Authorized manufacturing changes for therapeutic monoclonal antibodies (mAbs) in European Public Assessment Report (EPAR) documents

Figures & data

Figure 1. Manufacturing changes for biotechnology products were categorized as low/moderate/high risk¹. Adapted from Lee et al. Comparability and biosimilarity: considerations for the healthcare provider. CMRO 2012;28:1053-8.

Figure 2. Number of manufacturing changes for monoclonal antibodies in their European Public Assessment Reports according to risk category (during the search period all non-proprietary names relate only to the trade named medicines listed in Table 1).

Figure 3. Average number of manufacturing changes per product year elapsed since registration (during the search period all non-proprietary names relate only to the trade named medicines listed in Table 1).

Table 1. Monoclonal antibody medicines and their EPAR* ‘Procedural steps…’ documents from EMA** webpage during the search period¹⁰.

	International non-proprietary name	Trade name***	First EU (US) approval year	Regulatory status in EU	EPAR documents in analysis^****	Last update of ‘Procedural steps taken and scientific information after the authorisation’ document was evaluated
1	Muromonab-CD3	Orthoclone Okt3	1986 (1986)	Voluntarily withdrawn	N.A.
2	Abciximab	Reopro	1995 (1994)	Voluntarily withdrawn	N.A.
3	Rituximab	MabThera, Rituxan	1998 (1997)	Approved	Included	09/07/2014
4	Basiliximab	Simulect	1998 (1998)	Approved	Included	02/10/2014
5	Daclizumab	Zenapax	1999 (1997)	Voluntarily withdrawn	Included	08/04/2008
6	Palivizumab	Synagis	1999 (1998)	Approved	Included	15/09/2014
7	Infliximab	Remicade	1999 (1998)	Approved	Included	25/09/2014
8	Trastuzumab	Herceptin	2000 (1998)	Approved	Included	01/09/2014
9	Gemtuzumab ozogamicin	Mylotarg	NA (2000)	Voluntarily withdrawn	N.A.
10	Alemtuzumab	MabCampath, Campath-1H	2001 (2001)	Not authorised	Included	15/08/2012
11	Adalimumab	Humira	2003 (2002)	Approved	Included	14/10/2014
12	Tositumomab-I131	Bexxar	NA (2003)	Not authorized	N.A.
13	Efalizumab	Raptiva	2004 (2003)	Voluntarily withdrawn	Included	04/08/2009
14	Cetuximab	Erbitux	2004 (2004)	Approved	Included	14/08/2014
15	Ibritumomab tiuxetan	Zevalin	2004 (2002)	Approved	Included	17/06/2014
16	Omalizumab	Xolair	2005 (2003)	Approved	Included	03/10/2014
17	Bevacizumab	Avastin	2005 (2004)	Approved	Included	15/08/2014
18	Natalizumab	Tysabri	2006 (2004)	Approved, indication extension withdrawn	Included	11/08/2014
19	Ranibizumab	Lucentis	2007 (2006)	Approved	Included	24/04/2014
20	Panitumumab	Vectibix	2007 (2006)	Approved	Included	02/07/2014
21	Eculizumab	Soliris	2007 (2007)	Approved	Included	11/04/2014
22	Certolizumab pegol	Cimzia	2009 (2008)	Approved	Included	28/07/2014
23	Golimumab	Simponi	2009 (2009)	Approved	Included	18/08/2014
24	Canakinumab	Ilaris	2009 (2009)	Approved	Included	01/10/2014
25	Catumaxomab	Removab	2009 (N.A.)	Approved	Included	23/04/2014
26	Ustekinumab	Stelara	2009 (2009)	Approved	Included	23/05/2014
27	Tocilizumab	RoActemra, Actemra	2009 (2010)	Approved	Included	29/09/2014
28	Ofatumumab	Arzerra	2010 (2009)	Approved	Included	05/08/2014
29	Denosumab	Prolia	2010 (2010)	Approved	Included	29/08/2014
30	Belimumab	Benlysta	2011 (2011)	Approved	Included	12/08/2014
31	Ipilimumab	Yervoy	2011 (2011)	Approved	Included	11/03/2014
32	Brentuximab vedotin	Adcetris	2012 (2011)	Approved	Included	29/08/2014
33	Pertuzumab	Perjeta	2013 (2012)	Approved	Included	30/07/2014
34	Raxibacumab	(Pending)	N.A. (2012)	Granted orphan design	N.A.
35	Trastuzumab emtansine	Kadcyla	2013 (2013)	Approved	N.A.
36	Vedolizumab	Entyvio	2014 (2014)	Approved	N.A.

*European Public Assessment Report.

**European Medicines Agency.

***All medicine names are registered trademarks of their owner companies.

****Included or (N.A.) not available for analysis during the search period of 1 June 2014–15 October 2014.

Lee JF, Litten JB, Grampp G. Comparability and biosimilarity: considerations for the healthcare provider. Curr Med Res Opin 2012;28:1053–8

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European Medicines Agency. European public assessment reports. Available at: www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/epar_search.jsp&mid=WC0b01ac058001d125 [Last accessed July 2015]

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