Container closure systems description

Microbiological aspects will need to be discussed, but the amount of information will depend on the type of product. For nonsterile products there will need to be a description of the microbiological attributes of the product and, if appropriate, a rationale for not performing microbial limit tests. For preserved products the selection of the antimicrobial preservatives will need to be discussed and the effectiveness of the selected system demonstrated. For sterile products there will need to be appropriate process validation data and information on the integrity of the container-closure system. 

Primary container-closure system-related data will need to cover storage, transportation, and use. The choice of materials of construction, their description, and the ability of the container-closure system to protect from moisture and/or light will need to be considered. The compatibility of the container-closure and its contents will need to consider sorption, leaching, and safety. The performance of the container-closure system will also need to be considered in terms of dose delivery from any associated device that is to be supplied as part of the product. Container-closure components will require adequate specifications covering description, identification, critical dimensional tolerances, and test methodology (including pharma-copeial and noncompendial methods). More data are likely to be required for liquid or semi-liquid products than for solid dosage forms. In the latter, product stability data and container-closure system specifications may suffice. 

When information on a container closure system is submitted in an application, the emphasis would normally be on the primary packaging components. For a secondary packaging component, a brief description will usually suffice unless the component is intended to provide some additional measure of protection to the drug product. In this case, more complete information should be provided, along with data showing that the secondary packaging component actually provides the additional protection. 

A general description of the entire container closure system should be provided in the CMC section of the appli-... 

Although ophthalmic drug products can be considered topical products, they have been grouped here with inject-ables because they are required to be sterile (21 CFR 200.50(a)(2)) and the descriptive, suitability, and quality control information is typically the same as that for an injectable drug product. Because ophthalmic drug products are applied to the eye, compatibility and safety should also address the container closure system s potential to form substances which irritate the eye or introduce particulate matter into the product (see USP <771> Ophthalmic Ointments). 

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. 

Container/Closure System. A description of the container and closure system and its compatibility with the drug substance should be submitted. The section should include detailed information concerning the supplier and the results of compatibility, toxicity, and biologic tests. Alternatively, a drug master file (DMF) may be referenced for this information. 

A description of all the container/closure system configurations for the drug to be marketed should be presented. In addition, stability data and any other information that support the suitability of the container/closure components, including specifications and test methods, should be indicated. 

Description—Overall general description of the container-closure system plus specific information on suppliers, materials of construction, and postmanufacturing treatments. 

Container/closure system(s) and other packaging Detailed description (inc. liner or wadding, details of composition) describe other (e.g, outer) packaging state materials and specifications for part in contact with the product, or if protective. Parenteral BP, EP, JP or USP ... 

Stability testing A brief description of the stability study and the test methods used to monitor the stability of the drug product packaged in the proposed container/closure system and storage conditions should be submitted. Preliminary tabular data based on representative material may be submitted. Neither detailed stability data nor the stability protocol need to be submitted. 

A brief description and discussion of the container closure system for a drug substance is to include the identity of and specification for materials of construction of each primary packaging component. The suitability of each component should be summarized. 

A brief description of a drug product container closure system is to include the identity of materials of construction for each primary packaging component and their specifications. Where appropriate, noncompendial methods and their validation should be summarized. 

Information on the analytical reference standard Description of the container/closure system Stability data... 

Description of the container/closure system—K brief description of the primary and minimally functional secondary materials used in the packaging of the finished developmental API should be provided (e.g., double high-density polyethylene liner inside a fiberboard container/closure). Consideration should also be given to including appropriate acceptance criteria for the primary (i.e., product contact) material. The container/closure described in this section should be consistent with that used for stability testing of the compound, or exceptions should be noted. 

A description and statement of the composition of the container/ closure system used to store and/or ship the finished API should be provided. Where a nonroutine system is used, a drawing is often very useful. Although the requirements... 

Description or designation of the container or containers, of the type of packaging, label and approved package insert and, if necessary, the designation of the closure systems to be used ... 

The main postulate of quantum mechanics is that the whole information of a general system under study is contained in the total wave functions Tjt). This is known as completeness of the quantum-mechanical description. Such a circumstance is coherent with Eq. (6) since 2 is assumed to carry the whole information of the investigated system. This is formally expressed through the closure relation for the exact orthonormalized basis Tfc) ... 

In summary, one of the weakest links in modeling reactive systems operated in bubble columns is the fluid dynamic part considering multi-phase turbulence modeling, interfacial closures, and especially the impact and descriptions of bubble size and shape distributions. For reactive systems the estimates of the contact areas and thus the interfacial mass transfer rates are likely to contain large uncertainties. 

Chapter 4 contains a summary of the basic theory of granular flow. These concepts have been adopted describing particulate flows in fluidized bed reactors. The theory was primarily used for dense bed reactors, but modified closures of this type have been employed for more dilute flows as well. Compared to the continuum theory presented in the third chapter, the granular theory is considered more complex. The main purpose of introducing this theory, in the context of reactor modeling, is to improve the description of the particle (e.g., catalyst) transport and distribution in the reactor system. 

As discussed in Chapter 2, the one-particle NDF does not usually provide a complete description of the microscale system. For example, a microscale system containing N particles would be completely described by an A-particle NDF. This is because the mesoscale variable in any one particle can, in principle, be influenced by the mesoscale variables in all N particles. Or, in other words, the N sets of mesoscale variables can be correlated with each other. For example, a system of particles interacting through binary collisions exhibits correlations between the velocities of the two particles before and after a collision. Thus, the time evolution of the one-particle NDF for velocity will involve the two-particle NDF due to the collisions. In the mesoscale modeling approach, the primary physical modeling step involves the approximation of the A-particle NDF (i.e. the exact microscale model) by a functional of the one-particle NDF. A typical example is the closure of the colli-sionterm (see Chapter 6) by approximating the two-particle NDF by the product of two one-particle NDFs. 

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