《上海CMC培训 Investigational and Marketing New Drug Applications in the U.S.》由会员分享，可在线阅读，更多相关《上海CMC培训 Investigational and Marketing New Drug Applications in the U.S.（35页珍藏版）》请在金锄头文库上搜索。
1、Investigational and Marketing New Drug Applications in the U.S.Chi-wan Chen, Ph.D. Pfizer, Inc.AAPS/CPA Workshop (CMC): Quality, Regulatory and Scientific Requirements and Strategies Shanghai, China June 28-29, 2010 OutlineHow is IND regulated in the U.S.? How is NDA regulated in the U.S.? CMC diffe
2、rences between INDs and NDAs FDA meetings with IND sponsors/NDA applicants Minimal vs enhanced, quality-by-design (QbD) approach to drug development and submission FDA CMC Pilot Program on QbD Comparability protocol Summary2What is an Investigational New Drug (IND) and How is it Regulated?Law: Food
3、Drug 10 months for standard NDAFDA review30 days for original IND and major amendment (to the same IND)4 months for prior approval, 6 for changes- being-effected, supplementNDA/BL A12What is a New Drug Application (NDA) and How is it Regulated?NDA is an application required by law for approval befor
4、e a new drug can be introduced into interstate commerce in the U.S. 3 types of NDAs under the law: 505(b)(1) An NDA containing full safety and effectiveness data Established in 1938 and 1962 505(b)(2) An NDA where some safety or effectiveness information is not from the applicant and for which the a
5、pplicant does not have the right of reference 1938 also known as generic drug Established in 198413What is an NDA and How is it Regulated*? (cont.)505 (b)(1) and (b)(2) NDAs are administratively categorized based on therapeutic potentials Priority NDA Application for a drug that, if approved, would
6、provide meaningful benefit, efficacy and/or safety, over existing therapies 6-month review clock Standard NDA All other applications not categorized as priority 10-month review clock* http:/www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm090410.htm 14What is an NDA and How is it Regulated? (cont.)Re
7、gulation: 21 CFR 314 21 CFR 314.50 Content and Format (d)(1) CMC Technical Section: Drug Substance, Drug Product Numerous guidances for industry on format and Content ICH Quality Guidelines apply M4Common Technical Document Q1A-EStability Q2Method Validation Q3A-CImpurities Q5A-EBiotechnology Q6A-BS
8、pecifications Q8(R2)Pharmaceutical Development Many MaPPs* for FDA internal processes* Manuals of Policies and Procedures15Original NDAs Filed in CDER*Fiscal year# Priority NDAs# Standard NDAsTotal # NDAs 20002992121 20011086 96 20021294 96 200319821012004*291001292005*29731022006*32901222007*n/an/a
9、124* http:/www.fda.gov/cder/rdmt/histnda.htm *Includes BLAs after therapeutic biologics were transferred from CBER to CDER16NDA Content - GeneralDescribed in Regulation (21 CFR 312.23) Many guidances and MaPPs Goals of the NDA are to provide enough information to permit FDA reviewer to reach the fol
10、lowing key decisions: Whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks Whether the drugs proposed labeling (package insert) is appropriate, and what it should contain Whether the methods used in manufacturing the drug and the cont
11、rols used to maintain the drugs quality are adequate to preserve the drugs identity, strength, quality, and purity17Format of Quality Section of ICH Common Technical Document (CTD)Module 2: Quality Overall Summary Module 3: Quality Section of CTD 3.1.3 Table of Contents 3.2 Body of Data 3.2.S Drug S
12、ubstance 3.2.S.1 General Information 3.2.S.2 Manufacture 3.2.S.3 Characterization 3.2.S.4 Control of Drug Substance 3.2.S.5 Reference Standards or Materials 3.2.S.6 Container Closure System 3.2.S.7 Stability 18Format of Quality Section of CTD (cont.)3.2.P Drug Product 3.2.P.1 Description and Composi
13、tion of the Drug Product 3.2.P.2 Pharmaceutical Development 3.2.P.3 Manufacture 3.2.P.4 Control of Excipients 3.2.P.5 Control of Drug Product 3.2.P.6 Reference Standards or Materials 3.2.P.7 Container Closure System 3.2.P.8 Stability 3.2.A Appendices 3.2.A.1 Facilities and Equipment 3.2.A.2 Adventit
14、ious Agents Safety Evaluation 3.2.A.3 Novel Excipients 3.2.R Regional Information (U.S.)19Electronic Filing and CTD-QRegulation 21 CFR part 11 (1997): Electronic Records; Electronic Signatures provides for voluntary submission of parts or all of records in electronic format without an accompanying p
15、aper copy Electronic NDA is accepted, but not required CTD-Q format is required for electronic NDAs Electronic IND is not yet accepted in CDER Guidances Providing Regulatory Submissions in Electronic Format - General Considerations Providing Regulatory Submissions in Electronic Format - Human Pharma
16、ceutical Applications and Related Submissions Using the eCTD Specifications20Drug Registration and NDA Review Timelines6 months for priority NDA; 10 months for standard NDAFDA review30 days for original IND and major amendment (to the same IND)4 months for prior approval, 6 for changes- being-effected, supplementDevelopm
