Non-clinical Safety Evaluation of Biotherapeutics - Challenges, Opportunities and new Insights

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• 作者：Guenter Blaich^a ; ^{guenter.blaich@abbvie.com" class="auth_mail" title="E-mail the corresponding author} ; Andreas Baumann^b ; Sven Kronenberg^c ; Lolke de Haan^d ; Peter Ulrich^e ; Wolfgang F. Richter^c ; Jay Tibbitts^f ; Simon Chivers^g ; Edit Tarcsa^h ; Robert Caldwellⁱ ; Flavio Crameri^c
• 关键词：Biotherapeutics ; PEGylated biologics ; Gene and cell therapy ; Pharmacokinetics ; Nonclinical safety ; Antibody-drug conjugate ; Immunogenicity ; Cross-reactive species
• 刊名：Regulatory Toxicology and Pharmacology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：80
• 期：supp_S
• 页码：S1-S14
• 全文大小：935 K

文摘

New challenges and opportunities in nonclinical safety testing of biotherapeutics were presented and discussed at the 5th European BioSafe Annual General Membership meeting in November 2015 in Ludwigshafen. This article summarizes the presentations and discussions from both the main and the breakout sessions.

The following topics were covered in six main sessions:

(i)

Challenges around use of PEGylated biologics, results of BioSafe survey

(ii)

Unexpected side effects of biotherapeutics

(iii)

Safety testing of cell and gene therapies including vector safety and integration site analysis and setting up a GLP facility in this field

(iv)

Immunogenicity and PKPD including immunogenicity prediction or methodologies to prevent induction of anti-drug antibodies

(v)

Current approaches applied to antibody drug conjugate (ADC) development

(vi)

Approaches for non-clinical safety testing of human-selective biologics, including use of transgenic animals and MABEL

The following questions were discussed across 4 breakout sessions (i-iv) and a case-study based general discussion (v):

(i)

Do bi-specifics offer nonclinical and clinical development advantages over combinations ?

(ii)

Is the paradigm “SC is more immunogenic than IV” correct ” ?

(iii)

Why do we need a 6-month toxicology study for a monoclonal antibody (mAb) when we already have a 13-week toxicology study ?

(iv)

How do we investigate immune complex formation pre-clinically and does it translate clinically ?

(v)

Adversity in nonclinical safety studies: STP and ESTP opinion, your opinion needed ?