2024年3月17日发(作者：easyrecovery绿色版)

2.3

EXAMPLE QUALITY OVERALL SUMMARY

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Introduction to the Quality Overall Summary

Proprietary Name of Drug Product:

Non-Proprietary Name of Drug Product: Ersatzine Tablets, USP

Non-Proprietary Name of Drug Substance: Ersatzine

Company Name: ANDA Sponsor

Dosage Form: Immediate Release Tablets

Strength(s): 2 mg

Route of Administration: Oral

Proposed Indication(s): Depression

2.3.S DRUG SUBSTANCE

2.3.S.1 General Information

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

weight?

Chemical Name:

CAS #:

USAN:

[full chemical name]

[CAS#]

Ersatzine

[chemical structure]

C

x

H

y

O

z

N

300

Molecular Structure:

Molecular Formula:

Molecular Weight:

What are the physicochemical properties including physical description, pKa,

polymorphism, aqueous solubility (as function of pH), hygroscopicity, melting points, and

partition coefficient?

Physical Description: Ersatzine is a white, crystalline powder, practically insoluble in water at

pH 7.0, freely soluble in methylene chloride, sparingly soluble in acetone and alcohol.

pKa: The pKa of the secondary amine group in Ersatzine is 5.5.

Polymorphism: There are two anhydrous polymorphic forms, Forms I and II, and no known

hydrate forms. Form I is the most stable form and is used for the manufacture of the drug product.

Form I and II can be produced by crystallization from ethanol at different cooling rates.

Solubility Characteristics: The aqueous solubility as a function of pH at 37º C is:

This Quality Overall Summary does not contain real data and information and is meant only to demonstrate

examples of information/data/tests that may be used for scientific & regulatory justification of a drug product.

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Solvent Media

0.1 N HCl, pH 1.2

0.15 M acetate buffer, pH 3.0

0.15 M acetate buffer, pH 4.5

0.15 M phosphate buffer, pH 6.8

Solubility Form I

0.10 mg/ml

0.09 mg/ml

0.011 mg/mL

(< 0.001 mg/ml)

Solubility Form II

0.40 mg/mL

0.40 mg/mL

0.033 mg/mL

(< 0.001 mg/ml)

Calculated dose solubility volume: 2 mg (highest strength)/(0.001 mg/mL) = 2000 mL > 250 mL.

Therefore, Ersatzine is considered a low solubility according to the Biopharmaceutics

Classification System (BCS).

Hygroscopicity: Water uptake for the drug substance was less than 0.1% by weight after one

week at 25ºC/75±5% RH. (Details in 3.2.P.2.1.1)

Melting Point: The melting point of Form I and Form II are 225 ºC and 210 ºC, respectively.

Partition Coefficient: ClogP = 4.251.

2.3.S.2 Manufacture

Who manufactures the drug substance?

Drug Substance Maker Ltd (DMF nnnn)

111 Main Street

City 1, County 2

How do the manufacturing processes and controls ensure consistent production of the

drug substance?

Refer to DMF nnnn for information regarding chemistry manufacturing and controls used in the

production of Ersatzine. DMF holder for Ersatzine has proposed validated methods that are

suitable for stability-indicating purposes, and has documented stability data for the drug

substance.

2.3.S.3 Characterization

How was the drug substance structure elucidated and characterized?

For full details regarding proof of Ersatzine’s structure, based upon spectroscopy, analytical

testing, and inference from synthetic route refer to DMF nnnn.

How were potential impurities identified and characterized?

For full details regarding the characterization and identification of impurities refer to DMF nnnn.

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?

A summary of drug substance tests, analytical procedures, acceptance limits and results for the

drug substance batch (Lot #15531) (COAs located in 3.2.S.4.4) used for the manufacturing of the

submission batch (Lot #9A) is given in the table below.

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