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20 BioPharm International eBook October 2020 www.biopharminternational.com i nter pret at ion a nd appl ic at ion o f t h e U S P a n d t h e Na t i o n a l Formulary (NF). The requirements st ate d i n t he G e ne r a l Not ic e s apply to all ar ticles (e.g., stan- d a rd s, test s, a ssays, a nd ot he r specifications), otherwise known as the compendia in the USP, and to all general chapters unless spe- cifically stated otherwise (11). T herefore, before proceed ing with deriving a working analytical procedure from a monograph and a general chapter, it is important to understand the requirements of the General Notices. The General Notices cover definitions of the sub-ambient temperature range, defining "about" when weighing a substa nce, round ing r ules of analysis results before comparison with the specification, and many others. Cr iter ia in the General Notices are requirements unless stated in either a monograph or a general chapter. Monographs take precedence over general chapters. Mandatory and informational general chapters A na ly t ica l tech n iques used for analysis of APIs, excipients, and f i n i s h e d p r o d u c t s a r e d o c u - mented in the general chapters of the USP, and these are divided i nto t he fol low i ng t wo t y p e s, dependent on the numbering of an individual general chapter: • General chapters numbered below 10 0 0 a re ma ndator y and apply to the analysis of a substance in a monograph e xc e p t w h e n t h e r e q u i r e - ments of a monog raph d if- fe r f rom t he r e qu i r e me nt s sp e c i f ie d i n t he se G e ne ra l Notices or an applicable gen- eral chapter. In these cases, the monograph requirements a p p l y a n d s u p e r s e d e t h e requirements of the General Notices or applicable general chapters, whether or not the monograph explicitly states the difference. • General chapters numbered 1000 to 1999 are for informa- t iona l pu r poses on ly. T hey contain no mandatory tests, assays, or other requirements applicable to any official arti- cle, regardless of citation in a general chapter numbered below 1000, a monograph, or the General Notices. I n r e c e nt r e v i s io n s o f ge n - e r a l c h ap te r s, t he a i m of t he USP has been to issue pairs for t he sa me a na ly t ica l tec h n ique Regulatory Sourcebook Data Integrity Figure 1. Basic structure of the United States Pharmacopeia and relationships between the different sections. Revised fig 1 (colors added and some other changes) Revised fig 3 (only change is in bottom line text) United States Pharmacopoeia (USP) General Notices Monograph General Chapters < 1000 General Chapters >1000 Procedure implementation in an individual laboratory • USP <1058> Analytical Instrument Qualification • USP <1029> Good Documentation Practice Analytical Procedure for each Test • Reference Standards USP <11> • Reagents • Legal requirement • Tests for any sample taken over life (not batch) • Mandatory unless defined in Monograph or General Chapter • Mandatory • Key parameters and acceptance criteria • Informational (strong guidance) • Best practice approaches Classical Methods Observation Classical Methods Paper Records Classical Methods Some hybrid records but primarily paper Instrumental Methods Hybrid: electronic records with printouts Instrumental Methods E- working enforced by technical controls Spectrum of Pharmacopoeial Test Methods Greater data integrity risk through lack of objective evidence Procedural control can be inconsistent Technical controls lower data integrity risk Consistent operation Colour Odour Appearance Titration Analytical Balances pH Meters Loss on Drying Chrom Data Systems UV, IR systems Chrom Data Systems LIMS, ELN or LES interfaced to instruments FIGURES ARE COURTESY OF THE AUTHORS