If you are inspecting a contract sterilizer, Inspectional Objectives 2 through 5, described below, are applicable and must be performed. 1. An important linkage to consider at this point is Material Controls (820.50 Purchasing Controls). The sediment formed due to sitting should be easily re-dispersed by moderate shaking to yield a homogenous system. Copyright © 2008-2020 Cinergix Pty Ltd (Australia). When conducting a complete sterilization process validation study assessment, the items included in the narrative note under Objective 4 of the Production and Process Controls chapter of this Handbook apply. If you do not have a microbiology lab in-house, you will need to partner with one such as NAMSA, Nelson Labs, LexaMed or Wuxi Apptex to perform the microbiological testing. Sodium acetate, trihydrate, USP/NF/EP 0.68 10. Table 1 lists the samples: Pre-mix 1 is depicted in the top portion of FIG. Lecithin (Phospholipon 90H) 0.15 7. In its quest to guide manufacturers and regulators through this new standard, in August 1996 AAMI's TIR task group concluded that a flowchart with an accompanying text was the most practical approach. No. Step 2: Determine the Cycle Parameters: Time and Temperature. "Aseptic addition" may be attained by filtering through 0.22 micron filters, and by maintaining the mixing equipment sterile by well-known aseptic methods. Finally, combining all three pre-mixes in sterile fashion thereby achieving a sterile suspended pharmaceutical formulation. Next is heat-sterilizing a mixture of water, a water-insoluble pharmaceutical, and at least a partial amount of an electrolyte to provide a sub-saturated solution of the electrolyte, and adding under aseptic conditions an aqueous surfactant, to give a third sterile pre-mix. This recrystallization and/or other thermal effects disrupts the overall homogeneity characteristics of the suspension, which are critical to good manufacturing practice and reliability of dispensing the suspension product. Finally, combining all three pre-mixes in sterile fashion to achieve a sterile suspended pharmaceutical formulation. For instance, using the teachings contained herein one of skill in the art may be able to test and thereby select other combinations of electrolytes for use in pre-mixes 2 and 3 by optimizing the combination of a high flocculate reading combined with a low number of strokes for redispersion.
5,599,824 (Grunenberg et al. bioburden sampling, testing and results). The group also developed test protocols for manufacturers to use to simulate product use and show conformity with the requirements of the standard. Examples of nonconformances and sterilization process failures the investigator may encounter include: Test Failures (e.g. 6 is a histogram depicting the effect of the sterilization process on sediment height (mm) of the 4 samples of the different corticosteroids: Sample 1 is Hydrocortisone acetate; Sample 2 is Dexamethasone; Sample 3 is Dexamethasone acetate; and Sample 4 is Prednisone. Sedimentation rate was assessed by observing the height in millimeters of the column of sedimentation visible in 20 millimeters of specimen suspension contained in a cylinder after shaking and then standing overnight. The ethylene oxide method has been a widely used method for suspension products where product or components are thermolabile. The review of the sterilization process validation study may be limited to a review of the Validation Study Summary (if available) and Approval if the complete validation study was assessed during the previous inspection and there have been no significant changes in the process, product or package that may impact sterilization effectiveness. This review of the control and monitoring activities should be done on the shop floor by reviewing work instructions, product acceptance procedures, control charts, etc. This list can be verified against the DMR and brought to the shop floor to compare with the currently available documents. (a) heat-sterilizing an aqueous solution of a viscosity enhancer, to result in a first sterile pre-mix; (b) sterile-filtering an aqueous solution of a mixture of a pharmaceutically-active compound, which results in a second sterile pre-mix; (c) heat-sterilizing a mixture of water, a water-insoluble pharmaceutical, and at least a partial amount of an electrolyte to provide a sub-saturated solution of said electrolyte, and adding under aseptic conditions an aqueous surfactant, to give a third sterile pre-mix; (d) combining all three pre-mixes in sterile fashion to achieve a sterile suspended pharmaceutical formulation. Once the sterilization process is completed, the probes are kept in nutrition media to check the survival of microbes in it. Only packaging components, or containers etc. inspections and tests are aware of the defects and errors that may be encountered while performing their assigned responsibilities. These new combinations would be within the spirit and scope of this invention. reveals that the sterilization process is outside the firm's tolerance for operating or performance parameters: Determine whether the nonconformances were handled appropriately; and, Review the equipment adjustment, calibration and maintenance. FIG. This is done for all methods of sterilization. If a firm does not claim to comply with a recognized standard, it must provide a scientific rationale supporting the method used for validating and processing its sterilization loads. 1: This formulation has been shown to be effective as an antibiotic for treatment of otitis externa as shown in co-pending U.S. patent application Ser. For the 1st pre-mix, polyvinyl alcohol (PVA) (Airvol™ 125, Air Products Inc.; 99% hydrolyzed preferred) was dissolved in approx. An effective sterilization destroys all the bacterial spores during the process. Any pharmaceutically active compound or that may be formulated as a suspension comes within the scope of this invention. All rights reserved. Another embodiment of the invention is directed to a method for sterilizing a pharmaceutical suspension of a water-insoluble pharmaceutical, comprising the steps of first heat-sterilizing an aqueous solution of a viscosity enhancer, to give a first sterile pre-mix. All rights reserved. The need for sterility in certain pharmaceutical formulations is mandated both by concerns for the general public's safety, and a pharmaceutical company's reputation for producing quality products.