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U.S. Department of Health and Human Services

Drugs

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Office of Generic Drugs QbR Quality Overall Summary Outline

Questions to be completed by ANDA Sponsors for the preparation of a QbR-Quality Overall Summary

Pharmaceutical Product Quality: Question-based Review for ANDAs
Definition: Simple Dosage Form - Either a solution or an IR solid oral dosage form

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?