Packaging Components Testing

Packaging components for parenteral products are generally composed of three items glass/plastic containers, elastomeric closures, and plastic bags. Selection of the packaging components depends on the compatibility between the formulation and the packaging material and on any special requirement of the formulation. 

Plastic containers are also widely used for packaging parenteral products, such as intravenous (IV) infusion fluid containers, irrigation fluid containers, prefilled disposable syringes, and some administration sets. Polymeric containers have an added advantage of low breakage and are preferred when the SVP product is a highly toxic material such as oncolytic drugs. Typical polymeric 

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To establish safety and to ensure consistency, the complete chemical composition should be provided for every material used in the manufacture of a packaging component. Test results from appropriate qualification and characterization tests should be provided. Adequate information regarding the tests, methods, acceptance criteria, reference standards, and validation information should be also provided. 

The terms quality assurance and quality control are sometimes used interchangeably, but there is an important difference. Quality control generally refers to testing of raw materials, packaging components, and... 

The manufacture and sale of parenteral products is regulated by federal and state laws, as well as by the USP. Federal drug regulations are discussed in detail in Chapter 20. The USP provides specifications, test procedures, standards, etc. for parenteral products and their packaging components. In addition to individual monographs, the USP limits the use of certain additives (see Table 4), limits the size of multiple-dose containers to 30 mL, and requires a suitable preservative to be added to containers intended for multiple use. 

To address performance, the results of nonfunctionality tests are considered sufficient if the test and acceptance criteria are appropriate for the intended purpose. Tests described there are typically considered sufficient standards for establishing specified properties and characteristics of specified materials of construction or packaging components. For nonfunctionality tests, an applicant should provide justification for the use of the test, a complete and detailed description of how the test was performed, and an explanation of what the test is intended to establish. If a related test is available, comparative data should be provided using both methods. Supporting data should include a demonstration of the suitability of the test for its intended use and its validation. 

Testing on an assembled container closure system is usually performed by the applicant (or a testing laboratory commissioned by the applicant), and the test results are provided in the application. Such tests may include vacuum-leak testing, moisture permeation, and weight loss or media fill. Testing on an individual packaging component is typically performed by the manufacturer of the component and is reported via a DMF (see Section V). 

The tests and methods used by the applicant for acceptance of each batch of a packaging component that they receive should be described. If a batch is to be accepted based on a supplier s COA or COC, then the procedure for supplier validation should be described. The data from the supplier s COA or COC should clearly indicate that the lot meets the applicant s acceptance criteria. Acceptance criteria for extractables should also be included, if appropriate. 

Each manufacturer of a packaging component sold to a drug product manufacturer should provide a description of the quality control measures used to maintain consistency in the physical and chemical characteristics of the component. These measures generally include release criteria (and test methods, if appropriate) and a description of the manufacturing procedure. If the release of the packaging component is based on statistical process control, a complete description of the process (including control criteria) and its validation should be provided. 

The application (or Type II DMF) should include a detailed description of the complete container closure system for the bulk drug substance as well as a description of the specific container, closure, all liners, inner seal, and desiccant (if any), and a description of the composition of each component. A reference to the appropriate indirect food additive regulation is typically considered sufficient to establish the safety of the materials of construction. The tests, methods, and criteria for the acceptance and release of each packaging component should be provided. Stability studies to establish a retest period for bulk drug substance in the proposed container closure system should be conducted with fillers or desiccant packs in place (if used). Smaller versions that simulate the actual container closure system may be used. 

A change in an analytical procedure used for testing components, packaging components, the final intermediate, in-process materials after the final intermediate, or starting materials introduced after the final Inter-... 

As with other packaging components, the incoming tests and specifications of metered valves, inspection attributes, and AQLs (acceptable quality levels) will need to be coordinated with the supplier. The valve should be considered as a critical package component and have incoming performance tests, such as spray weights and weight loss [13,14], The performance test could be conducted on a sample of the valve lots from either scale-up or pilot trials before the validation lots are prepared. This information may also be available for each lot from the supplier. It is recommended that each test shown in Table 3 be conducted on at least three valve lots as part of the validation program. 

Operational verification of packaging components. A simulated production run is used to observe, assess, and document the performance of the equipment with packaging components. The behavior of the components on the equipment should be in accordance with the SOPs. Any discrepancies between the intended/planned and actual operation are corrected. After the corrections have been made, a simulated production run and the tests procedures are repeated and the results are documented. 

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