Biosimilars

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.