Diclofenac Sodium

精彩内容 第十一批集采文件终于出炉，将于10月21日开标。近几年在“国谈+集采”轮番施压下，200亿抗炎药和抗风湿药市场跌宕起伏，2025上半年止跌回升3.16%，正大制药“3连涨”挺进TOP2集团，32个品牌上榜两大TOP20榜单，独家注射剂暴涨335%。前十批集采已累计有15个抗炎药和抗风湿药中标，第十一批集采瞄准3.4亿热销注射剂，石家庄四药、华海药业、华东医药等20多家国内药企将出战。 200亿市场止跌回升，正大制药首进TOP2集团 在中国三大终端六大市场（统计范围见文末），抗炎药和抗风湿药的销售规模在2023-2024年保持在200亿元以上，2025上半年止跌回升3.16%，达104.9亿元。 表1：2025上半年中国三大终端六大市场抗炎药和抗风湿药TOP5集团（一级） 来源：米内网格局数据库 先声药业的抗炎药和抗风湿药从2021年起保持着双位数增长，2024年拿下超17亿元的销售成绩，并首次登上了TOP1集团（一级）宝座，2025上半年蝉联榜首，增长率为25.75%。 图1：正大制药的抗炎药和抗风湿药销售情况（单位：万元） 来源：米内网格局数据库 正大制药的抗炎药和抗风湿药在2021-2022年经历低迷时期，2023年起恢复高速增长态势，2023-2025上半年的增长率分别为52.48%、36.52%、18.48%，2025上半年首次升上TOP2集团（一级）。 第十一批集采来了，20多家药企决战3.4亿注射剂 9月20日，第十一批集采文件出炉，本次涉及的抗炎药和抗风湿药为氯诺昔康注射剂（8mg）。文件指出，属于采购品种范围，需在9月28日（含）前获得国内有效注册批件，预计在10月21日开标。 图2：氯诺昔康注射剂（8mg）的销售情况（单位：万元） 来源：米内网格局数据库 米内网数据显示，目前国内已上市的氯诺昔康注射剂为注射用氯诺昔康，规格均为8mg，用于急性中度手术后疼痛以及与急性腰部、坐骨神经相关的疼痛。在中国三大终端六大市场，该产品2023年的销售峰值为3.7亿元，2024年微降至3.4亿元，2025上半年恢复正增长7.03%，是抗炎药和抗风湿药注射TOP1产品。截至目前，该产品的过评企业达22家（按二级集团统计）。 表2：氯诺昔康注射剂集采相关信息 来源：上海阳光医药采购网，米内网制表 据第十一批集采文件，氯诺昔康注射剂（8mg）的最高有效申报价为6.0415元/支，全国首年机构需求量合计超过2837万支，预计该产品的集采规模在1.7亿元以上。 22家二级集团中，浙江震元制药、哈三联、天马医药天吉生物早前已是氯诺昔康注射剂（8mg）的领先企业，本次的全国首年机构需求量排在前三位，其中浙江震元制药高达1174万多支，遥遥领先。 其余19家均为2024年及2025年按新分类视同过评，其中石四药本次的全国首年机构需求量排在第四，超过80万支，华海药业和华东医药分别也有超过37万支、18万支的需求量，“光脚企业”也可借助集采之力，快速带来销售增量。 值得注意的是，该产品未指定厂牌的全国首年机构需求量也有375万多支，9月28日前获批的企业依然有机会分一杯羹。 32个品牌大卖，独家注射剂暴涨335%，恒瑞、苑东、国药发威 在中国城市公立医院、县级公立医院、城市社区中心及乡镇卫生院（简称中国公立医疗机构）终端，抗炎药和抗风湿药的销售规模在2019年达到峰值164亿元，随后集采持续施压，市场跌宕起伏，2024年跌至134亿元，2025年上半年回升2.84%，达68.6亿元。 表3：2025上半年中国公立医疗机构终端抗炎药和抗风湿药TOP20品牌 来源：米内网中国公立医疗机构终端竞争格局 2025上半年中国公立医疗机构终端抗炎药和抗风湿药TOP20品牌合揽接近40亿元，独家产品有4个，其中江苏恒瑞医药的艾瑞昔布片、南京正科医药的右酮洛芬氨丁三醇注射液、云南昊邦制药的草乌甲素片有正增长。 图4：江苏恒瑞医药的艾瑞昔布片销售情况（单位：万元） 来源：米内网中国公立医疗机构终端竞争格局 艾瑞昔布片是江苏恒瑞医药在2011年获批的国产1.1类新药，用于缓解骨关节炎的疼痛症状。在中国公立医疗机构终端，艾瑞昔布片2014-2021年一直保持高速增长态势，2021年销售额高达9.3亿元，2022年微跌5%，2023年起恢复正增长，2024年涨至9.9亿元，2025上半年增长率为1.09%，品牌排名上升1位至TOP2，全年将冲击10亿元关口。 图5：南京正科医药的右酮洛芬氨丁三醇注射液销售情况（单位：万元） 来源：米内网中国公立医疗机构终端竞争格局 南京正科医药在2023年5月拿下了右酮洛芬氨丁三醇注射液的国内首仿+首家过评，作为阿片类镇痛药的辅助，用于成人不适合口服给药的急性中度至重度术后疼痛，该产品在2023年底顺利进入国家医保谈判目录。在中国公立医疗机构终端，右酮洛芬氨丁三醇注射液2024年的销售额已突破1.3亿元，2025上半年增长率为335.43%，品牌排名上升10位至TOP9，成为了抗炎药和抗风湿药市场新黑马。 8个非独家品牌在2025上半年有正增长，其中海南先声药业的艾拉莫德片增长了25.38%，蝉联销冠；金华康恩贝生物制药的汉防己甲素片增长了17.15%，品牌排名上升1位至TOP6；浙江诚意药业的盐酸氨基葡萄糖胶囊增长了19.24%，品牌排名上升1位至TOP8；浙江震元制药的注射用氯诺昔康增长了18.48%，品牌排名继续在TOP16；成都苑东生物制药的依托考昔片增长了6.52%，品牌排名继续在TOP17。 表4：2025上半年中国零售药店终端抗炎药和抗风湿药TOP20品牌 来源：米内网中国零售药店终端竞争格局 在中国城市实体药店和网上药店（简称中国零售药店）终端，抗炎药和抗风湿药的销售规模从2021年起高速增长，2023-2024年均超过70亿元，2025年上半年继续稳步增长，增长率为3.78%。 2025上半年中国零售药店终端抗炎药和抗风湿药TOP20品牌合揽超过24亿元，独家产品仅有赞邦的精氨酸布洛芬片，增长率为16.67%，品牌排名上升4位至TOP12。 12个非独家品牌在2025上半年有正增长，其中江苏正大清江制药的盐酸氨基葡萄糖片增长了46.74%，品牌排名继续为TOP3；海南先声药业的艾拉莫德片增长了29.76%，品牌排名继续为TOP6；上药中西制药的硫酸羟氯喹片增长了3.88%，品牌排名为TOP10；四川绿叶制药的盐酸氨基葡萄糖片增长了56.03%，品牌排名上升6位至TOP19；国药致君(深圳)坪山制药的双氯芬酸钠缓释片增长了8.97%，品牌排名为TOP20。 资料来源：米内网数据库、上海阳光医药采购网等 注：米内网《中国三大终端六大市场药品竞争格局》，统计范围：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至9月25日，如有疏漏，欢迎指正！ 免责声明：本文仅作医药信息传播分享，并不构成投资或决策建议。本文为原创稿件，转载文章或引用数据请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092 【分享、点赞、在看】点一点不失联哦

CDER Researchers have been investigating how pharmacokinetic (PK) modeling can support a determination of bioequivalence (BE) for topical drug products. In the case of a generic diclofenac sodium topical gel, 1%, CDER found that physiologically based pharmacokinetic (PBPK) modeling supported an alternative BE approach that does not include a comparative clinical endpoint BE study. The abbreviated new drug application (ANDA) that was approved using this approach is a significant milestone for the Generic Drug User Fee Amendments (GDUFA) regulatory research program that is supported by FDA. Locally acting drug products deliver their active ingredient at or near the site of action which may be in or on the body. These products include, for example, orally inhaled, nasal, ophthalmic, and topical drug products applied directly to the skin and oral products that act locally in the gastrointestinal tract . 1 To demonstrate BE between a brand name product (reference) and its generic (test), there must be an “absence of significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study. ”2 FDA’s recent approval of generic diclofenac sodium topical gel, 1%, was a successful example of PBPK modeling supporting an alternative BE approach for an ANDA. This is the first time a virtual BE assessment leveraging dermal PBPK modeling and simulation supported a “totality of evidence” BE approach that led to drug approval. The decision to approve this generic drug was based on 1) qualitative and quantitative sameness and physical and structural similarity to the reference product, 2) an in vivo BE study with PK endpoints, and 3) a virtual BE assessment leveraging dermal PBPK modeling and simulation instead of a comparative clinical endpoint study in patients. Evidence from additional PBPK modeling and simulation activities conducted by CDER assessors bridged the gap between the in vitro evidence for comparable (upstream) bioavailability through the skin and the in vivo evidence for comparable (downstream) bioavailability in the systemic circulation so that a comparative clinical endpoint study was not needed. The Scientific Challenge Establishing BE for topical drug products by conducting comparative clinical endpoint studies can be costly, and the studies may not be sufficiently sensitive to detect certain formulation differences. Quantitative methods and modeling (e.g., PBPK) can support alternative BE approaches with reduced or no human testing. However, to be used for regulatory decision-making, these mathematical models need to be sufficiently verified and validated (V&V) for their intended purpose. Verification and Validation of a Dermal PBPK model for Diclofenac Sodium Topical Gel, 1% For this ANDA, the applicant implemented an innovative two-level approach for verifying and validating the fit-for-purpose dermal PBPK model developed for diclofenac sodium topical gel, 1%. Briefly, the first level V&V focused on assessing the performance of the developed models for topical products with diclofenac sodium as the active pharmaceutical ingredient (API). The dermal PBPK model for diclofenac sodium topical gel, 1%, incorporated product-specific formulation attributes generated by the applicant as part of its product characterization program and was validated leveraging clinical PK data supporting the ANDA submission. The second-level V&V aimed at assessing the performance of the computational platform that was used (i.e., the Multi-Phase Multi-Level Mechanistic Dermal Absorption model within the Simcyp® Simulator, version 17). The performance of the platform was evaluated by the ANDA applicant and CDER assessors validating a significant number of PBPK models for dermatological products using published data. The dermal PBPK models supporting the second-level validation included dermatological products with APIs other than diclofenac sodium, as these were covered under the first-level validation. The overview of the model validation process is presented in Figure 1. Figure 1. Overview of the V&V methodology proposed by the applicant in support of their fit-for-purpose dermal PBPK models for Voltaren topical gel, 1% (reference, R) and for the generic diclofenac sodium topical gel, 1% (test, T). Published literature sources 3-7 were used by the applicant and the Agency to validate the dermal PBPK models developed for diclofenac sodium topical drug products, including models for solution and gel (emulsion) formulations. Simulation scenarios captured model performance following a single or multiple product application. Model predictions were generated for a range of applied doses at multiple application sites (e.g., the back and the knee) and were compared with empirical data. The applicant validated their product-specific models developed for the reference and the test products by using an independent dataset of the in vivo BE study with PK endpoints that were generated in support of the ANDA. The model was developed based on a “bottom-up” approach. Although sensitivity analysis-guided parameter optimization may have resulted in improved model predictions when compared to observed data extracted from the in vivo BE study with PK endpoints supporting the ANDA, additional modeling work conducted internally by CDER assessors showed that the BE outcome would not be impacted by modest changes in certain model parameters. As shown in Figure 2, the population predictions for the reference and test drug products were informed by the differing formulation attributes (such as apparent viscosity, formulation pH and oil droplet distribution among others) and the variability assigned to model parameters (physiology, PK, and drug product parameters) within the Simcyp® Simulator. The two products were found to be bioequivalent. How does this research improve generic drug development and support their approval? CDER encourages applicants for generic drug products to consider novel quantitative tools as described in Agency guidances, draft guidances, and product specific guidances when submitting their ANDAs. Recently, a PBPK modeling and simulation approach for a generic diclofenac sodium topical gel, 1%, supported an alternative BE approach in lieu of the comparative clinical endpoint BE study recommended in the product-specific guidance. This led to the first ANDA approval for which a PBPK model supported the BE assessment and approval of a generic topical gel. The applicant utilized the pre-ANDA Program to obtain the Agency’s feedback on the proposed alternative BE approach, which the applicant incorporated in their original submission. In this case, the Agency was able to review and approve the generic diclofenac sodium topical gel, 1%, in the first review cycle of this ANDA. Outcome FDA approved a generic diclofenac sodium topical gel, 1%, under ANDA 211253 during its first review cycle. This was the first ANDA approval for which a PBPK model supported the BE assessment. The capability of the model to generate local and systemic diclofenac exposure predictions following the application of topical products that were sensitive to formulation differences was adequately validated. The development and enhancements of the modeling platform (i.e., Multi-Phase Multi-Level Mechanistic Dermal Absorption model within the Simcyp® Simulator) used for the development and V&V of the proposed model and the in vitro characterization-based BE methods were partially supported by GDUFA I and GDUFA II research grants. The applicant utilized the pre-ANDA program to obtain the Agency’s feedback on their alternative to the BE approach as found in the FDA’s Draft Guidance on Diclofenac Sodium , which was incorporated in the final ANDA submission. Final approval of the generic diclofenac sodium topical gel, 1%, provides a successful example of the utilization of novel quantitative modeling tools which were researched and published by FDA towards an alternative BE approach for topical generic drug products leading to an ANDA approval. The benefit of applying PBPK models to support regulatory decision-making, especially for locally acting products, warrants further investment, collaboration and joint effort from the Agency, industry, and academia. This Impact Story is based on: Tsakalozou E, Babiskin A, Zhao L. Physiologically-based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1. CPT Pharmacometrics Syst Pharmacol. 2021 May;10(5):399-411. doi: 10.1002/psp4.12600. Epub 2021 Mar 9. PMID: 33547863; PMCID: PMC8129718. This approval would not have been possible without the efforts of staff in the Office of Generic Drugs and Office of Pharmaceutical Quality in the development of in vitro characterization methods for topical products, the assessment of the data submitted in the ANDA and the integrated conclusion about the acceptability of the BE evidence. References Lionberger RA. FDA critical path initiatives: opportunities for generic drug development. AAPS J. 2008; 10: 103– 109. CFR. - Code of Federal Regulations Title 21, Volume 5, Revised as of April 1, 2019. Available from CFR - Code of Federal Regulations Title 2 1 (fda.gov)  [Accessed 10/27/2021] Radermacher J, Jentsch D, Scholl MA, Lustinetz T, Frolich JC. Diclofenac concentrations in synovial fluid and plasma after cutaneous application in inflammatory and degenerative joint disease. Br J Clin Pharmacol. 1991; 31: 537– 541. Brunner M, Davies D, Martin W, Leuratti C, Lackner E, Muller M. A new topical formulation enhances relative diclofenac bioavailability in healthy male subjects. Br J Clin Pharmacol. 2011; 71: 852– 859. Dehghanyar P, Mayer BX, Namiranian K, Mascher H, Muller M, Brunner M. Topical skin penetration of diclofenac after single- and multiple-dose application. Int J Clin Pharmacol Ther. 2004; 42: 353-359 Sioufi A, Pommier F, Boschet F, Godbillon J, Lavoignat D, Salliere D. Percutaneous absorption of diclofenac in healthy volunteers after single and repeated topical application of diclofenac Emulgel. Biopharm Drug Dispos. 1994; 15: 441– 449. Seth BL. Comparative pharmacokinetics and bioavailability study of percutaneous absorption of diclofenac from two topical formulations containing drug as a solution gel or as an emulsion gel. Arzneimittelforschung. 1992; 42: 120– 122. Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. 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