《FDA仿制药研发指南(原文 明胶软胶囊)》由会员分享，可在线阅读，更多相关《FDA仿制药研发指南(原文 明胶软胶囊)（8页珍藏版）》请在金锄头文库上搜索。
1、International Journal of Generic Drugshttp:/ International Journal 312of Generic Drugs e-? infolocumEURO.com ISSN 0793 694X US/Canada ISSN 0793 7784 EuroISSN 0793 7822 Pacific RimPRODUCT DEVELOPMENT GUIDE PRE-FORMULATION - SOFT GELATIN CAPSULES Introduction Guidelines for the development of a ANDA p
2、roduct for the US market, Note: some tests or procedures may be unnecessary. The order of performing the various stages may change depending on the product under development. These guidelines may be modified for other geographic zones. Development StageScope of Product DevelopmentStage 1Literature S
3、earch Literature ResearchUSP BP Pharm. Eur, PDR, Martindale, Merck, Florey, Vidal, Text and journals FDA - FOISummary Basis of Approval - On request form FDA On-line computerized searchFDA CDERElectronic Data Base (articles and publication on test methods, Dissolution synthesis procedures, drug impu
4、rities, pharmacokinetics and dynamics) Evaluation of Biostudy parameters, Dissolution methods.Patent evaluationOrange Guide + FDA CDER WWW Patent ConsultantStage 2 Active Sourcing Sourcing for Active Raw MaterialInternational Suppliers US, European, Asian, e.g. (ACIC- Canada) (AllChem-UK) (Lek-Czech
5、), (Esteves; Moehs; Uquifa-Spain); (Biopharma, S.I.M, Midy-Italy) (Chemcaps, Reddy; Tricon-India); (Federa-Brussels) - Review suppliers catalogs cotton and desiccants, blister packaging. Innovator Physical TestingPhysical testing Fill Weight Shell disintegration International PDRs (Italian, French,
6、Swiss) and Innovators products insert (obtain latest FOI -FDA) Perform actual analytical testing on innovators product. Microscopic observationParticle/crystal information on: Particle size, crystal shape, habit, rugosity Viscosity agents used (PVP 30 / 90) Presence of vegetable oil (type) Presence
7、of PEG 400 Presence of polyethylene glycol solventEvaluation of BiostudyReview FDA CDER Home page for listing and Biostudy parameters Dissolution profileUSP monograph and FDA method - (where present) Dissolution; 12 unit Dissolution Profile. Stage 8Bulk Active Testing FIRST BATCH FROM APPROVED SUPPL
8、IER Full Physical characterizationPhysical characterization of bulk batch Polymorphism B.E.T. Particle size distribution ( Dissolution ; Content Uniformity completed prior to Process Qualification PROCESS OPTIMIZATION DevelopmentScope of Product Development Stage 14Process Optimization GEL mixing ti
9、me ; propeller position Fill material uniformity Ribbon Thickness adjustments for correct shell weights (once per shell formula) Seal Thickness (once per shell formula NLT 0.006“)1 Wet Shell Weight variation ( 8%)1 Fill Weight variation ( 2%)1 1 Process capability performed. DRYING Drying time tempe
10、rature versus shell moisture (in rotary dryer) Primary drying time versus shell moisture (in tray dryer) Secondary drying time versus shell moisture (in tray dryer) Bareiss hardness versus drying times. Softgel properties (Fill weights and Content Uniformity). Evaluation of Fill weight Range Limits
11、(Qualification) Evaluation of stability results of optimized mfg. Process. Printing Inspection Limits PROCESS OPTIMIZATION REPORT (PO)Prepare PO Report. This Process Optimization Report forms part of the product Development ReportInternational Journal of Generic Drugshttp:/ International Journal 316
12、of Generic Drugs e-? infolocumEURO.com ISSN 0793 694X US/Canada ISSN 0793 7784 EuroISSN 0793 7822 Pacific RimESTABLISHING AND INVITRO INVIVO CORRELATION DevelopmentScope of Product DevelopmentStage 15Analytical Evaluation IVIV Correlation (search literature) Dissolution - in USP medium (Multipoint p
13、rofiles) and other relevant media versus Innovators product. Dissolution testing may not be possible where active strength is in micrograms (i.e. 0.25 or 0.5 mcg) Perform IVIV Bioavailability Study (where relevant)BSC SystemIVIVC1 : 1 CorrelationDissolution settingsPlasma parametersDevelopers are en
14、couraged to develop IVIVC for IR dosage forms, where applicable to the BCS, (Biopharmaceutical Classification System) in the expectation that the information will be useful in establishing appropriate dissolution specifications and thus permit certain post approval formulation and manufacturing chan
15、ges to be effected, - without additional bioequivalence studies. The objective of developing an IVIVC is to establish a predictive mathematical model describing the relationship between invitro dissolution settings and the actual invivo drug-plasma parameters found, (such as AUC, Cmax, Tmax). The in
16、vitro dissolution settings are adjusted (via media, pH agitation) until a I : I correlation is achieved (Level A) or a single dissolution point and a plasma parameter is shown to correlate (Level C). When more than one point correlates a multiple Level C is obtained - which may possibly be upgraded to a Level A with additional development work. This matching of dissolution settings with plasm
