ICH Guidelines Elemental Impurities: Strategies for Implementation for APIs

Transcription

1 ICH Guidelines Elemental Impurities: Strategies for Implementation for APIs Frankfurt, October 2017 Dr. Landry Le Chevanton 1

2 ICH Guidelines Elemental Impurities: Strategies for Implementation for APIs Introduction ICH Q3D: short history What has changed Increased complexity Practical implications Conclusions 2

3 Introduction What / who is APIC? A Technical European Industry Association, based in Brussels Focused on APIs from a quality and regulatory perspective 3

4 Introduction APIC s Mission To promote the use of compliant APIs in medicinal products to ensure patient safety To represent the interests of pharmaceutical and chemical companies producing APIs and intermediates in Europe by being recognized experts who advance and influence the global GMP and Regulatory environment 4

5 Introduction What / who is Landry Le Chevanton Working for DSM Nutritional Products Ltd. in Switzerland as Head of Global Regulatory Affairs and Quality Management Operations Over 10 years of experience in the regulatory field Excom member of APIC, Chair of APIC TaskForce on ICH Q3D. 5

6 Short History of ICH Q3D (1/2) The story started in 1995 with USP publishing a stimuli article identifying issues with the Heavy Metals Limit Test 1998 EMA drafted a guideline on Specification Limits for Residues of Metal Catalysts 2008 EMA issued the Guideline on Residual Catalysts and Reagents 2010, ICH convened Q3D to develop harmonized limits for elemental impurities in pharmaceuticals 6

7 Short History of ICH Q3D (2/2) June 2013 ICH Q3D reached step 2 16 December 2014, ICH Q3D (at step 4) was published on the ICH Website 7

8 What are the changes introduced by ICH Q3D Before (EMA Guideline) Apply to Drug Products ICH Q3D Apply to Drug Products 14 elements considered 24 elements considered PDE defined Focused on metals intentionally added during syntheses Certain PDE revised Takes into account all possible sources of EI Control strategy defined in guideline Risk Assessment is basis for control strategy 8

9 Consequences of the Change: Complexity Increased 9

10 Where to start? ICH Q3D Guidelines ICH Q3D Modules 1-9 The essentials EMA Implementation strategy of ICH Q3D guideline (Mar 2017) EDQM Implementation of ICH Q3D in the Certification Procedure (Aug 2016) 10

11 And also Trade Associations (ask APIC!) Webinars Further Support Conferences Scientific Literature 11

12 Primary sources of elemental impurities in API Metal Catalysts Packaging Manufact. Equip. Solvents API Processing aids Water Inorganic reagents Organic materials 12

13 Frequently encountered issues Issue Request for confirmation that API complies with ICH Q3D. APIC position ICH Q3D does not apply to APIs. This confirmation cannot be provided. Request for providing batch data on API for all 24 elements listed in ICH Q3D. Availability of such data is not required by ICH Q3D. ICH Q3D is not a testing guideline 13

14 Not all API are the same Contribution of the API to the total mass of the drug products varies a lot. Some APIs works at a really low dose. Levothyroxine µg/tablets Vitamin D3 20 µg/tablets In those case the contribution to potential contamination of elemental impurities are really negligible 14

15 The reality. (1/2) The reality is that to date there is simply no evidence of a substantive risk to patients regarding elemental impurities in pharmaceuticals. Assessments of both development compounds and marketed products across the industry have shown there to be virtually no risk, and specifically for established products, there has proven to be virtually no incidence where it has been necessary to replace the outdated heavy metals limit test with specific testing. (Teasdale A., Org. Process Res. Dev. 2016, 20, ) 15

16 The reality. (2/2) This is confirmed also at the API level, where EDQM communicated in June 2017 that approximatively 150 Risk Management Summary were submitted during CEP revisions to the agency, none of them indicated higher level of risks than before, on the contrary, in several cases, the control strategy could be relaxed. 16