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Clinical Trials
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
If a relevant level of efficacy is found in phase II, and no special toxicity concerns have been identified, the drug is ready for phase III – that is, a randomized trial comparing the new drug to placebo or standard treatment for the indication pursued. The gold standard for phase III trials is a randomized, double-blind, placebo-controlled and multicentre trial. Randomization means that the subjects are randomly assigned either to the experimental arm or to the standard/placebo arm. Double-blind means that neither the investigator/doctor nor the subject knows whether he or she is receiving the investigational drug or placebo/standard treatment. Placebo is an inactive substance that has been prepared in the same format as the investigational drug, and in such a way that it is impossible to know whether it contains the active substance or not. To include several centres in a trial is a way to minimize bias in patient selection, patient management, and so forth, that may otherwise differ between different sites/hospitals/countries in a way that may affect outcomes. The number of subjects required to prove a difference between the control arm and the experimental arm depends on how large the difference is between the two – the larger the difference the smaller the sample size required to prove it. Phase III trials generally include hundreds or even thousands of subjects.
Product Development in Biotechnology
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2020
Phase III studies are randomized controlled multicenter trials on large patient groups (usually ranging from 300 to 3000 or more, depending on the disease/medical condition studied) and are aimed at being the definitive assessment of how effective a drug is in comparison with the current “gold standard” treatment. Because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming, and difficult trials to design and run, especially in therapies for chronic medical conditions. It is common practice that certain Phase III trials will continue while the regulatory submission is pending at an appropriate regulatory agency. This allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. Other reasons for performing trials at this stage include attempts by the sponsor at “label expansion” (to show that the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), to obtain additional safety data, or to support marketing claims for the drug. Studies in this phase are categorized as Phase IIIB studies by some companies.
Enzyme Catalysis
Published in Harvey W. Blanch, Douglas S. Clark, Biochemical Engineering, 1997
Harvey W. Blanch, Douglas S. Clark
The first step in this process, once the biologic has been tested in vitro and in laboratory animals, is the filing of an investigational new drug application (IND) with the FDA. All preclinical information is supplied at this stage. If further studies are appropriate, IND status is granted for the material and human clinical trials commence. These are divided into three categories. In Phase I trials, volunteers are employed to assess pharmacological responses and dose levels, to test for side effects. If results are satisfactory, Phase II trials commence. These involve volunteer patients to test for efficacy and safety. Such trials may be of one to two years in duration. Phase III trials involve a large number of patients, perhaps several thousand, and safety and therapeutic response are further determined. Phase III trials may last up to three years. If successful, a new drug application (NDA) can be submitted, and it is then reviewed by the FDA. Once the NDA is approved, the drug may be marketed. The total time for the whole process may be 10 years or more, at a cost of up to $200 million. The potential market for the drug must therefore be sufficiently large to warrant this expense. The current markets for therapeutic proteins are illustrated in Table 8.5.
Good management practices of venomous snakes in captivity to produce biological venom-based medicines: achieving replicability and contributing to pharmaceutical industry
Published in Journal of Toxicology and Environmental Health, Part B, 2021
Lucilene Santos, Cristiano Oliveira, Barbara Marques Vasconcelos, Daniela Vilela, Leonardo Melo, Lívia Ambrósio, Amanda da Silva, Leticia Murback, Jacqueline Kurissio, Joeliton Cavalcante, Claudia Vilalva Cassaro, Luciana Barros, Benedito Barraviera, Rui Seabra Ferreira
The heterologous fibrin sealant, investigated for more than two decades by CEVAP, consists of a serine protease extracted from the venom of Crotalus durissus terrificus (South American rattlesnake) and a fibrinogen-rich cryoprecipitate extracted from blood of buffaloes (Bubalus bubalis) (Barros et al. 2009; Buchaim et al. 2019; Ferreira et al. 2017). Previous pre-clinical studies conducted with the sealant allowed the Brazilian Health Regulatory Agency (ANVISA) to authorize a phase I/II clinical trial treating 30 patients with chronic venous ulcers. The result showed a safe and promising product. Upon approval of this Phase I/II report, it might be possible to request the clinical efficacy trial (Phase III), which will be multicentric and comprised of hundreds of participants. In 2018, the Ministry of Health approved the construction of a Factory at the CEVAP to produce Samples of Biological Medicines for Clinical Research that will have the main mission to produce samples in accordance with the Good Manufacturing Practice required by ANVISA (Abbade et al. 2015, 2020; Ferreira et al. 2017; Pontes et al. 2017).