Review on 505(b)(2) Drug Products Approved by USFDA from 2010 to 2020 Emphasizing Intellectual Property and Regulatory Considerations for Reformulations and New Combinations.

Repurposing is considered an attractive approach for developing new drug products. However, it consists of challenges relating to intellectual property (IP) protection, and regulatory approvals. This study aimed to analyze the recent trends in repurposed drugs approved by USFDA from 2010 to 2020 and to assess the challenges connected with bridging study requirements, patent protection, and exclusivities. Out of 1001 NDAs, 570 were approved via 505(b)(2) pathway. Of 570 NDAs, the highest number of approvals are allied to type 5-new formulations (42.4%), followed by type 3-new dosage forms (26.4%) and type 4-new combinations (13.1%). Of 570 NDAs, 470 are considered to examine the patent and exclusivity protection of which 341 have patent and/or exclusivity. A total of 97 type-3 and type-5 and 14 type-4 drugs have been approved based on human bioavailability/bioequivalence (BA/BE) data. For 131 type-3 and type-5 and 34 type-4 drugs, the applicants conducted new clinical (efficacy and/or safety) studies along with BA/BE (100 drugs) or without BA/BE (65 drugs) studies. In this review, mechanistic reasons for conducting new clinical investigations, IP and regulatory considerations along with broader perspective on new pharmaceutical approaches employed in 505(b)(2) drugs are illustrated that provide guidance for development of reformulations and combinations.

Identifying dispensing errors in pharmacies in a medical science school in Trinidad and Tobago.

BACKGROUND: A dispensing error can be defined as an inconsistency between the drug prescribed and drug dispensed to a patient. These errors can lead to ineffective and sometimes unwanted pharmaceutical outcomes. Dispensing errors can be harmful or even fatal to patients. CASE PRESENTATION: The objective to this study was (a) to determine the types and frequency of dispensing errors at the Eric Williams Medical Sciences Complex (EWMSC), (b) to explore the reasons for the occurrence of dispensing errors, and (c) to make suitable recommendations for their prevention. An observational study for a period of 2 weeks was carried out at various in- and outpatient departments of the EWMSC. The observations were carried out during 7:00 am to 3:00 pm. Dispensing errors identified during this period were recorded and analyzed. RESULTS: Sixty-eight errors were identified in the adult outpatient pharmacy of the EWMSC; 19 errors in the pediatric outpatient pharmacy, whereas 22 errors were found in inpatient pharmacy. The most common plausible causes for the dispensing errors include high workload, failure to verify patient information, incorrect data in the pharmacy's record system, inadequate notes made by pharmacists during prior patient visit, and in a few cases, uncomfortable working conditions. CONCLUSION: Dispensing errors were encountered in 2.1% of all the prescriptions filled at the EWMSC pharmacies. The factors which influenced these dispensing errors include but are not limited to a heavy workload, distractions, failure to verify patient information, and uncomfortable working conditions.

Analysis of FDA Warning Letters Issued to Indian Pharmaceutical and Medical Device Companies: A Retrospective Study.

BACKGROUND: FDA issues warning letters to pharmaceutical manufacturers, distributors, or clinical investigators if it observes serious violations of federal regulations. These warning letters contain the details about the nature of the violations observed and the corrective actions recommended by the FDA. A follow-up inspection may be requested by the recipient after taking the corrective actions. METHODS: Analysis of warning letters issued to Indian pharmaceutical companies from January 1, 2005, to December 31, 2018, was carried out. The warning letters were extracted from FDA's public database. RESULTS: Across the 14-year study period, the number of warning letters issued to Indian pharmaceutical and medical device manufacturers has gradually increased. Of all the violations listed in these warning letters, 85.87% were related to the failure of compliance with the cGMP guidelines. Moreover, 80.72% of these warning letters were not followed by a close-out warning, which indicated that the violations listed in these warning letters could not be resolved. CONCLUSION: As the inability of the recipients to comply with the cGMP guidelines formed the majority of the violations observed in the warning letters, more resources and manpower have to be assigned to the manufacturing process of the pharmaceutical products.

Analysis of FDA Warning Letters Issued to Indian Pharmaceutical and Medical Device Companies: A Retrospective Study.

BACKGROUND: FDA issues warning letters to pharmaceutical manufacturers, distributors, or clinical investigators if it observes serious violations of federal regulations. These warning letters contain the details about the nature of the violations observed and the corrective actions recommended by the FDA. A follow-up inspection may be requested by the recipient after taking the corrective actions. METHODS: Analysis of warning letters issued to Indian pharmaceutical companies from January 1, 2005, to December 31, 2018, was carried out. The warning letters were extracted from FDA's public database. RESULTS: Across the 14-year study period, the number of warning letters issued to Indian pharmaceutical and medical device manufacturers has gradually increased. Of all the violations listed in these warning letters, 85.87% were related to the failure of compliance with the cGMP guidelines. Moreover, 80.72% of these warning letters were not followed by a close-out warning, which indicated that the violations listed in these warning letters could not be resolved. CONCLUSION: As the inability of the recipients to comply with the cGMP guidelines formed the majority of the violations observed in the warning letters, more resources and manpower have to be assigned to the manufacturing process of the pharmaceutical products.

Informed consent: Issues and challenges.

Informed consent is an ethical and legal requirement for research involving human participants. It is the process where a participant is informed about all aspects of the trial, which are important for the participant to make a decision and after studying all aspects of the trial the participant voluntarily confirms his or her willingness to participate in a particular clinical trial and significance of the research for advancement of medical knowledge and social welfare. The concept of informed consent is embedded in the principles of Nuremberg Code, The Declaration of Helsinki and The Belmont Report. Informed consent is an inevitable requirement prior to every research involving human being as subjects for study. Obtaining consent involves informing the subject about his or her rights, the purpose of the study, procedures to be undertaken, potential risks and benefits of participation, expected duration of study, extent of confidentiality of personal identification and demographic data, so that the participation of subjects in the study is entirely voluntary. This article provides an overview of issues in informed consent: The obligations of investigator, sponsor and Institutional Review Board to protect rights and welfare of human research subjects. It discusses about the basic elements of informed consent and the process to be followed while obtaining informed consent. Some of the circumstances under which informed consent can be waived and ethical challenges faced by physicians in obtaining informed consent from subjects are also highlighted in this article.

Medical device vigilance systems: India, US, UK, and Australia.

The term medical device includes a wide category of products ranging from therapeutic medical devices exerting their effects locally such as tissue cutting, wound covering or propping open clogged arteries, to highly sophisticated computerized medical equipment and diagnostic medical devices. To achieve uniformity among the national medical device regulatory systems and increase the access to safe, effective, and clinically beneficial medical technologies, the Global Harmonization Task Force (GHTF) was conceived in 1992 by five members: European Union, United States, Australia, Japan, and Canada. All regulated countries have clearly defined medical devices, as has the GHTF. Although GHTF has tried to achieve harmonization with respect to medical devices, some differences still exist in the national laws of the countries of GHTF. Further, regulated countries have classified medical devices on the basis of their associated risk. In the Indian regulatory system, medical devices are still considered as drugs. In 2006, the Medical Device Regulation Bill was recommended to consolidate laws for medical devices and to establish the Medical Device Regulatory Authority of India. In addition, medical devices are not classified by any Indian regulatory authority. Although India has moved towards harmonizing its medical device regulations with those of regulated countries, this study aims to identify whether India should have a vigilance system in harmony with those of GHTF or develop its own system for medical devices.