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A written description of specific training and performance evaluation program for individuals involved in the use of aseptic techniques for the preparation of sterile products must be developed for each site. This program equips the personnel with the appropriate knowledge and trains them in the required skills necessary to perform the assigned tasks. Each person assigned to the aseptic area in the preparation of sterile products must successfully complete specialized training in aseptic techniques and aseptic area practices prior to preparing CSPs (see Personnel Training and Evaluation in Aseptic Manipulation Skills section).
Aseptic Technique
Critical operations are carried out by appropriately trained and qualified personnel in a DCCA using proper aseptic techniques described in a written procedure (see Suggested Standard Operating Procedures). Aseptic technique is equally applicable to the preparation of sterile sensitizing and chemotoxic agents. However, it is essential to recognize that additional precautions must be utilized to protect the personnel and the compounding environment from the potential adverse effects of these chemotoxic products. The minimum requirements for this process include the following: working and verified vertical laminar airflow work bench, barrier isolator, or other environmental containment and control device with biohazard control capabilities; the protective capabilities of gowns, masks, bouffants, and gloves; sprayback and spill control techniques and equipment; the use specialized compounding devices and equipment; and proper disposal.
Compounding personnel ascertain that ingredients for CSPs are of the correct identity and appropriate quality using the following information: vendors' labels, labeling, certificates of analysis, direct chemical analysis, and knowledge of compounding facility storage conditions.
Commercially available sterile drug products, sterile ready-to-use containers and devices are examples of sterile components. A written procedure for unit-by-unit physical inspection preparatory to use is followed to ensure that these components are sterile, free from defects, and otherwise suitable for their intended use.
If any nonsterile components, including containers, devices, and ingredients are used to make a CSP, such CSPs must be compounded at a high-risk level. Nonsterile active ingredients and added substances, or excipients, for CSPs should preferably be official USP or NF articles. When nonofficial ingredients are used, they must be accompanied by certificates of analysis from their suppliers to aid compounding personnel in judging the identity, quality, and purity in relation to the intended use in a particular CSP. Physical inspection of a package of ingredients is necessary in order to detect breaks in the container, looseness in the cap or closure, and deviation from the expected appearance, aroma, and texture of the contents.
Bulk, or unformulated, drug substances and added substances, or excipients, must be stored in tightly closed containers under temperature, humidity, and lighting conditions that are either indicated in official monographs or approved by suppliers; also the date of receipt in the compounding facility must be clearly and indelibly marked on each package of ingredient. After receipt by the compounding facility, packages of ingredients that lack a supplier's expiration date cannot be used after one year, unless either appropriate inspection or testing indicates that the ingredient has retained its purity and quality for use in CSPs.
Careful consideration and evaluation of nonsterile ingredient sources is especially warranted when the CSP will be administered into the vascular, central nervous system, and eyes.
Upon receipt of each lot of the bulk drug substance or excipient used for CSPs, the individual compounding the preparation performs a visual inspection of the lot for evidence of deterioration, other types of unacceptable quality, and wrong identification. The bulk drug substance or excipient visual inspection is performed on a routine basis as described in the written protocol.
It is necessary that equipment, apparatus, and devices used to compound a CSP are consistently capable of operating properly and within acceptable tolerance limits. Written procedures outlining required equipment calibration, annual maintenance, monitoring for proper function, controlled procedures for use of the equipment and specified time frames for these activities are established and followed. Routine maintenance and time intervals are also outlined in these written procedures. Results from the equipment calibration, annual maintenance reports, and routine maintenance are kept on file for the lifetime of the equipment. Personnel is prepared through an appropriate combination of specific training and experience to operate or manipulate any piece of equipment, apparatus, or device they may use when preparing CSPs. Training includes gaining the ability to determine whether any item of equipment is operating properly or is malfunctioning.