R Common to both approaches

O High throughput screening O Informatics O Early toxicity studies Fig. 4.22. Selection and Improvement Tools project know ahead of time what the target is (the optimal specifications), as well as what would be acceptable (minimal specifications). Firm stopping rules that are realistic, practical, and set up-front avoid endless searching in discovery so a team can move on to more productive projects. Many groups have found it useful to work backwards through the development and approval process...

Selected Issues in Clinical Development

A collection of brief reviews of selected issues follows that can pose as controversies or extra challenges in clinical development (Fig. 8.35). Some topics, such as investigator-initiated INDs and compassionate use, have been perennially discussed within the pharmaceutical industry. Others, such as quality of life end points and pharmacogenomics, represent disciplines and concepts that are relatively new in their application to drug development. The purpose of this section is to introduce...

Product Development Paradigm

The R& D division needs an operational framework (paradigm) in which to function and achieve organizational effectiveness. The following proposed paradigm for product development at a pharmaceutical company, P to the eighth power, provides such a general working framework. This paradigm is based on a distillation of many observations and

Info

CYP450 Drug-Drug Interaction Probes Inhibition or induction of an interacting drug may or may not result in a clinically significant interaction. Drug(s) may induce inhibit one isoenzyme but may not be a substrate of it (quinidine is an inhibitor of CYP2D6 but a substrate of CYP3A4). Drug-drug interactions (DDI) can be of following types inhibition or induction. Inhibition is the more common form of DDI. Enzyme inhibition Decreased enzyme activity due to direct interaction with the...

Dosage Form Decisions

One of the initial steps in the drug development process is to select a desirable product profile and create the dosage form that fits well the product and disease (Fig. 9.1). This profile is based on the physicochemical characteristics of the active ingredient, disease-related issues, how the product will be used by providers and patients, and marketplace issues (e.g., competition). Characteristics such as permeability, solubility, stability, safety, potency, half-life, and molecular size will...

Protecting the Public Health

The FDA is responsible for not only drugs and biologics, but their regulatory authority also extends to food, medical devices, veterinary drugs, cosmetics, nutrition products, and radiation devices. Thus, they are responsible for protecting the health of the nation's citizens across a broad spectrum, including such areas as labeling of the nutritional content on food, approving only drugs found to be safe and effective for human or veterinary use, the allergenic potential of cosmetics, and the...

Cyp3a5

Pharmacogenetics & Pharmacogenomics Source Influences on Pharmacologic Responses. achieve the safe and effective use of the drug. Pharmacogenetics and pharmacogenomics are the sciences of understanding the correlation between an individual patient's genetic makeup (genotype) and their response to drug treatment. They already have influenced therapeutics. For a drug that is primarily metabolized by CYP2D6, approximately 7 of Caucasians will not be able to metabolize the drug, but...

Public Patient Outcomes

The benefit to patients for R& D outcomes is first and foremost the new products that will improve their disease status with the least amount of side effects, but it is not just any product (Fig. 3.1). The 2004 Health Report for the United States from the Centers for Disease Control and Prevention documents the major reductions in death rates for heart diseases, cerebrovascular disease, and cancer and states that new drugs and more use of existing drugs were primary contributors to this...

Advertising

Consistent with the FDA's mission to protect the public's health, the agency has regulatory authority over the advertising and promotion of prescription drugs (Fig. 7.25). The intent is to ensure that promotions of drug and biologic products to prescribers and or consumers are truthful, do not exaggerate the benefits, and fairly present the risks of the products. There are written regulations on what can and cannot be presented in advertising materials. It is a regulatory requirement that...

Bbbbbbbbbbbb

R Discovery - Identification of disease targets and potential therapeutic compounds c The most variable and least successful aspect of drug development r Non-Clinical Development - Translates discovery science into therapeutic candidates o Involves modifications, scale-up, purification, test methods and production Focusing more closely on discovery, we see that there are essentially five main steps target identification and validation, and lead identification, optimization, and validation....

Use knowledge and experience to effectively drive and direct discovery

Goals of Discovery Research for every 50 entering preclinical development), even starting with a recombinant human protein with known activity is no guarantee of clinical and market success. For example, at Amgen, GDNF (glial-derived neurotrophic factor) has been demonstrated in vitro cell cultures to arrest death of or heal the brain cells associated with Parkinson disease and even dramatically improved the signs of parkinsonism in primate animal models. However, GDNF was a failure...

Clinical Development Strategy

Corporate management determines which disciplines will provide the organizational leadership in the drug development process. Companies may drive the development process through their program management organization, their clinical organization, or their regulatory organization. Regardless of the source of development team leadership, as in any sport, team chemistry and good communication are the critical underpinnings required to be successful. The players and...

Contract Research Organizations CROs

As the pharmaceutical industry has expanded and matured, industry managers have become increasingly sensitized to the need to operate the clinical operations area as a scientific business in relation to the maintenance of large in-house clinical development organizations (Fig. 8.28). In response to these concerns, contract research organizations (CROs) began to spring up during the 1970s and to play a progressively more prominent role in the industry over the subsequent three decades. CROs have...

Compliance Quality Assurance

Compliance with the regulations, and the assurance that a company is in compliance, underlies all the regulatory aspects that have been discussed thus far in this chapter. The FDA requires that any drug or biologic product, whether at the investigational stage or being marketed, is manufactured, studied, and marketed in accordance with its regulations, and the FDA has substantial power to enforce their compliance to the regulations. Even the most innovative product for a highly unmet medical...

Acknowledgments

The members of the editorial board of this book have been professional associates in health care and research in the industry and academia during the editor's career, as well as friends. Each brings his own base of experience and talents to this scholarly work. Their advice and engagement as editorial advisors and authors have enriched the content and were indispensable to me as the editor. The authors comprise 24 talented group of researchers, clinicians, and educators in health care, both...

Helping the Public Get Accurate Science Based Information

The FDA is responsible for regulating the communications between the pharmaceutical, biotechnology, and medical device companies and the prescribing physicians, other providers, institutions, and patients who use their products. First and foremost, FDA fulfills this mission through approving the language in the package inserts of all drug and biological products, and regulating the educational and advertising materials for drug products. FDA communicates directly to the public through press...

Crf

Paper or electronic form designed to capture data from a clinical trial. assessments of efficacy and adverse event) subjects are informed of the study and are providing informed consent as required the data collected is accurate and is being recorded as required the drug is being stored, prepared, and accounted for as required the site is notifying the IRB of the progress of the study as required and study documents are being maintained appropriately. Monitoring site visits typically are done...

Elaine S Waller and Nancy L Kercher

Regulatory Authorities and the Laws Protecting the Public Health Advancing the Public Helping the Public Get Accurate, Science-Based Information Regulatory Development Strategies Fast-Track Priority Review Rolling Accelerated Approval Orphan Drugs Rx to OTC Submissions to Regulatory Authorities Product Review Package Advertising Postapproval Maintenance Compliance Quality Assurance General References The discipline of regulatory affairs integrates the scientific information obtained during the...

Editors and Authors

The book is authored by a multidisciplinary team of researchers, clinicians, and marketers from industry and the medical pharmaceutical community. They collectively have done extensive work in drug development, measured by the many product applications prepared and ushered through regulatory authorities, by scope and quality of institutions and companies at which they worked, by number of years devoted to research and product development, and by hundreds of publications. The experience base in...

Rx to OTC Switch

Dozens of products have been switched from prescription status to being available over-the-counter OTC without a prescription Fig. 7.13 . In order for a drug to be switched, the product must be used to treat or prevent symptoms in a disease where physician oversight is not necessary. The patient must also be able to self-diagnose the condition being treated. Sinus congestion, headache, pain, upset stomach, and itching are examples of symptoms a patient can recognize. Drugs that must be...

Value of PKPD

In drug development, the ADME processes of a compound are experimentally determined Figs. 6.2 and 6.3 . Absorption studies are conducted to answer the basic question whether the drug can reach the systemic circulation from the site of administration. There are several factors that can influence the absorption of the drug after oral administration. The drug needs to have a high solubility and high permeability in order to be absorbed adequately. A Biopharmaceutics Classification System BCS was...