**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?