In addition to detailed information on assays, characterization tests, impurities and equipment, USP-NF General Chapters include in-depth descriptions of good manufacturing practices (GMP) and good distribution practices (GDP) for bulk pharmaceutical excipients. Overview chapters that outline the structure of accepted GMP systems are further supplemented by chapters specifically addressing critical GMP-related topics, such as Certificates of Analysis, Significant Change Guide and Excipient Biological Safety Evaluation Guidelines.
Excipients are used in virtually all drug products and are essential for product manufacturing and performance. Thus, the successful manufacture of a pharmaceutical product requires the use of well-defined excipients and manufacturing processes that consistently yield a quality product. Excipients used in drug products typically are manufactured and supplied in compliance with compendial standards. However, the effects of excipient properties on the critical quality attributes (CQAs) of a drug product are unique for each formulation and process and may depend on properties of excipients that are not evaluated in USP or NF monographs. The effects of variations in excipient material attributes depend on the role of an excipient in a formulation and the CQAs of the drug product. This General Chapter provides a framework for applying Quality by Design (QBD) principles to excipient quality and performance.
This general information chapter provides guidelines for methods, facilities, and manufacturing controls to be used in the production of pharmaceutical excipients intended for use in human drugs, veterinary drugs and biologics, in order to ensure that they possess the quality, purity, safety, and suitability for use that they purport to possess. It covers the quality management system and the extent of good manufacturing practices (GMP) necessary throughout manufacturing for both batch and continuous processes.
Chapter <1078> combines the concepts of existing GMP principles from the following sources:
- World Health Organization (WHO) GMP Guidelines for Excipients,
- International Pharmaceutical Excipients Council (IPEC) Good Manufacturing Practices Guide for Bulk Pharmaceutical Excipients 2001,
- Institute of Quality Assurance (IQA) Pharmaceutical Quality Group (PQG) PS 9100:2002, Pharmaceutical Excipients,
- International quality management system requirements as developed by the International Organization for Standardization (ISO).
In light of the increasing globalization of the pharmaceutical industry and the harmonization of pharmaceutical registration requirements, deference to all schemes is becoming more essential. Therefore, relevant portions of the manufacturing concepts are employed throughout this chapter.
The pharmaceutical excipient supply chain participants include manufacturers, distributors, brokers, suppliers, traders, transporters, forwarding agents, and repackagers. The quality of pharmaceutical excipients is affected by inadequate control of activities including distribution, packaging, repackaging, labeling, and storage. Improper or inadequately controlled trade and distribution practices can pose a significant risk to the quality of pharmaceutical excipients and can increase the risk of contamination, cross-contamination, adulteration, mix-ups, degradation, or changes in physical or chemical properties. To maintain the original and intended quality, all participants in the excipient supply chain should carry out their activities according to appropriate standards for good trade and distribution practices.
This general information chapter provides recommendations for those activities and practices that ensure good trade and distribution practices for pharmaceutical excipients in order to ensure their intended quality. These activities and practices include quality management, organization, documentation, premises, storage, equipment, stability, prevention of adulteration, importation, packaging, repackaging, labeling, dispatch, transport, returned goods, and compounding practices. In addition, personnel, authenticity of data, expiration dating, retesting, complaints and recalls, handling of nonconforming materials, internal/external/third-party audits, quality agreements, shelf life, traceability, economically motivated adulteration, and conformance to compendial monographs are included.
- Chapter <202> Identification of Fixed Oils by Thin-Layer Chromatography
- Chapter <228> Ethylene Oxide and Dioxane
- Chapter <264> Nickel in Hydrogenated Oils and Saturated Esters
- Chapter <267> Porosimetry by Mercury Intrusion
- Chapter <268> Porosity by Nitrogen Adsorption-Desorption
- Chapter <311> Alginates Assay
- Chapter <401> Fats and Fixed Oils
- Chapter <402> Fatty Acid Assay
- Chapter <403> Fatty Alcohol Assay
- Chapter <431> Methoxy Determination
- Chapter <469> Ethylene Glycol, Diethylene Glycol, and Triethylene Glycol in Ethoxylated Substances
- Chapter <525> Sulfur Dioxide
- Chapter <616> Bulk Density and Tapped Density of Powders
- Chapter <651> Congealing Temperature
- Chapter <699> Density of Solids
- Chapter <784> Dropping Point
- Chapter <786> Particle Size Distribution Estimation by Analytical Sieving
- Chapter <811> Powder Fineness
- Chapter <911> Viscosity - Capillary Methods
- Chapter <912> Viscosity - Rotational Methods
- Chapter <913> Viscosity - Rolling Ball Method
- Chapter <914> Viscosity - Pressure-Driven Methods
- Chapter <1062> Tablet Compression Characterization (Stimuli Article: Responses to Comments on Stimuli for Proposed New <1062>)
- Chapter <1063> Shear Cell Methodology for Powder Flow Testing (Stimuli Article: USP Responses to Comments on Stimuli Article Proposed New USP General Information Chapter: Shear Cell Methodology for Powder Flow Testing)
- Chapter <1074> Excipient Biological Safety Evaluation Guidelines
- Chapter <1080> Bulk Pharmaceutical Excipients–Certificate of Analysis
- Chapter <1174> Powder Flow
- Chapter <1191> Rheometry
- Chapter <1195> Significant Change Guide for Bulk Pharmaceutical Excipients
- Chapter In Development: Good Importation Practices for Bulk Pharmaceutical Excipients