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LARGE MOLECULE
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Quality by Design (QbD) Approach to Generic Transdermal or Topical Product Development
Michael Fowler
Process Engineer Principal Actavis, Salt Lake City, UT
Introduction
As noted recently, FDA has issued several guidance documents to encourage companies to implement components of Quality by Design (QbD) into various phases of product lifecycles, with an emphasis on product development. Companies are expected to incorporate basic QbD elements in ANDA product filings1
and transition to more
complete QbD filings as industry and regulatory agencies sync knowledge gained from successful and unsuccessful experiences. As a starting point to guide companies in this endeavor, the International Conference on Harmonization of
Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH) issued Q8 (R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System.1-4
ICH Q8(R2) describes the scope
and principles of QbD and suggests examples and methodologies to enhance product and process knowledge in formulation and process development; ICH Q9 provides guidance to implement quality risk management into product development by using scientific knowledge to make risk assessments; ICH Q10 provides guidance for using ICH Q8 and ICHQ9 principles in regulatory strategies.1
FDA defines QbD
Submitted: 11/14/2014 Accepted for Publication: 11/26/2014
Fowler M. Quality by design (QbD) approach to generic transdermal or topical product development. Am Pharm Rev. 2015;18(1):16-22.
as “A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.” In addition, FDA has published 2 excellent, comprehensive examples for implementing QbD at all stages of development of immediate and modified release dosage forms.5,6
Sponsors developing generic products may frequently avoid implementing QbD in the early stages of development due to aggressive project timelines in the race to file first, a lack of resources, a lack of management support, or a combination of all 3 factors. The purpose of this paper is to submit that using a risk- and science-based approach is feasible to develop a generic topical product within the QbD paradigm. A Quality Target Product Profile (QTPP), process-centric risk assessment, a statistical design of experiment, and a process design space are discussed in the format of a case study for a topical product. The organization of the information printed, including formats and content of tables, risk assessments, and other figures, are only one way of communicating information to a group or regulatory body.
Quality Target Product Profile
The development of a topical or transdermal product can be divided into different phases, similar to other dosage forms. The approach
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