, senior medical officer at the EMA, who was speaking last week at a conference on clinical trial data
disclosure issues at the Harvard University School of Public Health.
The EMA, in fact, wants to proactively make trial data, which is submitted in connection with marketing
approval for a drug, available to researchers once an approval has been made. An aggressive online
campaign called AllTrials is trying to pressure drugmakers for greater disclosure. And BMJ, the British
Medical Journal, will no longer publish studies unless anonymized patient-level data is made available.
How has the pharmaceutical industry responded? Not as Eichler may have hoped. The trade groups in the
US and Europe released their own voluntary guidelines for data disclosure, which critics derided, but they
also attacked the EMA proposal and then made a clumsy effort to organize patient groups to protest.
Meanwhile, two drugmakers took the regulator to court to prevent data from being released.
In general, the pharmaceutical industry argues that releasing patient-level data may compromise patient
privacy, undermine trust in the regulatory system, increase the risk data would be misinterpreted and
weaken incentives for research. This last point refers to industry concerns that confidential commercial
information would be handed to rivals.
For their part, Glaxo and Pfizer maintain their panels are independent and, essentially, will function like
Data Safety Monitoring Boards that review trial data for safety and effectiveness signals as clinical studies
are under way. Just the same, the drugmakers are deciding on the composition of their panels, both of
which contain people who have worked as consultants (more here).
If we look 10 years from now, I think we will be able to say that data sharing has had a great public impact
on exploration and discovery (of medicines), Eichler said. But if you want to make full use of that
potential resource, then you must make full use of data. (Source: Forbes)

Pfizer to give data to participants in its studies

As the debate on data transparency continues, Pfizer has updated its policy "that will simplify and broaden
access" to information gathered in its clinical trials.

The drug giant says the move "meets or exceeds" the principles for responsible data sharing issued in July
by the Pharmaceutical Research and Manufacturers of America and the European Federation of
Pharmaceutical Industries and Associations. Its INSPIIRE public web portal for investigator-initiated
research will "offer qualified researchers a standard form and process for requesting access to anonymised
patient-level data from Pfizer-sponsored trials of approved (or discontinued) products/indications posted
on clinicaltrials.gov that have been complete for 24 months".
Other highlights of the updated policy will see the establishment of an external independent review panel
will consider "all requests denied or only partially approved by Pfizer". The company will also produce and
distribute lay-language summaries of clinical trial results to participants who wish to receive them, starting
with studies that begin enrolling in 2014. (Source: PharmaTimes)

Ditching Big Drugmakers for Biotech Brings Leukemia Boon

Its now one of at least five new medicines nearing or on the market that researchers say may change
chronic lymphocytic leukemia from a slow march to death to a manageable chronic disease. A cancer of the
blood and bone marrow, CLL is the second-most common form of leukemia among adults; about 15,680
people in the U.S. will be diagnosed with it this year, according to estimates from the National Cancer
Institute. Life expectancy can range from months to more than 10 years.
The new treatments, from Gilead Sciences Inc. (GILD), Pharmacyclics Inc. (PCYC), Infinity, Roche Holding AG
(ROG) and others, will be a focus of the annual American Society of Hematology meeting beginning Dec. 7
in New Orleans. Theyre collectively expected to generate as much as $9 billion in annual revenue by 2020,
according to analysts estimates compiled by Bloomberg. (Source: Bloomberg)

Vaccine May Prevent Progression to MS

A vaccine used in some countries to prevent tuberculosis given very early in the course of multiple sclerosis
(MS) appears to slow its development, preliminary results suggest.
In the study, published online December 4 in Neurology, individuals with clinically isolated syndrome (CIS)
given the Bacille Calmette-Gurin (BCG) vaccine had fewer MS type lesions and a lower probability of
developing clinically definite MS in the 5-year follow-up period.
Lead author, Giovanni Ristori, MD, University of Rome, Italy, explained to Medscape Medical News that a
pilot study conducted in the 1990s had suggested reduced MRI activity in patients with MS given BCG

vaccine. "As the vaccine is known to be safe, we thought it would be a good idea to test it in the very
earliest stages of MS in patients with CIS." "We did show an effect, with a reduction in MRI activity in the
vaccinated group mean of 3 lesions versus 7 lesions in the unvaccinated group," Dr. Ristori added. "And
in addition, 58% of the vaccinated group remained relapse free over the 5-year follow-up versus 30% of
unvaccinated controls. While these results must still be thought of as preliminary and no clinical
recommendations can be made, they do justify further studies to look at this intriguing effect." (Source:
MedScape)

Mopping up MRSA toxin with a sponge

After just one injection of the tiny sponges, half the infected mice survived compared with just one in 10 of
those treated with a conventional vaccine made from heat-treated bacterial toxin.
Two or more booster shots increased the survival rate to 100%.
The nanosponge vaccine was able to completely prevent the toxins damages in the skin, where MRSA
infections frequently take place, said Professor Liangfang Zhang, who led the US team from the University
of California at San Diego. In a series of experiments many thousands of nanosponges were injected into
infected mice. They proved effective at fighting the harmful effects of MRSA both in the bloodstream and on
the skin.
The scientists believe tailored nanosponge vaccines could be developed to neutralise pore-forming toxins
from a range of bacteria and other sources, such as snake venom.
The researchers wrote in the journal Nature Nanotechnology: Here, we show a nanoparticle-based toxindetainment strategy that safely delivers non-disrupted pore-forming toxins for immune processing.
We anticipate that this study will open new possibilities in the preparation of anti-toxin vaccines against
the many virulence factors that threaten public health. (Source: NursingTimes)

Police probe Novo Nordisk for late disclosure of drug setback

Novo Nordisk, the world's largest insulin maker, is facing a Danish police probe after it was reported by the
financial watchdog for not disclosing at once that its big new product hope Tresiba had been refused U.S.
approval.
Although the probe is unlikely to have a serious financial impact on the company, the largest by market
value in the Nordic region, it may tarnish its reputation and could leave it open to lawsuits from investors in
the United States, where its shares also trade.
The Danish Financial Supervisory Authority (FSA) said on Tuesday Novo should have issued a statement
about the U.S. decision not to approve Tresiba, its new long-acting insulin, on the evening of Friday, Feb. 8
instead of waiting until Sunday, Feb. 10.
Sydbank analyst Soren Lontoft Hansen said: "It will cost them more in terms of image than it will financially.
What might be a bigger problem financially is if U.S. shareholders get together in a joint action." (Source:
Reuters)

Le mythe du vaccin qui rend autiste

Comment pareille coquecigrue peut-elle prendre corps et prosprer ? Lenqute rvle un mix de
malhonntet, de partialit et de conflits dintrts dissimuls : La polmique est ne en 1998 avec la
publication dun article dans le Lancet voquant un lien possible entre lautisme et le vaccin contre la
4

rougeole. La publication rendait compte dune tude conduite par un gastro-entrologue anglais, Andrew
Wakefield, et portant sur 12 enfants (seulement). .... Si plusieurs tudes sont venues par la suite dmentir
tout lien entre le vaccin et lautisme, il a fallu attendre la publication, en 2010, dun rapport du Conseil
gnral de la mdecine britannique, pour rtablir la vrit.
Bien avant, il y avait eu la sinistre affaire du Mediator, lorigine de la loi dite Bertrand du 29 dcembre
2011, rigeant en culte la Transparence des liens entre industriels et prestataires de sant dune part et
tous professionnels et tablissements de sant de lautre, mais renvoyant au dcret les dtails de son
application. ... (Source : Lexcase)

WORLDWIDE

Government and Regulatory Bodies

http://www.pharmweb.net/pwmirror/pwk/pharmwebk.html

http://www.who.int/en/

Can Expert Gatekeepers Ensure Clinical Trial Transparency?

Over the past year, the controversy over disclosing clinical trial data has grown more heated.
Pharmaceutical industry trade groups have attacked a proposal by the European Medicines Agency, and
two drugmakers took court action to prevent the EMA from releasing data. The BMJ will no longer publish
studies unless anonymized patient-level data is made available. A UK parliamentary committee has also
criticized the government for failing to push industry harder for data. But the extent to which a new era of
transparency will emerge is uncertain at best. Stepping into the breach is a group that includes academics
and consultants, some of whom are affiliated with the Multi-Regional Clinical Trials Center at Harvard
University. In a recent essay in The New England Journal of Medicine, they proposed a learned intermediary
-- which would, essentially, be an independent board -- to act as a disinterested arbiter in sorting out
researcher requests and industry balking.
But how would a learned intermediary, or independent board, actually function? Besides assessing the
scientific soundness of each data request, the board would confirm that researchers have expertise that
qualifies them to conduct proposed analyses and determine whether public health benefits to be gained
from the research outweigh likely adverse effects on data generators and research participants, they
wrote in The New England Journal.
Gaining consensus is always the hardest part, but the MRTC hopes to form recommendations in the United
States and the European Commission over the next year or so as they go about obtaining definitive answers
to tough questions, such as:
What is confidential commercial information and should it be disclosed?
If so, when and how should that happen?
Should there be one central data repository?

If not, how many would agree to a consensus standard?

(Source: CPhI)

12 Things the Pharma Industry Can Do to Rebuild Real Public Trust

1. Stop overreaching on drug prices.
2. Support greater data transparency.
3. Get real about patient engagement.
4. Support the FDA, even when it might hurt.
5. Dont pay lip service to global health. Do something real.
6. Discover more great drugs.
7. Invest in your own employees.
8. Stop breaking the law in your sales and marketing departments.
9. Invest more in the basic public R&D system.
10. Stop direct-to-consumer TV advertising.
11. Work more on enabling technologies, and find creative ways to fix the clinical trial process.
12. Come up with a moonshot.

3 Life Sciences Companies That Are Built to Last

Lots of biotech companies today say they want to be great for a long, long time. But which of todays
companies are actually doing it? Which ones are truly visionary, and built to last?
Gilead Sciences: the Foster City, CA-based company (NASDAQ: GILD) built itself through acquisitions into
the worlds largest maker of HIV drugs in its first act. The companys second actspread over the last
decadeis all about diversifying into promising new fields like hepatitis C and cancer. Those ideas are now
well on their way to fruition, with a couple of important new drugs on deck for approval at the FDA.
Illumina. The San Diego-based maker of genetic analysis instruments (NASDAQ: ILMN) is the dominant
player in genomics, the maker of lab instruments and consumable reagents that biomedical researchers
and diagnostic companies rely on every day. This is a technical, competitive, fast-moving field at the
intersection of biology and technology. Many companies have tried and failed to attack Illumina on a
number of fronts. Few in the public recognize its name, but as the key enabler of the era of genomic
medicine, Illumina is in a position to have a greater impact on the world over the next 20 years than any
one drug company.
Genomic Health. The Redwood City, CA-based company (NASDAQ: GHDX) is widely admired in diagnostics
because it proved to skeptical insurers that diagnostics arent just cheap commodities anymorethey
provide information about health thats quite valuable. Genomic Health has continued to thrive and grow
under two CEOsRandy Scott and Kim Popovits. It is now rolling out new iterations of its original
OncotypeDx product that predict the risk of recurrence for patients with prostate and colon cancer, proving
its not a one-hit wonder in breast cancer. By showing the way in molecular diagnostics, Genomic Health
has inspired other entrepreneurs to think big about how new instruments can be used to better predict and
prevent disease before doctors have to turn to high-priced and often-toxic therapies. The company could

be highly profitable tomorrow if it wanted to be, but instead it chooses to get by on low margins while
continuing to invest in the future. Its a sure sign of a company with a view toward long-term excellence.
(Source: Xconomy)

Oral Contraceptives Linked to Glaucoma

Taking oral contraceptives for more than 3 years doubles a woman's risk for glaucoma, according to a large
population-based study.
"This study is the first to document this risk, and it's important for the general population," said lead
investigator Ye Elaine Wang, MD, from the University of California at San Francisco. "Postmenopausal
women should be reassured that the study does not prove causative effects, but women who have used
oral contraceptives for 3 years or more and who have additional risk factors for glaucoma should be
checked annually for the disease during their eye exams."
The cross-sectional study was based on 3406 women 40 years or older who participated in the National
Health and Nutrition Examination Survey (NHANES). The participants completed vision and reproductive
health questionnaires and underwent eye exams. (Source: MedScape)

Confirmed: Gabapentin Improves Alcohol Dependence Outcomes

"These results are consistent with the hypothesis that improved drinking outcomes with gabapentin may
be related to improvement in sleep measures that can be measured objectively with polysomnography,"
said lead author Kirk Brower, MD, a professor of psychiatry at the University of Michigan Medical School
and executive director of the University of Michigan Addiction Treatment Services, in Ann Arbor.
The findings build on those from a randomized, double-blind, placebo-controlled trial of 150 patients
published just last month, in which a 12-week regimen of oral gabapentin 900 mg or 1800 mg per day and
concomitant counseling showed efficacy in treating alcohol dependence and relapse-related symptoms of
insomnia, dysphoria, and craving, with a positive safety profile ( JAMA Intern Med. Nov. 4, 2013). (Source:
MedScape)

An effective eye drug is available for $50. But many doctors choose a
$2,000 alternative
Avastin costs about $50 per injection.
Lucentis costs about $2,000 per injection.
Doctors choose the more expensive drug more than half a million times every year, a choice that costs the
Medicare program, the largest single customer, an extra $1 billion or more annually.
Spending that much may make little sense for a country burdened by ever-rising health bills, but as is often
the case in American health care, there is a certain economic logic: Doctors and drugmakers profit when
more-costly treatments are adopted.
Genentech, a division of the Roche Group, makes both products but reaps far more profit when it sells the
more expensive drug. Although Lucentis is about 40 times as expensive as Avastin to buy, the cost of
producing the two drugs is similar, according to scientists familiar with the drugs and the industry.
Doctors, meanwhile, may benefit when they choose the more expensive drug. Under Medicare repayment
rules for drugs given by physicians, they are reimbursed for the average price of the drug plus 6 percent.

That means a drug with a higher price may be easier to sell to doctors than a cheaper one. In addition,
Genentech offers rebates to doctors who use large volumes of the more expensive drug. (Source:
TheWashingtonPost)

Could the Mini-Tablet Get Kids to Take Their Medicine?

A recent research study published in the Archives of Disease in Childhood has investigated the acceptability
of different oral formulations in young children and infants (aged 1-4) and this research indicated that
when given a choice, a small tablet was actually preferable and a more acceptable mechanism of drug
delivery than either syrups, suspensions, or powders for the group of children in the study. If we encourage
our children to take tablets, which is what the research suggests, then the market demand would grow
naturally. Maybe this research will encourage Pharma to consider specific tablets for young children.
(Source: CPhI)

Protective Packaging Solutions for Pharmaceutical Product Stability

The challenge for pharmaceutical packaging systems is medicinal product protection. ECA's Course
Protective Packaging Solutions for Pharmaceutical Product Stability from 2829 January 2014 in Berlin,
Germany, will show how to improve drug stability through barrier packaging and desiccants. Practical case
studies will be presented for specific packaging types and dosage forms. (Source: CPhI)

The ISO system - overview

Presentation_ISO_process_-_TC_276_Dec_2013.pdf

Prospoal of France for a new work item on Biobanks VF GD

ISO-TC276_N0007_Prospoal of France for a new work item on Biobanks.pdf

http://www.ich.org/

http://www.picscheme.org/

EUROPEAN UNION

http://www.ipec-europe.org

 Commission welcomes EU Member States' adoption of Horizon 2020

The European Commission today welcomed the adoption by EU Member States of Horizon 2020, the next
EU research and innovation programme. With a budget of nearly EUR 80 billion euro over seven years,
Horizon 2020 is the biggest EU research programme yet, and one of the biggest publicly funded worldwide.
Welcoming the adoption, Mire Geoghegan-Quinn, European Commissioner for Research, Innovation and
Science said: "I very much welcome the decision taken today, but the real work starts now. Over the next
seven years, we will use every cent of Horizon 2020's budget to build a stronger, more innovative Europe one that will be more competitive and improve the quality of life for everyone. We will launch the first calls
for funding under Horizon 2020 next week on December 11. These calls will be a huge opportunity for
scientists and businesses across the EU and beyond and are not to be missed." (Source: EC)

Industry says asking QPs to know laws in all EEA markets is

unrealistic
The European Commission (EC) proposed changes to Annex 16 of the EU good manufacturing practices
guidelines (GMP) in July , explaining that changes were needed to reflect globalisation of pharmaceutical
supply chains and the introduction of new quality control strategies.
The revision has been carried out in the light of Directive 2011/62/EU amending Directive 2001/83/EC as
regards the prevention of the entry into the legal supply chain of falsified medicinal products, and to
implement ICH Q8, Q9 and Q10 documents, and interpretation documents, such as the MIA interpretation
document, as applicable. Also, some areas, where the interpretation by member states has not been
consistent, have been clarified.
Industry group EFPIA was one of the first to comment. It suggested that while, the revisions reflect the
realities of the global supply chain, requiring QPs who work for global drugmakers to know the differing
quality rules in place in each European Economic Area (EEA) member state is unrealistic.
Due to the lack of harmonisation of international regulations, it is very unrealistic that the Qualified Person
can certify that the batch has been manufactured in compliance with laws of the destination country of the
medicinal product.
Instead EFPIA said that QPs should be required to certify that drugs are produced in compliance with EU
standards. (Source: InPharma)

 European drug trial secrecy case hit by delay

Officials said on Thursday that the vice president of the European Court of Justice had annulled earlier
interim orders preventing the release of data and had referred the matter back to the European Union's
General Court for further consideration.
With the legal situation still uncertain, sensitive data from trials involving AbbVie's rheumatoid arthritis
treatment Humira - the world's top-selling prescription medicine - and another drug from InterMune will
remain under wraps for now.
"Until a new decision is taken by the courts, we will not release the documents relating to the AbbVie and
InterMune products," EMA spokesman Martin Harvey said.
The EMA has already released millions of pages of detailed clinical trial information about different drugs an approach it says reflects growing public demands for more openness to ensure that drugmakers cannot
conceal adverse side effects.
AbbVie and InterMune argue in a case brought earlier this year that they have a right to the protection of
their business secrets, since this information could be used by competitors.
In 2010 the European Ombudsman, which investigates complaints about EU institutions, ruled that the
EMA should provide access to it - and the EMA plans to proactively release detailed data, rather than just
waiting for requests, from 2014.
A number of drug companies have recently shifted their position towards more transparency in the face of
this pressure from the agency and some stern critics in academia. (Source: Reuters)

Analysis: Copycat biotech drugs slow to take off in Europe

These cheaper versions of expensive biotech drugs, known as biosimilars, could slash the cost of treating
diseases like cancer and rheumatoid arthritis in the same way that generics have curbed spending on
traditional medicines.
But although Europe has pioneered their path to market - approving the first biosimilar drug in 2006 and
the latest, an antibody drug from U.S.-based Hospira and Celltrion of South Korea, in September - uptake
has been patchy.
Generic industry executives admit the market has been slower to develop than initially hoped, and a
number of firms have hit snags in developing the complex new products.
In theory, the use of biosimilars could produce savings of up to 33.4 billion euros ($45.5 billion) by 2020
across Europe, according to a study last year by researchers at the health-focused IGES Institut in Berlin.
Antibody drugs alone could contribute savings of 20.4 billion, the IGES analysis found.
In practice, the pace of savings may be a lot slower, reflecting caution among doctors, as well as the small
number of manufacturers competing in the biosimilar space and the modest 20-30 percent price discounts
on offer. (Source: Reuters)

EU Commission formally invites medtech, pharma to early

multiparty-HTA pilot (Source: Clinica)

10

 European Commission approves Fluenz Tetra for the prevention of

seasonal influenza in children
Fluenz Tetra is a nasally administered four-strain live attenuated influenza vaccine for the prevention of
influenza in children and adolescents from 24 months up to 18 years of age. The EC approval makes Fluenz
Tetra the first and only intra-nasal four-strain influenza vaccine available in Europe. The Marketing
Authorisation of Fluenz Tetra is based on data from a pivotal paediatric study. Findings showed that Fluenz
Tetra demonstrated a safety and immunogenicity profile that was comparable to Fluenz, a three-strain
(trivalent) live attenuated influenza vaccine already approved in Europe. (Source: FiercePharma)

Novo Nordisk gets final EU approval for haemophilia drug

The world's biggest insulin producer confirmed that the European Medicines Agency (EMA) approved its
marketing application after it had received a recommendation from the Committee for Medicinal Products
for Human Use on Sept. 20. (Source: Reuters)

Renewed version of the HTA Core Model available

Major revision of the underlying ontology, i.e. the generic questions and their allocation to various
domains. Relations of various elements have been considered and recorded in the Model (divided into
content relations and sequential relations).

Major revision of methodological guidance, including harmonization of advice across model

applications and updating the content to reflect recent methodological developments.

New application to enable full assessment of pharmaceuticals.

New standard consequences table to be included in collection summaries.

The legal domain and some appendices including auxiliary content are still in the same format as in versions
1.0 and 1.1r. The legal domain will be updated by April 2014 and the remaining appendices within 2014.
(Source: EUnetHTA)

European Medicines Agency

http://www.ema.europa.eu/ema/

Human medicines: Regulatory

11

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/landing/human_medicines_regulatory.js
p&mid=WC0b01ac058001ff89

Fee reductions for designated orphan medicinal products

EMA - Fee reductions for designated orphan medicinal products.pdf

PRAC considers benefits of Kogenate Bayer/Helixate NexGen

outweigh risks in previously untreated patients
Current evidence does not confirm increased risk of inhibitor development compared with other factor
VIII products
The European Medicines Agencys Pharmacovigilance Risk Assessment Committee (PRAC) has reviewed the
medicines Kogenate Bayer and Helixate NexGen and concluded that current evidence did not confirm an
increased risk of developing antibodies (factor VIII inhibitors) against these medicines when compared with
other factor VIII products in previously untreated patients with the bleeding disorder haemophilia A.
Therefore, the benefits from taking Kogenate Bayer and Helixate NexGen, which are known as second
generation factor VIII products, continue to outweigh the risks. Factor VIII is needed for blood to clot
normally and is lacking in patients with haemophilia A.
The review of the PRAC followed results from the RODIN study1, as well as preliminary 3-year data from the
European haemophilia safety and surveillance system (EUHASS). The RODIN study looked at data from 574
previously untreated children with haemophilia A who were given different factor VIII products. About a
third (177) of all the children developed factor VIII inhibitors against their medicine, which reduces the
benefit and makes bleeding more likely. This is a known risk of all factor VIII products but the authors of the
study concluded that children given so-called second generation full-length recombinant factor VIII
products such as Kogenate Bayer or Helixate NexGen were more likely to develop antibodies than those
given a third generation recombinant product. An increase in inhibitor formation was not seen with other
recombinant or plasma-derived factor VIII products.
The PRAC reviewed available scientific and clinical data on development of inhibitors in previously
untreated patients, including from RODIN and EUHASS, and concluded that the available data did not
support that Kogenate Bayer or Helixate NexGen were associated with an increased risk of developing
factor VIII inhibitors compared with other products. Although the existing risk minimisation measures were
considered adequate for both Kogenate Bayer and Helixate NexGen and should be continued, the PRAC
recommended that the product information should be updated with results from the RODIN study.
The PRAC recommendation will now be forwarded to the Committee on Human Medicinal Products
(CHMP), which will adopt a final opinion at its plenary meeting of 16-19 December 2013. (Source: EMA)

EMA: Conditions of use, conditions for distribution and patients

targeted and conditions for safety monitoring adressed to member
states for Sofosbuvir available for compassionate use (Source: EMA)

12

 Meeting highlights from the Pharmacovigilance Risk Assessment

Committee (PRAC) 2-5 December 2013
PRAC initiates further review of Iclusig
The European Medicines Agencys Pharmacovigilance Risk Assessment Committee (PRAC) has started a
further in-depth review of the benefits and risks of the leukaemia medicine Iclusig, particularly the risk of
blood clots or blockages in the arteries or veins that is associated with the medicine.
The Agency had recommended in November 2013 a number of measures to help minimise this risk,
however an additional review was considered necessary to further investigate issues related to this risk and
to assess the need for further changes to how the medicine is used.
PRAC recommendation on Kogenate Bayer and Helixate NexGen
The PRAC concluded that the benefits of Kogenate Bayer and Helixate NexGen, which are secondgeneration factor VIII products, continue to outweigh the risks in previously untreated patients with the
bleeding disorder haemophilia A.
Request for re-examination of the PRAC recommendation on diacerein-containing medicines
Some marketing-authorisation holders for diacerein-containing medicines have requested a re-examination
of the PRACs November 2013 recommendation to suspend these medicines. Upon receipt of the scientific
grounds of the requests, the PRAC will re-examine its recommendation and issue a final recommendation.
(Source: EMA)

Further review of Iclusig started

In November 2013, the European Medicines Agency reviewed updated clinical trial data with Iclusig
indicating that cases of blood clots and blockages in the arteries or veins were occurring at a higher rate
than was observed at the time of the medicines initial authorisation. The Agency therefore recommended
a number of measures to help minimise this risk. These included a warning against use in patients who
have had a heart attack or stroke in the past, and a recommendation that the cardiovascular risks (affecting
the heart and blood vessels) of all patients be assessed and measures be taken to reduce such risks before
and during treatment with Iclusig. Treatment with Iclusig should be stopped immediately in any patient
with signs of a blockage in the arteries or veins.
However, a number of issues required further investigation, including a better understanding of the nature,
frequency and severity of events obstructing the arteries or veins, the potential mechanism through which
the medicine leads to these side effects and whether there is a need to revise the dosing recommendation
of Iclusig. Therefore, the European Commission considered that a further in-depth review of relevant data
was necessary.
The Agency will now carry out this review to assess the need for further changes to how the medicine is
used. (Source: EMA)

EMA: Call for expression of interest to the attention of healthcare

product (pharmaceuticals or medical devices) developers (Source: EMA)

13

 Europe okay for AstraZeneca's Fluenz Tetra

The approved is based on data from a paediatric study which showed that the product demonstrated a
safety and immunogenicity profile comparable to the company's already-marketed three-strain vaccine
Fluenz. The EC decision follows a positive opinion from the Committee for Medicinal Products for Human
Use in September. (Source: PharmaTimes)

HERBAL MEDICINES FOR HUMAN USE

http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/herbal_search.jsp&mid=WC0b01ac058001fa1d

http://www.hma.eu/cmdh.html
WHATS NEW: http://www.hma.eu/186.html

HMA: Active Substance Master File (ASMF) worksharing procedure

(Source: HMA)

http://www.edqm.eu/en/edqm-homepage-628.html

147th Session of the European Pharmacopoeia Commission

At its 147th session, the European Pharmacopoeia Commission approved the priorities for the three
coming years, which are aimed at maintaining the scientific excellence, leading role and influence of
the Ph. Eur. worldwide.
During the session, 15 new texts covering all therapeutic areas were adopted: Agaricus phalloides for
homoeopathic preparations (2290), Agnus castus fruit dry extract (2309), Carrier proteins for the
production of conjugated polysaccharide vaccines for human use (5.2.11), Glucosamine sulfate potassium
chloride (2708), Homoeopathic pillules, coated (2786), Human normal immunoglobulin for subcutaneous
administration (2788), Ignatia for homoeopathic preparations (2513), Macrogols, high molecular mass
(2444), Meldonium dihydrate (2624), Methane (2413), Nettle root (2538), Nux vomica for homoeopathic
preparations (2514), Pullulan (2603), Sulfadimethoxine (2741) and Sulfadimethoxine sodium for veterinary
use (2745).
The Commission also adopted 94 revised monographs and three revised general chapters.
All of these texts will become effective on 1 January 2015 and will be published in supplement 8.3 of
the Ph. Eur. The list of all adopted texts will be published on the EDQM website.

Read the Press release of the 147th Session

More about the European Pharmacopoeia

14

 (Source: EDQM)

European Pharmacopoeia and Traditional Chinese Medicines

The EDQM, Council of Europe and the State Administration of Traditional Chinese Medicine of the Peoples
Republic of China (SATCM), jointly organised a symposium on Traditional Chinese Medicines (TCMs).

Read the Press release on the TCM Symposium

Read the Proceedings of the Symposium

More on the European Pharmacopoeia

(Source: EDQM)

FRANCE

+ 3,5 %, c'est le taux d'volution du CA (TTC) des mdicaments

remboursables dlivrs en officines de ville en cumul annuel mobile novembre 2013/ novembre
2012. Source Xpr-SO, le panel temps rel de CELTIPHARM (newsletter Celtinews du 6 dcembre 2013)

UVESTEROL: rappel des rgles d'administration chez le nouveau-n

et le nourrisson

L'ANSM (Agence nationale de scurit du mdicament et des produits de sant) et le laboratoire Crinex
rappellent les modalits d'administration des mdicaments UVESTEROL D et UVESTEROL vitamin
ADEC solution buvable chez le nouveau-n et le nourrisson.
En effet, malgr la mise en place de mesures de minimisation des risques inities en 2006 et renouveles
en 2011, des cas de malaises et de fausses-routes sont encore signals lors de l'administration de ces 2
mdicaments, en particulier chez des nouveau-ns prmaturs et des nourrissons gs de moins de 1
mois.
Dans ce contexte et dans l'attente de nouvelles formulations galniques demandes par l'ANSM au
laboratoire, des fiches conseils ont t labores, en complment de la notice, afin de sensibiliser les
parents sur l'importance de respecter les rgles d'administration de ces solutions buvables et d'utilisation

15

de la pipette doseuse. Ces fiches doivent tre remises par le mdecin lors de la prescription, ou par le
pharmacien lors de la dlivrance de ces mdicaments. (Source : Vidal)

Bta-2 mimtiques d'action courte par voie orale ou rectale: rapport

bnfice/risque dfavorable en obsttrique

Les mdicaments contenant des bta-2 mimtiques daction courte administrs par voie orale ou rectale ne
doivent plus tre utiliss dans le traitement des menaces daccouchement prmatur (MAP) en raison des
risques cardiovasculaires graves associs la prise de ces mdicaments.Cette conclusion de l'EMA
(Agence europenne du mdicament) fait suite une rvaluation europenne des indications en
obsttrique des bta-2-mimtiques, initie en dcembre 2012 par le PRAC (Comit pour lvaluation des
risques en matire de pharmacovigilance).
La rvaluation du rapport bnfice/risque na concern que les indications relatives lobsttrique. Ces
conclusions ne concernent pas l'utilisation des bta-2 mimtiques par voie injectable et par voie inhale
dans leurs indications en traitement des maladies respiratoires. (Source : Vidal)

Quand les applications lectroniques (e-apps) sont-elles des Dispositifs Mdicaux ?

Le Cabinet WHITE-TILLET est spcialiste de la question et peut vous aider y rpondre ; le cas chant,
nous pouvons vous assister pour le marquage CE de votre application.

http://ansm.sante.fr/

Nouveau format de rapport dinspection: phase pilote

L'Agence engage partir de janvier 2014 une phase pilote pour tester un nouveau format de rapport
dinspection qui intgre un certain nombre d'amliorations, dont la mise en application dlments de
gestion du risque.
La phase pilote se droulera sur une dure d'une anne dans le cadre habituel de la procdure
contradictoire mene aprs toute inspection de l'ANSM.

16

Nouveau format de rapport dinspection - Note explicative lattention des oprateurs

(11/12/2013)

(59 ko)

Rubrique Elaboration de bonnes pratiques

Mdicaments contenant de la diacrine et de la dompridone,

mdicaments base doctocog alpha et de zolpidem, vaccins anti-HPV
Retour dinformation sur le PRAC
Le Comit pour lvaluation des risques en matire de pharmacovigilance (PRAC) de lAgence europenne
des mdicaments sest runi du 2 au 5 dcembre 2013 Londres. Les rsultats intermdiaires ou finaux de
plusieurs procdures de rvaluation en cours ont t prsents et discuts. Le PRAC a ainsi recommand
la suspension de lAMM des mdicaments contenant de la diacrine, il a jug que le rapport
bnfice/risque de deux mdicaments base doctocog alpha reste positif. Des mesures de minimisation
des risques sont envisages pour les mdicaments contenant de la dompridone, ainsi que pour les
mdicaments base de zolpidem.
Mdicaments contenant de la diacrine et de la dompridone, mdicaments base doctocog alpha et de
zolpidem, vaccins anti-HPV Retour dinformation sur le PRAC (06/12/2013)

(53 ko)

Le Cabinet WHITE-TILLET sest entour de juristes de haut niveau pour vous aider
valider la publicit et la promotion de vos mdicaments. Leur expertise se
combine notre exprience rglementaire et notre matrise de la
mthodologie clinique. Contactez-nous pour le reviewing de vos documents
publicitaires ou promotionnels!

Iclusig (ponatinib): nouvelles recommandations concernant les

risques d'vnements vasculaires occlusifs - Lettre aux professionnels
de sant
Une augmentation du nombre d'vnements thrombotiques artriels et veineux a t observe chez des
patients traits par le ponatinib, lors du suivi prolong de deux essais cliniques en cours, lun de phase 1,
lautre de phase 2. Il sagit dvnements indsirables cardiovasculaires, crbrovasculaires et vasculaires
priphriques, ainsi que d'vnements thrombotiques veineux.
Les professionnels de sant peuvent continuer prescrire le ponatinib, conformment lindication
approuve, et en tenant compte des prcautions supplmentaires.
Le ponatinib ne doit pas tre prescrit chez les patients prsentant des antcdents d'infarctus du
myocarde ou d'accident vasculaire crbral, moins que le bnfice attendu du traitement soit suprieur
aux risques potentiels.
L'tat cardiovasculaire des patients doit tre valu et les facteurs de risque cardiovasculaire doivent tre
pris en charge et contrls avant linitiation du traitement par ponatinib. La surveillance cardiovasculaire
doit se poursuivre tout au long du traitement par ponatinib.
L'hypertension artrielle doit tre contrle au cours du traitement par le ponatinib. Linterruption du

17

traitement par le ponatinib doit tre envisage en labsence de contrle de lhypertension artrielle.
L'apparition de signes d'occlusion vasculaire ou de thromboembolie doit tre surveille ; en prsence de
tels signes, le traitement doit tre interrompu immdiatement.
Iclusig (ponatinib) : nouvelles recommandations concernant les risques d'vnements vasculaires
occlusifs - Lettre aux professionnels de sant (05/12/2013)

(166 ko)

Le Cabinet WHITE-TILLET a plus de 20 ans dexprience et dexpertise dans le

domaine des dossiers dAMM. Nous matrisons leCTD. Par notre structure et
notre rseau (cabinet associ au UK, rseau international), nous matrisons les
procdures et assurons un suivi efficace. Confiez-nous vos dossiers dAMM ou de
variations!

http://www.has-sante.fr/portail/jcms/j_5/accueil

Rappel dinformation sur la vaccination contre les papillomavirus

humains par le Gardasil
Les donnes de scurit actuellement disponibles, avec un recul de plus de 7 ans, ne remettent pas en
cause le rapport bnfice risque du Gardasil. Le service mdical rendu tel quil avait t dfini par la HAS
nest pas non plus remis en question : avis de la Commission de la Transparence de la HAS.
Les professionnels de sant sont invits poursuivre les efforts dj entrepris pour dvelopper la
couverture vaccinale en France en suivant les indications de lAMM et les recommandations dfinies par
le HCSP, cest dire en ciblant les jeunes filles de 11 14 ans au plus tt et notamment avant leur premier
rapport sexuel, avec un rattrapage entre 15 et 19 ans rvolus : Avis du HCSP
La vaccination ne se substitue pas au frottis cervico-utrin (FCU) de dpistage, qui doit tre ralis tous les
3 ans chez les femmes partir de 25 ans jusqu 65 ans. (Source: HAS)

Renouvellement du comit dontologie et indpendance de

lexpertise de la Haute Autorit de Sant (HAS)
A lexception du prsident M. Alain Christnacht qui est renouvel dans ses fonctions, le comit accueille 4
nouveaux membres, dont un reprsentant dusagers en la personne dEric Molini. Cette nomination
sinscrit dans le souhait de la HAS dassocier toujours davantage les associations de patients ses travaux et
son fonctionnement.
Par la prsence de deux spcialistes du droit M. Alain Christnacht et Mme Soraya Amrani-Mekki mais
aussi de deux professionnels de sant M. Daniel Couturier et M. Jean-Roger Legall la composition du
comit allie rigueur dans le respect du droit et pragmatisme.
18

Par souci dindpendance, le comit ne comprend en outre que des personnalits extrieures la HAS.
(Source: HAS)

CEPS
http://www.sante.gouv.fr/comite-economique-des-produits-de-sante-ceps.html

Le Cabinet WHITE-TILLET a prs de 30 ans dexprience et dexpertise dans le

domaine du remboursement des mdicaments, incluant la matrise de la
mthodologie clinique. La rdaction de ces dossiers est un art complexe. Les
consquences pour les firmes peuvent tre cruciales. Confiez-nous vos dossiers de
remboursement !

EUROPE

http://www.mhra.gov.uk/

Top UK and international marketers honoured

Shire and Lundbeck have claimed the top title of marketing companies of the year in the prestigious
PharmaTimes Marketer of the Year competition, the results of which were announced in London last night.
More than 75 marketers from 28 global pharmaceutical companies took part in the annual competencybased benchmarking competition, where finalists were tasked with a role-play challenge based on current
healthcare trends. Other winners on the night were: Simon Evans, Napp Pharmaceuticals, for Aspiring
Marketer of the Year; Michael Short, Merck Serono, for Senior Marketer UK; Artur Krzyzanowski, BristolMyers Squibb, for Senior Marketer Non-UK. (Source: PharmaTimes)

UK PPRS published, but industry discord remains

The government has published full details of the new Pharmaceutical Price Regulation Scheme (PPRS),
which, for the first time, will introduce an agreed limit on NHS spend on branded medicines, with all
additional expenditure above this level paid for by industry.
19

Under the five-year voluntary scheme, the branded medicines bill will stay flat over the first two years and
grow slowly afterwards, with the industry footing any overspend (within agreed boundaries), except those
companies pulling in annual sales of less than 5 million.
According to the government, the "breakthrough deal", which has been agreed with the Association of the
British Pharmaceutical Industry (ABPI), will "provide predictability and certainty to both the NHS and
industry on the spend for branded medicines", as well as "encourage the use of innovative and costeffective treatments".
Those on the other side of the fence, however, are not so sure, with the removal of the threshold taper for
SMEs a key sore point.
ABPI chief executive Stephen Whitehead said industry has agreed to keep medicines spend under control
given the financial challenges being faced by the NHS. But, he pointed out, "it's governments role to create
an environment that encourages industrial growth and therefore we are disappointed that [it] has chosen
not to maintain a taper for companies with NHS sales between 5 and 25 million", a crucial life-line for
SMEs. (Source: PharmaTimes)

UK drug shortages harming patients in 75% of cases

Royal Pharmaceutical Society spokesman Neal Patel has told PharmaTimes World News that the
government must take action to ensure that patients can access the medicines they need when they need
them, after worrying findings of a report indicate that the medicines supply chain is not working and
patients are being put at risk.
A year-long investigation by Chemist and Druggist shows that, on average, pharmacists are spending at
least two working days a month chasing manufacturers and wholesalers to source of out-of-stock
medicines.
Moreover, of those responding to C+D's Stocks Survey 2012, 57% said at least one of their patients' health
had suffered because of drug shortages, marking a 12% rise on the prior year.
The RPS agrees that the current system is faltering. "Patients have endured the effects of a failing supply
system for too long. Voluntary agreements have been signed between Government and others involved in
the supply chain to improve access to medicines, the C and D survey shows we have seen no improvements
at all at the sharp end," Patel told PT. (Source: PharmaTimes)

England's diabetes care lottery 'fuels major health crisis'

Diabetes UKs latest annual State of the Nation report finds huge regional variations in peoples ability to
access quality integrated diabetes care, right across the system. For example, it finds that::
- people with diabetes in the best-performing area are four times more likely to have the annual checks
they need to manage their condition than in the worst-performing area;
- in the best-performing area, 28% of people with diabetes have their condition under control defined as
meeting targets for blood glucose, blood pressure and cholesterol while in the worst-performing areas,
just 17% do so; and
- in the best-performing areas, about half of people newly-diagnosed with diabetes are offered structured
education. However, in many areas almost no-one is offered it, despite the fact that structured education,
together with giving people the support they need to manage their own condition, is seen as one of the
most important ways of ensuring people can access services and reducing the risk of complications.
20

Diabetes UK calls on the government and NHS England for a review into the reasons for these large
geographical variations and to put in place an action plan for people living in the worst-performing areas.
(Source: PharmaTimes)

Blood Consultative Committee meeting October 2013

Agenda

Agenda

(41Kb)

Minutes

Final minutes of March 2013 meeting

Draft minutes of October 2013 meeting

(230Kb)
(220Kb)

Presentations and papers

SABRE update presentation

BCR review process for reporting year 2012/13

Summary of common deficiencies for inspections to date in 2013/14

Update on BCC IT workgroup

Update on blood component labelling

Update from SHOT Annual Report

(290Kb)
(248Kb)
(254Kb)

(16Kb)
(198Kb)
(36Kb)

New learning unit for nurses on adverse drug reactions

Nursing Times Learning has teamed up with the Medicines and Healthcare products Regulatory Agency
(MHRA) to launch a new, free interactive learning unit on Adverse Drug Reactions (ADR) and the Yellow
Card Scheme to support nurses.
The learning unit will count for two hours of continuous professional development and teaches nurses to
know how and when to report side effects of medications an essential element of patient safety.
Effective reporting of suspected ADRs is an important way for healthcare professionals to contribute to the
safer use of medicines. In the UK, this is done by completing a Yellow Card and submitting it to the MHRA.
This is a quick and easy process, and can be done online or by post.
Although the Yellow Card Scheme provides valuable information, its effectiveness is limited by underreporting. Busy healthcare workers may mistakenly assume that reporting is a time consuming and
complicated process, or that the information they have is not useful.
After completing the learning unit, nurses will understand the importance of continuous monitoring and
reporting of suspected ADRs, know which type of situation should trigger a report through the Yellow Card
Scheme, and be able to fill out a Yellow Card correctly. They should also know where to find up-to-date
information on ADRs, and be able to use that information for patient safety.

21

The learning unit is available free to all nurses through the Nursing Times website (external link).
This e-learning module compliments other existing MHRA e-learning modules for healthcare professionals
on pharmacovigilance and the Yellow Card Scheme. (Source: MHRA)

J&J networks to link up with UK life science 'hot spots'

The healthcare giant says that while its London Innovation Centre, opened in March, "continues to be the
primary hub for interactions with the academic and entrepreneurial community" around the capital, it is
looking to link up with talent elsewhere. As such, it is opening offices in Cambridge, Oxford, Manchester,
Edinburgh and Cardiff.
The partnering offices extends an approach piloted with Stevenage Bioscience Catalyst earlier this year,
noted Kurt Hertogs, incubator strategy leader for the London centre. The experience with SBC "confirms
this model as an effective way for our scientific teams to interact with innovators and entrepreneurs," he
said. (Source: PharmaTimes)

Commission on Human Medicines recruiting for new members

In the public interest ministers require impartial advice relating to the regulation of medicines. This advice
is sought from a wide range of highly-skilled senior professionals who are well regarded in their respective
fields.
The Commission on Human Medicines (CHM) is responsible for providing advice on medicines to the
Licensing Authority (LA). The responsibilities include:

to advise ministers on matters relating to human medicinal products

to advise the LA where it has a duty to consult the Commission or where the LA chooses to consult
the Commission including providing advice in relation to the safety, quality and efficacy of human
medicinal products

to promote the collection and investigation of information relating to adverse reactions for human
medicines.

The following CHM appointments have arisen:

Oncology (one post)

Clinical neurology (one post)

Paediatrics (one post)

Toxicology (one post)

General practice (one post)

Infectious diseases (two posts)

The deadline for all applications is 3 January 2014.

Details of the vacancies are available on the Cabinet Office website: Public appointments: Commission on
Human Medicines (external link) (Source: MHRA)

22

 Cameron comes to defence of GSK in China

Prime Minister David Cameron has lent his support to GlaxoSmithKline and its activities in China on a highprofile trip where he is being accompanied by the drug major's chief executive Sir Andrew Witty.
GSK has been accused of bribery in China and the firm's reputation has taken a battering there but Mr
Cameron is in its corner. He is believed to have discussed the matter with China's top leadership and has
also spoken to reporters in Shanghai to defend the company.
He was quoted by Reuters as saying that "from all my dealings with GSK, I know that they are a very
important, very decent and strong British business that is a long-term investor in China". He added that "I
think it is right to raise a case like that. Britain has a record of properly standing up for British businesses
and British individuals, raising individual cases in the right way andhaving a proper dialogue with the
Chinese authorities about the issues". (Source: PharmaTimes)

http://www.nice.org.uk/

NICE: Final appraisal determination Teriflunomide for treating

relapsingremitting multiple sclerosis
Teriflunomide is recommended for treating adults with active relapsingremitting multiple sclerosis
(normally defined as 2 clinically significant relapses in the previous 2 years), only if
they do not have highly active or rapidly evolving severe relapsingremitting multiple sclerosis and
the manufacturer provides teriflunomide with the discount agreed in the patient access scheme.
(Source : NICE)

Multiple sclerosis (relapsing-remitting) - alemtuzumab: appraisal

consultation
The Department of Health has asked the National Institute for Health and Care Excellence (NICE) to
produce guidance on using alemtuzumab in the NHS in England. The Appraisal Committee has considered
the evidence submitted by the manufacturer and the views of non-manufacturer consultees and
commentators, and clinical specialists and patient experts.
This document has been prepared for consultation with the consultees. It summarises the evidence and
views that have been considered, and sets out the draft recommendations made by the Committee. NICE
invites comments from the consultees and commentators for this appraisal (see section 9) and the public.
This document should be read along with the evidence base (the evaluation report).
The Appraisal Committee is interested in receiving comments on the following:

Has all of the relevant evidence been taken into account?

Are the summaries of clinical and cost effectiveness reasonable interpretations of the evidence?

Are the provisional recommendations sound and a suitable basis for guidance to the NHS?

23

Are there any aspects of the recommendations that need particular consideration to ensure we
avoid unlawful discrimination against any group of people on the grounds of race, gender,
disability, religion or belief, sexual orientation, age, gender reassignment, pregnancy and
maternity?

(Source: NICE)

The day after its Lemtrada snub, NICE blesses Sanofi's Aubagio
Last thursday, Sanofi's ($SNY) multiple sclerosis drug Lemtrada was stymied by the U.K.'s cost-effectiveness
gatekeeper, which asked for more data on the med before it could determine its worth. But just one day
later, the regulatory body gave Sanofi's MS franchise a boost: It has recommended Aubagio, its oral
treatment, for use in Britain's National Health Service. (Source: FiercePharma)

UK regulators OK pSivida's Iluvien

The approval is for cataract surgery patients who don't respond to standard treatment for diabetic macular
edema, according to a press release. The win for Iluvien, which pSivida licenses to Alimera
Sciences (NSDQ:ALIM), comes almost exactly a year after the British health regulator dealt a blow to the
companies when it concluded that Iluvien is too expensive.
That decision led Alimera to create a "patient access scheme" for the non-responsive cataract surgery
subgroup. (Source: MassDevice)

NICE minded to reject Genzyme/Sanofi's Lemtrada for MS

Cost regulators for the NHS in England and Wales are currently minded not to recommend the use of
Sanofi's Lemtrada (alemtuzumab) for relapsing, remitting multiple sclerosis, because of gaps in the data
submitted. Accumulation of disability was also significantly slowed in patients taking Lemtrada, and
patients were significantly more likely to experience improvement in pre-existing disabilities versus Rebif.
Consequently, it has called on Sanofi's Genzyme unit to provide "a series of clarifications on the evidence
submitted", and the drugmaker has until January 9 to do so. (Source: PharmaTimes)

http://www.imb.ie/

Notice Information: - 3rd Party Publications

Restrictions to the Use of Short Acting Beta Agonists (SABAs) in Obstetric Indications

http://www.fagg-afmps.be/fr/

24

 Rglementation relative aux prcurseurs: codes tarifaires pour les

mdicaments contenant de lphdrine, de la pseudophdrine, de la
nor-phdrine ou leurs sels
Les mdicaments contenant de lphdrine, de la pseudophdrine, de la nor-phdrine ou leurs sels ont
maintenant des codes tarifaires spcifiques. Le code correct doit donc tre mentionn sur tous les
documents officiels relatifs chaque importation ou exportation dun de ces mdicaments.
Les mdicaments concerns sont marqus dune toile dans le document (PDF, 135.05 Kb) reprenant les
codes tarifaires publis dans le Journal officiel de lUnion europenne. (Source: AFMPS)

Rglementation relative aux prcurseurs: changements suite

ladhsion de la Croatie lUE
Depuis le 1er juillet 2013, toutes les transactions commerciales avec la Croatie sont considres comme
une activit intra-communautaire et entrane une modification de lagrment/ enregistrement pour les
oprateurs concerns. Ils sont invits introduire une demande de modification de cet agrment/
enregistrement la cellule des Prcurseurs.
Agrment/ enregistrement prcurseurs

New GDP (Good Distribution Practices): Q&A, liste de questions/

rponses
Le 7 Mars 2013, des nouvelles lignes directrices relatives aux bonnes pratiques de distribution (BPD) ou
good distribution practices (GDP) ont t publies au niveau europen. Celles-ci ont t transposes en
droit belge dans larrt royal du 19 septembre 2013 modifiant larrt royal du 14 dcembre 2006 relatif
aux mdicaments usage humain et vtrinaire. Un document reprenant les questions frquemment
poses ce sujet et les rponses qui y sont apportes est prsent disponible.
Document de questions/ rponses (PDF, 141.22 Kb) ou Questions and Answers (Q&A) ou Frequently
asked questions (FAQ).

http://www.bfarm.de/DE/Home/home_node.html

IQWiG: Enzalutamide in prostate cancer: hints of added benefit

Enzalutamide (trade name: Xtandi) has been approved since June 2013 for men with metastatic prostate
cancer in whom the commonly used hormone blockade is no longer effective and who have already been
treated with the cytostatic drug docetaxel. In an early benefit assessment pursuant to the Act on the
Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in
Health Care (IQWiG) examined whether this new drug offers an added benefit over the appropriate
comparator therapy specified by the Federal Joint Committee (G-BA).
In comparison with "best supportive care", there is a hint of a major added benefit in patients whose
internal organs are free of metastases of the tumour. In patients with such visceral metastases, the extent
of added benefit is "considerable". (Source: IQWIG)
25

 IQWiG: Added benefit of saxagliptin/metformin combination is not

proven
The drug saxagliptin (trade name: Onglyza) has been approved also as monotherapy in Germany since July
2013 for certain adults with type 2 diabetes mellitus. It is an option when drug treatment is needed, but the
drug metformin is not tolerated or cannot be used.
In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products
(AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether
saxagliptin offers an added benefit over the current standard therapy. Such an added benefit cannot be
derived from the dossier, however, as the manufacturer did not submit any suitable data. (Source:
IQWIG)

http://www.agenziafarmaco.gov.it/en

EU upholds Italy's ban on parapharmacy Rx drug sales

The Court of Justice of the European Union (CJEU) has upheld Italys ban on the sale through
parapharmacies of prescription medicines which are paid for entirely by the purchaser.
The Court was ruling in a case brought by three Milan pharmacists whose request to be allowed to sell such
products through their parapharmacies was rejected by their local health authorities and the Italian
Ministry of Health. They then brought their case to the regional administrative court in Lombardy, claiming
that this refusal was contrary to EU law.
In its judgement, the CJEU notes that the establishment of pharmacies in Italy is subject to planning rules.
The aim of these is, first, to avoid pharmacies becoming concentrated only in areas which are commercially
more attractive and to ensure that each pharmacy has a market share and, second, to ensure that
requirements for medicines can be met nationwide.
The EU judges point out that the geographic distribution of pharmacies and monopoly for dispensing
medicines remains a matter for individual EU member states. And in Italy, a pharmacist who wishes to set
up a parapharmacy is excluded from the economic benefits accruing from sales of prescription-only drugs
which are wholly paid for by the purchaser; these can only be sold through pharmacies. (Source:
PharmaTimes)

http://www.aemps.gob.es/en/home.htm

http://www.legemiddelverket.no/English/Sider/default.aspx

http://www.lakemedelsverket.se/english/

26

http://www.eum.hu/about-us/the-ministry/ministry-of-health

http://www.swissmedic.ch/index.html?lang=fr

Les Bonnes Pratiques de Fabrication (GMP) et les Bonnes Pratiques

Cliniques (GCP) sont au cur de nos proccupations et dans notre
champ de comptence. Nhsitez pas venir vers nous pour raliser vos
audits. Nous avons un rseau de des correspondants locaux en Asie et
aux Etats-Unis.

RUSSIA & RELATED COUNTRIES

Ministry of Healthcare of the Russian Federation
http://government.ru/eng/power/23/

Ministry of Health of Ukraine

http://www.kmu.gov.ua/control/en/publish/article?art_id=88456

NORTH AMERICA

http://www.fda.gov/

Pharmacy Compounding of Human Drug Products

FDA Implementation of the Compounding Quality Act

Outsourcing Facility Registration and Reporting

27

Traditional Compounding

Enhanced Communication with States

Creation of Advisory Committee

Nominations for Lists

Inspections and Enforcement

(Source: FDA)

Pharmacy Compounding of Human Drug Products Under Section

503A of the Federal Food, Drug, and Cosmetic Act
FDA - Pharmacy Compounding of Human Drug Products - Draft - Dec2013.pdf

Registration for Human Drug Compounding Outsourcing Facilities

Under Section 503B of the Federal Food, Drug, and Cosmetic Act
FDA - Registration for Human Drug Compounding Outsourcing Facilities - Draft - Dec2013.pdf

Interim Product Reporting for Human Drug Compounding

Outsourcing Facilities Under Section 503B of the Federal Food, Drug,
and Cosmetic Act
FDA - Interim Product Reporting for Human Drug Compounding Outsorting Facilities - Draft Dec2013.pdf

Good Review Practice: Clinical Review of Investigational New Drug

Applications
FDA - Clinical Review of Investigational New Drug Applications.pdf

FDA: Guidance for Industry - Bioequivalence Studies with

Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA DRAFT GUIDANCE (Source: FDA)
FDA Asks Drugmakers: Where Are Those Pediatric Studies?
A decade ago, the Pediatric Research Equity Act was enacted and gave the FDA the authority to require
drugmakers to complete studies in children for the same adult indications when existing medicines are
expected to be used in a substantial number of youngsters (read more here). And last year, the agency was
given the right to shame drugmakers that fail to comply.
And so, the FDA has now posted on its web site a batch of letters that were recently sent to drugmakers
that have not sought or obtained a deferral extension; submitted a deferred pediatric study by a final due

28

date or requested approval for a required pediatric formulation. An even dozen non-compliance letters
were sent to nine different drugmakers between April and October. (Source: Pharmalot)

Experts warn of multiple drug use 'failures'

Policy, medical training and clinical practice have failed to adapt to the significant increase in numbers of
patients taking multiple prescription drugs, experts warn.
The number of patients taking 10 or more medicines is estimated to have trebled during 1995-2010,
reflecting a large increase in people with complex, or several, long-term conditions (LTCs), says a new study
published by healthcare policy think tank The Kings Fund.
However, most research and health systems remain based on single-disease frameworks, so policy, medical
training and clinical practice have often not adapted to optimising the use of multiple medicines and
prescribing them according to best evidence. But integrated care is now widely accepted as the way
forward in caring for people with multiple, complex LTCs, and appropriate polypharmacy now needs to be
similarly accepted, says the study, which calls for:

better training for doctors in managing complex multi-morbidity and in polypharmacy;

more research set in the context of using treatments where people have several diseases, rather
than selecting subjects who have single conditions;

national guidelines for multi-morbidity to match those for single conditions;

improved systems, particularly for GPs, to flag problematic polypharmacy;

regular reviews of patients medication and a willingness to consider stopping medication,

particularly in cases of limited life expectancy: and

changes in systems of medical care to move away from increased specialisation towards a focus on
multi-morbidity.

The study also calls for more engagement with patients to ensure that medicines are taken in the way that
prescribers intend. This may require compromise between prescribers and patients to ensure that patients
feel confident in what they are taking, and situations where medicines go unused or are wasted are
avoided. (Source: PharmaTimes)

DEA Places Eisais Fycompa into Schedule III (Source: FDAnews)

FDA Grants Orphan Drug Status for Hepatitis C Treatment Developed
by MassBiologics
MassBiologics' monoclonal antibody, currently in a phase 2 clinical trial, is intended to prevent HCV from
damaging the transplanted liver.
"Being granted orphan drug status facilitates the goal of bringing this investigational product to patients,"
says Deborah C Molrine, MD, deputy director of clinical affairs at MassBiologics and professor of pediatrics.
"The economic incentives available to MassBiologics and potential commercial partners through the
Orphan Drug Act will contribute greatly to bringing this monoclonal antibody to market as a treatment
option for patients receiving liver transplants as a result of HCV infection." (Source: PMPNews)

29

 FDA approves Gilead's breakthrough hepatitis C pill

The once-a-day pill is the first approved to treat certain types of hepatitis C infection without the need for
interferon, an injected drug that can cause severe flu-like symptoms.
Gilead said Sovaldi can be used in combination with ribavirin, an older antiviral pill, for patients with
genotypes 2 and 3 infections, which account for about 28 percent of U.S. patients infected with the virus.
For patients with genotype 1, which accounts for about 70 percent of U.S. infections, the new drug must
still be used with both interferon and ribavirin, although it can be considered for use in patients with
genotype 1 infections who cannot use interferon. (Source: Reuters)

Dyax gets orphan designation for long-lasting HAE drug

Dyax is now developing its second drug to treat HAE, after getting approval for its first now marketed as
Kalbitor in 2010. Jennifer Robinson, spokeswoman for the company, said that while Kalbitor is intended
to be administered within a few hours of a flare-up of the disease, DX-2930 is intended as an injection to be
administered just once or twice a month to prevent inflammation. Orphan drug designation is reserved for
potential drugs to treat diseases afflicting less than 200,000 patients in the U.S. About 10,000 people in the
United States have HAE. (Source: BBJ)

FDA approves first drug for curved erections

The US Food and Drug Administration has approved Auxilium Pharmaceuticals' Xiaflex to treat Peyronie's
disease, which causes a bothersome curvature of the penis during sex. The approval is based on two
studies involving 832 men with Peyronies who were given up to four treatment cycles of Xiaflex or placebo
and were then followed for 52 weeks. The data revealed that the drug significantly reduced penile
curvature deformity and related bothersome effects compared with placebo.
The FDA stressed that Xiaflex is available only through a restricted programme because of the risks of
serious adverse reactions, including penile fracture. Martin Gelbard of the UCLA School of Medicine noted
that treating Peyronie's "has been a challenge as, until now, we have had few options to offer our
patients", so the FDA approval is "a significant achievement" to help doctors deal with "this physically and
psychologically devastating disorder". (Source: PharmaTimes)

Clobazam (Onfi) Can Cause Serious Skin Reactions, FDA Warns

The agency approved clobazam, a benzodiazepine, in 2011 as an add-on therapy to treat seizures that
accompany a severe form of epilepsy called Lennox-Gastaut syndrome. The FDA said other
benzodiazepines generally are not associated with serious skin reactions.
For clobazam, the skin reactions to watch for are Stevens-Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN). Patients taking clobazam can experience these disorders at any time, but the risk goes up
during the first 8 weeks of treatment or when treatment resumes after it was stopped. All the cases of
these 2 adverse events identified by the FDA landed patients in the hospital, with 1 patient going blind and
another dying.
The FDA advises clinicians to closely monitor patients taking clobazam for SJS and TEN, especially at the
start of therapy or when the drug is reintroduced. Signs and symptoms include rashes, blistered or peeling
skin, mouth sores, and hives. Clobazam should be halted at the first appearance of a rash, and if other signs
and symptoms point to a serious skin reaction, the therapy should not be resumed. (Source: MedScape)
30

 Takeda colitis drug raises PML concern: FDA staff

An experimental drug for ulcerative colitis and Crohn's disease from Takeda Pharmaceutical Co could pose
risk of a potentially fatal brain infection called PML even though the problem has not been seen in clinical
trials, staff members of the U.S. Food and Drug Administration said on Thursday.
Documents about the monoclonal antibody, called Entyvio, were released by the FDA staff ahead of a
planned meeting on Monday among a panel of outside medical experts who will review the safety and
effectiveness of the medicine and make recommendations to the FDA.
Japanese drugmaker Takeda earlier this year filed for marketing approval of Entyvio, whose chemical name
is vedolizumab, in the United States and Europe.
Some 3,326 patients have received one or more infusions of the medicine in its various clinical trials, with
no cases of the brain infection seen, the FDA staff said in a lengthy review document meant to flag
potential concerns to the panel of outside medical experts. (Source: Reuters)

FDA approves new topical scar treatment

The FDA has approved Microcyn scar-management hydrogel, used to treat scars resulting from burns,
surgery and trauma wounds. Oculus and a partnering company, Quinnova Pharmaceuticals, intend to start
selling the drug in the first half of next year. (Source: DSN)

FDA approves phase 3 stem cell trial for metastatic melanoma

The Special Protocol Assessment indicates the FDA agrees that design, clinical endpoints and planned
clinical analyses address regulatory objectives sufficient for market approval, according to a press
release. The FDA also granted the therapy fast track status, designed to accelerate the approval of
investigational therapies that show promise in treating life-threatening medical conditions.
Two hundred fifty patients with recurrent stage III or stage IV metastatic melanoma will be enrolled in the
multicenter, randomized double blind study that will compare California Stem Cells patient-specific cancer
immunotherapy, DC-TC, against a control group. Enrollment is expected to begin in early 2014.
Researcher Robert Dillman, MD, FACP, medical oncologist at the Hoag Family Cancer Institute of Hoag
Memorial Hospital Presbyterian in California, said in the release that in two phase 2 studies, the combined
median 5-year survival in patients with metastatic melanoma was 51%, double that of current treatments.
(Source: Healio)

Zogenix Announces FDA Approval of 4 mg SUMAVEL(R) DosePro(R)

(sumatriptan injection) Needle-Free Delivery System
SUMAVEL DosePro is the first and only needle-free delivery system for subcutaneous sumatriptan for the
treatment of acute migraine and cluster headache. Clinical data has shown that the current 6 mg dose of
SUMAVEL DosePro can provide migraine pain relief within 10 minutes for some patients (16% of patients
versus 4% for placebo). The product was launched in January 2010, reaching over 225,000 total
prescriptions at the end of the third quarter 2013. (Source: PMPNews)

31

USA
Hatch-Waxman Act
Hatch-Waxman Developments - Artificial Infringement Artificial Drugs.pdf

The Growing Need For Outcome Studies And The Impact On R&D
Costs
For many years, drugs were approved on the basis of their impact on markers of disease, rather than
determining the overall health outcome for patients taking these drugs. If a drug lowered LDL cholesterol,
it was approved for treating heart disease. However, over the last decade, long term studies measuring the
effect of drugs on ultimate disease outcomes have yielded surprisingly unexpected results. For example,
niacin, which had been prescribed for decades for use in heart patients because of its ability to raise HDL
cholesterol and lower LDL cholesterol, was discredited when long term studies showed that it was inferior
to statins.
In an accompanying editorial, Dr. Dick de Zeeuw, made the point that when either approved or off-label
drug use is guided by changes in surrogate markers without proof from hard-outcome trials, problems may
ensue. That certainly happened here. And yet this was a situation where two well established drugs were
studied not a new experimental medicine. What was hoped to be a relatively simple study instead
showed that 1 plus 1 sometimes comes to zero.
The greater need for outcome studies will strain even the biggest pharmaceutical company R&D budgets.
These studies, which can last 3 6 years and require 10,000 25,000 patients, can cost as much as $500
million. How many companies can afford to take multiple such shots? A company running a major
cardiovascular outcome trial and also a multiyear Alzheimers Disease trial probably cant afford to do
another outcome study in the same timeframe. Also, there is no guarantee that the study will be successful
as GSK recently learned with its cardiovascular study with darapladib. Thus, we can expect drug
development costs to continue to rise as more and more of these studies will be needed to bring a new
drug successfully to market. (Source: Forbes)

Medivation, Astellas launch trials in prostate, breast cancers

Medivation Inc. and partner Astellas Pharma Inc. started a pair of clinical trials of their cancer-fighting drug
enzalutamide one in prostate cancer, the other in breast cancer that could expand the use of the
capsules.
The drug, known commercially as Xtandi, has been one of the Bay Area drug-development success stories
of the past year. Since winning Food and Drug Administration approval in August 2012 as a treatment for
metastatic, castration-resistant prostate cancer patients, the $89,000-a-year drug has registered strong
sales, including $121 million in the third quarter alone.
Medivation and Astellas' new Phase III trial a nearly 1,500-patient study known as PROSPER will look
at safety and efficacy of Xtandi in patients with non-metastatic, castration-resistant prostate cancer. The
companies said Tuesday that the first patient had been enrolled in the trial, which is taking place at sites in
the United States, Canada, Europe, South America and Asia-Pacific.
32

The other study, a Phase II trial with 240 patients is looking at a combination of Xtandi and Pfizer Inc.'s
Aromasin, or exemestane, in women with a specific type of advanced breast cancer. (Source: SFBT)

White House Pushes 12-Year Exclusivity For Biologics In Trade Talks

The pharmaceutical industry, though, has long been active in pushing for the 12-year exclusivity period.
Brand-name drugmakers argue that 12 years is needed to recover R&D investments and to protect patents.
They have noted that biosimilars do not have to be identical and, as a result, patents may be circumvented
because these are not technically the same as the original drugs.
Toward that end, the pharmaceutical industry convinced dozens of members of Congress to write the
White House shortly after the Trans Pacific Partnership talks got under way to urge that 12 years of
exclusivity is obtained. The take-away message they have conveyed is that the US would be at a
disadvantage because foreign countries do not provide the same level of patent protection. (Source :
PharmaLive)

Supreme Court refuses to block Pfizer suits

The U.S. Supreme Court Monday rejected a request from pharmaceutical giant Pfizer to head off a slew of
lawsuits targeting off-label use of one of its drugs.
Healthcare insurers had sued Pfizer under the federal Racketeer Influenced and Corrupt Organizations Act,
better known as RICO. Under the law an enterprise is liable if it commits a number of "predicate acts."
The act is normally used against organized crime but it also has a number of civil applications.
Pfizer is being sued for marketing the pain management drug Neurontin "for off-label uses for which it is
allegedly ineffective."
In one case, Pfizer Inc. vs. Kaiser Foundation Health Plan Inc., Pfizer already lost a verdict awarding $142
million in damages, SCOTUSBLOG.com reported..
And because of the off-label campaign, Pfizer and its predecessors were fined $430 million in a U.S. Justice
Department case.
Following the Justice Department action, insurers sued Pfizer under RICO, saying the company had
persuaded doctors to prescribe the drug for off-label uses and caused insurers to pay for it. Despite the
$142 million award in the Kaiser case, a number of other suits were dismissed in U.S. District Court.
(Source: PMPNews)

United Therapeutics receives subpoena for 3 drugs

The subpoena, which follows an investigation by the Department of Justice, requires the company to
submit documents regarding its Remodulin injection, Tyvaso inhalation solution and Adcirca tablets, the
company said on Monday.
These three drugs are the only treatments for which United Therapeutics holds marketing approval from
the U.S. Food and Drug Administration, according to the company's website. (Source: Reuters)

33

 Pharmaceutical company on Midlothian Turnpike raided by Federal

agents
Armed federal agents worked well into the night Tuesday. They were removing documents from the offices
of a pharmaceutical company in Chesterfield. There is an odd connection to one of the stars of "Jersey
Shore." "We can confirm that federal officers from the US government presented a search warrant at the
offices of Reckitt Benckiser Pharmaceuticals, Inc. in Richmond, Virginia, USA on Tuesday morning," said a
RB spokesperson in a statement."RB is cooperating fully with the investigation, but the officials did not
disclose the purpose of the warrant."
Company officials say the warrant was presented by the US Attorney's office for Western Virginia. The
company has made headlines in recent weeks. The New York Times reported the FDA asked the Federal
Trade Commission to investigate potentially anti-competitive business practices by the company.
(Source: NBC12)

Gallant Pharma Company and Co-Owner Plead Guilty to Sixteen

Charges of Prescription Drug Fraud
Gallant Pharma International Inc., headquartered in Arlington, Va., pleaded guilty today to two counts of
importation fraud, five counts of selling misbranded drugs, and five counts of distributing prescription
drugs without a license. Co-founder and co-owner Syed "Farhan" Huda, 38, of Arlington, Va., entered the
guilty plea on behalf of Gallant Pharma, and he also pleaded guilty to one count each of importation fraud,
selling misbranded drugs, distributing prescription drugs without a license, and wire fraud. (Source:
FiercePharma)

http://www.pcori.org/

http://www.ahrq.gov/

Medication Therapy Management (Source: AHRQ)

http://www.iom.edu/

Oversight and Review of Clinical Gene Transfer Protocols: Assessing

the Role of the Recombinant DNA Advisory Committee (Source: IOM)

34

SANTE/HEALTH CANADA
http://www.hc-sc.gc.ca/index-fra.php#tabs1_3

Drugs for Chronic Hepatitis C Virus Infection

The Canadian Agency for Drugs and Technologies in Health (CADTH) is undertaking a therapeutic review
project to assess the clinical and economic impact of new and existing drugs to treat chronic hepatitis C
virus (HCV) infection.
The review will include drugs that are currently available in Canada, and those that may become available
in the near future.
The project has two key components:

A comparison of the clinical and cost-effectiveness of drug therapies for chronic HCV infection.

The development of recommendations or advice from the Canadian Drug Expert Committee
(CDEC).

The impending availability of new drugs for the treatment of chronic HCV infection could have significant
impact on treatment strategies. By reviewing the evidence and developing reports and tools, CADTH
provides health care policy- and decision-makers with the evidence-based resources they need to make
informed decisions. (Source: CADTH)

Tories introduce bill to crack down on unsafe medications

The Protecting Canadians from Unsafe Drugs Act is known as Vanessa's Law in honour of the late daughter
of Conservative MP Terence Young.
The 15-year-old died of a heart attack 13 years ago while on a prescription drug for a stomach ailment. The
medication was later deemed unsafe and pulled from the market.
Under the new legislation, the government now has the power to initiate mandatory recalls for unsafe
drugs and to demand reports from health-care institutions on adverse drug reactions.
The bill also allows the government to impose tough new penalties for unsafe products, including jail time
and new fines of up to $5 million a day instead of the current $5,000.
Drug companies must also revise labelling to provide details on health risks, and to do further testing on
medications when they are shown to pose dangers to some consumers, especially children. (Source:
CTVNews)

35

LATIN AMERICA

SSA http://www.salud.gob.mx/

http://portal.anvisa.gov.br/wps/portal/anvisa/home

Anvisa Unveils New Adverse Event Database (Source: ANVISA)

AFRICA
UEMOA - UNION ECONOMIQUE ET MONETAIRE OUEST
AFRICAINE : UN MARCHE UNIQUE AVEC DES REGLES UNIQUES

http://www.uemoa.int/Pages/Home.aspx

Fiscalit des mdicaments, consommables et quipements mdicaux

dans les pays membres de lUEMOA (Source: Cerdi)
LAfrique de lOuest: des opportunits daffaires dcouvrir
SlideShare)

https://www.dphm.ci/fr/dpm-c%C3%B4te-divoire-3

36

(Source:

 Promotion de l'Industrie Pharmaceutique (Source : DPHM)

Pharmacovigilance et Lutte contre les Mdicaments Illicites

(Source:

DPHM)

AUSTRALIA NEW ZELAND

http://tga.gov.au/

Nonclinical aspects on vaccines development

TGA presentation - Nonclinical aspects of vaccine development - October 2013.pdf

Nonclinical studies to support clinical trials on vaccines

TGA presentation - Nonclinical studies to support clinical trials - Oct 2013.pdf

TGA: Australian statistics on medicines and vaccines 2012

On an annual basis, the Office of Product Review (OPR) of the TGA prepares a report for incorporation into
the Department of Health publication Australian Statistics on Medicines.
Australian Statistics on Medicines is produced by the Drug Utilisation Sub-Committee (DUSC) of the
Pharmaceutical Benefits Advisory Committee (PBAC) and is aimed at providing comprehensive and valid
statistics on the Australian use of medicines and vaccines in the public domain to allow access by all
interested parties.
The report from the OPR includes a brief overview on the following aspects of post-market monitoring of
medicines and vaccines in Australia:

Adverse event reporting statistics for 2012

Processing and use of adverse event reports

Database of Adverse Event Notifications

Reporting adverse events

Expert advisory committee

Medicines Safety Update

Product vigilance

(Source: TGA)

37

 Dextropropoxyphene - questions and answers

Consumer questions

Doctor/Dentist questions

Hospital Doctor/Pharmacy question

Pharmacist questions

Alanylglutamine: Draft compositional guideline

As part of the evaluation of 'alanylglutamine' as a new complementary medicine substance available for
use as an active ingredient in listed medicines, the TGA has drafted a compositional guideline to describe,
identify and set limits that define the composition and characteristics of alanylglutamine. The TGA now
seeks comments from stakeholders on the draft guideline.
Interested parties should respond by close of business Friday, 17 January 2014. (Source: TGA)

E2B reports: frequently asked questions (Source: TGA)

Orphan drugs
Added Blinatumomab indications (Source: TGA)

Australian Public Assessment Reports for prescription medicines

(AusPARs)
Added Lisdexamfetamine dimesilate, Fentanyl citrate and Romidepsin (Source: TGA)

ANZTPA http://www.anztpa.org/
INDIA - PAKISTAN & ASIA

38

China SFDA | Hong Kong MDCO & PSDH | India CDSCO | Japan MHLW | Korea KFDA | Malaysia MOH |
Philippines DOH | Singapore HSA | Taiwan TFDA | Thailand FDA | Vietnam MOH

http://www.pmda.go.jp/english/

http://eng.sfda.gov.cn/WS03/CL0755/

Supply Chain Solution in China

Peters Technology is an ISO 13485, 9001, 14001, and OHSAS 18001 certified, and FDA compliant
manufacturer. We provide contract manufacturing for medical device final assemblies, sub-assemblies,
cable assemblies, wire harness assemblies, and precision components in a Class 100,000 Clean Room
We have capabilities in SMT assembly line, EDM wire cut, EDM drilling, CNC machining, laser welding, laser
cutting, laser marking, passivation, electro-polishing, resistance welding, plastic injection molding,
ultrasonic welding, soldering, pad printing, packaging etc. (Source: PetersTechnologie)

China Finally Allows FDA To Add Inspectors To Bolster Oversight

After a year of frustration and delay, the White House has finally reached agreement with the Chinese
government to allow the FDA to boost its inspection team as part of a plan to bolster oversight the
pharmaceutical supply chain. As a result, the agency will add another 10 drug inspectors to its existing staff
of one, an FDA spokeswoman tells us. (Source : Pharmalive)

Food and Drug Administration - Department of Health

http://www.taiwan.gov.tw/ct.asp?xItem=25613&ctNode=1970&mp=1001

KFDA
http://www.kfda.go.kr/eng/index.do;jsessionid=8WaGRaioTcYSanehB1hMj6KOHjYV58zMGvaefbMlRWUQqdgxsIWA05GwBX1zZoJG

39

 Pfizer, Hanmi fight over design of Viagra pill

Viagra, an erectile dysfunction drug, was released on the Korean market in 1998. In May last year, its
patent expired, triggering the release of some 50 generic versions. In the third quarter this year, Viagra
accounted for some 40 percent of the market of generic versions of Viagra, behind Hanmis generic Palpal
with 45 percent.
In October last year, the company filed a suit against Hanmi for trademark infringement, claiming that
consumers may mistakenly perceive Palpal as Viagra. (Source: KoreaTimes)

HSA

http://www.hsa.gov.sg/publish/hsaportal/en/home.html#page=tab1

CDSCO

http://www.cdsco.nic.in/

Pharma companies told to reveal quarterly drug data

The National Pharma Pricing Authority, in a letter to the state drug regulators last week, said that drug
"manufacturers be advised to ensure timely submission of the quarterly return", adding that the new drug
pricing order "provides for monitoring of production and availability of scheduled formulations and the API
(active pharmaceutical ingredient) contained in scheduled formulations".
Under the new drug pricing policy, manufacturers can no longer stop making essential drugs citing nonviability without informing the government.
They will have to issue a public notice and alert the government at least six months in advance about their
decision to exit essential drugs. Even so, the government may ask the manufacturer to continue producing
an essential drug at a certain level for another year in public interest for any of the 348 drugs that is part of
the National List of Essential Medicines . The new drug pricing order also makes it mandatory for
manufacturers to reveal on a quarterly basis the levels of essential drugs and bulk drugs they are
producing. The regulator's letter last week said, "Only a few companies have submitted the quarterly
40

return to NPPA." Officials at the NPPA told ET that the authority had already started receiving requests
from drugmakers to allow them to stop production of essential drugs in some cases.
After a gap of 18 years, the government is changing the way it fixes prices of essential drugs in the
Rs72,000-crore domestic market. However, the fundamental tenets of the new drug pricing policy have
been challenged by civil society groups in the Supreme Court, which is currently hearing the case.
(Source: EconomicTimes)

Drug retailing: SC upholds 15-day deadline for price-control rollout

The Supreme Court ruled on Monday that manufacturers and importers of pharmaceutical products must
implement the Drugs (Prices Control) Order within 15 days from the date of notification or receipt of the
order.
During these 15 days, they cannot manufacture or clear the bulk drug or formulation at the pre-notification
price.
The provisions of the DPC Order are clear, that prices should be revised within 15 days even in regard to
formulations manufactured prior to the date of notification or those manufactured within 15 days from the
date of notification, went the verdict by a bench headed by R M Lodha. The court thus dismissed the
appeals of the manufacturers, upholding the government stand. (Source: BS)

India Will Require Videotaped Evidence of Clinical Trial Consent

By embracing video consent, India apparently becomes the first country to adopt such a requirement,
according to Doug Peddicord, Head of the Association of Clinical Research Organizations (ACRO), an
industry trade group. He notes that the decision reflects, in part, the fact that India has a high illiteracy
rate, suggesting that study participants often were unaware of the specifics of informed consent forms.
However, the requirement also comes amid ongoing concern in India that multinational drug makers and
their local collaborators are using patients as unwitting guinea pigs. Earlier this year, the Indian Supreme
Court slammed regulators for shoddy oversight that has resulted in inadequate informed consent,
negligible compensation for harm, and a rising number of deaths. (Source: CPhI)

India to showcase drugmaking facilities to global regulators

India is showcasing its best pharmaceutical manufacturing facilities to regulators from emerging economies
to counter adverse publicity the country's drug industry has endured in recent times.
Health ministers and officials from countries including Kenya, Ghana, South Africa, Vietnam, Egypt and the
Philippines are being hosted by India, which is keen to dispel notions that Indian pharmaceutical companies
do not adhere to the highest quality standards.
"The idea behind this programme is to promote Indian pharmaceutical exports, apart from improving
confidence among the global community that India is a trusted source for quality generics at affordable
prices," said PV Appaji, director-general of the Pharmaceuticals Export Promotion Council. (Source:
EconomicTimes)

41

 India's Jubilant shares plunge after FDA warning for U.S. plant
Indian drugmaker Jubilant Life Sciences Ltd said on Thursday it had received a warning from the U.S. Food
and Drug Administration over manufacturing practices at one of its U.S. facilities, sending its shares the
limit-down 10 percent.
The FDA said it could withhold approval of new products from Jubilant HollisterStier LLC, a facility located
at Spokane, Washington, until the company takes action to comply with the regulator's good
manufacturing practices, Jubliant Life Sciences said. (Source: Reuters)

US FDA tells Wockhardt to evaluate its plants

Trouble for Mumbai-based drug maker Wockhardt has increased as the US Food and Drug Administration
(FDA) has raised concerns over the reliability and accuracy of tests conducted by the company at its plants
in Waluj and Chikalthana in Maharashtra. (Source: BS)

RESEARCH & DISCOVERY / BUSINESS DEVELOPMENT

Vitamin D status and ill health: a
systematic review
The Lancet Diabetes & Endocrinology - doi:10.1016/S2213-8587(13)70165-7
Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal
disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. We did a
systematic search of prospective and intervention studies that assessed the effect of 25(OH)D
concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290
prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or
survival), and 172 randomised trials of major health outcomes and of physiological parameters related to
disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong
inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid
concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple
sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause
mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal
cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease
occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean
25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 g per day or more did
not show better results. Supplementation in elderly people (mainly women) with 20 g vitamin D per day
seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention
studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease
occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is
reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and
lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in
survival. (Source : TheLancet)

42

 Vaccins dans la prvention de diarrhes Escherichia coli

entrotoxigniques (ETEC)
Ahmed T et Al. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD009029. DOI:
10.1002/14651858.CD009029.pub2
Une infection par la bactrie entrotoxignique (ETEC) est gnralement la cause de diarrhes chez l'adulte
et l'enfant dans les pays en dveloppement et principalement l'origine de la diarrhe du voyageur
chez les personnes visitant ou revenant de rgions endmiques. Un vaccin germes entiers inactivs
(Dukoral), principalement conu et homologu pour la prvention du cholra, a t recommand par
certains groupes pour prvenir des diarrhe du voyageur chez les personnes visitant des rgions
endmiques. Ce vaccin contient la sous-unit B de la toxine cholrique recombinante qui ressemble sur le
plan antignique la toxine thermolabile de l'ETEC. L'objectif de la prsente revue est d'valuer l'efficacit
clinique de ce vaccin et des autres vaccins spcialement conus pour protger les personnes des diarrhes
causes par une infection ETEC.
Objectifs: valuer l'efficacit, l'innocuit et l'immunognicit des vaccins dans la prvention de diarrhes
ETEC.
Conclusions des auteurs: l'heure actuelle, il existe des preuves insuffisantes pour recommander
l'administration orale du vaccin anticholrique Dukoral pour protger les voyageurs des diarrhes ETEC.
D'autres recherches sont ncessaires pour dvelopper des vaccins srs et efficaces afin d'assurer une
protection court et long terme contre les diarrhes ETEC. (Source : Cochrane)

Vernis au fluor pour la prvention des caries dentaires chez l'enfant

et l'adolescent
Marinho VCC et Al. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD002279.
DOI: 10.1002/14651858.CD002279.pub2
Contexte: Les vernis au fluor appliqus localement sont largement utiliss depuis plus de trente ans titre
d'intervention de prvention des caries pratique par l'oprateur. La prsente revue met jour la premire
revue Cochrane concernant les vernis au fluor pour la prvention des caries dentaires chez l'enfant et
l'adolescent, publie pour la premire fois en 2002.
Objectifs: Dterminer l'efficacit et la scurit des vernis au fluor pour prvenir les caries dentaires chez
l'enfant et l'adolescent et examiner les facteurs modifiant potentiellement leur effet.
Conclusions des auteurs: Les conclusions de cette revue mise jour restent identiques celles de la
premire publication. La revue suggre un effet substantiel d'inhibition des caries pour le vernis au fluor,
tant pour les dents permanentes que pour les premires dents, cependant la qualit des preuves a t
value comme modre, car elles ont inclus principalement des tudes ayant un risque de biais lev et
prsentant une importante htrognit. (Source : Cochrane)

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 GSK, Theravance asthma drug shows improved lung function in study

The therapy consists of the corticosteroid, fluticasone furoate, which reduces inflammation, and a longacting beta-agonist, called vilanterol, which is designed to open the airways.
The drug, already approved in the U.S. to treat chronic obstructive pulmonary disease (COPD) under the
brand name Breo, proved more effective than fluticasone furoate alone for patients with moderate to
severe asthma at the end of a 12-week treatment period.
The drug is inhaled through a palm-sized device called Ellipta. It is approved for both COPD and asthma in
Europe, where it is sold as Relvar.
The most common side effects reported in the treatment period included headache, upper respiratory tract
infection and influenza. (Source: Reuters)

Scientists Grow Lung Cells from Stem Cells

Scientists say they have been able to transform human stem cells into functioning lung and airway cells in
what theyre calling a first. The results could eventually lead to growing lung material that could be
transplanted with a much smaller chance of rejection.
Researchers have had relative success in turning human stem cells into heart cells, pancreatic beta cells,
intestinal cells, liver cells, and nerve cells, raising all sorts of possibilities for regenerative medicine, said
study leader Hans-Willem Snoeck, MD, PhD, of the Columbia University Medical Center.
The findings have implications for the study of a number of lung diseases, including idiopathic pulmonary
fibrosis.
No one knows what causes the disease, and theres no way to treat it, said Snoeck. Using this
technology, researchers will finally be able to create laboratory models of IPF, study the disease at the
molecular level, and screen drugs for possible treatments or cures.
Snoeck said that in the longer term, the development could lead the ability to make a make an autologous
lung graft. (Source: VOA)

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 Novartis investigational compound LBH589 significantly extended

time without disease progression in Phase III multiple myeloma study
Novartis today announced that results of a Phase III trial of the investigational compound LBH589
(panobinostat) in combination with bortezomib and dexamethasone, met the primary endpoint of
significantly extending progression-free survival (PFS) in patients with relapsed or relapsed and refractory
multiple myeloma when compared to bortezomib plus dexamethasone alone.
Full results from the PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) trial, continue to be
evaluated and will be presented at an upcoming medical congress and discussed with regulatory authorities
worldwide.
Multiple myeloma affects approximately 1 to 5 in every 100,000 people worldwide each year. The five year
survival-rate for patients with the disease is about 44%.
LBH589 showed significant clinical benefit bringing it a step closer to becoming the first in its class of
anticancer agents to be available to patients with multiple myeloma. As a pan-deacetylase (pan-DAC)
inhibitor, LBH589 works by blocking a key cancer cell enzyme which ultimately leads to cellular stress and
death of these cells. (Source: FierceBiotech)

Mayo Clinic: Drug Induces Morphologic, Molecular and Clinical

Remissions in Myelofibrosis
Imetelstat, a novel telomerase inhibiting drug, has been found to induce morphologic, molecular and
clinical remissions in some patients with myelofibrosis a Mayo Clinic study has found. The results were
presented at the 2013 American Society of Hematology Annual Meeting in New Orleans.
"These are early results but they are promising, says the study's lead author, Ayalew Tefferi, M.D. a
hematologist at Mayo Clinic. "Some patients in our clinical trial taking imetelstat obtained dramatic
responses and there have been some complete responses which is almost unheard of for drug therapy in
this disease."
Myelofibrosis is a chronic myeloid cancer in which bone marrow cells that produce blood cells develop and
function abnormally. The result is the formation of scar tissue in the bone marrow (fibrosis), severe anemia
that often requires transfusion, weakness, fatigue and an enlarged spleen and liver. Patients with
myelofibrosis harbor one of several genetic mutations in their blood stem cells, including JAK2, MPL, CALR,
ASXL1 and spliceosome pathway mutations. Researchers studied imetelstat in 33 patients at Mayo Clinic
and have now followed the first 22 patients for a minimum of six months. Among the 22, five patients
achieved complete or partial remissions, including reversal of bone marrow fibrosis in four of the five
patients. Two of the five patients with complete or partial remission have also experienced complete
molecular remissions. The overall response rate was 41 percent. (Source: FierceBiotech)

Eyedrops Using Novel Compound Restore Corneal Cells

Rho kinase inhibitor eyedrops stimulate the growth of corneal epithelium, according to a preliminary study
in patients with Fuchs dystrophy.
"Think outside the box," said Shigeru Kinoshita, MD, from Kyoto Prefectural University of Japan. The drops,
also known as rock inhibitors, could become a treatment reality in the future. "This is just the beginning,"

45

Dr. Kinoshita said. "We may be heading toward minimally invasive surgery for Fuchs dystrophy and other
forms of corneal problems."
The technique involves transcorneal freezing to remove the damaged endothelial cells and then adding the
eyedrops to promote cell proliferation. First, the investigators demonstrated that the technique could
result in cell proliferation and corneal wound healing in the rabbit model; next, they replicated their results
in monkeys and showed that the eyedrops could effectively treat corneal endothelial damage and promote
corneal cell proliferation.
They received approval from the university to treat 8 patients with corneal edema. Four had Fuchs
dystrophy and 4 had pseudophakic bullous keratophy. Patients were treated with eyedrop applications of
10 mmol/L 6 times per day for 7 days.
In the 4 patients with Fuchs dystrophy, corneal healing and restored visual acuity were observed. Three
months after treatment with the rock inhibitor, corneal thickness was reduced to 563 cells/mm from
700 cells/mm. (Source: MedScape)

Micro-Stent Safe With Cataract Surgery for Glaucoma

The CyPass Micro-Stent procedure for glaucoma can be safely combined with cataract surgery, according to
2-year results from the CYCLE trial. Investigators report that the procedure provided sustained control of
intraocular pressure and reduced medication use.
"This procedure is an attempt to have surgeries for glaucoma that are safer and easier for the patient," said
investigator Brian Flowers, MD, from Fort Worth, Texas. "Current surgical treatments for glaucoma are
associated with events such as suprachoroidal hemorrhage and bleb-related complications. Microinvasive
surgical stenting of the supraciliary space may improve aqueous flow, with fewer complications," he
explained here at the American Academy of Ophthalmology (AAO) 2013 Annual Meeting.
The study involved 136 eyes of patients with cataracts and a diagnosis of grade 3 or 4 open-angle
glaucoma. Patients underwent concurrent CyPass implantation and phaco-cataract surgery, and were
followed for 2 years.
The population was divided into 2 groups. Patients in cohort 1 had baseline pressure of at least 21 mm Hg,
and the goals of treatment were to lower intraocular pressure and reduce the need for medication.
Patients in cohort 2 had baseline pressure below 21 mm Hg, and the goals of treatment were to reduce
medication use and maintain pressure control.
Both groups were treated with an average of 2 medications at baseline, but more than one third needed at
least 3 agents.
"For this study, the entry criteria were fairly flexible, more like a real-world situation. Anyone who needed
intraocular pressure lowering was eligible," said Dr. Flowers. (Source: MedScape)

US firm developing malaria vaccine for pregnant women

46

US based CMC Biologics, focused on process development and cGMP manufacture of protein therapeutics,
has entered into an agreement with the University of Copenhagen for process development and cGMP
clinical production of VAR2CSA for a placental malaria vaccine. The project is focused on developing a novel
prophylactic vaccine designed to protect women against malaria during pregnancy. In 2003 Professor Ali
Salanti and others at University of Copenhagen discovered the antigen VAR2CSA, which enable parasite
accumulation in the placenta. The VAR2CSA molecule, developed by the University of Copenhagen, has the
potential to significantly reduce the effects of the parasite. The vaccine attempts not to eliminate the
infection, but to eliminate the disease. There are now collaborations with many groups around the world
that enabled the preclinical development of the vaccine, and now clinical development. The vaccine
antigen will be produced using ExpreS2ion Biotechnologies' proprietary insect cell-based recombinant
protein expression platform, ExpreS2. The ExpreS2 platform is well suited for novel and flexible production
modalities, allowing for more cost-effective processes. ExpreS2ion Biotechnologies is a partner of the
University of Copenhagen in placental malaria vaccine development. (Source: Biospectrum)

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