基于Question-Based Review的Quality Overall Summaries

beiwei5du

基于Question-Based Review的Quality Overall Summaries的相关questions

2.3 Introduction to the Quality Overall Summary

Proprietary Name of Drug Product

Non-Proprietary Name of Drug Product

Non-Proprietary Name of Drug Substance

Company Name

Dosage Form

Strength(s)

Route of Administration

Proposed Indication(s)

2.3.S    DRUG SUBSTANCE

2.3.S.1 General Information

What are the nomenclature, molecular structure, molecular formula, and molecular weight?

What are the physicochemical properties including physical description, pKa, polymorphism, aqueous solubility (as function of pH), hygroscopicity, melting points, and partition coefficient?

2.3.S.2 Manufacture

Who manufactures the drug substance?

How do the manufacturing processes and controls ensure consistent production of drug substance?

2.3.S.3 Characterization

How was the drug substance structure elucidated and characterized?

How were potential impurities identified and characterized?

2.3.S.4 Control of Drug Substance

What is the drug substance specification? Does it include all the critical drug substance attributes that affect the manufacturing and quality of the drug product?

For each test in the specification, is the analytical method(s) suitable for its intended use and, if necessary, validated? What is the justification for the acceptance criterion?

2.3.S.5 Reference Standards

How were the primary reference standards certified?

2.3.S.6 Container Closure System

What container closure system is used for packaging and storage of the drug substance?

2.3.S.7 Stability

What drug substance stability studies support the retest or expiration date and storage conditions for the drug substance?

2.3.P    DRUG PRODUCT

2.3.P.1 Description and Composition

What are the components and composition of the final product? What is the function(s) of each excipient?

Does any excipient exceed the IIG limit for this route of administration?

Do the differences between this formulation and the RLD present potential concerns with

respect to therapeutic equivalence?

2.3.P.2 Pharmaceutical Development

2.3.P.2.1 Components of the Product

2.3.P.2.1.1 Drug Substance

Which properties or physical chemical characteristics of the drug substance affect drug product development, manufacture, or performance?

2.3.P.2.1.2 Excipients

What evidence supports compatibility between the excipients and the drug substance?

2.3.P.2.2 Drug Product

What attributes should the drug product possess?

How was the drug product designed to have these attributes?

Were alternative formulations or mechanisms investigated?

How were the excipients and their grades selected?

How was the final formulation optimized?

2.3.P.2.3 Manufacturing Process Development

(If the Product is a NTI Drug or a Non-Simple Dosage Form)

Why was the manufacturing process described in 2.3.P.3 selected for this drug product?

How are the manufacturing steps (unit operations) related to the drug product quality?

How were the critical process parameters identified, monitored, and/or controlled?

What is the scale-up experience with the unit operations in this process?

2.3.P.2.4 Container Closure System

What specific container closure attributes are necessary to ensure product performance?

2.3.P.3 Manufacture

(For All Products)

Who manufactures the drug product?

What are the unit operations in the drug product manufacturing process?

What is the reconciliation of the exhibit batch?

Does the batch formula accurately reflect the drug product composition?  If not, what are the differences and the justifications?

What are the in-process tests and controls that ensure each step is successful?

(If Product is Not a Solution)

What is the difference in size between commercial scale and exhibit batch? Does the equipment use the same design and operating principles?

(If the Product is a NTI Drug or a Non-Simple Dosage Form)

In the proposed scale-up plan what operating parameters will be adjusted to ensure the product meets all in-process and final product specifications?

What evidence supports the plan to scale up the process to commercial scale?

2.3.P.4 Control of Excipients

What are the specifications for the inactive ingredients and are they suitable for their intended function?

2.3.P.5 Control of Drug Product

What is the drug product specification? Does it include all the critical drug product attributes?

For each test in the specification, is the analytical method(s) suitable for its intended use

and, if necessary, validated? What is the justification for the acceptance criterion?

2.3.P.6 Reference Standards and Materials

How were the primary reference standards certified?

2.3.P.7 Container Closure System

What container closure system(s) is proposed for packaging and storage of the drug product? Has the container closure system been qualified as safe for use with this dosage form?

2.3.P.8 Stability

What are the specifications for stability studies, including justification of acceptance criteria that differ from the drug product release specification?

What drug product stability studies support the proposed shelf life and storage conditions?

What is the post-approval stability protocol?

beiwei5du

Question-Based Review for CMC Evaluations of ANDAs

【讨论】QbR（Question-based Review）

beiwei5du

FDA 的仿制药品上市申请“问答式审评”质量评估体系简介
李雪梅, 　刘　璐
(国家食品药品监督管理局药品审评中心,北京100038)

• QbR White Paper
  

小金库

谢谢分享。