Biosimilars

Glycosylation technologies for biosimilars and ‘biobetters’

According to Mr Hans Baumeister and Mr Steffen Goletz of Glycotope, human cell lines providing a human glycosylation pattern – such as those of Crucell (PER.C6), Cevec (CAP) and Glycotope (GlycoExpress) – have attracted increasing amounts of attention over the past years. In the case of biosimilars, regulatory approval now requires an extensive programme of bioequivalence studies to be undertaken to characterise the product in terms of its biochemical properties, safety and activity. As a consequence, glycosylated biosimilars need to be equipped with a similar pattern of glycosylation. For example, the degree of sialylation should not deviate by more than 20% from that of the original product. Hence, the chosen cell clone with high productivity has to be able to provide post-translational modifications as closely related to the originator’s cell line as possible. However, since glycosylation differs within clones, during the bioequivalence study it is often realised that the product carries different carbohydrates, usually resulting in a hyposialylation; this requires the screening process to be repeated in order to identify a new cell clone that is able to provide the equivalent glycosylation. Several glycosylation analysis technologies are available for the development and production of glycosylated biotherapeutics, applicable to both biosimilars and second-generation ‘biobetters’ (see Table 1).

Biosimilar epoetin zeta gets positive EMA-CHMP opinion for SC route in renal patients in EU

Hospira announced on 22 February 2010 that the EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended for approval the administration of Retacrit (epoetin zeta) subcutaneously in the nephrology setting. This provides an alternative option to intravenous (IV) delivery of the drug for the symptomatic treatment of anaemia associated with chronic renal failure. Final approval by the European Commission is expected in the next few months, which will result in marketing authorisation for Retacrit subcutaneous (SC) administration in all EU Member States.

Rituximab gets US FDA approval for chronic lymphocytic leukaemia

The US FDA has approved Roche’s Genentech/Biogen Idec's anti-CD20 monoclonal antibody Rituxan/MabThera (rituximab) plus chemotherapy for people with either previously untreated or previously treated (relapsed or refractory) chronic lymphocytic leukaemia (CLL).

As pointed out by Scrip, MabThera was approved in the EU in 2009 for these same indications. However, US approval was held up by a complete response letter issued by the FDA in November 2009. The companies said then that the agency had not requested any new data to complete its review of these applications, but that they were continuing final labelling discussions.

How to tackle overcapacity in monoclonal antibody production

In the early days, most monoclonal antibody (MAb) therapies required high dosages, as pointed out by Ms Gail Dutton in a Genetic Engineering & Biotechnology News Feature Article on 15 February 2010 (see also Monoclonal antibodies modelling - predictive analytics, Improving monoclonal antibody production - antibody-drug conjugate technology and Modern monoclonal antibody production - focus on quality by design, timelines, cost)

Monoclonal antibodies modelling - predictive analytics

Improved analytics is helping to ensure that the active pharmaceutical ingredient (API) quality attributes of monoclonal antibodies (MAbs) are identified as early as possible, determining both the desirable and undesirable characteristics, as pointed out by Ms Gail Dutton in a Genetic Engineering & Biotechnology News Feature Article on 15 February 2010 (see also How to tackle overcapacity in monoclonal antibody production, Improving monoclonal antibody production - antibody-drug conjugate technology and Modern monoclonal antibody production - focus on quality by design, timelines, cost)

Improving monoclonal antibody production - antibody-drug conjugate technology

Researchers are developing new approaches to improve monoclonal antibody (MAb) production, as pointed out by Ms Gail Dutton in a Genetic Engineering & Biotechnology News Feature Article on 15 February 2010 (see also How to tackle overcapacity in monoclonal antibody production, Monoclonal antibodies modelling - predictive analytics and Modern monoclonal antibody production - focus on quality by design, timelines, cost)

Modern monoclonal antibody production - focus on quality by design, timelines, cost

In the decade since severe capacity constraints limited monoclonal antibody (MAb) production, the industry has adjusted, so that today, overcapacity is the issue, along with developing techniques to ensure product quality, reduce development timelines, and decrease costs, writes Ms Gail Dutton in a Genetic Engineering & Biotechnology News Feature Article on 15 February 2010. Many of these issues will be explored at IBC’s conference on ‘Antibody Development and Production’ in March 2010 as she points out.

Will the EU biosimilars pathway be applicable to monoclonal antibodies?

To what extent is the existing framework for biosimilars in Europe likely to be applicable to monoclonal antibodies (mAbs)? This question was verified in a paper by Dr Christian Schneider –member of the EMA’s Committee for Medicinal products for Human Use (CHMP), Chairman of EMA’s Biological Medicines Working Party (BMWP) and the Paul-Ehrlich-Institut in Langen, Germany– and Dr Ulrich Kalinke of the Paul-Ehrlich-Institut and Twincore Center for Experimental and Clinical Infection Research in Hannover, Germany, as published in Nature Biotechnology of September 2008.

A follow-on biologic drug is not a ‘biogeneric’: Lessons from Omnitrope and Valtropin

In an article by Dr Robert Roth and Dr Nicholas Fleischer of the Weinberg Group published in Journal of Generic Medicines of May 2009, it is stated that a follow-on biologic drug is not a ‘biogeneric’, based on lessons from Sandoz’s biosimilar human growth hormone Omnitrope (somatropin) and BioPartners’ Valtropin (somatropin).

PhRMA, Amgen correct NEJM article on biologics exclusivity

In a NEJM Letter to the Editor of 18 February 2010, Mr David Wheadon, Senior Vice President of the Scientific & Regulatory Affairs team of the Pharmaceutical Research and Manufacturers of America 
(PhRMA) –having been employed by several pharmaceutical companies (Eli Lilly, GlaxoSmithKline, Abbott) and holding stock in Abbott Laboratories and GlaxoSmithKline– corrects the NEJM Perspective article by Mr Engelberg et al. of 12 November 2009, writing that “the record should be set straight” with regard to the market exclusivity of biologicals in the biosimilars debate.