Recently, the US FDA pubished two Guidances for Industry "S6 Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals" and "S6 Addendum to Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals".
Scopes of these guidances are:
1. S6 Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals
This guidance is intended primarily to recommend a basic framework for the preclinical safety evaluation of biotechnology-derived pharmaceuticals. It applies to products derived from characterized cells through the use of a variety of expression systems including bacteria, yeast, insect, plant, and mammalian cells. The intended indications may include in vivo diagnostic, therapeutic, or prophylactic uses.
The active substances include proteins and peptides, their derivatives, and products of which they are components; they could be derived from cell cultures or produced using recombinant deoxyribonucleic acid (DNA) technology, including production by transgenic plants and animals. Examples include but are not limited to: Cytokines, plasminogen activators, recombinant plasma factors, growth factors, fusion proteins, enzymes, receptors, hormones, and monoclonal antibodies. The principles outlined in this guidance may also be applicable to recombinant DNA protein vaccines, chemically synthesized peptides, plasma derived products, endogenous proteins extracted from human tissue, and oligonucleotide drugs.
This document does not cover antibiotics, allergenic extracts, heparin, vitamins, cellular blood components, conventional bacterial or viral vaccines, DNA vaccines, or cellular and gene therapies.
2. Addendum to Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals
The purpose of the addendum is to complement, provide clarification on, and update the following topics discussed in ICH S6: species selection, study design, immunogenicity, reproductive and developmental toxicity, and assessment of carcinogenic potential. Scientific advances and experience gained since publication of ICH S6 call for this addendum. This harmonized addendum will help to define the current recommendations and reduce the likelihood that substantial differences will exist among regions.
This guidance should facilitate the timely conduct of clinical trials, reduce the use of animals in accordance with the 3Rs (reduce/refine/replace) principles and reduce the use of other drug development resources. Although not discussed in this guidance, consideration should be given to the use of appropriate in vitro alternative methods for safety evaluation. These methods, if accepted by all ICH regulatory authorities, can be used to replace current standard methods.
Axel H. Schroeder
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)