Running head: REGULATORY AFFAIRS

Regulatory Affairs Siddartha Mathur Reddy Robyn Conners February 21/2012

Regulatory Affairs

REGULATORY AFFAIRS

In the earlier days most of the countries had some form of government that control the human and veterinary medicine. However after the thalamide problem in 1960 in the UK, the Therapeutic Substance Act in the poisons law gave a legal structure to regulatory affairs. In USA food and drugs act 1906, 1912 gave a legal structure to the regulatory affairs. There are a lot new healthcare products are being invented or discovered now a days so there is increase in the formalistic control established. Regulatory affairs is the combination of the legislation, commercialization, science and management. It touches everything relating to drugs from the earliest non-clinical studies, development, to routine manufacture and marketing There is a lot of involvement of the regulatory affairs in the each and every step of the functioning of the pharmaceutical company. Regulatory officials lay a roadmap of the process of the new drug development by which the scientist will follow the path in the developing the new drugs which are safe and effective for use. Regulatory affairs professional plays a key role in drug developing strategy. Regulatory compliances are needed to be considered during drafting pharmaceutical preclinical and clinical development plan. There are a large number of regulatory authorities are there which are specific to their country or region. Some of the popular regulatory agencies are Food and Drug Administration which is known as FDA OR USFDA and European Commission. This gives in information about regulatory affairs, its role in new drug development, different regulatory agencies in different countries and its role in pharmaceuticals. What is a Regulatory Affairs? Regulatory Affairs (RA) mainly deals with documentation process in pharmaceutical company, in which it deals with getting permissions and license for the manufacturing of the drug and allied compounds. According to (RAPS) Regulatory affairs is a new profession which has huge importance in the health care product life cycle right from the process of product

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development to the post marketing process. They play a very important role in rendering strategic and technical advice which helps to deliver safe and potential healthcare products. In order to get into a better position in this profession they must always update their knowledge and skills. This profession needs to have legal and scientific knowledge. Roberts.c (2009) says Regulatory professional contribute to the company by ensuring in getting the license and marketing the product. They check safety and potentiality of the drug to meet legal compliance. They also advice on legal and scientific compliances and collect, collate and evaluate the research data generated. These professionals are the link between the companies and regulatory authorities. They check the compliance of the product with regulatory authority of the region; they do the required need of regulatory affairs. Role of Regulatory Affairs in New Drug Development Regulatory affairs play a very important role in the development of new drug, which involves developing a plan assisting in reviews and maintaining of the data and getting the license. Biomedical products need approval from the regulatory agency not only for marketing and commercial sale, but also for the development and testing. RA involved in new drug development from very first step by integrating regulatory principles in documentation and submissions to the regulatory agencies. RA involves in every stage of development of new drugs and also in post marketing activities. This deals with different stages of the new drug development and the role of regulatory affairs in new drug development.

Designing or developing a plan:

REGULATORY AFFAIRS

When developing a new drug, regulatory professional gives the blue print of the plan what are the experiments to be conducted and what reports are to be submitted for getting the successful approval of the product. Douglass.p.j, David.s.m (2008) said that According to laws, regulations, and guidelines of FDA it is noticeably specified in section 505 of the Food, Drug, and Cosmetic Act[21 USC 355]. The Act requires that application contain: (A) full reports of investigation which have been made to show whether or not such drug is safe for use and whether such drug is effective in use; (B) a full list of the articles used as components of such drug; (C) a full statement of the composition of such drug; (D) a full description of the methods used in, and the facilities and controls used for, the manufacture, processing and packing of such drug. (p. 71). One of the important functions of the regulatory professional is to design a development plan which serves as a route map for the new product development which is the primary and important step for the new drug development. Mathieu (2008) stated the development plan contain following steps any one of the following three classes of activities comes under the initial stage of the drug development process: (1) scientific testing designed in order to furnish information regarding safety and/or effectiveness of the product; (2) preparation of the regulatory application with the data and other information for the submission; (3) the FDS's review of regulatory submissions. Preclinical testing Preclinical test is testing the biological activity of the compound before testing on the humans, it is done in the laboratory. Mathieu (2008) explained that performing clinical trials are expensive and a risky process, so sponsors for the study seek the proof of the effective biological activity and less amount of toxicological effects. The data should be submitted to the regulatory

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agency showing the company can manufacture the drug, purpose of the clinical trials, evidence showing that the drug is safe for the small scale clinical studies. At this stage FDA ask for the pharmacological activity of the drug, toxicity study in any two animals and one shot term toxicity studies. Investigational New Drug Application This application is submitted when the sponsors believe that the preclinical results satisfactory. Mathieu (2008) explained Investigational New Drug Application (IND) is submitted by the company when they believe that that have adequate data that shows that the new drug is safe for small scale clinical trials. Following are the major three areas in which sponsors should submit the data: (1) how the pre-clinical testing results would comply with the pharmacology and safety results in clinical trials; (2) Analysis of the drug's chemical composition, manufacturing and quality control procedures implemented in manufacturing the drug; (3) sponsors plan for the initial-stage clinical studies mention in the IND, details about the qualifications of the investigators who carry out this process. The FDA's Review of the IND This is the first review in which the professionals in FDA members carry out the required experiments to check the data. Mathieu (2008) asserted that this is a unique process among the FDA's application review process. In this it reflects a delicate balance between federal government's responsibility to protect the clinical trial subjects from the risks involved and to avoid hindering the medical research process. The FDA's review of an IND focuses on following areas: Pharmacology/toxicology Review. Pharmacologist tests the results of animal pharmacology and toxicology and tries to relate these to human pharmacology.

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Chemistry Review. The chemist evaluates the compound whether it is reproducible and stable. The chemist also evaluates the compound's characterization and chemical structure, and compares the products structure and impurity profile to those of other drugs. Clinical Review. The medical officer, generally the physician checks the clinical protocols to assure: (1) that subjects are not subjected to unnecessary risks during clinical trials; and (2) there should be adequate valid data available in phase 2 and phase 3 trials. Microbiological Review. The microbiologist will evaluate the data on drug's in vivo and in vitro effects for the anti-infective and antiviral drug products. Clinical Trials As this involves the testing of the drug on the humans there should be some regulations laid down for ethical basis. According to National Academic press (2004), the participants must be informed about the risks involved , the risk to the participants must be minimized, and selection of the participants should be as such that that they are perfectly fit for the test and bond should be given to the participant about the procedure, process of research. There should be a great benefits from research if they are using humans as subjects.so there should be healthy regulations set up in order to protect humans form unnecessary suffering. This involves the testing of drug on humans which give the accurate and real results which involves different phases of clinical trials. Mathieu (2008) mentioned that this is the most important phase in the drug development process. FDA's ultimate approval decision will be mainly based on the data evolved in this phase. Even though the process of clinical trials varies for different kinds of drugs but they all fall under the three phases, they are

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Phase 1. The very careful use of drugs on few patients or normal human volunteers normally ranging from 20-80 subjects to evaluate the basic pharmacological and safety information. It used to determine clinical effectiveness of the drug. Phase 2.In this phase the drug is tested against the patients who are suffering with the disease which the drug is intended to cure, it is generally tested on 100-200 patients. These studies will give the key information which helps in designing the phase 3 clinical trials, which includes dose, dosing regimen, and target population. Phase 3. This is the last phase and important one because this phase is the deciding factor for the marketing of the drug in which the doctors prescribe this medicine and they see the effectiveness and any side effects. If the drug passes this stage successfully, then it has full permissions from regulatory agency for the marketing of the drug. The steps said above are the outline process of the new drug development almost all the country with some variations. The regulatory professionals play a very important role in the new drug discovery. Now let us discuss the branches of regulatory affairs and diffent regulatory agencies. The different branches of the Regulatory Affairs There are many branches depending up on the type of the medical application which are categorized and they have special professional for maintaining the regulatory affairs of the product. Drugs Submissions Drugs are the separate of entity in the treatment of diseases which is the one of the branch of regulatory affairs. (Regulatory Affairs Professionals Society[RAPS], 2009) stated that :

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Drugs are regulated under the 1938 Federal Food, Drug, and cosmetic Act of 1938. Under this act, the US Congress gave the Food and Drug Administration (FDA) authority to oversee and enforce the safety and efficacy of the drugs(as well as the efficacy and/or safety to medical devices, animal drugs, biological, food and cosmetics). A drug is broadly defined as: Any product intended for in diagnosis, cure, mitigation, treatment or prevention of a disease in a man. There are two types of regulatory compliances in the section of drugs they are the prescription drug submissions and generic drug submissions. Prescription drugs are the drugs under patent and generic drugs are the one which are not under patent (p. 126). There are many types of drugs approved, under approval and some are under the developing stage. Each kind will have different regulatory process for their different kind of approval. Medical device Submissions Medical device are the separate of entity in the treatment of diseases which is the one of the branch of regulatory affairs. According to (RAPS,2009 ) Medical devises are : Medical devices were first regulated by the Federal Food, Drug, and cosmetic Act of 1938(FD&C Act). Under this Act , the US Congress gave the Food and Drug Administration (FDA). FD&C Act was amended in 1976 to include premarket review of medical devices. FDA, through the Center for Devices and Radiological Health (CDRH), is responsible for assuring that medical devices are safe and effective. Medical devices, referred to as devices, are defines in section 201(h) of the FD&C Act: The term device means an instrument, apparatus, implemented, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is (1) recognized in the official National Formulary, or the United

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States Pharmacopeia, or any supplement to them, (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation treatment, or prevention of disease, in man or other animal(p.201). These are the equipment used in the surgery, not only that but the syringe which we use for injection also comes under medical devices. They are need to accurate in measurement and precise in their function. Biologics Submissions Biological products are the separate of entity in the treatment of diseases which is the one of the branch of regulatory affairs. According to Regulatory Affairs Professional Society (2009) biologics are defines as: Biologics are drug products derived from living sources, e.g., humans, animals and microorganisms, and are generally not easily identified or checked characterized. many are manufactured using biotechnology. The public health service act(PHS Act, 42 united states code(U.S.C.) 262), section 351(a) defines biological product as: any virus therapeutic serum, toxin, antitoxin, vaccine, blood, blood components or derivatives, allergic products or analogous product that is intended for the use in the Regulatory Bodies (p. 248). These are the sterile products which are very useful type of medications but if there is any slightest amount of toxic compounds in it would cause very harmful side effects and in many cases it would be lethal so there are tight regulations for these type of the compounds. Different Regulatory Bodies There are many regulatory bodies which are monitoring in their respective countries. There is no one particular body which governs the regulatory affairs all over the world. Depending on the

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country and region there are different regulations which is monitored by different regulatory bodies of their respective country, some of them are European commission, FDA and many regulatory bodies are there.

European commission This is the governing regulatory body in the European continent under which many European countries follow. Tobin, et.al (2008) stated that European commission is equal to the civil service department at the national level which deals with the drugs and medical devices the head of the commission is directorate general of Enterprise and Industry. There are many supportive consultative committees and experts assisting this European commission. Few of the consultative committees stated by Tobin, et.al(2008) are The Standing Committee on Medicinal Products for Human Use, The Standing Committee on Veterinary Medical Products, The Committee on Medical Devices, The Committee on Standards and Technical Regulations(p.28). As there are many consultative committees assisting the regulatory body in their specialized areas it is one of the best way of regulating the drugs and devices. National Competent Authorities These are the regulatory bodies of the particular countries of their own. Tobin, et.al (2008) stated that there are some regulatory bodies in some countries they are not government agencies but they work under the guidelines of the government, in which the Heath Minister takes the control of the agency. For example, Irish Medicines Board (IMB) covers the both the drugs and devices in Ireland. These are the authorities which deals with the regulation in the specialized area of the work, which works for the government.

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These govern medical devices. Tobin, et.al (2008) asserted these are not statutory bodies and they play an important role in the regulation of the medical devices. These are not big regulatory agencies as others mentioned but they are developing and increasing their activity now a days. The FDA This is the most efficient regulatory body which involves almost all countries regulatory affairs which has a wide network of branches and excellent professionals Tobin, et al(2008) reported that the Food and Drug Administration (FDA) is the main regulatory agency in the USA which regulates food, drugs, devices and cosmetics. FDA has developed many regulations which help in providing the safe drugs for the people. They give permissions for the new drug development and they conduct reviews on the data submitted by the company and also issue license for the marketing of the drug. It also play an important role in the harmonization of the regulatory bodies in all the countries. Because FDA has high standards and high network of the branches in many countries and highly qualified professionals it emerged as a on of the top regulatory authorities of the world. Job description Regulatory professional is a good team player should have ability to work in other disciplines it may be scientific or nonscientific. Stoner (2003) explained the main job of regulatory affairs professional is the product registration which mean obtaining and maintain authorizations of marketing drug. The job involves getting the license, to market medicines, review of the data submitted. The career starts as the junior member of the team, if any

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specialization in one area he is appointed in that area. He needs to gain wide range of experience in regulatory strategy. Conclusion Regulatory affairs is a new profession which involves in the regulation of the pharmaceuticals, medicines, medical devices, cosmetics, veterinary medicine, and many healthcare related products. RA has very important role in the new generation New Drug Development (NDD), which involves in the giving the plan about the what are the formalities to be completed in order to start NDD by a company. RA professionals play an important role in taking the NDD process to the next level of the approval process. There are RA professionals present in the FDA who reviews the data submitted by the companies for NDD process, FDA RA professionals take the help of the experts to review the data, if the data is satisfactory and satisfies the laws then they approve for the next level of the NDD process. The data submission by the company and reviewing of the data by the FDA continues till the drug is marketed and even during the post marketing time the regulatory body can regulate the marketing of the drug if it finds any dissatisfaction about the compound. There are different legislations in different countries, RA professionals need to know all the laws governing in the respective country in which their company wishes to market their product. The biggest disadvantage of the regulatory bodies of all over the world is that there is no specific body which governs all the laws of the world, by which the regulations of different countries hardly match. There are some harmonization bodies working for the harmony of the global regulatory bodies. So for the better healthcare for the world regulatory professionals and regulatory bodies should work well and harmonized.

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References Ashley-Roberts,c. (2009). Regulatory affair officer. Retrieved from http://www.prospects.ac.uk/regulatory_affairs_officer_job_description.htm. Mathueiu.M. (2008) New drug development: A Regulatory overview, 8TH edisionWaltham, MA: parexel International corp. National Academies Press(2004).Intentional human dosing studies for EPA regulatory purposes : scientific and ethical. (2004) Washington, D.C. National Academies Press. Pisano,D.J&Mantus,D.S (2008). FDA regulatory affairs: A Guide for prescription drugs,

medical devices, and biologics. New York: Informa Healthcare . RAPS.org. Who are regulatory professionals Retrieved from http://www.raps.org/YourCareer/Regulatory-Career-Advancement-Guide/About-Regulatory/Who-Are-RegulatoryProfessionals.aspx. Regulatory Affairs Professionals Society. Fundamentals of us regulatory affairs. (2009). Rockville, Md. Regulatory Affairs Professionals Society. Stonier,P.D.(Ed.) (2003).Careers with The Pharmaceutical Industry. chisester,NJ.Wiley. Tobin.J.& Walsh,G. (2008). Medical product regulatory affairs : pharmaceuticals, diagnostics, medical devices IPSwich,MA: Wiley-Blackwell.

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