Pharmaceutical preparations Flashcards
Pharmaceutical preparations monograph - API and excipients
Where specific monographs exist, the quality of the active substances and excipients used complies with the corresponding monographs.
Where no specific monographs exist, the required quality must be defined, taking into account the intended use and the involved risk.
When physicochemical characteristics of active substances and functionality-related characteristics (FRCs) of excipients (e.g. particle-size distribution, viscosity, polymorphism) are critical in relation to their role in the manufacturing process and quality attributes of the pharmaceutical preparation, they must be identified and controlled.
Pharmaceutical preparations monograph - microbiological quality
The formulation of the pharmaceutical preparation and its container must ensure that the microbiological quality is suitable for the intended use.
During development, it shall be demonstrated that the antimicrobial activity of the preparation as such or, if necessary, with the addition of a suitable preservative or preservatives, or by the selection of an appropriate container, provides adequate protection from adverse effects that may arise from microbial contamination or proliferation during the storage and use of the preparation.
If preparations do not have adequate antimicrobial efficacy and do not contain antimicrobial preservatives they are supplied in single-dose containers, or in multidose containers that prevent microbial contamination of the contents after opening.
Pharmaceutical preparations monograph - Nitrosamines
As many N-nitrosamines are classified as probable human carcinogens, manufacturers of medicinal products, except products for veterinary use only and unlicensed pharmaceutical preparations, are expected to evaluate the potential risk of N-nitrosamine formation and contamination occurring throughout their manufacturing process and throughout their shelf-life, according to the requirements of the relevant competent authorities. If the risk is confirmed, manufacturers should mitigate as much as possible the presence of N-nitrosamines – for example by modifying the manufacturing process – and a control strategy must be implemented to detect and control these impurities.
Pharmaceutical preparations monograph - containers
A suitable container is selected. Consideration is given to the intended use of the preparation, the properties of the container, the required shelf-life, and product/container incompatibilities. Where applicable, containers for pharmaceutical preparations comply with the requirements for containers and materials used for the manufacture of containers
Pharmaceutical preparations monograph - stability
Stability requirements of pharmaceutical preparations are dependent on their intended use and on the desired storage time.
Where applicable, the probability and criticality of possible degradation products of the active substance(s) and/or reaction products of the active substance(s) with an excipient and/or the immediate container must be assessed. Depending on the result of this assessment, limits of degradation and/or reaction products are set and monitored in the pharmaceutical preparation. Licensed products require a stability exercise.
Methods used for the purpose of stability testing for all relevant characteristics of the preparation are validated as stability indicating, i.e. the methods allow the quantification of the relevant degradation products and physical characteristic changes.
Pharmaceutical preparations monograph - tests
Appearance
The appearance (e.g. size, shape and colour) of the pharmaceutical preparation is controlled.
Identity and purity tests
Where applicable, the following tests are carried out on the pharmaceutical preparation:
— identification of the active substance(s);
— identification of specific excipient(s), such as preservatives;
— purity tests (e.g. investigation of degradation products, residual solvents or other related impurities, sterility;
— safety tests (e.g. safety tests for biological products).
Uniformity
Pharmaceutical preparations presented in single-dose units comply with the test(s) as prescribed in the relevant specific dosage form monograph. If justified and authorised, general chapter can be applicable only at the time of release.
Pharmaceutical preparations monograph - Assay
Unless otherwise justified and authorised, contents of active substances and specific excipients such as preservatives are determined in pharmaceutical preparations. Limits must be defined and justified.
Suitable and validated methods are used. If assay methods prescribed in the respective active substance monographs are used, it must be demonstrated that they are not affected by the presence of the excipients and/or by the formulation.
