Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May 24;15(6):1581.
doi: 10.3390/pharmaceutics15061581.

Robotics and Aseptic Processing in View of Regulatory Requirements

Andrea Tanzini  1 , Marco Ruggeri  2 , Eleonora Bianchi  2 , Caterina Valentino  2 , Barbara Vigani  2 , Franca Ferrari  2 , Silvia Rossi  2 , Hermes Giberti  3 , Giuseppina Sandri  2
Affiliations
Review

Robotics and Aseptic Processing in View of Regulatory Requirements

Andrea Tanzini et al. Pharmaceutics. .

Abstract

Several nanomedicine based medicinal products recently reached the market thanks to the drive of the COVID-19 pandemic. These products are characterized by criticality in scalability and reproducibility of the batches, and the manufacturing processes are now being pushed towards continuous production to face these challenges. Although the pharmaceutical industry, because of its deep regulation, is characterized by slow adoption of new technologies, recently, the European Medicines Agency (EMA) took the lead in pushing for process improvements using technologies already established in other manufacturing sectors. Foremost among these technologies, robotics is a technological driver, and its implementation in the pharma field should cause a big change, probably within the next 5 years. This paper aims at describing the regulation changes mainly in aseptic manufacturing and the use of robotics in the pharmaceutical environment to fulfill GMP (good manufacturing practice). Special attention is therefore paid at first to the regulatory aspect, explaining the reasons behind the current changes, and then to the use of robotics that will characterize the future of manufacturing especially in aseptic environments, moving from a clear overview of robotics to the use of automated systems to design more efficient processes, with reduced risk of contamination. This review should clarify the regulation and technological scenario and provide pharmaceutical technologists with basic knowledge in robotics and automation, as well as engineers with regulatory knowledge to define a common background and language, and enable the cultural shift of the pharmaceutical industry.

Keywords: GMP; annex 1; automation; nanomedicines; pharmaceutical processes; robotics; sterile manufacturing.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The company had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 2
Figure 2
Challenges in the development and commercialization of nanomedicines. Inspired from [16].
Figure 1
Figure 1
Overview of the nanomedicines that are available commercially or in clinical trial. Modified from [6].
Figure 3
Figure 3
Uncertainties related to the nanomedicine regulatory process. Inspired from [17] with permission.
Figure 4
Figure 4
Schematic of the environmental classes and the technological features to maintain them on the basis of Annex 1–2022 release modified from [22] with permission.
Figure 5
Figure 5
Chart that correlates quality and risk of contamination with investments for the conventional clean room, RABS, and isolators.
Figure 6
Figure 6
(a) Pneumatic gripper, (b) hydraulic gripper, (c) vacuum gripper, and (d) electric gripper; modified from [22].
Figure 7
Figure 7
Schematic representation of the concepts of repeatability, accuracy, and visualization: (a) bad repeatability and bad accuracy, (b) bad repeatability and good accuracy, (c) good repeatability and bad accuracy, and (d) good repeatability and good accuracy.
Figure 8
Figure 8
Example of robotic vial filling line (courtesy of Steriline).
Figure 9
Figure 9
Schematic of the tests needed to understand the robot suitability to the environment.
Figure 10
Figure 10
Simulation environment to analyze and visualize trajectories and equipment status forecast.
Figure 11
Figure 11
Smoke test study performed on a robotic open RABS filling line.
See this image and copyright information in PMC

References

    1. Thapa R.K., Kim J.O. Nanomedicine-based commercial formulations: Current developments and future prospects. J. Pharm. Investig. 2023;53:19–33. doi: 10.1007/s40005-022-00607-6. - DOI - PMC - PubMed
    1. Allahou L.W., Madani S.Y., Seifalian A. Investigating the application of liposomes as drug delivery systems for the diagnosis and treatment of cancer. Int. J. Biomater. 2021;2021:3041969. doi: 10.1155/2021/3041969. - DOI - PMC - PubMed
    1. European Medicines Agency Reflection Paper on Nanotechnology-Based Medicinal Products for Human Use. [(accessed on 16 May 2023)]. Available online: https://etp-nanomedicine.eu/wp-content/uploads/2018/10/reflection-paper-....
    1. Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology. [(accessed on 16 May 2023)]; Available online: https://www.fda.gov/regulatory-information/search-fda-guidance-documents....
    1. COMMISSION RECOMMENDATION of 10 June 2022 on the Definition of Nanomaterial (2022/C 229/01) [(accessed on 16 May 2023)]. Available online: https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:32022H061...