International Conference on Harmonisation

Des lignes directrices

Development Safety Update Report; E2F: étape 4, Août 2010 (PDF334 Ko)
Structure et contenu des rapports d'études cliniques; E3: Nov 1995 (PDF471 Ko)
Bonnes pratiques cliniques; E6(R1): étape 4, juin 1996 (PDF380 Ko; y compris le modèle IB)
Considérations générales pour les essais cliniques; E8: Juillet 1997 (PDF182 Ko)
Gestion des données de sécurité clinique: Définitions et normes pour les rapports accélérés; E2A: étape 4, Oct 1994 (PDF145KB)
Statistical Principles for Clinical Trials; E9: Feb 1998 (PDF284KB)
Validation of Analytical Procedures – Text and Methodology; Q2(R1): étape 4, Nov 2005 (PDF180KB)
Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products – Chemical Substances; Q6A: Oct 1995 (PDF211KB, Decision Trees PDF46KB)
All documents are in step 5 (implementation state) unless noted otherwise.
World Health Organization

Médicaments
Guidelines for GCP for trials on pharmaceutical products (WHO Technical Report Series No. 850, Annexe 3): 1995 (PDF104KB)
Handbook for GCP: 2005 (PDF560KB)
Prequalification Programme
Information for Applicants: Des lignes directrices: Génériques
Main text: Guideline on Generics – Pharmaceutical Quality and BE(333KB PDF); selected annex and supplement below.
Annexe 7, Presentation of BE Trial Information (BTIF): Jan 2010(DOC440KB, ZIP/DOC245KB), Août 2005 (DOC424KB, ZIP/DOC244KB)
Supplement 1 (Dissolution testing): Juillet 2005 (PDF103KB)
Guideline on the Requalification of Prequalified Dossiers: Draft Mar 2009 (PDF69KB)
Multisource (Generic) Products: 1998 (PDF666KB)
Multisource (Generic) Products: Draft Revision, 2005 (PDF277KB)
International Comparator: Draft Revision, 2005 (PDF142KB)
Biowaiver: Draft 2005 (PDF197KB)
Guidance for Organizations performing in vivo Bioequivalence Studies: Draft 2005 (PDF103KB)
WHO Expert Committee on Specifications for Pharmaceutical Preparations, Thirty-ninth Report (WHO TRS No. 929, Annexe 5); Fixed dose combinations: juin 2005 (PDF974KB)
WHO Expert Committee on Specifications for Pharmaceutical Preparations, Fortieth Report (WHO TRS No. 937): Peut 2006 (PDF1.9MB); Annexes 7–9 are available in separate documents:
Annexe 7: Multisource (generic) produits pharmaceutiques: guidelines on registration requirements to establish interchangeability (PDF425KB)
Annexe 8: Proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release, solid oral dosage forms (PDF464KB)
Annexe 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: Jan 2009 (PDF102KB)
Des lignes directrices: Clinical Efficacy and Safety HTML, Multidisciplinary HTML
Legislation
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 (Principes et lignes directrices des BPF concernant les médicaments à usage humain et les médicaments expérimentaux à usage humain): Oct 2003 (PDF115 Ko)
Directive 2004/9/CE (Inspection et vérification des BPL): Feb 2004 (dans de nombreuses langues et formats européens [HTML, PDF, TIFF], par exemple., PDF247KBen)
Directive 2004/10/CE (Harmonisation des lois, Règlements et dispositions administratives relatifs à l'application des principes des BPL et à la vérification de leurs applications pour les essais sur les substances chimiques): Feb 2004 (dans de nombreuses langues et formats européens [HTML, PDF, TIFF], par exemple., PDF239 Ko a)
Directive 2005/28/CE (Principes et lignes directrices détaillées des BPC en ce qui concerne les IMP à usage humain, ainsi que les exigences relatives à l'autorisation de fabrication ou d'importation de ces produits.): Apr 2005 (PDF66 Ko)
Exigences relatives à la documentation sur la qualité chimique et pharmaceutique concernant les IMP dans les essais cliniques: Mar 2006 (PDF141 Ko)
Définition des IMP et NIMP: Juillet 2006 (PDF51KB)
Additional Information on IMPs: Apr 2007 (PDF41KB)
BPF, Medicinal Products for Human and Veterinary Use, Annexe 13, IMPs: Jan 2010 (PDF66B)
Bioavailability / Bioéquivalence
Note for Guidance and associated documents
Bioéquivalence: Jan 2010 (PDF236KB), Overview of comments Jan2010 (PDF1.5MB) Draft Jul 2008 (PDF436KB) Recommendation on the Need for Revision of NfG on BA/BE: Peut 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)
Appendix IV of the Guideline on the Investigation on Bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1): Presentation of Biopharmaceutical and Bioanalytical Data in Module 2.7.1new: Draft Feb 2011 (PDF155KB)
Des questions & Answers on the BA and BE Guideline: Juillet 2006 (PDF118KB PDF)
Bioavailability / Bioequivalence*: Juillet 2001 (PDF99KB PDF).
BA/BE for HVDs/HVDPs: Apr 2006; removed in Oct 2007 from EMEA’s site (quote: Deleted – This topic will be addressed in the revision of “Note for guidance on the investigation of bioavailability and bioequivalence”CHMP/EWP/200943/07) PDF36KB.
Concept Paper on BCS-based Biowaiver: Peut 2007 (PDF43KB)
Reflection paper: Advice to Applicants/Sponsors/CROs of BEStudies: Sep 2008 (PDF104KB)
Modified Release Oral / Transdermals: Juillet 1999 (PDF122KB)
Concept paper on the need for revision of the note for guidance on modified release oral and transdermal dosage forms: Section II (pharmacokinetic and clinical evaluation): Peut 2010 (PDF78KB)
Concept paper on the need for revision of the note for guidance on modified release oral and transdermal dosage forms: Section I (quality): Juillet 2010 (PDF95KB)
Pharmacokinetics
Pharmacokinetic Studies in Man: Oct 1988 (PDF39KB)
PK Studies in Patients with Renal Impairment: juin 2004 (PDF213KB)
Evaluation of the PK of Medicinal Products in Patients with Impaired Hepatic Function: Feb 2005 (PDF92KB)
PK in the Development of Medicinal Products in the Paediatric Population: juin 2006 (PDF115 Ko)
Reflection paper: Use of Pharmacogenetics in the PK Evaluation of Medicinal Products: Peut 2007 (PDF61KB)
Concept Paper on the Development of a Guideline on the Use of Pharmacogenomic Methodologies in the PK Evaluation of Medicinal Products: Apr 2009 (PDF53KB)
Reporting Results of Population PK Analyses: juin 2007 (PDF68KB)
Strategies to Identify and Mitigate Risks for First-In Human Clinical Trials with IMPs: Juillet 2007 (PDF83KB)
Statistical Issues
Biostatistical Methodology in Clinical Trials*: Oct 1993 (PDF153KB PDF).
Points to Consider on Multiplicity Issues in Clinical Trials: Sep 2002 (PDF208KB)
Guideline on missing data in confirmatory clinical trials: Juillet 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: Jan 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: Juillet 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&UN: Positions on specific questions addressed to the Pharmacokinetics Working Party (PKWP): Jan 2011 (PDF195KB) Juillet 2010 ( PDF182 Ko) Jul2009 (PDF89KB PDF) juin 2009 (PDF94KB PDF) Jan 2009 ( PDF87KB)
Scientific Advice & Protocol Assistance: Revision 6, Peut 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)
Validation of Analytical Procedures. Text and Terminology: Nov 1994, Methodology: Dec 1996 (PDF186KB)
Test on Samples of Biological Origin: Juillet 1989 (PDF39KB)
Clinical Investigation of Chiral Active Substances: Apr 1994 (PDF52KB)
Topicals: Nov 1995 (PDF43KB)
Fixed Combination Medicinal Products: Feb 2009 (PDF92KB)
Drug Interactions: Dec 1997 (PDF79KB)
Concept Paper/Recommendation on the Need for Revision of NfG on the Investigation of Drug Interactions: Juillet 2008 (PDF31KB)
Drug Interactions: Draft Apr 2010 (PDF352KB)
Development Pharmaceutics: Jan 1998 (PDF58KB)

Dry Powder Inhalers*: juin 1998 (PDF45KB PDF).
Points to Consider on the Requirements for Clinical Documentation for Orally Inhaled Products (OIP): Apr 2004 (PDF159KB)
Recommendation on the Need for Revision of Points

to Consider on the Requirements for Clinical Documentation for Orally Inhaled Products (OIP): Feb 2007 (PDF36KB)
Requirements for Clinical Documentation for Orally Inhaled Products (OIP) including the Requirements for Demonstration of Therapeutic Equivalence between two Inhaled Products for Use in the Treatment of Asthma and Chronic Obstructive Pulmonary Disease (BPCO): Jan 2009 (PDF271KB), Draft Oct 2007 (PDF176KB), Appendix 1: Mar 2008 (PDF44KB)
Gender Considerations in the Conduct of Clinical Trials: Jan 2005 (PDF75KB)
Guideline on Pharmaceutical Development of Medicines for Paediatric Usenew: Draft May 2011 (PDF247KB)Consultation 31 Dec 2011
Inspections – Good Clinical Practice: Set of 13 documents, Sep 2007 – May 2008 (par exemple., Investigator Site PDF39KB, Sponsor and/or Contract Research Organisations PDF36KB, Phase I Units PDF31KB, Partie bioanalytique, 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 (MA)
Generics in MRP and DCP
Applicants response
Renewal Procedure
Variation Procedure
Urgent Safety Restriction

Art. 61.3 Procédure
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: Jan 2006 (HTML36KB en, HTML42KB da)
Pays-Bas (GBG-MEB)
Legislation & Guidelines en Wet – en regelgeving nl
Exemptions from BE-testing (positive list): for strict national registration only
(Jan 2008: HTML29KB en, Oct 2007: HTML31KB nl)
Etats-Unis (FDA)
CDER Guidances
OGD Homepage
Legislation (excerpts from Code of Federal Regulations, CFR)
Titre 21, Vol. 1, Ch. je, Part 11 [21CFR11]): Electronic records; electronic signatures (Overview containing links to Subparts/Sections)
Titre 21, Vol. 1, Ch. je, Part 50 (21CFR50): Protection of human subjects (Overview+links)
Titre 21, Vol. 1, Ch. je, Part 56 (21CFR56): Institutional review boards (Overview+links)
Titre 21, Vol. 1, Ch. je, Part 58 (21CFR58): GLP for Nonclinical Laboratory Studies (Overview+links)

Titre 21, Vol. 5, Ch. je, Part 312 (21CFR312): Investigational NDA(Overview+links)
Titre 21, Vol. 5, Ch. je, Part 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: Juillet 2006 (PDF26KB)
Review of BE Studies with Clinical Endpoints in ANDAs: Dec 2006 (PDF25KB)
Bioavailability / Bioéquivalence
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: Juillet 1992 (PDF1.4MB)
Statistical Approaches Establishing BE: Jan 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: Août 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]: Peut 1997 (PDF118KB)

BE Recommendations for Specific Products: juin 2010 (PDF80KB), Draft May 2007 (PDF45KB; Individual Product BE Recommendations by API)
Critical Path Opportunities for Generic Drugs: Peut 2007 (HTML12KB)
Handling/Retention of BA/BE Samples: Peut 2004 (PDF166KB)
ANDA Checklist for Completeness and AcceptabilityUD: Mar 2011(PDF140KB)
Model BE Data Summary Tables: Jan 2007 (PDF219KB, DOC634KB)
Submission of Summary BE Data for ANDAsUD: Final May 2011 (PDF137KB)
Miscellaneous
Size of Beads in Drug Products Labeled for Sprinklenew: Draft Jan 2011(PDF43KB)
Bioanalytical Method Validation: Peut 2001 (PDF63KB)
Reviewer Guidance—Validation of Chromatographic Methods: Nov 1994 (PDF703KB)
Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products: Peut 1998 (PDF129KB)
Pharmacokinetics in Patients with Impaired Renal Function—Study Design, Data Analysis, and Impact on Dosing and Labeling: Peut 1998 (PDF128KB), Draft Mar 2010 (PDF318KB)
General Considerations for Pediatric Pharmacokinetic Studies for Drugs and Biological Products: Nov 1998 (PDF37KB)
Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling: Peut 2003 (PDF222KB)
Guidance for Industry Providing Regulatory Submissions in Electronic Format—Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications: Revision 2, juin 2008 (PDF133KB)
Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers: Juillet 2005 (PDF702KB)
Current GMP for Phase 1 Investigational Drugs: Juillet 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, Data Analysis, and Implications for Dosing and Labeling: Draft Sep 2006 (PDF253KB)
Exposure-Response Relationships—Study Design, Data Analysis, and Regulatory Applications: Apr 2003 (PDF221KB)
Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: 1998—2010 (HTML8KB)
Investigator Responsibilities—Protecting the Rights, Sécurité, 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): Peut 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: Jan 2002 (PDF161KB, HTML39KB)
Part 11, Electronic Records; Electronic Signatures — Scope and Application: Août 2003 (PDF215KB)

Computerized Systems Used in Clinical Investigations: Peut 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: juin 1981, Dec 1999, Juillet 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).
Commanditaires, 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 (Peut 2007) see CDER’s document linked in the previous section.
Guideline for the Monitoring of Clinical Investigations: Jan 1988 (HTML9KB)
Institutional Review Boards: Oct 1994 (PDF293KB)
Canada (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): Draft Mar 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)
Drug Interactions: Sep 2000 (PDF69KB, HTML93KB)
CTAs for Comparative BA Studies: Draft Oct 2001; updated Feb 2008 (PDF241KB, HTML87KB)
Records Related to Clinical Trials: Peut 2006 (PDF137KB, HTML75KB)
Draft Policy: BE Requirements: Drugs Exhibiting Non-linear Pharmacokinetics, juin 2003 (HTML13KB)
BE of HVDs/HVDPs: Discussion Paper, juin 2003 (PDF61KB, HTML42KB)
Removal of Requirement for 15% Random Replicate Samples: Notice, Sep 2003 (PDF13KB, HTML21KB)
BE of Combination Drug Products: Notice, juin 2004 (PDF12KB, HTML22KB)
Metabolites in Comparative BA Studies: Draft May 2004 (PDF27KB, HTML29KB)
Préparation de renseignements comparatifs BA pour les présentations de drogues au format CTD: Draft May 2004 (PDF91 Ko, HTML106 Ko)
ÊTRE dans l'État fédéral: juin 2005 (PDF25KB, HTML30 Ko)
BE pour les médicaments à longue demi-vie: Notice, juin 2005 (PDF13KB, HTML21KB)
BE pour les médicaments à action rapide: Notice, juin 2005 (PDF15 Ko, HTML22KB)
BE pour les médicaments à dose critique: Peut 2006 (PDF45KB, HTML42KB)
Les médicaments à dose critique sont: cyclosporine, digoxine, flécaïnide, lithium, phénytoïne, sirolimus, tacrolimus, théophylline, et la warfarine.
Japon (NIHS)
Division des directives sur les médicaments fr ???????????? et
Études pharmacocinétiques cliniques des produits pharmaceutiques: juin 2001 (PDF502 Ko)
Bioéquivalence des médicaments génériques: Dec 1997 (PDF60KB, HTML109 Ko)
BE pour différentes forces: Feb 2000 (PDF33 Ko, HTML19 Ko)
Modifications de la formulation: Feb 2000 (PDF34 Ko)
Topicals: Juillet 2003 (PDF68KB)
Formes posologiques orales à libération prolongée: Mar 1988 (PDF53KB)
Les lignes directrices suivantes ont été révisées avec 24 Nov 2006:
Études BE pour les produits génériques: (Ligne directrice PDF175KB, PDF480 Ko et;Q&Un document PDF407KB et)
Ligne directrice pour le test BE sur la préparation orale solide avec différentes concentrations de médicaments: (Ligne directrice PDF78KB, PDF235 Ko et; Q&Un document PDF471KB et)
Guideline for BE Test on Oral Solid Preparation for which the Formulation has been changed: (Guideline PDF107KB, PDF251KB ja; Q&A DocumentPDF471KB ja)
Remark: The Q&A document seems to cover both topics.
Guideline for BE Studies of Generic Products for Topical Use: (Guidelineja, Q&A ja)
Guideline for BE Studies of Adding Dosage Form for Topical Use: new 24 Nov 2006 (Guideline236KB ja, Q&A43KB ja)
South Africa (MCC)
Des lignes directrices
MCC is redesigning their website. Links to documents marked with an asterisk* are broken as of Jul 8, 2011.
Quote: 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*: Juillet 2007 (ZIP/DOC76KB)
Biostudies: Juillet 2007 (ZIP/DOC66KB)
Dissolution: Juillet 2007, except section 4.1 (Juillet 2008, ZIP/DOC47KB)
Australie (TGA)
Des lignes directrices
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: juin 2004 (PDF178KB)
Clinical Guidelines of the European Union adopted in Australia: current (HTML)
New Zealand (Medsafe)
Des lignes directrices
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: Juillet 2006 (HTML5KB)
Inde (CDSCO)
Central Drugs Standard Control Organization
Bioavailability / Bioéquivalence: Current Draft Mar 2005 (PDF106KB), Draft Mar 2003 (HTML0.99MB)
Requirements and Guidelines for Permission to Import and / or Manufacture of New Drugs for Sale or to Undertake Clinical Trials: Schedule Y – Amended Version, juin 2005 (PDF8.7MB, HTML681KB)
Documents to be submitted for grant of permission to conduct Bioequivalence studies for export purpose: Août 2009 (DOC92KB)
GCP: 2005 (HTML834KB)
Submission of Clinical Trial Application for Evaluating Safety and Efficacy: v1.1 Dec 2008 (PDF704KB)

CRO registration: Draft Jan 2011 (PDF565KB)
Amended Checklist for Test Licence Applications effective from 15 Juin 2011(PDF69KB)
Clarification & Amendments in guidance for industry with respect to Post Approval Changes in Biologicals Products: Août 2010 (PDF147KB)
Ethical Guidelines for Biomedical Research on Human Participants (published by the Indian Council of Medical Research): Oct 2006 (PDF3.1MB)
Bangladesh (DGDA)

 

Directorate General of Drug Administration
Guidance for Industry (Submission of Clinical Trial Application for Evaluating Safety and Efficacy, Requirements for permission of New Drugs Approval, Post approval changes in biological products: 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
Bonnes pratiques cliniques – Document of the Americas: 2005 (PDF306KB)
Science Based Criteria for BE in vivo and in vitro, Bio-Waivers and Strategic Framework for Implementation: Draft >2001? (PDF971KB)
BA / BE / Biowaivers: Final Draft Aug 2004 (PDF868KB)
Brésil (ANVISA)
Legislation en Legisla??o pt

Note: ANVISA is redesigning their website starting in mid-August 2010. Most links are broken with no automatic redirects as of 12 Septembre 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, Peut 2003 HTML31KB pt)
Pharmaceutical Equivalence / Dissolution: Sep 2004 (HTML33KB pt, May 2003HTML46KB pt, Peut 2003 HTML27KB pt, Mar 2002 HTML29KB pt)
BA / BE: Peut 2003 (HTML46KB en, HTML31KB pt)
Exemption and Substitution of BE Studies: Peut 2003 (HTML31KB en,HTML15KB pt, Mar 2002 HTML23KB pt)

Bioanalytical Method Validation: Peut 2003 (PDF56KB en, HTML104KB pt, Mar 2002 HTML46KB pt)
Explanation of the Implementation of Re No. 899/2003 – Validation of Bioanalytical Methods: juin 2008 (PDF34KB pt)
National Registry of Volunteers in BE Studies: juin 2008 (HTML26KB pt)
Statistics for BA/BE Studies: Peut 2003 (PDF48KB en, HTML49KB pt, Mar 2002HTML24KB pt)
Protocol of BE Studies: Peut 2003 (HTML32KB en, HTML16KB pt, Mar 2002HTML28KB pt)
Report of BE Studies: Peut 2003 (HTML63KB en, HTML55KB pt)
List of Reference Products: Current (PDF265KB pt)
Rules / Technical Regulations for CROs: Peut 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 Peut 2008.
Annexes I, III–V are given as screenshots (JPEG-format); Annex II is given below‘CLASSIFICA??INSPER LES ARTICLES??O' dans la version portugaise.
Lignes directrices pour l'équivalence pharmaceutique et la bioéquivalence des sprays et aérosols nasaux: juin 2008 (PDF110 Ko pt, en PDF132 Ko)
Remark: Le document en anglais est une traduction non officielle.
BA BE Manuel de Bonnes Pratiques fr
Bon manuel de relations publiques?Éthique en biodisponibilité et bioéquivalence fr
Volume 1 (cliniques, analytique, statistiques): 2002 (ZIP/PDF6,1 Mo un,ZIP/PDF4,3 Mo pt)
Volume 2 (micropipettes, eau pour analyse, instrumentation): 2002 (ZIP/PDF6,2 Mo un, ZIP/PDF4,7 Mo pts)
Mexique
secrétaire?a de la santé est
BA / BE: Final, Peut 1999 (PDF100KB fr)
BA / ÊTRE Mise à jour, Biowaivers: Mar 2000 (HTML4 Ko)
Commission?n Permanent de la Pharmacopée des États-Unis du Mexique:Les législateurs?sanitaire n lié à l'industrie pharmaceutique?Utique est
argentin

ANMAT est

Ligne directrice BPC pour les études sur des sujets humains: Nov 2007 (PDF201KB est)
BPC dans les études cliniques: 1997, modifié 2005 (PDF143 Ko est)
Bonnes pratiques en recherche en pharmacologie clinique: Nov 2010 (PDF1,0 Mo est)
BA / BE: Finale septembre 2006, modifié en mars 2007 (PDF1,8 Mo est, 1999 PDF389KB es)
BCS based Biowaivers for oral solid IR dosage forms: Feb 2009 (PDF97KB es)
Post approval changes: Feb 2009 (PDF154KB es)
Bioanalytical Method Validation: 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: Draft Feb 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)
Jordan
Jordan Food and Drug Administration en ??????? ?????? ?????? ??????? ar
Law of clinical studies: 2003 (DOC55KB ar), 2001 (DOC59KB en)
Egypt
Egyptian Drug Authority
BE Studies Guidelines: Jan 2010 (PDF1.0MB)
BE Requirements: Mar 2009 (DOC111KB ar)
BE Report: Oct 2008 (DOC132KB)
GLP Checklist: Draft Mar 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&UN: Version 2, Peut 2009 (PDF67KB); Version 1, Juillet 2008 (PDF16KB)
Malaysia (BPFK
Des lignes directrices
Conduct of BA and BE Studies: Final, Sep 2000 (PDF89KB, DOC191KB)
GCP: Second Edition, Jan 2004 (PDF646KB)
BPL: Draft Jul 2006 (PDF1.7MB)

BPL: juin 2009 (OECD’s adopted; see PDF368KB)
Guidance Document and Guidelines for Registration of Biosimilars: Août 2008 (PDF166KB)
Thaïlande (FDA)
DCD
BA / BE: Mar 2009 (PDF224KB)
BA / BE: Current? (HTML146KB th)
BA / BE: Août 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)
Singapore (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)
Validation of Analytical Procedures: Final(?), Jan 2005 (PDF123KB)
(South) Corée
KFDA
Guidance Document for BE Study: Dec 2008 (PDF604KB)
Minimum Requirements for BE Test: Dec 2005 (PDF493KB)
Taïwan
CDE ??????????? zh
Regulations ?????????zh
BA / BE: Dec 2006 (PDF171KB zh, HTML47KB zh)
GCP: Jan 2005 (PDF248KB zh, HTML230KB zh)
Pediatric PK: Juillet 2002 (PDF195KB zh, HTML158KB zh)

Ethnic Factors in the Acceptability of Foreign Clinical Data: Peut 2002 (PDF323KB zh)
BPL: Mar 2006 (PDF200KB zh, HTML197KB zh)
Nonclinical Pharmacology/Toxicology: juin 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: Jan 2000 (PDF223KB zh, HTML172KB zh)
Chine
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)
Bonnes pratiques cliniques: Août 2003 (HTML46KB zh)
Statistical Guidelines for Clinical Trials of Drugs and Biologics: Mar 2005 (PDF324KB zh)
Pharmacokinetics: 2005 (PDF300KB zh)
Bioéquivalence: 2005 (PDF328KB zh)
Hong Kong; GCP for Proprietary Chinese Medicines: Feb 2004 (PDF242KB en,PDF669KB zh)
Suisse
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

Lignes directrices pour l'archivage de données brutes électroniques dans un environnement BPL: Peut 2003 (PDF124 Ko)
Lignes directrices pour la gestion des SOP électroniques en BPL: Sep 2006 (PDF134 Ko)
Lignes directrices pour l'acquisition et le traitement de données brutes électroniques dans un environnement BPL: Sep 2006 (PDF166KB)
Lignes directrices pour la validation des systèmes informatisés dans un environnement BPL: Dec 2007 (PDF344 Ko)
Turquie
Ministère de la Santé et MoH tr
Principes de bonnes pratiques de laboratoire: juin 2002 (HTML55 Ko tr)
Règlement sur les licences pour les produits pharmaceutiques: 2003 (PDF147KB)
Dépôt des dossiers BA/BE: Jan 2006 ( PDF287 Ko)
Remark: Le document est une traduction non officielle que j'ai reçue lors de mon atelier à Istanbul en mars. 2006; Je ne sais pas si quelque chose a changé entre-temps.
Israël
Ministère de la Santé fr ???? ??????? il
Section d'enregistrement des médicaments
Lignes directrices pour les essais cliniques chez des sujets humains: Jan 2006 (PDF888KB il,PDF204 Ko un)
SOP pour effectuer un BE chez des sujets humains: Sep 2002 (DOC132KB il)
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: Juillet 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: juin 1995 (PDFs en, fr, en/fr).
Revised Guidance for the Conduct of Laboratory Inspections and Study Audits: juin 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: juin 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: juin 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).
PIC/S
Guides Recommendations

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

Quality Assurance Activities Guidelines
Validation of Analytical Procedures: juin 2005 (PDF605KB)
Uncertainty of Measurements
Première partie (compliance testing): Dec 2007 (PDF703KB)
Partie II (other than compliance testing): Dec 2007 (PDF1.0MB)
Qualification of Equipment (core document): Sep 2008 (PDF1.0MB)
Annexe 1: Qualification of HPLC Equipment: Feb 2007 (PDF1.4MB)
Annexe 2: Qualification of GC Equipment: Oct 2006 (PDF897KB)
Abbreviations

ACCSQ Consultative Committee for Standards and Quality (? ASEAN)
AGIT Arbeitsgruppe Informationstechnologie (Working Group on Information Technology, Suisse)
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, Brésil)
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 (Taïwan)
CDER Center for Drug Evaluation and Research (of the ? FDA)
CDSCO Central Drugs Standard Control Organization (Inde)
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 ? je)
DCD Drug Control Division (Thaïlande)
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 ? je)
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 (États-Unis)
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 (Singapore)
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 (South Africa)
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 (Japon)
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 ? je)
Q&A Questions and Answers
RTF Rich Text Format
SFDA Saudi Food & Drug Authority (Saudia Arabia)
SFDA State Food & Drug Administration (Chine)
SS Semisolid
SUPAC Scale-Up and Post-Approval Changes (according to ? FDA)
TGA Therapeutic Goods Administration (Australie)
TIFF Tagged Image File Format
TPD Therapeutic Products Directorate (de ? HPFB)
WHO World Health Organization
ZIP Compressed file (format)