Quality by Design for Generics - Case Studies

The Generic Pharmaceutical Association (GPhA, USA) has published two extensive and very interesting "Case Studies" for the application of Quality by Design (QbD) for ANDAs; the first for "Immediate-Release Dosage Forms" and the second for "Modified Release Dosage Forms".

In this way, the GPhA wants to show how generic drug manufacturers - subject to the ANDA authorisation (ANDA = Abbreviated New Drug Application) in the USA - can implement QbD.

These examples are indented to present in detail what pharmaceutical development studies generic manufacturers should perform for the implementation of QbD. Together with this approach, the discussion with FDA's Office of Generic Drugs (OGD) should be encouraged. Both Case Studies merely serve as example. Other possibilities may be considered or even required in the pharmaceutical development practice.

The document "QbD for ANDAs: An Example for Immediate-Release Dosage Forms" is composed of 69 pages and presents a pharmaceutical development report about the fictive product "Acetriptan 20 mg tablets". Among other things, following points are presented:

  • Analysis of the Reference Listed Drug (RLD) Product

  • QTPP (Quality Target Product Profile) for the ANDA Product - as a table

  • Risk Assessment of Potential Impact of API Attributes on Drug Product CQAs (Critical Quality Attributes)

  • Identification of Critical Process Parameters

  • Scale Up of the Blending, Compaction and Compression Processes, etc. 

  • Control Strategy

The Quality Target Product Profile (QTPP) contains all product attributes which are required to ensure equivalent safety and efficacy of the generic drug product compared to the original one.

Some of the elements of the QTPP might change during pharmaceutical development as more information is learned about the product. What results at the end of development is not a final QTPP but a control strategy with the corresponding specifications for the marketing authorisation of the generic drug product. The critical elements, derived from the QTPP must be tracked during development and critical quality attributes must be identified and defined. Process parameters and material attributes are considered as critical when a realistic change can result in the impossibility to meet the QTPP.

In the document, you can find interesting detailed tables, pictures and diverse examples of risk assessments in development. Because the fictive API Acetriptan has been given low solubility in water, the particle size is for example of particular importance; or, the small particle size enables no direct compression and further tests must be performed and documented to elaborate the right process steps for the manufacture.

For further details please see the complete case study

 and the example for "Modified Release Dosage Forms".

Learn more about real case studies from the pharmaceutical industry during the University of Heidelberg QbD/PAT Conference in Heidelberg, Germany, from 5 - 7 October 2011. For more information please visit:


Dr Günter Brendelberger
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)

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