Pharmaceutical Development for Historic Dossiers: An Overview

Getting historic dossiers registered in new markets can have its difficulties, especially when the dossier might have been developed before the development of current guidance and requirements. One such difficulty is the concept of Pharmaceutical Development and Quality by Design (QbD). Acorn Regulatory Project Manager Janet Fitzgerald looks at QbD in this article and how it can be used in developing historic dossiers.

What Is Quality By Design?

Quality by Design  (QbD) is the recommended approach to the development of new dossiers in the US and EU.  It involves a systematic approach to development using multivariant analysis and risk analysis to develop a control strategy and reduce the need for lifecycle management.

Using the concepts of QbD can be very helpful in avoiding quality questions during the assessment of a new application. Where a drug was developed before the introduction of QbD, it is still possible to introduce the basic concepts into a Pharmaceutical Development section (3.2.P.2) without carrying out new development studies and Design of Experiments (DoE).

When writing a Pharmaceutical Development section for an older dossier, any information that may be available in the old NtA part 2.A.4 Development Pharmaceutics may still be applicable and used as a starting point, but there is also a wealth of information available from batches that have been in commercial manufacture for years.

Readily Available Information

Without the need for carrying out additional studies the following information can be readily available:

Quality Target Product Profile (QTPP): The target product to be developed is already defined in the original dossier including the product description and shelf life.

Critical Quality Attributes (CQAs): The quality attributes required to achieve the target product quality can be found in the finished product specification e.g. description, assay, impurities, etc. Batch analysis and stability data can be assessed to see what attributes really are critical, and possibly reduced stability testing can be applied if certain tests are proven not to be stability indicating.

Critical Material Attributes (CMAs): The material attributes of all components which may affect product quality can be found in the specifications of raw materials such as API, excipients, packaging materials, and also equipment e.g. API/excipient particle size, impurities, etc. It can similarly be shown if certain attributes do not affect finished product quality and thus do not need to be controlled. Some functionality related characteristics of excipients are stated in Ph Eur and should be assessed for risk of impact on quality.

Critical Process Parameters (CPPs): The process parameters which may affect product quality are defined in the manufacturing process and in-process controls e.g. mixing speeds and times, temperatures, etc. Any batch analysis or stability data which supported changes in the manufacturing process over time can also be used. If data is available to support multiple mixing speeds with no effect on product quality, then ranges can be registered as opposed to a single set speed, this will allow for greater flexibility and reduction in lifecycle management.

Writing the 3.2.P.2

By keeping these concepts and terms in mind while writing the 3.2.P.2 and carrying out a risk assessment on each attribute and parameter, and using data to hand, it can greatly reduce questions received from agencies during the assessment. By setting a risk-based control strategy it builds a strong justification of specifications and can also lead to the ability to reduce controls that may have been in place historically or allow for greater flexibility by registering ranges rather than set parameters.

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About the Author:
Janet Fitzgerald
Project Manager
Janet Fitzgerald manages some of the larger projects that the company's pharmaceutical and CMC team are working on. She has a wealth of experience in the regulatory affairs sector. You can read other articles by Janet by clicking the link below.
Other articles by Janet Fitzgerald