Aid conditionalities, international Good Manufacturing Practice standards and local production rights: a case study of local production in Nepal

Globalization and Health

Allyson M. Pollock⁴  Nabin Rawal³  Samita Bhattarai¹  Madhusudan Subedi⁵  Ian Harper²  Petra Brhlikova⁴ 

[1] Northeastern University, Boston, MA, USA;School of Social and Political Science, University of Edinburgh, 15a George Square, Edinburgh EH8 9LD, UK;Central Department of Sociology/Anthropology, Tribhuvan University, Kathmandu, Nepal;Centre for Primary Care and Public Health, Queen Mary University of London, 58 Turner Street, London E1 2AB, UK;Patan Academy of Health Sciences, Nepal and Central Department of Sociology and Anthropology, Tribhuvan University, Kathmandu, Nepal

关键词: Harmonisation;    Good manufacturing practice (GMP);    Local pharmaceutical production;    Nepal;   

Others  :  1220797
DOI  :  10.1186/s12992-015-0110-3

 received in 2014-11-06, accepted in 2015-06-01,  发布年份 2015

【 摘 要 】

Background

Local pharmaceutical production has been endorsed by the WHO as a means of addressing health priorities of developing countries. However, local producers of essential medicines must comply with international pharmaceutical standards in order to be eligible to compete in donor tenders. These standards determine production rights for on-patent and off-patent medicines, and guide international procurement of medicines. We reviewed the literature on the impact of Good Manufacturing Practice (GMP) on local production; a gap analysis from the literature review indicated a need for further research. Over sixty interviews were conducted with people involved in the Nepali pharmaceutical production and distribution chain from 2006 to 2009 on the GMP areas of relevance: regulatory capacity, staffing, funding and training, resourcing of GMP, inspectors’ interpretation of the rules and compliance.

Results

Although Nepal producers have increased their overall share of the domestic market, only the public manufacturer, Royal Drugs, focuses on medicines for public health programmes; private producers engage mainly in brand competition for private markets, not essential medicines. Nepali regulators and producers state that implementation of GMP standards is hindered by low regulatory capacity, insufficient training of staff in the industry, financial constraints and lack of investment for upgrading capital. The transition period to mandatory compliance with WHO GMP rules is lengthy. Less than half of private producers had WHO GMP in 2013. Producers are not directly affected by international harmonisation of standards as they do not export medicines and the Nepali regulator does not enforce the WHO standards strictly. Without an international GMP certificate they cannot tender for donor dependent health programmes.

Conclusions

In Nepal, local private manufacturers focus mainly on brand competition for private consumption not essential medicines, the government preferentially procures essential medicines from the only public producer while donor funded programmes rely on international manufacturers compliant with international GMP standards. We also found evidence of private hospitals bypassing national medicines approvals process.

Policies in support of local pharmaceutical production in developing countries as a source of essential medicines need to examine carefully how GMP regulations impact on regulators, local industry and production of essential medicines in practice.

【 授权许可】

   
2015 Brhlikova et al.

【 参考文献 】

• [1]Global strategy and plan of action on public health, innovation and intellectual property. World Health Organization, Geneva; 2011.
• [2]Losse K, Schneider E, Spennemann C. The viability of local pharmaceutical production in Tanzania. Deutsche Gesellschaft für Technische Zusammenarbeit (GTZ) GmbH, Eschborn; 2007.
• [3]Chaudhuri S. The WTO and India’s Pharmaceuticals Industry: Patent Protection, TRIPS, and Developing Countries. Oxford University Press, New Delhi; 2005.
• [4]Local production for access to medical products: developing a framework to improve public health. World Health Organization, Geneva; 2011.
• [5]Kaplan W, Laing R. Local production of pharmaceuticals: industrial policy and access to medicines. An overview of key concepts, issues and opportunities for future research, in HNP Discussion Paper. The World Bank, Washington; 2005.
• [6]Investment in Pharmaceutical Production in the Least Developed Countries: A Guide for Policymakers and Investment Promotion Agencies. United Nations, Geneva; 2011.
• [7]World Medicines Situation. World Health Organization, Geneva; 2004.
• [8]Kaplan WA, Ritz LS, Vitello M. Local production of medical technologies and its effect on access in low and middle income countries: a systematic review of the literature. Southern Med Rev. 2011; 4(2):51-61.
• [9]Mujinja PG et al.. Local production of pharmaceuticals in Africa and access to essential medicines: ‘urban bias’ in access to imported medicines in Tanzania and its policy implications. Glob Health. 2014; 10:12. BioMed Central Full Text
• [10]Timmermans K. Harmonization, regulation, and trade: interactions in the pharmaceutical field. Int J Health Serv. 2004; 34(4):651-61.
• [11]Abraham J, Reed T. Trading risks for markets: the international harmonization of pharmaceuticals regulation. Health Risks Soc. 2001; 3(1):113-28.
• [12]Grimes DA et al.. The Good Clinical Practice guideline: a bronze standard for clinical research. Lancet. 2005; 366(9480):172-4.
• [13]The Impact of Implementation of ICH Guidelines in Non-ICH Countries. Regulatory Support Series, No. 9. World Health Organization, Geneva; 2002.
• [14]Santhosh M, Singh A. Booklet on Access to Medicines in India. CLRA-Centad, New Delhi; 2009.
• [15]WHO Expert Committee on Specifications for Pharmaceutical Preparations, in WHO Technical Report Series. 2011.
• [16]WHO. Guidelines on the implementation of the WHO certification scheme on the quality of pharmaceutical products moving in international commerce. 2014 [cited 2014 July 3]; Available from:. http://www. who.int/medicines/areas/quality_safety/regulation_legislation/certification/guidelines/en/ webcite
• [17]PIC/S. Pharmaceutical Inspection Co-operation Scheme: Role. 2014 [cited 2014 July 14]; Available from:. http://www. picscheme.org webcite
• [18]Annex 2: WHO good manufacturing practices for active pharmaceutical ingredients in WHO Technical Report Series. World Health Organization, Geneva; 2010.
• [19]Assessment of medicines regulatory systems in 26 sub-Saharan African countries: An overview of findings from 26 assessment reports. World Health Organization, Geneva; 2010.
• [20]Drug Safety: Better Data Management and More Inspections Are Needed to Strengthen FDA’s Foreign Drug Inspection Program. United States Government Accountability Office, Washington, D.C; 2008.
• [21]Global Fund. 6th Invitation to manufacturers of antimalarial medicines to submit an Expression of Interest (EoI) for product evaluation by Expert Review Panel (ERP). 2011.
• [22]Fiscal year 2008: PEPFAR operational Plan. 2008.
• [23]Blake S et al. U.N. Commission on Life Saving Commodities for Women and Children:Country Case Studies. 2012. [cited 2015 June 7]; Available from: http://can-mnch.ca/wp-content/uploads/2012/06/Life-Saving-Commodities-New_Concept_Note1.pdf.
• [24]Hill S, Johnson K. Emerging challenges and opportunities in drug registration and regulation in developing countries. DFID Health Systems Resource Centre, London; 2004.
• [25]Brhlikova P et al.. Trust and the regulation of pharmaceuticals: South Asia in a globalised world. Glob Health. 2011; 7:10. BioMed Central Full Text
• [26]Meshkini AH et al.. Assessment of the vaccine industry in Iran in context of accession to WTO: a survey study. DARU J Pharm Sci. 2012; 20:19. BioMed Central Full Text
• [27]Pinheiro ES et al.. Production of antiretroviral drugs in middle- and low-income countries. Antivir Ther. 2014; 19 Suppl 3:49-55.
• [28]Abdo-Rabbo A, Bassili A, Atta H. The quality of antimalarials available in Yemen. Malar J. 2005; 4:28. BioMed Central Full Text
• [29]Trouiller P, Folb P, Weerasuriya K. Legal and regulatory issues affecting drug development for neglected diseases: harmonization of technical requirements for registration of pharmaceuticals for human use. 2001.
• [30]Trouiller P et al.. The globalisation of regulatory requirements, and the development and availability of medicinal products in developing countries: quality, efficacy and safety issues. 2002.
• [31]Independent evaluation: Strengthening the local production of essential generic drugs in least developed/developing countries. UNIDO, Vienna; 2010.
• [32]Guimier J-M, Lee E, Grupper M. Processes and issues for improving access to medicines: the evidence base for domestic production and greater access to medicines. DFID Health Systems Resource Centre, London; 2004.
• [33]WHO WHO. Prequalification: Building quality-assured manufacturing capacity in Nigeria. WHO Drug Inf. 2014; 28(4):425-30.
• [34]WHO. WHO List of Prequalified Medicinal Products. 2015 [cited 2015 17 April]; Available from:. http://apps. who.int/prequal/query/ProductRegistry.aspx webcite
• [35]WHO. WHO List of Prequalified Active Pharmaceutical Ingredients. 2015 [cited 2015 April 17]; Available from:. http://apps. who.int/prequal/info_applicants/API_PQ-List.htm webcite
• [36]Dixit H. Nepal’s Quest for Health. Educational Books Publishing (P) Ltd, Kathmandu; 2000.
• [37]WTO and public health policy priorities for Nepal. SAWTEE, Kathmandu; 2006.
• [38]Quality assurance of medicines in Nepal: identified needs for capacity enhancement. Deutsche Gesellschaft für Internationale ZusammenarbeitHealth Sector Support Programme, Kathmandu; 2012.
• [39]Budhathoki S. Drug Drive: The Rising Business of Pharmaceutical Companies in Nepal, in New Business Age. 2012.
• [40]Department of Drug Administration: Objectives. 2007.
• [41]Nepal Pharmaceutical Country Profile. 2011.
• [42]Jeffery R. Tracing Pharmaceuticals in South Asia: Project Design and Basic Data. 2010. [cited 2015 June 7]; Available from: http://www.csas.ed.ac.uk/__data/assets/pdf_file/0005/49244/Tracing_Pharmaceuticals_in_South_Asia_WP2010.pdf.
• [43]Editorial: GMP Certification for Assuring the Quality of Pharmaceutical Products. Drug Bull Nepal. 2004; 16(1):3-4.
• [44]DDA. Regulatory news. Drug Bulletin of Nepal. 2012;24(1)
• [45]Shrestha B et al.. Nepal National Health Accounts, 2006/2007 - 2008/2009. Health Economics and Financing Unit, Ministry of Health and Population, Government of Nepal, Kathmandu; 2012.
• [46]Mosites E, et al. Nepal zinc case study. University of Washington Global Health START Program; 2012 ect.org/sites/default/files/resources/Nepal_Zinc%20Case%20Study_0.pdf.
• [47]Toledo E. USP DQI Good Manufacturing Practices Assessment for Manufacturers of Zinc Sulfate Tablets and Chlorhexidine Kathmandu, Nepal; January 14–22, 2008. Submitted to the U.S. Agency for International Development by the United States Pharmacopeia Drug Quality and Information Program, Rockville, Maryland: United States Pharmacopeia; 2009.
• [48]Palaian S, Mishra P. Role of drug and therapeutics committee towards drug safety–experiences from western Nepal. Kathmandu Univ Med J (KUMJ). 2005; 3(1):79-80.
• [49]Shakya B. Nepal: Exports of Ayurvedic Herbal Remedies and SPS Issues. Managing the Challenges of WTO Participation: 45 Case Studies. Gallagher P, Low P, Stoler A, editors. Cambridge University Press, Cambridge; 2005.
• [50]Morimoto K et al.. Promoting GMP implementation: developing training materials for the international audience. Qual Assur. 2003; 10(1):11-27.
• [51]Harper I, Rawal N, Subedi M. Disputing distribution: ethics and pharmaceutical regulation in Nepal. Studies Nepali Hist Soc. 2011; 16(1):1-39.