spacer
home > ebr > spring 2007 > without a trace
PUBLICATIONS
European Biopharmaceutical Review

Without a Trace

Tanja Beilke, Oliver Halbig and Andreas Richter at NewLab BioQuality AG examine the development and validation of generic host cell protein assays

Host cell proteins (HCP) are potential impurities which might be co-purified with the drug substance and could be a potential cause of adverse immune responses or allergic reactions (1). To date there is only limited clinical evidence that shows an allergic reaction was clearly attributable to residual host cell protein. However, there is growing concern about the potential induction of anti-drug antibodies (2,3,4).

The risk of contaminants and impurities in biopharmaceuticals is anticipated by a set of measurements, including the rigorous control of the material entering a production process. According to the European Agency for the Evaluation of Medicinal Products (EMEA) the concept of controlling impurities can either be a ‘routine approach’ or a ‘validation approach’ (5). A routine approach would be to develop analytical tools that allow monitoring the level of those impurities as closely as possible at various steps of the process and setting fixed limits to be met, so that the impurities of the final product are well monitored in the final product.

A validation approach means to validate the production process to establish that, at given steps of the purification scheme, those impurities are removed in a consistent and reproducible manner. Based on the reduction factors, it may be possible to predict and guarantee the residual level of impurity in the final product. The EMEA suggests that HCPs should be analysed either on a routine or validation basis depending on the individual product and process. In either case, powerful analytical methods are needed to accurately determine the concentration of the impurities in the different process steps.

DEVELOPMENT OF A RESIDUAL HCP ASSAY

An HCP assay is usually an immunological-based assay using an antiserum produced against proteins obtained from a mock fermentation process (6,7,8). The development of such an assay is usually time consuming due to the necessary immunisation of animals.

The first step is the generation and isolation of the appropriate antigen to be used for immunisation. This requires the fermentation of the native cell line without the gene sequence of the target protein. This is commonly referred to as a mock fermentation run. As illustrated in Figure 1, it is important to choose the correct step in the purification scheme for the production of the antigen. By using the protein following the first purification step, a very wide spectrum of HCPs would be detectable, but this is not representative of the potential HCP in the final product. By using a protein derived from the final purification step as the antigen, the HCP may be more representative of the final product but may also be too specific and not demonstrate sufficient HCP removal.


Read full article from PDF >>

Rate this article You must be a member of the site to make a vote.  
Average rating:
0
     

There are no comments in regards to this article.

spacer

Tanja Beilke is currently Scientific Officer at NewLab BioQuality AG, and heads the Protein Chemistry Department. She also has approximately 10 years’ experience in protein analysis. Tanja Beilke studied Biotechnology at the University of Applied Sciences, Jülich. After finishing her diploma she gained experience in protein chemistry at Roche in Penzberg.

Oliver Halbig belongs to the technical staff of the Protein Chemistry Department. He has been working for NewLab for 13 years, and is an expert in all kinds of immunological assays used for protein analysis.

Dr Andreas Richter is Director of Operations at the Erkrath site of NewLab BioQuality. He is responsible for protein chemistry, molecular biology and research and development at NewLab. He received his PhD in Biology from the Heinrich-Heine University in Düsseldorf.

spacer
Tanja Beilke
spacer
spacer
spacer
Oliver Halbig
spacer
spacer
spacer
Dr Andreas Richter
spacer
spacer
Print this page
Send to a friend
Privacy statement
News and Press Releases

CPhI China opens with analysis pointing to a surge in growth in 2019

Shanghai, 23rd May 2019: New analysis released ahead of CPhI & P-MEC China (#CPhIChina and #PMECChina) – co-organized by Informa Markets, CCCMHPIE, and Shanghai Sinoexpo Informa Markets – forecasts that China will continue to grow strongly through 2019/20, thanks in part to a marked improvement in its global reputation.
More info >>

White Papers

The Process of Informed Consent (written by ACRP)

CenterWatch

Every investigator and clinical research coordinator (CRC) should recognize the importance of obtaining valid and appropriate informed consent as an important protection of the rights and welfare of human subjects. The purpose of this ACRP guidance document is not to provide a literature review or summarize the recommendations of various working groups. Instead, the Association decided it would be helpful to provide short and focused guidance which describes how to best structure the informed consent process in accordance with best practices.
More info >>

 
Industry Events

ELRIG Drug Discovery 2019 – Looking Back to the Future

5-6 November 2019, ACC, Liverpool

Now in its 13th year, ELRIG’s flagship conference Drug Discovery 2019 will take place at ACC in Liverpool. This year’s focus, ‘A Look Back to the Future’ is planned to include plenary introductions assessing how we got to where we are now and setting the challenges for discovering the drugs of the future. These will be followed by cutting edge talks and examples of new directions in drug discovery. Our scientific programme will feature over 40 world-class speakers with 6 main session tracks. In partnership with key academic and charitable groups, we will also run joint disease and biology-oriented tracks focusing on the basic sciences that underpin successful drug discovery.
More info >>

 

 

©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement