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Pharmaceutical Technology REGULATORY SOURCEBOOK MARCH 2020 19 the first such monograph adopted in 2015 (17). By contrast, the BP has long included monographs for small-molecule drug products, in addition to all the other content of the Ph. Eur. that is required for pharmacopoeia compliance in the United Kingdom. In the absence of an applicable Ph. Eur. monograph, compliance with BP drug product monographs is often the expectation of regulatory agencies throughout Europe and in many other countries around the world. For several practical and regulatory reasons, the BP drug prod- uct monograph, however, cannot usually be established until after the Ph. Eur. monograph has been developed for the drug substance. The pursuit of harmonized monographs has enabled concurrent development of Ph. Eur. drug sub- stance monographs and the associated BP drug product monographs. Alternatively, the product monograph may be established in the Ph. Eur. rather than the BP, with the Ph. Eur. product monograph then published also in the BP. These considerations enter the determination of when and where to submit the monographs for drug substances and their associated products. Turning to the other pharmacopoeias shown in Figure 1, the key take-away is that the appropriate time for mono- graph development is not consistently or precisely defined, but typically would occur after the USP, Ph. Eur., and BP monographs have been established, possibly by several years. For the Indian Pharmacopoeia (IP), there appears to be a correlation between the approval of two to three companies in India and the development of a monograph, although this is not entirely clear in the authors' experience. There seems to be a good deal of variability in the IP monograph timing, and in some cases, the IP monograph may be developed be- fore the USP, Ph. Eur., or BP monographs. For pharmacopoeias in other countries, including the Japanese Pharmacopoeia (JP), Korean Pharmacopoeia (KP), and ChP, there also seems to be some correlation with approval of several companies for a par- ticular drug product and the elaboration of a monograph. While this timing for IP, JP, ChP, and KP activity seems to decrease the possibility of developing harmonized monographs across several pharmacopoeias—monographs that could truly serve as global pharmacopoeia standards—there is clear interest and commitment by the pharmacopoeia authorities to collaborate with each other and with the industry to establish consistent public quality standards. Industry timing. The other timing perspective to consider for monograph development is that of an individual company, and this, in turn, may vary based on whether the company is in the innovator or generic sector of the industry (Figure 2). After an innovator company (Manufacturer 1 in Figure 2) receives regulatory approval for a new drug application containing a new chemical entity, there is a period of patent protection and marketing exclusivity during which the innovator is the single source for the product. During this time period, generic-drug companies begin to develop similar versions of the drug sub- stance and product, in terms of pharmaceutical and therapeutic equivalence. One goal is to become the first company (Manu- facturer 2 in Figure 2) to market a generic version of the product, realizing all the business benefits that accompany this position. Once the first generic version has been approved, which may occur perhaps 10–15 years after the innovator's approval, fol- lowed by the approval of other generic versions, potentially from many other companies around the world, the product situation changes to reflect this multi-source availability. Manufacturer … Manufacturer 3 Regulatory Approval Official Monographs (Drug Substance / Drug Product) Manufacturer 1 • Identity • Strength • Quality • Purity Prospective Manufacturer 2 • Identity • Strength • Quality • Purity Single-Source Product Multi-Source Product Harmonization Monograph Change Control? Regulatory Approval Figure 2. Monograph timing considerations for industry.