Noncompendial methods

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. 

History and rationale for the development of all major noncompendial methods for excipients and the finished product. 

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. 

Equipment and methods will be operated/performed in accordance with cGMPs. Instruments will be calibrated, automatic analyzers and equipment will be qualified computer-related systems will be validated analytical methods from USP/NF will be verified and glassware preparation, media preparation, and noncompendial methods will be validated. 

Quality controls for packaging components and materials. Identity of materials of the primary packaging components and their specifications. Noncompendial methods (with validation) should be provided where appropriate. 

USP Dissolution Apparatus 1 (basket) and 2 (paddle) are commonly used for immediate-release formulations. USP Apparatus 3 (reciprocating cylinders) is the system of choice for testing extended-release products or a dosage form that requires release profiling at multiple pH levels and time points. Low-dose products may require the use of flow-through analysis or other low-volume test techniques (noncompendial 100- or 200-mL dissolution vessels). Once the apparatus is selected and has been shown to be suitable during method development, no further evaluation of another apparatus is required during validation. 

Since the small volume vessels and minipaddles were noncompendial, additional studies were performed to confirm the appropriateness of the method parameters selected and the discriminatory ability of the method. The effect of paddle speed, paddle height and sampling zone were evaluated in an experimental design of experiment study. In addition, the discriminatory ability of the method was evaluated using purposefully perturbed or aberrant tablets, to model poorly dissolving tablets. 

Specifications and Methods for Drug Product Ingredients. If the information is not specified in the drug substance section, this section should include a description of tests and specifications for all active ingredients. The specifications for all ancillary products included in the drug product should be provided as well. Information on all excipients, including process gases and water, should be included and should include a list of compendial excipients (and their citations) and tests and specifications for noncompendial excipients. 

P.4.1 Specifications Reference for compendial items Additional requirements for compendial items, if any Specifications and methods for noncompendial items... 

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