Pharmaceutical Technology - September 2019

Pharmaceutical Technology - Regulatory Sourcebook

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Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2019 31 available public standards to help ensure the quality of medicines. Pharmacopoeia standards support regulatory authorities in controlling the quality of pharmaceutical substances, their finished pharmaceutical products (FPPs), and related materials and will provide a tool with which the user or procurer can make an independent judgment regarding qualit y, thus safeguarding the health of the public." A search through the pharmacopoeias reveals that they contain general notices, general chapters, general mono- graphs, specific monographs for drug products, drug sub- stances and excipients, and additional information related to packaging, labeling, storage, etc. All this information must be taken together to determine the specific quality requirements for bio/pharmaceutical products. Within each pharmacopoeia, there is a section referred to as general notices, which is critical to the full under- standing of the scope and technical approaches in that pharmacopoeia. As stated in the USP–NF, the genera l notices section presents the basic assumptions, def ini- tions, and default conditions for the interpretation and application of the USP–NF, and the requirements apply to all articles recognized in the compendia and to all general chapters, unless specifically stated otherwise. Similarly, the general notices in Ph. Eur. and other pharmacopoeias apply to all monographs and other texts in the pharmaco- poeia. The general notices provide a wide range of impor- tant information, from a statement of what conformance to compendial standards means, to a description of spe- cific monograph components, considerations for the use of alternative methods, rules for rounding, and a defini- tion of "about". They have been described anecdotally as the most important pages of the pharmacopoeia that most users have never read. Thus, reading and understanding the general notices is critical to ongoing pharmacopoeia compliance. During formulation development, consideration must also be given to compendial monographs for excipients. There are more than 350 general chapters in USP–NF, and more than 370 general texts in Ph. Eur., including general monographs and chapters. Many of the general chapters in the pharmacopoeias are mandatory and en- forceable by regulatory authorities, containing informa- tion on specific chemical, biological, and microbiological test methods and assays, as well as specific requirements for particulate contamination and packaging components, for example. Other general chapters may instead be in- formational and not necessarily enforceable, intended to Table II. Examples of compendial compliance observations from FDA 483s. USP is United States Pharmacopeia. Year Observation 2018 The firm has not established that your purified water system is adequately designed, controlled, maintained, and monitored to ensure it consistently produces water that meets Purified Water USP monograph specifications and appropriate microbial limits. 2017 The firm has not established or implemented all appropriate specifications for the active pharmaceutical ingredient in accordance with the accepted USP standards and consistent with the manufacturing process. Specifically, the firm has not included a control of all process impurities such as residual solvents. 2017 The firm does not always follow official USP monographs when testing drug products for release and distribution to the United States. 2016 Growth promotion test is not performed in accordance with standard pharmacopeia. 2016 The USP test method for Loss on Drying, which is used for the release of finished product to market has not been verified. 2016 The firm could not provide documentation to show that you did not use an expired batch of USP reference standard. The laboratory staff does not document and record the expiration dates for official USP standards. 2013 USP-grade active pharmaceutical ingredients are not always fully tested against USP monographs (e.g., Identification, Acidity, Alkalinity, Chloride, Sulfate, Residue on Ignition). 2012 Compendial methods for active pharmaceutical ingredients are not verified under actual conditions of use (e.g., Water Determination, Loss on Drying, Reside on Ignition). 2010 The firm does not perform current USP monograph testing (e.g., Assay, Identification, Distillation Range) on the final active pharmaceutical ingredients prior to distribution for use in human and veterinary drug products. 2009 USP active pharmaceutical ingredients have been released for distribution by the firm prior to testing and/or which did not meet USP specifications (e.g., Assay, Loss on Drying). 2009 The firm's procedure for stability testing is insufficient. The firm does not test the stability samples of USP-grade material to ensure compliance with the USP method and limit for moisture content.

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