International harmonization guidelines

The quality of a drug substance is controlled by its specification. An internationally harmonized guideline on specifications and tests for chemical substances as active ingredients and in drug products makes reference to chiral compounds. This has recently been finalized and is discussed in Section 13.5.2. 

Some internationally harmonized guidelines regarding specifications and tests, impurities and validation of analytical methods have particular relevance to the development of chiral drugs and are discussed below. In addition, the impact of work on the common technical document is considered. 

Fujimori, K. (1999). The role of general pharmacological studies and pharmacokinetics in the evolution of drugs (1) The role of general/safety pharmacology studies in the development of pharmaceuticals International harmonization guidelines. Folia Pharmacologica Japo-... 

ICH guidelines. In addition to these Japanese original guidelines for clinical development, internationally harmonized guidelines are now implemented in Japan ... 

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

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

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

Lumley, C.E., General pharmacology, the international regulatory environment, and harmonization guidelines, Drug Dev. Res., 32, 223-232, 1994. 

Source International Conference on Harmonization. Guideline for Good Clinical Practice E6(R1). http //www.ich.org/LOB/media/MEDIA482.pdf [accessed September 17,2007]. 

There are some guidelines on the requirements for proficiency testing schemes. The most important is the new ISO/IEC 17043 Conformity assessment - General requirements for proficiency testing . It describes the development and operation of a PT scheme with all quality management requirements related to that. The first version of the International Harmonized Protocol for the Proficiency Testing of (Chemical) Analytical Laboratories was a result of a joint workshop of lUPAC, ISO and AOAC and was published in 1993. A 2nd, revised version was published in 2006. This protocol also sets out the requirements for the provider and for the PT scheme itself. 

On the international level, we distinguish IUPAC, ISO, and the AOAC International. All three bodies develop validation and standardization frameworks for analytical chemistry. AOAC International introduced the AOAC Peer Verified Methods Program [62]. Different harmonized guidelines and protocols are developed by the IUPAC, ISO, and AOAC International together [4,8,63-67], in addition to a number of ISO standards [68-71]. The FDA, USP, and ICH developed guidelines specific for pharmaceutical and biotechnological methods [55,72-74]. 

It is clear that the fundamental tenets of safety, quality, and efficacy should remain but considerable scope exists to produce a more easily understood core of requirements among which the subject of risk analysis should also be included. International harmonization cannot be mandatory either for government or for industry. Nevertheless, a commitment can and should be entered into both by individual governments and by pharmaceutical associations to accept specific guidelines that have drawn up and agreed. Such a commitment would preempt the demands to provide additional data requirements unless the scientific validity of such requirements were proven (53). 

The reliability of measurements plays a pivotal role in food and agricultural areas, particularly in the case of undesirable toxic compounds such as mycotoxins. Quality-control principles for mycotoxin analysis are common to other trace analyses, so good laboratory practices, such as EN 4500, represent the heart of quality assurance requirements. Harmonized Guidelines for Internal Quality Control in Analytical Chemistry Laboratories, published by IUPAC (23), also presents valuable guidelines for the determination of mycotoxins. 

IUPAC Harmonized Guidelines for Internal Quality Control in Analytical Chemistry Laboratories. Pure Appl Chem 67(4) 649- 666,1995. 

The International Pharmaceutical Excipient Council in the United States (Arlington, Virginia 703-521-3338) has issued a GMP guideline for excipient bulk pharmaceutical chemicals. In conjunction with both the European and Japanese Pharmaceutical Excipient Councils, the council is currently engaged in establishing international harmonization excipient monographs for the more popular pharmaceutical excipients. A list of important and popular pharmaceutical excipients is given in Table 1. 

The FDA is announcing the Agency s policy on the development and use of standards with respect to international harmonization of regulatory requirements and guidelines. Specifically, the policy is intended to address the conditions under which the FDA plans to participate with standards bodies outside of the FDA, domestic or international, in the development of standards applicable to products regulated by the FDA. The policy also covers the conditions under which the FDA intends to use the resultant standards, or other available domestic or international standards, in fulfilling its statutory mandates for safeguarding the public health. 

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