Definition

5) Determining According to the ICH Q8 (R2) guideline, design

space is the multidimensional combination and
the design interaction of input variables (e.g., material
space attributes) and process parameters established
to provide quality assurance.

An applicant proposes the design space and it is

subjected to regulatory assessment and approval.

MEng Silvia Ordaz

Design of
A branch of applied statistics that deals with:
Experiments (DoE)
planning, conducting, analyzing,
and interpreting controlled tests to evaluate the
impact of the factors on the process parameters.

(Tavares et al., 2021)

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 Screening
FULL FACTORIAL DESIGN
Contains all possible combinations between the different factors (K) and their levels. 2K or
3K designs (2 or 3 levels).
The main drawback of full factorial designs is that the number of experiments increases
exponentially with the number of factors.

FRACTIONAL FACTORIAL DESIGN

Design in which experimenters conduct only a selected subset or "fraction" (2k-p) of the
runs in the full factorial design. Are a good choice when resources are limited or the number
of factors in the design is large because they use fewer runs than the full factorial designs.

MEng Silvia Ordaz

 Screening
PLACKET BURMANN

Plackett–Burman (PB) designs are considered the main alternative for saturated fractional
factorial designs. PB designs are saturated factorial designs of resolution III that examine
N–1 factors in N (a multiple of four) experiments. They only allow the main effects to be
estimated.

(Hejduk et al., 2022)

 Optimization
CENTRAL COMPOSITE DESIGNS (CCD)

An experimental design, useful in response surface methodology, for building a second

order (quadratic) model for the response variable without needing to use a complete three-
level factorial experiment. CENTRAL COMPOSITE DESIGNS (CCD) BOX-BEHNKEN DESIGNS (BBD)

BOX-BEHNKEN DESIGNS (BBD)

In this design, the treatment combinations are at the midpoints of the edges of the process
space and in the center, avoiding the extreme axial points, which are sometimes difficult to
run in practice, as in the CCD. In addition, the BBD requires a smaller number of
experimental runs.
6) Identifying a With all the information that has been obtained,
control we proceed to:

strategy. Standardize the manufacturing process,

ensuring that the critical quality attributes
are met.
Establish control strategies for the product,
including intermediates.
Understanding of the Validate processes.
process in the
framework of
continuous Once the product has been transferred to
production, it is necessary to be in constant
improvement
review, highlighting the concept of continuous
improvement for the adjustment of any
parameter.
MEng Silvia Ordaz
 References
Beg, S., Haneef, J., Rahman, M., Peraman, R., Taleuzzaman, M., & Almalki, W. H. (2021). Introduction to
analytical quality by design. In Handbook of Analytical Quality by Design (pp. 1-14). Academic Press.

How to Identify Critical Quality Attributes and Critical Process Parameters (De J. Maguire, D. Peng, & Office of
Process and Facility (OPF) [OPQ/CDER/FDA]). (2015, 6 octubre). https://pqri.org/wp-
content/uploads/2015/10/01-How-to-identify-CQA-CPP-CMA-Final.pdf

Guideline, I.C.H.H.T. Pharmaceutical development. Q8 (2R).

Guideline, I.C.H.H.T. Quality risk management. Q9.

Luiz, M. T., Viegas, J. S. R., Abriata, J. P., Viegas, F., de Carvalho Vicentini, F. T. M., Bentley, M. V. L. B., ... & Tapia-
Blacido, D. R. (2021). Design of experiments (DoE) to develop
and to optimize nanoparticles as drug delivery
systems. European Journal of Pharmaceutics and Biopharmaceutics, 165, 127-148.

Hejduk, A., Teżyk, M., Jakubowska, E., Krüger, K., & Lulek, J. (2022). Implementing the design of experiments (DoE)
concept into the development phase of orodispersible minitablets (ODMTs) containing melatonin. AAPS
PharmSciTech, 23(1), 60.