Simulated Leaching (Migration) Study for a Model Container-Closure System Applicable to Parenteral and Ophthalmic Drug Products.

A simulating leaching (migration) study was performed on a model container-closure system relevant to parenteral and ophthalmic drug products. This container-closure system consisted of a linear low-density polyethylene bottle (primary container), a polypropylene cap and an elastomeric cap liner (closure), an adhesive label (labeling), and a foil overpouch (secondary container). The bottles were filled with simulating solvents (aqueous salt/acid mixture at pH 2.

Extractables characterization for five materials of construction representative of packaging systems used for parenteral and ophthalmic drug products.

Unlabelled: Polymeric and elastomeric materials are commonly encountered in medical devices and packaging systems used to manufacture, store, deliver, and/or administer drug products. Characterizing extractables from such materials is a necessary step in establishing their suitability for use in these applications. In this study, five individual materials representative of polymers and elastomers commonly used in packaging systems and devices were extracted under conditions and with solvents that are relevant to parenteral and ophthalmic drug products (PODPs).

The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP).

Unlabelled: The Product Quality Research Institute (PQRI) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The collaborative activities of PQRI participants have, in the case of orally inhaled and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted recommendations for leachables assessments to help ensure patient safety with respect to this class of packaged drug products. These recommendations, which include scientifically justified safety thresholds for leachables, represent a significant milestone towards establishing standardized approaches for safety qualification of leachables in OINDP.

Perspectives on the PQRI Extractables and Leachables "Safety Thresholds and Best Practices" Recommendations for Inhalation Drug Products.

Unlabelled: In 2006, the Product Quality Research Institute's (PQRI) Leachables and Extractables Working Group released a comprehensive and detailed recommendation document related to leachables and extractables for inhalation drug products. The document includes best pharmaceutical development practice recommendations regarding container closure/delivery system component composition and selection, controlled extraction studies, drug product leachables studies, and routine extractables testing for component release. Also included in the document are two safety-based thresholds for leachables in inhalation drug products, the qualification threshold (QT) and the safety concern threshold (SCT), the first such safety-based thresholds for leachables in any drug product type.

Automated Solid Phase Extraction (SPE) LC/NMR Applied to the Structural Analysis of Extractable Compounds from a Pharmaceutical Packaging Material of Construction.

Unlabelled: The structural analysis (i.e., identification) of organic chemical entities leached into drug product formulations has traditionally been accomplished with techniques involving the combination of chromatography with mass spectrometry.

N-nitrosamines as "special case" leachables in a metered dose inhaler drug product.

N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level.

Study and characterization of crystalline hydrate/polymorph forms of 5,11-dihydro-11-ethyl-5-methyl-8-(2-(1-oxido-4-quinolinyl)ethyl-6H-dipyrido(3,2-B:2',3'-E)(1,4)diazepin-6-one by solid-state NMR and solution NMR.

A novel inhibitor of reverse transcriptase was studied by solid-state NMR. Three phases of the compound were examined which included the dihydrate and two anhydrous polymorphs (Form I and Form III). By correlating (1)H and (13)C solution NMR with the solid-state (13)C NMR CP/MAS and CPPI spectral editing experiments, comparative (13)C assignments were made for each phase.

(31)P solid state NMR study of structure and chemical stability of dichlorotriphenylphosphorane.

Solid state (31)P NMR spectroscopy was used to examine, monitor and quantify the compound integrity of the chemical reagent dichlorotriphenylphosphorane. Comparison was also made with solution (31)P NMR spectra which showed that this highly reactive species could be observed in dry benzene prior to conversion to the hydrolyzed product. This is the first reported solid state NMR study of the stability and reactivity of dichlorotriphenylphosphorane and the first account of its observation and comparison in the solution state.

Identification of a process impurity formed during synthesis of a nevirapine analogue HIV NNRT inhibitor using LC/MS and forced degradation studies.

Impurities in pharmaceutical products do not enhance the desired therapeutic effect and may, of course, have adverse effects. Impurities must therefore be limited or controlled for quality and safety considerations. Structural identification of an impurity is the first step in understanding the chemistry of its formation and subsequently controlling the impurity.

Best practices for extractables and leachables in orally inhaled and nasal drug products: an overview of the PQRI recommendations.

The Product Quality Research Institute Leachables and Extractables Working Group includes pharmaceutical development scientists representing industry, government, and academia. The Working Group was created and constituted to address scientific and regulatory questions concerning the pharmaceutical development process for Orally Inhaled and Nasal Drug Products (OINDP) related to organic extractables and leachables. This effort has resulted in the creation of a detailed "Recommendation Document", which was submitted to the U.

Development of safety qualification thresholds and their use in orally inhaled and nasal drug product evaluation.

Safety thresholds for chemical impurities and leachables in consumer products such as foods and drugs have helped to ensure public health while establishing scientifically sound limits for identification and risk assessment of these compounds. The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group, a collaboration of chemists and toxicologists from the U.S.