FDA Activities Research Articles

Factors influencing participation of tribes in the activities of forest development agencies in Tamil Nadu

In Tamil Nadu, there were 32 Forest Development Agencies were functioning in 12 Forest Circles. Coimbatore forest circle is the one in which three FDAs were established and this formed the study area. The study was carried out in Coimbatore Forest Circle following a Multi Stage Random Sampling technique by selecting three hundred tribal households. FDAs were implementing several activities with the participation of tribes to avert man-animal conflicts and to improve the socio economic status of tribes. This study was focusing on documenting the activities and the participation of tribes in those activities. Among the activities, erection of Elephant trenches, plantation development and the Project Elephant schemes implemented by both Forest and Line Department officials have imparted some impacts in reducing the Man-Animal Conflicts by promoting higher employment generation. Because of higher employment opportunities, the participation of tribes were much influenced in FDA activities which are statistically significant at one per cent level. Besides, impact of FDA implementation, Plantation development activities and wild life protection measures are also discussed.

New Drugs Regulatory Program Modernization: Vision, Strategic Objectives, and Impact.

In response to a rapid increase in drug development activity during the past two decades, the Food and Drug Administration’s Center for Drug Evaluation and Research launched a multi-year effort in 2017 to modernize the program by which new drug products are regulated, known as the New Drugs Regulatory Program. Following a detailed analysis of FDA activities in new drug development, premarket review, and postmarket monitoring, the Office of New Drugs was restructured to therapeutically align its clinical offices and to add new cross-functional offices for regulatory support. An interdisciplinary review process for new drug and biologics applications was rolled out to reduce redundancy and produce review documents that effectively communicate the scientific basis for the regulatory decision. The investigational new drug (IND) review process was also streamlined. During the next 2 years, the modernization initiative will seek to attract and retain new scientific and regulatory staff, improve postmarket safety monitoring, increase efficiency of drug review via technology-enabled workflows, and standardize the capture and use of scientific data to inform future regulatory decisions. The modernization effort will position the New Drugs Regulatory Program to continually improve and adapt to innovations in science, technology, and drug development.

Microbial Biomass and Enzyme Activity of Soil Under Clonal Rubber Tree Plantations

Abstract Our study aimed to evaluate the influence of rubber tree plantations (Clones IAN 873 and FX 3864) on microbial activity, total organic carbon (TOC), and soils chemical attributes, using as reference pasture and secondary forest, in Rio de Janeiro. The plantations areas showed pH; Mg2+, Ca2+, K+ levels; sum of bases; base saturation, basal respiration; metabolic quotient; and arylsulfatase and FDA activities in the soil similar to or greater than the values found in the forest. In contrast, showed lower P and TOC levels; carbon and nitrogen in the microbial biomass; and β-glucosidase activity than of forest and pasture. Higher acid phosphatase and laccase enzymes activities was observed in the forest and plantations than in the pasture. Thus, we verified that the rubber tree plantations (Clones: IAN 873; FX 3864) maintain or improve the quality of some chemical and microbiological attributes of the soil regarding secondary forest and pasture.

Are raw materials or composting conditions and time that most influence the maturity and/or quality of composts? Comparison of obtained composts on soil properties

Abstract Waste composting is a process which is spreading worldwide to reduce waste disposal in landfill. The composting technical currents give little attention to the type and chemical composition of biomass that are mixed not considering that these can affect quality and maturity of the compost produced. In addition, during the composting process the amount of oxygen and temperature are generally only monitored but not set up. Our hypothesis is that composts, prepared from different organic wastes, can be chemically different with consequent different fertilizer properties. Stability and quality of composts are dependent on multivariate parameters such as raw material source, proportions used, composting procedure, and maturation time. Starting from this consideration a composting experiment was carried out to evaluate if were the raw materials (chemical composition, mixture and ratio), or the composting conditions and time, to influence the maturity or the quality of composts. We prepared four composts starting from different combinations and ratios of vegetable residues and/or olive pomace. After 120 days, the four composts were physically, chemically and biologically characterized to evaluate maturity degree, stability and quality of the products obtained under the same composting conditions and time. Their ability, as soil improver, was evaluated assessing soil chemical and biochemical properties 90 days after the compost addition. Here we show that the chemical composition of raw materials and the set up parameters of composting processes can have a different weight in influencing compost stability and quality. Our results evidenced that during the composting process all the composts had a similar percentage of C/N ratio reduction and all of them achieved an acceptable maturity degree. The composts produced by olive pomace showed the highest degree of maturity as demonstrated by T value and organic matter loss, both indices of compost stability. Conversely the composts coming from green vegetable residues were richest in nutrients and phenols and had the highest CSC all indices of better quality. In this work we identified two composts able to increase carbon stock, and water holding capacity parameters that positively influence soil structure, and two compost able to increase the amount of soil microbial biomass, their activity and soil biodiversity, improving soil biological fertility. These results highlighted that compost maturity doesn't mean compost quality, suggesting that compost maturity is mainly linked to composting setup parameters, while compost quality is mainly linked to chemical composition. FDA and DHA activities have been identified as markers for assessing the quality of amended soils.

Aggregate-associated N and global warming potential of conservation agriculture-based cropping of maize-wheat system in the north-western Indo-Gangetic Plains

Despite conservation agriculture (CA) is being promoted as a climate resilient technology, limited information is available on its impacts on N storage within soil aggregates vis a vis global warming potential (GWP) under tropical agro-ecosystems. Hence, this study assessed the effects of a medium-term (5-years) CA on total soil N (TSN) changes in bulk soils and aggregates, N2O and CO2emission, GWP and total C fixed in soils under maize (Zea mays L.)- wheat (Triticum aestivum L.) system on the Indo-Gangetic Plains (IGP). The treatments were: conventional tillage (CT), zero tillage (ZT) with planting on permanent narrow beds (PNB), PNB with residue (PNB + R), ZT with planting on permanent broad beds (PBB), PBB with residue (PBB + R), ZT on flat land/plains without crop residue (ZT) and with crop residue retention (ZR + R). Soil samples were collected after five years of a maize–wheat system and TSN in bulk soils and their aggregates of the 0–5 and 5–15 cm soil layers were measured along with N2O and CO2 emissions during the fifth year (2014–15).The soils under PBB + Rhad 37 and 9% more macro-aggregate-and micro-aggregate-associated N concentrations in topsoil (0–5 cm layer) than CT (248 and 299 kg N ha−1). However, topsoil soil aggregation and aggregate-associated N contents of PNB + R and ZT + R were similar to CT plots. The dehydrogenase and fluorescein diacetate activities and TSN, microbial biomass N, NO3-N and NH4-N concentrations were also highest in PBB + R plots in topsoil. The topsoil dehydrogenase activity was significantly correlated (r = 0.426, n = 21, p < 0.05) with CO2emission and with N2O emission (r = 0.770, n = 21, P < 0.01) during wheat (2014–15). However, topsoil FDA activities and MBN concentrations were only significantly correlated with N2O emission in wheat. In the maize–wheat system, highest N2O emission was observed in PNB + R plots and least in CT plots. But, PBB + R and PNB + R plots had similar CO2 emissions to CT plots in both crops. Despite GWP of ZT + R and PBB + R plots in the maize-wheat system were ∼5% higher than CT, greenhouse gas (GHG) intensities in the CT, PBB + R and ZT + R plots were similar. Thus, PBB + R practice is a better management alternative for soil N improvement (and a reduced fertilizer N dose could be adopted in future) than CT since this practice also had 36% and 8.2% higher biomass productivities of maize and wheat, respectively in the maize-wheat cropping system and similar GHG intensity to CT plots.

Transparency at the U.S. Food and Drug Administration

Given the profound public health and economic ramifications of decisions made by the U.S. Food and Drug Administration, the degree to which FDA activities should reflect an approach founded on complete transparency versus one focused on preserving confidentiality of information deserves public discussion. On one hand, reasonable requirements for transparency are critical to stimulating effective innovation, knowledge dissemination, and good business practice. On the other, ensuring the vitality of the medical products industry requires protecting legitimately proprietary information. With current standards reflecting a lengthy accumulation of legal, regulatory, and practical precedent, recent significant changes in the environment in which the FDA operates should prompt a critical examination of current practices. In this article, I comment on Sharfstein and colleagues’ “Blueprint for Transparency,” which calls for multiple specific actions to increase transparency at the agency across five key areas, including interactions between FDA and industry, public disclosure of internal FDA analyses, deliberations concerning generics and biosimilars, expanded access to raw study data, and approaches to countering misleading information in the public sphere. I evaluate these recommendations in light of my experience as a clinician, researcher, and former FDA Commissioner, and reflect on possible outcomes that could result from enacting these practices.

Phytoremediation effect of Scirpus triqueter inoculated plant-growth-promoting bacteria (PGPB) on different fractions of pyrene and Ni in co-contaminated soils

At present, few reveal the mechanism of inoculation plants with PGPB to remediate PAH-metal co-contaminated soil by analyzing the chemical speciations of contaminants. This study investigated the influence of inoculation plants with PGPB on different fractions of pyrene and Ni in rhizospheric and non-rhizospheric soil. The results demonstrated that the addition of PGPB brought the extensive increase of FDA activities in pyrene-Ni co-contaminated soil. PGPB increased the resistance of plants in nickel and pyrene-Ni contaminated soil, but decreased the plant biomass in single pyrene contaminated soil. The addition of PGPB efficiently decreased bioaccessible fractions of pyrene and increased the bioavailability of Ni in both rhizospheric and non-rhizospheric soil. Although inoculation plants with PGPB significantly increased the accumulation of Ni in single Ni and pyrene-Ni co-contaminated soil, the poor bioavailability of Ni in rhizospheric soil still restricted the phytoremediation of the heavy metal. The presence of pyrene hindered the inoculated plant from accumulating Ni to some extent. On the contrary, the presence of Ni significantly promoted the degradation of pyrene in both rhizospheric and non-rhizospheric soil after inoculation plants with PGPB.

McNeil, Ft. Washington: FDA Case Study

FOOD AND DRUG ADMINISTRATION CASE STUDY The FDA is the supervisory agency that provides oversight and guidance to the bio-pharmaceutical (BP) industry. It safeguards the public by ensuring that BP products are safe, effective, and manufactured in accordance with current Good Manufacturing Practice (U. S. Food and Drug Administration, 2004a). This paper provides a case study of McNeil Consumer Healthcare and its main manufacturing facility at Ft. Washington, Pennsylvania, from 2000 to 2011. Over this 12-year period, the case study details FDA activities at this site. This includes plant inspections, Form 483 observational reports (483), and warning letters (WLs), as well as recalls and plant closures. While it would be premature to extrapolate from one case study to overall FDA performance, it is fair to say that certain insights can be gained concerning procedures, performance, oversight, and governance. Similarly, these findings about FDA performance provide an opportunity to review how its newly adopted risk methodology and quality assurance practices are incorporated into its oversight practices. To put this case study into appropriate perspective, the findings were compared with other research that focuses on more quantitative studies of FDA performance using sector-wide data. The two principal academic investigations of FDA and quality assurance (QA) that we are aware of are Adis' risk studies (2007; 2008), and Marcher and Nickerson's (2006) review of quality systems. Both were sector evaluations, rather than a case study. The McNeil Ft. Washington facility is noteworthy in that it posed significant compliance challenges to the FDA during the 12-year period. There were several FDA Field Alerts about failed manufacturing processes and several large scale recalls of such popular product as Motrin, Tylenol, and Listerine. The problems at this site have caused the FDA to take the unusual step of making available the Establishment Inspection Reports (EIRs) for this facility. With these reports, one can track FDA interactions with the Ft. Washington site and review FDA oversight and plant compliance (Betterchem, 2008). In other words, the researcher has an insider's picture of quality assurance and risk prevention activities at Ft. Washington. The FDA rarely makes EIRs available because it respects manufacturers' concerns about releasing proprietary and confidential information. In addition, part of its mandate is to provide guidance, so a non-adversarial environment is preferred. Therefore findings from EIR plant inspections are regularly withheld, even from the provisions of the Freedom of Information Act (U. S. Food and Drug Administration, 2008a). But in this instance, due to the seriousness of the infractions at the McNeil site, the FDA has released the 12-year history of inspections and oversight. Though this material has been heavily redacted to maintain confidentiality, it is still a valuable resource. Furthermore, due to the extent and flagrance of the violations, there are additional public documents: a consent Decree to close the Ft. Washington plant, transcripts of the FDA testimony at congressional hearings about McNeil's recalls, and public statements from McNeil's management and their parent company Johnson and Johnson. These were helpful in piecing together the activities of the principals, during this time period of 7 major recalls. The Center for Drug Evaluation Research (U. S. Food and Drug Administration, Center for Drug Evaluation and Research, 2007) is the FDA agency directly responsible for the Finished Pharmaceuticals sector that includes over-the-counter drugs. It has thousands of employees and performs hundreds of inspections per year. Consequently, this case study review can be only a very narrow investigation into its quality assurance activities. By reviewing the data in this case study, the research is establishing some anecdotal evidence about CDER performance and its use of quality assurance techniques. …

Performance Measures for Cardiology Focus on Improving Patient Outcomes

M. Schwartz, MD, MS, of Dartmouth Medical School in Hanover, NH, have noted that while the FDA has been criticized for being too close to industry, its reviews are a unique source of published and unpublished data about drug performance (a search page for FDA reviews of drugs is available at http://www .accessdata.fda.gov/scripts/cder /drugsatfda/index.cfm), and readers can learn of the reviewers’ opinions of the drugs they evaluated (Woloshin S and Schwartz LM. Arch Intern Med. 2009; 169[21]:1985-1987). However, they also noted that the FDA should make its reviewers’ knowledge more accessible through standardized executive summaries of drug reviews. Other critics point out that the FDA does not make available unpublished clinical trial data that are not discussed at advisory committee meetings. “The FDA is now somewhat more transparent, but it’s not transparent enough,” said Steven Nissen, MD, chair of the department of cardiovascular medicine at the Cleveland Clinic. “For reasons I can’t understand, it still keeps information secret,” he added. The FDA recently formed an internal Transparency Task Force to develop recommendations for making information about FDA activities and decision making more readily available while protecting confidential information (http: //tinyurl.com/3mazd5q). According to Avorn, this initiative focuses primarily on access to reports of adverse events that are spontaneously provided by physicians and patients after a drug has been approved. “Of greater concern are adverse events identified by drug companies during the clinical trials that they conduct,” he said. “This is more relevant information, but it is also where company ownership of data often comes into conflict with the public’s right to know, and the public often loses that battle.”

Increasing Transparency at the FDA: The Impact of the FDA Amendments Act of 2007

On September 27, 2007, the Food and Drug Admin istration Amendments Act (FDAAA)1 was signed into law. Containing 11 titles, the legislation addresses a wide variety of legal and scientific issues facing the FDA currently and in the future. At the same time, the primary purpose of the law, and the speed with which it moved through the 110th Congress, was to reauthorize major mechanisms by which FDA activities are financed, with new provisions on product safety. In addition, the legislation addresses the manner in which the FDA carries out its core agency functions of expert consultation, scientific publication, and diffu sion of scientific information. This installment of Law and the Public's Health examines those provisions of the Act that focus on the approval decision-making process and financial conflicts of interest (COIs), increased access to data flowing from clinical studies, and publication of scien tific research by FDA scientists.

Influence of gap size on organic matter decomposition, microbial biomass and nutrient cycle in Calabrian pine ( Pinus laricio, Poiret) stands

The present study aimed to examine the impacts of small (380 m 2), medium (855 m 2) and large (1520 m 2) gaps on microclimate, soil properties and microbial biomass, a ‘sink’ and ‘source’ of plants nutrients, in Pinus nigra ( Pinus laricio Poiret) stands in Calabrian Apennine Southern Italy. PAR transmittance significantly increased with increasing size of the gaps, consequently an effect of gaps size was found on microclimate: soil moisture and temperature were different among the gaps of different size showing the highest values of temperature in the large gaps and the highest values of moisture in the small gaps. Within small gaps the greatest amount of organic matter, humic matter and microbial biomass, and the highest C/N value were observed. The highest values of phosphatases, urease and FDA activities were detected in small gaps. An impact of gap size on C, N and P cycles was significant in small gaps in terms of higher availability of these nutrients and greater amount of humic matter, suggesting that small gaps may be important from an ecosystem perspective representing the appropriate management procedures for an adequate conservation of ecological functions, capable to preserve soil properties and favour Pinus laricio natural regeneration.

Current Status of Carcinogenicity Assessment of Peroxisome Proliferator-Activated Receptor Agonists by the US FDA and a Mode-of-Action Approach to the Carcinogenic Potential

Since it has been revealed that PPAR (Peroxisome Proliferator-Activated Receptor) agonists induce various types of tumors in various organs and tissues in rodents, the US FDA has been requesting performance of 2-year carcinogenicity studies prior to initiation of clinical studies longer than 6 months, and does not accept data from alternative carcinogenicity studies such as those in transgenic mouse models, which are recommended in the ICH S1B guideline. In general, although PPAR agonists do not possess genotoxic potential, the tissue distribution of PPAR does correspond to the target organs and tissues of tumor induction, and carcinogenic potential is closely correlated with potency of PPAR agonistic effect. It is thus not possible to rule out the possibility that the mode of action (MOA) of tumorigenesis by PPAR agonists is receptor- mediated. The ILSI-HESI PPAR Agonist Project was organized and is currently conducting collaborative research to elucidate the MOA of PPAR agonist-induced carcinogenicity (for urinary bladder tumor, hemangioma/hemangiosarcoma, and fibrosarcoma/liposarcoma) and to evaluate the human relevance of the results of rodent bioassays of PPAR agonists. In this paper, carcinogenicity data on PPAR agonists disclosed by the CDER of the US FDA and current activities of the ILSI-HESI PPAR Agonist Project are explained, and the possible usefulness of transgenic mouse models, especially rasH2 mice, for assessing carcinogenic potential and the MOA of PPAR agonists are addressed.

FDA CBER（生物医薬品局）の法規適合性活動と査察について

FDA CBER（生物医薬品局）の法規適合性活動と査察について

最近の FDA の動向分析およびシステム査察にみる米国製薬企業の問題領域

最近の FDA の動向分析およびシステム査察にみる米国製薬企業の問題領域

Complementarity of bioassays and microbial activity measurements for the evaluation of hydrocarbon-contaminated soils quality

In order to describe a soil polluted with hydrocarbons, the complementarity of bioassays and microbial activities measurements was studied. The samples of soil were taken from a site which had received oil tank residues over 50 years. Five zones were sampled. Each sample was characterized by chemical analyses, the measurement of dehydrogenase, phosphatase, hydrolysis of FDA and urease activities, soil respiration, and Microtox and Metplate bioassays. The chemical analyses revealed different levels of total hydrocarbon concentrations (from 1.5 to 78.8mg/kg of dry soil) but also relatively high quantities of nickel (from 14.5 to 841.6mg/kg of dry soil) and lead (30.9–355.4mg/kg of dry soil) or cadmium (0–1.2mg/kg of dry soil) in the different zones. Urease and dehydrogenase were sensitive to the presence of metals (31% inhibition of urease and 50% inhibition of dehydrogenase in the most contaminated soil). Measurements of Substrate Induced Respiration showed that the soil microflora were stressed in the presence of the pollutants. In the zone containing the highest concentration of metals, the microbial activities were low and the bioassays revealed a high potential toxicity (e.g. IC50 for Microtox obtained with a 15% dilution of soil, 90% inhibition of β-galactosidase activity). In the other zones, the soil microbial activities were not depressed in comparison to the reference zone whereas the bioassays revealed the presence of toxic compounds extracted with the solvent used.

The development of the E. Stanley Crawford Critical Issues Forum

The development of the E. Stanley Crawford Critical Issues Forum

Quantifying the benefits of automation

Process automation, CIM and paperless manufacturing are operational strategies being developed to support the changing business strategies in pharmaceuticals. Present FDA activities appear to make automation an attainable GMP regulatory reality. Operations are being required to provide greater benefits in the form of efficiencies, manpower rationalization, and productivity gains in order to justify new CIM and automation projects. This paper describes where benefits have been identified and quantified in operational environments.

Foodservice Sanitation Training and Reciprocity in the 80s

This is a review of FDA activities during the 1970s in development and implementation of foodservice manager sanitation training/certification programs. A number of these programs have resulted in reciprocal recognition by regulatory agencies in the United States. Suggested steps to be taken in the 80s to continue this trend are discussed. FDA encourages establishment of uniform manager training programs which meet the national criteria and result in reciprocal agreements. A vital component of any effective foodservice program is sanitation training. If it is provided, an additional step has been taken to protect the food the consumer receives.

Device standards: the view from the FDA.

This paper constitutes an overview of FDA's functions and activities, offering a brief introduction to the Medical Device Amendments, and performance standard requirements from FDA's point of view. It discusses the agency's voluntary standards policy and the required conditions for deferral of mandatory standards. This paper also describes the Medical Device Standards Survey, and the role of the clinical engineer in standards development. It lists new Problem Definition Studies of the Bureau of Medical Devices which represent the first step in the new standards development process.