ICH QSEM Guidelines

Guidelines By ICH and special emphasis on Quality.

1. Overview of ICH Guidelines- QSEM 1 PRESENTED BY -ASHWIN D. DIGARSE M.PHARMA I ST YEAR {QA} SMT. KISHORIAI BHOYAR COLLEGE OF PHARMACY, KAMPTEE

2. ICH What is ICH? The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is unique in bringing together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration . ICH was created in April 1990. 2

3. ICH Guidelines The ICH topics are divided into four categories and ICH topic codes are assigned according to these categories. Quality Guidelines Safety Guidelines Efficacy Guidelines Multi Disciplinary Guidelines 3

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5. Harmonization 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 Guidelines 5

6. Safety Guidelines ICH 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. 6

7. 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. 7

8. Multidisciplinary Guidelines Those 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). 8

9. Special emphasis on Q-series guidelines The “Q-Family ” Q 1 – Stability Testing Q 2 – Analytical Validation Q 3 – Impurities Q 4 – Pharmacopoeias Q 5 – Biotechnological Products 9

10. Q 6 – Specifications Q 7 – Good Manufacturing Practices Q 8 – Pharmaceutical Development Q 9 – Quality Risk Management Q 10 – Pharmaceutical Quality System 10

11. ICH Q 1 – Stability Testing ICH Q 1 – Stability Testing A set of originally five guidelines (Q1A to Q1F) Defining General aspects of stability testing (storage conditions, batch size and number, length of time...) Photostability Application to new dosage forms Possibilities for reduced test designs (bracketing and matrixing ) Stability Testing - Statistical evaluation of stability data and possibilities for extrapolation Storage conditions for stability testing in climatic zones III and IV (withdrawn) 11

12. ICH Q1A Stability Testing for New Drug Substances and Products: Stability Testing for New Drug Substances and Products Developed with in the Expert Working Group of ICH Stability testing requirement for a Registration Application within Tripartite Objective is to provide evidence of how the quality of a drug substance or drug product varies with time under variety of environmental forces (temp., humidity, light) and enables recommended storage conditions, re-test periods and shelf lives to be established. 12

13. CH Q2 (R1) Validation of Analytical Procedures : Text and Methodology: ICH Q2 (R1) Validation of Analytical Procedures : Text and Methodology Demonstrate that it is suitable for its intended purpose. Four most common types of analytical procedures: Identification tests Quantitative tests for impurities' content Limit tests for the control of impurities Quantitative tests of the active moiety in samples of drug substance or drug product or other selected component(s) in the drug product 13

14. ICH Q3A Impurities in New Drug Substances : Provide guidance for registration applications on the content and qualification of impurities in new drug substances produced by chemical syntheses and not previously registered in a region or member state. Impurities in new drug substances are addressed from two perspectives: Chemistry aspects include classification and identification of impurities, report generation, listing of impurities in specifications, and a brief discussion of analytical procedures Safety aspects include specific guidance for qualifying those impurities that were not present , or were present at substantially lower levels, in batches of a new drug substance used in safety and clinical studies. Second revision of the Q3A guidance, which was published in 1996 and revised in 2003 . Impurities can be classified into the following categories: Organic impurities (process- and drug-related Inorganic impurities Residual solvents 14

15. ICH Q4B Regulatory Acceptance of Analytical Procedures and/or Acceptance Criteria (RAAPAC) : Pharmacopeial Discussion Group (PDG) comprised of representatives of the United States Pharmacopeia (USP), Japanese Pharmacopoeia (JP), and the European Pharmacopoeia ( Ph.Eur . or EP) Activity of Q4B are as follows: Effective way to raise and resolve issues that might impact both industry and regulators. For FDA, interchangeability means the possible use of the harmonized methods of JP and EP, where deemed appropriate and based on our scientific review, to be considered as equivalent to the USP method. A savings in time and effort: Given the unified approach and strength of working directly with the three regulatory regions, it is an effective way to partner in the pharmacopeial process to effect change, where single, independent efforts might not be as successful. Maintains FDA's review authority In case of any question, the local regional method prevails. Establishes a process for multi-center input into scientific review for determining the interchangeability 15

16. ICH Q 5 C Quality of Biotechnological Products: Applies to well- characterised proteins and Polypeptides,their derivatives and products of which they are components, and which are isolated from tissues, body fluids, cell cultures, or produced using rDNA technology . Covers the generation and submission of stability data for all biotechnological products (vaccines, growth hormones, etc.) The document does not cover antibiotics, allergenic extracts, heparins, vitamins or whole blood . Purpose: Guidance to applicants regarding the type of stability studies that should be provided in support of marketing applications. 16

17. ICH Q6A Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances :   It 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 United States, the European Union, or Japan " Conformance to specifications" means that the drug substance and / or drug product, when tested according to the listed analytical procedures, will meet the listed acceptance criteria . Addresses only marketing approval of new drug products and substances but not during the CT development 17

18. ICH-Q7A Guidance for Active Pharmaceutical Ingredients: Provide guidance regarding GMP for the manufacturing of active pharmaceutical ingredients (APIs) under an appropriate system for managing quality Define manufacturing operations to include Receipt of material Production Packaging and Repackaging Quality control Labeling and Re-labeling Release Storage Distribution of APIs and related controls Vaccines are not included Should not use a stand-alone section Covers cell culture, fermentation (CCF), tissue or animal sources including transgenic animals 18

19. ICH – Q8(R1) Pharmaceutical Development: Pharmaceutical development should include the following elements: Defining the target product profile as it related Q,S and E Identifying Critical Quality Attributes (CQA) of the drug product to study and control the product quality. Determining the quality attributes of the drug substance and Excipients, etc to get desired quality. Selecting an appropriate manufacturing process and a control strategy. 19

20. Q8(R2 ) Pharmaceutical Development :  Describes science and risk-based approaches for pharmaceutical product and manufacturing process Development to consistently deliver the intended performance of the product Introduced concepts of design space and flexible regulatory approaches Scientific understanding to support the establishment of design space, specifications and manufacturing controls Introduced concepts of Quality by Design ( QbD ) and provided examples of QbD development approaches and design space 20

21. ICH-Q9 Quality Risk Management Describes systematic processes for the assessment, control, communication and review of quality risks Applies over product lifecycle: development, manufacturing and distribution Includes principles, methodologies and examples of tools for quality risk management Assessment of risk to quality should: - Be based on scientific knowledge - Link to the protection of the patient - Extend over the lifecycle of the product Risk: Combination of the probability of occurrence of harm and severity of that harm. 21

22. ICH-Q10 Pharmaceutical Quality System Incorporates the concepts behind Q8 and Q9 by providing a pharmaceutical quality system that can be implemented through out the product life cycle. Facilitates continual improvement and strengthen the link between Q8 and Q9. Quality attributes to meet patients need. Establish and maintain State of Control (Process performance and Product quality). - Track and trend product quality - Maintain and update models as needed - Internally verify that process changes are successful Good scientific development (Q8) in combination with QRM (Q9) and PQS (Q10) will improve drug quality and efficiency of pharmaceutical manufacturing 22

23. ICH-Q11 Development and Manufacture of Drug Substances  High level technical guidance relevant to the design, development and manufacture of drug substances as a part of total strategy. Provide guidance for drug substances (Q6A & Q6B) Identify similarities and differences of biologics and chemical entities. Facilitate regulatory evaluation process To demonstrate process and product understanding Address the complexity of different manufacturing process & product Outline science based concepts Address systematic and enhances approaches for design space, control strategies and real-time release 23

24. Thank you 24