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Jul 31 2019

General Chapters: PHARMACEUTICAL COMPOUNDING-STERILE PREPARATIONS, pharmaceutical compounding.#Pharmaceutical #compounding


pharmaceutical compounding

RESPONSIBILITY OF COMPOUNDING PERSONNEL

  1. Compounding personnel are adequately skilled, educated, instructed, and trained to correctly perform and document the following activities in their sterile compounding duties:

CSP MICROBIAL CONTAMINATION RISK LEVELS

  1. The CSPs are compounded with aseptic manipulations entirely within ISO Class 5 (see Table 1 ) or better air quality using only sterile ingredients, products, components, and devices.
  2. The compounding involves only transfer, measuring, and mixing manipulations with closed or sealed packaging systems that are performed promptly and attentively.
  3. Manipulations are limited to aseptically opening ampuls, penetrating sterile stoppers on vials with sterile needles and syringes, and transferring sterile liquids in sterile syringes to sterile administration devices and packages of other sterile products.
  4. For a low-risk preparation, in the absence of passing a sterility test, the storage periods cannot exceed the following time periods: before administration, the CSPs are properly stored and are exposed for not more than 48 hours at controlled room temperature (see General Notices and Requirements ), for not more than 14 days at a cold temperature (see General Notices and Requirements ), and for 45 days in solid frozen state at 20 Pharmaceutical compoundingor colder.
  1. Single transfers of sterile dosage forms from ampuls, bottles, bags, and vials using sterile syringes with sterile needles, other administration devices, and other sterile containers. The contents of ampuls require sterile filtration to remove any glass particles.
  2. Manually measuring and mixing no more than three manufactured products to compound drug admixtures and nutritional solutions.
  1. Routine disinfection and air quality testing of the direct compounding environment to minimize microbial surface contamination and maintain ISO Class 5 air quality (see Table 1 ).
  2. Visual confirmation that compounding personnel are properly donning and wearing appropriate items and types of protective garments and goggles.
  3. Review of all orders and packages of ingredients to assure the correct identity and amounts of ingredients were compounded.
  4. Visual inspection of CSPs to ensure the absence of particulate matter in solutions, the absence of leakage from vials and bags, and the accuracy and thoroughness of labeling.
  1. Multiple individual or small doses of sterile products are combined or pooled to prepare a CSP that will be administered either to multiple patients or to one patient on multiple occasions.
  2. The compounding process includes complex aseptic manipulations other than the single-volume transfer.
  3. The compounding process requires unusually long duration, such as that required to complete dissolution or homogeneous mixing.
  4. The sterile CSPs do not contain broad-spectrum bacteriostatic substances, and they are administered over several days (e.g., an externally worn or implanted infusion device).
  5. For a medium-risk preparation, in the absence of passing a sterility test, the storage periods cannot exceed the following time periods: before administration, the CSPs are properly stored and are exposed for not more than 30 hours at controlled room temperature (see General Notices and Requirements ), for not more than 7 days at a cold temperature (see General Notices and Requirements ), and for 45 days in solid frozen state at 20 Pharmaceutical compoundingor colder.
  1. Compounding of total parenteral nutrition fluids using manual or automated devices during which there are multiple injections, detachments, and attachments of nutrient source products to the device or machine to deliver all nutritional components to a final sterile container.
  2. Filling of reservoirs of injection and infusion devices with multiple sterile drug products and evacuation of air from those reservoirs before the filled device is dispensed.
  3. Filling of reservoirs of injection and infusion devices with volumes of sterile drug solutions that will be administered over several days at ambient temperatures between 25 Pharmaceutical compoundingand 40Pharmaceutical compounding.
  4. Transfer of volumes from multiple ampuls or vials into a single, final sterile container or product.
  1. Nonsterile ingredients, including manufactured products for routes of administration other than those listed under c. in the Introduction are incorporated or a nonsterile device is employed before terminal sterilization.
  2. Sterile ingredients, components, devices, and mixtures are exposed to air quality inferior to ISO Class 5 (see Table 1 ). This includes storage in environments inferior to ISO Class 5 of opened or partially used packages of manufactured sterile products that lack antimicrobial preservatives.
  3. Nonsterile preparations are exposed for at least 6 hours before being sterilized.
  4. It is assumed, and not verified by examination of labeling and documentation from suppliers or by direct determination, that the chemical purity and content strength of ingredients meet their original or compendial specifications in unopened or in opened packages of bulk ingredients (see Ingredient Selection under Pharmaceutical Compounding Nonsterile Preparations Pharmaceutical compounding795 Pharmaceutical compounding).
  5. For a high-risk preparation, in the absence of passing a sterility test, the storage periods cannot exceed the following time periods: before administration, the CSPs are properly stored and are exposed for not more than 24 hours at controlled room temperature (see General Notices and Requirements ), for not more than 3 days at a cold temperature (see General Notices and Requirements ), and for 45 days in solid frozen state at 20 Pharmaceutical compoundingor colder.
  1. Dissolving nonsterile bulk drug and nutrient powders to make solutions, which will be terminally sterilized.
  2. Sterile ingredients, components, devices, and mixtures are exposed to air quality inferior to ISO Class 5 (see Table 1 ). This includes storage in environments inferior to ISO Class 5 of opened or partially used packages of manufactured sterile products that lack antimicrobial preservatives.
  3. Measuring and mixing sterile ingredients in nonsterile devices before sterilization is performed.
  4. Assuming, without appropriate evidence or direct determination, that packages of bulk ingredients contain at least 95% by weight of their active chemical moiety and have not been contaminated or adulterated between uses.
  1. Dissolve 3 g of nonsterile commercially available Soybean Casein Digest Medium in 100 mL of nonbacteriostatic water to make a 3% solution.
  2. Draw 25 mL of the medium into each of three 30-mL sterile syringes. Transfer 5 mL from each syringe into separate sterile 10-mL vials. These vials are the controls, and they generate exponential microbial growth, indicated by visible turbidity upon incubation.
  3. Under aseptic conditions and using aseptic techniques, affix a sterile 0.2- m porosity filter unit and a 20-gauge needle to each syringe. Inject the next 10 mL from each syringe into three separate 10-mL sterile vials. Repeat the process into three more vials. Label all vials, affix sterile adhesive seals to the closure of the nine vials, and incubate them at 25 Pharmaceutical compoundingto 35Pharmaceutical compounding. Inspect for microbial growth over 14 days as described in the Personnel Training and Evaluation in Aseptic Manipulation Skills section.

VERIFICATION OF COMPOUNDING ACCURACY AND STERILIZATION

  1. CSPs have been ascertained to remain physically and chemically stable when subjected to the selected sterilization method.
  2. Glass and metal devices may be covered tightly with aluminum foil, then exposed to dry heat in an oven at a mean temperature of 250 Pharmaceutical compoundingfor 2 hours to achieve sterility and depyrogenation (see Dry-Heat Sterilization under Sterilization and Sterility Assurance of Compendial Articles Pharmaceutical compounding1211 Pharmaceutical compounding). Such items are either used immediately or stored until use in an environment suitable for compounding low- and medium-risk CSPs.
  3. Personnel ascertain from appropriate information sources that the sterile microporous membrane filter used to sterilize CSP solutions, either during compounding or administration, is chemically and physically compatible with the CSP.

PERSONNEL TRAINING AND EVALUATION IN ASEPTIC MANIPULATION SKILLS

ENVIRONMENTAL QUALITY AND CONTROL

Pharmaceutical compounding

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