Biosimilars

When will the US biosimilars pathway be used

FDA Commissioner Margaret Hamburg presented the latest statistics on the US biosimilar pathway during a speech at the Massachusetts Biotechnology Council’s (MassBio) Annual Meeting on 15 March 2013.

Greece says no to automatic substitution of biologicals

Greece’s Medicines Agency (National Organization for Medicines, Ethnikos Organismos Farmakon, EOF) released a document on 13 March 2013 recommending against automatic substitution/interchangeability of reference biologicals and their biosimilars.

Pharma companies sue EMA to block release of data

US-based biotech companies AbbVie and InterMune have both sued EMA in a bid to block publication of clinical trial data for their drugs.

Research on biosimilars in rheumatology

Period: September to December 2012 

Over the past decade, the availability of targeted biological therapies has revolutionized the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. However, the significant cost of these biologicals is often prohibitive and limits universal access to these effective therapeutic agents. Whereas generic drug equivalents are commercially available for many small-molecule medications, such lower cost alternatives to targeted biological therapies are not yet available in the US or the EU.  The first biological therapeutics in rheumatology is now approaching patent expiration and biosimilars are now in randomized controlled trials. This means that cheaper biosimilars for the treatment of rheumatic diseases are likely to enter the market in the near future, increasing patient access to these life-changing treatments.

Japan approves second biosimilar G-CSF

Japan has granted regulatory approval to a second biosimilar granulocyte colony-stimulating factor (G-CSF).

XBiotech moves into biosimilars

US-based biotech company XBiotech announced on 26 February 2013 that the company would be expanding its portfolio to include biosimilars.

Prospects for producing follow-on biological products in Brazil

New research shows the need for local production of biologicals in Brazil in order to offset the increasing medicines budget and reduce the trade deficit when it comes to drugs [1].

US FDA defends biosimilar substitution

US FDA Commissioner Margaret Hamburg defended the substitution of interchangeable biosimilars at the Generic Pharmaceutical Association (GPhA) Annual Meeting which was held in Orlando, Florida, USA, on 20–22 February 2013.

MS patient dies from immunogenicity to biological drug

A Swedish woman diagnosed with multiple sclerosis (MS) appears to have died after developing unwanted immunogenicity toward the biological drug Tysabri (natalizumab), according to a report in the journal Neurology [1].

Mylan and Biocon to partner on insulin products

Generics giant Mylan announced on 13 February 2013 that it had entered into an agreement with India-based Biocon to develop and market Biocon’s biosimilar versions of three insulin analogue products.

Oncobiologics and Viropro make biosimilar deal

US-based Oncobiologics and monoclonal antibody developer Viropro announced on 25 February 2013 that they had signed a biosimilar collaboration agreement between the two companies.

Assessment of interchangeability under the BPCI Act

The Biologics Price Competition and Innovation (BPCI) Act gives FDA the authority to designate a biosimilar as interchangeable with its reference product. This means that the biosimilar may be substituted for the originator product by the pharmacist without reference to the prescribing physician [1]. The criteria for establishing interchangeability of biosimilars, despite FDA issuing three draft guidance documents, are still not clear [2].

Amgen’s response to biosimilar substitution legislation in US

Amgen, in a statement issued on 1 February 2013, has hit back at accusations that the biotech giant is attempting to limit the uptake of biosimilars in the US by backing state bills, which constrain the use of biosimilars.

The ethics of biosimilars

Biosimilars in the EU have to undergo a strictly regulated comparability exercise against the reference medicinal product on the physicochemical, analytical, functional, non-clinical and clinical level. Only if a biosimilar is a close copy of the reference medicine will it be approved as a biosimilar [1]. Despite this fact, however, ethical issues have been raised on the use of granulocyte colony-stimulating factor (G-CSF, filgrastim) in healthy volunteers by the European Group for Blood and Marrow Transplantation (EBMT) and the World Marrow Donor Association (WMDA).

Merck makes biosimilars deal with Samsung Bioepis

Pharma Giant Merck announced on 20 February 2013 that it had made a deal to develop and commercialize biosimilars with Samsung Bioepis.

Medicines spending in Brazil

The Brazilian pharmaceutical market is the third largest in the Americas region, behind the US and Canada; it ranks first in the Latin American region. Pharmaceutical demand will continue to rise, fuelled by increasing disposable income. Despite this positive outlook, the trade deficit in Brazil grew from US$700 million at the end of the 1980s to a cumulative US$7.13 billion in 2008. In 2008 alone, Brazil imported US$1.4 billion in vaccines, serum and blood products, while exporting US$37 million in medicinal products with low added value [1].

Biosimilars to replace 70% of chemical drugs

Biosimilars will replace some 70% of global chemical drugs over the next couple of decades, according to industry experts. This replacement will occur due to the better safety profiles of biosimilars compared to chemical drugs and the fact that many originator biologicals will lose their patent protection in the coming years, according to Mr Appaji, Director General of Pharmaceuticals Export Promotion Council of India (Pharmexcil).

AMAC and GPhA hit back at Big Pharma over biosimilars

The Association of Mature American Citizens (AMAC) and the Generic Pharmaceutical Association (GPhA) have reacted strongly to the actions by Amgen and Genentech, which aim to make it more difficult for patients to get access to biosimilar medicines [1].

Biologicals boom

Researchers predict that the present list of top 10 blockbuster drugs will change dramatically by 2014. The predictions are that by 2014 biological drugs will topple the present market leaders Pfizer’s Lipitor (atorvastatin) and Sanofi’s Plavix (clopidogrel), both of which are small molecule chemical entities [1].

Biotech firms try to limit biosimilar substitution in US

FDA is still to approve a biosimilar and has yet to issue final guidelines outlining the regulatory requirements for approval of a biosimilar in the US.

Assessment of biosimilarity under the BPCI Act

The Biologics Price Competition and Innovation (BPCI) Act defines a biosimilar as a product that is highly similar to the reference product notwithstanding minor differences in clinically inactive components and without clinically meaningful differences in terms of safety, purity, and potency. Although draft guidances issued by FDA do begin to clarify the issue, little or no discussion regarding how similar is considered highly similar is given in the BPCI Act and no criteria for assessing biosimilarity were mentioned [1].

G-CSF biosimilars – World Marrow Donor Association position

The World Marrow Donor Association (WMDA) has expressed its position on the use of granulocyte colony-stimulating factor (G-CSF) biosimilars in healthy donors in an article published in the journal Haematologica [1].

Mobilization of stem cells in healthy donors by G-CSF biosimilars shows comparable efficacy and safety to Neupogen

Originator human recombinant granulocyte colony-stimulating factor (G-CSF) filgrastim has been widely used for the mobilization of CD34⁺ stem cells in healthy donors. However, there is limited experience with the use of biosimilar G-CSF for the mobilization of peripheral blood stem cells (PBSCs), especially in healthy donors. A recent study by Professor Schmitt and co-authors has addressed this issue and found that biosimilar G-CSF showed comparable efficacy and safety with reference G-CSF (Neupogen) when used for the mobilization of CD34⁺ stem cells, as well as CD3⁺ T-cells and nucleated cells, in healthy donors [1].

Top developments in biosimilars during 2012

Much has happened in the biosimilars’ industry over the last year.

Overview of research on G-CSF biosimilars in 2012

Period: January to August 2012 

A life-threatening complication for patients undergoing chemotherapy is febrile neutropenia, involving a loss of neutrophils (white blood cells) and fever [1]. Granulocyte colony-stimulating factors (G-CSFs) are growth factors, which stimulate the bone marrow to produce white blood cells and restore neutrophil production. In oncology and haematology, G-CSF is used with certain cancer patients to accelerate recovery from neutropenia after chemotherapy, allowing higher-intensity treatment regimens.

Biosimilarity and interchangeability under the BPCI Act

In the US, the Biologics Price Competition and Innovation (BPCI) Act was signed into law on 23 March 2010, giving FDA the authority to approve biosimilars. FDA then issued guidelines for biosimilar applications in February 2012 in the form of three draft guidance documents [1]. Despite this, there remain scientific issues regarding the assessment biosimilars and the criteria for establishing biosimilarity and interchangeability of biosimilars [2].

Positive phase I data for infliximab biosimilar

US-based Epirus Biopharmaceuticals (Epirus) announced on 4 January 2013 that its biosimilar infliximab candidate had ‘achieved bioequivalence’ to Remicade (infliximab) in a single dose comparator trial.

ProCognia completes global glycoanalysis centre

Israeli biotech company ProCognia announced on 14 January 2013 the completion of its global centre of excellence for glycoanalytics.

Overview of research on analytical techniques in the manufacturing of biosimilars in 2012

Period: January to August 2012 

Biologicals are large, complex and heterogeneous proteins with variable molecular weights, typically ranging from 18,000 to 45,000 Da. The active substance of a biological is a collection of large protein isoforms and not a single molecular entity. This fact makes manufacturing of biosimilars much more of a challenge than when producing traditional small molecule generics. It also makes it highly unlikely that the active substances between two products are identical and makes it extremely difficult to establish biopharmaceutical equivalence using analytical techniques.

Teva asks FDA to delay approval of Biogen’s MS drug

Teva Pharmaceutical Industries (Teva) has petitioned FDA not to approve Biogen Idec’s (Biogen’s) investigational pill for treatment of multiple sclerosis, BG-12 (dimethyl fumarate), citing safety concerns.

Biosimilar trastuzumab made in tobacco plants

Canada-based PlantForm have altered tobacco plants to create a biosimilar version of Roche’s breast cancer drug Herceptin (trastuzumab).

Finox submits r-FSH biosimilar application to EMA

Finox Biotech announced on 20 December 2012 that it had submitted a Marketing Authorisation Application (MAA) for its biosimilar recombinant follicle stimulating hormone (r-FSH) to EMA on 30 October 2012.

Biosimilar monoclonal antibodies on the horizon in Europe

European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use adopted the final guideline on biosimilar monoclonal antibody (mAb) and it came into effect in December 2012. The agency is also currently reviewing two marketing authorization applications (MAAs) for the biosimilar mAb infliximab.

Significance of locally produced biosimilars in Iran

Biopharmaceuticals, drugs produced by live cell culture, have a fast growing market for the treatment of a range of conditions. Despite their clinical importance, however, their cost could impose an increasing burden on either national healthcare systems or patients’ out-of-pocket expenses. The potential for reducing the costs of biopharmaceuticals is therefore attracting the attention of policymakers in the health sector.

Biosimilars applications under review by EMA – 2012 Q4

Last update: 23 August 2013 

European Medicines Agency (EMA) is the body responsible for approval of biosimilars within the EU. A legal framework for approving biosimilars was established in 2003. Approval of biosimilars is based on an abbreviated registration process, which allows biosimilars manufacturers to provide a reduced package of information compared to originator drugs, provided they can prove ‘similarity’ to the originator or ‘reference drug’.

CCM and Biocon make biosimilar insulin deal

Malaysia-based Chemical Company of Malaysia Berhad (CCM), announced on 14 December 2012 an agreement between its subsidiary, CCM Pharmaceuticals Sdn Bhd (CCMP), and India-based Biocon, giving CCMP exclusive licence and distribution rights to market, sell and distribute a range of insulin products in Malaysia and Brunei.

History of biosimilar monoclonal antibodies regulation in EU

Monoclonal antibodies (mAbs) are high molecular weight proteins (~150 kDa), with highly complex secondary and tertiary structures, subject to post-translational modifications, such as glycosylation.

Overview of research on manufacturing statistics and innovations of biosimilars in 2012

Period: January to August 2012 

Manufacturing of biosimilars is much more challenging than producing traditional small molecule generics. Reasons for this include, in the first place, the huge costs associated with manufacturing of biosimilars, along with the fact that the risk of failure for biosimilars is significantly higher than that for small molecule generics. Secondly, biosimilars are larger and more complex molecules to manufacture. Finally, minor changes in the manufacturing process can cause significant changes in efficacy or immunogenicity.

Comparison of EPARs for G-CSF biosimilars approved in Europe

EMA approved its first biosimilar granulocyte colony-stimulating factor (G-CSF, filgrastim) for use in Europe back in 2008, since then, several biosimilar G-CSFs have been approved, including Biograstim, Filgrastim ratiopharm, Ratiograstim, Tevagrastim, Filgrastim Hexal, Zarzio and Nivestim. All biosimilar G-CSFs were approved using Amgen’s Neupogen as the reference product. Filgrastim ratiopharm was withdrawn on 20 April 2011.

Originator biologicals approved and marketed in Germany

Last updated: 14 December 2012 

The Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) is responsible for the approval, i.e. marketing authorization, of medicinal products, including biologicals, in Germany.

Overview of research on regulatory issues surrounding biosimilars in 2012

Period: January to August 2012 

In the area of regulation of biosimilars Europe has by far the best-established framework for approval and EMA has already issued both general and product specific guidelines for biosimilar applications to the EU [1]. The first biosimilar was approved in the EU in 2006 for Omnitrope (somatropin). There are now 14 biosimilars approved for use in Europe for three reference products: erythropoietin, granulocyte-colony stimulating factor and somatropin [2].

China-based Innovent gains funding for expansion

Innovent Biologics (Innovent) has raised US$25 million in Series B financing to put towards the continued expansion of its pipeline and manufacturing capabilities.

Marvel withdraws biosimilar insulin applications

EMA announced on 27 November 2012 that it had been informed by Marvel LifeSciences (Marvel) that the company would be withdrawing its authorization applications for its three biosimilar human insulins.

Approval of first biosimilar G-CSF in Japan

Mochida Pharmaceuticals (Mochida) and development partner Fuji Pharma announced on 21 November 2012 that they had gained approval for the first biosimilar granulocyte colony-stimulating factor (G-CSF) in Japan.

ASBM publishes paper on biosimilar naming

The US-based Alliance for Safe Biologic Medicines (ASBM) announced on 28 November 2012 that its recommendations with respect to identification and substitution of biosimilars have been published in the Food and Drug Law Institute (FDLI) policy forum.

Overview of research on US regulatory issues surrounding biosimilars in 2012

Period: January to August 2012 

The US is somewhat behind Europe in the biosimilars race, but has issued draft guidance and is expected to have a practical biosimilar approval pathway in place in the near future.

Competing biosimilars to Amgen’s biologicals

Amgen has been a leading biotechnology company since 1980. Amgen pioneered the development of novel products based on advances in recombinant DNA and molecular biology and launched the biotechnology industry’s first blockbuster medicines.

ABPI issues position paper on biosimilars

The Association of the British Pharmaceutical Industry (ABPI), which represents innovative research-based biopharmaceutical companies in the UK, announced on 12 November 2012 the publication of its position paper on biosimilars.

Biosimilars approved and marketed in Germany

Last updated: 23 November 2012 

The Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) is responsible for the approval, i.e. marketing authorization, of medicinal products, including biosimilars, in Germany.

Saving money in the European healthcare system with biosimilars

Biotechnology-derived medicines are increasingly popular for treating a range of conditions from cancer to autoimmunity, and yet they are among the most expensive healthcare products owing to their manufacture using live cell cultures. As healthcare providers become increasingly concerned about rising costs, interest is turning to the idea of substituting reference biological drugs with cheaper but similar biological products, or biosimilars, after patents expire on reference products. The use of biosimilars has the potential to reduce healthcare expenditure, particularly for long-term treatments, which incur high annual treatment costs.

Dialogue needed to build confidence in biosimilars

Concerns about the safety and efficacy of biosimilars have led many healthcare professionals to become reluctant to prescribe these products for their patients [1]. According to a commentary by Dr Hans C Ebbers and co-authors, these concerns could be addressed through more engagements taking place between regulatory authorities and the medical community over the drafting of regulatory guidelines [2]. This would result in greater confidence in the regulatory process and trust in the products that gain approval.

American dermatologists update position statement on biosimilar substitution

On 3 November 2012, the American Academy of Dermatology (AAD) updated its position statement on generics and biosimilar substitution to reflect its views, in particular on interchangeability* and naming of biosimilars.

Positive results from phase III study with biosimilar human insulin

One of Asia’s leading biotechnology companies, Biocon, announced on 31 October 2012 positive results from its global phase III study for its recombinant human insulin (Insugen). The study, which was carried out in type 1 diabetes mellitus (T1DM) patients, demonstrated comparable safety and efficacy compared to the originator product.

Sandoz starts phase III US trial for biosimilar epoetin alfa

Sandoz, the generic drug division of Swiss drug giant Novartis, announced on 25 October 2012 that it had started patient enrolment in a phase III clinical trial in the US for biosimilar epoetin alfa (Amgen/Johnson & Johnson’s Epogen/Procrit).

The latest biosimilars agreements

Biosimilar is still the hottest subject around.  Just a few of the latest collaborations for the development of biosimilars include agreements made on 6 November 2012 between AET BioTech and BioXpress Therapeutics; Oncobiologics and Boston Oncology; ProCognia and UniTargetingResearch; and the Innovent Biologics and Pharmatech Associates agreement made on 1 November 2012.

Japanese firms developing biosimilars

Japanese firms are definitely not dragging their heels when it comes to biosimilars. The latest agreement for biosimilar development involves LG Life Sciences (LGLS) and Mochida Pharmaceutical (Mochida), while joint venture Fujifilm Kyowa Kirin Biologics has announced it is to initiate development of a biosimilar version of bevacizumab.

Biosimilar terminology confusion

Imprecise usage of the term biosimilar in the literature is an issue that has already been highlighted by EMA [1].

Glossary of key terms

Last update: 9 June 2017

Confusion may sometimes surround terms used in the fields of generics and biosimilars. This has been recognized as a problem by EMA, who has expressed the need to propose a more precise definition for biosimilars due to problems arising from imprecise usage of the terms in the scientific literature and elsewhere [1].

Reliance Life Sciences starts ‘similar’ infliximab trial in India

Reliance Life Sciences is starting a clinical trial for a ‘similar biologic’ version of infliximab in patients suffering with rheumatoid arthritis in India.

STC Biologics receives US$2.5 million for biosimilar mAb development

US-based biotechnology company STC Biologics announced on 10 October 2012 that it had entered into a US$2.5 million phase II Small Business Innovation Research (SBIR) contract with the National Cancer Institute (NCI) to develop a STC101, a biosimilar monoclonal antibody (mAb), for the treatment of cancer.

Samsung halts biosimilar rituximab development

South Korean electronics giant Samsung has halted clinical development for the biosimilar version (SAIT101) of Roche’s Rituxan/MabThera (rituximab).

Pfizer carrying out biosimilar trastuzumab trial in US

Pharma giant Pfizer is carrying out a phase I trial in the US for a biosimilar version of trastuzumab.

Biosimilars applications under review by EMA

Last update:  11 January 2013 

EMA is the body responsible for approval of biosimilars within the EU. A legal framework for approving biosimilars was established in 2003.  Approval of biosimilars is based on an abbreviated registration process, which allows biosimilars manufacturers to provide a reduced package of information compared to originator drugs, provided they can prove ‘similarity’ to the originator or ‘reference drug’.

Medicago and Cellectis in successful biosimilars research collaboration

Canadian biopharmaceutical company Medicago and Cellectis plant sciences, a subsidiary of Cellectis SA, French genome engineering specialist, announced on 4 October 2012 the successful completion of the first step in their research collaboration to improve therapeutic proteins produced in tobacco plants.

Overview of research on biosimilarity/comparability and interchangeability of biosimilars 2012

Period: January to August 2012 

After the patent on a biological medicine expires ‘similar’ versions of the originator biological can be produced. These biosimilars or ‘similar biological medicinal products’ are similar (but not identical) in terms of quality, safety and efficacy to an authorised reference biological medicine.

Teva halts phase III biosimilar rituximab trial

Israeli generics giant Teva Pharmaceutical Industries (Teva) has suspended its phase III trial of its biosimilar version (TL011) of Roche’s Rituxan/MabThera (rituximab).

Boehringer Ingelheim completes biosimilar adalimumab trial

Biopharmaceutical specialist Boehringer Ingelheim Pharmaceuticals (Boehringer Ingelheim) has completed its phase I trial for a biosimilar version of adalimumab.

EMA publishes revised biosimilar Q&A document for patients

On 27 September 2012 EMA published its revised Questions and Answers (Q&A) document on biosimilar medicines aimed at patients and the general public.

Overview of research on safety and immunogenicity of biosimilars in 2012

Period: January to August 2012 

Biosimilars or ‘biosimilar medicinal products’ are medicinal products that are similar (but not identical) in terms of quality, safety and efficacy to an authorised biological reference medicine. Manufacturing of biologicals is complex, and the quality of the resulting biological is dependent on careful control of manufacturing processes and conditions. Unlike traditional small molecule (chemical) drugs, the development of biologicals is different and variable with respect to the manufacturing process and environmental factors, such as light and temperature. The complexity and heterogeneity of the molecular structure, complicated manufacturing processes, different analytical methods and possibility of immunogenicity reactions make quantitative evaluation of biosimilars a challenge to both the scientific community and regulatory agencies.

EMA receives second application for biosimilar infliximab

According to EMA’s list of applications for new human medicines under evaluation by the Committee for Medicinal Products for Human Use released in September 2012, the agency will be reviewing a second application for a biosimilar version of infliximab.

Bioton and Medipolis sign insulin analogue technology licensing agreement

Polish biotechnology company Bioton and Finnish-based contract research organisation (CRO) Medipolis GMP (Medipolis) have signed a licensing agreement on the manufacturing technology of an insulin analogue.

Naming and interchangeability of biosimilars raised in new survey

The contentious issues of naming and interchangeability of biosimilars in the US have been raised once again, as a result of a survey carried out by the Alliance for Safe Biologic Medicines (ASBM). The survey, released on 13 September 2012, examined physician practices and perspectives with regard to identification and substitution of biosimilars. These remain issues that are as yet unresolved by FDA.

Roche does not see a threat from biosimilars until 2015

Switzerland-based drugmaker F. Hoffmann-La Roche (Roche) expects results from 19 late-stage clinical trials over the next 18 months to provide a stream of products to offset potential near-term threats to its cancer drugs Herceptin (trastuzumab) and Rituxan (rituximab).

Boehringer Ingelheim starts biosimilar rituximab trial

Germany-based Boehringer Ingelheim Pharmaceuticals (Boehringer Ingelheim) is starting a Phase III trial for a biosimilar version of rituximab.

Sun recalls biosimilar brain treatment

India-based Sun Pharmaceutical Industries (Sun Pharma) is once again in the news, but for the wrong reasons.

Biosimilar comparability debate continues

Authors Schellekens and Moors comment on the response from EMA’s Biosimilar Medicinal Products Working Party to questions that they raised regarding EMA’s comprehensive biosimilar regulatory pathway [1]. While the authors express their appreciation of the openness of EMA in the way it has pioneered the biosimilars pathway in Europe, they still argue that EMA has failed to show the scientific need for biosimilar comparability [2].

Teva receives FDA approval for filgrastim in the US

Teva Pharmaceutical Industries (Teva) announced on 30 August 2012 that FDA had granted approval for tbo-filgrastim (XM02 filgrastim), the first new granulocyte colony-stimulating factor (G-CSF) to be approved in the US in more than 10 years.

Dr Reddy’s plans EU launch for biosimilar rituximab

India-based generics drugmaker Dr Reddy’s Laboratories (Dr Reddy’s) is planning to launch its biosimilar monoclonal antibody Reditux (rituximab) in Europe.

EMA responds to questions over biosimilar comparability

EMA has responded to questions regarding its comprehensive biosimilar regulatory pathway. The pathway, which includes the need for new clinical trials and comparability studies that demonstrate quality, efficacy, and safety, has been accused of proving to be a barrier for the development of clinically superior compounds [1].

‘Similar biologics’ approved and marketed in India

Last update: 15 February 2018

There have been established guidelines for approving generic versions of small molecule chemical drugs in India for some time already. However, no specific guidelines for ‘similar biologics’, as the Indian regulatory authorities call these products, existed in India until 2012. This has been the case despite the fact that the requirements for granting regulatory approval for such ‘similar biologics’ required more data than for a simple generic drug application [1].