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24 BioPharm International eBook September 2019 www.biopharminternational.com Regulatory Sourcebook Pharmacopoeia Compliance Series pharmaceutical companies must understand and apply these phar- macopoeial requirements within this context. A guide, titled "How to Use the BP," was posted on the British Pharmacopoeia website (5) that prov ides an over v iew and illustration of the inter-relation of pharmacopoeia content. This guide forms a framework for navi- gating compendial requirements in the BP, and should be helpful, especially for those who may be less familiar with the structure and use of pharmacopoeias. Pharmacopoeias impact drugs and their ingredients throughout the entire product lifecycle. PHARMACOPOEIA IMPACT THROUGHOUT DRUG PRODUCT LIFECYCLE Pha r macop o e ia s i mpac t d r ugs and their ing redients through- out t he ent i re pro duc t l i fe c y- cle ( Figure 1). Beginning with the development of a new drug sub- stance or API, many of the phar- m a c o p o e i a g e n e r a l c h a p t e r s should be considered for poten- t ia l qu a l it y a nd f u nc t iona l it y testing. For example, the compen- dial tests listed in general chap- ters for water content or loss on drying, residual solvents, elemen- tal impurities, and microbiologi- cal evaluation will likely be used for quality release of the material later in the lifecycle. Similarly, information listed in the chroma- tography chapter should be con- sidered during analytical method development, because many of the compendial requirements can be incorporated into the test pro- cedures, such as method repeat- ability and resolution for system suitability. Consideration should also be given at the appropriate st age of pro duc t deve lopme nt to compendial requirements for method validation, such as USP <1225> "Validation of Compendial Procedures," because this informa- tion will ultimately be used to sup- port the product registration. Once dosage form development is initiated, additional compen- dial content becomes important. General chapters and general prod- uct monographs provide require- ments for a given dosage form that must be considered before a prod- uct is registered or licensed. Drug product qualit y and f unctional characteristics should be evaluated according to these compendial requirements, because this is the regulatory expectation. Depending on the dosage form being devel- oped, applicable chapters include uniformity of dosage units (con- tent uniformity or mass variation), dissolution, particulate contamina- tion, microbiological tests, steril- ity, and chromatography for assay and impurities. Pharmacopoeias also contain general chapters and general dosage form monographs that provide core requirements for drug products, including USP <1> "Injections," Ph. Eur. monograph [520] on Parenteral preparations and Ph. Eur. monograph [478] on Tablets. Dur ing for mulation develop - ment, considerat ion must a lso be given to compendial mono - graphs for excipients. As stated i n t h e p h a r m a c o p o e i a s , a n d p e rhaps more i mp or t a nt ly, a s expec ted by health author ities around the world, excipients used in dr ug produc ts must comply with the applicable monograph requ irements published in t he pharmacopoeias. Lack of awareness or attention to this point jeopar- dizes drug product approval and ultimate compliance. The exis- tence of so many pharmacopoeias around the world with excipient monographs that do not broadly align is a significant complicating factor for compendial compliance and global product registrations. Moving to regulatory submis- sions and product commercializa- tion, it is important to understand the compendial requirements for packaging, storage, and distribu- tion. Failure to take these general chapters into account as contained in the various pharmacopoeias may again have adverse impact on regulatory approval and long- term compliance. Consideration of these requirements may also be important when planning for and evaluating drug product stability. The use of compendial reference standards for pharmacopoeial test- ing, or alternatively, of qualifying in-house primar y or secondar y standards, must also be considered at an appropriate stage in prod- uct and analytical development to meet the expectations of regula- tory agencies. Nomenclature used in pharma- copoeias for excipients, drug sub- stances, and drug products must also be considered during the prod- uct lifecycle. The link between a product's generic name and the content of the active ingredient can be important in clinical trials to support dosing studies, in devel- oping product strengths, and for filing and labeling purposes, espe- cially in the United States. USP <1121> states that USP–NF titles for monograph articles are legally recognized under the FD&C Act as the designations for use in label- ing the articles to which they apply and relate to the adulteration and misbra nd ing prov isions of t he