Biopharmaceutics studies

Summary of Biopharmaceutic Studies and Associated Analytical Methods Summary of Clinical Pharmacology Studies Summary of Clinical Efficacy Summary of Clinical Safety Literature References Synopses of Individual Studies... 

Zbinden G. Biopharmaceutical studies, a key to better toxicology. Xenobiotica 1988 18(suppl 1) 9. 

Fugioka, ., Kurosaki, Y., Sato, S., Noguchi, T., andYamahira, Y. 1983. Biopharmaceutical study of inclusion complexes. I. Pharmaceutical advantages of cyclodextrin complexes of bencyclane fuffibeate. 

Y. Yamahira, T. Noguchi, H. Takenaka and T. Maeda, Biopharmaceutical studies of lipid containing oral dosage forms relationship between drug absorption rate and digestibility of vehicles, Int. J. Pharmaceut. 3 23-31 (1979). 

Summary of Biopharmaceutic Studies and Associated Analytical Methods... 

Comparison of Preclinical Development Programs for Small Molecules (Drugs/Pharmaceuticals) and Large Molecules (Biologics/Biopharmaceuticals) Studies, Timing, Materials, and Costs... 

Four-week toxicology studies in rodent and nonrodent The four-week studies are designed for subchronic exposure of rodents and nonrodents to the test article. These studies also look at reversibility of any toxicity observed. Many times these are the pivotal studies used to support the first in human dosing. Toxicokinetic assessments are generally included in repeat-dose toxicity studies. When testing biopharmaceuticals, studies also include assessment and characterization of immune response (immunogenicity). 

Included in the first portion of this section should be an overall tabulated summary of all in vivo biopharmaceutical studies carried out on the drug grouped by type of study. The study number, route of administration, dosage form, batch number, plant and date of manufacture, number of subjects, IND or NDA number under which the study was conducted or study submitted, date of submission, conclusions regarding the study, and previous agency response on the study or the protocol together with the date of the correspondence should be included. 

Dissolution data on each strength and dosage form for which approval is being sought should be provided in the fifth portion of this technical section. A comparative dissolution study with the lot(s) used for in vivo biopharmaceutic studies should also be included. 

Phase 2 dosage forms Clinical biopharmaceutical studies... 

Table 3 Examples of in vitro and in vivo biopharmaceutic studies...

Biopharmaceutic studies (in vivo) Bioavailability study Measurement of drug in plasma, urine or other tissues... 

Biopharmaceutic studies (in vitro) Drug release/dissolution Measurement of the rate of drug dissolved under specified conditions... 

Obviously, not all conditions are met, but by every compound we keep this direction in mind, it is easier to sift through many possibilities offered. It requires testing a range of selected compounds in in vitro and in vivo animal studies and thus, preformulation work gets combined with biopharmaceutic studies to identify product design issues. 

One of the major factors that often slows down preformulation studies is the availability of a sufficient quantity of a compound at this stage, especially if biopharmaceutic studies are conducted as a result, methods need to be devised that would utilize the smallest quantity of the substance this is amply emphasized throughout the testing phases in this book. Another factor that often slows down work at this stage is often misplaced importance on validated test methods and documentation while this is desired, the perennial shortage of manpower requires that some things take secondary importance. 

The pharmacological activity, efficacy, and toxicity of an administered medicament may be profoundly affected by the physico-chemical properties of the drug and the drug dosage form. Thus, such parameters as solubility, particle size, diffusional characteristics, availability and rate of dissolution of the drug have been the areas emphasized in most biopharmaceutical studies. The effect of these parameters on drug absorption is the subject of this review. 

R. T. Borchardt, P. L. Smith, and G. WUson, General principles in the characterization and use of model systems for biopharmaceuticals studies. Pharm Biotechnol 8 1-11 (1996). 

A Clinical Summary is to start with a subsection on Biopharmaceutical Studies, and Associated Analytical and Bioanalytical Chemistry Methods conducted during the clinical development of a drug candidate. The background of the formulation development process is to be briefly provided and is to include information on in vitro and in vivo dosage form performance and the general approach and rationale for developing the bioavailability (BA), comparative BA, bioequivalence (BE), and in vitro dissolution profile database. Also to be included is a summary of the analytical and bioanalytical chemistry methods and the validation characteristics of these methods. 

A tabular listing (ETA) of all biopharmaceutical studies conducted is recommended. Brief narrative descriptions (e.g., similar to an abstract for a journal article) are to share relevant features and outcomes of each study that provided important in vitro or in vivo data and information relevant to the BA and/or BE of a drug candidate. These narratives can be abstracted from clinical study reports (i.e., the synopsis of reports prepared according to ICE guideline E3) and should include reference to the full report. A comparison of results across studies, using both text and tables, is to pay particular attention to differences in in vitro dissolution, BA, and comparative BA results. This comparison is to consider... 

SMITH, D.A. (1997) Pharmacokinetics and pharmacodynamics in toxicology. Xenobiotica 27, 513. YANG, R.S.H. and ANDERSEN, M.E. (1994) Pharmacokinetics. In Introduction to Biochemical Toxicology, edited by E.Hodgson and P.E.Levi, 2nd edition (Connecticut Appleton-Lange). ZBINDEN, G. (1988) Biopharmaceutical studies, a key to better toxicology. Xenobiotica, 18, Suppl. 1,9. 

For pharmaceutical development, risk may be associated with the technical challenges anticipated in developing a novel or complex drug delivery system or manufacturing process. Information from early preformulation and biopharmaceutics studies should indicate the potential problems for drug delivery, formulation development and manufacture. 

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