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Drug, device & diagnostics approvals & clinical trials glossary
Evolving Terminology for Emerging Technologies
Comments? Questions? Revisions? mchitty@healthtech.com
Last revised December 21, 2001

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Related glossaries include Applications: Clinical genomics, Drug discovery & development, Pharmacogenomics Informatics Algorithms & data management, Research

510(K) A medical device that is considered substantially equivalent to a device that was or is being legally marketed. A sponsor planning to market such a device must submit notification to the FDA 90 days in advance of placing the device on the market. If the FDA concurs with the sponsor, the device may then be marketed. 510(k) is the section of the Food, Drug and Cosmetic Act that describes premarket notification; hence the designation "510(k) device." [IRB] http://ohrp.osophs.dhhs.gov/irb/irb_glossary.htm

A 510(k) application involves demonstrating that the new product is substantially equivalent to an existing product on the market. It is limited to devices and diagnostics, and by definition, applies only to "me-too" type devices. That is, it represents an incremental improvement over something that is already on the market ... Because of its similarity to a product that has already had a thorough regulatory review, it does not bring up any new issues. .. For 510(k)s, we [the FDA] have been averaging about 1,000 a year.  [Joseph Hackett, in CHI Summit Pharmacogenomics Report]

biologics: Drug discovery & development glossary 

Regulation of biologics: CBER, FDA

Veterinary biologics (vaccines, bacterins, diagnostics, etc, which are used to prevent, treat, or diagnose animal diseases) are regulated by the U.S. Department of Agriculture. http://www.aphis.usda.gov/vs/cvb/

CBER Center for Biologics Evaluation and Research: Part of the US FDA. CBER is responsible for ensuring the safety of this nation's entire blood supply and the products derived from it; the production and approval of safe and effective childhood vaccines, including any future AIDS vaccines; the proper oversight of human tissue for transplantation; an adequate and safe supply of allergenic materials and anti- toxins; the safety and efficacy of biological therapeutics, including an exciting new array of biotechnology- derived products used to treat diseases such as cancer and AIDS. http://www.fda.gov/cber/index.html Related term: biologics

Biologics, in contrast to drugs that are chemically synthesized, are derived from living sources (such as humans, animals, and microorganisms). Most biologics are complex mixtures that are not easily identified or characterized, and many biologics are manufactured using biotechnology. Biological products often represent the cutting-edge of biomedical research and, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have no other treatments available. http://www.fda.gov/cber/about.htm

biopharmaceutical: Any therapeutic biological compound, including recombinant proteins, monoclonal and polyclonal antibodies, antisense oligonucleotides, therapeutic genes, and recombinant and DNA vaccines. [Tufts Center for the Study of  Drug Development "Outlook 2001" Glossary of terms, 2001] http://www.tufts.edu/med/csdd/images/otlk2001.pdf

CDER Center for Drug Evaluation and Research:  http://www.fda.gov/cder/  Part of the US FDA.

CDRH Center for Devices and Radiologic Health: http://www.fda.gov/cdrh/index.html  Part of the US FDA.

CLIA Clinical Laboratory Improvement Amendments: Regulates all laboratory testing (except research) performed on humans in the U.S. Part of the Health Care Financing Administration. http://www.hcfa.gov/medicaid/clia/cliahome.htm

CRO: Contract Research Organization or Clinical Research Organization. Clinical trials are increasingly being run by outsourcing to these groups.

clinical endpoint: A characteristic or variable that reflects how a patient feels, functions, or survives.  Clinical endpoints are distinct measurements or analyses of disease characteristics reflecting the effect of a therapeutic intervention in a clinical trial or study. [NIEHS, US concept clearance for Biomarkers of Toxicity and Surrogate Endpoints for Safety, Feb. 14-15, 2000]  http://www.niehs.nih.gov/dert/council/2000/surro1.pdf  Related terms surrogate endpoints, surrogate markers Pharmacogenomics glossary

clinical informatics: The application of informatics approaches to the clinical- evaluation phase of drug development. These approaches can include clinical- trial simulations to improve trial design and patient selection, as well as electronic capturing and storing of clinical data and protocols. The goal is to reduce expenses and time to market. [CHI Bioinformatics]

clinical trials: Pharmacogenomics is a key tool for the design and interpretation of clinical trials. It contributes to a precise definition of a disease. It has the ability to correlate drug response to genetic markers and predict dose response and adverse events in some cases. It allows for representative subject populations within the clinical trial, and it allows for the stratification of patient populations. The potential benefits of that include reduction of drug development time due to the demonstration of efficacy in specific populations; the optimization of clinical utility by linking sub- types and efficacy; and reduction of time to market. Other potential benefits include the ability to differentiate between responder and non- responder populations, which may lead to a greater likelihood of reimbursement in the end. [CHI Summit Pharmacogenomics]

Related terms CRO Clinical Research Organization, clinical informatics, comparative data mining, Phase I, Phase II, Phase III, Phase IV/postmarketing surveillance, preclinical, predictive data mining.

comparative data mining: Algorithms & data management glossary In-depth  Useful for clinical trial meta-analyses.

drug: Any substance which when absorbed into a living organism may modify one or more of its functions. The term is generally accepted for a substance taken for a therapeutic purpose, but is also commonly used for abused substances. Synonymous with medicine, pharmaceutical. [IUPAC Compendium] Regulation of drugs in the US see CDER, FDA

EMEA: European Agency for the Evaluation of Medicinal Products http://www.emea.eu.int/

FDA: Food and Drug Administration, US regulatory agency http://www.fda.gov/

FDAMA: The Food and Drug Modernization Act of 1997 reauthorized the collection of user fees by the FDA and amended the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act to improve the regulation of food, drugs, devices, and biological products, and facilitate the development and evaluation of new drugs and biologics designed to treat serious and life - threatening illnesses.  [Tufts Center for the Study of  Drug Development "Outlook 2001" Glossary of terms, 2001] http://www.tufts.edu/med/csdd/images/otlk2001.pdf

See also http://www.fda.gov/ora/fdama/default.htm

fast- track: The fast track process was established in the FDA Modernization Act of 1997. Under this act, NDAs are deemed either "standard" or "priority" (fast track). With the "standard" designation, the FDA’s goal is to complete the review and make a decision on the NDA within ten months after it has been filed. With the "priority" designation, used for drugs that address unmet medical needs, the target date is six months after the filing. However, actual approval times are typically longer. In certain cases, the FDA also offers "accelerated approval" to allow the marketing of drugs for life-threatening diseases, before the benefits to patients are formally demonstrated. This approval is made on the basis of a surrogate marker (e.g., a drug’s effect on survival). [CHI Breaking Bottlenecks]

The Food and Drug Administration Modernization Act of 1997 (FDAMA) includes Section 112, “Expediting study and approval of fast track drugs.” This section mandates the Agency to facilitate the development and expedite review of drugs and biologics intended to treat serious or life- threatening conditions and that demonstrate the potential to address unmet medical needs. Fast track adds to existing programs, such as accelerated approval, the possibility of a “rolling submission” for a marketing application. An important feature of fast track is that it emphasizes the critical nature of close early communication between the FDA and sponsor to improve the efficiency of product development.  [CBER, FDA, US "CBER Fast Track Designation Request Performance"  2001]  http://www.fda.gov/cber/inside/fastrk.htm

harmonization of pharmaceutical regulations: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a unique project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of product registration.

The purpose is to make recommendations on ways to achieve greater harmonisation in the interpretation and application of technical guidelines and requirements for product registration in order to reduce or obviate the need to duplicate the testing carried out during the research and development of new medicines. The objective of such harmonisation is a more economical use of human, animal and material resources, and the elimination of unnecessary delay in the global development and availability of new medicines whilst maintaining safeguards on quality, safety and efficacy, and regulatory obligations to protect public health. [ICH Official website, International Federation of Pharmaceutical Manufacturers' Associations] http://www.ifpma.org/ich1.html

home brew:  Reagents or the combination of reagents made in a laboratory, or purchased reagents used by that laboratory for clinical tests and not for sale to other laboratories. [Neal Holtzman, Michael Watson "Promoting Safe and Effective Genetic Testing in the United States: Final Report" glossary, 1997] http://www.nhgri.nih.gov/ELSI/TFGT_final/glossary.html

IND Investigational New Drug Application: A request for Food and Drug Administration (FDA) authorization to administer an investigational drug to humans. Such authorization must be secured prior to interstate shipment and administration of any new drug that is not the subject of an approved new drug application. [CDER, FDA, US "Information for Sponsor- Investigators Submitting Investigational New Drug Applications (INDs) 2001] http://www.fda.gov/cder/forms/1571-1572-help.html

For biologicals http://www.fda.gov/cber/ind/ind.htm

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH: SEE under harmonization of pharmaceutical regulations: 

IRB Institutional Review Board: A specially constituted review body established or designated by an entity to protect the welfare of human subjects recruited to participate in biomedical or behavioral research [Federal Policy §§___.102(g), ___.108, ___.109]. [IRB]

lure of initial value: What we observe [in clinical trials] is not so much a placebo response, but a so- called lure of initial value, where extreme symptoms tend to get spontaneously better. To get a handle on this problem, it would be useful to identify genes that are predictive of rapid disease remission, because many of our problems in terms of testing drugs are driven by the placebo group.  ... One needs very large groups to detect that small difference. Obtaining genes predictive of response might also lead to defining the group of people who, because they are likely to get better spontaneously, are going to get minimal benefit from the drug. {CHI Summit Pharmacogenomics]

me too drug: A compound that is structurally very similar to already known drugs, with only minor pharmacological differences. [IUPAC Medicinal Chemistry]

medical device: Medical devices range from simple tongue depressors and bedpans to complex programmable pacemakers with micro- chip technology and laser surgical devices. In addition, medical devices include in vitro diagnostic products, such as general purpose lab equipment, reagents, and test kits, which may include monoclonal antibody technology. Certain electronic radiation emitting products with medical application and claims meet the definition of medical device. Examples include diagnostic ultrasound products, x-ray machines and medical lasers. If a product is labeled, promoted or used in a manner that meets the following definition in section 201(h) of the Federal Food Drug & Cosmetic (FD&C) Act it will be regulated by the Food and Drug Administration (FDA) as a medical device and is subject to premarketing and postmarketing regulatory controls. A device is: "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, 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 animals, or intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of it's primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes." [FDA, Center for Devices and Radiological Health, US "Is the product a medical device?" 1998] http://www.fda.gov/cdrh/devadvice/312.html#contents

Device Advice, FDA, CDRH http://www.fda.gov/cdrh/devadvice/

A diagnostic or therapeutic article that does not achieve any of its principal intended purpose through chemical action within or on the body. Such devices include diagnostic test kits, crutches, electrodes, pacemakers, arterial grafts, intraocular lenses, and orthopedic pins or other orthopedic equipment. [IRB]

meta-analyses: A statistical technique which summarises the results of several studies into a single estimate of their combined result. It is a key element of many systematic reviews or overviews. It is also what is meant when people talk about 'pooling data'. Meta- analysis is the technique which produces a graph depicting the confidence intervals of all the studies. [Cochrane Collaboration "Research glossary for consumers"1999] http://www.cochrane.org/cochrane/cngloss.htm 

NCE New Chemical Entity: A compound not previously described in the literature. [IUPAC Medicinal Chemistry] 

Any new molecular compound not previously approved for human use, excluding diagnostic agents, vaccines and other biologic compounds not approved by the FDA's Centers for Drug Evaluation and Research (CDER). Also excluded are new salts, esters and dosage forms of previously approved compounds.  [Tufts Center for the Study of  Drug Development "Outlook 2001" Glossary of terms, 2001] http://www.tufts.edu/med/csdd/images/otlk2001.pdf

Compare with me too  

NDA New Drug Application: CDER (FDA) New and generic drug approvals interim index http://www.fda.gov/cder/approval/index.htm

NME New Molecular Entity:  A medication containing an active substance that has never before been approved for marketing in any form in the United States. [Center for Drug Evaluation and Research, FDA, US "FDA's Drug review and approval times" 2001]   http://www.fda.gov/cder/reports/reviewtimes/default.htm#New%20Molecular%20Entity%20(NME)

off label: The use of an FDA- approved drug or device for a purpose other than that intended by the manufacturer and described on the label. FDA only approves drugs or devices for their intended use as described on the label. [Neal Holtzman, Michael Watson "Promoting Safe and Effective Genetic Testing in the United States: Final Report" glossary, 1997] http://www.nhgri.nih.gov/ELSI/TFGT_final/glossary.html

orphan products: The Orphan Drug Act (ODA) provides for granting special status to a product/indication combination upon request of a sponsor, and if the product/indication combination meets certain criteria. This status is referred to as orphan designation. Orphan designation qualifies the sponsor of the product for the tax credit and marketing exclusivity incentives of the ODA. [FDA, US Orphan Product Designation, 2001] http://www.fda.gov/orphan/designat/index.htm

Drug discovery & development glossary

PDUFA Prescription Drug User Fee Act (1992):Another effort to shorten the FDA review process. Under this act, fees the FDA collected from drug developers between 1993 and 1997 were to be used to shorten the timelines needed for evaluating certain drug applications, in part through the hiring of more reviewers. At the same time, the FDA committed to a set of goals for streamlining the review process. The original PDUFA act expires on September 30, 1997, but the FDA Modernization Act of 1997 extended the act through September 30, 2002. [CHI Breaking Bottlenecks]

Legislation passed by Congress authorizing the FDA to collect "user fees" for regulatory review of human drug applications. The FDA agreed to use the income from the fees to hire more reviewers to speed up drug review without compromising review quality. [Tufts Center for the Study of  Drug Development "Outlook 2001" Glossary of terms, 2001] http://www.tufts.edu/med/csdd/images/otlk2001.pdf

See also http://www.fda.gov/oc/pdufa/reports.html

placebo non- responders: [Non- responders on placebo] define a group that would never improve their condition unless given the drug. They may be a group that, if we could identify them, could be used to reduce clinical trial size. Using this group in a proof- of -concept, it may be possible to test a drug even without a comparative placebo and determine whether it is likely to be active. Related terms: disease resistant individuals, lure of initial value, placebo responders

placebo responders: Most people think of the placebo response as a true response. But much of it is actually regression to the mean.  Clinical trial subjects with more extreme symptoms are often selected because it is desirable to see a dramatic effect upon treatment with the drug. CHI Summit Pharmacogenomics] Related terms: disease resistant individuals, lure of initial value, placebo non- responders

Phase I: The main aim of this phase is to determine drug safety. At this stage, drugs are tested in a small group of healthy volunteers to determine the drug’s activity. [CHI Breaking Bottlenecks]

Phase II: These trials are aimed at identifying the optimal dose to be used in Phase III trials and, ideally, they identify drugs that will not make it through the next phase of testing. Typically, Phase II trials are double-blinded and have placebo controls. [CHI Breaking Bottlenecks]

Phase III: These studies, which take several years, can involve thousands of patients at multiple trial centers. They are aimed at definitively determining the drug’s effectiveness and its side- effect profiles. These studies are also typically double- blinded and placebo- controlled. [CHI Breaking Bottlenecks]

Phase IV/postmarketing surveillance: At this stage, after a drug has been launched, pharmaceutical companies may conduct further studies of its performance, often examining long-term safety.

postmarketing surveillance: See under Phase IV/postmarketing surveillance.

preclinical investigations: Laboratory and animal studies designed to test the mechanisms, safety, and efficacy of an intervention prior to its applications to humans [IRB]

preclinical testing: Compounds are tested on cell lines (human and animal) for effectiveness. Also, the compounds are tested in live animals for toxicity and to ensure that they maintain their pharmacological properties. [CHI Breaking Bottlenecks]

premarket approval PMA: The Medical Device Amendments of 1976 to the Federal Food, Drug, and Cosmetic Act (the act) established three regulatory classes for medical devices. The three classes are based on the degree of control necessary to assure that the various types of devices are safe and effective. The most regulated devices are in Class III. The amendments define a Class III device as one that supports or sustains human life or is of substantial importance in preventing impairment of human health or presents a potential, unreasonable risk of illness or injury.  [Information on Premarket Approval Applications, FDA, CDRH, 2001] http://www.fda.gov/cdrh/pmapage.html  Related term medical device

For the Pre-Market Approval (PMA) application, the issue is not substantial equivalence. It involves instead an entirely new product, something that has not been previously introduced into the market. For these products, the FDA has no knowledge or precedent for its safety and efficacy, and therefore it has to be shown to be safe and effective on its own merit. For these applications, we invariably make use of an external panel review. ... For PMA’s, we [the FDA] will receive 13-15 submissions a year. [Joseph Hackett, in CHI Summit Pharmacogenomics Report] 

protocol: The formal design or plan of an experiment or research activity; specifically, the plan submitted to an IRB for review and to an agency for research support. The protocol includes a description of the research design or methodology to be employed, the eligibility requirements for prospective subjects and controls, the treatment regimen(s), and the proposed methods of analysis that will be performed on the collected data. [IRB}

regulatory agencies: See FDA, EMEA. Related term Business of the life sciences harmonization

risk ratio: The ratio of risk in the treated group (EER) to the risk in the control group (CER): RR = EER/CER. RR is used in randomised trials and cohort studies. http://cebm.jr2.ox.ac.uk/docs/glossary.html

Single Controlled Trial SCT: Since 1998, the FDA has allowed drug developers to use what is known as the single controlled trial (SCT) to support their drug approval applications. The SCT provision allows applicants to prove the effectiveness of new drugs by submitting data from only one controlled clinical study instead of multiple studies. [CHI Breaking Bottlenecks Report]

stratification- clinical trials: The FDA has been cautious in forwarding any policy on genotyping and clinical trial stratification, while at the same time trying to engage the industry in discussions on the subject. [CHI Summit Pharmacogenomics]

third party review: Another example of the FDA making use of external resources to ensure quality submission and flexibility in its approval process. In the pilot program for third party review, we obtained the assistance of the State of California Department of Health. The FDA provided them with a guidance document, clearly outlining the objectives, the type of information we are interested in, the process of review and the key points to look for when considering an application. Based on those guidelines, the Department of Health reviewed one 501(k) case and concluded that it was a substantial equivalent to a marketed product. The FDA then had 30 days to review it. Actual review time was only 15 days. The role of the FDA was that of quality control, essentially to oversee the procedure and make sure the third party did everything right. The procedure has worked out fairly well, but the actual number of submissions to this program was low. In 1999, there were only two. To date, the total is only eleven.  [Joseph Hackett, in CHI Summit Pharmacogenomics Report]

Bibliography

[CHI Summit Pharmacogenomics:] Finding the Competitive Edge in Genetic Variation, Editor: Mike Silver, Cambridge Healthtech Institute report, May 2001.  

Clinical Trials Primer, the healthexchange.org , 2001 http://www.thehealthexchange.org/search/nih.cfm

[Cochran] Collaboration, Cochran Glossary 30+ definitions http://www.cochrane.org/cochrane/glossary.htm

Evidence- Based Medicine Glossary, Centre for Evidence- Based Medicine, National Health Service, UK 2001 http://cebm.jr2.ox.ac.uk/docs/glossary.html

[FDA] Glossary of Computerized System and Software Development Terminology 1998] http://www.fda.gov/ora/inspect_ref/igs/gloss.html 

[IRB] Institutional Review Board Glossary, Office for Human Research Protection, US Dept. Health & Human Services, 2001. 150+ definitions.  http://ohrp.osophs.dhhs.gov/irb/irb_glossary.htm

Alpha glossary index