Understanding the language of biotech can be tough for those of us that don’t work in a medical field. Often, I find myself searching the internet for some acronym or word  I’ve read  about in a company press release or a research paper.

Knowing there are hundreds of other investors that are doing the same thing I decided to compile a Biotech Glossary of Terms used in the course of our studies. What sets this apart from other glossaries you may find is that I’ve added a bunch of simple video explainers to some of the more tricky to understand concepts.

Don’t know the difference between your interferons and interleukins? I’ve got you covered. You think fetal bovine serum is milk? Let me set you straight.

This list is far from exhaustive but it still took me many hours to put together. My focus was mostly on the words and phrases to do with stem cells, but I got a little carried away.

If there’s anything you think I should add, particularly anything obvious I missed, send me an email at :

[email protected]

A 

Abbreviated New Drug Application (ANDA) – An Abbreviated New Drug Application (ANDA) is an application to the FDA specifically for a generic drug product. Generic drug applications are called “abbreviated” because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness.

Instead, a generic applicant must scientifically demonstrate that its product is bioequivalent (i.e., performs in the same manner as the innovator drug). Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the American public.

Accelerated Approval – Sometimes the approval of a new drug can be expedited. Accelerated Approval can be applied to promising therapies that treat a serious or life-threatening condition and provide therapeutic benefit over available therapies. This approach allows for the approval of a drug that demonstrates an effect on a “surrogate endpoint” that is reasonably likely to predict clinical benefit, or on a clinical endpoint that occurs earlier but may not be as robust as the standard endpoint used for approval.

The drug maker is then required to conduct post-marketing clinical trials to verify and describe the drug’s benefit. If further trials fail to verify the predicted clinical benefit, FDA may withdraw approval

Active Ingredient – An active ingredient is any component that provides pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or animals.

Adenovirus and adenovirus vaccines – Are group of common viruses that cause a range of illnesses, usually causing cold-like symptoms such as fever, sore throat bronchitis, pneumonia, diarrhea and conjunctivitis

Adult stem cells – A commonly used term for  tissue-specific stem cells , cells that can give rise to the specialized cells in specific tissues. Includes all stem cells other than pluripotent stem cells such as embryonic and induced pluripotent stem cells.

Adverse Event – drug reaction is also known as a side effect, is any undesirable experience associated with the use of a medicine in a patient. Adverse events can range from mild to severe. Serious adverse events are those that can cause disability, are life-threatening, result in hospitalization or death, or are birth defects.

All-Cause Mortality -A measure of all deaths, due to any cause, that occur during a clinical study.

Allogeneic – Cells or tissue obtained from donors for use in transplantation. The term applies if the donor is related or unrelated to the transplant recipient.

Amino Acids – Building blocks of proteins. There are twenty common amino acids: alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

Antibody – A protein produced by the immune system in response to an antigen (a molecule that is perceived to be foreign). Antibodies bind specifically to their target antigen to help the immune system destroy the foreign entity.

Antigen – A substance to which an antibody will bind specifically

Approval Letter – An approval letter is an official communication from FDA to a drug application (NDA, BLA, or ANDA) sponsor that allows the commercial marketing of the product.

ARDS -Acronym that stands for a disorder known as or Acute Respiratory Distress Syndrome.

Assay – An analytic procedure for detecting or measuring the presence, amount, state or functional activity of a  biomarker .

Autoimmune Disease – A disease in which the body produces antibodies against its own tissues

Autologous – Cells or tissues from the same individual; an autologous bone marrow transplant involves one individual as both donor and recipient.

B

 Bacteria – Single cell organisms (microorganisms) that
can be seen only under a microscope. Although there
are thousands of different kinds of bacteria in our
environment and in or on our bodies, only a few
actually cause disease in human beings. Patients with
certain kinds of immune defect may have problems
with specific kinds of bacteria that do not cause
disease in individuals with a normal immune system.
Certain other kinds of bacteria infect both immune
deficient and normal individuals, but the immune
deficient individuals have more trouble clearing this
infection and therefore the infection may progress to
develop organ damage or other serious
consequences.

Batch – fixed measure of starting material, packaging material or product processed in one or a series of processes at one time. Batching allows all repeats to be tracked to ensure uniform character and quality

Batch Processing – Growth in a closed system with a specific amount of nutrient medium. In bioprocessing, defined amounts of nutrient material and living matter are placed in a bioreactor and removed when the process is completed.

B-lymphocytes (B-cells) – White blood cells of the
immune system derived from bone marrow and
involved in the production of antibodies.

Biodegradable – Capable of being broken down by the action of microorganisms, usually by microorganisms and under conditions generally in the environment

Biological Drug – A substance that is made from a living organism or its products and is used in the prevention, diagnosis, or treatment diseases. Biological drugs include antibodies, interleukins, stem cells, and vaccines.

Biologic License Application (BLA)
A biologics license application is a submission from an applicant that contains specific information on the manufacturing processes, chemistry, pharmacology, clinical pharmacology and the medical affects of the biologic product. If the information provided meets FDA requirements, the application is approved and a license is issued allowing the firm to market the product.

Biomarker – A defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions

Bioreactor – A type of Vessel used for growing living cells or other biological material in large volumes.

Biotechnology – Development of products by a biological process. Production may be carried out by using intact organisms, such as yeasts and bacteria, or by using natural substances (e.g. enzymes or cells) from organisms.

Blastocyst – An early stage embryo about seven days following fertilization and containing about 150 cells. A blastocyst consists of two types of cells: the inner cell mass cells, which gives rise to all the organs and tissues of a future embryo and fetus; and the trophoblast which forms a portion of the placenta. Embryonic stem cells are derived from the inner cell mass of donated IVF embryos.

Blinding/Masking – One or more parties of the clinical trial are kept unaware of the treatment assignment. Patients, investigators, and health care providers may all be blinded to the treatment a patient is receiving.

Bone marrow – Soft tissue located in the hollow centers of
most bones; the marrow contains developing red
blood cells, white cells, platelets and cells of the
immune system.

Breakthrough Therapy – Breakthrough Therapy designation is a FDA process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

For purposes of Breakthrough Therapy designation, clinically significant endpoint generally refers to an endpoint that measures an effect on irreversible morbidity or mortality (IMM) or on symptoms that represent serious consequences of the disease. A clinically significant endpoint can also refer to findings that suggest an effect on IMM or serious symptoms, including:

• An effect on an established surrogate endpoint
• An effect on a surrogate endpoint or intermediate clinical endpoint considered reasonably likely to predict a clinical benefit (i.e., the accelerated approval standard)
• An effect on a pharmacodynamic biomarker(s) that does not meet criteria for an acceptable surrogate endpoint, but strongly suggests the potential for a clinically meaningful effect on the underlying disease
• A significantly improved safety profile compared to available therapy (e.g., less dose-limiting toxicity for an oncology agent), with evidence of similar efficacy

A drug that receives Breakthrough Therapy designation is eligible for the following:

• All Fast Track designation features
• Intensive guidance on an efficient drug development program, beginning as early as Phase 1
• Organizational commitment involving senior managers

Breakthrough Therapy designation is requested by the drug company. If a sponsor has not requested breakthrough therapy designation, FDA may suggest that the sponsor consider submitting a request if: (1) after reviewing submitted data and information (including preliminary clinical evidence), the Agency thinks the drug development program may meet the criteria for Breakthrough Therapy designation and (2) the remaining drug development program can benefit from the designation.

C

CAP -See Community-Acquired Pneumonia.

Cardiovascular disease – also called heart disease is a class of diseases that involve the heart, the blood vessels (arteries, capillaries, and veins) or both.

Cardiomyocytes – The functional muscle cells of the heart that allow it to beat continuously and rhythmically.

Catalyst – An agent (such as an enzyme or a metallic complex) that facilitates a reaction but is not itself changed at completion of the reaction

CD4 Cells – A type of lymphocyte. CD4 T lymphocytes (CD4 cells) help coordinate the immune response by stimulating other immune cells, such as macrophages, B lymphocytes (B cells), and CD8 T lymphocytes (CD8 cells), to fight infection.

Cell – The smallest structural unit of living organisms that is able to grow and reproduce independently.

Cell Based Therapies – A treatment that administers cells required to repair or rebuild depleted cell populations or tissues. These may include cells derived from stem cells.

Cell Culture – The growth of cells in a laboratory where nutrients, growth factors and all other requirements for cell survival are provided.

Chemotherapy – is the use of powerful drugs to kill or slow the growth of cancer cells. The drugs are called cytotoxics, which means toxic to cells (cyto). Some of these drugs come from natural sources such as plants, while others are completely made in a laboratory.

Chromosomes -Subcellular structures which convey the genetic material of an organism. Thread like components in the cell that contain DNA and proteins. Genes are carried on the chromosomes.

Chronic – Descriptive term used to describe an illness or
infection that may be recurrent or last a long time

Chronic Obstructive Pulmonary Disease (COPD) – is a group of progressive lung diseases. The most common are  emphysema  and  chronic bronchitis .

COPD causes narrowing of the airways in the lung, making it difficult to breathe. It gets worse over time.

Cleanroom (or clean facility) – environment in which contamination from airborne particles is controlled (specified by the number of particles of a specific size per cubic meter) that is designed to minimize the introduction and generation of disallowed airborne particles inside the room, and where control over other relevant elements such as humidity, temperature and pressure is possible

Clinical Benefit – A therapeutic intervention may be said to confer clinical benefit if it prolongs life, improves function, and/or improves the way a patient feels.

Clinical Trial – A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

A few weeks back I compiled a blog post explainer on clinical trials. You can view it here:

Clinical trials explained.

ClinicalTrials.Gov – is an online registry of clinical trials that are being conducted around the world.  ClinicalTrials.gov is operated by the National Library of Medicine at the National Institutes of Health and can be accessed by anyone who has access to the internet.

Clone – A group of genes, cells, or organisms derived from a common ancestor. Because there is no combining of genetic material (as in sexual reproduction), the members of the clone are genetically identical or nearly identical to the parent.

Collaborator – An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.

Community-Acquired Pneumonia (CAP) – CAP is pneumonia acquired ouutside a hospital environment by somebody who is not immunocompromised

Comparison – To learn more, researchers compare results from patients in the experimental groups with results from patients in the control groups.

Compassionate Use – Expanded access, also called “compassionate use,” provides a pathway for patients to gain access to investigational drugs, biologics and medical devices for serious diseases or conditions.

Investigational drugs and devices have not yet been approved by the FDA and they have not been proven to be safe and effective. Therefore, they may be effective in the treatment of a condition, or they may not. It is important to remember that the drug/biologic/medical device may have unexpected serious side effects and that patients need to consider all the possible risks when seeking access to an investigational medical product.

To gain access to an investigational medical product outside of a clinical trial, the sponsors must decide whether to make their experimental medical product available to patients via expanded access.  FDA regulations specify two groups of people eligible for expanded access:

•  those with life-threatening diseases or conditions for which “there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment”
•  those with serious diseases or conditions that have a “substantial impact on day-to-day functioning”

In most cases, patients who seek compassionate use must have exhausted all approved therapies for their condition, and be unable to enroll in a clinical trial.

Complete Response Letter – When the FDA cannot approve a BLA or NDA they may issue an Complete Response Letter to the applicant.

In the letter they will describe specific deficiencies in the application. They may be minor, such as labelling, or major, such as a new clinical trial

When possible, FDA recommends actions that might be taken to place the application in an approval standing.

Conflict of Interest – A conflict of interest occurs when individuals involved with the conduct, reporting, oversight, or review of research also have financial or other interests, from which they can benefit, depending on the results of the research.

Congenital – Present at birth.

Contaminant –  Impurity of a chemical or microbiological nature, or foreign matter, not intended to be present in or on a raw material (including compounds that can leach from sources such as plastic containers), intermediate or active substance introduced during production, packaging and repackaging, sampling, storage or transport

Control group – The group of participants that receives standard treatment or a placebo. The control group may also be made up of healthy volunteers. Researchers compare results from the control group with results from the experimental group to find and learn from any differences.

Covid-19 – The disease caused by the Severe Acute Respiratory Syndrome-Related Coronavirus 2

Cord blood – The blood in the umbilical cord and placenta after child birth.

Cord blood contains hematopoietic stem cells, also known as cord blood stem cells, which can regenerate the blood and immune system and can be used to treat some blood disorders such as leukemia or anemia. Cord blood can be stored long-term in blood banks for either public or private use. Also called umbilical cord blood.

C-Reactive Protein (CRP) – is a substance produced by the liver in response to inflammation. A high level of CRP in the blood is a marker of inflammation. It can be caused by a wide variety of conditions, from infection to cancer.

Cryopreservation –  is a process that preserves cells, tissues, or any other biological constructs by cooling the samples to very low temperatures.

Culture – As a noun, cultivation of living organism in prepared medium; as a verb, to grow in prepared medium.

Culture Medium – Any nutrient system for the artificial cultivation of bacteria or other cells; usually a complex mixture of organic and inorganic materials

Cytokines – Cytokines are small proteins released by many different cells in the body, including those of the immune system where they coordinate the body’s response against infection and trigger inflammation. The name ‘cytokine’ is derived from the Greek words for cell (cyto) and movement (kinos).

Cytokine Storm – A severe immune reaction in which the body releases too many cytokines into the blood too quickly. Cytokines play an important role in normal immune responses, but having a large amount of them released in the body all at once can be harmful.

Sometimes, a cytokine storm may be severe or life threatening and lead to multiple organ failure.

Cytotoxic – Toxic to cells, cell-toxic, cell-killing. Any agent or process that kills cells.  Chemotherapy  and radiotherapy are forms of cytotoxic therapy. They kill cells.

D

Data Monitoring Committee (DMC) –  A group of independent scientists who monitor the safety and scientific integrity of a clinical trial. The DMC can recommend to the sponsor that the trial be stopped if it is not effective, is harming participants, or is unlikely to serve its scientific purpose. Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB.

Diabetic Kidney Disease (DKD) –

Differentiation – The process by which cells become increasingly specialized to carry out specific functions in tissues and organs.

DME or Diabetic Macular Edema – DME is the leading cause of blindness in diabetics.

https://www.youtube.com/watch?v=XgDyqKnIsEM

DNA or Deoxyribonucleic Acid – The molecule that carries the genetic information for most living systems. The DNA molecule consists of four bases (adenine, cytosine, guanine, and thymine)and a sugar-phosphate backbone, arranged in two connected strands to form a double helix.

DNA Sequencing – Technologies through which the order of base pairs in a DNA molecule can be determined.

Dosage Form – A dosage form is the physical form in which a drug is produced and dispensed, such as a tablet, a capsule, or an injectable.

Double-blind research design – A study in which neither the participant nor the researcher knows whether the participant is in the treatment or control group.

Double-blind, randomized, controlled clinical trial – This is a clinical trial in which the researchers evenly divide study participants into a group receiving the experimental intervention and a group receiving standard or no treatment. Neither group knows how it has been assigned. This practice reduces the chance for a “placebo effect,” in which a treatment with no active ingredient produces results expected from a treatment with an active ingredient.

Dose – Measured quantity of a therapeutic drug taken at one time

Dose Response Curve – Graph that describes the response of a biological system, typically the fraction of drug bound to its target, versus drug concentration, expressed as log[dose]

Drug  – A drug is defined as:

• A substance recognized by an official pharmacopoeia or formulary.
• A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.
• A substance (other than food) intended to affect the structure or any function of the body.
• A substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device.
• Biological products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical process versus biological process.)

E

Efficacy – Indication that the clinical trial intervention produces a desired therapeutic effect on the disease or condition under investigation.

Eligibility Criteria – The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

EMA – European Medicines Agency. An agency of the European Union that oversees the use of medicinal products.

Embryonic stem cells (ESCs) – Undifferentiated cells derived from the inner cell mass of the blastocyst; these cells have the potential to give rise to all cell types in the fully formed organism and undergo self-renewal.

Endpoint – Principal indicator(s) used for assessing the primary question (i.e., hypothesis) of a clinical trial. A variable that pertains to the efficacy or safety evaluations of a trial. An endpoint is more specific as compared to an outcome since it relate to the planned objective of the study.

Enrollment – The process of registering or entering a patient into a clinical trial. Once a patient has been enrolled, the participant would then follow the clinical trial protocol. Clinical investigations are designed to enroll a set number of participants to increase the likelihood of answering the trial questions.

Enzyme – A protein catalyst that facilitates specific chemical or metabolic reactions necessary for cell growth and reproduction.

Experiment – A study done to answer a question. Other words to describe an experiment are “research,” “study,” and “protocol.”

Expanded Access – also called “compassionate use,” provides a pathway for patients to gain access to investigational drugs, biologics and medical devices for serious diseases or conditions. Investigational drugs and devices have not yet been approved by the FDA and they have not been proven to be safe and effective. Therefore, they may be effective in the treatment of a condition, or they may not. It is important to remember that the drug/biologic/medical device may have unexpected serious side effects and that patients need to consider all the possible risks when seeking access to an investigational medical product.

To gain access to an investigational medical product outside of a clinical trial, the sponsors must decide whether to make their experimental medical product available to patients via expanded access.  FDA regulations specify two groups of people eligible for expanded access:

• those with life-threatening diseases or conditions for which “there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment”
• those with serious diseases or conditions that have a “substantial impact on day-to-day functioning”

In most cases, patients who seek compassionate use must have exhausted all approved therapies for their condition, and be unable to enroll in a clinical trial.

Expression – In genetics, manifestation of a characteristic that is specified by a gene. With hereditary diseases, for example, a person can carry the gene for the disease but not actually have the disease. In this case, the gene is present but not expressed.

In molecular biology and industrial biotechnology, the term is often used to mean the production of a protein by a gene that has been inserted into a new host organism

F

Fast track – is a FDA process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.

Determining whether a condition is serious is a matter of judgment, but generally is based on whether the drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the condition, if left untreated, will progress from a less severe condition to a more serious one. AIDS, Alzheimer’s, heart failure and cancer are obvious examples of serious conditions. However, diseases such as epilepsy, depression and diabetes are also considered to be serious conditions.

A drug that receives Fast Track designation is eligible for some or all of the following:

• More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
• More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
• Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
• Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA

FDA – Food and Drug Administration. A government agency within the U.S. Department of Health and Human Services that oversees the Nation’s public health by making sure that human and veterinary drugs, vaccines, biological products, medical devices, cosmetics, dietary supplements, the food supply, and any products that give off radiation are safe, effective, and secure.

 FDA Approval  – means the final regulatory approval of the FDA required to commence commercial marketing of a health product.

Fetal Bovine Serum (FBS) – Fetal bovine serum is a byproduct of harvesting cattle for the meatpacking industry–it offers essential growth factors for the maintenance and growth of cultured cells.

Fibroblast – A common connective or support cell found within most tissues of the body.

First-In-Class – novel drug which utilizes a unique mechanism of action when interacting with its target

Focal Segmental Glomerulosclerosis (FSGS) – A rare but serious kidney disease.

G

Gas Chromatography – Analytical technique in which compounds are separated based on their differential movement in a stream of inert gas through a (coated) capillary at elevated temperature. This technique is suitable for the analysis of volatile compounds or compounds that can be made volatile by derivatization reactions and that are also stable at higher temperatures.

Gene – A segment of chromosome that encodes the necessary regulatory and sequence information to direct the synthesis of a protein or RNA product.

Generic Drug – A generic drug is the same as a brand name drug in dosage, safety, strength, how it is taken, quality, performance, and intended use. Before approving a generic drug product, FDA requires many rigorous tests and procedures to assure that the generic drug can be substituted for the brand name drug.

The FDA bases evaluations of substitutability, or “therapeutic equivalence ,” of generic drugs on scientific evaluations.

By law, a generic drug product must contain the identical amounts of the same active ingredient(s) as the brand name product. Drug products evaluated as “therapeutically equivalent” can be expected to have equal effect and no difference when substituted for the brand name product.

Genetic Code – The mechanism by which genetic information is stored in living organisms. The code uses sets of three nucleotide bases (codons) to make the amino aids that, in turn, constitute proteins.

Genetic Engineering – A technology used to alter the genetic material of living cells in order to make them capable of producing new substances or performing new functions.

Genome – The total hereditary material of a cell, comprising the entire chromosomal set found in each nucleus of a given species.

Genomics – Science that studies the genomes (i. e., the complete genetic information) of living beings. This commonly entails the analysis of DNA sequence data and the identification of genes.

Gene Therapy – The replacement of a defective gene in an organism suffering from a genetic disease. Recombinant DNA techniques are used to isolate the functioning gene and insert it into cells. Over three hundred single-gene genetic disorders have been identified in humans. A significant percentage of these may be amenable to gene therapy.

GMP – Good Manufacturing Practice defines quality standards set by the US Food and Drug Administration (USFDA) for the production of materials used in the clinical setting.

Graft-versus-host disease – A reaction that occurs after a bone marrow transplant where the transplanted cells attack the tissue of the recipient.

H

Healthy volunteer – In a clinical study, a person who does not have the disorder or disease being studied. Results from healthy controls are compared to results from the group being studied.

Hematopoietic – Blood-forming

Host – A cell or organism used for the growth of a virus, plasmid, or other form of foreign DNA, or for the production of cloned substances.

Hypothesis – A testable statement regarding the investigational medical device safety or performance (effectiveness) that is used to design the clinical trial and that can be accepted or rejected based on the results of the clinical trial and statistical calculations.

I

Immunomodulatory – The ability to modify the immune system or an immune response.

Immune Response – The response of the immune system
against foreign substances.

Immune System – The aggregation of cells, biological substances (such as antibodies), and cellular activities that work together to provide resistance to disease.

Immunity – Nonsusceptibility to a disease or to the toxic effects of antigenic material.

Immunoglobulin – General name for proteins that function as antibodies. These proteins differ somewhat in structure, and are grouped into five categories on the basis of these differences: immunoglobulin G (IgG) IgM, IgA, IgD and IgE.

Immunology – Study of all phenomena related the body’s response to antigenic challenge (i.e. immunity, sensitivity, and allergy).

Immunomodulators -A diverse class of proteins that boost the immune system. Many are cell growth factors that accelerate the production of specific cells that are important in mounting an immune response in the body.

Immunotoxins – Specific monoclonal antibodies that have a protein toxin molecule attached. The monoclonal antibody is targeted against a tumor cell and the toxin is designed to kill that cell when the antibody binds to it. Immunotoxins have also been termed “magic bullets.”

Induced pluripotent stem cells (iPSCs) – Embryonic-like stem cells that are derived from reprogrammed, adult cells, such as skin cells. Like ESCs, iPSC cells are pluripotent and can self-renew.

In vitro – In glass, as in a test tube. An in vitro test is one that is done in glass or plastic vessels in the laboratory. In vitro is the opposite of in vivo.

In vivo – In the living organism. For example, an experiment that is done in vivo is done in the body of a living organism. In vivo is the opposite of in vitro.

Inclusion/exclusion criteria – are the factors that allow someone to participate in a clinical trial. Exclusion criteria are the factors that prevent someone from participating in the trial. These factors may include a person’s illness, health history, past treatment, age, sex, or where he or she lives.

Indication – A disease, symptom, or particular set of circumstances that make a particular test, medication, procedure, or surgery advisable. For a treatment, an indication refers to the use of that treatment in treating a particular disease.

Inflammatory Response – The inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause.

Informed consent – When a participant provides informed consent, it means that he or she has learned the key facts about a research study and agrees to take part in it.

Intellectual Property (IP) – Intellectual property encompasses any new creation of the mind such as an invention or drug discovery which is given the legal status of property. Tools to protect IP include: patents, copyrights, trademarks, plant variety protection rights, trade secrets, and protection of regulatory data.

Interferon – A class of lymphokine that interferes with the ability of viruses to reproduce. Interferon also boosts the immune system.

There are a number of different interferons. They fall into three main classes : alpha (leukocyte), beta (fibroblast), and gamma (immune). All are proteins (lymphokines) normally produced by the body in response to infection.

Interim Analysis – Any analysis intended to compare treatment arms with respect to efficacy or safety at any time prior to the formal completion of a trial.

Interleukin – One of a group of related proteins made by leukocytes (white blood cells) and other cells in the body. Interleukins regulate immune responses.  An interleukin is a type of cytokine. Also called IL along with an identifying number. They are synthesized by lymphocytes, monocytes, macrophages, and certain other cells

Intervention – A procedure or treatment such as a drug, nutritional supplement, gene transfer, vaccine, behavior or device modification that is performed for clinical research purposes.

Investigational Drug – can also be called an experimental drug and is being studied to see if your disease or medical condition improves while taking it. Scientists are trying to prove in clinical trials:

• If the drug is safe and effective.
• How the drug might be used in that disease.
• How much of the drug is needed.
• Information about the potential benefits and risks of taking the drug.

Investigational New Drug Application (IND) – An IND is a request for authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans.

Ischemia – Ischemia is usually described as a blockage or a build up in your arteries, such as plaque from a poor diet.

Isoenzyme (isozyme) – One of the several forms that a given enzyme can take. The forms may differ in certain physical properties, but function similarly as biocatalysts.

J

K

L

Label – The FDA approved label is the official description of a drug product which includes indication (what the drug is used for); who should take it; adverse events (side effects); instructions for uses in pregnancy, children, and other populations; and safety information for the patient. Labels are often found inside drug product packaging.

Leukocyte (white blood cell) – Group of small colorless
blood cells that play a major role in the body’s
immune response. There are five basic types of
leukocytes: monocytes, lymphocytes, neutrophils,
eosinophils, and basophils.

Liquid Chromatography – Analytical technique in which substances are separated based on their differential movement within a liquid stream. A common form of liquid chromatography is column chromatography in which the dissolved substances may bind from the liquid differentially to a column of solid material with different affinities and subsequently be released thus be carried from the column into the at different speeds by the liquid through the column liquid, thus creating a basis for separation.

Lymph – Fluid made up of various components of the
immune system that flows throughout tissues of the
body via the lymph nodes and lymphatic vessels.

Lymph nodes – Small bean-sized organs of the immune
system, distributed widely throughout the body. Each
lymph node contains a variety of specialized
compartments that house B-lymphocytes,
T-lymphocytes and macrophages.

Lymphocytes – Small white cells, normally present in the
blood and in lymphoid tissue, that bear the major
responsibility for carrying out the functions of the
immune system. There are two major forms of
lymphocytes, B-lymphocytes and T-lymphocytes,
which have distinct but related functions in generating
an immune response.

Lymphokines – A class of cytokines specifically secreted
by lymphoid cells that are important in regulating
inflammation and immune responses and for
recruiting other cells to participate in immune and
inflammatory responses

M

Macrophages -A type of white blood cell produced in blood vessels and loose connective tissues that can ingest dead tissue and cells and is involved in producing interleukin 1.When exposed to the lymphokine “macrophage-activating factor,” macrophages also kill tumor cells

Marker – Any genetic element (locus, allele, DNA sequence or chromosome feature) which can be readily detected by phenotype, cytological or molecular techniques, and used to follow a chromosome or chromosomal segment during genetic analysis. See centromere marker; chromosome marker; DNA marker; genetic marker; inside marker; outside marker

Masking/Blinding – A procedure in which the investigator administering the assessments and intervention as well as the participants in a clinical trial are kept unaware of the treatment assignment(s). Single blinding usually refers to the study participant(s) being unaware, and double blinding usually refers to the study participant(s) and any of the following being unaware of the treatment assignment(s): investigator(s), monitor, and data analyst(s).

Mass Spectrometry – Analytical technique by which compounds in a vacuum compartment are ionized, eventually fragmented, accelerated, and detected based upon the mass-dependent behavior of the ionized compounds or their fragments in response to the application of a magnetic or electric field in a vacuum.

Mean – Nasty. Just kidding.  Mean is used in statistics to create an average, Care should be taken not to confuse “mean” with “median”

Mechanism of Action – In medicine, a term used to describe how a drug or other substance produces an effect in the body.  Also called a Mode of Action

Medium – A liquid or solid (gel) substance containing nutrients needed for cell growth.

Mesenchymal stem cells (MSCs) – A term used to describe cells isolated from the connective tissue that surrounds other tissues and organs.

MSCs were first isolated from the bone marrow and shown to be capable of making bone, cartilage and fat cells. MSCs are now grown from other tissues, such as fat and cord blood. Not all MSCs are the same and their characteristics depend on where in the body they come from and how they are isolated and grown. May also be called mesenchymal stromal cells.

Metabolism – All biochemical activities carried out by an organism to maintain life.

Metabolite – A substance produced during or taking part in metabolism.

Microbiology – Study of living organisms and viruses, which can be seen only under a microscope.

Micronutrient – Any substance, such as a vitamin or trace element, essential for healthy growth and development but required only in minute amounts.

Microorganism – Any organism that can be seen only with the aid of a microscope. Also called microbe.

Mode of Action – Mode of action is the means by which a product achieves an intended therapeutic effect or action.

Molecular Biology -The study of biological processes at the molecular level.

Molecules – The smallest unit of matter of an element or
compound

Monoclonal Antibody – Highly specific, purified antibody that is derived from only one clone of cells and recognizes only one antigen.

Monocyte – Phagocytic cell found in the blood that acts
as a scavenger, capable of destroying invading
bacteria or other foreign material; these cells develop
into macrophages in tissues.

Monokines – Chemical messengers produced and
secreted by monocytes and macrophages.

mRNA and mRNA vaccines – Messenger ribonucleic acid.

 Multicenter Trial – A clinical trial conducted according to a single protocol but at more than one site, and, therefore, carried out by more than one investigator.

Multipotent stem cells – Stem cells that can give rise to several different types of specialized cells in specific tissues; for example, blood stem cells can produce the different types of cells that make up the blood, but not the cells of other organs such as the liver or the brain.

Multisystem Inflammatory Syndrome (MIS-C) – is a serious condition that appears to be linked to coronavirus disease 2019 (COVID-19).

Most children who become infected with the COVID-19 virus have only a mild illness. But in children who go on to develop MIS-C, some organs and tissues — such as the heart, lungs, blood vessels, kidneys, digestive system, brain, skin or eyes — become severely inflamed. Signs and symptoms depend on which areas of the body are affected.

Mutation – A structural change in a DNA sequence resulting from uncorrected errors during DNA replication.

N

Nanotechnology – The production and application of structures, devices and systems by controlling shape and size at nanometre scale.

National Institutes of Health (NIH) – Part of the U.S. Department of Health and Human Services, NIH is the primary Federal agency for conducting and supporting medical research. NIH scientists investigate ways to prevent disease as well as the causes, treatments, and even cures for common and rare diseases. Composed of 27 Institutes and Centers, NIH provides leadership and financial support to researchers in every state and throughout the world.

Natural Killer Cells –

A cell that can react against and destroy another cell without prior sensitization to it. Abbreviated NK cell.

NK cells are part of our first line of defense against  cancer  cells and virus-infected cells and are stimulated by interferon.

NK cells are small lymphocytes that originate in the bone marrow and develop without the influence of the thymus. An NK cell attaches to a target cell, releases chemicals that breach its cell wall, and causes it to lyse (break up).

New Drug Application (NDA) – When the sponsor of a new drug believes that enough evidence on the drug’s safety and effectiveness has been obtained to meet FDA’s requirements for marketing approval, the sponsor submits to FDA a new drug application (NDA). The application must contain data from specific technical viewpoints for review, including chemistry, pharmacology, medical, biopharmaceutics, and statistics. If the NDA is approved, the product may be marketed in the United States.

New Drug Approval Process – After the animal testing stage, FDA decides whether it is reasonably safe for the company to move forward with clinical trials—studies that evaluate the safety and effectiveness of a drug in healthy people and in patients. The drug company submits the results of such studies to FDA for review. The agency conducts a thorough review of the safety and effectiveness data, and considers how the benefits compare to the risks when making a decision of whether or not to approve a drug.

NSCs (neural stem cells) – specialized stem cells responsible for repairing nerve-insulating myelin in the brain. These can be derived from other types of stem cells such as mesenchymal cells.

Null Hypothesis – The null hypothesis is a typical statistical theory which suggests that no statistical relationship and significance exists in a set of given single observed variable, between two sets of observed data and measured phenomena.

O

ODAC ( Oncoloogic Drugs Advisory Committee. – When a scientific, technical, or policy question arises, such as whether an unapproved product is safe and effective, FDA often relies on Advisory Committees to provide independent advice. Committee members include scientific experts—such as physician-researchers and statisticians—and members of the public, including a FDA Patient Representative.

“Off Label Use” – 

• Describes the legal use of a prescription drug to treat a disease or condition for which the drug has not been approved by the U.S. Food and Drug Administration.
• A drug prescribed for conditions other than those approved by the FDA.

Oncology – Study of tumors.

Open-Label Trial – A clinical trial in which investigators and participants know which intervention is being administered.

Orphan Drug – An FDA category that refers to medications used to treat diseases and conditions that occur rarely.

There is little financial incentive for the pharmaceutical industry to develop medications for these diseases or conditions. Orphan drug status, however, gives a manufacturer specific financial incentives to develop and provide such medications

P

P- Value -A p value is used in  hypothesis testing  to help you  support or reject the null hypothesis . The p value is the evidence against a  null hypothesis . The smaller the p-value, the stronger the evidence that you should reject the null hypothesis.

Parasite – A plant or animal that lives, grows, and feeds
on or within another living organism.

Passive Immunity – Immunity acquired from receiving preformed antibodies.

Patent – A patent is an exclusive right granted for an invention, which is a product or a process that provides, in general, a new way of doing something, or offers a new technical solution to a problem. To get a patent, technical information about the invention must be disclosed to the public in a patent application.

Pathogen – Agent or microorganism that can cause disease

Pediatric – of, relating to, affecting, or being an infant, child, or adolescent

Peer Review – Review of a clinical trial by experts chosen by the study sponsor. These experts review the trials for scientific merit, participant safety, and ethical considerations.

Phagocyte – A type of white blood cell that can ingest invading microorganisms and other foreign material. See also Macrophage.

Pharmacoeconomics (PE) – Study of the value of one pharmaceutical product compared with another

Phase – Categories, defined by the Food and Drug Administration (FDA), for describing the clinical trial of a drug based on the study’s characteristics, such as the objective and number of participants. There are four phases:

• Phase I trials test an experimental drug, vaccine or device in a small group of people to evaluate safety, identify side effects and determine safe dosages.
• Phase II trials involve larger groups of people than Phase I and they are designed to assess whether an experimental treatment is safe and whether it works. This phase can last several years.
• Phase III trials are usually large studies comparing the experimental drug or vaccine to a placebo or standard treatment, to evaluate whether the drug works and collect information to allow it to be used safely.
• Phase IV trials are performed once a drug has reached the market, to provide additional information about the best use of the drug.

Phenotype – Observable characteristics, resulting from interaction between an organism’s genetic make-up and the environment

Placebo –

• A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment’s effectiveness.
• An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Placebo effect – Sometimes people taking a study medication receive benefits that are not from the chemicals in the medicine. This is called a “placebo effect.” For example, if a participant feels hopeful about a treatment, he or she may be more likely to notice positive changes than negatives ones. A researcher’s hope may also sway a participant’s response. Double-blind research design helps minimize the placebo effect.

Plasma cells – Antibody-producing cells descended from
B-lymphocytes

Platelets – Smallest and most fragile of the blood cells;
primary function is associated with the process of
blood clotting

Pluripotent stem cells – Stem cells that can become all the cell types that are found in an embryo, fetus or adult, such as embryonic stem cells or induced pluripotent (iPS) cells.

Post-Market Surveillance – is the process by which a drug’s safety is monitored on an ongoing basis after a drug is approved by FDA. Post-market surveillance looks to identify problems that were not observed or recognized before approval and any problems that may arise because a drug may not be used as described in the drug labeling, or because a drug is being manufactured incorrectly.

Potency – Dose of medicinal product that produces a given biological response or expression of the activity of a drug or medicinal product, in terms of the concentration or amount needed to produce a defined biological effect

Pre-Clinical Data – Before a drug can be tested in people in the United States; sponsors (drug manufacturers, research institutions, and other organizations that develop drugs) must show FDA results of testing they have done in laboratory animals and what they propose to do for human testing.

Precursor cells – An intermediate cell type between stem cells and differentiated cells. Precursor cells have the potential to give rise to a limited number or type of specialized cells. Also called progenitor cells.

Primary Endpoint – The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins.

Principal Investigator – A Principal Investigator is a doctor who leads the clinical research team and, along with the other members of the research team, regularly monitors study participants’ health to determine the study’s safety and effectiveness.

Priority Review – A FDA Priority Review designation will direct overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.

Significant improvement may be demonstrated by the following examples:

• evidence of increased effectiveness in treatment, prevention, or diagnosis of condition;
• elimination or substantial reduction of a treatment-limiting drug reaction;
• documented enhancement of patient compliance that is expected to lead to an improvement in serious outcomes; or
• evidence of safety and effectiveness in a new subpopulation.

FDA decides on the review designation for every application. However, an applicant may expressly request priority review as described in the Guidance for Industry Expedited Programs for Serious Conditions – Drugs and Biologics. It does not affect the length of the clinical trial period. FDA informs the applicant of a Priority Review designation within 60 days of the receipt of the original BLA, NDA, or efficacy supplement. Designation of a drug as “Priority” does not alter the scientific/medical standard for approval or the quality of evidence necessary.

Progenitor cells – see Precursor cells

Prognosis – The likely outcome or course of a disease; the chance of recovery or recurrence.

Prophylaxis – Medical therapy initiated to prevent or
guard against disease or infection.

Protein – A class of chemicals found in the body made
up of chains of amino acids (building blocks)

Protocol – A written study plan on which the clinical trial is based. A protocol describes what types of people may or may not participate in the trial; the schedule of tests, procedures, medications, and dosages to be administered; the outcome measures that will be evaluated; and the length of the study.

Purity – Degree that a substance is free from contaminants or impurities.

Q

Quality Assurance (QA) – Systematic approach to ensure that the data are generated, documented (recorded), and reported in compliance with the protocol and good clinical practice (GCP) standards.

Quality Control (QC) – The internal operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of trial related activities have been fulfilled (e.g., data and form checks, monitoring by study staff, routine reports, correction actions, etc.).

R

Randomization – The process of assigning clinical trial participants to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.

Randomized Controlled Trial (RCT) – A study in which randomization is used to assign patients to treatments. The purpose of the randomized controlled trial is to:

(1) to guard against any use of judgment or systematic arrangements leading to one treatment getting preferential assignment; i.e., to avoid bias;

(2) to provide a basis for the standard methods of statistical analysis such as significance tests.

Reagent – Substance used in a chemical reaction, often for analytical purposes

Receptor – Cellular macromolecule, or an assembly of macromolecules, that is concerned directly and specifically with chemical signaling between and within cells, and induces a cellular or tissue response upon binding a ligand

Recruitment – Active efforts by investigators to identify subjects who may be suitable for enrollment into a clinical trial. Subjects are selected on the basis of the protocol’s inclusion and exclusion criteria during the clinical trial recruitment period.

The number of subjects that must be recruited for enrollment into a study and meet the requirements of the protocol. In multicenter studies, each investigator has a recruitment target or defined number of subjects to be enrolled

Regenerative Medicine – An interdisciplinary branch of medicine with the goal of replacing, regenerating or repairing damaged tissue to restore normal function. Regenerative treatments can include cellular therapy, gene therapy and tissue engineering approaches.

Regulatory Agency – is a public authority or government agency responsible for exercising autonomous authority over some area of human activity in a regulatory or supervisory capacity. An independent regulatory agency is a regulatory agency that is independent from other branches or arms of the government. Regulatory agencies deal in the area of administrative law—regulation or rulemaking (codifying and enforcing rules and regulations and imposing supervision or oversight for the benefit of the public at large).

Reproducibility – precision between multiple measurements of a sample or sample sets, which may include collaborative studies between laboratories or analysis at different times, and is often applied to the standardization of methodology

Reprogramming – In the context of stem cell biology, this refers to the conversion of differentiated cells, such as fibroblasts, into embryonic-like iPS cells by artificially altering the expression of key genes.

Research – A study done to answer a question. Scientists do research when they’re not sure what will work best to help people with an illness. Other words to describe clinical research are “clinical trial,” “protocol,” “study,” and “experiment.”

RNA – Ribonucleic acid; it “reads” DNA and acts as a messenger for carrying out genetic instructions.

S

Safety – Safety is relative freedom from harm. In clinical trials, this refers to an absence of harmful side effects resulting from use of the product and may be assessed by laboratory testing of biological samples, special tests and procedures, psychiatric evaluation, and/or physical examination of subjects.

Scale-up – Transition from small-scale production to production of large industrial quantities.

Self-renewal – A special type of cell division in stem cells by which they make copies of themselves.

Sepsis – An infection of the blood.

Serious Adverse Event (SAE) – Any adverse event that:

• Results in death
• Is life threatening, or places the participant at immediate risk of death from the event as it occurred
• Requires or prolongs hospitalization
• Causes persistent or significant disability or incapacity
• Results in congenital anomalies or birth defects
• Is another condition which investigators judge to represent significant hazards

Side Effect –

• A problem that occurs when treatment affects healthy tissues or organs. (NCI)
• Any undesired actions or effects of a drug or treatment. Negative or adverse effects may include headache, nausea, hair loss, skin irritation, or other physical problems. Experimental drugs must be evaluated for both immediate and long-term side effects

Single-blind research design – A study in which one party, either the investigator or participant, is unaware of what medication or intervention the participant is taking; also called single-masked study.

Sponsors – Clinical trials are sponsored or funded by various organizations or individuals, including physicians, foundations, medical institutions, voluntary groups, and pharmaceutical companies, as well as Federal agencies such as NIH, FDA, the Department of Defense, and the Department of Veterans Affairs.

Standard deviation – The standard deviation is used in statistics to measure the spread of scores in a data set.

Standard treatment – The treatment that medical professionals consider at the time of the study to be the most prevalent and best available treatment.

Standardized procedures – These are study rules that researchers must follow exactly for every participant, regardless of what each participant is used to. For example, if you normally take a medicine by injection but the experiment is testing the same medicine in pill form, the researcher must prescribe pills to you. The researcher cannot use a different method for you.

Statistical Significance – The probability that an event or difference occurred by chance alone. In clinical trials, the level of statistical significance depends on the number of participants studied and the observations made, as well as the magnitude of differences observed.

Stem Cells – Cells from which all blood cells and immune
cells are derived, bone marrow is rich in stem cells.

Stem Cell Line – Stem cells that have been established and propagated in culture and which maintained consistent characteristics and developmental potential.

Stem Cell Tourism – The travel to another state, region or country specifically for the purpose of undergoing a stem cell treatment available at that location. This phrase is also used to refer to the pursuit of untested and unregulated stem cell treatments.

Study – Conducted by a principal investigator who is often a doctor. Members of the research team regularly monitor the participant’s health to determine the study’s safety and effectiveness. Other words to describe a study are “clinical trial,” “protocol,” “experiment,” and “research.”

T

Tissue – A group of cells with a similar function or embryological origin. Tissues organize further to become organs.

Tissue-specific stem cells – Stem cells that can give rise to the specialized cells in specific tissues; blood stem cells, for example, can produce the different types of cells that make up the blood, but not the cells of other organs such as the liver or the brain. Includes all stem cells other than pluripotent stem cells such as embryonic and induced pluripotent cells. Also called adult or somatic stem cells.

T-lymphocytes (or T-cells) – Lymphocytes that are
processed in the thymus; they are responsible in part
for carrying out the immune response

TNF (Tumor Necrosis Factor) – A pro inflammatory cytokine that is produced by macrophages (TNF-α) and some T cells (TNF-β). They can exert a direct toxic effect on neoplastic cells. It has an antineoplastic effect but causes inflammation (as in rheumatoid arthritis)

Totipotent – The ability to give rise to all the cells of the body and cells that aren’t part of the body but support embryonic development, such as the placenta and umbilical cord.

Toxicity – An adverse effect produced by a drug that is detrimental to the participant’s health. The level of toxicity associated with a drug will vary depending on the condition which the drug is used to treat.

Type A Meeting (with FDA) – A meeting that is immediately necessary for an otherwise stalled drug development program to proceed. Type A meetings may include:

• Dispute resolution meetings
• Meetings to discuss clinical holds in which development is stalled and a new path forward should be discussed
• Special protocol assessment meetings that are requested by sponsors or applicants after receipt of FDA evaluation of protocols under the special protocol assessment procedures
• Post-action meetings requested by the sponsor within 3 months after an FDA regulatory action other than an approval

U

Unmasking/Unblinding – A procedure in which one or more parties to the trial are made aware of the treatment assignment(s).

Unmet Need – Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy.

Any drug being developed to treat or prevent a condition with no current therapy obviously is directed at an unmet need. If there are available therapies, a fast track drug must show some advantage over available therapy, such as:

• Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
• Avoiding serious side effects of an available therapy
• Improving the diagnosis of a serious condition where early diagnosis results in an improved outcome
• Decreasing a clinical significant toxicity of an available therapy that is common and causes discontinuation of treatment
• Ability to address emerging or anticipated public health need

V

Vaccine – (refer also to mRNA vaccine and Adenovirus vaccine) A substance that contains components from an infectious organism which stimulates an immune response in order to protect against subsequentinfection by that organism

VEGF or Vascular Endothelial Growth Factor – VEGF’s are important regulators of vascular development during embryogenesis (vasculogenesis) as well as during blood vessel formation (angiogenesis) in the adult.

Virology – Study of viruses

Virus – A submicroscopic microbe causing infectious
disease; can reproduce only in living cells.

W

Wet AMD (Age-related macular degeneration –

White blood cells – See leukocyte.

X

Y

Z

Author – Ratfink