Comparability studies biopharmaceuticals

Reproductive and Developmental Toxicity Studies The requirement for reproductive and developmental toxicity studies depends on the clinical indication and intended patient population. For example, when (1) no relevant animal species exists, (2) a biopharmaceutical is not used for pregnant women or women of child-bearing potential (3) there is a structurally comparable natural biopharmaceutical for which there is much experience in clinical practice, or (4) a biopharmaceutical is indicated for patients with minimal childbearing potential and indicated for those with serious diseases, reproductive, and developmental toxicity studies could be obviated. 

The features of a particular biopharmaceutical are the result of the basic characteristics of the molecule such as amino acid sequence and three-dimensional structure as well as the specihc production, purihcation, formulation, and storage conditions (Box 12.4-2). To produce a biopharmaceutical of constant required quality, a company also needs the experience and the in-house standards to apply the methods used to analyze the structure of a given product. There are various guidelines of the European Medicine Evaluation Agency, the Food and Drug Administration, the Japanese Ministry of Health and Welfare, and the ICH, which require manufacturers to show that they control the production process and are capable of reproducibly manufacturing batches that not only meet product specih-cations, but also conform to the dehnition of the product as established through full characterization. Modihcations of the established process are only accepted if the manufacturer can show that the product of the new process is comparable with the initially manufactured product. Comparability studies include revalidation of... 

Houde, D Berkowitz, S.A., Engen, J.R. (2011) The utility of hydrogen/deuterium exchange mass spectrometry in biopharmaceutical comparability studies. J Pharm Sci, 100 (6), 2071-2086. 

D. Houde, S. A. Berkowitz and J. R. Engen. (2011) The Utility of Hydrogen/Deuterium Exchange Mass Spectrometry in Biopharmaceutical Comparability Studies, Journal of Pharmaceutical Sciences, 100 (6),... 

Once a peptide map is characterized using online MS, the chromatographic profile alone can serve as a routine analytical tool to monitor the protein s primary structure and covalent modifications, and is often used for batch release or stability testing of biopharmaceuticals. However, whenever in-depth characterization of a protein is needed, such as that required for comparability studies or reference material characterization, the peptide map should be coupled with MS to ensure a thorough examination of all peptides in the map. 

Tewes, F. et al. Comparative study of doxorubicin-loaded poly(lactide-co-glycoUde) nanoparticles prepared by single and double emulsion methods. European Journal of Pharmaceutics and Biopharmaceutics 66,488-492,2007. 

Biopharmaceutical issues to be addressed will include a discussion of the pharmaceutical development process as it relates to in vivo and in vitro performance and the general approach taken concerning bioavailability, bioequivalence, and in vitro dissolution profiles. There should be a comparative analysis of relevant studies—objectives, study design, conduct, outcome, and data analyses. The effects of formulation changes (including different strengths of product and... 

Nabi has successfully completed several phase II studies for NicVAX. The results from a phase Ilb dose-ranging study in 301 heavy smokers showed that a significantly greater number of vaccinated participants met abstinence endpoints compared to placebo. Furthermore, vaccinated participants who successfully achieved abstinence were shown to have a higher level of antibody response than those vaccinated participants who did not achieve abstinence (Nabi Biopharmaceuticals 2007). Nabi is expected to start phase III trials this year. 

The aim of the present study was to repeat the experiments of the previous study using a multiple-unit verapamil formulation instead of the single-unit tablet. The in vitro dissolution patterns of both formulations are approximately equal, thus allowing their biopharmaceutical properties to be compared. 

Repeat-Dose Toxicity Studies Typically toxicity studies are performed in two animal species. However, for toxicity studies for which there is only one relevant animal species, these studies may be performed using one animal species. When two animal species show the same toxicity profile in short-term studies, only one animal species may be used in long-term studies. Comparison of toxicity profiles means comparing the type and severity of any toxicity observed. However, biopharmaceuticals with a low toxicity may display no toxicity at high doses in some cases. It such cases it may still be important to select one species for assessment of chronic toxicity. More important, in cases where toxicity has not been clearly demonstrated justification of human... 

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