18 BioPharm International
®
Quality and Regulatory Sourcebook eBook March 2024 www.biopharminternational.com
Quality
by
Design
erned and monitored in 'real time' for tracking changes,
as well as ensuring the process and analytical procedure
recipes are available to the end users as a single source of
truth that evolves through development and the product
lifecycle. This will enable the digital risk assessments to
be integrated with other key development data items such
as material specifications, product characteristics, process
design and equipment, quality specifications, and master
data management.
A common data model including the elements above
can be defined and subsequently leveraged to accelerate
product development and transfer activities.
Summary and conclusion
This article explores the pivotal role of digitalization in
QbD risk assessments within the pharmaceutical devel-
opment and manufacturing processes. Digital QbD risk
assessments provide significant benefits moving from
traditional spreadsheets and documents to integrated,
digital, database-driven systems. There are other poten-
tial benefits to regulatory and product lifecycle manage-
ment, including improving the management of multiple
versions of control strategies (13), ICH Q12 established con-
ditions, and other market-specific registered detail.
While the promised benefits of this digital strategy are
clear, challenges associated with its tactical implementa-
tion should be acknowledged. First, a key requirement to
realize the full set of benefits associated with a truly tran-
scription/check-free data flow is GxP validation of the plat-
form(s). This has not yet been attempted by the authors;
however, many commercial off-the-shelf systems for dig-
ital product profile, enterprise recipe management, prod-
uct lifecycle management, and QbD risk management (i.e.,
iRISK) are designed to be compliant with FDA, European
Union Good Manufacturing Practice Annex 15, Euro-
pean Medicines Agency, and ICH guidelines. A related
challenge is the initial establishment of a common data
standard and data model across different technical stake-
holder groups and digital platforms. As explored above,
the use of a digital risk assessment platform, along with
related ERM and digital product profile tools, require and
enable the governance of data standards. Lastly, the shift
to conducting risk assessments, and indeed the whole of
process development and lifecycle management, in a fully
digital format requires deliberate change management of
people and organizations. Here, improvement of digital
fluency can accelerate movement along the 'change curve'.
In summary, the development and integration of a
digital risk assessment platform into a wider digital eco-
system, encompassing QbD and product development
processes, such as ERM and Manufacturing Execution
Systems, are means to expedite the overall drug devel-
opment process. This article is aimed at serving as an ex-
ploration of the transformative potential of a digital risk
assessment platform in reshaping pharmaceutical devel-
opment processes and improving regulatory compliance.
References
1. ICH. ICH Q8(R2) Pharmaceutical Development. Step 4 Ver-
sion (August, 2009).
2. ICH. ICH Q9(R1) Quality Risk Management. Final Version
(January, 2023).
3. ICH. ICH Q10 Pharmaceutical Quality System. Step 4 Ver-
sion (June, 2008).
4. ISPE. Good Practice Guide: Technology Transfer. Third Edi-
tion, ISPE, Jan. 1, 2018.
5. ICH. ICH Q12 Technical and Regulatory Considerations for
Pharmaceutical Product Lifecycle Management. Final Ver-
sion (November, 2019).
6. Yu, L. X.; Raw, A.; Wu, L.; Capacci-Daniel, C.; Zhang, Y.;
Rosencrance, S. FDA's New Pharmaceutical Quality Ini-
tiative: Knowledge-Aided Assessment & Structured Ap-
plications. Int. J. Pharm.: X 2019, 1, 100010. DOI: 10.1016/j.
ijpx.2019.100010.
7. European Commission. Guidelines on Good Manufac-
turing Practice Specific to Advanced Therapy Medici-
nal Products. EudraLex Volume 4, Nov. 22, 2017. https://
health.ec.europa.eu/system/files/2017-11/2017_11_22_
guidelines_gmp_for_atmps_0.pdf
8. EFPIA. EFPIA White Paper on CMC Development, Man-
ufacture and Supply of Pandemic COVID-19 Therapies
and Vaccine. EFPIA.eu, June 8, 2020.
9. ICH. ICH Q14 Analytical Procedure Development. Final
Version (November, 2023).
10. Valgenesis. iRISK. https://www.valgenesis.com/product/
valgenesis-irisk (accessed March 5, 2024).
11. Borman, P.; Chatfield, M.; Nethercote, P.; Thompson,
D.; Truman, K. The Application of Quality by Design to
Analytical Methods. Pharm. Tech. 2007, 31 (12), 142–152.
12. ICH. The Common Technical Document for the Registration
of Pharmaceuticals for Human Use: Quality—M4Q(R1),
Quality Overall Summary of Module 2, Module 3: Quality.
Step 4 Version (September, 2002).
13. Beierle, J.; Cauchon, N.; Graul, T.; et al. Toward a Single
Global Control Strategy: Industry Study. Pharm. Eng.
2022, 42 (1), 20–31.
14. Popkin, M.E.; Borman, P.J.; Omer, B.A.; et al. The De-
livery of Flexibility from the Application of QbD to API
Development. J. Pharm. Innov. 2018, 13 (4), 367–372,. DOI:
10.1007/s12247-018-9339-8.
15. Jackson, P.; Borman, P.; Campa, C.; et al. Using the Ana-
lytical Target Profile to Drive the Analytical Method Life-
cycle. Anal. Chem. 2019, 91 (4), 2577–2585. DOI: 10.1021/
acs.analchem.8b04596.
16. Borman, P.; Campa, C.; Delpierre, G.; et al. Selection of
Analytical Technology and Development of Analytical
Procedures Using the Analytical Target Profile. Anal.
Chem. 2022, 94 (2), 559–570. DOI: 10.1021/acs.anal-
chem.1c03854 Scopus.
17. Popkin, M.E.; Borman, P.J.; Omer, B.A.; Looker, A.; Kalle-
meyn, J.M. Enhanced Approaches to the Identification,
Evaluation, and Control of Impurities. J. Pharm. Innov.
2019, 14 (2), 176–184. DOI: 10.1007/s12247-018-9363-8.
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