ing the run, even penetration at all points within the load, and reproducible conditions across three of the four runs. The second run was significantly different from the first, but an SAL of 10 9.98 was attained. This ensured compliance with the BP, which states that an SAL equal to 10 6 or higher must be achieved (10). The conditions used to sterilize the load are halfway between the overkill approach and the bioburden approach, which were described in Part I of this article. They provide an optimum balance between an acceptable degree of sterilization and an acceptable stability of the broth after sterilization. The authors concluded that for this step of qualification the autoclave worked properly within its functional parameters in four consecutive runs and provided an SAL of 10 9.2 or higher.

hensive validation is the meticulous documentation of all activities performed during the process. Documentation provides a comprehensive review of validation results that is essen

tial for acceptance by the quality control unit and also serves to satisfy the scrutiny of regulatory bodies.

AcknowledgmentRoche Products Pty. (Ltd.) Isando, South Africa, is greatly acknowledged for sponsoring this work.

References1. American National Standard ANSI/AAMI/ISO 11134,“Sterilization of Health Care Products: Requirements for Validation and Routine Control—Industrial Moist Heat Sterilization,” (American National Standards Institute, 16 December 1993), pp. 737–763. 2. USP 24–NF 19 (United States Pharmacopeial Convention, Rockville, MD, 2000), pp. 1813, 1819, 2143–2145. 3. British Standard 2646,“Autoclaves for Sterilization in Laboratories, Part I: Specification for Design, Construction, Safety, and Performance,” (British Standard Institution, 1993), pp. 1–36. 4. Guidance for Industry for the Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products,“Information for Terminal Moist Heat Sterilization Processes,” (Center for Drug Evaluation and Research, November 1994) pp. 3–7. 5. T. Trotter,“The Basics of Validating Steam Sterilization Cycles,” J. Valid. Technol. 2 (4), 332–340 (1996). 6. T.E. Ransdell,“The Art and Science of Autoclave Qualification,” J. Valid. Technol. 2 (3), 220–227 (1996).

ConclusionAlthough the validation approach follows several standard steps, exact methods for validation cannot be offered because various autoclave types exist and each unit has specific operating parameters. Practical examples and requirements for validation are offered in this article for readers who may be inexperienced at qualifying steam sterilizers. Some of the principles presented here can be applied to other sterilization procedures. As long as the strategy for validation is based on a logical, systematic approach, and meaningful tests are performed to prove the suitability of the autoclave for its intended use, the validation can only be successful. A key factor for a compre-

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7. British Standard 2646,“Autoclaves for Sterilization in Laboratories. Part 5: Methods of Test for Function and Performance,” (British Standard Institution, 1993), pp. 1–11. 8. M.J. Akers and N.R. Anderson,“Sterilization Validation of Sterile Products,” in Fundamentals in Pharmaceutical Process Validation, I.R. Berry and R.A. Nash, Eds. (Marcel Dekker, New York, NY, 2d ed., 1993), pp. 25–87. 9. European Pharmacopoeia (Council of Europe, Strasbourg, 3d ed., 1997), pp. 283–285. 10. British Pharmacopoeia, Volume II (The Stationary Office, London, 2001), pp. A332–A335. 11. P. Hoet,“Validation and Parametric Release for a Sterile Product,” S.T.P. Pharma Practiques 7 (5), 372–374 (1997). P T

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