China NMPA Drug Regulatory Framework Reform
Speaker: Yang Meng Center for Drug Evaluation, National Medical Product Administration(NMPA)

Agenda

I. Organization
II. Main Drug Regulations in China
III. Drug Regulatory framework Reform
IV. Challenges and Future Perspectives

II. Regulations by NMPA

Laws:
-Drug Administration Law of the PRC(2015 amendment)
-Implementation Rules of the Drug Administration Law of the PRC
Many regulations including:
-Drug Registration Regulation
Two main types of guidance:
-Generally clarifications of policy-e.g.
-technical standards.
All posted on NMPA’s website
Be noted that product quality needs to meet with those standards in Chinese Pharmacopeia

III. Drug Regulatory Reform: Clearing Backlog

Creating an efficient process to clear the severe registration backlog of drug applications
-roughly form 2015 to the end of 2017
-increased the drug registration fee
-mandated self-examination and inspection of clinical data
-identification of redundant generic applications
-rejection of deficient applications

III. Drug Regulatory Reform: Encouraging Innovation

Encouraging innovation
-MAH (Doc. 44 & 42)
-Approval process acceleration
-Clinical trial management
-Lifecycle management
-Intellectual property protection: exploring a drug patent linkage system, initiating a patent term restoration pilot programme, implementing a clinical trial data protection system
-China’s joining the International Conference on Harmonization

III. Drug Regulatory Reform: Encouraging Innovation

Encouraging innovation
-MAH (Doc. 44 & 42)
-Approval process acceleration
-Clinical trial management
-Lifecycle management
-Intellectual property protection: exploring a drug patent linkage system, initiating a patent term restoration pilot programme, implementing a clinical trial data protection system
-China’s joining the International Conference on Harmonization

Optimize the Procedures for IND/NDA Approval
– 60 working days for the approval timelines of IND, 150wds for NDA
– Ph 1 trial is allowed in China to enable China joining global simultaneous development
– Review based registration test and inspection
– One CTA approval is valid for Phase I, II and III trials
– CHANGE MANAGEMENT based on risk assessment
– A linked review and approval regime(similar to US DMF)for API, excipients and packaging materials with DP application together

Accelerate Review and Approval of Drugs In Urgent Medical Needs
– Implement the priority review and approval: AIDS, Tuberculosis, Viral hepatitis, Rare disease, Malignant tumor, Pediatric, Diseases with high incidence or unique in elderly people
– Conditional Approval to Meet the Medical Need,e.g., orphan drugs, innovative drugs targeting life threatening diseases without effective therapies
– CPP is no longer required for NDA submission: would shorten China approval gap with US/EU.

Guidelines for Acceptance of Overseas Clinical Trial Data
– Foreign data can be accepted if the data package meets China’s regulatory requirements:
– For Approved overseas orphan drugs and those drugs which are effective in treating life threatening diseases without any current available treatment in China , sponsors could submit NDA applications directly (they needn’t first submit an IND application ) , if it has been proven to be effective among all races and ethnic groups.This process is Not suitable for vaccines.
– For an NDA registration of drugs being developed Globally Simultaneously, sponsors should submit an unabridged clinical trial data package that contains all of the clinical trial data obtained from all regions, both in china and overseas.
Changes management based on risk assessment – CFDA published Guideline for Site Changes to An Approved NDA/ANDA (draft for comments )

ICH guidance alignment/Integration
– CFDA held several meetings and seminars to discuss the applicability of ICH guidelines, find controversial articles, by comparing CHINA’s current drug regulations, Chinese pharmacopeia and guidelines.
– CFDA decided to apply five ICH secondary guidelines, namely M4, E2A, E2D, M1, E2B(R3)
– We Encourage applicants to submit their application dossier in CTD form, in addition we held many lectures about M4
– We Invited foreign pharmaceutical companies, to introduce Q12, as it is related to QbD, and continuous manufacture

CAR-T CMC Requirements
-CAR design : costimulatory domains, scFvaffinity
-Quality of T cells: T cell subsets, vectors, culture condItions
-Host Specific Factors : TME, ICMs, Tumor heterogeneity
-Quality Control:
-plasmid: DNA sequencing, concentration , DNA homogeneity, HOST CHROMOSOMAL DNA, host RNA, host protein, residual antibiotics
-virus vector: CAR gene identify, host DNA, host protein, BSA, size distribution of residual DNA, viral titer
-CAR-T: CAR expression, cell viability, CAR+T cells, CD3+ T cells, residual beads, in vitro IFN-gamma secretion, sterility, replication competent lentivirus

IV. Challenges

• Globalization: Global simultaneous development
• New technologies & new methods
• ICH guidance alignment/Integration
• Drug life cycle management, e.g., drug withdrawal system building
• Drug Accessibility, encouraging development of biosimilars

↓↓↓↓請點擊廣告鼓勵我們付出,謝謝!!

廣告