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      FDA Critical Path Initiatives: Opportunities for Generic Drug Development

      research-article
      The AAPS Journal
      Springer US
      bioequivalence, critical path initiative, generic drugs

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          Abstract

          FDA’s critical path initiative documents have focused on the challenges involved in the development of new drugs. Some of the focus areas identified apply equally to the production of generic drugs. However, there are scientific challenges unique to the development of generic drugs as well. In May 2007, FDA released a document “Critical Path Opportunities for Generic Drugs” that identified some of the specific challenges in the development of generic drugs. The key steps in generic product development are usually characterization of the reference product, design of a pharmaceutically equivalent and bioequivalent product, design of a consistent manufacturing process and conduct of the pivotal bioequivalence study. There are several areas of opportunity where scientific progress could accelerate the development and approval of generic products and expand the range of products for which generic versions are available, while maintaining high standards for quality, safety, and efficacy. These areas include the use of quality by design to develop bioequivalent products, more efficient bioequivalence methods for systemically acting drugs (expansion of BCS waivers, highly variable drugs), and development of new bioequivalence methods for locally acting drugs.

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          Most cited references28

          • Record: found
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          Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies.

          This study was conducted to compare the luminal composition of the upper gastrointestinal tract in the fasted and fed states in humans, with a view toward designing in vitro studies to explain/predict food effects on dosage form performance. Twenty healthy human subjects received 250 mL water or 500 mL Ensure plus (a complete nutrient drink) through a nasogastric tube and samples were aspirated from the gastric antrum or duodenum for a period up to 3.5 h, depending on location/fluid combination. Samples were analyzed for polyethylene glycol, pH, buffer capacity, osmolality, surface tension, pepsin, total carbohydrates, total protein content, and bile salts. Following Ensure plus administration, gastric pH was elevated, buffer capacity ranged from 14 to 28 mmoL L-1 DeltapH-1 (vs. 7-18 mmol L-1 DeltapH-1), contents were hyperosmolar, gastric pepsin levels doubled, and surface tension was 30% lower than after administration of water. Post- and preprandial duodenal pH values were initially similar, but slowly decreased to 5.2 postprandially, whereas buffer capacity increased from 5.6 mmol L-1 DeltapH-1 (fasted) to 18-30 mmol L-1 DeltapH-1 (p 30%, bile salt levels were two to four times higher, luminal contents were hyperosmotic, and the presence of peptides and sugars was confirmed. This work shows that, in addition to already well characterized parameters (e.g., pH, and bile salt levels), significant differences in buffer capacity, surface tension, osmolality, and food components are observed pre-/postprandially. These differences should be reflected in test media to predict food effects on intralumenal performance of dosage forms.
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            • Record: found
            • Abstract: found
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            Particle size analysis in pharmaceutics: principles, methods and applications.

            Physicochemical and biopharmaceutical properties of drug substances and dosage forms can be highly affected by the particle size, a critical process parameter in pharmaceutical production. The fundamental issue with particle size analysis is the variety of equivalent particle diameters generated by different methods, which is largely ascribable to the particle shape and particle dispersion mechanism involved. Thus, to enable selection of the most appropriate or optimal sizing technique, cross-correlation between different techniques may be required. This review offers an in-depth discussion on particle size analysis pertaining to specific pharmaceutical applications and regulatory aspects, fundamental principles and terminology, instrumentation types, data presentation and interpretation, in-line and process analytical technology. For illustration purposes, special consideration is given to the analysis of aerosols using time-of-flight and cascade impactor measurements, which is supported by a computational analysis conducted for this review.
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              • Record: found
              • Abstract: found
              • Article: not found

              Bioavailability and bioequivalence: an FDA regulatory overview.

              Bioavailability and/or bioequivalence studies play a key role in the drug development period for both new drug products and their generic equivalents. For both, these studies are also important in the postapproval period in the presence of certain manufacturing changes. Like many regulatory studies, the assessment of bioavailability and bioequivalence can generally be achieved by considering the following three questions. What is the primary question of the study? What are the tests that can be used to address the question? What degree of confidence is needed for the test outcome? This article reviews the regulatory science of bioavailability and bioequivalence and provides FDA's recommendations for drug sponsors who intend to establish bioavailability and/or demonstrate bioequivalence for their pharmaceutical products during the developmental process or after approval.
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                Author and article information

                Contributors
                +1-240-2769315 , +1-240-2769327 , robert.lionberger@fda.hhs.gov
                Journal
                AAPS J
                The AAPS Journal
                Springer US (Boston )
                1550-7416
                20 February 2008
                20 February 2008
                March 2008
                : 10
                : 1
                : 103-109
                Affiliations
                Office of Generic Drugs, Food and Drug Administration, 7519 Standish Place, Rockville, Maryland 20850 USA
                Article
                9010
                10.1208/s12248-008-9010-2
                2751455
                18446510
                bbffc364-f583-47ca-8c0c-3e8ba31acb97
                © American Association of Pharmaceutical Scientists 2008
                History
                : 15 August 2007
                : 17 January 2008
                Categories
                Review Article; Themed Issue: Bioequivalence, Biopharmaceutics Classification System, and Beyond/Guest Editor: James E. Polli
                Custom metadata
                © American Association of Pharmaceutical Scientists 2008

                Pharmacology & Pharmaceutical medicine
                critical path initiative,generic drugs,bioequivalence

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