The Quality Overall Summary (QOS) is a summary that follows the scope and the outline of the Body of Data in Module 3. The QOS should not include information, data or justification that was not already included in Module 3 or in other parts of the CTD. The QOS should include sufficient information from each section to provide the Quality reviewer with an overview of Module 3. The QOS should also emphasize critical key parameters of the product and provide, for instance, justification in cases where guidelines were not followed. The QOS should include a discussion of key issues that integrates information from sections in the Quality Module and supporting information from other Modules (e.g. qualification of impurities via toxicological studies discussed under the CTD-S module), including cross-referencing to volume and page number in other Modules. This QOS normally should not exceed 40 pages of text, excluding tables and figures.

• International non proprietary names / INN
• Chemical names
• Synonyms
• CAS No

• Structural formula (relative and absolute chemistry)
• Molecular formula
• Molecular weight
• Molecular weight (base)

The PRH is responsible to confirm the availability of the following information:

• Physical form
• Solubility
• Melting point
• Hygroscopicity
• Polymorphism
• Particle size
• Isomerism
• Chirality
• pKa
• Partition coefficient (log P)
• pH
• Others

• Name and address of manufacturer that produced the API

*Not applicable to generics

Description of the drug substance manufacturing process and process control that represents the applicant’s commitment for the manufacture of the drug substances

*Not applicable to generics

• A flow diagram should be presented giving the steps of the process and showing where materials enter the process. 
• The critical steps and points at which process controls, intermediate tests or final product controls are conducted should be identified.

*Not applicable to generics

·     Raw materials, starting materials, solvents, reagents, catalysts and any other materials used in the manufacture of the drug substance

 *Not applicable to generics

·      Critical steps & process control including test and acceptance criteria (with justification including experimental data

·      Control of Intermediates: List of Intermediates, specification, analytical procedure

 *Not applicable to generics

Applicable to sterile API only (aseptic processing and sterilization)

*Not applicable to generics

·     Description and discussion of significant changes made to the manufacturing process and/or manufacturing site of the drug substance used in producing non-clinical, clinical, scale-up, pilot and if available, production scale batches.

·      The development history of the manufacturing process as described in S 2.2.

*Not applicable to generics

i)      Pharmacopoeial API:

Comparison of spectral data between pharmacopoeial reference standard & API(If comparison is not available, assess as per non-pharmacopoeial API). 

ii)   Non pharmacopoeial API:

•  Elemental analysis
•  Infrared Spectrophotometry (IR)
•  Ultraviolet absorption spectrum (UV)
•  Mass Spectrometry
•  Nuclear Magnetic Resonance Spectrometry (NMR); 1H-NMR, 13C-NMR
•  X-ray Diffraction
•  Differential Scanning Calorimetry (DSC)
•  Thermogravimetric analysis (TGA)
•  Others 

iii) Polymorphism

• Description & characteristics of various polymorphic forms
• Potential for formation of the polymorphic forms
• Stability of the polymorphic forms
• Evidence to prove the commercial scale process consistently produce desired polymorphic forms
• Particle size distribution
• Isomerism

 *Not applicable to generics

·    Summary of impurities monitored or tested for during and after manufacture of drug substance (Compendial requirements (if pharmacopoeial item) or appropriate information from the manufacturer (non-pharmacopoeial item)

Specification

• Detailed specification, tests and acceptance criteria
• Reference for the specifications (Compendial or Manufacturer’s)

*Not applicable to generics

• The analytical procedures used for testing of API should be provided in sufficient details to enable reproducible testing by another laboratory
• Compendial methods or appropriate information from the manufacturer

*Not applicable to generics

i)       Analytical validation information, including experimental data for the analytical procedures used for testing the API

ii)      Typical validation characteristics to be considered:

•        Selectivity
•        Precision(repeatability, intermediate precision and reproducibility)
•        Accuracy
•        Linearity
•        Range
•        Limit of Quantitation
•        Limit of detection
•        Robustness

iii)     Non- compendial method

• Description of batches and results of the analysis to establish the specification
• Information in table form e.g.: batch number, batch size, manufacturing date, manufacturing site and batch use (validation, stability, commercial etc.)

• COA of 2 current batches

*Not applicable to generics

• Discussion on inclusion/ omission of tests and analytical procedures
• Justification on range of acceptance criteria set for in-house tests

 *Not applicable to generics

·         Official reference standard used, with batch number

·         Primary reference standard used, with batch number

·         Working standard used, with batch number

·         CoA of Reference Standard 

 *Not applicable to generics

·        Description: primary packaging, secondary packaging, specifications

·      Non-functional secondary packaging components (e.g. those that do not provide additional protection nor serve to deliver the product) – only a brief description should be provided

·        Functional secondary packaging components (if applicable)

·        Suitability: Moisture and light, Compatibilty (e.g: Sorption or leeching)

*Not applicable to generics

i)      Stress Testing Study - API batch details (eg: moisture, light, acidic, basic, oxidative and thermal stress conditions).

ii)     Long Term Stability Data

•   Minimum of 1 batch, (with recent results)
•  Batch information (manufacturing date, site, batch size
• Temperature/RH/Packaging

iii)    Post-approval Stability Protocol and Stability Commitment