ICH S6 guidelines

Since the adoption of the ICH S6 guideline, and with the growing number of biopharmaceuticals entering development, the EMEA have developed a number of specific guidelines in relation to the preclincial testing of biopharmaceuticals. The current draft and approved EU-specific preclinical guidance documents that apply to biopharmaceuticals are listed in Table 4.5. In addition... 

The major difference between application of the ICH S6 guideline in the European Union, compared to the United States and Japan, is the rather more complex interaction with the regulatory agencies in relation to agreeing on the preclinical testing strategy for biopharmaceuticals. While sponsor compa-... 

In vitro Studies Table 5.3 shows the in vitro preclinical studies conducted for the 34 biopharmaceuticals. Most were in vitro genotoxicity studies that are not required by the ICH S6 guideline. This is not the case of poor understanding of the ICH S6. In vitro genotoxicity studies are usually conducted at the early stage of development. Almost all the in vitro genotoxicity studies examined by the JPMA survey in 2001 were conducted before the ICH S6 notification. The cross-reactivity studies were used to understand interspecies reactivity to a biopharmaceutical, especially in case of antibodies. 

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... 

TABLE 5.4 Type of biopharmaceuticals/related biological medicines and scope of the ICH S6 guideline... 

Other Biological Medicines The conventional biologies shown in the bottom section of Table 5.4 are not covered by the ICH S6 guideline. Pre-clinical safety evaluation based on relevant standards is necessary for this group of pharmaceuticals. (Refer to the Points-to-Consider paper [4] for references.)... 

Points-to-Consider document helps industry scientists and regulatory reviewers understand the ICH S6 guideline. In particular, it is helpful for the clarification of case-by-case approaches to preclinical programs depending on the biopharmaceutical type. However, further updates of the Japanese Points-to-Consider document may be needed as newer types of biopharmaceuticals, technologies, and assays have developed. 

To examine the requirements to take an immunotoxin into the clinic, the preclinical developmental strategy of VB4-845 is described to examine the challenges encountered to progress this antibody from bench to clinic by following the ICH S6 guidelines. 

The FDA has applied many of the principles in the draft ICH S6 guideline. The implementation of the final ICH guideline will require training of regulatory, academic and industry scientists. As with all ICH guidance, once implemented it will be important not only to assess compliance but to update when needed. 

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