Biomedical Engineering Reference
In-Depth Information
understanding of the product and process by applying Quality by Design principles, and
built on the team-based integrated review and assessment process that was developed for
PAT; companies were encouraged to file applications under the new system with an
agreement that if the appropriate level of process and product understanding was
demonstrated, then the companies would be free to make changes within the approved
design space based on internal quality systems and GMP controls.
The greater flexibility available permits greater freedom to make improvements in
the process and facilitates the transfer of processes from one site to another and even one
manufacturer to another, provided the appropriate analytical tools and assays are
available.
Amajor industry concern is that none of these changes should trigger differences in
filing approaches from one region to another. The International Conference on Harmo-
nization (ICH) has sought to avoid the development of separate approaches through
guidelines for quality, safety, efficacy, and multidisciplinary topics. The ICH Guidelines
Q8, Pharmaceutical Development, which describes the concept of design space, and Q9,
which provides guidelines for risk management, were both finalized in 2005, with an
annex to Q8 (R1) expanding on the description of design space (albeit written in
the context of small-molecule drugs) becoming available, but not yet finalized, in 2007.
A draft became available for Q10 in 2007, which addresses pharmaceutical quality
systems [5-8].
The EMEA PAT teamwas formed in late 2003 to review the implications of the PAT
initiative and ensure that the European framework and regulatory authorities were
adequately prepared to conduct effective evaluations. The EMEA inspections Web site
for process analytical technology states that “Quality by Design is an established concept
in Europe” [9]. In general the EMEA position is that the current regulatory framework in
Europe is open to the implementation of PAT in marketing authorization applications
through existing guidance for pharmaceutical development and parametric release. The
EMEA published a reflection paper in 2006 [9], and there is a document of questions and
answers on their Web site [10].
During the development of this framework, it was recognized that the PAT
guidance would be general and would not provide specifics, which would be
developed instead in the form of best practices. The FDA encouraged the pharmaceutical
industry to take an active role in drafting these practices in the form of consensus
standards, which led to the formation of the ASTM E55 Committee on Manufacture of
Pharmaceutical Products in 2003, shifting the onus for continued development of
the concepts to the manufacturers. The original aim was to develop standards to
support the implementation of PAT, but the committee subsequently broadened its
scope to all aspects of manufacture to include the “development of standardized
nomenclature and definitions of terms, recommended practices, guides, test methods,
specifications, and performance standards for the manufacture of pharmaceutical
products” [11]. Quality and consistency are additional goals, as are transparency and
cost effectiveness.
Standards can be general recommendations, such as guides, or can be increasingly
specific recommendations, such as practices and specifications. They are developed in a
consensus process, which requires that they are open (all can participate), balanced (i.e.,
