Regulatory pharmaceuticals

These provide a safer alterative to glass containers although limited availability, the need to use specialist filling and sealing equipment and the requirement to conform to regulatory pharmaceutical requirements has restricted their use. 

In 1995, discussions among the United States, the European Community (EC), and Japan occurred to achieve harmonization of dmg and dmg product standards and to provide guidance to the worldwide pharmaceutical industry for acceptance of global regulatory filings. The International Committee on Harmonization (ICH) has proposed initial guidelines for the estabUshment of stabihty studies. 

The Japanese regulatory authority is the Ministry of Health and Welfare (MHW) and the Pharmaceutical and Medical Safety Bureau (PSMB) is responsible for the promulgation of national and international guidelines in the form of Notifications. Guidelines are available on the Internet web-site of the National Institute of Health and Science (http //www.nihs.go.jp). The MHW has not issued specific guidance on the development of chiral drugs, but has nonetheless responded to the enantiomer-versus-racemate scientific debate. The attitude of the MHW and its advisory body, the Central Pharmaceutical Affairs Council (CPAC) is discussed in two articles by Shindo and Caldwell published in 1991 and 1995 [17, 18]. The latter paper analyzes the results of a survey of the Japanese pharmaceutical industry which sought responses on chirality issues. 

The search for inhibitors of this pathway began with the first key regulatory enzyme, HMG CoA reductase. Several clinically useful inhibitors of HMG CoA reductase are now known. One of the most successful, Mevacor, produced by Merck, is one of the pharmaceutical industry s best selling products. However, the problem with inhibiting a branched biosynthetic pathway at an early point is that the biosynthesis of other crucial biomolecules may also be inhibited. Indeed, there is some evidence that levels of ubiquinone and the dolichols are affected by some HMG CoA reductase inhibitors. Consequently, efforts have recently been directed towards finding inhibitors of squalene synthase, the enzyme controlling the first step on the route to cholesterol after the FPP branch point. 

Pharmacopoeia publications provide a final important source of information for the pharmaceutical industry, regulatory authorities, and the healthcare professions. These are concerned with establishing quality standards. These publications include monographs that define specifications for the purity and identity of established pharmaceutical ingredients, both active and non-active, together with recognised analytical methods that may be used to evaluate them. The most relevant are the United States Pharmacopoeia (USP) and the European Pharmacopoeia (Ph.Eur). 

The International Conference on Harmonisation (ICH) of technical requirements for the registration of pharmaceuticals for human use was established in 1990 as a joint regulatory/industry project to improve, through harmonisation, the efficiency... 

The Global Harmonisation Task Force (GHTF) was conceived in 1992 to address similar issues for medical devices. It has a broader regional base than its pharmaceutical counterparts in that it includes representatives from Canada and Australia in its core group, in addition to those from the EU, US and Japan. In some ways, it also faces a stiffer challenge in that there is more divergence in the regulatory... 

The Pharmaceutical Inspection Cooperation Scheme (PICS) was established in 1995. It brings together regulatory authorities from different countries, for the purpose of developing harmonised GMP requirements and inspection techniques, with the goal... 

S1 C(R1) Dose Selection for Carcinogenicity Studies of Pharmaceuticals Limit Dose S2A Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals S2B Genotoxicity A Standard Battery for Genotoxicity Testing of Pharmaceuticals Toxicokinetics and Pharmacokinetics... 

To ensure that regulatory review, compliance, and inspection policies are based on state-of the-art pharmaceutical science. 

Regulatory agencies currently set stringent standards on the quantities of nucleic acids allowed in recombinant biological products. In the pharmaceutical industry these requirements necessitate the quantification of trace amounts of nucleic acids in the presence of large quantities of protein and other excipients. Flourescence methods offer advantages for such analyses, but also have limitations. The use of a variety of fluorescent dyes and techniques is described here, and practical examples of such use are presented. 

Laboratory notebooks—It may be debatable to consider laboratory notebooks as text documents, but they should be mentioned here because of their importance in preclinical development. Laboratory notebooks are used to record experimental procedures, observations, raw data, and other important information. Although laboratory notebooks are rarely used for submission to regulatory agencies directly, they are available for inspection by the authorities in the Preapproval Inspection (PAI) and other GMP/GLP-related inspections. Currently, most of the major pharmaceutical companies still use paper-based laboratory notebooks. Electronic-based notebook systems are being developed and commercialized, which are discussed in Chapter 9. 

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