Development of generic drug product by pharmaceutical industry is a scientific and technical approach which is totally different from developing a reference or innovator product. Most of the developing countries focus...Development of generic drug product by pharmaceutical industry is a scientific and technical approach which is totally different from developing a reference or innovator product. Most of the developing countries focus on developing the generic drug products because huge amount of investment is required for innovation and to develop reference product. The generic medicine has to be bioequivalent to the innovator drug and ensure the same biological effect with proper safety and efficacy. Nowadays, the pharmaceutical industries focus on the development of generic product as this does not require that much time and cost compared to the innovator company. But development of generic product is also difficult as it contains the same therapeutic efficacy as innovator. The development approach is based on the target market, i.e. US market, EU market. If a manufacturer targets the US market, then all excipients should be USP grade, analysis should be conducted by USP method or in-house method and stability studies as well. Prior and during the development of generic drug product API selection, dosage form selection, reference product selection and characterization, formulation development, analytical method development, tech transfer or submission batch are prime concern. Then again, bioequivalence study, drug registration procedure and commercialization of the generic product considering regulatory guidance of respective regulatory agencies and the approaches taken by the regulatory agencies for the development of registration of generic medicines are also crucial as well for the development of generic drug product. The aim of this study was to review the entire stage of a generic drug development by a generic pharmaceutical company.展开更多
The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of ago...The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C m of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C-max of 7-desmethyl-agomelatine and 3-hydroxyagomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log transformed ratios of C-max, AUC(0-t), and AUC(0-infinity) of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C-max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
The Approved Drug Products with Therapeutic Equivalence Evaluations(commonly known as the Orange Book)includes the products approved by Food and Drug Administration(FDA)to be marketed in the USA,and it is an essential...The Approved Drug Products with Therapeutic Equivalence Evaluations(commonly known as the Orange Book)includes the products approved by Food and Drug Administration(FDA)to be marketed in the USA,and it is an essential source for the selection of suitable reference listed drugs(RLD)for a chemical generic medicinal product.The Orange Book assigns a therapeutic equivalence(TE)evaluation code for approved multisource prescription drug products to serve as public information in the area of medicinal product selection.In the present study,we introduced the TE coding system and its influence on the selection of the RLD in China by taking the Topiramate Extended-release Capsules as an example.As a result,it was suggested to determine its TE evaluation code in the Orange Book previously when we choose an RLD and select suitable RLD the first letter of whose TE evaluation code is A to carry out the research and development of a generic medicinal product,which can improve the probability of success of clinical bioequivalence(BE)test and reduce the risk of generic medicinal product development.展开更多
文摘Development of generic drug product by pharmaceutical industry is a scientific and technical approach which is totally different from developing a reference or innovator product. Most of the developing countries focus on developing the generic drug products because huge amount of investment is required for innovation and to develop reference product. The generic medicine has to be bioequivalent to the innovator drug and ensure the same biological effect with proper safety and efficacy. Nowadays, the pharmaceutical industries focus on the development of generic product as this does not require that much time and cost compared to the innovator company. But development of generic product is also difficult as it contains the same therapeutic efficacy as innovator. The development approach is based on the target market, i.e. US market, EU market. If a manufacturer targets the US market, then all excipients should be USP grade, analysis should be conducted by USP method or in-house method and stability studies as well. Prior and during the development of generic drug product API selection, dosage form selection, reference product selection and characterization, formulation development, analytical method development, tech transfer or submission batch are prime concern. Then again, bioequivalence study, drug registration procedure and commercialization of the generic product considering regulatory guidance of respective regulatory agencies and the approaches taken by the regulatory agencies for the development of registration of generic medicines are also crucial as well for the development of generic drug product. The aim of this study was to review the entire stage of a generic drug development by a generic pharmaceutical company.
基金supported by the National Natural Science Foundation of China(No.81102499)Hunan Science and Technology Project(No.2011SK3261)+1 种基金the Fundamental Research Funds for the Central Universities of Central South University(No.2014zzts313)the support from Chongqing Fu An Pharmaceutical Group Qingyutang Pharmaceutical Co.,Ltd
文摘The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C m of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C-max of 7-desmethyl-agomelatine and 3-hydroxyagomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log transformed ratios of C-max, AUC(0-t), and AUC(0-infinity) of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C-max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
基金Carry out quality evaluation research of generic medicinal product control based on domestic product,NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,Beijing,China。
文摘The Approved Drug Products with Therapeutic Equivalence Evaluations(commonly known as the Orange Book)includes the products approved by Food and Drug Administration(FDA)to be marketed in the USA,and it is an essential source for the selection of suitable reference listed drugs(RLD)for a chemical generic medicinal product.The Orange Book assigns a therapeutic equivalence(TE)evaluation code for approved multisource prescription drug products to serve as public information in the area of medicinal product selection.In the present study,we introduced the TE coding system and its influence on the selection of the RLD in China by taking the Topiramate Extended-release Capsules as an example.As a result,it was suggested to determine its TE evaluation code in the Orange Book previously when we choose an RLD and select suitable RLD the first letter of whose TE evaluation code is A to carry out the research and development of a generic medicinal product,which can improve the probability of success of clinical bioequivalence(BE)test and reduce the risk of generic medicinal product development.
