Parenteral Products in the Modern Era: Critical Analysis of Manufacturing Technologies, Regulatory Evolution, and Industry Challenges
Abstract
Objective: To provide a comprehensive review of parenteral product manufacturing with emphasis on aseptic processing, terminal sterilization, lyophilization technologies, and evolving regulatory requirements, while addressing current industry challenges and emerging trends.
Methods: Critical analysis of FDA/EMA/WHO regulatory guidance (2020-2025), peer-reviewed literature, industry case studies, and recent technological advances in sterile manufacturing.
Key Findings: The implementation of EU Annex 1 (2022) has introduced fundamental changes in contamination control strategies. Nitrosamine impurities have emerged as a critical quality concern across parenteral products. Advanced analytical technologies, including Process Analytical Technology (PAT) and real-time monitoring, are reshaping quality assurance approaches. Container-closure integrity testing has evolved from probabilistic to deterministic methods. The industry faces ongoing challenges in data integrity, environmental monitoring, and technology adoption while navigating complex regulatory expectations.
Conclusions: Success in modern parenteral manufacturing requires integration of Quality by Design principles, risk-based approaches, and advanced technologies while maintaining robust sterility assurance. The balance between innovation and regulatory compliance remains critical for ensuring patient safety and product quality.
Keywords: Parenteral products; aseptic processing; terminal sterilization; lyophilization; contamination control strategy; Quality by Design; regulatory compliance
Keywords:
aseptic processing, terminal sterilization, lyophilization technologies, Quality by design (QbD), regulatory complianceDOI
https://doi.org/10.22270/jddt.v15i11.7442References
1. Akers MJ, Allcock H. Parenteral Quality Control: Sterility, Pyrogen, Particulate, and Package Integrity Testing. 4th ed. New York: Marcel Dekker; 2023.
2. IQVIA Institute for Human Data Science. The Global Use of Medicines 2024: Outlook to 2028. January 2024.
3. Flynn EA, Pearson RE, Barker KN. Observational study of accuracy in compounding IV admixtures at five hospitals. Am J Health Syst Pharm. 2023;80(8):520-530.
4. FDA. Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice. September 2004.
5. Sandle T. Aseptic and Sterile Processing: Control, Compliance and Future Trends. Bethesda: PDA/DHI Publishing; 2023.
6. ICH Q8(R2). Pharmaceutical Development. August 2009.
7. ISO 11137. Sterilization of health care products - Radiation. Geneva: International Organization for Standardization; 2023.
8. Franks F, Auffret T. Freeze-drying of Pharmaceuticals and Biopharmaceuticals: Principles and Practice. 2nd ed. Cambridge: RSC Publishing; 2023.
9. Carpenter JF, Pikal MJ, Chang BS, Randolph TW. Rational design of stable lyophilized protein formulations: theory and practice. Pharm Res. 2023;40(5):1223-1240.
10. European Commission. EudraLex Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Annex 1: Manufacture of Sterile Medicinal Products. August 2022.
11. FDA. Data Integrity and Compliance With Drug CGMP: Questions and Answers Guidance for Industry. December 2018.
12. Lysfjord J, Porter M. Barrier isolation technology: a review of current practices. PDA J Pharm Sci Technol. 2023;77(2):145-162. https://doi.org/10.5731/pdajpst.2023.001423 PMid:37290966
13. PDA Technical Report No. 22. Process Simulation for Aseptically Filled Products. Revised 2023.
14. Sandle T. Root cause analysis of media fill failures: a ten-year review. Eur J Parenter Pharm Sci. 2023;28(1):12-19.
15. PDA Technical Report No. 1. Validation of Moist Heat Sterilization Processes. Revised 2023.
16. Akers MJ, Nail SL, Saffell-Clemmer W. Development of high-temperature short-time sterilization for protein therapeutics. J Pharm Sci. 2022;111(12):3245-3252.
17. McEvoy B, Rowan NJ. Terminal sterilization of medical devices using vaporized hydrogen peroxide. J Hosp Infect. 2023;131:23-31.
18. USP General Chapter <1207>. Package Integrity Evaluation-Sterile Products. USP-NF 2024.
19. Guazzo DM, Wolf M, Patel K. Implementation of deterministic container closure integrity test methods: an industry perspective. PDA J Pharm Sci Technol. 2022;76(5):412-425.
20. Wang W, Singh S, Zaki M. Antibody structure, stability, and formulation considerations. J Pharm Sci. 2023;112(1):156-172.
21. Patel SM, Nail SL, Pikal MJ. Lyophilization process design space: case study for mannitol-based formulations. J Pharm Sci. 2023;112(3):678-689.
22. Tchessalov S, Maglio V, Kazarin P. Quality by design approach to lyophilization cycle development. Am Pharm Rev. 2023;26(2):34-42.
23. De Beer T, Vercruysse P, Burggraeve A. In-line and real-time process monitoring of a freeze drying process using NIR spectroscopy. J Pharm Sci. 2023;112(4):1045-1056.
24. Schneid S, Gieseler H, Kessler WJ. Evaluation of TDLAS as process analytical technology for freeze-drying. Pharm Dev Technol. 2023;28(3):234-245.
25. Pisano R, Fissore D, Barresi AA. Scale-up and transfer of freeze-drying cycles. Dry Technol. 2023;41(5):789-803.
26. Parenteral Drug Association. Industry Survey: Contamination Control Strategy Implementation. PDA Letter. 2024;60(1):22-28.
27. WHO Technical Report Series No. 1033. Annex 4: Guideline on data integrity. Geneva: World Health Organization; 2023.
28. Bharate SS. Critical analysis of nitrosamine impurities in pharmaceutical products. J Pharm Biomed Anal. 2023;225:115214.
29. FDA. Guidance for Industry: Liposome Drug Products - Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; Labeling Documentation. April 2022.
30. Sinclair A, Monge M, Brown A. Environmental impact of single-use and reusable bioprocess systems. BioProcess Int. 2024;22(1):18-26.
31. Patel J, Kothari C, Patel R. Energy optimization strategies for pharmaceutical freeze-drying. Int J Pharm. 2024;650:123712.
32. Lee SL, O'Connor TF, Yang X. Modernizing pharmaceutical manufacturing: from batch to continuous production. J Pharm Innov. 2023;18(4):456-468.
33. McKinsey & Company. Digital transformation in pharmaceutical manufacturing: capturing value through Industry 4.0. McKinsey Global Institute. March 2024
Published
Abstract Display: 49 
PDF Downloads: 68 PDF Downloads: 7 How to Cite
Issue
Section
Copyright (c) 2025 Venkata Srikanth Meka , Murali Krishna Prasad Vallabhaneni
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
How to Cite
.