Issue link: https://www.e-digitaleditions.com/i/1171476
www.biopharminternational.com September 2019 BioPharm International eBook 23 Regulatory Sourcebook Pharmacopoeia Compliance Series also true for Ph. Eur. Chapter 5.20 "Elemental Impurities," USP <232> "E lementa l I mpu r it ies – L i m its," and the ICH Q3D Guideline on Elemental Impurities, along with the associated removal of the com- pendial test for heavy metals from the pharmacopoeias, which fur- ther serves as an example of the significant challenges for the bio/ pharmaceutical industry to ensure compliance with updated regula- tory and compendial requirements. General monographs typically prov ide overall qualit y require- ments t hat a re applicable to a specific dosage form or route of administration for drug products. In the Ph. Eur., there are general dosage form monographs for cap- sules, tablets, eye preparations, nasal preparations, parenteral prep- arations and many others. In USP– NF, the general chapters numbered <1> through <5> serve the same function as the Ph. Eur. general monographs, and include quality requirements for injections, oral drug products, topical and trans- dermal products, mucosal products, and inhalation products. Spec if ic monog raphs prov ide t he m i n i mu m qua l it y requ i re - ments that must be met for drug pro duc t s a nd i ng re d ient s, a nd apply to all manufacturers of these mate r ia ls, b ot h i n novator a nd generic-drug companies. A mono- graph includes the name of the ingredient or preparation; the def- inition, packaging, storage, and labeling requirements; a nd t he specification, consisting of a series of tests, procedures and acceptance criteria. In the USP–NF, there are c ur rent ly more t ha n 490 0 spe- cific monographs, and in Ph. Eur., there are more than 2400 mono- graphs. These specific monographs cover the entire range of bio/phar- maceut ica l produc ts, includ ing excipients, small-molec ule dr ug substances, biological products, and vaccines. A few examples are the monographs 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 tab- lets, infliximab concentrated solu- tion, and human papillomavirus vaccine. Monographs often require official reference standards, which are physical materials that may be purchased from the pharma- copoeia to be used in conjunc- tion with the test methods in the monograph to assess specific qual- ity attributes of the drug product or ingredient, including assay and impurities. Information contained in the pha r macopoeia is inter-related, and the requirements from one section must be utilized in con- junction w ith other sections. A specific monograph may include a reference to a general dosage form monograph, along with references to applicable genera l chapters, with the basic underpinnings con- tained in the general notices. Bio/ Early Development Commercialization Supply Nomenclature Excipient Monographs API Monographs Product Monographs General Chapters (e.g.): Water/Loss on Drying, Elemental Impurities, Residual Solvents, Chromatography, Dissolution, Dose Uniformity, Microbial Limits, Sterility Patent Expiration Entry Generic Marketing Exclusivity Regulatory Submission/Approval API Development Dosage Form Development Clinical Trials Figure 1. Impact of pharmacopoeia throughout drug product lifecycle. FIGURE COURTESY OF THE AUTHORS