Review of Quality Deficiencies Found in Active Pharmaceutical Ingredient Master Files Submitted to the WHO Prequalification of Medicines Programme

Purpose. The aim of this work was to determine the number and type of active pharmaceutical ingredient (API) quality deficiencies in API Master Files (APIMFs) as submitted to the World Health Organization (WHO) Prequalification of Medicines Programme (PQP). Methods. We conducted a retrospective review of API quality deficiencies identified following the assessment of new APIMFs for non-sterile APIs during a 6-year period from 1 January 2007 to 31 December 2012. All deficiencies were collected, classified and quantified according to the Common Technical Document (CTD) sections and subsections and as groups of commonly raised questions. Results. There were 5446 deficiencies collected from 159 APIMF deficiency letters by CTD section, by selected CTD subsections and by selected CTD subsections and year. More than 50% of the total number of deficiencies related to the manufacturing sections of the CTD, followed by deficiencies concerning the impurities, the API specification and the stability sections of the CTD. A pattern of API deficiencies across the different CTD subsections and over time was identified. Conclusions. The most frequent critical deficiencies were related to how the specific manufacturing process and the key materials used, in particular the API starting material, impact the API impurities content. The number and pattern of APIMF deficiencies did not change over time. The results are compared to the findings in similar studies as reported by the United States Food and Drug Administration (USFDA), the European Directorate for the Quality of Medicines (EDQM) and the European Medicines Agency (EMA) and similarities and differences are discussed. Our findings highlight the need for greater guidance and technical assistance for API manufacturers submitting APIMFs to the PQP. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Download Full-text

SARS: Political Pathology of the First Post-Westphalian Pathogen

The Journal of Law Medicine & Ethics ◽

10.1111/j.1748-720x.2003.tb00117.x ◽

2003 ◽

Vol 31 (4) ◽

pp. 485-505 ◽

Cited By ~ 37

Author(s):

David P. Fidler

Keyword(s):

Infectious Disease ◽

Infectious Diseases ◽

The United States ◽

First Century ◽

World Health ◽

Health Security ◽

The World ◽

Twenty First Century ◽

The Stability ◽

Health Organization

In March 2003, the world discovered, again, that I humanity's battle with infectious diseases continues. The twenty-first century began with infectious diseases, especially HIV/AIDS, being discussed as threats to human rights, economic development, and national security. Bioterrorism in the United States in October 2001 increased concerns about pathogenic microbes. The global outbreak of severe acute respiratory syndrome (SARS) in the spring of 2003 kept the global infectious disease challenge at the forefront of world news for weeks. At its May 2003 annual meeting, the World Health organization (WHO) asserted that SARS is “the first severe infectious disease to emerge in the twenty-first century” and “poses a serious threat to global health security, the livelihood of populations, the functioning of health systems, and the stability and growth of economies.”

Download Full-text

Has survival improved for nasopharyngeal carcinoma in the United States?

Otolaryngology ◽

10.1016/j.otohns.2004.09.018 ◽

2005 ◽

Vol 132 (2) ◽

pp. 303-308 ◽

Cited By ~ 29

Author(s):

Jivianne T. Lee ◽

Clifford Y. Ko

Keyword(s):

United States ◽

Nasopharyngeal Carcinoma ◽

Survival Rates ◽

The United States ◽

Incidence Rates ◽

World Health ◽

Type Iii ◽

Favorable Histology ◽

Health Organization ◽

Over Time

OBJECTIVE: To analyze the epidemiologic patterns and survival rates for patients with nasopharyngeal carcinoma over the last three decades. METHODS: The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) program tumor registries were used to identify patients with nasopharyngeal carcinoma in the United States from 1973 to 1999. Incidence and survival rates for each decade were then determined according to age, gender, race, histological type, and stage using the SEER statistical program. RESULTS: From 1973 to 1999, 4680 cases of patients with nasopharyngeal carcinoma in the United States were sampled by the NCI/SEER database. Overall incidence rates for each decade essentially remained unchanged over time (0.7/100,000). Asians exhibited the highest incidence rates (3.0–4.2), followed by blacks (0.7–1.1) and then whites (0.4–0.7). In contrast, survival rates have gradually improved over time for all stages and histological types (35.7% 5-year survival in the 1970s vs. 44.1% in the 1980, and 51% in the 1990s). With respect to race, Asians demonstrated the best 5-year survival rate (62.9%) followed by whites (42.6%) and then blacks (36.2%). However, this may be due to histology, because Asians were also found to have a greater proportion of World Health Organization (WHO) type III cases (27.6%) in comparison to the other 2 groups (22.4% for blacks and 15% for whites). CONCLUSIONS: Although the incidence rates of nasopharyngeal carcinoma have remained essentially unchanged in the United States in the last 3 decades, survival rates for each stage and histological subtype have exhibited considerable improvement over time. The higher survival rates in Asians may be partially attributed to the more favorable histology (type III) often seen in this group. EBM rating: B-3.

Download Full-text

Comparison of the NeuMoDX, Diasorin Simplexa, Cepheid and Roche CDC SARS-CoV 2 EUA assays using nasopharyngeal/nasal swabs in universal transport media (UTM) and sputum and tracheal aspirates

10.1101/2020.05.26.118190 ◽

2020 ◽

Cited By ~ 1

Author(s):

Robert Tibbetts ◽

Kathy Callahan ◽

Kareem Rofoo ◽

Richard J. Zarbo ◽

Linoj Samuel

Keyword(s):

The United States ◽

World Health ◽

Molecular Testing ◽

Additional Specimen ◽

Significant Difference ◽

Nasal Swabs ◽

Henry Ford ◽

United States Food ◽

Health Organization ◽

Tracheal Aspirates

AbstractIn March 2019 the outbreak of SARS-CoV 2 was officially defined as a pandemic by the World Health Organization and shortly after, the United States Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) to the Centers for Disease Control (CDC) for reverse transcription polymerase chain reaction (rtPCR) molecular testing for the detection of the SARS-CoV-2 virus from NP swabs. Since then, EUA with relaxed regulations were granted to numerous manufacturers and clinical microbiology laboratories to implement in-house testing assays with nasopharyngeal swabs (NP) and subsequently additional specimen types. Because of supply chain shortages leading to competition for reagents, sustaining any significant volume of testing soon became problematic. As a countermeasure, within several weeks the Henry Ford Microbiology Laboratory validated 4 different rtPCR assays and multiple specimen types using NeuMoDX, Diasorin Simplexa, Cepheid and Roche platforms. The purpose of this study was to analyze the analytic sensitivity of these rtPCR assays with NP/nasal swabs and sputum/tracheal aspirates. Qualitative analytic agreement between the 4 platforms for NP/nasal swabs ranged 95% - 100% overall with no statistically significant difference in threshold cT values. Similar results were obtained with the sputum/tracheal aspirates. These data demonstrate the high accuracy and reproducibility in detection of SARS-CoV 2 between the rtPCR assays performed on 4 different platforms with numerous specimen types.

Download Full-text

World Health Organization

International Organization ◽

10.1017/s0020818300015083 ◽

1949 ◽

Vol 3 (4) ◽

pp. 722-724

Keyword(s):

World Health Organization ◽

Technical Assistance ◽

The United States ◽

World Health ◽

Executive Board ◽

Assistance Program ◽

Technical Assistance Program ◽

Health Organization ◽

Second World ◽

Voluntary Basis

The Second World Health Assembly met in Rome from June 13 to July 2, 1949 under the presidency of Dr. Karl Evang (Norway) and approved the program, policies and budget of the World Health Organization for 1950. Adopted by the Assembly and subsequently approved by the Executive Board was the regular budget of $7,893,000 of the usual contributions of member governments and a supplementary budget of $9,152,520 to be raised on a voluntary basis from member governments and used not only to extend the projects covered by the regular budget but to include projects under the United Nations technical assistance program for under-developed areas. By mid-summer Yugoslavia, Ceylon, the Dominican Republic, India and the United States had indicated their willingness to make contributions to the supplementary budget.

Download Full-text

Availability of Authorizations from EMA and FDA for Age-Appropriate Medicines Contained in the WHO Essential Medicines List for Children 2019

Pharmaceutics ◽

10.3390/pharmaceutics12040316 ◽

2020 ◽

Vol 12 (4) ◽

pp. 316 ◽

Cited By ~ 3

Author(s):

Jose-Manuel delMoral-Sanchez ◽

Isabel Gonzalez-Alvarez ◽

Marta Gonzalez-Alvarez ◽

Andres Navarro-Ruiz ◽

Marival Bermejo

Keyword(s):

Drug Product ◽

Essential Medicines ◽

World Health ◽

European Medicines Agency ◽

Drug Products ◽

United States Food ◽

Age Appropriate ◽

States Food ◽

Health Organization ◽

Medicines For Children

Lack of age-appropriate commercially drug products availability is a common problem in pediatric therapeutics; this population needs improved and safer drug delivery. In addition, biopharmaceutic aspects, dosage requirements, and swallowing abilities demand pediatric forms different to adult formulations. The objective of this study was to evaluate the authorization availability from United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) of oral essential medicines for children and analyze its age-appropriateness for oral administration in children. All oral drugs from 7th List of Essential Medicines for Children by World Health Organization (WHO) were selected. Availability of commercial drug products was collected from OrangeBook, Spanish drug product catalogue, British electronic Medicines Compendium, and the International Vademecum. Tablets, effervescent tablets, and capsules were considered as not age-appropriate forms. Liquid forms, powder for oral suspension, mini tablets, granules, and soluble films were considered as age-appropriate forms due to their flexibility. More than 80% of the studied drugs possess a commercial authorization in oral forms in both EMA and FDA. Nevertheless, around 50% of these formulations are not age-appropriate for most pediatric groups. This study shows the lack of age-appropriate medicines for children. More efforts are needed to improve development and approval of pediatric medicines.

Download Full-text

IMPACT OF ACTIVE PHARMACEUTICAL INGREDIENT (API) SCARCITY IN PHARMACEUTICAL SECTORS AMIDST COVID-19 PANDEMIC

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2020v12i12.39396 ◽

2020 ◽

pp. 22-25

Author(s):

ARPAN SAHA ◽

SANTANU MALLIK

Keyword(s):

Pharmaceutical Industry ◽

Generic Drugs ◽

Low Cost ◽

Active Pharmaceutical Ingredient ◽

World Health ◽

United States Food ◽

Pharmaceutical Industries ◽

Novel Coronavirus ◽

Health Organization ◽

Indian Pharmaceutical Industry

The novel coronavirus disease 2019 (COVID-19) was characterized as a global pandemic by the World Health Organization (WHO) on March 11, 2020. The present pandemic has caused an intolerable impact on the health structure as well as the pharmaceutical sector, which in ultimatum has created enormous issues in the everyday lives of the patient community. On the other hand, the situation may appear in short and long-term time-horizon and need identification along with appropriate planning to reduce their socio-economic burden. The Indian pharmaceutical industry is the world's third-largest drug producer by volume. India supplies affordable and low-cost generic drugs to millions of people around the globe and operates more than 250 United States Food and Drug Administration (USFDA) and United Kingdom Medicine and Healthcare products Regulatory Agency (UKMHRA) approved plants. Given the Indian pharmaceutical industry, the source of Active Pharmaceutical Ingredients (APIs) for multiple diseases is much crucial part of the Pharma industry’s strategic plan to combat the COVID-19 pandemic. China is the top global producer and exporter of APIs by volume and Indian pharmaceutical industries are also rely heavily on APIs from China for the production of their medicine formulations by importing around 70 percent of the total requirement. However, the present pandemic situation has exposed the world's over-reliance on China in terms of API import and bound world leaders to fig. out sustainable alternatives.

Download Full-text

Partnerships in Health Development

Journal of Health Management ◽

10.1177/0972063421995007 ◽

2021 ◽

Vol 23 (1) ◽

pp. 143-154

Author(s):

Palitha Abeykoon

Keyword(s):

Technical Assistance ◽

Communicable Disease ◽

Moral Rights ◽

World Health ◽

Service Access ◽

Health Coverage ◽

Health Development ◽

The Sustainable Development ◽

Provision Of Services ◽

Health Organization

The COVID-19 pandemic has thrown into bold relief the need for an all-of-society response supported by regional and global partnerships to control the epidemic. Addressing the social determinants of health, Universal Health Coverage, the non-communicable disease (NCD) burden, the other communicable diseases and the achievement of the Sustainable Development Goals (SDGs) all would require a close collaboration among different sectors and stakeholders, including the private sector. Partnerships connote three fundamental themes—a relative equality between the partners, mutual commitment to agreed objectives and mutual benefit for the stakeholders involved. The decisions are made jointly, and roles are not only respected but are also backed by legal and moral rights. The World Health Organization (WHO) has been and continues to be the foremost promoter as well as the host for many of the global and regional partnerships in health. A typological classification would include technical assistance partnerships supporting service access and provision of services including drugs, partnerships focusing on research and development, advocacy and resource mobilisation and financing partnerships mainly to provide funds for definite disease programmes. Partnerships in health have brought and continue to bring multiple benefits to the countries. But they also engender several challenges, including the duplication of effort and waste, high transaction costs (usually to government), issues of accountability and consequent lack of alignment with country priorities. As partnerships become increasingly significant in the twenty-first century, better coordination, particularly in terms of donor harmonisation with national priorities, would be needed. It is not ambitious to attempt the elusive ideal where all parties will benefit from one other with a give and take between all stakeholders. Partnerships in health could well herald a new dawn for health development in the South-East Asia Region.

Download Full-text

New Insights into the Pathogenesis of Systemic Mastocytosis

International Journal of Molecular Sciences ◽

10.3390/ijms22094900 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4900

Author(s):

Zhixiong Li

Keyword(s):

Molecular Mechanisms ◽

Kinase Inhibitor ◽

Systemic Mastocytosis ◽

Treatment Strategies ◽

The United States ◽

European Medicines Agency ◽

Myeloid Neoplasm ◽

Organ Systems ◽

United States Food ◽

Kit D816v

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management of SM is highly individualized and was largely palliative for patients without a targeted form of therapy in past decades. Targeted therapy with midostaurin, a multiple kinase inhibitor that inhibits KIT, has demonstrated efficacy in patients with advanced SM. This led to the recent approval of midostaurin by the United States Food and Drug Administration and European Medicines Agency. However, the overall survival of patients treated with midostaurin remains unsatisfactory. The identification of genetic and epigenetic alterations and understanding their interactions and the molecular mechanisms involved in mastocytosis is necessary to develop rationally targeted therapeutic strategies. This review briefly summarizes recent developments in the understanding of SM pathogenesis and potential treatment strategies for patients with SM.

Download Full-text

Extracranial metastases in secondary glioblastoma multiforme: a case report

BMC Neurology ◽

10.1186/s12883-020-01959-y ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Jessica Rossi ◽

Lucia Giaccherini ◽

Francesco Cavallieri ◽

Manuela Napoli ◽

Claudio Moratti ◽

...

Keyword(s):

Brain Lesion ◽

Rare Event ◽

Subsequent Development ◽

World Health ◽

Who Grade ◽

Systemic Involvement ◽

Grade Ii ◽

The Stability ◽

Health Organization ◽

Extracranial Metastases

Abstract Background Glioblastoma (GBM) is known for its devastating intracranial infiltration and its unfavorable prognosis, while extracranial involvement is a very rare event, more commonly attributed to IDH wild-type (primary) GBM evolution. Case presentation We present a case of a young woman with a World Health Organization (WHO) grade II Astrocytoma evolved to WHO grade IV IDH mutant glioblastoma, with subsequent development of lymphatic and bone metastases, despite the favorable biomolecular pattern and the stability of the primary brain lesion. Conclusions Our case highlights that grade II Astrocytoma may evolve to a GBM and rarely lead to a secondary metastatic diffusion, which can progress quite rapidly; any symptoms referable to a possible systemic involvement should be carefully investigated.

Download Full-text

The International Transfer of Medical Technology—An Analysis and a Proposal for Effective Monitoring

International Journal of Health Services ◽

10.2190/w5nm-m358-5m6l-4v3t ◽

1977 ◽

Vol 7 (3) ◽

pp. 443-458 ◽

Cited By ~ 11

Author(s):

Michael B. Bader

Keyword(s):

Technology Transfer ◽

Foreign Aid ◽

Medical Technology ◽

Technical Assistance ◽

Code Of Conduct ◽

World Health ◽

Health Technologies ◽

Four Levels ◽

Aid Programs ◽

Health Organization

The international transfer of medical technology to the developing countries occurs at four levels-medical education, research, and missions; multinational corporate transactions; technical assistance projects sponsored by the World Health Organization; and bilateral foreign aid programs. In this article, a proposal is made for effective monitoring of international medical technology transfer through political and legal means, including a specific code of conduct for corporations engaged in medical technology transfer. The development of “intermediate health technologies” along the lines suggested by E. F. Schumacher, and the advantages of such an innovation in terms of population issues and economic development are also discussed.

Download Full-text