Container/closure material

Degradation products are those compounds produced through the chemical or thermal decomposition of the analyte. Container/closure adducts are generally the result of an interaction between a drug substance or intermediate with the container/closure material or extracta-bles from these materials. 

Chemical instability reactions appear with or without microbiological contribution through reactions such as hydrolysis, oxidation, isomerization, and epi-merization. Interactions between ingredients and ingredients with container closure materials are established as the principal causes of these reactions [1], for instance, the hydrolysis of cefotaxime sodium, the oxidation of vitamin C, the isomerization of epinephrine, and the epimerization of tetracycline [7],... 

Bulk drug substance container closure Material-specific surface effects Bnlk drng snbstance may typically be stored in teflon, polycarbonate, polypropylene bottles, or flexible bags constructed of various types of multUaminar films... 

The rubbers are also used for such diverse applications as blood transfusion tubing capable of sterilisation, antibiotic container closures, electric iron gaskets, domestic refrigerators and non-adhesive rubber-covered rollers for handling such materials as confectionery and adhesive tape. The cold-curing rubbers are of value in potting and encapsulation. 

A description of the drug product containers, closures, and packaging materials, including a specimen or copy of each label and all other labeling signed and dated by the person or persons responsible for approval of such labeling ... 

A complete record of all data secured in the course of each test, including all graphs, charts, and spectra from laboratory instrumentation, properly identified to show the specific component, dmg product container, closure, in-process material, or drug product, and lot tested. 

Container Closure. The stainless steel containers (3) of material minced in ben-... 

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. 

The packaging material should normally be selected so as to allow the optimal sterilization process to be applied to the product as a whole. Lfowever, factors other than the method of sterilization have to be taken into account in selecting a container material, such as the route of administration and patient convenience and compliance. Where the choice of container-closure precludes the use of terminal processing in the final container, the application should include appropriate documentation to explain and scientifically justify such a choice. The guidelines indicate that in such cases it is still the manufacturer s duty to continue the search for alternative containers that would allow terminal processes while providing the necessary product characteristics. 

Thought has to be given to the appropriate type of container, closure and label before setting out to collect the sample. Glass may be thought of as an inert material but it is not suitable for some samples. 

Organization and personnel describe that in the dispensing of all prescriptions, the pharmacist has the responsibility and authority to inspect and approve or reject all components, drug product containers, closures, in-process materials, and labeling. It also has the authority to prepare and review all compounding records to assure that no errors have occurred in the compounding process. The pharmacist is also responsible for fhe proper maintenance, cleanliness, and use of all equipmenf used in prescription compmmding practice. 

Starting materials, solvents, intermediates, degradation products, and by-products are often organic impurities found in drug substances and excipients, while excipient impurities, solvents, by-products, degradation products, and container/closure adducts may be found as organic impurities in drug products. 

The cGMP regulations assign specific duties to the quality control unit. The unit is required to have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material,... 

Stability data should be generated on at least three primary batches, which should be manufactured to a minimum of pilot scale by the same synthetic route and manufacturing process as the production batches. The quality of the API placed on a formal stability program should be similar to the quality of the material to be made on a commercial production scale. The container closure system must be the same or simulate the packaging proposed for storage and distribution of marketed product. 

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