Conferencia Internacional sobre Armonización

Pautas

Informe de actualización de seguridad del desarrollo; E2F: paso 4, Ago 2010 (PDF334KB)
Estructura y contenido de los informes de estudios clínicos.; E3: Nov 1995 (PDF471KB)
Buena práctica clínica; E6(R1): paso 4, Jun 1996 (PDF380KB; incluyendo plantilla IB)
Consideraciones generales para ensayos clínicos; E8: Jul 1997 (PDF182KB)
Gestión de datos de seguridad clínica: Definiciones y estándares para informes acelerados; E2A: paso 4, Oct 1994 (PDF145KB)
Principios estadísticos para ensayos clínicos; E9: Feb 1998 (PDF284KB)
Validación de Procedimientos Analíticos – Texto y Metodología; Q2(R1): paso 4, Nov 2005 (PDF180KB)
Procedimientos de prueba y criterios de aceptación para nuevas sustancias farmacológicas y nuevos productos farmacéuticos – Sustancias químicas; P6A: Oct 1995 (PDF211KB, Árboles de decisión PDF46KB)
Todos los documentos están en el paso. 5 (estado de implementación) a menos que se indique lo contrario.
Organización Mundial de la Salud

Medicamentos
Directrices de BPC para ensayos de productos farmacéuticos (Serie de Informes Técnicos de la OMS No.. 850, Anexo 3): 1995 (PDF104KB)
Manual de GCP: 2005 (PDF560KB)
Programa de Precalificación
Información para los solicitantes: Pautas: Genéricos
Texto principal: Guía sobre Genéricos – Calidad Farmacéutica y BE(333PDF de base de conocimientos); anexo seleccionado y suplemento a continuación.
Anexo 7, Presentación de la información del ensayo BE (BTIF): Ene 2010(DOC440KB, ZIP/DOC245KB), Ago 2005 (DOC424KB, ZIP/DOC244KB)
Suplemento 1 (Pruebas de disolución): Jul 2005 (PDF103KB)
Directriz sobre la Recalificación de Expedientes Precalificados: Proyecto de marzo 2009 (PDF69KB)
Fuente múltiple (Genérico) Productos: 1998 (PDF666KB)
Fuente múltiple (Genérico) Productos: Borrador de revisión, 2005 (PDF277KB)
Comparador Internacional: Borrador de revisión, 2005 (PDF142KB)
Bioexención: Borrador 2005 (PDF197KB)
Guía para organizaciones que realizan estudios de bioequivalencia in vivo: Borrador 2005 (PDF103KB)
Comité de Expertos de la OMS en Especificaciones para Preparaciones Farmacéuticas, Trigésimo noveno informe (OMS TRS No. 929, Anexo 5); Combinaciones de dosis fijas: Jun 2005 (PDF974KB)
Comité de Expertos de la OMS en Especificaciones para Preparaciones Farmacéuticas, Cuadragésimo informe (OMS TRS No. 937): Puede 2006 (PDF1.9MB); Los anexos 7 a 9 están disponibles en documentos separados.:
Anexo 7: Fuente múltiple (genérico) productos farmaceuticos: Directrices sobre requisitos de registro para establecer la intercambiabilidad. (PDF425KB)
Anexo 8: Proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release, solid oral dosage forms (PDF464KB)
Anexo 9: Additional guidance for organizations performing in vivobioequivalence studies (PDF371KB)
WHO Expert Committee on Biological Standardization; Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs): Oct 2009 (PDF256KB)
Handbook Good Laboratory Practice (BPL): 2001 (PDF1.1MB)
Training manual for the trainer: 2001 (chapters as PDFs)
Training manual for the trainee: 2001 (chapters as PDFs)
European Union (EMA)

EudraLex – The Rules Governing Medicinal Products in the European Union
Please note: EMA redesigned the website on July 15, 2010.
Links to documents marked with an asterisk* are broken as of Jul 8, 2011. Copies available at our site are denoted by this icon: .
Procedure for European Union Guidelines and Related Documents within the Pharmaceutical Legislative Framework: Ene 2009 (PDF102KB)
Pautas: Clinical Efficacy and Safety HTML, Multidisciplinary HTML
Legislación
Directive 2001/20/EC (Implementation of GCP in the Conduct of Clinical Trials on Medicinal Products for Human Use): Apr 2001 (PDF152KB)
Directive 2003/94/EC (Principles and Guidelines of GMP in Respect of Medicinal Products for Human Use and Investigational Medicinal Products for Human Use): Oct 2003 (PDF115KB)
Directive 2004/9/EC (Inspection and Verification of GLP): Feb 2004 (in many European languages and formats [HTML, PDF, TIFF], P.EJ., PDF247KBen)
Directive 2004/10/EC (Harmonisation of Laws, Regulations and Administrative Provisions relating to the Application of the Principles ofGLP and the Verification of their Applications for Tests on Chemical Substances): Feb 2004 (in many European languages and formats [HTML, PDF, TIFF], P.EJ., PDF239KB en)
Directive 2005/28/EC (Principles and detailed Guidelines for GCP as regards IMPs for Human Use, as well as the Requirements for Authorisation of the Manufacturing or Importation of such Products): Apr 2005 (PDF66KB)
Requirements to the Chemical and Pharmaceutical Quality Documentation concerning IMPs in Clinical Trials: Mar 2006 (PDF141KB)
Definition of IMPs and NIMPs: Jul 2006 (PDF51KB)
Additional Information on IMPs: Apr 2007 (PDF41KB)
BPM, Medicinal Products for Human and Veterinary Use, Anexo 13, IMP: Ene 2010 (PDF66B)
Bioavailability / Bioequivalence
Note for Guidance and associated documents
Bioequivalence: Ene 2010 (PDF236KB), Overview of comments Jan2010 (PDF1.5MB) Draft Jul 2008 (PDF436KB) Recommendation on the Need for Revision of NfG on BA/BE: Puede 2007 (PDF38KB)
Concept paper on the Need to Develop an Appendix to the Guideline on BE Regarding the Presentation of Biopharmaceutical and Bioanalytical Data in Application Dossiers: Apr 2010 (PDF99KB)
Apéndice IV de la Guía para la Investigación de la Bioequivalencia (CPMP/EWP/QWP/1401/98 Rev.1): Presentación de datos biofarmacéuticos y bioanalíticos en el módulo 2.7.1 nuevo: Borrador febrero 2011 (PDF155KB)
Preguntas & Respuestas sobre la Guía BA y BE: Jul 2006 (PDF118KBPDF)
Bioavailability / Bioequivalencia*: Jul 2001 (PDF99KBPDF).
BA/BE para HVD/HVDP: Apr 2006; eliminado en octubre 2007 del sitio de EMEA (cita: Eliminado: este tema se abordará en la revisión de la “Nota de orientación sobre la investigación de la biodisponibilidad y la bioequivalencia”CHMP/EWP/200943/07) PDF36KB.
Documento conceptual sobre la bioexención basada en BCS: Puede 2007 (PDF43KB)
papel de reflexión: Asesoramiento a Solicitantes/Patrocinadores/CRO de BEStudies: Sep 2008 (PDF104KB)
Oral de liberación modificada / Transdérmicos: Jul 1999 (PDF122KB)
Documento conceptual sobre la necesidad de revisar la nota de orientación sobre formas farmacéuticas orales y transdérmicas de liberación modificada: Sección II (Evaluación farmacocinética y clínica.): Puede 2010 (PDF78KB)
Documento conceptual sobre la necesidad de revisar la nota de orientación sobre formas farmacéuticas orales y transdérmicas de liberación modificada: Sección I (calidad): Jul 2010 (PDF95KB)
Farmacocinética
Estudios farmacocinéticos en el hombre: Oct 1988 (PDF39KB)
Estudios farmacocinéticos en pacientes con insuficiencia renal: Jun 2004 (PDF213KB)
Evaluación de la farmacocinética de medicamentos en pacientes con insuficiencia hepática: Feb 2005 (PDF92KB)
PK en el desarrollo de medicamentos en la población pediátrica: Jun 2006 (PDF115KB)
papel de reflexión: Uso de la farmacogenética en la evaluación farmacocinética de medicamentos: Puede 2007 (PDF61KB)
Documento conceptual sobre el desarrollo de una guía sobre el uso de metodologías farmacogenómicas en la evaluación farmacogenómica de medicamentos: Apr 2009 (PDF53KB)
Informe de los resultados de los análisis farmacocinéticos de la población: Jun 2007 (PDF68KB)
Estrategias para identificar y mitigar los riesgos de los primeros ensayos clínicos en humanos con IMP: Jul 2007 (PDF83KB)
Cuestiones estadísticas
Metodología Bioestadística en Ensayos Clínicos*: Oct 1993 (PDF153KBPDF).
Puntos a considerar sobre cuestiones de multiplicidad en los ensayos clínicos: Sep 2002 (PDF208KB)
Guideline on missing data in confirmatory clinical trials: Jul 2010(PDF142KB) Draft Apr 2009 (PDF99KB) Recommendation for the Revision of the Points to Consider on Missing Data (CPMP/EWP/1776/99): Dec 2007 (PDF35KB) Points to Consider on Missing Data: Nov 2001 (PDF38KB)
Biotechnological and Biological Products, Biosimilars
Development Pharmaceutics for Biotechnological and Biological Products – Annex to Note for Guidance on Development Pharmaceutics: Oct 1999 (PDF36KB)
Clinical Investigation of the PK of Therapeutic Proteins: Ene 2007 (PDF98KB, Draft Jul 2005 (PDF101KB)
Similar Biological Medicinal Product: Oct 2005 (PDF106KB)
q&A on biosimilar medicines: Oct 2008 (PDF30KB)
Biosimilars containing Biotechnology-Derived Proteins as Active Substance: Quality Issues: Sep 2005 (PDF137KB)
Biosimilars containing Biotechnology-Derived Proteins as Active Substance: Non-Clinical and Clinical Issues: Feb 2006 (PDF102KB)
Comparability of Biotechnology-Derived Medicinal Products after a change in the Manufacturing Process – Non-Clinical and Clinical Issues: Jul 2007 (PDF118KB) Draft Jan 2007 (PDF171KB) Concept paper Feb 2006 (PDF38KB) Final Dec 2003 (PDF194KB)
Product specific biosimilar guidelines
Recombinant Human Insulin: Feb 2006 (PDF102KB)
Somatropin: Feb 2006 (PDF78KB)
Recombinant Granulocyte-Colony Stimulating Factor: Feb 2006 (PDF89KB)
Recombinant Erythropoietins: Apr 2010 (PDF133KB) Draft Jul 2009(PDF108KB) Concept paper Jul 2008 (PDF43KB) Final Mar 2006 (PDF45KB)
Low-molecular-weight-heparins: Mar 2009 (PDF63KB) Draft Apr 2008 (PDF55KB) Concept paper Jan 2007 (PDF72KB)
Interferon alpha: Reflection paper Jun 2009 (PDF97KB) Draft Oct 2007 (PDF102KB) Concept paper Apr 2006 (PDF72KB)
Immunogenicity assessment of monoclonal antibodies: Concept paper Mar 2009 (PDF39KB)
Monoclonal antibodies: Draft Nov 2010 (PDF192KB)
Follicle stimulation hormone: Concept paper Mar 2010 (PDF125KB)
Interferon beta: Concept paper Mar 2010 (PDF179KB)
Miscellaneous
q&A: Positions on specific questions addressed to the Pharmacokinetics Working Party (PKWP): Ene 2011 (PDF195KB) Jul 2010 ( PDF182KB) Jul2009 (PDF89KB PDF) Jun 2009 (PDF94KB PDF) Ene 2009 ( PDF87KB)
Scientific Advice & Protocol Assistance: Revision 6, Puede 2010 (PDF280KB)
Validation of Bioanalytical Methods: Draft Nov 2009 (PDF135KB)Finalisation expected Q3 2011
Concept Paper/Recommendations on the Need for a (CHMP) Guideline on the Validation of Bioanalytical Methods: Dec 2008 (PDF52KB)
Validación de procedimientos analíticos. Texto y terminología: Nov 1994, Metodología: Dec 1996 (PDF186KB)
Prueba en Muestras de Origen Biológico: Jul 1989 (PDF39KB)
Investigación clínica de sustancias activas quirales.: Apr 1994 (PDF52KB)
Temas: Nov 1995 (PDF43KB)
Medicamentos de combinación fija: Feb 2009 (PDF92KB)
Interacciones farmacológicas: Dec 1997 (PDF79KB)
Documento conceptual/Recomendación sobre la necesidad de revisar la NfG sobre la investigación de interacciones farmacológicas: Jul 2008 (PDF31KB)
Interacciones farmacológicas: Draft Apr 2010 (PDF352KB)
Farmacéutica de desarrollo: Ene 1998 (PDF58KB)

Inhaladores de polvo seco*: Jun 1998 (PDF45KBPDF).
Puntos a considerar sobre los requisitos de documentación clínica para productos inhalados por vía oral (OPI): Apr 2004 (PDF159KB)
Recomendación sobre la necesidad de revisión de puntos

a considerar sobre los requisitos de documentación clínica para productos inhalados por vía oral (OPI): Feb 2007 (PDF36KB)
Requisitos de documentación clínica para productos inhalados por vía oral (OPI) including the Requirements for Demonstration of Therapeutic Equivalence between two Inhaled Products for Use in the Treatment of Asthma and Chronic Obstructive Pulmonary Disease (EPOC): Ene 2009 (PDF271KB), Draft Oct 2007 (PDF176KB), Appendix 1: Mar 2008 (PDF44KB)
Gender Considerations in the Conduct of Clinical Trials: Ene 2005 (PDF75KB)
Guideline on Pharmaceutical Development of Medicines for Paediatric Usenew: Draft May 2011 (PDF247KB)Consulta 31 Dec 2011
Inspections – Good Clinical Practice: Set of 13 documents, Sep 2007 – May 2008 (P.EJ., Investigator Site PDF39KB, Sponsor and/or Contract Research Organisations PDF36KB, Phase I Units PDF31KB, Parte bioanalítica, Pharmacokinetic and Statistical analyses of BE Trials PDF99KB, …)
Heads of Medicines Agencies / Human Medicines
All pages refer to current documents (PDF).
General Information
Application for Marketing Authorisation (MAMÁ)
Generics in MRP and DCP
Applicants response
Renewal Procedure
Variation Procedure
Urgent Safety Restriction

Art. 61.3 Procedimiento
Post Referral Phase
Danish Medicines Agency (DKMA)
Guidelines and Forms en Vejledninger og skemaer da
Bioequivalence and labelling of medicinal products with regard to generic substitution: Ene 2006 (HTML36KB en, HTML42KB da)
Países Bajos (GBG-MEB)
Legislación & Guidelines en Wet – en regelgeving nl
Exemptions from BE-testing (positive list): for strict national registration only
(Ene 2008: HTML29KB en, Oct 2007: HTML31KB nl)
EE.UU (FDA)
CDER Guidances
OGD Homepage
Legislación (excerpts from Code of Federal Regulations, CFR)
Título 21, volumen. 1, Ch. I, Parte 11 [21CFR11]): Electronic records; electronic signatures (Overview containing links to Subparts/Sections)
Título 21, volumen. 1, Ch. I, Parte 50 (21CFR50): Protection of human subjects (Overview+links)
Título 21, volumen. 1, Ch. I, Parte 56 (21CFR56): Institutional review boards (Overview+links)
Título 21, volumen. 1, Ch. I, Parte 58 (21CFR58): GLP for Nonclinical Laboratory Studies (Overview+links)

Título 21, volumen. 5, Ch. I, Parte 312 (21CFR312): Investigational NDA(Overview+links)
Título 21, volumen. 5, Ch. I, Parte 320 (21CFR320): BA and BE Requirements (Overview+links)
CDER’s Manual of Policies and Procedures
Inspections of Clinical Facilities and Analytical Laboratories ConductingBE Studies Submitted in ANDAs: Dec 2000 (PDF19KB)
Review of BE Study Protocols: Jul 2006 (PDF26KB)
Review of BE Studies with Clinical Endpoints in ANDAs: Dec 2006 (PDF25KB)
Bioavailability / Bioequivalence
The ‘Orange Book’: 31th Edition, 2011 (PDF19.2MB, Cumulative supplement [published monthly], Electronic ‘Orange Book’: Current version [including online search])
Statistical Procedures for BE Studies using a Standard Two-Treatment Crossover Design: Jul 1992 (PDF1.4MB)
Statistical Approaches Establishing BE: Ene 2001 (PDF130KB)
BA/BE—General Considerations: Revision 1, Mar 2003 (PDF268KB)
Food-Effect BA / Fed BE: Dec 2002 (PDF166KB)
ER / in vitro/in vivo Correlations: Sep 1997 (PDF170KB)
Biowaivers / BCS: Ago 2000 (PDF54KB)
BA/BE for Nasal Aerosols / Sprays for Local Action: Draft Apr 2003 (PDF519KB; Statistical Information PDF185KB)
SUPAC [IR]: Nov 1995 (PDF60KB, 1997 Questions and Answers HTML16KB)
SUPAC [MR]: Sep 1997 (PDF215KB)
SUPAC [SS]: Puede 1997 (PDF118KB)

BE Recommendations for Specific Products: Jun 2010 (PDF80KB), Draft May 2007 (PDF45KB; Individual Product BE Recommendations by API)
Critical Path Opportunities for Generic Drugs: Puede 2007 (HTML12KB)
Handling/Retention of BA/BE Samples: Puede 2004 (PDF166KB)
Lista de verificación de ANDA para comprobar su integridad y aceptabilidadUD: Mar 2011(PDF140KB)
Tablas de resumen de datos del modelo BE: Ene 2007 (PDF219KB, DOC634KB)
Envío de datos resumidos de BE para ANDAsUD: mayo final 2011 (PDF137KB)
Miscellaneous
Tamaño de las perlas en los productos farmacéuticos etiquetados para Sprinklenew: Draft Jan 2011(PDF43KB)
Validación del método bioanalítico: Puede 2001 (PDF63KB)
Guía para revisores: validación de métodos cromatográficos: Nov 1994 (PDF703KB)
Proporcionar evidencia clínica de la eficacia de medicamentos y productos biológicos para humanos: Puede 1998 (PDF129KB)
Farmacocinética en pacientes con insuficiencia renal: diseño del estudio, Análisis de datos, e impacto en la dosificación y el etiquetado: Puede 1998 (PDF128KB), Proyecto de marzo 2010 (PDF318KB)
Consideraciones generales para estudios farmacocinéticos pediátricos de fármacos y productos biológicos: Nov 1998 (PDF37KB)
Farmacocinética en pacientes con función hepática alterada: Diseño de estudio, Análisis de datos, e impacto en la dosificación y el etiquetado: Puede 2003 (PDF222KB)
Guidance for Industry Providing Regulatory Submissions in Electronic Format—Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications: Revision 2, Jun 2008 (PDF133KB)
Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers: Jul 2005 (PDF702KB)
Current GMP for Phase 1 Investigational Drugs: Jul 2008 (PDF132KB)
Population PK: Feb 1999 (PDF135KB)
Safety Testing of Drug Metabolites: Feb 2008 (PDF86KB)
Drug Metabolism/Interactions: Nov 1999 (PDF44KB)
Drug Interaction Studies—Study Design, Análisis de datos, and Implications for Dosing and Labeling: Draft Sep 2006 (PDF253KB)
Exposure-Response Relationships—Study Design, Análisis de datos, and Regulatory Applications: Apr 2003 (PDF221KB)
Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: 1998—2010 (HTML8KB)
Investigator Responsibilities—Protecting the Rights, Seguridad, and Welfare of Study Subjects: Oct 2009 (PDF163KB)
Information Sheet Guidance for Sponsors, Clinical Investigators, andIRBs; Frequently Asked Questions–Statement of Investigator (Form FDA 1572): Puede 2010 (PDF105KB)
Safety Reporting Requirements for INDs and BA/BE Studiesnew: Sep2010 (PDF688KB)
Compilation of International Human Subjects ProtectionsUD: 2011(PDF938KB)
General Principles of Software Validation; Final Guidance for Industry and FDA Staff: Ene 2002 (PDF161KB, HTML39KB)
Parte 11, Electronic Records; Electronic Signatures — Scope and Application: Ago 2003 (PDF215KB)

Computerized Systems Used in Clinical Investigations: Puede 2007 (PDF53KB)
If you experience problems with missing fonts in PDF-documents, have a look at this postin the forum.
ORA Bioresearch Monitoring Information Page
BPL(Non-Clinical Laboratories)
Compliance Program Guidance Manual: Feb 2001 (PDF117KB, HTML7KB)
Final Rule: Dec 1978 (PDF6.4MB)
Proposed Rule: Oct 1984 (PDF1.7MB, HTML20KB)
Final Rule: Sep 1987 (PDF3.0MB, HTML34KB)
Questions and Answers: Jun 1981, Dec 1999, Jul 2007 (PDF52KB,HTML22KB)
Remark: In the USA two sets of GLP regulations are in force; the other one is issued by the Environmental Protection Agency (EPA).
For a comparison between FDA’s, EPA’s, and OECD’s GLPs see the comparison charts (HTML3KB, PDF1.79MB).
Patrocinadores, Contract Research Organizations and Monitors: Feb 2001 (PDF80KB,HTML3KB)
Clinical Investigators: Dec 2008 (PDF240KB, HTML3KB)
Computerized Systems Used In Clinical Trials: Apr 1999 (PDF46KB, HTML12KB); for the current version (Puede 2007) see CDER’s document linked in the previous section.
Guideline for the Monitoring of Clinical Investigations: Ene 1988 (HTML9KB)
Institutional Review Boards: Oct 1994 (PDF293KB)
Canadá (HPFB/TPD)
HPFB Guidances en, Lignes directrices fr
Conduct and Analysis of Comparative BA Studies: Draft Jan 2010 (PDF190KB,HTML198KB)
Comparative BA Standards: Formulations used for Systemic Effects: Draft Jan2010 (PDF58KB, HTML42KB)
Information and Submission Requirements for Subsequent Entry Biologics (SEBs): Proyecto de marzo 2010 (PDF96KB, HTML71KB)
BA / BE – Part A [IR]: 1992 (PDF151KB, HTML126KB)
BA / BE – Part B [MR]: Nov 1996 (PDF594KB, HTML396KB)
BA / BE – Part C [IR, complicated or highly variable PK]: Dec 1992 (PDF40KB,HTML52KB)
Inclusion of Women in Clinical Trials: Apr 1997 (PDF24KB, HTML29KB)
Interacciones farmacológicas: Sep 2000 (PDF69KB, HTML93KB)
CTAs for Comparative BA Studies: Draft Oct 2001; updated Feb 2008 (PDF241KB, HTML87KB)
Records Related to Clinical Trials: Puede 2006 (PDF137KB, HTML75KB)
Draft Policy: BE Requirements: Drugs Exhibiting Non-linear Pharmacokinetics, Jun 2003 (HTML13KB)
BE of HVDs/HVDPs: Discussion Paper, Jun 2003 (PDF61KB, HTML42KB)
Removal of Requirement for 15% Random Replicate Samples: Notice, Sep 2003 (PDF13KB, HTML21KB)
BE of Combination Drug Products: Notice, Jun 2004 (PDF12KB, HTML22KB)
Metabolites in Comparative BA Studies: Draft May 2004 (PDF27KB, HTML29KB)
Preparation of Comparative BA Information for Drug Submissions in the CTDFormat: Draft May 2004 (PDF91KB, HTML106KB)
BE in Fed State: Jun 2005 (PDF25KB, HTML30KB)
BE for Long Half-life Drugs: Notice, Jun 2005 (PDF13KB, HTML21KB)
BE for Rapid Onset Drugs: Notice, Jun 2005 (PDF15KB, HTML22KB)
BE for Critical Dose Drugs: Puede 2006 (PDF45KB, HTML42KB)
Critical Dose Drugs are: ciclosporina, digoxin, flecainide, lithium, phenytoin, sirolimus, tacrolimús, theophylline, and warfarin.
Japón (NIHS)
Division of Drugs Guidances en ???????????? ja
Clinical Pharmacokinetic Studies of Pharmaceuticals: Jun 2001 (PDF502KB)
Bioequivalence of Generic Drugs: Dec 1997 (PDF60KB, HTML109KB)
BE para diferentes fortalezas: Feb 2000 (PDF33KB, HTML19KB)
Cambios de formulación: Feb 2000 (PDF34KB)
Temas: Jul 2003 (PDF68KB)
Formas de dosificación oral de liberación prolongada: Mar 1988 (PDF53KB)
Las siguientes pautas fueron revisadas con 24 Nov 2006:
Estudios BE para productos genéricos: (Guía PDF175KB, PDF480KB y;q&Un documento PDF407KB ja)
Directrices para la prueba BE en preparaciones sólidas orales con diferentes concentraciones de fármacos: (Guía PDF78KB, PDF235KB y; q&Un documento PDF471KB ja)
Guía para la prueba BE en preparaciones sólidas orales cuya formulación ha sido modificada: (Guía PDF107KB, PDF251KB y; q&Un documentoPDF471KB ja)
Remark: la q&Un documento parece cubrir ambos temas..
Guía para estudios de BE de productos genéricos para uso tópico: (Pautas, q&y yo)
Guía para estudios de BE sobre la adición de formas farmacéuticas para uso tópico: nuevo 24 Nov 2006 (Directriz236KB y, q&A43KB y)
Sudáfrica (MCC)
Pautas
MCC está rediseñando su sitio web. Links to documents marked with an asterisk* are broken as of Jul 8, 2011.
Cita: We are aware of broken document links caused by a programming error and we are working with the developers to have it corrected in the shortest possible time.
Thank you for your patience.
Generic Substitution*: Final, Dec 2003 (ZIP/DOC28KB)
Pharmaceutical and Analytical Guideline*: Jul 2007 (ZIP/DOC76KB)
Biostudies: Jul 2007 (ZIP/DOC66KB)
Disolución: Jul 2007, except section 4.1 (Jul 2008, ZIP/DOC47KB)
Australia (TGA)
Pautas
BA and BE: Apr 2002 (PDF212KB)
Summary of a BA or BE Study: Dec 2002 (PDF107KB)
Australian Regulatory Guidelines for Prescription Medicines, Appendix 15: Biopharmaceutic Studies: Jun 2004 (PDF178KB)
Clinical Guidelines of the European Union adopted in Australia: current (HTML)
Nueva Zelanda (Medsafe)
Pautas
Guidance notes for applicants for consent to distribute new and changed medicines and related products (including BA/BE): Final, Oct 2001 (DOC5.0MB)
Biostudy Reference Products: Jul 2006 (HTML5KB)
India (CDSCO)
Central Drugs Standard Control Organization
Bioavailability / Bioequivalence: Current Draft Mar 2005 (PDF106KB), Proyecto de marzo 2003 (HTML0.99MB)
Requirements and Guidelines for Permission to Import and / o Fabricación de Nuevos Medicamentos para la Venta o para Realizar Ensayos Clínicos: Anexo Y – Versión Enmendada, Jun 2005 (PDF8.7MB, HTML681KB)
Documentos a presentar para la concesión de permiso para realizar estudios de bioequivalencia con fines de exportación: Ago 2009 (DOC92KB)
PCG: 2005 (HTML834KB)
Presentación de solicitud de ensayo clínico para evaluar la seguridad y eficacia: v1.1 diciembre 2008 (PDF704KB)

Registro CRO: Draft Jan 2011 (PDF565KB)
Lista de verificación modificada para solicitudes de licencia de prueba a partir de 15 Junio 2011(PDF69KB)
Clarificación & Modificaciones en la guía para la industria con respecto a los cambios posteriores a la aprobación de productos biológicos: Ago 2010 (PDF147KB)
Directrices éticas para la investigación biomédica en participantes humanos (publicado por el Consejo Indio de Investigación Médica): Oct 2006 (PDF3.1MB)
Bangladesh (DGDA)

 

Dirección General de Administración de Medicamentos
Orientación para la industria (Presentación de solicitud de ensayo clínico para evaluar la seguridad y eficacia, Requisitos para el permiso de Aprobación de Nuevos Medicamentos, Cambios posteriores a la aprobación de productos biológicos: Quality safety and Efficacy Documents, Preparation of the Quality Information for Drug Submission for New Drug Approval: Biotechnological/Biological Products): 2010 (PDF555KB)

PAHO
Pan American Health Organization

Working Group on Bioequivalence
Buenas Prácticas Clínicas – Document of the Americas: 2005 (PDF306KB)
Science Based Criteria for BE in vivo and in vitro, Bio-Waivers and Strategic Framework for Implementation: Borrador >2001? (PDF971KB)
BA / BE / Biowaivers: Final Draft Aug 2004 (PDF868KB)
Brasil (ANVISA)
Legislation en Legisla??o pt

Nota: ANVISA is redesigning their website starting in mid-August 2010. Most links are broken with no automatic redirects as of 12 Septiembre 2008. We are trying to update links as soon as possible.
Implementation of Relative BA and BE Studies: Apr 2006 (HTML42KB pt, Nov 2004 HTML41KB pt, Puede 2003 HTML31KB pt)
Pharmaceutical Equivalence / Disolución: Sep 2004 (HTML33KB pt, May 2003HTML46KB pt, Puede 2003 HTML27KB pt, Mar 2002 HTML29KB pt)
BA / BE: Puede 2003 (HTML46KB en, HTML31KB pt)
Exemption and Substitution of BE Studies: Puede 2003 (HTML31KB en,HTML15KB pt, Mar 2002 HTML23KB pt)

Validación del método bioanalítico: Puede 2003 (PDF56KB en, HTML104KB pt, Mar 2002 HTML46KB pt)
Explanation of the Implementation of Re No. 899/2003 – Validation of Bioanalytical Methods: Jun 2008 (PDF34KB pt)
National Registry of Volunteers in BE Studies: Jun 2008 (HTML26KB pt)
Statistics for BA/BE Studies: Puede 2003 (PDF48KB en, HTML49KB pt, Mar 2002HTML24KB pt)
Protocol of BE Studies: Puede 2003 (HTML32KB en, HTML16KB pt, Mar 2002HTML28KB pt)
Report of BE Studies: Puede 2003 (HTML63KB en, HTML55KB pt)
List of Reference Products: Current (PDF265KB pt)
Rules / Technical Regulations for CROs: Puede 2003 (HTML720KB en,HTML586KBpt)
Annex I: Certification for BA/BE Centers: (Application Form DOC395KB,DOC148KB; Renewal Form DOC370KB, RTF365KB)
Annex II: Guidelines for Inspection at Centers of BA/BE of Medicines (DOC pt)
Annex III: Certificate of Good Practices of BA/BE of Medicines (GIF1KB pt)
Annex IV: Form for Outsourcing of Phase for Assays of BA/BE of Medicines (DOC pt)
Annex V: Form for Monthly Report of Assays of BA/BE of Medicines (DOC pt)
Remarks: The Renewal Form is not linked in Annex I, Annex II is given below ‘CLASSIFICATION OF ITEMS OF THE INSPECTION GUIDELINES’; links to Annexes II, IV, and V are broken in the English version as of 31 Puede 2008.
Annexes I, III–V are given as screenshots (JPEG-format); Annex II is given below‘CLASSIFICA??O DOS ITENS DO ROTEIRO DE INSPE??O’ in the Portuguese version.
Guidance for Pharmaceutical Equivalence and Bioequivalence of Nasal Sprays and Aerosols: Jun 2008 (PDF110KB pt, PDF132KB en)
Remark: The document in English is an unofficial translation.
BA BE Good Practices Manual en
Manual de Boas Pr?ticas em Biodisponibilidade e Bioequivalencia pt
Volumen 1 (clínicas, analytics, statistics): 2002 (ZIP/PDF6.1MB en,ZIP/PDF4.3MB pt)
Volumen 2 (micropipets, water for analysis, instrumentation): 2002 (ZIP/PDF6.2MB en, ZIP/PDF4.7MB pt)
México
Secretar?a de Salud es
BA / BE: Final, Puede 1999 (PDF100KB es)
BA / BE Update, Biowaivers: Mar 2000 (HTML4KB es)
Comisi?n Permanente de la Farmacopea de los Estados Unidos Mexicanos:Legislaci?n santitaria relacionada con la industria farmac?utica es
Argentin

ANMAT es

GCP Guideline for studies in human subjects: Nov 2007 (PDF201KB es)
GCP in Clinical Studies: 1997, amended 2005 (PDF143KB es)
Good Practices in Clinical Pharmacology Research: Nov 2010 (PDF1.0MB es)
BA / BE: Final Sep 2006, amended Mar 2007 (PDF1.8MB es, 1999 PDF389KB es)
BCS based Biowaivers for oral solid IR dosage forms: Feb 2009 (PDF97KB es)
Post approval changes: Feb 2009 (PDF154KB es)
Validación del método bioanalítico: Sep 2005 (PDF130KB es)
Saudia Arabia
Saudi Food & Drug Authority en ??????? ?????? ?????? ?????? ar

BE: Draft May 2005 (PDF297KB)
Clinical Trials Requirements Guideline: Draft Oct 2009 (PDF374KB), Draft May 2005 (PDF318KB)
BPL: Borrador febrero 2006? (PDF269KB)
Guidelines for IND requirements: Draft Aug 2009 (PDF318KB)
Guideline on Pharmaceutical Equivalence Requirements: Draft Aug 2009(PDF139KB)
Drug Master File Requirements for the Registration of Biosimilars: Draft Aug 2008 (PDF105KB)
Guidelines on Biosimilars: Draft Oct 2009 (PDF971KB)
Jordán
Jordan Food and Drug Administration en ??????? ?????? ?????? ??????? ar
Law of clinical studies: 2003 (DOC55KB ar), 2001 (DOC59KB en)
Egipto
Egyptian Drug Authority
BE Studies Guidelines: Ene 2010 (PDF1.0MB)
BE Requirements: Mar 2009 (DOC111KB ar)
BE Report: Oct 2008 (DOC132KB)
GLP Checklist: Proyecto de marzo 2006 (DOC754KB)
ASEAN States (ACCSQ)
Pharmaceutical Product Working Group
BA / BE: Final Draft Jul 2004 (PDF82KB)
BE Studies Reporting Format: Feb 2008 (PDF37KB)
BE, q&A: Versión 2, Puede 2009 (PDF67KB); Versión 1, Jul 2008 (PDF16KB)
Malaysia (BPFK
Pautas
Conduct of BA and BE Studies: Final, Sep 2000 (PDF89KB, DOC191KB)
PCG: Second Edition, Ene 2004 (PDF646KB)
BPL: Draft Jul 2006 (PDF1.7MB)

BPL: Jun 2009 (OECD’s adopted; see PDF368KB)
Guidance Document and Guidelines for Registration of Biosimilars: Ago 2008 (PDF166KB)
Tailandia (FDA)
DCD
BA / BE: Mar 2009 (PDF224KB)
BA / BE: Current? (HTML146KB th)
BA / BE: Ago 2004(?), adopted 2005 (DOC171KB)
Instruction for the In Vivo BE Study Protocol Development: Oct 2006 (PDF1.4MB th)
BE Study Protocol / Report: 2003 (PDF52KB th)
Singapur (HSA)
HSA
Drug Registration Information and Guidelines
Guidance on Medicinal Product Registration in Singapore: Feb 2007 (complete document PDF3.7MB)
Product Interchangeability and Biowaiver Request for chemical Generic Drug Applications: Feb 2007 (Appendix 15 PDF47KB)
ASEAN Common Technical Requirements (ACTR)
BA / BE: Final Draft Jul 2004 (PDF127KB)
Validación de procedimientos analíticos: Final(?), Ene 2005 (PDF123KB)
(South) Corea
KFDA
Guidance Document for BE Study: Dec 2008 (PDF604KB)
Minimum Requirements for BE Test: Dec 2005 (PDF493KB)
Taiwán
CDE ??????????? zh
Reglamentos ?????????zh
BA / BE: Dec 2006 (PDF171KB zh, HTML47KB zh)
PCG: Ene 2005 (PDF248KB zh, HTML230KB zh)
Pediatric PK: Jul 2002 (PDF195KB zh, HTML158KB zh)

Ethnic Factors in the Acceptability of Foreign Clinical Data: Puede 2002 (PDF323KB zh)
BPL: Mar 2006 (PDF200KB zh, HTML197KB zh)
Nonclinical Pharmacology/Toxicology: Jun 2000 (PDF1.0MB zh,HTML1.9MB zh)
Warning: The HTML-document was produced by means of M$ Word 11 (Office 2003), presents no valid HTML, and contains 2000+ Errors! Standard-conform browsers like Firefox <v3 were reported to crash opening this file, while M$ IE is able to render the gibberish.
Analytical Method Validation: Ene 2000 (PDF223KB zh, HTML172KB zh)
Porcelana
SFDA en ??????????? zh
Center for Drug Evaluation ?????? zh
Drug Administration Law: Dec 2001 (HTML64KB)
Regulations for Implementation of the Drug Administration Law: Sep 2002 (HTML63KB)
Buena práctica clínica: Ago 2003 (HTML46KB zh)
Statistical Guidelines for Clinical Trials of Drugs and Biologics: Mar 2005 (PDF324KB zh)
Farmacocinética: 2005 (PDF300KB zh)
Bioequivalence: 2005 (PDF328KB zh)
Hong Kong; GCP for Proprietary Chinese Medicines: Feb 2004 (PDF242KB en,PDF669KB zh)
Suiza
Swissmedic en
Instructions for Generics: Dec 2002 (PDF704KB de/fr)
Reference Formulations for BE / CTDs for Generics: Apr 2004 (PDF659KB de/fr)
Biosimilars: Feb 2008 (PDF64KB de)
Federal Office of Public Health – AGIT
Guidelines on computerized systems

Guidelines for the archiving of Electronic Raw Data in a GLP Environment: Puede 2003 (PDF124KB)
Guidelines for the management of electronic SOPs in GLP: Sep 2006 (PDF134KB)
Guidelines for the acquisition and processing of electronic raw data in a GLPenvironment: Sep 2006 (PDF166KB)
Guidelines for the validation of computerised Systems in GLP Environment: Dec 2007 (PDF344KB)
Pavo
Ministry of Health en MoH tr
Good Laboratory Practice Principles: Jun 2002 (HTML55KB tr)
Licensing Regulation for Pharmaceutical Products: 2003 (PDF147KB)
Submission of BA/BE Dossiers: Ene 2006 ( PDF287KB)
Remark: The document is an unofficial translation I received at my workshop in Istanbul in March 2006; I have no idea whether anything has changed in the meantime.
Israel
Ministry of Health en ???? ??????? he
Drug Registration Section he
Guidelines for Clinical Trials in Human Subjects: Ene 2006 (PDF888KB he,PDF204KB en)
SOP for Performing BE in Human Subjects: Sep 2002 (DOC132KB he)
Requirments for Registration of a Generic Product: Sep 2002 (DOC167KB he)
Uganda
National Drug Authority
Drug Registration
Guidelines on the Registration of Pharmaceuticals for Human use: Jul 2006 (PDF154KB)
Variations: Oct 2009 (PDF1.5MB)
OECD
Environment Directorate
OECD Environmental Health and Safety Publications, Series on Principles of Good Laboratory Practice and Compliance Monitoring

OECD Principles of Good Laboratory Practice: Apr 1999 (PDFs en, fr, en/fr,de).
Revised Guides For Compliance Monitoring Procedures for Good Laboratory Practice: Jun 1995 (PDFs en, fr, en/fr).
Revised Guidance for the Conduct of Laboratory Inspections and Study Audits: Jun 1995 (PDFs en, fr, en/fr).

Quality Assurance and GLP: Dec 1999 (PDFs en, fr, de, es).
Compliance of Laboratory Suppliers with GLP Principles: Sep 2000 (PDFs en,fr, de, es).
The Application of the GLP Principles to Field Studies: Sep 2000 (PDFs en, fr,de, es) – not applicable for PK/BA/BE/PK, just for completeness.
The Application of the GLP Principles to Short Term Studies: Dec 1999 (PDFsen, fr, de, es).
The Role and Responsibility of the Study Director in GLP Studies: Oct 1999 (PDFs en, fr, de).
Guidance for the Preparation of GLP Inspection Reports: Oct 1999 (PDFs en,fr, en/fr).
The Application of the Principles of GLP to Computerised Systems: Oct 1995 (PDFs en, fr, de, es: 4th link, also denoted as German).
The Role and Responsibilities of the Sponsor in the Application of the Principles of GLP: Mar 1998 (PDFs en, fr).
Requesting and Carrying Out Inspections and Study Audits in Another Country: Sep 2000 (PDFs en, fr).
The Application of the OECD Principles of GLP to the Organisation and Management of Multi-Site Studies: Jun 2002 (PDFs en, fr, de).
The Application of the Principles of GLP to in vitro Studies: Nov 2004 (PDFsen, fr).
Establishment and Control of Archives that Operate in Compliance with the Principles of GLP: Jun 2007 (PDFs en, fr).
Remark: For a comparison between OECD’s, US-FDA’s, and US-EPA’s GLPs see the comparison charts (HTML, 1.8MB PDF).
FOTO/S
Guides Recommendations

Good Practices for Computerized Systems in Regulated “GXP” Environments: Versión 3, Sep 2007 (PDF443KB)
EDQM

Quality Assurance Activities Guidelines
Validación de procedimientos analíticos: Jun 2005 (PDF605KB)
Uncertainty of Measurements
Parte I (compliance testing): Dec 2007 (PDF703KB)
Parte II (other than compliance testing): Dec 2007 (PDF1.0MB)
Qualification of Equipment (core document): Sep 2008 (PDF1.0MB)
Anexo 1: Qualification of HPLC Equipment: Feb 2007 (PDF1.4MB)
Anexo 2: Qualification of GC Equipment: Oct 2006 (PDF897KB)
Abreviaturas

ACCSQ Consultative Committee for Standards and Quality (? ASEAN)
AGIT Arbeitsgruppe Informationstechnologie (Working Group on Information Technology, Suiza)
ANDA Abbreviated New Drug Application (? FDA)
ANMAT Administraci?n Nacional de Medicamentos, Alimentos y Tecnolog?a M?dica (National Administration for Medicines, Food and Medical Technology, Argentina)
ANVISA Ag?ncia Nacional de Vigil?ncia Sanit?ria (National Agency for Sanitary Monitoring, Brasil)
API Active Pharmaceutical Ingredient
ASEAN Association of Southeast Asian Nations
BA Bioavailability
BCS Biopharmaceutics Classification System
BE Bioequivalence
BPFK Biro Pengawalan Farmaseutikal Kebangsaan (National Pharmaceutical Control Bureau, Malaysia)
CDE Center For Drug Evaluation (Taiwán)
CDER Center for Drug Evaluation and Research (of the ? FDA)
CDSCO Central Drugs Standard Control Organization (India)
CHMP Committee for Medicinal Products for Human Use (of the ? EMA)
CRO Contract Research Organization
CTA Clinical Trial Application
CTD Common Technical Document (according to ? I)
DCD Drug Control Division (Tailandia)
DCP Decentralised Procedure (in the ? UE)
DGDA Directorate General of Drug Administration (Bangladesh)
DOC Micro$oft’s Word Format
DKMA Danish Medicines Agency
E Efficacy (Topic of ? I)
eCTD Electronic Common Technical Document (? CTD)
EDA Egyptian Drug Authority
EDQM European Directorate for the Quality of Medicines & HealthCare
EMA European Medicines Agency (formerly European Medicines Evaluation Agency – EMEA)
ER Extended Release

EU European Union
EWP Efficacy Working Party (of the ? EMA)
FDA Food and Drug Administration (Estados Unidos)
FIM First-In-Man (Clinical Study)
GCP Good Clinical Practice(s)
GLP Good Laboratory Practice(s)
GIF Graphics Interchange Format
GMP Good Manufacturing Practice(s)
HPFB Health Products and Food Branch (of Health Canada)
HSA Health Sciences Authority (Singapur)
HVD Highly Variable Drug
HVDP Highly Variable Drug Product
ICH International Conference on Harmonisation (of Technical Requirements for the Registration of Pharmaceuticals for Human Use)
IMP Investigational Medicinal Product
IND Investigational New Drug
IR Immediate Release
IRB Institutional Review Board
JPEG Joint Photographic Experts Group (graphics format)
JFDA Jordan Food and Drug Administration
KB Kilobyte = 1024 Bytes (filesize)
KFDA (South) Korea Food & Drug Administration
MA Marketing Authorisation (in the ? UE)
MB Megabyte = 1024KB = 1048576 Bytes (filesize)
MCC Medicines Control Council (Sudáfrica)
MoH Ministry of Health
MR Modified Release
MRP Mutual Recognition Procedure (in the ? UE)
NDA National Drug Authority (Uganda)
NfG Note for Guidance (of the ? EMA)
NIHS National Institute for Health Sciences (Japón)
NIMP Non Investigational Medicinal Product
OECD Organisation for Economic Co-operation and Development
OGD Office of Generic Drugs (of the ? FDA)
PAHO Pan American Health Organization
PDF Adobe’s Portable Document Format
PIC/S Pharmaceutical Inspection Co-operation Scheme
PK Pharmacokinetics
Q Quality (Topic of ? I)
q&A Questions and Answers
RTF Rich Text Format
SFDA Saudi Food & Drug Authority (Saudia Arabia)
SFDA State Food & Drug Administration (Porcelana)
SS Semisolid
SUPAC Scale-Up and Post-Approval Changes (according to ? FDA)
TGA Therapeutic Goods Administration (Australia)
TIFF Tagged Image File Format
TPD Therapeutic Products Directorate (de ? HPFB)
WHO World Health Organization
ZIP Compressed file (format)