International Nonproprietary Names (INN)
International Nonproprietary Names
- 1 International Nonproprietary Names
- 2 History of the International Nonproprietary Names System
- 3 Use of International Nonproprietary Names
- 4 Modified International Nonproprietary Names (INNM)
- 5 CFR — Code of Federal Regulations Title 21
- 6 ELIMINATION KINETICS
- 7 2019 Suggested Inhaler Sequence
- 8 Suggested Sequence of Administration
- 9 FDA Drug Approval Process
- 10 Steps from Test Tube to New Drug Application Review
- 11 FDA Approval Process
- 12 Sources
- 13 Further information
International Nonproprietary Names (INN) identify pharmaceutical substances or active pharmaceutical ingredients. Each INN is a unique name that is globally recognized and is public property. A nonproprietary name is also known as a generic name. The INN system is managed by the World Health Organization (WHO).
History of the International Nonproprietary Names System
The INN system was established in 1950 by the World Health Assembly and the first list of International Nonproprietary Names for pharmaceutical substances was published in 1953. The cumulative list of INN now stands at some 7000 names designated since that time, and this number is growing every year by some 120-150 new INN.
Since its inception, the aim of the INN system has been to provide health professionals with a unique and universally available designated name to identify each pharmaceutical substance. The existence of an international nomenclature for pharmaceutical substances, in the form of INN, is important for the clear identification, safe prescription and dispensing of medicines to patients, and for communication and exchange of information among health professionals and scientists worldwide.
As unique names, INN have to be distinctive in sound and spelling, and should not be liable to confusion with other names in common use. To make INN universally available they are formally placed by WHO in the public domain, hence their designation as «nonproprietary». They can be used without any restriction whatsoever to identify pharmaceutical substances.
Another important feature of the INN system is that the names of pharmacologically-related substances demonstrate their relationship by using a common «stem». By the use of common stems the medical practitioner, the pharmacist, or anyone dealing with pharmaceutical products can recognize that the substance belongs to a group of substances having similar pharmacological activity.
Use of International Nonproprietary Names
Nonproprietary names are intended for use in pharmacopoeias, labeling, product information, advertising and other promotional material, drug regulation and scientific literature, and as a basis for product names, e.g. for generics.
As a result of ongoing collaboration, national names such as British Approved Names (BAN), Dénominations Communes Françaises (DCF), Japanese Adopted Names (JAN) and United States Accepted Names (USAN) are nowadays, with rare exceptions, identical to the INN. These national naming schemes can be country specific. That is, they refer to ingredients used in the particular country with names intended to meaningful to its citizens. As a result, there is significant overlap and yet some differences between various national schemes. For example, differences exist between BAN and USAN names for the same substance (e.g. acetaminophen is also called paracetamol). In addition to having different names for the same substances, different countries permit the use of different medicinal ingredients. It is assured that all US medications do not have approved names under other countries’ naming schemes. Likewise, these international naming schemes cover medications not currently employed in the USA.
To avoid confusion, which could jeopardize the safety of patients, trade-marks cannot be derived from INN and, in particular, must not include their common stems. The creation of further names within a series would be seriously hindered by the use of a common stem in a brand-name.
Modified International Nonproprietary Names (INNM)
In principle, INN are selected only for the active part of the molecule which is usually the base, acid or alcohol. In some cases, however, the active molecules need to be expanded for various reasons, such as formulation purposes, bioavailability or absorption rate. In 1975 the experts designated for the selection of INN decided to adopt a new policy for naming such molecules. In future, names for different salts or esters of the same active substance should differ only with regard to the inactive moiety of the molecule. For example, oxacillin and ibufenac are INN and their salts are named oxacillin sodium and ibufenac sodium. The latter are called modified INN (INNM).
Before the existence of this rule, some INN were published for salts. In such cases, the term «modified INN» may also be used for a base or acid. For example, levothyroxine sodium was published as an INN and levothyroxine may thus be referred to as an INNM.
CFR — Code of Federal Regulations Title 21
The information on this page is current as of April 1 2019.
For the most up-to-date version of CFR Title 21, go to the Electronic Code of Federal Regulations (eCFR).
Subpart D—Exemptions From Adequate Directions for Use
BOLD ALL CAPS indicate BRAND NAMES
Clear boxes in the chart indicate “short–acting” medications:
Suggested Sequence of Administration
1.) Take short–acting drugs at least 2 hours before long–acting drugs in the same class to avoid interfering with the long–acting drug’s action.
2.) If you MUST take the short acting medications FIRST, ALWAYS wait at least 2 hours before taking any long–acting medications! If SABA is used on a regular scheduled basis, always take it after the LABA, and never less than 2 hours before it.
If you MUST take the SABA agonist before taking the LABA, wait at least 2 hours before taking the LABA after taking the SABA!
3.) If you must use a SABA on a rescue basis, wait at least 2 hours before taking your next dose of LABA.
4.) If you use a SAMA in addition to your LAMA, ALWAYS take it after the LAMA and never less than 2 hours before the LAMA.
Updated October 28, 2016 Noah Greenspan, DPT, CCS, EMT–B & Mark W Mangus (updated 4/27/17), Sr, BSRC, RRT, RPFT, FAARC
FDA Drug Approval Process
Medically reviewed by Leigh Ann Anderson, PharmD Last updated on Apr 13, 2020.
Steps from Test Tube to New Drug Application Review
FDA Approval Process
The U.S. Food and Drug Administration’s (FDA’s) Center for Drug Evaluation and Research (CDER) is a science-led organization in charge of overseeing the drug approval process before a drug is marketed. CDER ensures that both brand and generic drugs work correctly and that the health benefits outweigh the known risks. They review each drug closely using an independent team of clinicians and scientists who evaluate safety, efficacy and labeling of the drug product. After approval, FDA follow-up continues to make sure new drugs continue to be safe and effective.
It takes over $2.6 billion for a manufacturer to get a new drug from the laboratory onto the pharmacy shelf, according to the Tufts Center for the Study of Drug Development. The full research, development and approval process can last from 12 to 15 years. What happens during this time period to be sure that the drug you pick up at the pharmacy is safe and effective?
Investigational New Drug (IND) Application
In the manufacturer’s early phases of drug discovery (preclinical research) they are synthesizing and screening a drug candidate for toxicity in animals before the medicine moves on to human trials. The sponsor files an Investigational New Drug (IND) Application that details specifics such as chemistry, manufacturing and the initial plans for human testing.
The IND is reviewed by the FDA to ensure that clinical trials will be safe for humans and that adequate informed consent is included to protect humans subjects.
Once a company develops a drug, it undergoes several years of laboratory testing before a New Drug Application (NDA) is made to the FDA to begin testing the drug in humans. Only one in 1000 of the compounds that enter laboratory testing will ever make it to human testing.
Phases of Human Testing for Investigational Drugs
If the FDA gives the green light, the investigational drug will then enter three phases of clinical trials:
New Drug Application (NDA)
For an NDA, the company writes and submits an application which includes thousands of pages to the FDA for review and approval. The NDA is the official request for US approval of a drug. The NDA includes all animal and human data, plus side effects, dosing, and effectiveness. Other information, such as pharmacokinetics (how the drug moves through the body), and specifics of manufacturing are also addressed. The FDA team has 60 days to review the NDA and determine if it will be filed for further review.
Once an NDA is filed, the FDA review the product label (package insert) to be sure the clinical information needed to safely use this drug is outlined. The FDA also takes action to inspect manufacturing plants where the drug will be made.
Drugs that may be the first available treatment for an illness or with a significant benefit over existing drugs may receive a special designation:
FDA Advisory Board
A group of independent physicians and other clinicians, called an FDA Advisory Board, meets to discuss the NDA with the FDA reviewers and manufacturer of the product. These meetings often take one or two days. After the meeting, the Advisory Board will make a recommendation for approval, or not, to the FDA, usually through a vote. The FDA often follows the advice of the Board, but is not obligated to do so. This advisory team includes physicians, pharmacists, chemists, pharmacologists, statisticians, and even patient representatives.
Final Drug Approval
After final approval, the drug becomes available for physicians to prescribe. However, drugs may not come to the market immediately because of patents disputes, manufacturing issues, or controlled substance designation from the DEA. Pricing is usually revealed after approval, but the FDA does not consider drug pricing or economics as part of the FDA approval process. This is in contrast to many other countries that do consider the economic impact of new drugs in their society.
MedWatch: At this stage, the drug company will continue to report cases of adverse reactions and other clinical data to the FDA. Patients and healthcare providers can also report side effects or other concerns through the MedWatch Program run by the FDA. When a new risk of a drug is identified, the FDA will update the product label to inform everyone. MedWatch can be access online or at 1-800-FDA-1088. See up-to-date FDA MedWatch Alerts here.
Phase 4 post-marketing studies may take place in groups of patients who are using the drug in a real-world setting. These studies may identify additional uses, long-term effectiveness, and previously undetected side effects. Rare side effects that occur in fewer than 1 in 5,000 patients are unlikely to be seen in Phase 1 to 3 studies before approval, but groups of patients this large are not usually studied. These rare side effects are more likely to be found when large numbers of patients use a drug after it has been approved and marketed.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.