Biomedical Engineering Reference
In-Depth Information
Figure 6.1 shows a QTPP for a solid oral dosage form. A QTPP should
be the first controlled document developed when designing a new product. All
disciplines involved in ultimately bringing the product to market—engineering,
maintenance, production (the process owner), quality, R&D, purchasing, sales
and marketing, as well as any other stakeholders—should sign off on the doc-
ument. Sales and marketing requirements can be particularly important to allow
for designing of any unique features such as package configurations for tablets
that may directly impact product stability. The QTPP is a controlled document
that is assigned a version number and date. The document will be periodi-
cally updated as development progresses and some of the ideal requirements
are found to be unachievable except at the expense of others. A team meet-
ing should be called to make a decision regarding which requirement takes
precedence and this usually requires senior management input. For example,
marketing wants the tablets packaged in a securitainer, with a three-year shelf
life at room temperature. After studying the stability profile, R&D offers sev-
eral possibilities: three years at room temperature in a blister pack; 18 months
at room temperature in a securitainer; and three years refrigerated in a secu-
ritainer. Marketing will probably have the overriding vote regarding the final
presentation, but the preliminary hazard analysis, which considered product pack-
aged in a securitainer with a shelf life of three years at room temperature, will
now need to be reviewed in light of the new decision. Some of the previously
identified risks and their controls may have changed as indicated in Tables 6.1
and 6.2.
The QTPP will also be the basis for the first draft of the finished product
specification. Consideration should be given to the fact that drug substance or
active pharmaceutical ingredient (API) development often progresses in parallel
with the finished product and analytical methods development. As a result, there
is an overlap of activity between the different project development teams, which
can result in increased uncertainty and therefore increased risk. For example, API
synthesis experiments with different solvents to reduce certain impurities while
development of analytical methods is under way. QC invests effort in developing
methods to identify the impurities from solvent A, while process development
eliminates them and introduces others. At the same time, work moves forward
on formulation and development of analytical methods for drug products (often
different to the API ones taking into account excipients). A preliminary hazard
TABLE 6.1
Initial Hazard Analysis
Identified Risk
Item #
for Original QTPP
Control
Monitoring
Comment
1.
Moisture absorbed by
tablets during storage
Insert dessicator in
each container
Stability data
2.
Wrong number of tablets
in container
Check weight
Calibration
Periodic manual
count
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