16 February Cannabis Standards and their relationship to Clinical Health Outcomes

Transcription

1 Cannabis Standards and their relationship to Clinical Health Outcomes Andrew Samann CEO and Founder Orion GMP Solutions Follow us on 16 February 2018

2 Cannabis Standards and their relation to Clinical Health Outcomes 1. What are the sources of variation? 2. How does Chemistry Manufacturing and Controls (CMC) apply to Botanical Drug Substances and Products? 3. How do batch records relate to CMC 4. Why is it important to understand product variation in relation to clinical health outcomes?

3 Genetic Variation Figure from: Cascini and Boschi. (2017) 2018 Emerald Conference

4 Proteomic Variation Flower Proteome Glandular Proteome Figure from: TJ Raharjo, et al. (2004)

5 Chemotype Variation Figure from: JT Fischedick, et al. (2010) 2018 Emerald Conference

6 Anecdotal and Scientific Variation CONCLUSION 4-1 There is substantial evidence that cannabis is an effective treatment for chronic pain in adults. CONCLUSION 4-6 There is insufficient evidence to support or refute the conclusion that cannabinoids are an effective treatment for epilepsy. (The National Academies Press, 2017)

7 National Academies of Science Recommendations, distilled: Pharmacokinetic and Pharmacodynamic Properties Minimum datasets for Clinical and Epidemiological studies with conclusive, actionable evidence Delivery Methods, Concentrations, and Dose Dependent Relationships Standards Development for Manufacturing and Clinical Studies

8 A drug shall be deemed adulterated if it is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess (Office of the Federal Registrar. 351 (a)(2)(b). Adulterated drugs and devices, Part A )

9 Early-Phase Development (P1 & P2) Trained personnel Genotyping Retention Samples Raw Material Reference Specimen Certificate of Authenticity Identity Testing Microscopic Examination Organoleptic Testing Macroscopic Examination Food and Drug Administration, Center for Drug Evaluation and Research. (2016) Emerald Conference

10 Botanical Drugs Therapeutic Consistency "Because of the heterogeneous nature of a botanical drug and possible uncertainty about its active constituents, one of the critical issues for botanical drugs is ensuring that the therapeutic effect for marketed drug product batches is consistent. FDA, Totality of Evidence Approach Dose- Response GACP QC Figure from: JT Fischedick, et al Emerald Conference

11 Chemistry Manufacturing & Controls Drug Substance 1. Description 2. Manufacture 3. Control of Materials 4. Control of Critical Steps 5. Characterization 6. Control of Drug Substance 7. Reference Standards 8. Container Closure System 9. Stability Drug Product 1. Description 2. Manufacture and Batch Formula 3. Control of Excipients 4. Control of Drug Product 5. Container Closure System 6. Stability FDA Center for Drug Evaluation and Research. (2003).

12 Batch Production Records Dates/ Times Release Equip Deviation Batch Records Batch Number Yields CCP Results Signatures QC ICH Q7. (2000).

13 Monographs & Certificates of Analysis Office of Medicinal Cannabis. (2014). Example of Bluebird Botanicals Batch Certificate of Analysis. Reused with permission Emerald Conference

14 Product Variation and its relation to Clinical Health Outcomes Pharmacokinetic and Pharmacodynamic Properties Minimum datasets for Clinical and Epidemiological studies with conclusive, actionable evidence Delivery Methods, Concentrations, and Dose Dependent Relationships Standards Development for Manufacturing and Clinical Studies

15 Next Actions 1. Lobby for funding and support of a Cannabis Research Agenda 2. Consider alternative methods for supporting cannabis research e.g. Crowd sourced research 3. Participate in Standards Generation ASTM D37

16 References F. Cascini, I. Boschi. Tetrahydrocannabinol Concentration and Genetic Characterization of Cannabis. Handbook of Cannabis and Related Pathologies, JT Fischedick, et al. Metabolic Fingerprinting of Cannabis Sativa L., Cannabinoids and Terpenoids for Chemotaxonomic and Drug Standardization Purposes. Phytochemistry, Oct Food and Drug Administration, Center for Drug Evaluation and Research. Botanical Drug Development Guidance for Industry. Dec Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for Industry INDs for Phase 2 and Phase 3 Studies: Chemistry, Manufacturing, and Controls Information. May International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use. ICH Q7: Good Manufacturing Practice Guide For Active Pharmaceutical Ingredients. Step 4, 10 Nov. 2000, p4/q7_guideline.pdf. Office of Medicinal Cannabis. Analytical Monograph Cannabis Flos. Nov TJ Raharjo, et al. Comparative Proteomics of Cannabis Sativa Plant Tissues. Journal of Biomolecular Techniques, The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. The National Academies Press, 2017.

17 Thank You! Instagram: Orion_GMP