Basics of Sterilization Methods

Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 6)

Abstract

The manufacturing of parenteral formulations should include a sterilization step in order to maintain product quality. How the most common sterilization techniques are performed and some of the advantages and disadvantages of each type will be summarized. Sterilization methods that will be covered include the fundamentals of steam, radiation, and ethylene oxide terminal sterilizations, as well as aseptic processing. Once a sterilization cycle or procedure has been chosen and developed, its effectiveness should be validated according to the guidelines of the respective authorities. Some of the documentation that regulators may review to decide whether they believe a method is acceptable is summarized in this chapter. While regional regulatory authorities may differ on what types of information should be submitted to their agencies and what should be reviewed during field inspections of a manufacturing facility, the focus for this chapter will be validation information and Good Manufacturing Practices aspects of sterilization techniques.

Keywords

Porosity Hydrogen Peroxide Filtration Cobalt Steam 

References

  1. AAMI/ANSI/ISO 10993–7 (1995) Biological evaluation of medical devices—part 7: ethylene oxide sterilization residuals. Association for the Advancement of Medical Instrumentation, Arlington, VAGoogle Scholar
  2. Adler N (1965) Residual ethylene oxide and ethylene glycol in ethylene oxide sterilized pharmaceuticals. J Pharm Sci 54:735–742PubMedCrossRefGoogle Scholar
  3. Agalloco J (2011) Steam sterilization process validation. In: Moldenhauer J (ed) Thermal validation in moist heat sterilization. Davis Healthcare International, River Grove, ILGoogle Scholar
  4. ANSI/AAMI/ISO TIR11139:2006, Sterilization of health care products-vocabulary. Association for the Advancement of Medical Instrumentation, Arlington, VAGoogle Scholar
  5. ANSI/AAMI/ISO 11135–1:2007, Sterilization of health care products–ethylene oxide—part 1: requirements for development, validation and routine control of a sterilization process for medical devices. Association for the Advancement of Medical Instrumentation, Arlington, VAGoogle Scholar
  6. ANSI/AAMI/ISO 11137–2:2006, Sterilization of health care products—radiation—part 2: establishing the sterilization dose. Association for the Advancement of Medical Instrumentation, Arlington, VAGoogle Scholar
  7. ANSI/AAMI/ISO 17665–1:2006 Sterilization of health care products—moist heat—part 1: requirements for the development, validation, and routine control of a sterilization process for medical devices. Association for the Advancement of Medical Instrumentation, Arlington, VAGoogle Scholar
  8. ANSI/IEST/ISO 14644–2:2000 (2000) Cleanrooms and associated controlled environments-part 2: specifications for testing and monitoring to prove continued compliance with ISO 14644–1. International Organization for Standardization, GenevaGoogle Scholar
  9. ASTM, Committee F 838–05 (2005) Standard test method for determining bacterial retention of membrane filters utilized for liquid filtration. ASTM International, West Conshohocken, PAGoogle Scholar
  10. Chmielewski AG, Sadat T, Zimek Z (2008) Electron accelerators for radiation sterilization. In: Trends in radiation sterilization of health care products. International Atomic Energy Agency, Vienna. http://www-pub.iaea.org/MTCD/publications/PDF/Pub1313_web.pdf
  11. Coon AS, Sadowski MJ (2011) Practical aspects of thermal validation for moist heat sterilization. In: Moldenhauer J (ed) Thermal validation in moist heat sterilization. Davis Healthcare International, River Grove, ILGoogle Scholar
  12. Dosage Form Drug Manufacturers cGMPs (1993) Guide to inspections of dosage form drug manufacturer’s—cGMPR’s. http://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074927.htm
  13. EMEA (European Agency for the Evaluation of Medicinal Products) (2000) Decision trees for the selection of sterilisation methods, annex to note for guidance on development pharmaceutics. EMA, London. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003520.pdf
  14. Ethylene oxide, ethylene chlorohydrin, and ethylene glycol—proposed maximum residue limits and maximum levels of exposure. U.S. Federal Register, Vol 43, No. 121, 23 June 1978. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM078413.pdf
  15. EudraLex (2008) The rules governing medicinal products in the European Union, volume 4—EU guidelines to good manufacturing practice, medicinal products for human and veterinary use, Annex 1—manufacture of sterile medicinal products. http://ec.europa.eu/health/files/eudralex/vol-4/pdfs-en/2008_02_12_gmp_annex1_en.pdf
  16. European Union (1992) The use of ionizing radiation in the manufacture of medicinal products. http://www.emea.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002918.pdf
  17. European Pharmacopoeia (2011) 5.1.1 Methods of preparation of sterile products, 7th edn (7.0), European Directorate for the Quality of Medicines, StrasbourgGoogle Scholar
  18. European Agency for the Evaluation of Medicinal Products Committee for Proprietary Medicinal Products (1996) Note for guidance on manufacture of the finished dosage form. EMEA, London. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002916.pdf
  19. FDA (1994) Guidance for industry for the submission documentation for sterilization process validation in applications for human and veterinary drug products. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072171.pdf
  20. FDA (2004) Guidance for industry—sterile drug products produced by aseptic processing—current good manufacturing practice. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070342.pdf
  21. Hammad AA (2008) Microbiological aspects of radiation sterilization. In: Trends in radiation sterilization of health care products. International Atomic Energy Agency, Vienna. http://www-pub.iaea.org/MTCD/publications/PDF/Pub1313_web.pdf
  22. Huang C, Wu C, Shih W, Chen M, Chen C, Chien Y, Liou S, Chiang K (2011) Comparative analysis of urinary N7-(2-hydroxyethyl)guanine for ethylene oxide and non-exposed workers. Toxicol Lett 202:237–243PubMedCrossRefGoogle Scholar
  23. ISO 11135–2:2008(E), Sterilization of health care products-ethylene oxide-Part 2: guidance on the application of ISO 11135–1, International Organization for Standardization, GenevaGoogle Scholar
  24. ISO 14644–1:1999(E) (1999) Cleanrooms and associated controlled environments—part 1: classification of air cleanliness. First edition, International Organization for Standardization, GenevaGoogle Scholar
  25. ISO 14644–3:2005 (2005) Cleanrooms and associated controlled environments—part 3: test methods. First edition, International Organization for Standardization, GenevaGoogle Scholar
  26. ISO/ASTM 51261-2002. Guide for selection and calibration of dosimetry systems for radiation processing. ASTM International, West Conshohocken, PAGoogle Scholar
  27. Jurado AS, Pinheiro TJ, Madeira VM (1991) Physical studies on membrane lipids of Bacillus stearothermophilus temperature and calcium effects. Arch Biochem Biophys 289:167–179PubMedCrossRefGoogle Scholar
  28. Lemieux P (2006) Destruction of spores on building decontamination residue in a commercial autoclave. Appl Environ Microbiol 72:7687–7693PubMedCrossRefGoogle Scholar
  29. Loo JSC, Tan ZYS, Chow YJ, Lin SLI (2010) Drug release from irradiated PLGA and PLLA multilayer films. J Pharm Sci 99:3060–3071PubMedGoogle Scholar
  30. Lucas AD, Merritt K, Hitchins VM (2004) Damage of office supply, personal use items, and over-the-counter medical devices after sterilization by ethylene oxide gas, electron beam, and gamma radiation. Biomed Instrum Technol 38:476–484PubMedGoogle Scholar
  31. Mankel G (2008) The challenges of packaging combination devices. Med Device Technol 19:19–25PubMedGoogle Scholar
  32. Matthews IP, Gibson C, Samuel AH (1994) Sterilization of implantable devices. Clin Mater 15:191–215PubMedCrossRefGoogle Scholar
  33. EMA (European Medicines Agency) (2010) Compilation of community procedures in inspections and exchange of information—conduct of inspections of pharmaceutical manufacturers or importers. Rev 1. EMA, London. http://www.ipqpubs.com/wp-content/uploads/2010/05/EMA-Conduct-of-Inspections-of-Pharmaceutical-Manufacturers.pdf
  34. Mehta K (2008) Gamma irradiators for radiation sterilization. In: Trends in radiation sterilization of health care products. International Atomic Energy Agency, Vienna. http://www-pub.iaea.org/MTCD/publications/PDF/Pub1313_web.pdf
  35. Nims RW, Gauvin G, Plavsic M (2011) Gamma irradiation of animal sera for inactivation of viruses and mollicutes—a review. Biologicals 39:370–377PubMedCrossRefGoogle Scholar
  36. Oxborrow GS, Placencia AM, Danielson JW (1983) Effects of temperature and relative humidity on biological indicators used for ethylene oxide sterilization. Appl Environ Microbiol 45:546–549PubMedGoogle Scholar
  37. PDA Technical Report 16 (1992) Effects of gamma irradiation on elastomeric closures. PDA J Pharm Sci Technol 46 Suppl 2:S1–13Google Scholar
  38. PDA Technical Report 26 (1998) Sterilizing filtration of liquids. PDA J Pharm Sci Technol 52 Suppl 1:1–31Google Scholar
  39. Sharpe P and Miller A (2009) NPL Report CIRM 29, guidelines for the calibration of routine dosimetry systems for use in radiation processing. National Physical Laboratory, Middlesex. http://www.chemdos.npl.co.uk/docs/NPLReportCIRM29.pdf
  40. Singh B, Parwate DV, Shukla SK (2011) Radiosterilization of fluoroquinolones and cephalosporins: assessment of radiation damage on antibiotics by changes in optical properties and colorimetric parameters. AAPS PharmSciTech 10:34–43CrossRefGoogle Scholar
  41. Sundaram S, Eisenhuth J, Howard G, Brandwein H (2001) Retention of water-borne bacteria by membrane filters part I, bacterial challenge tests on 0.2 and 0.22 micron rated filters. PDA J Pharm Sci Technol 55:65–86PubMedGoogle Scholar
  42. The Japanese Pharmacopoeia Fifteenth Edition (2006) General information chapter 25: sterility assurance for terminally sterilized pharmaceutical products. http://jpdb.nihs.go.jp/jp15e/JP15.pdf
  43. The Japanese Pharmacopoeia Fifteenth Edition (2006) General information chapter 13: microbiological evaluation of processing areas for sterile pharmaceutical products. http://jpdb.nihs.go.jp/jp15e/JP15.pdf
  44. United States Department of Labor, Occupational Safety and Health Administration report analytical methods for ethylene oxide (1981) https://www.osha.gov/dts/sltc/methods/organic/org030/org030.html
  45. United States Pharmacopeia 34 (2011a) Chapter <1035> Biological indicators for sterilization. The United States Pharmacopeial Convention, Rockville, MDGoogle Scholar
  46. United States Pharmacopeia 34 (2011b) Chapter <1116> Microbiological control and monitoring of aseptic processing environments. The United States Pharmacopeial Convention, Rockville, MDGoogle Scholar
  47. Use of Ethylene Oxide as a Sterilant in Medical Facilities. (1977) NIOSH Special Occupational Hazard Review with Control Recommendations, U.S. Department of Health and Human Services, Rockville, MDGoogle Scholar
  48. Woo L, Purohit KS (2002) Advancements and opportunities in sterilization. Med Device Technol 13:12–17PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  1. 1.U.S. Food and Drug Administration, Center for Veterinary MedicineRockvilleUSA

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