Adaptive Licensing

In the month of March the European Medicines Agency (EMA) launched its adaptive licensing pilot project.

So what is Adaptive licensing...

Adaptive licensing is a new approach to licensing medicines, which is still in the early stages of development. In this model, licensing is based on stepwise learning under conditions of acknowledged uncertainty, data and regulatory evaluation. This is in contrast to traditional drug-licensing approaches, where an experimental therapy is transformed into a fully evaluated therapy at the moment of licensing.

The adaptive licensing approach, sometimes called staggered approval or progressive licensing, is aimed at improving timely access for patients to new medicines especially when there are no satisfactory alternative therapies. Adaptive licensing builds on existing regulatory processes and intends to extend the use of elements that are already in place, including scientific advice, centralised compassionate use, the conditional marketing authorisation mechanism (for medicines addressing life-threatening conditions), patients’ registries and pharmacovigilance tools that allow collection of real-life data and development of risk management plans. Ongoing medicine development programmes submitted by companies should be experimental medicines in the early stage of clinical development, i.e., prior to the initiation of confirmatory studies.

This approach could allow approval to align more closely with patient needs for timely access to new technologies and for data to inform medical decisions.

AL will take into consideration impressive preliminary animal/human data; positive benefit risk; commitment of sponsor to conduct further studies after initial MA; adequate infrastructure to observe AL etc. Thus AL is designed to manage the entire life span of a drug, during which data continue to be generated on the product through various ways, including active surveillance and additional studies after initial and “full” licensing.

Refer below link for more information.

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/03/news_detail_002046.jsp&mid=WC0b01ac058004d5c1

 

First medicine on Castleman disease a rare disorder gets EMA approval

Castleman’s disease is an uncommon lymphoproliferative disorder that may be localized to a single lymph node (unicentric) or occur systemically (multicentric). It is a non-cancerous growth of the lymph nodes and related tissues, but it is associated with a higher risk of a type of cancer called lymphoma.

Affected patients have an increased risk of infection, kidney failure and certain cancers. Castleman’s disease is life threatening, especially for patients with more than one affected lymph node. The most common Symptoms are high fevers, anemia, weight loss, loss of appetite, and low white blood cell counts, which may to be due to the overproduction of interleukin 6.

Sylvant (siltuximab), a medicine for the treatment of adult patients with multicentric Castleman’s disease who are HIV negative and human herpesvirus‑8 (HHV‑8) negative have received European Medicines Agency (EMA) recommendation for MAA under orphan legislation. The active substance of Sylvant is siltuximab, a human‑mouse chimeric monoclonal antibody that specifically binds to and neutralizes human IL-6 with high affinity.

There are currently no medicinal products authorized in the European Union (EU) for the treatment of Castleman’s disease. In clinical trials, Sylvant has shown its ability to reduce tumour burden and improve the symptoms of the disease with a safety profile.

The CHMP opinion on Sylvant will now be sent to the European Commission for adoption of a decision on an EU-wide marketing-authorization.

For more details refer http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/03/news_detail_002048.jsp&mid=WC0b01ac058004d5c1

 

The tough road ahead for Biosimilars or follow-on-biologics

I may call it a coincidence...that on women’s day I am posting this blog about a drug on breast cancer. I was just assessing the regulatory perception of the news and its relevance to the women in India...oh but before that let’s get to the core news.

On 5 February, Delhi high court restricted Biocon and Mylan from claiming similarity to the Roche breast cancer drug HERCEPTIN® in India.

The new biosimilar product was to be launched under the trade name Hertraz by Mylan and as CANMAb by Biocon in early 2014 under co exclusive rights for the product in India.

Biocon and Mylan have challenged Roche’s contention, insisting that the package insert is duly approved by the drug authority. The approval of what is essentially a generic version of the targeted drug came three months after Roche's patent on HERCEPTIN® expired in India.

Significance of the approval was that it was the first biosimilar trastuzumab to be accorded regulatory approval.

Monoclonal antibodies (MABs) currently represent the fastest growing segment within the biopharmaceutical industry. Biosimilar manufacturers face many challenges considering the complicated structure and larger size of MABs. Moreover, this market is dominated by leading players and making market entry a difficult plan for biosimilar manufacturers. Regulatory Authority’s concern about transparency and safety with patients are also likely to be critical in a competitive and dynamic environment.

 In addition to the above challenges currently an issue on International Non-proprietary names (INN’s) is fetching attention on international platform.  Under the WHO's current INN policy, nonglycosylated biosimilar receive the same INN as the reference drug, as they're considered highly similar. But glycosylated biosimilar, considered comparable but distinct, get a suffix – such as alpha or beta – added to the INN.

 Debate is on whether Biosimilars should be treated as unique products with uniquely distinguishable International Non-proprietary names. Generic drug makers that are getting into the market want Biosimilars treated as generics, which means they would have the same INN as the reference product. But companies with extensive experience in developing biologics think distinguishable names are necessary because no two biologics are expected to be identical.

Future of biosimilar of HERCEPTIN® in India is unknown yet, but the importance of the fact that an access to affordable and safe medicines to women in India cannot be ignored.

E-cigarettes will not be controlled as medicinal products in Europe

On 8 October 2013, European Parliament adopted anti-smoking bill but refused to control e-cigarettes as medicinal products.

Electronic cigarettes will therefore continue to be available in tobacco shops or specialist stores, with the exception of any brands claiming curative properties. They will also be banned for sale to minors and no advertising allowed.

The parliament’s vote will set the stage for negotiations with the EU’s member states over final legislation.

Refer following links for more information.

http://www.europarl.europa.eu/plenary/en/texts-adopted.html

http://www.eubusiness.com/news-eu/health-tobacco-law.qse

European Medicines Agency (EMA) publishes a video explaining the concept of medicines under additional monitoring on 1 October 2013.

The concept of additional monitoring and the black symbol were introduced by new EU laws on the safety-monitoring of medicines, started to come into effect in 2012.

Any new medicine authorized after 1 September 2013 which is subject to additional monitoring will include the black symbol in the package leaflet and the summary of product characteristics when it is placed on the EU market.

The legislation affects medicines authorized in the EU after 1 January 2011. Therefore, there will be a transition period for medicines authorized between January 2011 and August 2013.

For medicines that are already authorized, marketing-authorization holders are encouraged to use the new template at the next regulatory procedure affecting the product information. If there are no such procedures, companies should submit a type-IA_IN variation no later than 31 December 2013.

The European Medicines Agency has published a video and a factsheet in all official European Union (EU) languages today 1 October explaining the meaning of the black triangle, which is now starting to appear in the product information of certain authorized medicines in the EU.

All medicines on the EU market are carefully monitored. If a medicine is labelled with the inverted black triangle, it does not mean that it is unsafe; the purpose of the symbol is to actively encourage healthcare professionals and patients to report any suspected adverse reactions observed with the medicine, either because the medicine is new to the market or because there is a limitation to the data available on its safety.

This system will help Regulatory authorities to collect information to monitor real-life experience with medicines. Regulatory authorities look at all reports of adverse reactions, alongside all the information they already have, to make sure that the benefits of medicines remain greater than their risks and to take any necessary action to optimize safe and effective use.

Following criteria applies for additional monitoring status to a medicine:

• it contains a new active substance authorized in the EU after 1 January 2011;
• it is a biological medicine, such as a vaccine or a medicine derived from plasma (blood), authorized in the EU after 1 January 2011
• it has been given a conditional approval (where the company that markets the medicine must provide more data about it) or approved under exceptional circumstances (where there are specific reasons why the company cannot provide a comprehensive set of data)
• the company that markets the medicine is required to carry out additional studies, for instance, to provide more data on long-term use of the medicine or on a rare side effect seen during clinical trials.

Other medicines can also be placed under additional monitoring, based on a decision by the Agency's Pharmacovigilance Risk Assessment Committee (PRAC). 

 

For detailed information refer: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/09/news_detail_001900.jsp&mid=WC0b01ac058004d5c1

New Drug marketing within a period of six months from obtaining permission is mandatory in India

The principal national drug authority for India - the Central Drug Standards Control Organization (CDSCO) has announced that the new drug should be launched for marketing within a period of six months from obtaining the license from CDSCO.

CDSCO reviews the new drug applications under the Drugs and Cosmetics Rules, 1945 and grants the permission to manufacture a new drug. Based on the permission received from CDSCO, manufacturer obtains manufacturing licence from the concerned State Licensing Authorities.

As per schedule Y, Periodic safety Update reports (PSURs) of new drugs are required to be submitted every six months for initial 2 years and then annually for subsequent 2 years. However CDSCO observed that the manufacturers do not launch their products even after years of getting approval from the authority and do not submit required PSUR, while the drug does not remain new drug after a period of 4 years. The assessment of safety and efficacy of such new drugs in post marketing scenario remains incomplete.

Therefore CDSCO has decided that in case manufacturer fails to launch the product for marketing in the country within a period of 6 months from obtaining the permission from CDSCO, the permission will be treated as cancelled.

For information refer http://www.cdsco.nic.in/

New Identification System for Medical Devices gets finalized in the USA

On 20 September the U.S. Food and Drug Administration announced the unique device identification system (UDI) that, once implemented, will provide a consistent way to identify medical devices.

FDA News release says, UDI represents a landmark step in improving patient safety, modernizing post market surveillance system for medical devices, and facilitating medical device innovation.

As part of the UDI system, the FDA is also creating the Global Unique Device Identification Database (GUDID) which will include a standard set of basic identifying elements for each device with a UDI. Most of this information will be made available to the public so that users of a medical device can easily look up information about the device.

The UDI system consists of two core items. The first is a unique number assigned by the device manufacturer to the version or model of a device, called a unique device identifier. This identifier will also include production-specific information such as the product’s lot or batch number, expiration date, and manufacturing date when that information appears on the label.

 The second component is a publicly searchable database administered by the FDA, called the Global Unique Device Identification Database (GUDID) that will serve as a reference catalogue for every device with an identifier. No identifying patient information will be stored in this device information center.

UDI system will help trace the devices quickly in analyzing any adverse events.  A more robust post market surveillance system can also be leveraged to support premarket approval or clearance of new devices and new uses of currently marketed devices. It will also help to efficiently manage Medical devices recall. Finally UDI system will serve a foundation for global distribution chain and help address counterfeiting.

Compliance dates for UDI implementation are defined in UDI rule. In general, high-risk medical devices (Class III) will be required to carry unique device identifiers on their label and packaging within one year and this number and corresponding device information must be submitted to the new database. Manufacturers will have three years to act for most Class II (moderate risk) devices. Manufacturers of Class I devices not exempt from UDI requirements will have five years to act.

For more information refer

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm369276.htm

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentification/default.htm