Applied Clinical Research, Clinical Trials and Regulatory Affairs - Volume 7, Issue 2, 2020

United States Food and Drug Administration (USFDA) is a federal agency functioning under United States Federal Executive Departments, which strives to regulate the food products and drug substances being manufactured or brought into US market, upholding Quality and Safety as prime goals. It takes care of its goals by inspecting firms which market products in the United States. It chalks out good manufacturing procedures for obtaining quality end-products. Based on inspections conducted and data collected thereby, those not abiding by rules shall be issued with Warning Letters and marketing license shall be cancelled for those who fail to justify the warning letter. This brings about discipline amongst manufacturers and sets a goal of quality that needs to be achieved to survive in market.

The pharmaceutical industry is developed every year with the aim of public health, safety, and financial growth. Keeping public safety in mind, the industry is mostly concentrated on novel plans in the drug development process and plans on how to increase the curing rate of a disorder and building up the accuracy in patient care. The increase in the number of diseases has led to the generic and branded drug competition by which the pressure on the market has increased. The pharmaceutical manufacturers are attempting to find the needs of patients in different ways. The industries were manufacturing the drugs in unique ways which help to increase their productivity and also to increase the patient experience. Due to this, all pharmaceutical manufacturers are trying to manufacture drugs using 3D printing. In 2015, the industries succeeded by manufacturing the drug Spritam using 3D printing and it was the first prescribed drug manufactured by using 3D printing (3DP). 3DP is the process of depositing powder in a layer upon layer that was opposite to subtractive manufacturing and it is perfect for pharmaceuticals because it provides enhanced accuracy in the development and formulation of dosage forms. The 3DP has different advantages to companies and patients like an increase in dissolution rate, absorption, adherence, efficacy, and long life of branded drugs along with the decrease in pill burden. This process leads to a break in the manufacturing method of drugs but helps to overcome several problems and also helps in better patient outcomes in the solid dose markets.

Over the years, a number of dietary supplements and health foods are being utilized and are available at pharmacy stores. These medicinally or nutritionally functional foods are considered as ‘Nutraceuticals’. The term was defined in 1989 by Stephen De Felice, founder and chairman of the Foundation for Innovation in Medicine, an American organization which encourages medical health research. He defined a nutraceutical as a “food, or parts of a food, that provide medical or health benefits, including the prevention and treatment of disease”. As these substances are neither be considered as drug or as food, the risk of toxicity and safety should be considered for better health management which requires the research and safety evaluation of Nutraceuticals as per the regulations. Therefore, the aim of the present work is to review regulatory prospects of these Nutraceutical products in ASEAN countries.

The product registration in the rest of the World is a challenging task because the regions under it are not harmonized. CIS and Latin American regions come under semi-regulated market. These regions have somewhat harmonized their regulatory organization. The significance of an emerging market is increasing globally. It is important for pharmaceutical companies to be up-to-date with the latest regulatory development. Both the regions follow their regional checklist for Drug Product Registration. Latin America includes a group of countries like Brazil, Guatemala and Peru etc, whereas CIS includes Russia, Ukraine, Uzbekistan, Armenia and Tajikistan etc.

According to “Medical Device Rules-2017” (MDR-2017), “Medical Devices (MDs) are the substances which are used for in-vitro diagnosis and surgical dressings, surgical bandages, surgical staples, surgical sutures, ligatures, blood, and blood component collection bag with or without anticoagulant and substances including mechanical contraceptives, disinfectants and insecticides and devices notified from time to time under sub-clause (iv) of clause (b) of section 3 of the Drugs and Cosmetics Act, 1940”. According to this definition, MDs are classified into four classes: - class A, class B, class C and class D. The purpose of this review article is to present an overview of the regulatory registration requirement of MD in India according to the new MDR-2017.

Background: Glomerulonephritis mostly results from dysregulated immune system. Impaired immune mechanisms can be primary or secondary to an autoimmune disorder. Antinuclear antibodies (ANA) are hallmark of autoimmunity and are frequently present at high titer (≥ 1: 160). ANA are characterized via anti-double stranded deoxyribonucleic acid (dsDNA) and antiextractable nuclear antigen (ENA) antibodies for the identification of underlying autoimmune disease. Heavy proteinuria can affect assessment of autoantibodies hence special attention is required for the definitive diagnosis in such cases. Objective: Our aim was to determine impact of heavy proteinuria on ANA titer, anti-dsDNA and anti-ENA antibodies in glomerulonephritis patients. Methods: 150 glomerulonephritis patients were enrolled in this study. All had antinuclear antibodies, samples were tested for anti-dsDNA and anti-ENA. ANA titer of ≥1:160 was taken significant. Proteinuria was assessed by spot protein/creatinine ratio. Data was analyzed using SPSS software version. 20. Results: Heavy proteinuria was present in 119(79%) patients. Low ANA titer(≤1:80) was present in 37(25%) patients. Of 33 patients with heavy proteinuria and low ANA titer, ANA was characterized in 11 patients. These include anti-dsDNA(two), anti-SSA(four), anti-Sm (one), antihistones( one), anti-RNP(two), anti-Pm-Scl(one) and anti-ribosomal P protein (two).There was no significant difference in the prevalence of various autoantibodies in patients with high or low ANA titer with heavy proteinuria. Conclusion: This study highlights the importance of low ANA titer in glomerulonephritis patients in the setting of heavy proteinuria. Significant protein loss may alter actual titer of autoantibodies. Hence in this scenario clinically correlation along with ANA characterization via specific autoantibodies is required for adequate patient management.

Background: Rheumatoid arthritis (RA) is a common progressive chronic inflammatory autoimmune disease which affects mostly small joints, causing pain, swelling, deformity, and disability. Although progress has been made in exploring RA nature, still there is a lot to know about the disease pathogenesis, diagnosis, and treatment. Aim of the Work: To investigate the role of serum anti-carbamylated protein antibodies and 14-3-3η in the diagnosis of RA compared to rheumatoid factor (RF), anti-CCP antibodies, and highfrequency musculoskeletal ultrasound used to assess the disease activity and joint damage. Methods: Serum anti-carbamylated protein antibodies and 14-3-3η were measured using ELISA in 61 RA patients and 26 normal controls. RA Disease Activity Score (DAS 28), X-ray and musculoskeletal ultrasound (hands and feet), carotid ultrasound (Intima-Media Thickness {IMT}) were used in assessing the RA disease. Results: Anti-carbamylated protein antibodies were significantly elevated in RA patients 4.5 (4.1- 8.9 U/ml) compared to the control 3.2(1.9- 4.3 U/ml) (p< 0.001) but 14-3-3η showed no significant difference. There was a significant positive correlation between anti-carbamylated protein antibodies, 14-3-3η levels and disease activity score assessed by DAS 28, increased IMT measured by carotid duplex, total synovitis and total erosion score were assessed by musculoskeletal ultrasound. There was no correlation between RF and anti-CCP antibodies. Anti-carbamylated protein antibodies were found to have 66.7% sensitivity and 85.2% specificity in RA diagnosis, while 14-3-3η had 51.9% sensitivity and 72.1% specificity. Conclusion: Anti-carbamylated protein antibodies and 14-3-3η have a high sensitivity and specificity in RA diagnosis and had a correlation with the disease activity and joint damage.