Calidad Desde El Diseño En Industria Farmaceutica

Pharmaceutical Research, Vol. 25, No. 4, April 2008 (# 2007)
DOI: 10.1007/s11095-007-9511-1

Research Paper
Pharmaceutical Quality by Design: Product and Process Development,
Understanding, and Control
Lawrence X. Yu1,2

Received September 9, 2007; accepted November 26, 2007; published online January 10, 2008
Purpose. The purpose of this paper is to discuss the pharmaceutical Quality by Design(QbD) and
describe how it can be used to ensure pharmaceutical quality.
Materials and Methods. The QbD was described and some of its elements identified. Process parameters
and quality attributes were identified for each unit operation during manufacture of solid oral dosage
forms. The use of QbD was contrasted with the evaluation of product quality by testing alone.
Results. The QbD is a systemicapproach to pharmaceutical development. It means designing and
developing formulations and manufacturing processes to ensure predefined product quality. Some of the
QbD elements include:
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Defining target product quality profile
Designing product and manufacturing processes
Identifying critical quality attributes, process parameters, and sources of variability
Controlling manufacturingprocesses to produce consistent quality over time

Conclusions. Using QbD, pharmaceutical quality is assured by understanding and controlling
formulation and manufacturing variables. Product testing confirms the product quality. Implementation
of QbD will enable transformation of the chemistry, manufacturing, and controls (CMC) review of
abbreviated new drug applications (ANDAs) into ascience-based pharmaceutical quality assessment.
KEY WORDS: pharmaceutical quality by design; pharmaceutical quality by testing; process control;
process design; process parameter; process variability; product design; quality attribute; question-based
review.

INTRODUCTION
The Food and Drug Administration (FDA) Office of
Generic Drugs (OGD) has developed a question-based
review (QbR) for its chemistry,manufacturing, and controls
(CMC) evaluation of abbreviated new drug applications
(ANDAs). QbR is a new quality assessment system that is
focused on critical pharmaceutical quality attributes. It is a
concrete and practical implementation of some underlying
concepts and principles outlined by the FDA’s Pharmaceutical
CGMPs for the twenty-first century and quality by design
(QbD) initiatives (1).
Thisnew QbR system incorporates some elements of
QbD (2). It recommends that ANDAs be submitted using the
common technical document (CTD) and include the quality
overall summary (QOS) that addresses all the QbR questions.
The main benefits of this QbR system are to (1) assure

The views presented in this article do not necessarily reflect those of
the Food and Drug Administration.
1

Food and DrugAdministration, Office of Generic Drugs, 7519
Standish Place, Rockville, Maryland 20855, USA.
2
To whom correspondence should be addressed. (e-mail: Lawrence.
Yu@hhs.fda.gov)

product quality through design and performance-based specifications, (2) facilitate continuous improvement and reduce
CMC supplements, (3) enhance the quality of CMC reviews
through standardized review questions, and (4)reduce CMC
review time when applicants submit a QOS that addresses the
QbR questions.
This commentary focuses on the QbD for generic drugs.
The concept of QbD was mentioned in the ICH Q8 guidance
(3), which states that “quality cannot be tested into products,
i.e., quality should be built in by design”. This paper discusses
the pharmaceutical quality by design and describes how it can
be used toensure pharmaceutical quality with emphasis on
solid oral dosage forms of small molecules.
PHARMACEUTICAL QUALITY BY TESTING
Figure 1 shows a simplified quality control diagram
under the current quality by testing (QbT) regulatory framework for generic drugs. In this system, product quality is
ensured by raw material testing, drug substance manufacturing, a fixed drug product manufacturing process,...