Regulatory Affairs Tutorial Notes

1. Why do Drugs need to be regulated ?: - They are not ordinary consumers' products - Professional advice from either prescribers or dispensers is needed for consumers in making these decisions - The production of medicines, their distribution and dispensing also requires special knowledge and expertise 2. What triggered the British Medical Association to set up an independent body to assess drug safety ?: - A number of sudden deaths were reported following the introduction of chloroform as an anaesthetic - BMA working party suggested in 1880 setting up of independent body to assess drug safety. 3. Therapeutic Substances Act 1925: Introduced regulations concerning the manufacture of biological substances - strengthened in 1956. 4. Thalidomide disaster of 1961: - First on sale in 1956 - widely prescribed for treatment of vomiting in early pregnancy - drug caused major birth defects if taken by a woman during the first trimester of pregnancy 5. Committee on Safety of Drugs (CSD): - set up in 1963 - created to prevent another disaster such as with Thalidomide - has not legal powers = worked effectively with the pharmaceutical industry to advise on clinical trials and the marketing of new medicines - set up ADR reporting system = Yellow Card Scheme 6. MHRA - Medicines and Healthcare products Regulatory Agency: - responsible for regulating all medicines and medical devices in the UK by ensuring they work and are acceptably safe - regulate blood - assess all applications for new medicines to ensure they meet the required standards - Safety monitoring is also continuous and the MHRA also ensures that doctors and patients receive up-to-date and accurate information about their medicines 7. Principle responsibilities of Regulatory authorities:: •Licensing of the manufacture, import, export, distribution, promotion and advertising of medicines •Assessing the safety, efficacy and quality of medicines, and issuing marketing 1/5 authorisation for individual products •Inspecting and surveillance of manufacturers, importers, wholesalers and dispensers of medicines •Controlling and monitoring the quality of medicines on the market •Controlling promotion and advertising of medicines •Monitoring safety of marketed medicines including collecting and analysing adverse reaction reports •Providing independent information on medicines to professionals and the public 8. Three main types of EU Legislation:: Regulations Directives Decisions 9. Three main types of EU Legislation: Regulations: - addressed to all member states and are applied in full. - directly applicable without the need for national legislation 10. Three main types of EU Legislation: Directives: - addressed to all member states - National authorities must draw up legislation in order to conform with the directive 11. Three main types of EU Legislation: Decisions: - issued by the Council or Commission; these are not of general application - may be addressed to particular member states, individuals or companies and they are binding on those to whom they are addressed 12. The Dossier - CTD - Module 1: - for administrative information and product information (SmPC, PIL), and should contain documents that are specific to each region 13. The Dossier - CTD - Module 2: - contains the CTD summaries and should begin •with a general introduction to the drug, including its pharmacological class, mode of action and proposed clinical use. - should also provide the overall summary of the 'quality' information provided, the non-clinical overview and the clinical overview, as well as the non-clinical written summaries and the tabulated summaries, and the clinical summary. 2/5 14. The Dossier - CTD - Module 3: Contains detailed information on quality topics: - divided into S (substance) and P (product) - often called the CMC section of the dossier 15. Dossier - CTD - Modules 4: Contains the nonclinical study reports 16. Dossier - CTD - Modules 5: - contains clinical study reports - clinical study report (CSR) on a clinical trial is a detailed document about the methods and results of a clinical trial. - A CSR is a scientific document addressing efficacy and safety 17. Why would a MA application be rejected ?: It appears that: •the risk-benefit ratio is not seen as favourable; •its therapeutic effect is insufficiently substantiated; •its qualitative and quantitative composition is not as declared; •the particulars and documents which accompany the application are inconsistent with the provisions of the Directive. 18. National Procedure: - A licence to market a product in an individual EU member state. 19. Mutual Recognition Procedure (MRP): - Once a national application has been approved in a Member State, to gain approval in other member states the Mutual Recognition Procedure (MRP) must be used. - A 90 day procedure (no 'clock stops' are allowed) during which the recipients of the applications are asked to 'recognise' the positive opinion of the member state that granted the first (National) MA. - This procedure results in a series of national MAs. 20. Decentralised Procedure (DCP):: - a means of obtaining Marketing Authorisations in two or more EU member states simultaneously. - In order to be eligible for the Decentralised Procedure, the applicant must not hold a licence for the product in question in any EU member state. - Decentralised Procedure follows tight timelines and is characterised by close coordination between the Health Authorities of the participating Member States. 3/5 - It is the principle route to market for generic products 21. The Orange Guide: - Medicines Act (1968) covers most aspects of GMP (Good manufacturing practice) in what is commonly referred to as "The Orange Guide" - its officially known as "Rules and Guidance for Pharmaceutical Manufacturers and Distributors". 22. Post approval changes: Once a marketing authorisation has been granted, changes to aspects of the dossier are required, for example: •moving manufacturing sites to a different location, •changes in the manufacturing process, •changes to the QC methods of analysis, •changes to the Patient Information such as the SmPC, PIL or Labelling, •Inclusion of new safety information in the SmPC or PIL 23. Variations: Changes to a marketing authorisation are typically managed by 'Variations' to the product licence. - Guidance on variations is published by the European commission 24. Classifications of variations:: • Type IA - minor changes • Type IA (IN) - minor changes that need immediate notification • Type IB - minor changes • Type II - major changes 25. Type IA and IA (IN): - Type IA = also known as 'do and tell' variations - can only be submitted AFTER the change has been made - variations are only for minor changes to the product licence - must be submitted within one year from implementation of the change 4/5 - Type IAIN variations or "immediate notification" variations must be submitted within two weeks of implementation of a change 26. Type IB: - Minor changes - must be submitted and approved BEFORE the change is implemented - Typically, competent authority approval is required before implementation of the change - although if they don't respond within 30 days, the change may be implemented 27. Type II: Major variation that may have a significant impact on the quality, safety or efficacy of a medicinal product. 28. Northern Ireland Protocol: - agreed as part of the Withdrawal Agreement In October 2019. - Establishes a single regulatory zone on the island of Ireland (UK (NI) and IE) - Northern Ireland remains as part of the EU single market and they are required to align with EU rules. - MHRA continue to act as the overseeing Regulatory Authority for the whole of the UK. - NI business have "unfettered access" to move goods to the GB market. 29. Project Orbis: - a programme coordinated by the US Food and Drug Administration (FDA) to review and approve promising cancer treatments. 30. Access Consortium: A medium-sized collation of regulatory authorities that that work together to promote greater regulatory collaboration and alignment of regulatory requirements, reduce duplication and increase each agency's capacity to ensure patients have timely access to high quality, safe and effective medicines. 5/5