FDA CVM GFI #100 (VICH GL18) Residual Solvents in New Veterinary Medicinal Products

标准简介

CVM GFI #100 (VICH GL18) Residual Solvents in New Veterinary Medicinal Products[附网盘链接]由Food&Drug Administration于之前发布，适用于美国。

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IMPURITIES: RESIDUAL SOLVENTS IN NEW VETERINARY MEDICINAL PRODUCTS, ACTIVE SUBSTANCES AND EXCIPIENTS 1. INTRODUCTION The objective of this guidance is to recommend acceptable amounts for residual solvents in pharmaceuticals for the safety of the target animal as well as for the safety of residues in products derived from treated food producing animals. The guidance recommends use of less toxic solvents and describes levels considered to be toxicologically acceptable for some residual solvents. Residual solvents in pharmaceuticals are defined here as organic volatile chemicals that are used or produced in the manufacture of active substances or excipients, or in the preparation of veterinary medicinal products. The solvents are not completely removed by practical manufacturing techniques. Appropriate selection of the solvent for the synthesis of active substance may enhance the yield, or determine characteristics such as crystal form, purity, and solubility. Therefore, the solvent may sometimes be a critical parameter in the synthetic process. This guidance does not address solvents deliberately used as excipients nor does it address solvates. However, the content of solvents in such products should be evaluated and justified. Since there is no therapeutic benefit from residual solvents, all residual solvents should be removed to the extent possible to meet product specifications, good manufacturing practices, or other quality-based requirements. Veterinary medicinal products should contain no higher levels of residual solvents than can be supported by safety data. Some solvents that are known to cause unacceptable toxicities (Class 1, Table 1) should be avoided in the production of active substances, excipients, or veterinary medicinal products unless their use can be strongly justified in a risk-benefit assessment. Some solvents associated with less severe toxicity (Class 2, Table 2) should be limited in order to protect target animals and human consumers from potential adverse effects. Ideally, less toxic solvents (Class 3, Table 3) should be used where practical. The complete list of solvents included in this guidance is given in Appendix 1. The lists are not exhaustive and other solvents can be used and later added to the lists. Recommended limits of Class 1 and 2 solvents or classification of solvents may change, as new safety data becomes available. Supporting safety data in a marketing application for a new veterinary medicinal product containing a new solvent may be based on concepts in this guidance or the concept of qualification of impurities as expressed in the guidance for active substance (VICH GL 10(R), Impurities in New Veterinary Drug Substances) or veterinary medicinal product (VICH GL 11(R), Impurities in New Veterinary Medicinal Products), or all three guidances. 2. SCOPE OF THE GUIDANCE Residual solvents in active substances, excipients, and in veterinary medicinal products are within the scope of this guidance. Therefore, testing should be performed for residual solvents when production or purification processes are known to result in the presence of such solvents. It is only necessary to test for solvents that are used or produced in the manufacture or purification of medicinal substances, excipients, or veterinary medicinal products. Although manufacturers may choose to test the veterinary medicinal product, a cumulative method may be used to calculate the residual solvent levels in the product from the levels in the ingredients used to produce the product. If the calculation results in a level equal to or below that recommended in this guidance, no testing of the veterinary medicinal product for residual solvents need be considered. If, however, the calculated level is above the recommended level, the veterinary medicinal product should be tested to ascertain whether the formulation process has reduced the relevant solvent level to within the acceptable amount. The veterinary medicinal product should also be tested if a solvent is used during its manufacture. This guidance does not apply to potential new active substances, excipients, or veterinary medicinal products used during the clinical research stages of development, nor does it apply to existing marketed veterinary medicinal products. The guidance applies to all dosage forms and routes of administration. Higher levels of residual solvents may be acceptable in certain cases or topical application. Justification for these levels should be made on a case by case basis.

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