Industry and fda laision &

Pharmaceutical Regulataory Affairs

1. INDUSTRY AND FDA Liaison & ICH – Q GUIDELINES K. Bhanu Sri Chandana 2020MPH40A023 M. PHARMACY Dept. of Pharmaceutics Under the guidance of Dr. K. Sai Sruthi M. Pharmacy, Ph. D

2. FDA and Industrial Liaison FDA and its responsibilities Missions of FDA FDA Organizations and contacts FDA initiatives for speed drug approval ICH Introduction to ICH Working groups of ICH ICH – Q guidelines References CONTENTS

3. Industry and FDA Liaison

4. Introduction Liaison means Communication or Co-operation. Every Pharmaceutical industry must follow some of the regulations held by its higher authorities. FDA also lays some of the regulations in order to maintain the quality and safety of drugs and pharmaceutical products. Effective communication should be maintained between Pharmaceutical Industries and FDA .

5. Food and Drug Administration FDA is one of the United States oldest consumer protection agencies. It is a federal agency of the Department of Health and Human Services, formed on June 30, 1906. Its Headquarters is the White Oak Campus which is located at Maryland. It is led by the ‘Commissioner of Food and Drugs’ who as appointed by the President along with the consent of the Senate. Currently, Janet Wood Cook is acting as the commissioner of FDA since January 20, 2021. FDA is charged with protecting American consumers by enforcing the Federal Food, Drug and Cosmetic Act and some of the public related health laws and has 223 field offices and 13 laboratories located throughout 50 states.

6. Responsibilities of FDA FDA is responsible for protecting and promoting public health through control and supervision of the following categories : Food safety and Dietary supplements Animal foods and feeds Tobacco products Prescription and other OTC drugs Vaccines and Biopharmaceuticals Blood transfusions Medical devices Cosmetics Veterinary products

7. Missions of FDA Inspections and legal sanctions Scientific expertise Product safety To ensure the safety and effectiveness of the products under its jurisdiction, FDA sets the following missions:

8. 1. Inspections and Legal sanctions The investigators and inspectors visit more than 16,000 facilities a year, for ensuring the product safety and label truthfulness. As a part of investigation, FDA scientists collect about 80,000 domestic and imported samples for the examination of label checks. Any company found violating the laws, FDA suggests to correct the problem voluntarily or asks to recall the product from the market. If the company does not obey FDA, it has all the rights to enforce legal actions and proceed to the court to stop the product selling. Criminal penalties and prison sentences can be imposed against manufacturers and distributors.

9. 2. Scientific expertise Scientific evidence needed for filing a case against any company can be prepared by nearly 2,100 scientists including 900 chemists and 300 microbiologists. Among all these scientists, some look after analyzing samples and others review the test results which are submitted by the companies seeking approval for drugs, vaccines, food additives, coloring agents. This agency determines the benefits of the new drug products over its side effects.

10. 3. Product Safety To protect the safety and wholesomeness of product, the samples are tested for any pesticidal residues that are unacceptable. If contaminants are identified, FDA takes corrective action and also sets labelling standards for consumers knowledge. FDA is also responsible for nations blood supply. Investigators routinely examine the blood banks and records the contaminants FDA ensures the purity and effectiveness of cosmetics, medical devices vaccines and insulin.

11. FDA’s Organizations National Center for Toxicological Research Center for Food Safety and Applied Nutrition Center for Tobacco Products Center for Veterinary Medicine Office of Women’s Health

12. Center for Biologics Evaluation and Research Office of Regulatory Affairs Office of International Programes Center for Drug Evaluation and Research Center for Devices and Radiological Health

13. Center Area of Responsibility Center for Drug Evaluation and Research Safety and effectiveness of Prescription and OTC drugs Center for Biologics Evaluation and Research Safety and effectiveness of vaccines, nation’s blood supply, Biologics Center for Devices and Radiological Health Safety and effectiveness of Medical devices, diagnostic tests, Radiation emitting devices Center for Food Safety and Applied Nutrition Safety of domestic and imported food supply, cosmetics and dietary supplements Center for Veterinary Medicine Safety and effectiveness of veterinary drugs Center for Tobacco Products Implementation of the Family Smoking Prevention and Tobacco Control Act National Center for Toxicological Research Research to support regulatory decisions and reduce risks associated with FDA regulated products Office of Regulatory Affairs Enforcement of Laws and regulations Table

14. FDA initiatives to speed drug approval Subpart E in Section 312 of the Code of Federal Regulations, FDA establishes some procedures to speedup the process of development, evaluation, and marketing of new therapies to treat people with life-threatening and severely debilitating illnesses, especially where no satisfactory alternatives exist. Accelerated development or Review Program Treatment IND FDA guidelines

15. ICH – Q Guidelines

16. ICH International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) It is a joint initiative involving both the regulatory authorities and research based pharmaceutical industries of the European Union, Japan and the United states. It is an international non-profitable association that involves the scientific and technical discussions of the testing procedures required to assess and ensure the safety, quality, efficacy and other multidisciplinary activities of medicines. ICH is formed in April 1990, with an objective of coordinating the regulatory authorities and pharmaceutical industries for better harmonisation.

17. Mission Harmonisation for Better Health ICH's mission is to achieve greater harmonisation worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner. Harmonisation is achieved through the development of ICH Guidelines via a process of scientific consensus with regulatory and industry experts working side-by-side. Reason for the success of this process is the commitment of the ICH regulators to implement the final Guidelines. ICH is an international non-profit Association which is under Swiss law on October 23, 2015.

18. Organisation of ICH

19. Auditors The Auditors are responsible to audit the financial statements of the Association upon conclusion of each Fiscal Year. They should ensure that the accounting of the Association complies with Swiss law and generally accepted Swiss accounting principles. The Auditors are appointed for a period of two years

20. Assembly The ICH Assembly brings together all Members and Observers of the ICH Association as the overarching governing body of ICH. It makes decisions on matters such as on the Articles of Association, admission of new Members & Observers and adoption of ICH Guidelines. The Assembly meets biannually and the reports are made available on the ICH website summarizing the main decisions taken at each meeting 

21. Members European Union (EU) European Federation of Pharmaceutical Industries and Associations (EFPIA) Ministry of Health , Labour and Welfare (MHLW) Japan Pharmaceutical Manufacturers Association (JPMA) Food and Drug Administration (FDA) Pharmaceutical Research and Manufacturers of America (PhRMA) Observers World Health Organization (WHO) International Federation of Pharmaceutical Manufacturers and Associations (IFPMA)

22. Management Committee The ICH Management Committee (MC) is the body that oversees operational aspects of ICH on behalf of all Members, including administrative and financial matters and oversight of the Working Groups (WGs). The MC is responsible for submitting recommendations or proposals to the Assembly in preparation of Assembly discussions. MedDRA Management Committee The MedDRA Management Committee (MC) has responsibility for direction of MedDRA . It is a ICH standardised dictionary of medical terminology. The MedDRA MC is composed of the EC, EFPIA - Europe; ; MHLW, JPMA - Japan; ; FDA, PhRMA - United States; Health Canada - Canada; and WHO 

23. Working Groups

24. Quality Guidelines Harmonisation achievements in the Quality area includes 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. Safety Guidelines ICH has produced a comprehensive set of safety Guidelines to uncover potential risks like carcinogenicity and genotoxicity.

25. Efficacy Guidelines The work carried out by ICH under the Efficacy 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. Multidisciplinary Guidelines These are the cross-cutting topics which do not fit uniquely into one of the Quality, Safety and Efficacy categories. It includes the ICH medical terminology (MedDRA), the Common Technical Document (CTD) and the development of Electronic Standards for the Transfer of Regulatory Information (ESTRI)

26. ICH – Q Guidelines

27. Q1A – Q1F Stability Q2 Analytical Validation Q3A – Q3E Impurities Q4A – Q4B Pharmacopoeias Q5A – Q5E Biotechnological Products Q6A – Q6B Specifications Q7 Good Manufacturing Practices Q8 Pharmaceutical Development Q9 Quality Risk Management Q10 Pharmaceutical Quality System Q11 Development and Manufacture of drug substances Q12 Lifecycle Management Q13 Continuous Manufacture of drug substances and Drug Products Q14 Analytical Procedure Development

28. Sub – parts of ICH – Q Guidelines Q1A (R2) - Stability Testing of New Drug Substances and Products This guideline provides recommendations on stability testing protocols including temperature, humidity and trail duration for different climatic zones in order to minimize the difference storage conditions for global submission. Q1B - Stability Testing : Photostability Testing of New Drug Substances and Products This Guideline gives basic testing protocols required to evaluate the light sensitivity and stability of new drugs and products. Q1C - Stability Testing For New Dosage Forms It extends the main stability guideline for new formulations of already approved medicines.

29. Q1D - Bracketing and Matrixing Designs For Stability Testing of New Drug Substances and Products This is intended to address recommendations on the application of Bracketing and Matrixing to stability studies. Q1E - Evaluation of Stability Data Q1F - Stability Data Package For registration Applications in Climatic Zones III and IV Q2 (R1) - Validation of Analytical Procedures : Text and Methodology Q2 (R2) - Analytical Procedure Development and Revision of Q2 (R1) Analytical Validation Q3A (R2) - Impurities in New Drug Substances This guideline Addresses the chemistry and safety aspects of impurities and identification and qualification of the drug products

30. Q3B (R2) - Impurities in New Drug Products This guideline focuses on impurities in new drug substances and provides advice in regard to impurities in products containing new, chemically synthesized drug substances . It deals with the impurities that arises by degradations, interactions between drug substance and excipients. Q3C (R8) - Maintenance of The Guideline For Residual Solvents It provides recommendations on the use of less toxic solvents in the manufacture of drug substances and dosage forms. It sets the pharmaceutical limits for residual solvents in drug products. Q3D (R1) - Guidelines for Elemental Impurities This guideline is implemented for the control of elemental impurities in new drug products

31. Q3D (R2) - Revision of Q3D (R1) c utaneous and transdermal products Q3D Training - Implementation of Guideline For Elemental Impurities Q3E - Impurity : Assessment and Control of Extractables and Leachables For Pharmaceutical and Biologics Q4A - Pharmacopoeial Harmonisation The pharmacopoeial authorities works together through the Pharmacopoeial Discussion Group Q4B - Evaluation and Recommendation of Pharmacopoeial Texts for Use in The ICH Regions Q5A - Viral Safety Evaluation of Biotechnology Products Derived form Cell Lines of Human or Animal Origin Q5B - Analysis of The Expression Construct in cells Used for Production of r - DNA Derived Protein Products This document is intended to describe the types of information that are considered valuable in assessing the structure of expression construct used to produce r - DNA derived proteins

32. Q5C - Quality of Biotechnological Products : Stability Testing of Biological Products This document augments the stability Guideline (Q1A) and deals with the particular aspects of stability test procedures needed to take account of the special characteristics of products in which the active components are typically proteins and/or polypeptides. Q5D - Derivation and Characterization of Cell Substrates Used for Production of Biological Products This document provides broad guidance on appropriate standards for the derivation of human and animal cell lines and microbial cells used to prepare biotechnological/biological products, and for the preparation and characterization of cell banks to be used for production. Q5E - Comparability of Biological Products Subject to Changes in their Manufacturing Process The objective of this document is to provide principles for assessing the comparability of biotechnological/biological products before and after changes are made in the manufacturing process for the drug substance or drug product .

33. Q6A - Specifications : Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products This document provides guidance on the setting and justification of acceptance criteria and the selection of test procedures for new drug substances of synthetic chemical origin, and new drug products produced from them, which have not been registered previously in the ICH regions. Q6B - Specifications : Test Procedures and Acceptance Criteria for Biological Products This document provides general principles on the setting and justification of a uniform set of international specifications for proteins and polypeptides which are produced from recombinant or non-recombinant cell-culture expression systems. Q7 - Good Manufacturing practice for active Pharmaceutical Ingredients This document is intended to provide guidance regarding Good Manufacturing Practice (GMP) for the manufacturing of Active Pharmaceutical Ingredients (APIs) under an appropriate system for managing quality.

34. It is also intended to help ensure that APIs meet the requirements for quality and purity that they purport or are represented to possess. This Guideline applies to the manufacture of APIs for use in human drug (medicinal) products. It applies to the manufacture of sterile APIs only up to the point immediately prior to the APIs being rendered sterile. The sterilization and aseptic processing of sterile APIs are not covered by this guidance, but should be performed in accordance with GMP guidelines for drug (medicinal) products as defined by local authorities.

35. Q8 (R2) - Pharmaceutical Development This Guideline is intended to provide guidance on the contents for drug products as defined the Common Technical Document Q9 - Quality Risk Management This Guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality. These aspects include development, manufacturing, distribution, and the inspection and submission/review processes throughout the lifecycle of drug substances, drug products, biological and biotechnological products. Q10 - Pharmaceutical Quality System This Guideline applies to the systems supporting the development and manufacture of pharmaceutical drug substances and drug products, including biotechnology and biological products, throughout the product lifecycle.

36. Q11 - Development and Manufacture of Drug Substances Q12 - Technical and Regulatory considerations for Pharmaceutical Product Lifecycle Management This new Guideline is proposed to provide a framework to facilitate the management of post-approval Chemistry, Manufacturing and Controls (CMC) changes in a more predictable and efficient manner across the product lifecycle . Q13 - Continuous Manufacturing of Drug substances and Drug Products Capture key technical and regulatory considerations that promote harmonisation, including certain Current Good Manufacturing Practices (CGMP) elements specific to Continuous Manufacturing (CM), Allow drug manufacturers to employ flexible approaches to develop, implement, or integrate CM for the Manufacture – drug substances and drug products – of small molecules and therapeutic proteins for new and existing products.

37. Q14 – Analytical procedure Development and Revision of Q2 (R1) Analytical Validation This new guideline is proposed to harmonise the scientific approaches of Analytical Procedure Development, and to provide the principles relating to the description of Analytical Procedure Development process. This new guideline is intended to improve regulatory communication between industry and regulators and facilitate more efficient, sound scientific and risk-based approval as well as post-approval change management of analytical procedures.

38. References New Drug Approval Process – Fourth edition Accelerating Global Regulations, Edited by Richard A. Guarino, M.D. www.fda.gov www.ich.org