1. Assay development for immunogenicity testing of therapeutic proteins (FDA)
2. Guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins (EMEA)
3. FDA current thinking on formulating a risk-based approach, 3 publications
4. Two publications addressing regulatory considerations and/or direct quotes from regulatory documents
5. The application of quality by design (QbD) to biopharmaceuticals, 2 publications
6. The importance of immunogenicity in assessing biosimilars
7. The ‘Safe-Harbor’ Concept
8. Identifying CDERs Science and Research Needs Report (PDF)
A draft guidance for industry. The presentation clarifies that this is a draft document and not finalized. Nonetheless this draft is disseminated by the FDA to the general public and available from the Office of Communication, CDER and online.
Published by the EMEA.
Material from a series of three articles by Rosenberg & Worobec (of the FDA).
(i) Rosenberg, A.S. & Worobec, A. A risk-based approach to immunogenicity concerns of therapeutic protein products, Part 1: Considering consequences of the immune response to a protein.
Biopharm. Int. 17, 22–26 (2004)
(ii) Rosenberg, A.S. & Worobec, A. A risk-based approach to immunogenicity concerns of therapeutic protein products, Part 2: Considering host-specific and product-specific factors impacting immunogenicity.
Biopharm. Int. 17, 34–42 (2004)
(iii) Rosenberg, A.S. & Worobec, A. A risk-based approach to immunogenicity concerns of therapeutic protein products, Part 3: Eeffects of manufacturing changes in immunogenicity and the utility of animal immunogenicity studies.
Biopharm. Int. 18, 32–36 (2005)
(i) Shankar, G., Shores, E., Wagner, C. & Mire-Sluis, A.R. Scientific and regulatory considerations on the immunogenicity of biologics.
Trends Biotechnol. 24, 274–280 (2006)
(ii) Shankar G, Pendley, G & Stein, K.E. A risk-based bioanalytical strategy for the assessment of antibody immune responses against biological drugs.
Nature Biotech. 25, 555-561 (2007)
(i) Rathore, A.S. & Winkle, H. Quality by design for biopharmaceuticals
Nature Biotech. 27, 26-34 (2009)
(ii) Rathore, A.S. Roadmap for implementation of quality by design (QbD) for biotechnology products
Trends Biotechnol. 27, 546-553 (2009)
A very recent perspective in the New England Journal of Medicine. The authors, Kozlowski, Woodcock, Midthun and Behrman Sherman are all employees of the FDA.
Kozlowski, S, Woodcock, J, Midthun, K & Behrman-Sherman, R. Developing the Nation’s Biosimilars Program
N. Engl. J. Med. 365, 385-388 (2011)
The concept of a ‘safe harbor’ comes from a program initiated by the FDA in 2004. The aim of this program was to enhance understanding of the regulatory significance of genomic biomarker data by regulators and sponsors. Thus the US Food and Drug Administration permitted sponsors to submit exploratory genomic data voluntarily, without immediate regulatory impact. This program was called, voluntary genomic data submissions (VGDS). Of interest to individuals interested in using cutting edge (but not routine) techniques in immunogenicity is that VGDS meetings have expanded in scope to include non-genomic biomarkers, and so the submissions have been renamed voluntary exploratory data submissions (VXDS) and are no longer restricted to genomic markers. The scope of such meetings, relevant regulatory guidance, the kinds of data submitted and the FDA experience are discussed in the following article.
Goodsaid, F.M. et al. Voluntary exploratory data submissions to the US FDA and the EMA: experience and impact
Nature Rev. Drug Discov. 9, 435-445 (2010).
With thanks to Zuben Sauna and Bonita Rup for providing the content for this page.
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