International Conference on Harmonization ICH guidances

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. 

Adding to this problem is the lack of unambiguous, scientifically valid guidelines from the International Conference on Harmonization (ICH) guidance (1). This leads to having to choose between what the user thinks the regulators want and the scientific approach. 

Excipient impurity profiles and how to evaluate this important aspect of excipient manufacture, particularly in light of the International Conference on Harmonization (ICH) guidance published in 1999, also are addressed. Care must also be taken that residual solvent levels do not exceed those prescribed in the ICH Guidance for Residual Solvents published in 1999. Solvents are divided into three classes ... 

International Conference on Harmonization (ICH). Guidance for Industry. S5A Detection of Toxicity to Reproduction for Medicinal Products. 1994. 

The Electronic Common Technical Document (eCTD) is the vision for future electronic submissions to the FDA. This specification was developed by the International Conference on Harmonization (ICH) as an open-standards solution for electronic submissions to worldwide regulatory authorities. The FDA has adopted the eCTD as the future replacement for its other e-submission guidance, although for now the older guidance is still in effect. Note that the eCTD still depends largely on submitting text documents as PDF files and submitting data sets as SAS XPORT transport format files. 

Guidance can be found regarding the validation of chemical methods applicable to mierobial testing. Examples inelude the USP Chapter (1225) Validation of Compendial Methods, and a recent publieation by the International Conference on Harmonization (ICH) Validation of Analytical Methods. These publications provide specific instruction regarding the demonstration of new ehemical analytical methods and then-equivalence to existing methods. 

International Conference on Harmonization (1996), Guidance for Industry Validation of Analytical Procedures Methodology, ICH-Q2B, available http //www.fda.gov/cder/ guidance/index.htm. 

In recent years, the International Conference on Harmonization (ICH) has published two documents that serve as expert guidance on analytical and related validation [53,54], As part of the outsourcing process, the client and provider should review these and related regulatory guidances (e.g cleaning validation) to ensure that there is a mutual understanding and agreement on the scientific basis of methods validation. 

Method validation has received considerable attention in the literature and from industrial committees and regulatory agencies. The international standard ISO/ IEC [1] requires validation of nonstandard methods, laboratory designed/devel-oped methods, standard methods used outside their intended scope, and amplifications and modifications of standard methods to confirm that the methods are suitable for their intended use. The Guidance on the Interpretation of the EN 45000 Series of Standards and ISO/IEC Guide 25 includes a chapter on the validation of methods [2] with a list of nine validation parameters. The International Conference on Harmonization (ICH) of Technical Requirements for the... 

ICH S6. International Conference on Harmonization ICH S6. Preclinical Safety Evaluation of Biotechnology-derived Pharmaceuticals, 1997. http //www.fda.gov/ cder/guidance/index.htm... 

The FDA refers to a few official documents for guidance in accomplishing a valid preclinical development program. These include International Conference on Harmonization (ICH) accepted guidances as well as US FDA guidance documents ... 

The International Conference on Harmonization (ICH), representing FDA, EU, and Japanese regulatory authorities, produced guidance in 2000 on the manufacmre of active pharmaceutical ingredients (APIs) that included computer validation expectations. Not too surprisingly, essential principles were unchanged compared to computer vahdation for fiitished dmg products. The key topics covered were ... 

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