Issue link: http://www.e-digitaleditions.com/i/1222740
Pharmaceutical Technology REGULATORY SOURCEBOOK MARCH 2020 15 • To which pharmacopoeias should the monograph be submitted? • Which functional group in the company should sub- mit the monograph? How does the company connect with the pharmacopoeias? Who should follow-up re- garding the submission? • What information is needed for the submission? How should the information be pulled together? What physical materials (e.g., samples, impurities, potential reference standards) are needed to support mono- graph development? • Does the company need a procedure for monograph submission? What is the procedure that the pharma- copoeias follow to develop a monograph? • What can Company A do if a monograph is developed based on a submission from Company B? Can Com- pany A inf luence the outcome? Does Company A still need to comply? Value of public standards in the pharmacopoeias Before considering the factors that impact a company's deci- sion on whether and how to participate in the development of new and revised monographs, it is helpful to differentiate the various sectors within the broad scope of the bio/pharma- ceutical industry. For the purpose of these articles, the term "bio/pharmaceutical" includes innovator, generic-drug, virtual, and start-up companies that discover, develop, manufacture, and/or distribute small-molecule drug products, biotherapeu- tic products, and vaccines, as well as the drug substances and excipients used in these products. In this context, the value of the public quality standards published by the pharmacopoeias around the world can be explored. The Good Pharmacopoeial Practices (GPhP) guidance pub- lished by the World Health Organization states, "A pharmaco- poeia's core mission is to protect public health by creating and making available public standards to help ensure the quality of medicines" (8). The GPhP guidance continues, "Pharmaco- poeial monographs provide an important tool for assurance of the quality of marketed pharmaceutical ingredients and products through testing of their quality." These monographs are generally available for excipients, drug substances, and drug products, providing the tests, analytical procedures, and acceptance criteria that enable assessment of the quality of the material. Taken together with the other requirements contained in the pharmacopoeia, these monographs can help safeguard the health of patients around the world through the availability of public quality standards. The bio/pharmaceutical industry is focused on delivering quality products to patients. Earlier in this series of articles, the content of the pharmacopoeia was described with consid- eration of the impact of the pharmacopoeia throughout the lifecycle of a drug product (1). From a practical business per- spective, the value and benefit of the pharmacopoeia content to a specific company may vary based on the sector in which the company operates (e.g., innovator, generic-drug company, contract manufacturer) and the specific pharmacopoeia con- tent under discussion. General chapters. The general chapters in the pharmacopoeias provide a wide range of information, including analytical and biological procedures that are used to test materials and prod- ucts. It is broadly agreed these general chapters are beneficial for all bio/pharmaceutical companies because they facilitate product development, enabling greater focus on specific attri- butes that are critical to the quality of a material or product. These procedures, whether a simple test for loss on drying for an excipient, or a microbiological test for a drug substance, or a dissolution test for a tablet formulation, enable routine testing by providing details on how to perform the test and, in some cases, the applicable acceptance criteria. Importantly, the information in pharmacopoeia general chapters is broadly accepted as an appropriate quality standard by regulatory au- thorities around the world. Excipients. There is also general agreement across the indus- try regarding the value and benefit of having specific tests and acceptance criteria contained in monographs for excipients. From the perspective of excipient suppliers, the availability of a monograph provides a quality standard for the material that should be acceptable to multiple customers. For bio/phar- maceutical companies, the benefits include having multiple suppliers that can provide excipients meeting the same core requirements, simplifying the sourcing of these materials, and reducing the burden of laboratory assessments to determine comparability of materials from alternate sources. Excipient monographs also facilitate communication with health au- thorities regarding excipient quality attributes. Using compen- dial-grade excipients in drug products aligns with regulatory expectations for review and inspection, simplifying product registrations by allowing reference to the pharmacopoeia monograph as the standard of quality for the material. Refer- encing the monograph eliminates the need to include specific acceptance criteria, methodology, and validation information for the excipient in the drug product registration. Drug substances and products. Divergent perspectives begin to emerge across the industry when considering the value and benefit of specific monographs for drug substances and drug products. Monographs for small-molecule drug substances and products have long been established in the pharmaco- poeias, and the quality requirements in the monographs apply to both innovator and generic-drug companies alike. These monographs, however, do not typically become available until later in the drug product lifecycle. Indeed, the new drug sub- stances and products must first be discovered and developed by an innovator company, and the applicable monographs fol- low. The initial quality requirements are approved by health authorities as submitted in new drug applications. Generic drugs. As with the innovator company, drug sub- stance and product monographs are generally not available for those generic-drug companies that are first to enter the market; product development work is typically well underway before specific monographs are available for the materials. The