International Conference on Harmonization,

The US, EU and Japan have implemented this GMP Guide, and the details are presented in Exhibit 9.3. The Q7A GMP Guidance sets out the requirements for GMP manufacturing. Details are summarized in Exhibit 9.4. Most of the requirements of ICH Q7A are derived from the 21 CFR and EU GMP Directive. The important additional sections in ICH Q7A are 

Internal Audits (Self Inspection), Contract Manufacturers and Agents, Brokers, Traders, Distributors, Repackers and Relabelers. The section on APIs for Use in Clinical Trials clarifies the regulatory authorities expectations for drugs designated for clinical trials, as opposed to approved drugs manufactured on a routine production basis. 

Adopted by CPMP, November 2000, issued as CPMP/ICH/1935/00 http //dg3.eudra.org/ 

CDER http //www.fda.gov/cder/auidance/index.htm CBER http //www.fda.gov/ cber/auidelines.htm 

Responsibilities for Production Activities Internal Audits (Self Inspection) 

There are four major categories of guidelines quality, safety, efficacy, and multidisciplinary. Details are provided in Exhibit 7.6. 

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The method was validated in accordance to the guidelines of the international conference on harmonization (ICH). Data with respect to accuracy, within- and between run precision, recovery, detection and quantitation limits were reported and found to be within the accepted international criteria. Neither endogeneous substances nor the commonly used dmgs were found to interfere with the retention times of the analytes. Standard solutions of the dmg and quality control preparations at high and low level concentrations were demonstrated to be stable at room temperature and/or -20°C for long and short periods of time. 

International Conference on Harmonization (Step 5, 1996), Q24A Validation of Analytical Procedures, Definitions and Terms. 

Fig. 13-1. International Conference on Harmonization (ICH) process for developing harmonized guidelines.

International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use... 

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. 

The Medical Dictionary for Regulatory Activities (MedDRA) is a creation of the International Conference on Harmonization, and it is used to categorize and code diseases, disorders, and adverse events. The five levels and associated codes to the MedDRA coding hierarchy are as follows ... 

Timing of Non-Clinical Safety Studies for the Conduct of Human Clinical trials for Pharmaceuticals. Fourth International Conference on Harmonization. International Conference on Harmonization, Brussels, 1997. 

In recent years, regulatory authorities and industry associations have undertaken several important initiatives to promote international harmonization of regulatory requirements. These efforts are designed to enhance harmonization and are committed to seeking scientifically based harmonized technical procedures for pharmaceutical development. These efforts are undertaken under the auspices of the International Conference on Harmonization (ICH), which is organized to provide an opportunity for tripartite... 

International Conference on Harmonization, Guideline on validation of analytical procedures definition and terminology, Fed. Reg., 60(40), 11260 (1995). 

International Conference on Harmonization, Validation of analytical procedures methodology, step 2. The Third International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Yokohama, Japan. Nov. 29-Dec. 1, (1995). 

The single-dose toxicity studies were performed in two mammalian species, rat and mouse, by the route used in clinical practice, that is oral, as well as that ensuring adequate systemic exposure to the drug, that is intravenous. The subacute (3 months) toxicity studies were correctly carried out in the two animal species (rat, dog) in which also the pharmacokinetics was studied. Since in accordance with the International Conference on Harmonization (CPMP/ICH/286/95), 3-month toxicity studies support clinical trials for up to 1 month s duration (the longest duration of drug administration in clinical use), chronic toxicity studies have not been performed. 

The International Conferences on Harmonization has published its document S6, Preclincial Safety Evaluation of Biotechnology-Derived Pharmaceuticals. The FDA (the Center for Drug Evaluation and Research, and the Center for Biologies Evaluation and Research jointly) has published the document as a Guidance for Industry (Anon., 1997a, b FDA, 1989, Hayes and Reyffel, 1999). 

Barton, B. (1998). International Conference on Harmonization good clinical practices update. Drug Information J. 32 1143-1147. 

ICH. (1997). International Conference on Harmonization Safety Steps 4/5 Documents. Interpharm Press, Inc., Buffalo Grove, IL. 

ISO 10993-3 (1993) sets forth clear guidance on testing requirements as summarized in Table 6.1. ICH (International Conference on Harmonization) guidance, shown in Table 6.2, has different but also clear requirements. They want to see an in vivo test conducted. While FDA has no clear guidelines, it expects that an appropriate adaptation of one of these two be performed. 

FDA International Conference on Harmonization Guideline on detection of toxicity to reproduction for medicinal products. Federal Register, September 22, 1994, Vol. 59, No. 183. 

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