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28 BioPharm International eBook September 2019 www.biopharminternational.com Regulatory Sourcebook Pharmacopoeia Compliance Series Table I. Challenges to pharmacopoeia compliance. Overall • Need to comply throughout entire product lifecycle. • Need to comply with both product registration and pharmacopoeia requirements on release and stabilit y. • Complex compendial revisions and shor t time available to implement changes. External • Multiple regulator y expectations and processes around the world. • Multiple pharmacopoeia requirements published around the world. • Lack of broad regulator y and pharmacopoeia harmonization. • Significant number of compendial revisions published by pharmacopoeias. • Appropriate use of compendial reference standards; qualification of in-house standards. Internal • Lack of broad understanding of the need for, the complexit y of, and the challenges to compliance. • Need to establish and maintain par tnerships with internal stakeholders, with clearly defined roles and responsibilities. • Lack of compendial line-of-sight (C-LOS) in product and analy tical development. • Need for ef fective compendial processes, with tracking and communication tools. • Complex change control processes that make on-time implementation dif ficult. Compendial changes often put additional strain on systems and processes. In the authors' experience, the majority of compendial changes impact central or site testing stan- dards that are used to ensure the qualit y of pharmaceutical prod- ucts and their ingredients. Some comp e nd ia l c ha nge s may a l s o i mpac t cent ra l or lo c a l pro ce - dures, including those in f unc- tional areas such as packag ing, lab e l i ng , storage, d ist r ibut ion, and even research and develop- ment. T hese c ha nges resu lt i ng from new or revised compendial requirements are usually imple- mented according to change con- trol procedures established by the company. For qualit y document updates, revisions typically occur w it h i n a g lo b a l c h a n ge - m a n - agement system, which is sepa- rate f rom compend ia l systems, although each system and pro - cess needs to provide visibility to the other to ensure no compli- ance gaps emerge. Change con- trol should require the compendial rev isions to be rev iewed by all impacted stakeholders, and in par- ticular those in regulatory/chem- istry, manufacturing, and controls (CMC) f unctions who have v is- ibility to the global registrations for the company's product portfo- lio. Compendial changes represent only one type that are typically broug ht i nto t he c ha nge con- trol process, which also includes changes driven by regulatory and manufact uring process updates. Compend ia l cha nges of ten put additional strain on systems and pro c e s s e s t h at a r e ut i l i z e d to implement the necessary revisions on time, given the complex supply and reg ulatory environment for bio/pharmaceutical companies. Up s t r e a m f r om t he c ompl i- ance function are the surveillance activities, which encompass the review of compendial updates at the proposed and official stage. E f fe c t ive su r ve i l la nce re qu i res the appropriate processes, people, and tools to enable compliance. As shown in Figure 1, this work is based upon user-centric partner- ships and teams to develop and execute implementation plans for ongoing compendial compliance. As mentioned earlier, the surveil- lance activ ities also prov ide an advocacy opportunity to respond a nd p ote nt ia l ly i n f lue nc e t he course of compendial revisions. Further upstream are the strat- eg y ac t iv it ies t hat help enable compl ia nce t h roug h proac t ive engagement w it h t he pha r ma- copoeias. This work includes the submission of new a nd rev ised monographs and chapters for con- sideration by the pharmacopoe- ias, as well as involvement with pharmaceutical industry associa- tions that engage in constructive dialog with the pharmacopoeias. One recent advocacy development that has generated much interest is the elaboration of new compendial monographs and chapters that are prospectively har monized f rom the beginning; an initiative that has been enabled by bilateral and