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30 Pharmaceutical Technology REGULATORY SOURCEBOOK DECEMBER 2019 P h a r mTe c h . c o m Pharmacopoeia Compliance Series The process used in the bio/pharmaceutical industry for surveillance of compendial changes (Figure 1) starts with publication of proposed changes by the pharmacopoeias and continues to the publication of of ficial updates. The first steps of the industry surveillance process are the same for proposed and of ficial revisions: monitor pharmaco- poeia publications, filter for potential impact, and communicate the changes. Having an effective process for these initial steps is crucial to the ultimate success of complying with pharmacopoeia updates. The subsequent steps involve a deeper look into proposed changes to as- sess the impact and develop an implementation plan, followed by evaluation of the official changes and execution of the implementation plan. The process also provides opportunities to respond to proposed changes and submit revision requests for of ficial changes, if needed. Monitor pharmacopoeia publications. The compendial af fairs function needs to have access to the publications it intends to monitor (i.e., new editions, supplements, and forum publications). For official editions and supplements to the global pharmacopoeias, this can be done mainly on-line by purchasing the appropriate licenses. For proposals in the global pharmacopoeia forum, access is available through free on- line website postings. Because the global pharmacopoeias are published in English, the compendial af fairs function in many multi-national companies can review the table of contents (TOC) in the publications/ website postings to identif y relevant items. This work may be more difficult for companies where English is not the primary language. Many companies monitor and filter the items in the TOC when each publication is received; alternatively, this may be done on a monthly basis to capture revisions in all publications identified within that time frame. National pharmacopoeias present challenges for the compendial affairs function due to less regular publication schedules and the fact that revisions may not be available in English. To successfully monitor these pharmacopoeias, the compendial affairs function needs a strong tie to the company's local responsible group in that country, if available. This local group could reside in the quality, regulatory affairs, or other area, or in a local manufacturing site in that country. With well-defined roles and responsibilities, this local contac t group (or in-countr y partner) monitors the local language pharmacopoeia publication or website to identif y new items for review and impact assessment by the company. Once identified, the local group would determine the urgency for a complete and accurate translation into English, based on the time allowed for commenting on proposals or implementation of official changes. The roles and responsibilities are best defined in a cross-functional process with agreement between the partners and should be reviewed periodically to ensure it is working ef fectively. Filter for potential impact. Reviewing the TOC in a pharmacopoeia publication represents the first in a series of "filters" through which changes are passed to determine if it applies to a company. To perform this filtering properly, the compendial affairs function must have a way to identify all excipients, APIs (procured or manufactured internally), and drug products across their entire supply chain. Gathering this information can be overwhelming and inef ficient, as many business systems are not designed to provide this comprehensive "where- used list ". This information must be combined from several sources within a company, a time-consuming activity that is repeated each time the TOC filtering needs to occur, as the list needs to be current. This list of materials and products is used to filter the TOC in the pharmacopoeia publication to identify individual monographs of interest to the company. One complicating factor is the nomenclature used by the pharmacopoeias and by a company for materials, with a single material potentially having multiple names. It is important to know how each material is named in a pharmacopoeia publication and how it may be named in your company's systems (e.g., trade name, chemical name, or some other abbreviated name due to field-size limitations in the enterprise system, such as SAP). See the following examples: • Avicel PH-102 (DuPont)= Microcrystalline Cellulose • Glycerin (USP) = Glycerol (Ph. Eur.) • Dibasic Sodium Phosphate (USP) = Disodium Phosphate Dihydrate (Ph. Eur.). Another complex task is identif ying which general chapters in the pharmacopoeias apply to the company. Combined, there are over 2000 general chapters contained in the global and national pharmacopoeias that need to be considered. There is redundanc y in several of the chapters across the many pharmacopoeias, but the compendial af fairs function needs to identif y the respective chapter in each. For example, the harmonized chapter for uniformity of dosage units appears as United States Pharmacopeia (USP) <905>, European Pharmacopoeia (Ph. Eur.) 2.9.40, and Japanese Pharmacopoeia (JP) 6.02, while the non-harmonized chapters for weight/mass variation and content uniformit y appear as Ph. Eur. 2.9.5 and 2.9.6, Indian Pharmacopoeia (IP) 2.5.3 and 2.5.4, and Chinese Pharmacopoeia (ChP) 0101 and 0941. It is impor tant to establish this list to f ilter the TOC for general chapters, so time and resources are only spent on fur ther assessment of those items that impac t your company. The publication of a new general chapter requires a company to determine whether to add this to their TOC filter list. A company must also decide whether to monitor and comment on non-mandatory, informational chapters in the pharmacopoeia (e.g., chapters above <1000> in USP or above 9000 in ChP). There is an additional factor in considering these informational chapters: some of the "non-binding" information may be critical and should possibly be monitored and/or adopted, especially because the chapters may be referenced in other chapters that are mandatory, and regulatory agencies may decide to enforce certain aspects contained within the chapters, even though listed as informational. To minimize the risk of missing a general chapter Bio/pharmaceutical industry surveillance of compendial changes: Process in detail The first steps of an industry surveillance process are: monitor pharmacopoeia publications, filter for potential impact, and communicate the changes.