Quality- by-design in pharmaceutical development - Computer-Aided Applications in Pharmaceutical Technology - page 10

Table 1.3

QbD for industry and regulatory bodies

Industry Regulatory agency

Development of scientifi c
understanding of critical process
and product attributes.

Scientifi cally based assessment of product
and manufacturing process design and
development.

Controls and testing are designed
based on limits of scientifi c
understanding at development
stage.

Evaluation and approval of product quality
specifi cations in light of established
standards (e.g. purity, stability, content
uniformity, etc.).

Utilization of knowledge gained
over the product's lifecycle for
continuous improvement.

Evaluation of post-approval changes based
on risk and science.

Source: Shah, 2009

regulatory submissions, and lacking in links appointed between control
strategies and pharmaceutical development, etc.
There were several EMA marketing authorization applications (MAA)
with QbD and PAT elements (for the following products: Avamys®,
Torisel ® , Tyverb ® , Norvir ® , Exjade ® , Revolade ® , Votrient ® , etc.). Up to
2011, there was a total of 26 QbD submissions to EMA (for the new
chemical entities); 18 of them were initial MAAs (4 including the real-
time release), 6 of them were concerning post-authorization, and 2 were
scientifi c advice requests. An additional two MAAs were submitted for
biological products, but none of the submissions were related to the
generics industry (Korakianiti, 2011). Up to 2011, there were
approximately 50 QbD related applications to the FDA (Miksinski,
2011). FDA authorities state that QbD is to be fully implemented by
January 2013 (Miksinski, 2011).
Pfi zer was one of the fi rst companies to implement QbD and PAT
concepts. Through these concepts, the company gained enhanced process
understanding, higher process capability, better product quality, and
increased fl exibility to implement continuous improvement changes
(Migliaccio, 2011). Also, much of the QbD investment occurs in process
development, and the benefi t is realized in commercial manufacturing
(Migliaccio, 2011). Another important issue addressed by the Pfi zer
researchers is that some compendial specifi cations may not be adequate
to analyze physical, chemical, microbiological, and biological properties
of materials that may impact product quality or process performance
(potential CQAs). The process performance index Ppk of the fi rst QbD
Pfi zer product was 1.2 (3-4 σ ) at launch and 1.8 (5-6 σ ) 6 months after

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