Development of Advanced Sterile Drug Delivery Manufacturing Capabilities for Injectable and Ophthalmic Products in Saudi Arabia

References

[1] World Health Organization. WHO good manufacturing practices for sterile pharmaceutical products. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-sixth report. Annex 2, WHO Technical Report Series No. 1044. Geneva: World Health Organization; 31 October 2022.

[2] European Commission. EudraLex — The Rules Governing Medicinal Products in the European Union, Volume 4: EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. Annex 1: Manufacture of Sterile Medicinal Products. Brussels: European Commission; 22 August 2022 (in force 25 August 2023; section 8.123 from 25 August 2024).

[3] Saudi Food and Drug Authority. Guide to Good Manufacturing Practice for Medicinal Products, Version 4.3, document reference OPS-G-080-V4.3/110726. Riyadh: Saudi Food and Drug Authority; 29 November 2023. [Revised Annex 1, Manufacture of Sterile Medicinal Products, was introduced at Version 4.2 (15 December 2022) for implementation from 25 August 2023; the superseded Annex 1 was deleted at Version 4.3.]

[4] U.S. Food and Drug Administration. Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice: Guidance for Industry. Silver Spring, MD: Center for Drug Evaluation and Research, FDA; September 2004.

[5] Alzhrani RF, Alrasheed M, Alzammam I, Alruthia Y. Sterile injectable products shortage in Saudi Arabia: a survey-based cross-sectional study. Saudi Pharmaceutical Journal. 2025;33(6):article 53. Springer International Publishing. doi:10.1007/s44446-025-00053-z.

[6] Alshibli F, Alqarni K, Balfaqih H. Analyzing the causes and impact of essential medicines and supplies shortages in the supply chain of the Ministry of Health in Saudi Arabia: a quantitative survey study. Informatics in Medicine Unlocked. 2024;45:101457. Elsevier. doi:10.1016/j.imu.2024.101457.

[7] Alyami HS, Naser AY, Alyami MH, Al Garsan M, Al-Nahdi AY, Alalhareth IS, Alyami SM. Drug shortages in Najran region, Saudi Arabia: a cross-sectional survey. Clinical Epidemiology and Global Health. 2023;21:101305. Elsevier. doi:10.1016/j.cegh.2023.101305.

[8] Alruthia YS, Alwhaibi M, Alotaibi MF, Asiri SA, Alghamdi BM, Almuaythir GS, et al. Drug shortages in Saudi Arabia: root causes and recommendations. Saudi Pharmaceutical Journal. 2018;26(7):947–951. Elsevier. doi:10.1016/j.jsps.2018.05.002.

[9] Alshehri S, Alshammari R, Alyamani M, Dabbagh R, Almalki B, Aldosari O, Alsowayigh R, Alkudeer A, Aldosari F, Sabr J, Shakeel F. Current and future prospective of pharmaceutical manufacturing in Saudi Arabia. Saudi Pharmaceutical Journal. 2023;31(4):605–616. Elsevier. doi:10.1016/j.jsps.2023.03.001.

[10] Tawfik EA, Tawfik AF, Alajmi AM, Badr MY, Al-jedai A, Almozain NH, Bukhary HA, Halwani AA, Al Awadh SA, Alshamsan A, Babhair S, Almalik AM. Localizing pharmaceuticals manufacturing and its impact on drug security in Saudi Arabia. Saudi Pharmaceutical Journal. 2022;30(1):28–38. Elsevier. doi:10.1016/j.jsps.2021.12.002.

[11] Halwani AA, Balkhi B, Alamoudi AA, Almozain NH, Alajmi AM, Noorwali A, Badr MY, Noor AO, Bagalagel A, Tawfik EA. Current status and vision of local pharmaceutical industries in Saudi Arabia: the focus on nanomedicines. Saudi Pharmaceutical Journal. 2023;31(8):101674. Elsevier. doi:10.1016/j.jsps.2023.06.007.

[12] Kingdom of Saudi Arabia. National Industrial Development and Logistics Program (NIDLP). Riyadh: Saudi Vision 2030; launched 2019. Available at: https://www.vision2030.gov.sa/v2030/vrps/nidlp/

[13] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q8(R2): Pharmaceutical Development. Geneva: ICH; August 2009.

[14] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q9(R1): Quality Risk Management. Geneva: ICH; 18 January 2023.

[15] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q10: Pharmaceutical Quality System. Geneva: ICH; June 2008.

[16] U.S. Food and Drug Administration. Process Validation: General Principles and Practices — Guidance for Industry. Current Good Manufacturing Practices, Revision 1. Silver Spring, MD: FDA; January 2011.

[17] Parenky AC, Wadhwa S, Chen HH, Bhalla AS, Graham KS, Shameem M. Container closure and delivery considerations for intravitreal drug administration. AAPS PharmSciTech. 2021;22(3):article 100. Springer. doi:10.1208/s12249-021-01949-4.

[18] O'Brien MN, Jiang W, Wang Y, Loffredo DM. Challenges and opportunities in the development of complex generic long-acting injectable drug products. Journal of Controlled Release. 2021;336:144–158. Elsevier. doi:10.1016/j.jconrel.2021.06.017.

[19] Panchal K, Katke S, Dash SK, Gaur A, Shinde A, Saha N, Mehra NK, Chaurasiya A. An expanding horizon of complex injectable products: development and regulatory considerations. Drug Delivery and Translational Research. 2023;13(2):433–472. Springer. doi:10.1007/s13346-022-01223-5.

[20] Alexeenko A, Korang-Yeboah M, Tchessalov S. Critical needs and opportunities for advanced manufacturing of lyophilized injectables. Pharmaceutical Research. 2025;42:1119–1131. Springer. doi:10.1007/s11095-025-03869-5.

[21] Butreddy A, Dudhipala N, Janga KY, Gaddam RP. Lyophilization of small-molecule injectables: an industry perspective on formulation development, process optimization, scale-up challenges, and drug product quality attributes. AAPS PharmSciTech. 2020;21(7):article 252. Springer. doi:10.1208/s12249-020-01787-w.

[22] Jameel F, Alexeenko A, Bhambhani A, Sacha G, Zhu T, Tchessalov S, Kumar L, Sharma P, Moussa E, Iyer L, Fang R, Srinivasan J, Tharp T, Azzarella J, Kazarin P, Jalal M. Recommended best practices for lyophilization validation — 2021 Part I: process design and modeling. AAPS PharmSciTech. 2021;22(7):article 221. Springer. doi:10.1208/s12249-021-02086-8. [Correction published: AAPS PharmSciTech. 2021;22(8):article 245.]

[23] Jameel F, Alexeenko A, Bhambhani A, Sacha G, Zhu T, Tchessalov S, Sharma P, Moussa E, Iyer L, Luthra S, Srinivasan J, Tharp T, Azzarella J, Kazarin P, Jalal M. Recommended best practices for lyophilization validation 2021 Part II: process qualification and continued process verification. AAPS PharmSciTech. 2021;22(8):article 266. Springer. doi:10.1208/s12249-021-02107-6.

[24] U.S. Food and Drug Administration. Quality Considerations for Topical Ophthalmic Drug Products — Revised Draft Guidance for Industry. Docket No. FDA-2023-D-4177. Silver Spring, MD: Center for Drug Evaluation and Research, FDA; December 2023. [Revised draft superseding the draft guidance of the same title issued 13 October 2023 (88 FR 70997); draft guidance, non-binding, not for implementation.]

[25] World Health Organization. Good manufacturing practices: water for pharmaceutical use. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-fifth report. Annex 3, WHO Technical Report Series No. 1033. Geneva: World Health Organization; 17 November 2021.

[26] World Health Organization. WHO guidelines on technology transfer in pharmaceutical manufacturing. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-sixth report. Annex 4, WHO Technical Report Series No. 1044. Geneva: World Health Organization; 2022.

[27] Tanzini A, Ruggeri M, Bianchi E, Valentino C, Vigani B, Ferrari F, Rossi S, Giberti H, Sandri G. Robotics and aseptic processing in view of regulatory requirements. Pharmaceutics. 2023;15(6):1581. MDPI. doi:10.3390/pharmaceutics15061581.

[28] Wong WP, Saw PS, Jomthanachai S, Wang LS, Ong HF, Lim CP. Digitalization enhancement in the pharmaceutical supply network using a supply chain risk management approach. Scientific Reports. 2023;13:22287. Nature Portfolio. doi:10.1038/s41598-023-49606-z.

[29] McCall J, Barnard N, Gadient K, Kasireddy C, Kurtz A, Li Y, Page T, Putnam T, Brennan Á. Environmental monitoring for closed robotic workcells used in aseptic processing: data to support advanced environmental monitoring strategies. AAPS PharmSciTech. 2022;23(6):article 215. Springer. doi:10.1208/s12249-022-02360-3. [Correction published: AAPS PharmSciTech. 2022;23(7):article 245. doi:10.1208/s12249-022-02398-3.]

[30] Vogler S. Tackling medicine shortages during and after the COVID-19 pandemic: compilation of governmental policy measures and developments in 38 countries. Health Policy. 2024;143:105030. Elsevier. doi:10.1016/j.healthpol.2024.105030.

[31] Serchen J, Hilden D, Silberger JR; Health and Public Policy Committee of the American College of Physicians. Bolstering the medication supply chain and ameliorating medication shortages: a position paper from the American College of Physicians. Annals of Internal Medicine. 2025;178(10):1464–1468. American College of Physicians. doi:10.7326/ANNALS-25-00607.

@article{1722847,
      author = {Habeeb Shaikh},
      title = {Development of Advanced Sterile Drug Delivery Manufacturing Capabilities for Injectable and Ophthalmic Products in Saudi Arabia},
      journal = {Iconic Research And Engineering Journals},
      year = {2026},
      volume = {10},
      number = {3},
      pages = {774-787},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1722847.pdf},
      abstract = {Saudi Arabia's pharmaceutical localisation agenda is moving beyond import substitution and secondary packaging towards technically independent manufacture. Sterile injectables and ophthalmic products are decisive test cases, because uninterrupted supply depends on simultaneous mastery of contamination control, sterile utilities, terminal sterilisation or aseptic processing, specialised packaging, analytical release and a mature pharmaceutical quality system. This integrative review synthesises Saudi supply-side evidence with current normative requirements from the Saudi Food and Drug Authority (SFDA), the World Health Organization, the European Commission, the United States Food and Drug Administration and the International Council for Harmonisation. The Saudi evidence is consistent across independent datasets. In a survey of 350 stakeholders conducted between November 2024 and February 2025, 73.0% of supply-chain respondents agreed that disruption significantly affects the availability of sterile injectable products, and 65.7% of healthcare professionals reported adverse effects on patient care. A separate survey of 379 personnel within the Ministry of Health supply chain found that 90.0% had experienced shortages of essential medicines or supplies, with 48.5% identifying inadequate planning, forecasting and procurement as the leading cause. An analysis of the SFDA formulary covering items available between 2010 and 2019 attributed 22.55% of registered medicines to Saudi manufacture. The review proposes a capability-based architecture integrating terminal sterilisation wherever scientifically feasible, barrier-enabled aseptic filling, ready-to-use containers, lyophilisation, blow-fill-seal ophthalmic platforms, deterministic container-closure integrity testing and digital quality systems. Localisation should be measured by qualified releasable capacity, process robustness and reduction in shortage exposure rather than by the number of products packaged domestically.},
      keywords = {sterile manufacturing; aseptic processing; injectables; ophthalmic products; pharmaceutical localisation; Saudi Arabia; contamination control; supply resilience},
      month = {September},
      doi = {https://doi.org/10.64388/IREV10I3-1722847}
  }