Biopharmaceuticals, safety assessment

Types of Biopharmaceuticals Survey data on preclinical safety assessment programs were analyzed for 34 biopharmaceuticals cases. The numbers of antibodies, human proteins, and human protein analogues either in the development or marketed as of 2001 in Japan were 13,12, and 6, respectively. The remainder were bioconjugates, DNA-derived vaccines, and human T cell epitopes. Thus antibodies and human proteins are the two major biopharmaceuticals. 

Scientists from NIHS, PMDA, and JPMA collaborated to publish a Points-to-Consider document regarding the safety assessment of biopharmaceuticals in preclinical studies in 2002 [3], The collaboration team intended to clarify their interpretation of the ICH S6 guideline and share recent Japanese practices on this matter. However, it was written in Japanese. Thus the collaboration team made an English translation of the document and also collected comments on the contents from experts in the United States and the European. The experts agreed to most ideas presented in the Japanese Points-to-Consider document. They also suggested more clarification of some other ideas. In light of these comments, the collaboration team revised and published the English translation of the document, such that the nonnative Japanese could correctly understand the contents [4], In this section, I summarize the key points of the document, as they may be of some help to scientists in the pharmaceutical... 

The safety assessment of biopharmaceuticals in preclinical studies has been improved in Japan with the implementation of the ICH S6. The analysis of data from a questionnaire survey conducted by JPMA suggests that the ICH S6 was well understood and adequately implemented in Japan. The Japanese... 

Figure 9.1 Proposed rank ordering of methods informing species selection for safety assessment of biopharmaceuticals. Various methods used for selecting pharmacologically relevant species for toxicological studies of biopharmaceuticals are presented, ordered (top to bottom) by the extent to which the data might impact the decision on which species to use. In cases where the methods are further discussed in this chapter, the relevant figure/table numbers are provided. These types of analyses may also be used for creating data packages for small molecules, although not typically for species selection.

Biopharmaceuticals represent a broad but discrete class of large molecular weight therapeutic entities that are characterized by their specific pharmacological activities and distinctive pharmacokinetics. The selection of an appropriate animal model is dependent on a combination of PD and PK factors. As described in this chapter, it is essential to understand the relationship of the basic pharmacology of a biopharmaceutical (signaling, receptor presence, binding properties, etc.) and the associated PK properties to that expected in humans, in order to select animal species that will have the most predictive value in safety assessments. 

Green J, Black, L. Overview of preclinical safety assessment for immunomodulatory biopharmaceuticals. Hum Exp Toxicol 200 19(4) 208-12. 

Toxicity testing of biopharmaceuticals is highly dependent on species specificity. Every program could be different in the type of studies that are needed to support safety assessment (i.e., case-by-case approach). If the biopharmaceuti-cal cross-reacts with the rodent target, then general toxicity tests can be conducted in two species similar to what is done with pharmaceuticals. If the... 

The impact of the drug attributes of biopharmaceuticals on preclinical safety assessment programs for oncology products is not unique to this therapeutic area. As is true for all biopharmaceuticals, species cross-reactivity must be determined prior to selection of an appropriate animal model for safety evaluation. The nature of cross-reactivity can be based on a combination of phar-... 

Additional safety studies may be required to support the movement into new indications, and the complex designer biopharmaceuticals will continue to require creative approaches to safety assessment. In either case, the requirement for, and design and execution of, those studies should be driven by sound scientific rationale. Ultimately, the objective of preclinical safety evaluation is well articulated in ICH S6 ... 

Practical Considerations in the Design of Preclinical Safety Assessments for Biopharmaceuticals... 

The publication of the results of clinical trials and preclinical research has resulted in the general understanding that biopharmaceuticals can be toxic as well as beneficial in humans and animals and that many aspects of their toxicity can be studied with relevance in animals. Toxicology as a science has benefited from this experience in many ways by improved and widely applicable understanding of basic biological mechanisms of health and disease and the introduction of novel methods to detect and assess effects. Case-by-case assessment based on science encourages scientific advancement in toxicology and infuses excitement and quality research into safety assessment. 

Chuang-Stein C, Xia A. The practice of pre-marketing safety assessment in drug development. Journal of Biopharmaceutical Statistics, 23(l) 3-25,2013. 

SAFETY ASSESSMENT STRATEGIES AND PREDICTIVE SAFETY OF BIOPHARMACEUTICALS AND ANTIBODY DRUG CONJUGATES... 

Target Safety Assessment for Biopharmaceuticals Targeting the Immune System... 

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