The Key Processes and Issues in the Stages of Obtaining a License for the Supply of Medicines - Essay Example

Trialling Drugs: What are the Key Processes and Issues in the Stages of Obtaining a License for the Supply of Medicines Introduction: Trialling a newdrug is a human experiment, and drug development is a long and costly process fraught with tribulation. The tortuous pathway travelled by a new drug from synthesis to sale requires the constant percolation of data through rigorous clinical and regulatory filters. The process is complex, and success cannot be guaranteed. It is, indeed, very difficult to predict which drug will have qualities necessary to gain regulatory approval and to be marketed. New drugs do make it from discovery to the market, but it is a long, costly, and extremely risky process involving a steady progression through multiple stages with treacherous decision process along the way (Cartwright AC, Matthews BR, 1994). Most importantly, it is a process involving the constant percolation of data through rigorous filters strewn with tribulations and complicated by the difficulty of making decisions that affect human health when all the facts are not known. Overview: The process of phases I to IV clinical trials is the cornerstone of drug registration and regulation process. Most countries require evidence of efficacy and safety for licensing new drugs. The implications of such a process are significant. Research discoveries whether it is publicly funded or funded by commercial organizations must be transferred to companies so that they can be developed into a commercial product to allow people to have benefit. This benefit should come after ensuring the safety of the population. Licensing system is utilized for ascertaining the regulation of the new drug while performing the trial (Cartwright AC, Matthews BR, 1994). Prelicensing System: This indicates that the authorities believe and acknowledge the fact that before a drug is manufactured even for trial, a favourable balance between the beneficial and harmful effects would need to be demonstrated. Therefore, the regulatory system should provide timely access to the effective treatment, protect patient safety, and foster research into new treatments (NIH Data Book 1994). The respective agencies protect public health by ensuring that only products with favourable benefits to risk profile are licensed. It also means that since the authority is required to foster research, at the same time, the authority should not create unnecessary regulatory impediments, especially in relation to licensing. Putting it straight, innovative medications, if they are promising would need to move in the fast track out of the red tape so that benefits are available to the people quickly (NIH Data Book 1994). Product Assessment: All medicinal products need to be licensed before they can be marketed unless they meet one of a small number of exemptions. This covers a very wide range of medicine types ranging from those available over-the-counter in pharmacies and on general sale to the latest prescription-only new drugs (Fazzari M, Heller G, Scher HI., 2000). Regulatory Principles: The regulatory principles applied are common to all types of medicines and are based on evaluation of their quality, safety, and efficacy. It is impossible to evaluate these three criteria in an isolated fashion since these are interrelated. The product quality is assessed not just in absolute terms but taking into account its effect on safety and efficacy and considering the manufacturing standards in place. The assessment of safety and efficacy must include a rigorous evaluation of the risk versus benefit balance since the acceptability of the unintended side effects will be different for life saving drugs than for those used to treat minor ailments (Cartwright AC, Matthews BR, 1994, p 422). However, this is dependent on the data provided by the manufacturer that summarizes innovative aspects of the drug based on chemistry of the drug, animal toxicology, mechanism of action, and initial clinical trials. These would identify the special approaches to drug development that would be considered during licensing. It is also required to summarise the characteristics of the disease or diseases for which the drug is to be used. Healthcare needs and benefits are to be enumerated. The data about the drug must be collected from countries outside the region in which the licensing is applied and the summary of the data about drugs marketed by the competitors are to be recorded (Food and Drug Administration). Multidisciplinary teams of assessors work on the product license application and can consult external experts on a formal or informal basis when needed. All new products are assessed and then the report is submitted formally to the Committee on Safety of Medicines, the statutory committee responsible for advising ministers on regulatory issues for advice. It can be argued that since the work of regulating medicines funded by user fees on each product license, not only the licensing investigation, but also inspection of manufacturing facilities and authorization of clinical trials may be affected because the funding is done by the licensee. Naturally, this may prevent regulators from taking difficult decisions. The basic goal should be to ensure scientific independence of the regulatory system (Eisenberg, R. S., 1996). Despite this, there have been great backlogs in processing the applications of license. Criticisms have been raised as to the possibility that pharmaceutical industry may influence the license decision and that may cause a faulty drug to get a license and an appropriate drug is pushed in the backseat. The irony of the whole situation is that despite expressing grave concerns about the potential dangers inherent in user-funded regulation, the House of Commons Health Committee did not propose any alternatives (House of Commons Health Committee, 2005). Procedures for Product Assessment: The Legal Basis: The European legislation has also earmarked the framework for establishing the scientific guidelines. These ensure maintenance of high standards for product approval and continuity of single market in pharmaceuticals. Alternative Centralized Procedure: The alternative centralized procedure is administered by the European Medicines Agency based in London. This body grants a single authorization for the whole community. The scientific assessment is carried out by one or more rapporteurs from national authorities and is reviewed by a committee of similar experts from all the member states. There has been much of debate regarding the competency of the assessors. An important role of the agency is to ensure that there is good manufacturing quality in factories and there is a thorough examination of the research records. These data are to be corroborated with the licensing application, but in all probability, there might be a conflict of interest in verifying the application since assessors might have belonged to the same company (NIH, 1997). Quality Assurance: The licensing ensures the quality of the product and determines its standards. In view of the significance of its decision for public health, the work of the licensing division is subject to a number of quality assurance systems as well as internal and external audits. These include verification of data and adequacy of information for evaluation of the drug’s suitability for use. There would need to adequate safety data according to safety standards that ensures that human subjects would not be subjected to unreasonable and significant risks. The regulatory body must be convinced that the study has an acceptable likelihood of providing data capable of meeting statutory standards (Wilson JT., 1999). The dose and duration of administration must be supported by nonclinical pharmacology and toxicology studies. This is one of the six sections that comprise almost all regulatory licensing submissions. These are pharmacology and toxicology; CMC or chemistry, manufacturing, and controls; clinical; microbiology; statistics; and human pharmacokinetics and bioavailability (Nies AS., 1990). The information and the associated documentation would need to be extensive. This is meant for review; therefore, it is not merely summaries of data (Pharmaceutical Research and Manufacturers Association (PhRMA) Industry Profile 2000). The results of nonclinical toxicology studies would support human use of the drug. Fundamentally, these studies are done to explore and characterize the spectrum of the drug’s toxicity in vitro and in animals. Such studies provide the manufacturer with some expectations of which organ systems are likely to exhibit toxicity-related findings in humans as well as an expectation of the magnitude of drug exposure at which such toxicities may occur. Therefore, an adequate characterization of the drug’s toxicity is an essential precursor to licensing (NIH, 1997). These studies may include acute and repeat-dose toxicity studies to provide a screen for initial detection and characterization of the spectrum of the drug’s toxicity on all major organ systems. Present Scenario: The initial goal of prelicensing drug evaluation have been modified to include new questions directed at goals other than drug efficacy and safety. As a result, the clinical drug trials have moved from a role of drug assessment to physician education and competitive marketing (Eisenberg, R. S., 1996). These changes have required a new management system dominated by calculation of sample size, goals for patient recruitment to accomplish large clinical trials, and the emergence of a new industry to organize clinical trials. So a fresh approach to drug licensing is emerging (National Audit Office, 2003). These approaches include initiation of flexible drug development based on drug type and scientific database. Decision making is now increasingly being done on interactive, pharmaceutical, and regulatory experts at the end of phase II to accomplish flexibility. In these discussions, the estimates of drug sales, prices, and worldwide distributions are integrated. All data from phases I and II are ensured to be available to the medical community. Postmarketing surveillance for drug safety assessment is increasingly being used when phase III and phase IV placebo controlled trials are being discontinued (Hutton J, Borowitz M, Olesky I, Luce BR., 1994). For most, drugs licensing would proceed at this point. For some other drugs, additional studies of dose ranging or safety would be needed. As mentioned earlier, placebo controlled phase III studies would no longer be needed, while drug licensing would be based on complete presentation of the data from phase I and II that comprise dose range studies in healthy subjects and challenge studies in healthy subjects. Support studies from other countries and confirmed data from preclinical trials in patients with specific disease are used to this end. References Cartwright AC, Matthews BR, (1994). eds. International Pharmaceutical Product Registration: Aspects of Quality, Safety and Efficacy. London: Ellis Horwood,:411–552. Eisenberg, R. S., (1996). Public research and private development: patents and technology transfer in government-sponsored research. Virginia Law Rev., 83: 1663–1727. Fazzari M, Heller G, Scher HI., (2000). The Phase II/III transition. Toward the proof of efficacy in cancer clinical trials. Control Clin Trials ;21: 360­8. Food and Drug Administration, Center for Drug Evaluation and Research, Guideline Documents. fda. gov/cder/guidance Accessed on November 17, 2007 House of Commons Health Committee. The Influence of the Pharmaceutical Industry. Fourth Report of Session 2004–05, ev 9-14. Hutton J, Borowitz M, Olesky I, Luce BR., (1994). The pharmaceutical industry and reform: lessons from Europe. Health Aff (Millwood);13:98-111. National Audit Office. Safety, quality, efficacy: regulating medicines in the UK. London: Stationery Office, 2003. Nies AS., (1990). Principles of therapeutics. In Gilman AG, Rall TW, Nies AS, Taylor P, eds. The pharmacological basis of therapeutics. Oxford: Pergamon Press,:62­83. NIH Data Book 1994 (NIH Pub. No. 95-1261). Bethesda, MD: NIH, 1995. NIH, (1997). The NIH Director’s Panel on Clinical Research Report to the Advisory Committee to the NIH Director. December, 1997. Bethesda, MD: NIH, 1997. Pharmaceutical Research and Manufacturers Association (PhRMA) Industry Profile 2000. Washington, DC: PhRMA, 2000. Wilson JT., (1999). An Update on the therapeutic orphan. Pediatric;104 (suppl):585–590 Read More