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Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2019 33 cluding excipients, small-molecule drug substances, biologi- cal products, and vaccines. A few examples are the mono- graphs for the excipient hypromellose, the drug substances acetaminophen (as it is named in the USP) or paracetamol (as it is named in Ph. Eur.), and sitagliptin phosphate, and a variety of drug products, including sitagliptin tablets, inf- liximab concentrated solution, and human papillomavirus vaccine. Monographs often require official reference stan- dards, which are physical materials that may be purchased from the pharmacopoeia to be used in conjunction with the test methods in the monograph to assess specific qual- ity attributes of the drug product or ingredient, including assay and impurities. Moving to regulatory submissions and product commercialization, it is important to understand the compendial requirements for packaging, storage, and distribution. Information contained in the pharmacopoeia is inter-re- lated, and the requirements from one section must be utilized in conjunction with other sections. A specific monograph may include a reference to a general dosage form monograph, along with references to applicable general chapters, with the basic underpinnings contained in the general notices. Bio/ pharmaceutical companies must understand and apply these pharmacopoeial requirements within this context. A guide, titled "How to Use the BP," was posted on the British Pharma- copoeia website (5) that provides an overview and illustration of the inter-relation of pharmacopoeia content. This guide forms a framework for navigating compendial requirements in the BP, and should be helpful, especially for those who may be less familiar with the structure and use of pharmacopoeias. Pharmacopoeia impact throughout drug product lifecycle Pharmacopoeias impact drugs and their ingredients through- out the entire product lifecycle (Figure 1). Beginning with the development of a new drug substance or API, many of the pharmacopoeia general chapters should be considered for potential quality and functionality testing. For example, the compendial tests listed in general chapters for water con- tent or loss on drying, residual solvents, elemental impuri- ties, and microbiological evaluation will likely be used for quality release of the material later in the lifecycle. Similarly, information listed in the chromatography chapter should be considered during analytical method development, because many of the compendial requirements can be incorporated into the test procedures, such as method repeatability and resolution for system suitability. Consideration should also be given at the appropriate stage of product development to compendial requirements for method validation, such as USP <1225> "Validation of Compendial Procedures," because this information will ultimately be used to support the product registration. Once dosage form development is initiated, additional compendial content becomes important. General chapters and general product monographs provide requirements for a given dosage form that must be considered before a prod- uct is registered or licensed. Drug product quality and func- tional characteristics should be evaluated according to these compendial requirements, because this is the regulatory ex- pectation. Depending on the dosage form being developed, applicable chapters include uniformity of dosage units (con- tent uniformity or mass variation), dissolution, particulate contamination, microbiological tests, sterility, and chroma- tography for assay and impurities. Pharmacopoeias also con- tain 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. During formulation development, consideration must also be given to compendial monographs for excipients. As stated in the pharmacopoeias, and perhaps more importantly, as expected by health authorities around the world, excipi- ents used in drug products must comply with the applicable monograph requirements published in the pharmacopoeias. Lack of awareness or attention to this point jeopardizes drug product approval and ultimate compliance. The existence of so many pharmacopoeias around the world with excipient monographs that do not broadly align is a significant compli- cating factor for compendial compliance and global product registrations. Moving to regulatory submissions and product commer- cialization, it is important to understand the compendial re- quirements for packaging, storage, and distribution. 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. Consid- eration of these requirements may also be important when planning for and evaluating drug product stability. The use of compendial reference standards for pharmacopoeial testing, or alternatively, of qualifying in-house primary or secondary standards, must also be considered at an appropriate stage in product and analytical development to meet the expecta- tions of regulatory agencies.