CERTIFICATION ICH MEMERS OBJECTIVES GUIDELINES FDA CFR ORGANIZATION CDER CBER ORANGE BOOK

ISO UKAS DRUG MARKET CDSCO MHRA ORANGE GUIDE

CERTIFICATIONCertification is a affirmation or proof that the products or services are approved and evaluated by a governing body that has the ability to create reserved rights.

List of certifying agencies:ISO (International Organization for Standardization) WHO (World Health Organization) FDA (Food and Drug Administration) ICH (International conference on Harmonization) MHRA (Medicines and Healthcare products Regulatory Agency) ASTM (American Society of Testing and Materials) EPA (Environmental Protection Agency) TGA (Therapeutic Goods Administration) UKAS (United Kingdom Accreditation Service)

Regulatory Authorities: WHO USFDA ICH MHRA TGA

Standard Institutions ISO ASTM EPA UKAS

International Conference on HarmonizationWhat is ICH?ICH is a joint initiative involving both regulators and research based industry representatives of the EU, Japan and the US in scientific and technical discussions of the testing procedures required to assess and ensure the safety, quality and efficacy of medicines.

Who are the members?ICH is comprised of representatives from the six cosponsoring parties as well as three Observers and the International Federation of Pharmaceutical Manufacturers Associations (IFPMA)Japan: Ministry of Health & Welfare (MHW) and the Japan Pharmaceutical Manufacturers Association (JPMA) EU: European Commission (EC) and European Federation of Pharmaceutical Industries Associations (EFPIA) USA: Food & Drug Administration (FDA) and the Pharmaceutical Research and Manufacturers of America (PhRMA) Observers: WHO, EFTA, and Canada

What is the objective of ICH?

The objective of ICH is to increase international harmonization of technical requirements to ensure that safe, effective, and high quality medicines are developed and registered in the most efficient and cost effective manner

ICH Guidelines

Quality guidelines

Safety guidelines

Efficacy guidelines

Multidisciplinary Guidelines

Quality GuidelinesHarmonization achievements in the Quality area include pivotal milestones such as the conduct of stability studies, defining relevant thresholds for impurities testing and a more flexible approach to pharmaceutical quality based on Good Manufacturing Practice (GMP) risk management

Quality GuidelinesQ1A (R2) Q1B Q1C Q1D Q1E Q1FStability Testing of New Drug Substances and Products Stability Testing : Photostability Testing of New Drug Substances and Products Stability Testing for New Dosage Forms Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products Evaluation of Stability Data Stability Data Package for Registration Applications in Climatic Zones III and I

Analytical Validation Q2 Impurities Q3A - Q3DQ2 (R1) Validation of Analytical Procedures: Text and Methodology Q3A (R2 ) Q3B (R5) Q3C (R5) Q3D Impurities in New Drug Substances Impurities in New Drug Products Impurities: Guideline for Residual Solvents Impurities: Guideline for Metal Impurities

Pharmacopoeias Q4 - Q4BQ4 Q4A Q4B Q4B 1R1 Q4B 2R1 Q4B Annex 3R1 Q4B Annex 4AR1 Q4B Annex 4BR1 Q4B Annex 4CR1 Pharmacopoeias Q4APharmacopoeial Harmonisation Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions Residue on Ignition/Sulphated Ash Test for extractable volume of parenterals. Test for Particulate Contamination: Sub-Visible Particles Q4B Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-Organisms Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use

Q4B Anx 5R1 Q4B Anx 6R1 Q4B Anx 7R2 Q4B Anx 8R1 Q4B Anx 9R1 Q4B Anx 10R1 Q4B Annex 11 Q4B Annex 12 Q4B Annex 13 Q4B Annex 14

Disintegration Test Uniformity of Dosage Units Dissolution Test Sterility Test Tablet Friability Polyacrylamide Gel Electrophoresis Capillary Electrophoresis Analytical Sieving Bulk Density and Tapped Density of Powders General Chapter Bacterial Endotoxins Test

Quality of Biotechnological Products Q5A - Q5EQ5A(R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Product Stability Testing of Biotechnological/Biological Products Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing process

Q5B Q5C Q5D

Q5E

Specifications Q6A- Q6BQ6A Specifications : Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances Specifications : Test Procedures and Acceptance Criteria for Biotechnological/Biological ProductsGood Manufacturing Practice Q7Q7Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

Q6B

Q8 , Q9 ,Q10 , Q11 Pharmaceutical Development Q8 Q8(R2) Pharmaceutical Development Quality Risk Management Q9 Q9 Quality Risk Management Pharmaceutical Quality System Q10 Q10 Pharmaceutical Quality System Development and Manufacture of Drug Substances Q11 Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/ biological entities.

Safety GuidelinesICH has produced a comprehensive set of safety Guidelines to uncover potential risks like carcinogenicity, genotoxicity and reprotoxicity. A recent breakthrough has been a non-clinical testing strategy for assessing the QT interval prolongation liability: the single most important cause of drug withdrawals in recent years.

Safety GuidelinesS1 S2 S3 S4 S5 S6 S7 S8 S9 S10 Carcinogenicity Studies Genotoxicity Studies Toxicokinetics and Pharmacokinetics Toxicity Testing Reproductive Toxicology Biotechnological Products Pharmacology Studies Immunotoxicology Studies Nonclinical Evaluation for Anticancer Pharmaceuticals Photosafety Evaluation

Carcinogenicity Studies S1A - S1C S1A-Need for Carcinogenicity Studies of Pharmaceuticals S1B-Testing for Carcinogenicity of Pharmaceuticals S1C(R2)-Dose Selection for Carcinogenicity Studies of Pharmaceuticals

Genotoxicity Studies S2S2(R1)-Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human use.

Toxicokinetics and Pharmacokinetics S3 S3A-Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies S3B-Pharmacokinetics: Guidance for Repeated Dose Tissue Distribution Studies

Toxicity Testing S4S4-Duration of Chronic Toxicity Testing in Animals (Rodent and Non Rodent Toxicity testing)

Reproductive Toxicology S5S5(R2)Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male fertility

Biotechnological Products S6S6(R1)Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals

Pharmacology Studies S7A - S7BS7A-Safety Pharmacology Studies for Human Pharmaceuticals S7B-The Non-Clinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals

Immunotoxicology Studies S8S8-Immunotoxicity Studies for Human Pharmaceuticals

Nonclinical Evaluation for Anticancer Pharmaceuticals S9S9-Nonclinical Evaluation for Anticancer Pharmaceuticals

Photosafety Evaluation S10S10-Photosafety Evaluation of Pharmaceuticals

Efficacy Guidelines

The work carried out by ICH under the Efficacy heading is concerned with the design, conduct, safety and reporting of clinical trials. It also covers novel types of medicines derived from biotechnological processes and the use of Pharmacogenetics / genomics techniques to produce better targeted medicines.

Efficacy Guidelines Clinical Safety E1 - E2FE1The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life Threatening Conditions Clinical Safety Data Management: Definitions and Standards for Expedited Reporting Maintenance of the Clinical Safety Data Management including Data Elements for Transmission of Individual Case Safety Reports

E2A E2B(R2)

E2B(R3)

Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting Pharmacovigilance Planning

E2C(R1)

E2D

E2E

E2F

Development Safety Update Report

E3 , E4 , E5 , E6 Clinical Study Reports E3 E3 Structure and Content of Clinical Study Reports Dose-Response Studies E4 E4 Dose-Response Information to Support DrugRegistration

Ethnic Factors E5 E5(R1) Ethnic Factors in the Acceptability of ForeignClinical Data

Good Clinical Practice E6 E6(R1) Good Clinical Practice

E7-E11E7 E8 E9 E10 E11 Studies in Support of Special Populations: Geriatrics General Considerations for Clinical Trials Statistical Principles for Clinical Trials Choice of Control Group and Related Issues in Clinical Trials Clinical Investigation of Medicinal Products in the Pediatric Population

E12 , E14 Clinical Evaluation by Therapeutic Category E12 E12 Principles for Clinical Evaluation of New Antihypertensive Drugs

Clinical Evaluation E14 E14 The Clinical Evaluation of QT Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs

E15 , E16 Pharmacogenomics E15 - E16E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories E16 Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure and Format of qualification submissions.

Those are the cross-cutting topics which dont fit uniquely into one of the Quality, Safety and Efficacy categories. It includes ICH medical terminology, Common Technical Document (CTD) Development of Electronic Standards for the Transfer of Regulatory Information (ESTRI)

Multidisciplinary Guidelines

Multidisciplinary GuidelinesM1 M2 M3 M4 M5 M6 M7 M8 MedDRA Terminology Electronic Standards Nonclinical Safety Studies Common Technical Document Data Elements and Standards for Drug Dictionaries Gene Therapy Genotoxic Impurities Electronic Common Technical Document (eCTD)

MedDRA Terminology M1MedDRA Medical Dictionary for Regulatory Activities

Electronic Standards M2ESTRI Electronic Standards for the Transfer of Regulatory Information

Non clinical Safety Studies M3M3(R2)-Guidance on Non clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.

Common Technical Document M4CTD The Common Technical Document

Data Elements and Standards for Drug Dictionaries M5M5-Data Elements and Standards for Drug Dictionaries

Gene Therapy M6M6-Virus and Gene Therapy Vector Shedding and Transmission

Genotoxic Impurities M7M7Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk

Electronic Common Technical Document (eCTD) M8Electronic Common Technical Document (eCTD)

FDA History1862-USDA-Division of Chemistry. In 1901 Bureau of chemistry. Dr. Harvey Wiley, is described by some as the father of the FDA. Dr. Wiley was primarily responsible for enforcing the 1906 Food and Drug Act. FDA is a scientific, regulatory, public health agency. The agency grew from a single chemist in the US department of Agriculture In 1862 to a staff of approximately 9100 employees, staffing over 150 field officers, 5 regional offices and 20 district offices. Harvey Wiley unified a variety of groups in the federal law to prohibit the adulteration and misbranding of food and drugs. Head Quarter is situated in Maryland.

FDA MissionThe Food and Drug Modernization Act states that the FDA has 4 roles:

To promote health by reviewing research and approving new products To ensure foods and drugs are safe and properly labeled To work with other nations to reduce the burden of regulation To cooperate with scientific experts and consumers to effectively carryout these obligations

CFRCFR is the codification of the general and permanent rules and regulations (also called administrative law) published in the Federal Register by the executive departments and agencies of the Federal Government of the United States. The CFR is published by the Office of the Federal Register, an agency of the NATIONAL ARCHIVES AND RECORDS ADMINISTRATION (NARA). The CFR is divided into 50 titles that represent broad areas subject to Federal regulation.

Title 21: Food and Drugs

Title 21 is the portion of the Code of Federal Regulations that governs food and drugs within the United States for the Food and Drug Administration (FDA), the Drug Enforcement Administration (DEA), and the Office of National Drug Control Policy (ONDCP).

Chapter I Food and Drug Administration Chapter II Drug Enforcement Administration Chapter III Office of National Drug Control Policy

Organization:The foundation of FDA Department of Health and Human services is formed by the following centers:Center for Food Safety and Applied nutrition (CFSAN) Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) Center for Devices and Radiological Health (CDRH) National Center for Toxicological Research (NCTR) Center for Biologics Evaluation and Research (CBER)

Center for Drug Evaluation and ResearchCDER is charged with reviewing and ensuring the safety of new drugs, generic drugs, and over-the-counter drugs.

Centers Office of New Drugs. Centers Office of Drug Safety. Centers Office of Medical Policy-Division of Drug Marketing, Advertising and Communications (DDMAC) Centers Office of Pharmaceutical Science. Centers Office of Compliance.

Center for Biologics Evaluation and ResearchCBER has jurisdiction over blood and blood products, drugs derived from biological organisms, tissues, and allergen tests and extracts used for treatment. Office of Vaccine Research and Review. Office of Therapeutics Research and Review. Office of Cellular, Tissue & Gene Therapies. Office of Blood Research and Review. Office of Compliance and Biologics Quality. The FDA recently announced that jurisdiction over certain biological therapeutic products, including cytokines, enzymes, interferon's, monoclonal antibodies, and therapeutic proteins, will be transferred from the CBER to the CDER. yThe CBER will maintain continue to be responsible for the review and approval of yblood and blood products, cell and gene therapy products, in vitro diagnostic products, yand vaccines, according to agency documents.

Orange BookApproved Drug Products with Therapeutic Equivalence Evaluations. It identifies drug products approved on the basis of safety and effectiveness by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act. The Orange Book Search was added to the FDA website on October 31, 1997.

The main criterion for the inclusion of any product is that the product is the subject of an application with an effective approval that has not been withdrawn for safety or efficacy reasons.

Orange Book Search You can search by : Active ingredient Proprietary name Applicant Application number.

Reference Listed Drug (RLD)RLD is an approved drug product to which new generic versions are compared to show that they are bioequivalent. A drug company seeking approval to market a generic equivalent must refer to the Reference Listed Drug in its Abbreviated New Drug Application (ANDA). By designating a single reference listed drug as the standard to which all generic versions must be shown to be bioequivalent, FDA hopes to avoid possible significant variations among generic drugs and their brand name counterpart.

International Organization for StandardizationISO is World's largest developer and publisher of International Standards. It is network of the national standards institutes of 163 countries, one member per country, with a Central Secretariat in Geneva, Switzerland, that coordinates the system. ISO is non-governmental organization that forms a bridge between the public and private sectors. ISO is made up of 163 members which are divided into three categories: Member bodies (Example India BIS) Correspondent members Subscriber members ISO has developed over 18,500 International Standards on a variety of subjects and some 1100 new ISO standards are published every year.

United Kingdom Accreditation Service (UKAS)UKAS is the sole national accreditation body recognised by government to assess, against internationally agreed standards, organisations that provide certification, testing, inspection and calibration services. Accreditation by UKAS demonstrates the competence, impartiality and performance capability of these evaluators. UKAS is a non-profit-distributing private company. UKAS is independent of Government but is appointed as the national accreditation body by the Accreditation Regulations 2009 (SI No 3155/2009) and operates under a Memorandum of Understanding with the Government through the Secretary of State for Business, Innovation and Skills. UKAS is a signatory to the EA (European co-operation for Accreditation), mutual recognition agreements, which helped to lower barriers to trade by ensuring international acceptance of certificates issued under the umbrella of UKAS accreditation.

Drug Markets1.Regulated Market or Brand Market:It includes US, Europe, UK, Canada, Japan, South Africa, Australia, Germany.

2. Semi Regulated or Emerging MarketChina, Africa, India, Philippines, Brazil.

3. Rest of the WorldZimbabwe, Nigeria, Sri Lanka, Maldives, Indonesia, Germany.

4. Domestic MarketThey are emerging markets or semi regulated, which introduce their brand within the country (like territories, zones, provinces, states, districts, towns)

Example : India : DCGI CDSCO

Government and Regulatory BodiesPharmaceutical, medical and health-related government and regulatory bodies around the world.

International :International Conference on Harmonization (ICH) World Health Organization (WHO) World Trade Organization (WTO)

Australia:Australia's Department of Health and Aged Care Therapeutic Goods Administration (TGA)

Brazil:National Health Surveillance Agency (Anvisa)

CanadaHealth Canada

China:State Food and Drug Administration (SFDA)

Europe:EU Legislation Eudralex European Directorate for the Quality of Medicines and Healthcare (EDQM) European Medicines Agency (EMEA) Heads of Medicines Agencies (HMA)

Germany:Federal Institute for Drugs and Medical Devices (BfArM) Ministry of Health Paul-Ehrlich-Instituts in Langen (PEI)

India:Central Drug Standard Control Organization (CDSCO) Government of India Directory of Health and Family Welfare Indian Council of Medical Research (ICMR) Ministry of Health and Family Welfare

Indonesia:Ministry of Health

Japan:Ministry of Health and Welfare National Institute of Infectious Diseases National Institute of Health Sciences

Maldives:Ministry of Health and Family

Nigeria:National Agency for Food and Drug Administration and Control (NAFDAC)

Philippines:Department of Health Philippine Council for Health Research and Development (PCHRD)

Russia:Association of International Pharmaceutical Manufacturers Ministry of Health Public Health Institute

Sri Lanka:Ministry of Healthcare and Nutrition

South Africa:Department of Health Medicines Control Council (MCC)

United Kingdom:Association of the British Pharmaceutical Industry (ABPI) Department of Health Medicines and Healthcare Products Regulatory Agency (MHRA) National Health Service (NHS) National Institute for Biological Standards and Control (NIBSC) Prescription Services NHS

United States Of America:Centers for Disease Control and Prevention Department of Health and Human Services (DHHS) FedWorld - US Government Information The Food and Drug Administration (FDA) National Center for Complementary and Alternative Medicine (NCCAM) National Institutes of Health (NIH) National Library of Medicine National Science Foundation Office of Disease Prevention

Central Drug Standard Control organizationThe DCGI (Drug Controller General of India) is the main personality of CDSCO responsible for approving new drugs, clinical trials, licensing and to ensure quality, safety and efficacy of pharmaceuticals in India.

In India drugs are regulated both at central and state level at the central level CDSCO under the Ministry of Health and Family Welfare is responsible for approving new drug, clinical trials, and licensing of drugs, issues licenses to manufacture approved drugs and to monitor the quality of drugs.

Functions of CDSCO Approval of new drugs and clinical trails. Import registration and licensing. Licensing of blood banks, vaccines, rDNA products, some medical devices. Amendments to D & C act and rules. Banning of drugs and cosmetics. Grant of test license, NOCS for export. Testing of drugs.

Medicines and Healthcare products Regulatory AgencyMHRA was formed on 1 April 2003 with the merger of the Medicines Control Agency (MCA) and the Medical Devices Agency (MDA). It is an executive agency of the Department of Health. MHRA is a part of the European system of approval. In October and November 2010, the MHRA moved from its Market Towers address to a new location on Bucking Buckingham Palace Road

MHRA is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe.

MHRA hosts and supports a number of expert advisory bodies, including the Commission on Human Medicine which replaced the Committee on the Safety of Medicines in 2005, and the British Pharmacopoeia Commission.

Roles of the MHRA Operate post-marketing surveillance for reporting, investigating and monitoring of adverse drug reactions to medicines and incidents with medical devices. Assessment and authorization of medicinal products for sale and supply in UK. Oversee the Notified Bodies that ensure medical device manufacturers comply with regulatory requirements before putting devices on the market. Operate a quality surveillance system to sample and test medicines to address quality defects and to monitor the safety and quality of unlicensed products. Investigate internet sales and potential counterfeiting of medicines, and prosecute where necessary. Regulate clinical trials of medicines and medical devices. Monitor and ensure compliance with statutory obligations relating to medicines and medical devices. Promote safe use of medicines and devices. Manage the General Practice Research Database and the British Pharmacopoeia.

The 'Orange Guide'In the United Kingdom, the Medicines Act in 1968 which gave birth to orange guide. It was first publication in 1971. It has been an essential reference for all involved in the manufacture and distribution of medicines in Europe. Convenient and authoritative source in European and UK guidance, documents and information on legislation relating to the manufacture and distribution of medicines for human use. It covers most aspects of GMP

http://www.ich.org/ http://www.fda.gov/ http://www.ukas.com/about-accreditation/about-ukas/default.asp http://www.fda.gov/regulatoryinformation/guidances/ucm122049.htm http://en.wikipedia.org/wiki/Center_for_Drug_Evaluation_and_Research http://www.emea.europa.eu http://www.iso.org/iso/about/how_iso_develops_standards.htm http://www.mhra.gov.uk/Aboutus/index.htm