1. Regulatory Approval Process for Veterinary Drugs – A Global Perspective M. R. Srinivasan and P. Sriram Laboratory Animal Medicine, Centre for Animal Health Studies, Tamil Nadu Veterinary and Animal Sciences University, Madhavaram Milk Colony, Chennai – 600 051 Regulatory Approval Process for Veterinary Drugs – A Global Perspective M. R. Srinivasan and P. Sriram Laboratory Animal Medicine, Centre for Animal Health Studies, Tamil Nadu Veterinary and Animal Sciences University, Madhavaram Milk Colony, Chennai – 600 051 Introduction  Similar to the human pharmaceutical industry, innovation is essential to the existence of animal health companies.  The development of new vet drugs take 5–15 yrs  More than US$100 million to advance an animal health drug from initial concept to market.  Total Indian animal health market ~$212 Mn, 1/100 th of world market (Source: Express Pharma, May 2008) with largest livestock population in the world  All animal health drugs (excluding medical devices) are required to be approved by an appropriate regulatory agency prior to marketing.  The goal is to ensure quality, safety & effectiveness Source: Vetnosis Phases in New Veterinary Drug Development: Discovery Phase: Unmet animal health needs & satisfactory return on investments (market assessment)  Patentability  Ease of manufacture  Initial PoC – In Vitro & In Vivo studies  Preliminary ADME  API Stability  Target animal safety and Preliminary toxicology studies Development Phase: Further characterisation of drug substance  Detailed ADME Studies, plasma & tissue bio-analytical methods, 14 C studies  Manufacture potential; scale-up batches  Business decision to advance the lead to more expensive registration phase  Contact regulatory agency & open INAD file Registration Phase: Fulfil the requirement of NADA application  All Studies in GLP, and GCP mode  GMP API material  Robust validated analytical & bio-analytical methods  Effectiveness, Target animal safety, CMC, Environmental assessment, Human Food safety, FoI summary, and labelling Approval Process – United States of America New animal drugs are approved and regulated by FDA’s Center for Veterinary Medicine (CVM) AAVPT Veterinary Drug Regulatory Life Cycle Online Course – Free http://www.fda.gov/AnimalVeterinary/DevelopmentApprovalPro cess/ucm249768.htm Case Study: A new antibiotic“drug X” for Bovine Respiratory Disease(BRD) Discovery & Development Phase – Drug X Demonstrate acceptable activity against BRD pathogens: In vitro assay- Mannheimia hemolytica, Pasteurella multocida, etc. :‘hits’ Discovery & Development Phase – Drug X Demonstrate acceptable activity against BRD pathogens: In vitro assay- Mannheimia hemolytica, Pasteurella multocida, etc. :‘hits’ Bovine model of induced BRD: In vivo efficacy, No acute target animal toxicity at efficacy dose ADME studies - IV/SC PK study Bio-analytical method development in plasma & tissue “Truck & shoot” study – mimic transportation of bovines 14 C study – Preliminary total residue study Preliminary target animal safety studies – acutely safe API Manufacturing & finalization of formulation Registration Phase Open INAD file with ONADE office of FDA’s CVM – Discuss development plan of new animal drug Five Major Technical Sections Studies are conducted as per V-ICH guidelines (www.vichsec.org) Harmonised guidelines for 3 regions, ie. USA, EU & Japanwww.vichsec.org Five Major Technical Sections Studies are conducted as per V-ICH guidelines (www.vichsec.org) Harmonised guidelines for 3 regions, ie. USA, EU & Japanwww.vichsec.org 1. Effectiveness: in vitro study, study in laboratory animals, study in target species, Field study, bioequivalence study 4. Chemistry, Manufacturing and Control (CMC): Describes the plan for making the drug a)What ingredients will be used to make the drug b)Where the ingredients will come from c)Where the drug will be made d)How it will be made & packaged e)How it can be stored (under what conditions) and f)How long it can be stored (determine expiration date) 4. Chemistry, Manufacturing and Control (CMC): Describes the plan for making the drug a)What ingredients will be used to make the drug b)Where the ingredients will come from c)Where the drug will be made d)How it will be made & packaged e)How it can be stored (under what conditions) and f)How long it can be stored (determine expiration date) 5. Environmental Impact: a)Categorical Exclusion b)Environmental introduction and fate studies c)Environmental effects studies d)Environmental assessment 5. Environmental Impact: a)Categorical Exclusion b)Environmental introduction and fate studies c)Environmental effects studies d)Environmental assessment New Animal Drug Application Approved for marketing Approval Process – India  Drugs and Cosmetics Act and Rules 1945 and revised on 2003  No separate guidelines for approval of Veterinary medicine  For Vet Biological follow Schedule F(1)-Purity, Strength & Quality  For other standards – follow British Pharmacopoeia (Veterinary) Schedule F(1) Part I: Vaccines Bacterial Viral Part II: Antisera Antibacterial sera Antiviral sera Antitoxin sera Part III: Diagnostic Antigens Conclusion  Veterinary medicine market in India – very small Vs world market  Drug Discovery and Development – costly affair, 5-15 yrs  Veterinary medicine approval process well regulated globally  Indian regulatory process for Vet medicine  human medicine  A global perspective on regulatory approval process is essential  to change regulatory process in India – ‘at par’ globally  to develop expertise in regulatory studies  to attract top R&Ds to India – tap the resources 2. Human Food Safety: a)Toxicology: To determine ADI – Mutagenicity, 90-day study in rodent and non-rodent, Reproductive toxicity study & Teratology study b)Residue Chemistry: Using ADI, set the tolerance limit & set the withdrawal time c)Microbial food safety: Bacterial resistance to antibiotics and it’s impact on public health d)Regulatory Method: CVM ensures appropriate and accurate testing methods in human food safety studies 2. Human Food Safety: a)Toxicology: To determine ADI – Mutagenicity, 90-day study in rodent and non-rodent, Reproductive toxicity study & Teratology study b)Residue Chemistry: Using ADI, set the tolerance limit & set the withdrawal time c)Microbial food safety: Bacterial resistance to antibiotics and it’s impact on public health d)Regulatory Method: CVM ensures appropriate and accurate testing methods in human food safety studies 3. Target Animal Safety: Tolerance study, Reproductive Safety Study, Animal Class Safety (e.g., young, geriatric), Special Cases (specific breeds) Recommendations of the “Confluence of Veterinary Regulatory Reforms in India” – 6 th Oct 2012  A Separate Veterinary Drug Control Authority  Drug Consultative Committee – Vet. Drugs & Formulations (VDFs)  New Drug Approval Committees – include Vets for VDFs  Veterinary Pharmacopeia – required  Vets as Veterinary Drug Officers/Inspectors for VDFs at State level  Veterinary Drug Portal & Harmonization of Standards  Govt. policy: pro-development & attract industry and investment