Biomedical Engineering Reference
In-Depth Information
or characteristics of amaterial or process. Care needs to be taken to include attributes that
can be experimentally measured.
Commonly identified quality attributes of a biologic product include color, clarity,
subvisible particulates, pH, concentration, aggregation, oxidation, deamidation, bioac-
tivity, and sterility. In this case study of a liquid biologic drug product, the primary quality
attributes of the compounding step are identified as concentration of active, deamidation,
oxidation, aggregation, pH, color/clarity, fragmentation, content uniformity, bioactivity,
and process time.
10.3.2 Ranking Quality Attributes (QA) and Parameters
After completing the process map, delineating the unit operations in each focus area and
identifying the process parameters and quality attributes, the next step is to rank the
quality attributes and parameters for each focus area.
The process parameter rank scores are assigned as follows, in relation to a specific
quality attribute:
The process parameters for the compounding steps (FA3) were ranked as mixing
speed
¼
7, mixing time
¼
7, hold time
¼
10, temperature
¼
10, excipient quality
¼
5,
excipient handling
¼
7, balance accuracy
¼
10, and operator training
¼
5 (see case study
Risk Assessment sheet in Table 10.1).
QA scoring takes into account prior knowledge, experience, and expectations. For
example, the current emphasis on aggregation and its potential impact on immunogenicity
suggest that aggregate levels in a product will be a high-rankedQA. Similarly, it is possible
that the level of oxidation in a biologic has no impact on its potency/activity, efficacy or
safety, the case in which oxidation QA may be scored lower. Oxidation in this case is an
attribute that could demonstrate control from a process and product consistency point of
view in this case, but would have a lower QA score from a compounding perspective.
Quality attributes are ranked similarly with the following:
Scoreof10isgivento thoseattributeswhere it isestablishedor expected that adirect
relationship to product quality or safety (including manufacturing safety) exists
.
Score of 7 is given to attributes where it is unsure, but an impact to product quality
or safety or key business drivers is expected;
.
Score of 5 is given to attributes that are unlikely to impact product quality or safety
.
Score of 1 is given to attributes where no product quality or safety impact is
expected.
.
The quality attributes for the compounding steps (FA3) were ranked as concentration
of active
¼
10, deamidation
¼
7, oxidation
¼
7, aggregation
¼
10, pH
¼
10, color/clarity
7, fragmentation
¼
7, content uniformity
¼
10, bioactivity
¼
10, and process time
¼
5.
10.3.3 Prioritizing Experiments and Experimental Strategies
Scoring is the next step in the process. By combining the process and the quality attribute
ranks from the risk assessment table (Table 10.1) along with the scoring for each
