Journal of parenteral science and technology : a publication of the Parenteral Drug Association最新文献

This paper presents a brief review of the basic issues of lyophilization and the fundamentals of quadrupole mass spectrometry. The emphasis of the paper is on the application of a quadrupole mass spectrometer as a process monitor. The details of sampling and data collection are discussed. Data taken while monitoring lyophilization is presented in conjunction with cycle optimization, end point detection and contaminant detection.

To say that the FDA preapproval inspection program has generated much interest is an understatement. There have been multiple Commissioner Exchange Meetings at various locations throughout the United States and several multi-day workshops sponsored by the industry to help clarify how to prepare for this inspection. In order to establish a baseline of understanding, we will look, briefly, at the agency expectations. We will then look at the general trends that we have observed either directly from the preapproval inspections we have experienced or indirectly from 483 observations from other preapproval inspections. Finally, the ten steps which are used at Eli Lilly and Company to prepare for preapproval inspections will be presented.

The objective of this study was to investigate the behavior of lactate dehydrogenase (LDH) upon freezing and thawing, alone or in the presence of several selected cryoprotectants. Also, the influence of the freezing rate on retainment of LDH activity was investigated. It was observed that fast freezing caused less loss of LDH activity than slow freezing. The probable mechanisms of loss of activity after freeze-thaw cycles were discussed. Selected cryoprotectants were evaluated for their ability to protect LDH during freeze-thaw cycles. Surface tension and pH change measurements upon freezing of the cryoprotectant solutions were carried out. Based on the results of these experiments, a potential mechanism of cryoprotection has been developed.

Environmental monitoring is an essential requirement in the pharmaceutical industry. Results which the manufacturer obtains from environmental monitoring must be reproducible and assure that the aseptic environment is under control. Today, more than ever, environmental data is scrutinized during FDA CGMP and preapproval NDA inspections and this trend will likely continue. Environmental test methods which have been in existence for years are accepted throughout the industry, but the user must bear the responsibility of proving that the methods yield reproducible results. New test methodologies must be validated to be as good as or better than the methods they are replacing. Currently, environmental result alert/action levels in existing facilities should be based on industry guidelines and facility performance validation. The pharmaceutical manufacturer must demonstrate that the levels which have been established for the facility have a statistical basis related to the historical performance of the facility. As time goes on, environmental levels may be readjusted to coincide with the operational performance levels of the facility.

With the upcoming abundance of sterilization techniques applied to various pharmaceutical product types, it has appeared useful to the committee to compile general guidelines for the proper mastery of this critical step of many pharmaceutical processes. Derived from the experience gained with conventional and more recent sterilization processes, this reports offers guidance for the definition of product sterility and the validation and control of the safety, reliability, efficiency, and proper operation of the non-standard sterilization processes.

This paper discusses the performance and sterilizability attributes of several different types of capacitance manometers as used in steam sterilizable lyophilizers. Recommendations are made for proper capacitance manometer selection, installation, operation, and calibration. An overview of vacuum gauging methods and the performance and sterility benefits of a new high-temperature (125 degrees C)/high-overpressure capacitance manometer are discussed.

Using a rabbit ear model and techniques developed previously (1) the relationship between injection rate and injection phlebitis is investigated for amiodarone HCl and its vehicle. A number of injection rates ranging from 0.02 to 3.0 ml/min are studied using this model. Thermal measurements and visual evaluations are used for phlebitis quantitation. The severity of phlebitis is found to be dependent upon the injection rate for amiodarone HCl while the vehicle did not produce phlebitis at any rate. Strong correlations between the thermal measurements and visual evaluations are found for both amiodarone HCl and its vehicle.