ICH guidance

ICH Guidance for Industry Q1B, Photostability testing of new drug substances and products, November 1996. 

ICH Guidance for Industry Topic Q 1 A Stability testing of New Drug Substances and Products, 2003. 

Single-dose studies are performed in two species, usually rat and mouse, by two routes of administration, usually intravenous, to ensure systemic exposure, and the proposed clinical route. Following the ICH guidance in November 1991, non-rodent, single-dose tests are no longer required. If the proposed clinical route is intravenous, then one route is usually acceptable. 

According to the ICH guidance, the objective of method validation is to demonstrate that analytical procedures are suitable for their intended purpose. Therefore the method s purpose should be linked to the clinical studies and the pharmaceutical purpose of the product being studied. 

Several documents describe the requirements for viral clearance studies. The ICH guidance on viral safety evaluation provides information on the design of viral clearance studies and their interpretation [37], Unlike most other aspects of process validation, viral clearance cannot be performed at full scale. There are several reasons for this. Direct testing methods may not detect low concentrations of virus, which requires that viruses be spiked into the feedstream. Assays may detect only known viruses, and they may also fail to detect variants. Worker safety is another issue that necessitates the need to perform the validation at a small scale. Scaling down is addressed in the ICH guidelines and in the literature [38,39]. 

GMP guide for APIs issued by the World Health Organization (WHO) in July 2001 (also reflects ICH guidance documentation). 

The ICH guidance document covers the following essential topics ... 

According to the ICH guidance document, introducing an intermediate (key or final) or API that does not conform to standards or specifications back into the process by repeating a crystallization step or other physical manipulation (i.e., distillation, filtration, chromatography, milling, and drying) that is part of the... 

International Conference on Harmonisation (ICH). GMP Guide for APIs (Nov. 2000). International Conference on Harmonisation (ICH). Guidance for Industry Photo stability Testing of Drug Substances (Nov. 1996). 

Bakshi M, Singh B, Singh A, Singh S. The ICH guidance in practice stress degradation studies on ornidazole and development of a validated stability-indicating assay. J Pharm Biomed Anal 2001 26 891-897. 

To date, no studies on the metabolism of cetuximab have been performed in humans or in animals. Indeed, metabolism studies are not generally performed for mAbs. Several pathways have been described that may contribute to antibody metabolism, all of which involve biodegradation of the antibody to smaller molecules (i. e., small peptides or amino acids). This fact has been recognized in the International Conference on Harmonization (ICH) guidance document Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals [22], where it is stated in Section 4.2.3 that "... the expected consequence of metabolism of biotechnology-derived pharmaceuticals is the degradation to small peptides and individual amino acids. .. and that therefore classical biotransformation studies as performed for traditional small molecule pharmaceuticals are not needed. 

ICH Guidance for Industry—QIC Stability Testing of New Dosage Forms, November 1996... 

ICH Guidances. Steps 2 and 4 guidances grouped into four sections (1) quality, (2) safety, (3) efficacy, and (4) multidisciplinary... 

ICH Guidance for Industry Q3B(R2) Impurities in New Drug Products, July 2006. 

In addition to the unique regulatory structure in the European Union and the specific guidelines referred to above, there are a few other comments and issues relating to the interpretation and application of the ICH guidance. 

Several years ago an ICH guidance (ICH S6 Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals) was written to address the preclinical development and safety issues of products derived from biotechnology. ICH S6 defined biotechnology-derived pharmaceuticals as products derived... 

In the early days of biotechnology product development, the focus was on quality issues [4] or process-related impurities.The concerns at that time were for carryover of other cellular proteins and DNA and for contamination with endotoxins, chemicals, and viruses. Of course, these concerns still exist, but methods for purification and assays for evaluation of clearance have alleviated the need for the safety assessment scientist to focus on contaminants instead they are now asked to focus on the pharmacological activity of the molecules. An ICH guidance (Q6B Specifications Test Procedures and Acceptance Criteria for Biotechnological/Biological Products) addresses the specific issues related to the manufacturing process [6], Other product-related issues such as impurities do need to be considered by the safety assessment scientist, for... 

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