Current Status of Expiry of Homeopathic Medicines in Brazil, Germany, India and the United States: A Critical Review

Abstract

Background Assignment of expiry date to homeopathic medicines is a subject of important concern to its pharmacists and practitioners. This study compares the regulatory framework for the expiry of homeopathic medicines in four countries: Brazil, Germany, India and the United States.

Findings Different or no expiry periods are variously followed. Whereas Germany, with some exceptions, employs a maximum expiry of 5 years for both potencies and finished products, Brazil adopts a 5-year expiry for finished products only, potencies used in manufacture being exempted from an assigned expiry date. In India, all homeopathic medicines except dilutions and back potencies have a maximum of 5 years' shelf-life, including those supplied to consumers. In the United States, homeopathic medicines are exempted from expiry dates.

Comments There is neither a rational basis nor scientific evidence for assigning a short (3–5 years) expiry period for homeopathic medicines as followed in some of the countries, particularly in light of the fact that some studies have shown homeopathic medications to be effective even after 25 years. Homeopathic ultra-dilutions seem to contain non-material activity that is maintained over time and, since these exhibit different chemical properties compared to the original starting material, it is quite possible they possess properties of longer activity than conventional medicines. Regulators should acknowledge this feature and differentiate expiry of homeopathic medicinal products from that of conventional drugs.

Keywords

expiry - quality control - homeopathic medicines - drug stability - active pharmaceutical ingredient

Highlights

• Regulatory frameworks for expiry of homeopathic medicines in Brazil, Germany, India and the United States are compared.

• A short expiry of 3 to 5 years, to exemption from expiry, is followed across these countries.

• There are differences in the physico-chemical properties and stability aspects of UHDs compared with homeopathic low potencies; scientific studies and clinical experience indicate that UHDs possess a longer shelf-life.

• Regulatory bodies should consider this aspect by differentiating UHDs from low potencies, and also from conventional medicines.

• References

• 1 Sheffield Clinical Commissioning Group. Good Practice Guidance for Care Homes – Expiry Dates. Available at: http://psnc.org.uk/sheffield-lpc/wp-content/uploads/sites/79/2013/06/Expiry-Dates-Guidance-Oct-2013.pdf . Accessed April 24, 2019
• 2 Coffey KC. Is there a role for expired medications in developing countries?. Clin Pediatr 2013; 52: 7-9
• 3 Endler PC, Schulte J, Stock-Schroeer B, Stephen S. “Ultra High Dilution 1994” revisited 2015—the state of follow-up research. Homeopathy 2015; 104: 223-226
• 4 Oberbaum M, Gropp C. Update on hormesis and its relation to homeopathy. Homeopathy 2015; 104: 227-233
• 5 Endler PC, Scherer-Pongratz W, Harrer B, Lingg G, Lothaller H. Amphibians and ultra high diluted thyroxine—further experiments and re-analysis of data. Homeopathy 2015; 104: 250-256
• 6 Smith CW. Electromagnetic and magnetic vector potential bio-information and water. Homeopathy 2015; 104: 301-304
• 7 Bellavite P, Marzotto M, Olioso D, Moratti E, Conforti A. High-dilution effects revisited. 1. Physicochemical aspects. Homeopathy 2014; 103: 4-21
• 8 Bellavite P, Marzotto M, Olioso D, Moratti E, Conforti A. High-dilution effects revisited. 2. Pharmacodynamic mechanisms. Homeopathy 2014; 103: 22-43
• 9 Bonamin LV, Bellavite P. Immunological models in high dilution research following M Bastide. Homeopathy 2015; 104: 263-268
• 10 Kardile MV, Patil C, Haidar A, Mahajan UB, Goyal S. Homeopathic drug standardization through biological evaluations: an untrodden avenue. Int J High Dilution Res 2015; 14: 16-37
• 11 Chikramane PS, Suresh AK, Bellare JR, Kane SG. Extreme homeopathic dilutions retain starting materials: a nanoparticulate perspective. Homeopathy 2010; 99: 231-242
• 12 Elia V, Ausanio G, Gentile F, Germano R, Napoli E, Niccoli M. Experimental evidence of stable water nanostructures in extremely dilute solutions, at standard pressure and temperature. Homeopathy 2014; 103: 44-50
• 13 Lenger K, Bajpai RP, Spielmann M. Identification of unknown homeopathic remedies by delayed luminescence. Cell Biochem Biophys 2014; 68: 321-334
• 14 Lenger K. Homeopathic potencies identified by a new magnetic resonance method. Subtle Energies Energy Med 2004; 15: 225-243
• 15 Lenger K. Homeopathy – a regulation therapy healing hypo- or hyper-functions of pathological pathways by magnetic photons according to the resonance principle. J Life Sci 2017; 11: 53-64
• 16 Lenger K, Bajpai RP, Drexel M. Delayed luminescence of high homeopathic potencies on sugar globuli. Homeopathy 2008; 97: 134-140
• 17 Betti L, Elia V, Napoli E. , et al. Biological effects and physico-chemical properties of extremely diluted aqueous solutions as a function of aging-time. Front Life Sci 2011; 5: 117-126
• 18 Elia V, Elia L, Marchettini N, Napoli E, Niccoli M, Tiezzi E. Physico-chemical properties of aqueous extremely diluted solutions in relation to ageing. J Therm Anal Calorim 2008; 93: 1003-1011
• 19 Barve R, Kulkarni S. Stability and expiry date of remedies. Homœopathic Links 2014; 27: 110-114
• 20 Brazilian Homeopathic Pharmacopoeia in English. 3rd ed. 2011 . Available at: http://portal.anvisa.gov.br/documents/33832/259147/Farmacopeia+HOMEOPATICA+3a+EDICAO+INGLES+com+alerta.pdf/49a48a50-0d3e-4ab9-bc41-eb361c8afbb1 . Accessed April 24, 2019
• 21 Committee for Proprietary Medicinal Products, European Medicines Agency. Guideline on stability testing: Stability testing of existing active substances and related finished products. CPMP/QWP/122/02, rev 1 corr. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003466.pdf . Accessed April 24, 2019
• 22 Homeopathic Medicinal Product Working Group (HMPWG). Heads of medicines agencies. Points to consider on stability testing of homeopathic medicinal products. Available at: http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/HMPWG/2009_07_Points_on_Stability_testing.pdf . Accessed April 24, 2019
• 23 Homeopathic Medicinal Product Working Group (HMPWG). Heads of medicines agencies. Guidance on module 3 of the homeopathic medicinal products dossier. Available at: http://www.hma.eu/uploads/media/HMPWG_dossier_guidance_mod3.pdf . Accessed April 24, 2019
• 24 Das Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM). Stability testing for medicinal products prepared in accordance with homeopathic manufacturing procedures. Recommendations on how to use the “Guideline on stability testing: stability testing of existing active substances and related finished products”. CPMP/QWP/122/02, rev 1 corr. June 23, 2006. Available at: http://www.bfarm.de/SharedDocs/Downloads/EN/Drugs/licensing/zulassungsarten/pts/Leitf_Stabi_060623_en.pdf?__blob=publicationFile&v=2 . Accessed April 24, 2019
• 25 European Medicines Agency. ICH Topic Q 1 D, Bracketing and Matrixing designs for stability testing of drug substances and drug products: note for guidance on bracketing and matrixing designs for stability testing of drug substances and drug products. CPMP/ICH/4104/00. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002652.pdf . Accessed April 24, 2019
• 26 The Gazette of India. Government of India. Notification published by the Ministry of Health and Family Welfare on 31st October 2006. Available at: http://egazette.nic.in/WriteReadData/2006/E_528_2011_009.pdf . Accessed April 24, 2019
• 27 The Gazette of India. Government of India. Notification published by the Ministry of Health and Family Welfare on 1st February 2017. Available at: http://egazette.nic.in/WriteReadData/2017/173993.pdf . Accessed April 24, 2019
• 28 The Gazette of India. Government of India. Notification published by the Ministry of Health and Family Welfare on 10th November 2017. Available at: http://egazette.nic.in/WriteReadData/2017/180174.pdf . Accessed April 24, 2019
• 29 U.S. Food and Drug Administration. Code of Federal Regulations, Title 21, Volume 4, PART 211 – Current good manufacturing practice for finished pharmaceuticals, Sec. 211.137 Expiration dating. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=211.137 . Accessed May 27, 2019
• 30 Homeopathic Pharmacopoeia of the United States. HPUS homeopathic drug stability guidelines. Available at: http://www.hpus.com/homeopathic-drug-stability-guidelines-4-14.pdf . Accessed April 24, 2019
• 31 Bell IR, Schwartz GE. Enhancement of adaptive biological effects by nanotechnology preparation methods in homeopathic medicines. Homeopathy 2015; 104: 123-138
• 32 Elia V, Baiano S, Duro I, Napoli E, Niccoli M, Nonatelli L. Permanent physico-chemical properties of extremely diluted aqueous solutions of homeopathic medicines. Homeopathy 2004; 93: 144-150
• 33 Elia V, Marchettini N, Napoli E, Niccoli M. The role of ethanol in extremely diluted solutions. J Therm Anal Calorim 2014; 116: 477-483
• 34 Jones J, Jones K. The Provident Prepper: A Common-Sense Guide to Preparing for Emergencies. Springville: Cedar Fort, Inc.; 2014
• 35 DiMarco P. . Expiration Dates for Reagent Chemicals. SOP #: 8–2-3-A, Rev 2.1. Available at: https://studylib.net/doc/8746738/subject–expiration-dates-for-reagent-chemicals—pharmco . Accessed April 24, 2019
• 36 Scholar Chemistry. Material Safety Data Sheet. Ethyl Alcohol 95%, Denatured. Available at: https://www.mccsd.net/cms/lib/NY02208580/Centricity/Shared/Material%20Safety%20Data%20Sheets%20_MSDS_/MSDS%20Sheets_Ethyl_Alcohol_95Pct_denatured_274_00 . Accessed April 24, 2019
• 37 Oh DH, Marshall DL. Antimicrobial activity of ethanol, glycerol monolaurate or lactic acid against Listeria monocytogenes. Int J Food Microbiol 1993; 20: 239-246
• 38 Adler UC. Q potencies found to be effective even after 25 years. Oral Presentation at: World Integrated Medicine Forum: Regulating Homeopathic Medicinal Products: National And Global Strategies; Delhi; February 23–24; 2017
• 39 Shah J. Longer shelf-life of homeopathic high potencies as experienced in clinical practice. Oral Presentation at: World Integrated Medicine Forum: Regulating Homeopathic Medicinal Products: National And Global Strategies; Delhi; February 23–24; 2017
• 40 Adler UC, Acorinte AC, Calzavara FO. , et al. Double-blind evaluation of homeopathy on cocaine craving: a randomized controlled pilot study. J Integr Med 2018; 16: 178-184