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Friday December 13, 2013 (SW50 2013) Send a surprise gift to your friends, sign them up to receive our free weekly Webzine by sending their email address to: white-tillet@white-tillet.com

NEWS …………………………….. p. 2

WORLDWIDE …………………………….. p. 5

EUROPEAN UNION …………………………….. p. 8

FRANCE …………………………….. p. 15

EUROPE …………………………….. p. 19

RUSSIA & RELATED COUNTRIES …………………………….. p. 27

NORTH AMERICA …………………………….. p. 27

LATIN AMERICA …………………………….. p. 36

AFRICA …………………………….. p. 36

AUSTRALIA & NEW ZELAND …………………………….. p. 37

INDIA, PAKISTAN & ASIA …………………………….. p. 38

DISCOVERY AND BUSINESS DEVELOPMENT …………………………….. p. 42

Parmi les sujets sélectionnés dans ce numéro :

Do Drugmaker plans to release trial data go far enough? p.2 ANSM: Nouveau format de rapport d’inspection: phase pilote p.16

Le mythe du vaccin qui rend autiste p.4 HAS : Rappel d’information sur la vaccination contre les papillomavirus humains par le Gardasil® p.18

Can expert gatekeepers ensure clinical trial transparency? p.5 UK PPRS published, but industry discord remains p.19

Oral contraceptives linked to glaucoma p.7 FDA implementation of the Compouding Quality Act p.27

Could the ‘Mini-tablet’ get kids to take their Medicine? p.8 FDA: Good review practice: Clinical review of investigational new drug applications p.28

EU Commission formally invites medtech, pharma to early multiparty-HTA pilot p.10

FDA: Guidance for industry – Bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA – Draft guidance p.28

EMA: Fee reductions for designated orphan medicinal products p.12 TGA: Australian statistics on medicines and vaccines 2012 p.37

HMA : Active Substance Master File (ASMF) worksharing procedure p.14

Supply chain solution in China p.39

European Pharmacopoeia and traditional Chinese Medicines p.15 India will require videotaped evidence of clinical trial consent p.41

«Beyond words, the world »

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© Adrien Tillet

NEWS

Do Drugmaker Plans To Release Trial Data Go Far Enough?

“What we’ve 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.

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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

It’s 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. They’re 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-Guérin (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

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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 toxin’s 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 toxin-

detainment 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 prospérer ? L’enquête révèle un mix de

malhonnêteté, de partialité et de conflits d’intérêts dissimulés : « La polémique est née en 1998 avec la

publication d’un article dans le Lancet évoquant un lien possible entre l’autisme et le vaccin contre la

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rougeole. La publication rendait compte d’une étude conduite par un gastro-entérologue anglais, Andrew

Wakefield, et portant sur 12 enfants (seulement). .... Si plusieurs études sont venues par la suite démentir

tout lien entre le vaccin et l’autisme, il a fallu attendre la publication, en 2010, d’un rapport du Conseil

général de la médecine britannique, pour rétablir la vérité.

Bien avant, il y avait eu la sinistre affaire du Mediator, à l’origine de la loi dite « Bertrand » du 29 décembre

2011, érigeant en culte la Transparence des liens entre industriels et prestataires de santé d’une part et

tous professionnels et établissements de santé de l’autre, mais renvoyant au décret les « détails » 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?

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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. Don’t 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 today’s

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 world’s largest maker of HIV drugs in its first act. The company’s second act—spread over the last

decade—is 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 aren’t just cheap commodities anymore—they

provide information about health that’s quite valuable. Genomic Health has continued to thrive and grow

under two CEOs—Randy 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

it’s 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

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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. It’s 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.

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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 28–29 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/ http://www.ipec-europe.org

EUROPEAN UNION

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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, Máire 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)

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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)

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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

12

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/landing/human_medicines_regulatory.jsp&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 Agency’s 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)

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Meeting highlights from the Pharmacovigilance Risk Assessment

Committee (PRAC) 2-5 December 2013

PRAC initiates further review of Iclusig

The European Medicines Agency’s 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 second-

generation 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 PRAC’s 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 medicine’s 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)

14

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 WHAT’S 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

15

… (Source: EDQM)

European Pharmacopoeia and Traditional Chinese Medicines

The EDQM, Council of Europe and the State Administration of Traditional Chinese Medicine of the People’s

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'évolution du CA (TTC) des médicaments remboursables délivrés en officines de ville en cumul annuel mobile novembre 2013/ novembre

2012. Source Xpr-SO®, le panel temps réel de CELTIPHARM (newsletter Celtinews du 6 décembre 2013)

UVESTEROL: rappel des règles d'administration chez le nouveau-né

et le nourrisson

L'ANSM (Agence nationale de sécurité du médicament et des produits de santé) et le laboratoire Crinex

rappellent les modalités d'administration des médicaments UVESTEROL D et UVESTEROL vitaminé

ADEC solution buvable chez le nouveau-né et le nourrisson.

En effet, malgré la mise en place de mesures de minimisation des risques initiées en 2006 et renouvelées

en 2011, des cas de malaises et de fausses-routes sont encore signalés lors de l'administration de ces 2

médicaments, en particulier chez des nouveau-nés prématurés et des nourrissons âgés de moins de 1

mois.

Dans ce contexte et dans l'attente de nouvelles formulations galéniques demandées par l'ANSM au

laboratoire, des fiches conseils ont été élaborées, en complément de la notice, afin de sensibiliser les

parents sur l'importance de respecter les règles d'administration de ces solutions buvables et d'utilisation

16

de la pipette doseuse. Ces fiches doivent être remises par le médecin lors de la prescription, ou par le

pharmacien lors de la délivrance de ces médicaments. … (Source : Vidal)

Bêta-2 mimétiques d'action courte par voie orale ou rectale: rapport

bénéfice/risque défavorable en obstétrique

Les médicaments contenant des bêta-2 mimétiques d’action courte administrés par voie orale ou rectale ne

doivent plus être utilisés dans le traitement des menaces d’accouchement prématuré (MAP) en raison des

risques cardiovasculaires graves associés à la prise de ces médicaments.Cette conclusion de l'EMA

(Agence européenne du médicament) fait suite à une réévaluation européenne des indications en

obstétrique des bêta-2-mimétiques, initiée en décembre 2012 par le PRAC (Comité pour l’évaluation des

risques en matière de pharmacovigilance).

La réévaluation du rapport bénéfice/risque n’a concerné que les indications relatives à l’obstétrique. Ces

conclusions ne concernent pas l'utilisation des bêta-2 mimétiques par voie injectable et par voie inhalée

dans leurs indications en traitement des maladies respiratoires. … (Source : Vidal)

Quand les applications électroniques (e-apps) sont-elles des Dispositifs Médicaux ? Le Cabinet WHITE-TILLET est spécialiste de la question et peut vous aider à y répondre ; le cas échéant, nous pouvons vous assister pour le marquage CE de votre application.

http://ansm.sante.fr/

Nouveau format de rapport d’inspection: phase pilote

L'Agence engage à partir de janvier 2014 une phase pilote pour tester un nouveau format de rapport

d’inspection qui intègre un certain nombre d'améliorations, dont la mise en application d’éléments de

gestion du risque.

La phase pilote se déroulera sur une durée d'une année dans le cadre habituel de la procédure

contradictoire menée après toute inspection de l'ANSM.

17

Nouveau format de rapport d’inspection - Note explicative à l’attention des opérateurs

(11/12/2013) (59 ko)

Rubrique Elaboration de bonnes pratiques

Médicaments contenant de la diacéréine et de la dompéridone,

médicaments à base d’octocog alpha et de zolpidem, vaccins anti-HPV –

Retour d’information sur le PRAC

Le Comité pour l’évaluation des risques en matière de pharmacovigilance (PRAC) de l’Agence européenne

des médicaments s’est réuni du 2 au 5 décembre 2013 à Londres. Les résultats intermédiaires ou finaux de

plusieurs procédures de réévaluation en cours ont été présentés et discutés. Le PRAC a ainsi recommandé

la suspension de l’AMM des médicaments contenant de la diacéréine, il a jugé que le rapport

bénéfice/risque de deux médicaments à base d’octocog alpha reste positif. Des mesures de minimisation

des risques sont envisagées pour les médicaments contenant de la dompéridone, ainsi que pour les

médicaments à base de zolpidem.

Médicaments contenant de la diacéréine et de la dompéridone, médicaments à base d’octocog alpha et de

zolpidem, vaccins anti-HPV – Retour d’information sur le PRAC (06/12/2013) (53 ko)

Le Cabinet WHITE-TILLET s’est entouré de juristes de haut niveau pour vous aider à valider la publicité et la promotion de vos médicaments. Leur expertise se combine à notre expérience réglementaire et à notre maîtrise de la méthodologie clinique. Contactez-nous pour le reviewing de vos documents publicitaires ou promotionnels!

Iclusig® (ponatinib): nouvelles recommandations concernant les

risques d'évènements vasculaires occlusifs - Lettre aux professionnels

de santé

Une augmentation du nombre d'évènements thrombotiques artériels et veineux a été observée chez des

patients traités par le ponatinib, lors du suivi prolongé de deux essais cliniques en cours, l’un de phase 1,

l’autre de phase 2. Il s’agit d’évènements indésirables cardiovasculaires, cérébrovasculaires et vasculaires

périphériques, ainsi que d'évènements thrombotiques veineux.

Les professionnels de santé peuvent continuer à prescrire le ponatinib, conformément à l’indication

approuvée, et en tenant compte des précautions supplémentaires.

Le ponatinib ne doit pas être prescrit chez les patients présentant des antécédents d'infarctus du

myocarde ou d'accident vasculaire cérébral, à moins que le bénéfice attendu du traitement soit supérieur

aux risques potentiels.

L'état cardiovasculaire des patients doit être évalué et les facteurs de risque cardiovasculaire doivent être

pris en charge et contrôlés avant l’initiation du traitement par ponatinib. La surveillance cardiovasculaire

doit se poursuivre tout au long du traitement par ponatinib.

L'hypertension artérielle doit être contrôlée au cours du traitement par le ponatinib. L’interruption du

18

traitement par le ponatinib doit être envisagée en l’absence de contrôle de l’hypertension artérielle.

L'apparition de signes d'occlusion vasculaire ou de thromboembolie doit être surveillée ; en présence de

tels signes, le traitement doit être interrompu immédiatement.

Iclusig® (ponatinib) : nouvelles recommandations concernant les risques d'évènements vasculaires

occlusifs - Lettre aux professionnels de santé (05/12/2013) (166 ko)

Le Cabinet WHITE-TILLET a plus de 20 ans d’expérience et d’expertise dans le

domaine des dossiers d’AMM. Nous maîtrisons l’eCTD. Par notre structure et

notre réseau (cabinet associé au UK, réseau international), nous maîtrisons les

procédures et assurons un suivi efficace. Confiez-nous vos dossiers d’AMM ou de

variations!

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

Rappel d’information sur la vaccination contre les papillomavirus

humains par le Gardasil®

Les données de sécurité actuellement disponibles, avec un recul de plus de 7 ans, ne remettent pas en

cause le rapport bénéfice risque du Gardasil®. Le service médical rendu tel qu’il avait été défini par la HAS

n’est pas non plus remis en question : avis de la Commission de la Transparence de la HAS.

Les professionnels de santé sont invités à poursuivre les efforts déjà entrepris pour développer la

couverture vaccinale en France en suivant les indications de l’AMM et les recommandations définies par

le HCSP, c’est à dire en ciblant les jeunes filles de 11 à 14 ans au plus tôt et notamment avant leur premier

rapport sexuel, avec un rattrapage entre 15 et 19 ans révolus : Avis du HCSP

La vaccination ne se substitue pas au frottis cervico-utérin (FCU) de dépistage, qui doit être réalisé tous les

3 ans chez les femmes à partir de 25 ans jusqu’à 65 ans. … (Source: HAS)

Renouvellement du comité déontologie et indépendance de

l’expertise de la Haute Autorité de Santé (HAS)

A l’exception du président M. Alain Christnacht qui est renouvelé dans ses fonctions, le comité accueille 4

nouveaux membres, dont un représentant d’usagers en la personne d’Eric Molinié. Cette nomination

s’inscrit dans le souhait de la HAS d’associer toujours davantage les associations de patients à ses travaux et

à son fonctionnement.

Par la présence de deux spécialistes du droit – M. Alain Christnacht et Mme Soraya Amrani-Mekki – mais

aussi de deux professionnels de santé – M. Daniel Couturier et M. Jean-Roger Legall – la composition du

comité allie rigueur dans le respect du droit et pragmatisme.

19

Par souci d’indépendance, le comité ne comprend en outre que des personnalités extérieures à la HAS. …

(Source: HAS)

CEPS

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

Le Cabinet WHITE-TILLET a près de 30 ans d’expérience et d’expertise dans le

domaine du remboursement des médicaments, incluant la maîtrise de la

méthodologie clinique. La rédaction de ces dossiers est un art complexe. Les

conséquences pour les firmes peuvent être 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 competency-

based 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, Bristol-

Myers 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.

20

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 cost-

effective 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 government’s 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 UK’s latest annual State of the Nation report finds huge regional variations in people’s 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.

21

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 (230Kb)

Draft minutes of October 2013 meeting (220Kb)

Presentations and papers

SABRE update presentation (290Kb)

BCR review process for reporting year 2012/13 (248Kb)

Summary of common deficiencies for inspections to date in 2013/14 (254Kb)

Update on BCC IT workgroup (16Kb)

Update on blood component labelling (198Kb)

Update from SHOT Annual Report (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 under-

reporting. 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.

22

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)

23

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 high-

profile 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 and…having a proper dialogue with the

Chinese authorities about the issues". … (Source: PharmaTimes)

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

NICE: Final appraisal determination Teriflunomide for treating

relapsing–remitting multiple sclerosis

Teriflunomide is recommended for treating adults with active relapsing–remitting 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 relapsing–remitting 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?

24

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/

25

Réglementation relative aux précurseurs: codes tarifaires pour les

médicaments contenant de l’éphédrine, de la pseudoéphédrine, de la

nor-éphédrine ou leurs sels

Les médicaments contenant de l’éphédrine, de la pseudoéphédrine, de la nor-éphédrine ou leurs sels ont

maintenant des codes tarifaires spécifiques. Le code correct doit donc être mentionné sur tous les

documents officiels relatifs à chaque importation ou exportation d’un de ces médicaments.

Les médicaments concernés sont marqués d’une étoile dans le document (PDF, 135.05 Kb) reprenant les

codes tarifaires publiés dans le Journal officiel de l’Union européenne. … (Source: AFMPS)

Réglementation relative aux précurseurs: changements suite à

l’adhésion de la Croatie à l’UE

Depuis le 1er juillet 2013, toutes les transactions commerciales avec la Croatie sont considérées comme

une activité intra-communautaire et entraîne une modification de l’agrément/ enregistrement pour les

opérateurs concernés. Ils sont invités à introduire une demande de modification de cet agrément/

enregistrement à la cellule des Précurseurs.

Agrément/ enregistrement précurseurs

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

réponses

Le 7 Mars 2013, des nouvelles lignes directrices relatives aux bonnes pratiques de distribution (BPD) ou «

good distribution practices » (GDP) ont été publiées au niveau européen. Celles-ci ont été transposées en

droit belge dans l’arrêté royal du 19 septembre 2013 modifiant l’arrêté royal du 14 décembre 2006 relatif

aux médicaments à usage humain et vétérinaire. Un document reprenant les questions fréquemment

posées à ce sujet et les réponses qui y sont apportées est à présent disponible.

Document de questions/ réponses (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)

26

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 Italy’s 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/

27

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 cœur de nos préoccupations et dans notre champ de compétence. N’hésitez pas à venir vers nous pour réaliser vos audits. Nous avons un réseau 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

28

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

29

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 King’s 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 Eisai’s 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)

30

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 Peyronie’s 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)

31

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 Cell’s 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)

32

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 Alzheimer’s Disease trial probably can’t 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.

33

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)

34

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)

35

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)

36

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

Fiscalité des médicaments, consommables et équipements médicaux

dans les pays membres de l’UEMOA (Source: Cerdi)

L’Afrique de l’Ouest: des opportunités d’affaires à découvrir (Source:

SlideShare)

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

37

Promotion de l'Industrie Pharmaceutique (Source : DPHM)

Pharmacovigilance et Lutte contre les Médicaments 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)

38

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

39

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

Peter’s 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: Peter’sTechnologie)

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

40

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 Hanmi’s 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 non-

viability 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

41

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)

42

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 μg per day or more did

not show better results. Supplementation in elderly people (mainly women) with 20 μg 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)

43

Vaccins dans la prévention de diarrhées à Escherichia coli

entérotoxigéniques (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 bactérie entérotoxigénique (ETEC) est généralement la cause de diarrhées chez l'adulte

et l'enfant dans les pays en développement et principalement à l'origine de la « diarrhée du voyageur »

chez les personnes visitant ou revenant de régions endémiques. Un vaccin à germes entiers inactivés

(Dukoral®), principalement conçu et homologué pour la prévention du choléra, a été recommandé par

certains groupes pour prévenir des « diarrhée du voyageur » chez les personnes visitant des régions

endémiques. Ce vaccin contient la sous-unité B de la toxine cholérique recombinante qui ressemble sur le

plan antigénique à la toxine thermolabile de l'ETEC. L'objectif de la présente revue est d'évaluer l'efficacité

clinique de ce vaccin et des autres vaccins spécialement conçus pour protéger les personnes des diarrhées

causées par une infection à ETEC.

Objectifs: Évaluer l'efficacité, l'innocuité et l'immunogénicité des vaccins dans la prévention de diarrhées à

ETEC.

Conclusions des auteurs: À l'heure actuelle, il existe des preuves insuffisantes pour recommander

l'administration orale du vaccin anticholérique Dukoral® pour protéger les voyageurs des diarrhées à ETEC.

D'autres recherches sont nécessaires pour développer des vaccins sûrs et efficaces afin d'assurer une

protection à court et long terme contre les diarrhées à ETEC. … (Source : Cochrane)

Vernis au fluor pour la prévention 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 appliqués localement sont largement utilisés depuis plus de trente ans à titre

d'intervention de prévention des caries pratiquée par l'opérateur. La présente revue met à jour la première

revue Cochrane concernant les vernis au fluor pour la prévention des caries dentaires chez l'enfant et

l'adolescent, publiée pour la première fois en 2002.

Objectifs: Déterminer l'efficacité et la sécurité des vernis au fluor pour prévenir 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 à jour restent identiques à celles de la

première publication. La revue suggère un effet substantiel d'inhibition des caries pour le vernis au fluor,

tant pour les dents permanentes que pour les premières dents, cependant la qualité des preuves a été

évaluée comme modérée, car elles ont inclus principalement des études ayant un risque de biais élevé et

présentant une importante hétérogénéité. … (Source : Cochrane)

44

GSK, Theravance asthma drug shows improved lung function in study

The therapy consists of the corticosteroid, fluticasone furoate, which reduces inflammation, and a long-

acting 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 they’re 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 there’s 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)

45

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,"

46

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/mm² from

700 cells/mm². … (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

47

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)

48

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49

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