{"id":227,"date":"2019-10-08T22:15:05","date_gmt":"2019-10-08T16:45:05","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=227"},"modified":"2019-10-08T22:15:05","modified_gmt":"2019-10-08T16:45:05","slug":"bioavailability-bioequivalence-studies","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/bioavailability-bioequivalence-studies\/","title":{"rendered":"Bioavailability &#038; Bioequivalence Studies"},"content":{"rendered":"\n<p><strong>Bioavailability and &nbsp;Bioequivalence Studies<\/strong><\/p>\n\n\n\n<p><strong>Introduction <\/strong><\/p>\n\n\n\n<ul><li>It is essential to <strong>ensure\nuniformity in standards of quality, efficacy &amp; safety of Pharmaceutical\nproducts<\/strong><\/li><li>Reasonable assurance is to be provided that <strong>various products containing the same active ingredient, marketed by\ndifferent licensees are clinically equivalent &amp; interchangeable<\/strong><\/li><li>Release of an active substance should be known &amp; reproducible<\/li><li>Both Bioavailability &amp; Bioequivalence focus on the release of the\ndrug substance from its dosage form &amp; subsequent absorption in circulation<\/li><li>Similar approaches to measure Bioavailability should be followed in\ndemonstrating Bioequivalence&nbsp; <\/li><\/ul>\n\n\n\n<p><strong>Bioavailability<\/strong><\/p>\n\n\n\n<ul><li>Measurement of the <strong>relative\namount &amp; rate at which, the drug from the administered dosage form, reaches\nthe systemic circulation &amp; becomes available at the site of action<\/strong><\/li><li>Bioavailable fraction (F), refers to the fraction of administered\ndose that enters the systemic circulation<\/li><\/ul>\n\n\n\n<p>F&nbsp;&nbsp; =&nbsp;\nBioavailable dose\/Administered dose<\/p>\n\n\n\n<p><strong>OBJECTIVES OF BIOAVAILABILITY STUDIES<\/strong><\/p>\n\n\n\n<ul><li><strong>Primary stages of development<\/strong> of a suitable dosage for a <strong>new drug\nentity.<\/strong><\/li><li>Development of a <strong>new\nformulation of the existing drugs<\/strong>.<\/li><li><strong>Control of quality of a drug<\/strong> product during the early stages of marketing\nin order to determine the <strong>influence of processing factors, storage and\nstability on drug absorption.<\/strong><\/li><li>Useful in determining\nthe <strong>safety and efficacy<\/strong> of the drug product. <\/li><\/ul>\n\n\n\n<p>&nbsp;<strong>Concept of\nEquivalents<\/strong><\/p>\n\n\n\n<ul><li><strong>Bioequivalence<\/strong><\/li><li>Pharmaceutical equivalent\/alternative of the test product,<\/li><li>when administered at the same molar dose,<\/li><li>has the rate and extent of absorption<\/li><li>not statistically significantly&nbsp;\ndifferent from that of the reference product<\/li><\/ul>\n\n\n\n<ul><li><strong>Pharmaceutical equivalents<\/strong><\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"239\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-61.png?w=480\" alt=\"\" class=\"wp-image-228\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-61.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-61-300x149.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure><\/div>\n\n\n\n<ul><li><strong>Pharmaceutical alternatives<\/strong> <\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"242\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-62.png?w=480\" alt=\"\" class=\"wp-image-229\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-62.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-62-300x151.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure><\/div>\n\n\n\n<ul><li><strong>Therapeutic equivalence &#8211; FDA <\/strong>classifies those products as therapeutically\nequivalent which<\/li><li>Same active substance or therapeutic moiety <\/li><li>Clinically show the same efficacy &amp; safety profile<\/li><\/ul>\n\n\n\n<p><strong>Reference\nProduct<\/strong><\/p>\n\n\n\n<ul><li>Identified by the Regulatory Authorities as \u201c<strong>Designated Reference Product\u201d<\/strong><\/li><li>Usually the <strong>Global Innovator\u2019s Product<\/strong><\/li><li>Protected by a <strong>patent<\/strong><\/li><li>Marketed under <strong>manufacturers brand name<\/strong><\/li><li>Clinical efficacy &amp; safety profile is well documented in extensive trials<\/li><li>All generics must be Bioequivalent to it<\/li><li>In India, CDSCO may approve another product as a Reference product<\/li><\/ul>\n\n\n\n<p><strong>Generic Drug<\/strong><\/p>\n\n\n\n<ul><li>Drug product which is identical or <strong>bioequivalent to Brand\/ Reference<\/strong> drug in:\u00a0Active ingredient (s), Route of administration, Dosage form, Strength, Indications, Safety<\/li><\/ul>\n\n\n\n<ul><li>May have <strong>different:<\/strong><\/li><li>Inactive ingredients, \u00a0Colour, Shape<\/li><li>Almost <strong>half of the drugs in the market <\/strong>have Generics<\/li><li>An <strong>Abbreviated New Drug Application<\/strong> (ANDA) is an application for a U.S. generic drug approval for an existing licensed medication or approved drug<\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"229\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-63.png?w=480\" alt=\"\" class=\"wp-image-230\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-63.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-63-300x143.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure><\/div>\n\n\n\n<p><strong><em>Fundamental Bioequivalence Assumption<\/em><\/strong><\/p>\n\n\n\n<p>When\na generic drug is claimed <strong>bioequivalent<\/strong> to a Reference drug, it is\nassumed that they are <strong>therapeutically equivalent<\/strong><\/p>\n\n\n\n<p><strong>Bioequivalence\nBackground<\/strong><\/p>\n\n\n\n<ul><li>&nbsp;Using bioequivalence as the\nbasis for approving generic copies in the US<\/li><\/ul>\n\n\n\n<p><strong>\u201cDrug Price Competition and Patent Term Restoration\nAct of 1984,\u201d also known as the Waxman-Hatch Act<\/strong><\/p>\n\n\n\n<ul><li>\u00a0Created Generic Industry &amp; \u2191 their availability<\/li><li>\u00a0Most successful legislation<\/li><li>\u00a0Benefited Brand &amp; Generic firms<\/li><li>\u00a0<strong>Generic firms\u2192 Rely\u00a0 on<\/strong> findings of safety &amp; efficacy of Innovator drug after <strong>Patent expiration<\/strong><\/li><li>\u00a0<strong>Innovator firms\u2192 Patent extensions of 5yrs<\/strong> to make up for time lost while their products were going through FDA&#8217;s approval process<\/li><\/ul>\n\n\n\n<p><strong>Indian\nLegislation<\/strong><\/p>\n\n\n\n<ul><li>&nbsp;In India, CDSCO provides \u201c<strong>Guidelines\nfor Bioavailability &amp;&nbsp; <\/strong><\/li><\/ul>\n\n\n\n<p><strong>&nbsp;&nbsp;&nbsp; Bioequivalence Studies<\/strong>\u201d&nbsp; mentioned in Schedule Y<\/p>\n\n\n\n<ul><li>&nbsp;As per the Drugs &amp;\nCosmetics Rules (II<sup>nd<\/sup> Amendment) 2005, all bioavailability and\nbioequivalence studies should be conducted in accordance with these Guidelines <\/li><\/ul>\n\n\n\n<p><strong>The\nrequirement of BA &amp; BE Studies<\/strong><\/p>\n\n\n\n<ul><li><strong>&nbsp;For IND\/NDAs:<\/strong><\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp; To establish equivalence between:<\/p>\n\n\n\n<ul><li><em>Early &amp; late <\/em>clinical trial formulations<\/li><li>Formulations used in clinical trial &amp; stability studies <\/li><li><em>Clinical trial formulations &amp; to-be-marketed <\/em>drug product<\/li><li>Any <em>other comparisons<\/em>, if appropriate<\/li><li><strong>ANDA for a generic drug product<\/strong><\/li><li>Change in components, composition, &amp;\/or\u00a0 manufacturing process<\/li><li>Change in dosage form (capsules to tablet)<\/li><\/ul>\n\n\n\n<p><strong>Objectives of BA &amp; BE Studies<\/strong><\/p>\n\n\n\n<ul><li>&nbsp;<strong>Development of suitable dosage form for a New Drug Entity<\/strong><\/li><li>&nbsp;<strong>Determination of the influence of excipients, patient-related factors\n&amp; possible interactions<\/strong> with other drugs<\/li><li>&nbsp;Development of <strong>new drug formulations of existing drugs<\/strong><\/li><li>&nbsp;<strong>Control of quality<\/strong> of drug products, the influence of \u2192 processing\nfactors, storage &amp; stability <\/li><li>&nbsp;<strong>Comparison of availability of a drug substance<\/strong> from a different\nform or same dosage <strong>form produced by different\nmanufacturers<\/strong><\/li><\/ul>\n\n\n\n<p><strong>When is Bioequivalence not necessary (Biowaivers)?<\/strong><\/p>\n\n\n\n<ol><li><strong>Aqueous parental Solution<\/strong>; a same active substance with the same concentration, same excipient<\/li><li><strong>Oral Solution<\/strong>; a same active substance with the same concentration, excipient not affecting GI transit or absorption<\/li><li><strong>Gas<\/strong><\/li><li><strong>Powder for reconstitution<\/strong> as a solution; meets criterion (a) or (b)<\/li><li><strong>Otic\/Ophthalmic\/Topical Solution<\/strong>; a same active substance with the same concentration, same excipient<\/li><li><strong>Inhalational Product<\/strong>\/ Nasal Spray; administered with or w\/o same device as reference product; prepared as an aqueous solution; a same active substance with the same concentration, same excipient<\/li><\/ol>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"383\" height=\"226\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-64.png?w=383\" alt=\"\" class=\"wp-image-231\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-64.png 383w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-64-300x177.png 300w\" sizes=\"(max-width: 383px) 100vw, 383px\" \/><\/figure><\/div>\n\n\n\n<p><strong>Orange\nBook<\/strong><\/p>\n\n\n\n<ul><li>&nbsp;All FDA approved drugs listed\n(NDA\u2019s, ANDA\u2019s &amp; OTC\u2019s)<\/li><li>&nbsp;Expiration of patent dates<\/li><li>&nbsp;Drug,\nPrice and Competition Act (1984) &#8211; FDA required to publish Approved Drug Products with Therapeutic\nEquivalence &amp; Evaluations<\/li><\/ul>\n\n\n\n<p><strong>Methods used to assess Equivalence<\/strong><\/p>\n\n\n\n<ol><li>Pharmacokinetic Studies<\/li><li>Pharmacodynamic Studies<\/li><li>Comparative Clinical Studies<\/li><li>Dissolution Studies<\/li><\/ol>\n\n\n\n<p><strong>Pharmacokinetic<\/strong> <strong>Studies<\/strong><\/p>\n\n\n\n<p><strong>Subject selection<\/strong><\/p>\n\n\n\n<ul><li>Healthy adult volunteers<\/li><li>Age: 18-45 yrs<\/li><li>Age\/Sex representation corresponding to a therapeutic &amp; safety\nprofile<\/li><li>Weight within normal limits\u2192 BMI<\/li><li>Women: Pregnancy test prior to 1<sup>st<\/sup>\n&amp; last dose of study; OC pills C\/I<\/li><li>Drug use intended in Elders&nbsp;\n(Age &gt;60yrs)<\/li><li><strong>Teratogenic Drugs\u2192 Male\nvolunteers<\/strong><\/li><li>Highly toxic drugs: Patients with the concerned\ndisease (stable) eg. Cancer<\/li><\/ul>\n\n\n\n<p><strong>Exclusion Criteria<\/strong><\/p>\n\n\n\n<ul><li>H\/o allergy to test drug<\/li><li>H\/o liver or kidney dysfunction<\/li><li>H\/o jaundice in the past 6 months<\/li><li>Chronic diseases eg. Asthma, arthritis<\/li><li>Psychiatric illness<\/li><li>Chronic smoker, alcohol addiction, drug abuse<\/li><li>Intake of enzyme modifying drug in the past 3 months<\/li><li>Intake of OTC\/Prescription drugs past 2 weeks<\/li><li>HIV positive<\/li><li>BA &amp; BE studies in the past 3 months<\/li><li>H\/o bleeding disorder<\/li><\/ul>\n\n\n\n<p><strong>Selection of Number of Subjects<\/strong><\/p>\n\n\n\n<ul><li>\u00a0The sample size is estimated by:<\/li><li>\u00a0Pilot experiment<\/li><li>\u00a0Previous studies<\/li><li>\u00a0Published data<\/li><li>\u00a0Significance level desired, usually\u00a0 0.05<\/li><li>\u00a0Power of the study, normally 80% or more<\/li><li>\u00a0Expected deviation (\u0394) from the reference product, as compatible with BE<\/li><li>\u00a0If no data available, reference ratio of 0.95 (\u0394 = 5%) used<\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"199\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-65.png?w=480\" alt=\"\" class=\"wp-image-232\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-65.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-65-300x124.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure><\/div>\n\n\n\n<p><strong>Study Design<\/strong><\/p>\n\n\n\n<ul><li>Good experimental design enhances the power of the study<\/li><li>Depends on: question to be answered, nature of reference drug\/ dosage form, the benefit-risk ratio<\/li><li>As far as possible, the study should be of crossover design &amp; suitably randomized<\/li><li><strong>Ideal design: Randomized two-period, two-sequence, Crossover design with an adequate washout period<\/strong><\/li><li>If the half-life is long: Parallel design<\/li><li>For highly variable drugs: Replicate design <\/li><\/ul>\n\n\n\n<ol><li><strong>Two-Period Crossover Design<\/strong><\/li><li>2 formulations, even number of subjects, randomly divided into 2 equal groups<\/li><li>First period, each member of one group receive a single dose of the test formulation; each member of the other group receive the standard formulation<\/li><li>After a wash period (5 half-lives), in the second period, each member of the respective groups will receive an alternative formulation &amp; the experiment will be repeated.<\/li><\/ol>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"435\" height=\"200\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-66.png?w=435\" alt=\"\" class=\"wp-image-233\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-66.png 435w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-66-300x138.png 300w\" sizes=\"(max-width: 435px) 100vw, 435px\" \/><\/figure><\/div>\n\n\n\n<p><strong>Parallel-Group Design<\/strong><\/p>\n\n\n\n<ul><li>Even the number of subjects in two groups<\/li><li>Each receives a different formulation<\/li><li>No washout necessary <\/li><li>For drugs with a long half-life<\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"417\" height=\"273\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-67.png?w=417\" alt=\"\" class=\"wp-image-234\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-67.png 417w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-67-300x196.png 300w\" sizes=\"(max-width: 417px) 100vw, 417px\" \/><\/figure><\/div>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"369\" height=\"223\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-68.png?w=369\" alt=\"\" class=\"wp-image-235\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-68.png 369w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-68-300x181.png 300w\" sizes=\"(max-width: 369px) 100vw, 369px\" \/><\/figure><\/div>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"313\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-69.png?w=480\" alt=\"\" class=\"wp-image-236\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-69.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-69-300x196.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure><\/div>\n\n\n\n<p><strong>Genetic Phenotyping<\/strong><\/p>\n\n\n\n<ul><li>The drug is known to be subject to <strong>genetic polymorphism<\/strong><\/li><li>Cross-over design\u2192 Safety &amp; Pharmacokinetic reasons<\/li><li>All Parallel group design<\/li><li>Indian population:<\/li><li>Captures genetic diversity of the world<\/li><li>Forms continuum of the genetic spectrum<\/li><li>&gt;1000 medically relevant genes<\/li><li>Diverse patient\/ volunteer pool for conducting BA &amp; BE studies<\/li><\/ul>\n\n\n\n<p><strong>Characteristics to be measured<\/strong><\/p>\n\n\n\n<ul><li>Accessible <strong>biological fluids<\/strong> like <strong>blood, plasma &amp;\/or serum <\/strong>to indicate the release of the drug substance from the drug product into the systemic circulation<\/li><li>Mostly: <strong>Active drug substance<\/strong><\/li><li><strong>Active \/ Inactive metabolite may be measured in cases of:<\/strong><\/li><li>The concentration of drug too low, Limitation of the analytical method, Unstable drug, Drug with a very short half-life, Pro-drugs<\/li><li><strong>Excretion of drug &amp;<\/strong> its metabolites in urine\u2192 Non-linear\u00a0 kinetics<\/li><\/ul>\n\n\n\n<ul><li><strong>Drugs that are not absorbed systemically from the site of application <em>surrogate marker<\/em> needed for BA &amp; BE determination<\/strong><\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"465\" height=\"282\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-70.png?w=465\" alt=\"\" class=\"wp-image-237\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-70.png 465w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-70-300x182.png 300w\" sizes=\"(max-width: 465px) 100vw, 465px\" \/><\/figure><\/div>\n\n\n\n<p><strong>Blood Sampling points\/ Schedule<\/strong><\/p>\n\n\n\n<p>A single-dose study of an immediate release product:<\/p>\n\n\n\n<ul><li>&nbsp;For at least three\nelimination half-lives (cover &gt;80% of AUC)<ul><li>&nbsp;Absorption phase: 3-4 points<\/li><\/ul><ul><li>&nbsp;Around T<sub>max<\/sub>: 3-4points<\/li><\/ul><ul><li>&nbsp;During elimination: 4 points<\/li><\/ul><\/li><li>&nbsp;Intervals not longer than the\nhalf-life of the drug<\/li><li>&nbsp;If urine tested, collect it\nfor at least 7 half-lives<\/li><\/ul>\n\n\n\n<p><strong>Parameters to be measured<\/strong><\/p>\n\n\n\n<ul><li>Pharmacokinetic Parameters\u00a0 measured are:<\/li><li>\u00a0C<sub>max<\/sub><\/li><li>\u00a0T<sub>max<\/sub><\/li><li>\u00a0AUC<sub>0-t<\/sub><\/li><li><sub>\u00a0<\/sub>AUC<sub>0-\u221e<\/sub><\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"328\" height=\"239\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-71.png?w=328\" alt=\"\" class=\"wp-image-238\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-71.png 328w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-71-300x219.png 300w\" sizes=\"(max-width: 328px) 100vw, 328px\" \/><\/figure><\/div>\n\n\n\n<p><strong>Fasting &amp; Fed State Conditions<\/strong><\/p>\n\n\n\n<p><strong>Fasting Conditions:<\/strong><\/p>\n\n\n\n<ul><li>Single-dose study: <\/li><li>Overnight fast (10 hrs) and subsequent fast of 4 hrs<\/li><li>Multiple-dose study:<\/li><li>\u00a0Two hours fasting before and after the dose<\/li><\/ul>\n\n\n\n<p><strong>Fed State Studies<\/strong><\/p>\n\n\n\n<ul><li>Required when:<\/li><li>\u00a0The drug recommended with food<\/li><li>\u00a0Modified release product<\/li><li>\u00a0Assessment of C<sub>max<\/sub> and T<sub>max <\/sub>difficult with fasting state study<\/li><li>\u00a0Requires consumption of high-fat food, 15 minutes before dosing<\/li><li>\u00a0Provide 950-1000 kcals<\/li><li>\u00a0Fat- 50%, Proteins 15-20%, Carbohydrate- 30-35%<\/li><li>\u00a0Ethnic &amp; cultural variation considered<\/li><li>\u00a0Specified in protocol<\/li><\/ul>\n\n\n\n<p><strong>&nbsp; Statistical\nEvaluation<\/strong><\/p>\n\n\n\n<ul><li>C<sub>max<\/sub> &amp; AUC analyzed\nusing ANOVA<\/li><li>&nbsp;T<sub>max<\/sub> analyzed by non-parametric\nmethods<\/li><\/ul>\n\n\n\n<p><strong>To establish\nBE:<\/strong><\/p>\n\n\n\n<ul><li>&nbsp;The calculated 90% CI for <strong>C<sub>max<\/sub>\n&amp; AUC<\/strong>, should fall within&nbsp; range:\n80-125%&nbsp; (Range of Bioequivalence)<\/li><li>&nbsp;Non-parametric data 90% CI\nfor <strong>T<sub>max<\/sub><\/strong> should lie within a clinically acceptable range<\/li><\/ul>\n\n\n\n<p><strong>Documentation<\/strong><\/p>\n\n\n\n<ul><li>&nbsp;Signed detailed protocol <\/li><li>&nbsp;Approval by Ethics Committee <\/li><li>&nbsp;Participant Information sheet <\/li><li>&nbsp;Informed Consent Form (ICF)<\/li><li>&nbsp;Case Record Form (CRF)<\/li><li>&nbsp;Undertaking by investigator<\/li><li>&nbsp;CV of investigator <\/li><li>&nbsp;Randomization chart<\/li><li>&nbsp;Laboratory certification <\/li><li>&nbsp;Analytical method validation details<\/li><li>&nbsp;Chromatograms of all volunteers including any\naberrant ones<\/li><li>&nbsp;Tabulated Raw Data of volunteers<\/li><\/ul>\n\n\n\n<p><strong>Maintenance of Records &amp; Retention of Study\nSamples<\/strong><\/p>\n\n\n\n<ul><li>&nbsp;All <strong>Records<\/strong> of in vivo\ntests on any marketed batch of a drug product should be maintained by the\nSponsor <\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp; <strong>for at least 2 years after the expiry date\nof the batch<\/strong><\/p>\n\n\n\n<ul><li>All <strong>Drug samples<\/strong> to be retained for a period of <strong>at least 3 years after the conduct of the study<\/strong> <\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; OR\n<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp; <strong>1year after the expiry of the batch [<\/strong>Stored\nin conditions consistent with the product labeling]\n","protected":false},"excerpt":{"rendered":"<p>Bioavailability and &nbsp;Bioequivalence Studies Introduction It is essential to ensure uniformity in standards of quality, efficacy &amp; safety of Pharmaceutical products Reasonable assurance is to be provided that various products containing the same active ingredient, marketed by different licensees are clinically equivalent &amp; interchangeable Release of an active substance should be known &amp; reproducible Both[&#8230;]\n","protected":false},"author":3,"featured_media":228,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/227"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=227"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/227\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media\/228"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=227"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=227"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=227"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}