Guidance for Industry: Contents of a Complete Submission for the Evaluation of Proprietary Names

Wednesday April 7, 2010

Guidance for Industry: Contents of a Complete Submission for the Evaluation of Proprietary Names

Name: Contents of a Complete submission for the Evaluation of Proprietary Names

Status of Guidance: Final Guidance

Guidance Released: February 2010

Link to Guidance: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM075068.pdf

Audience: This guidance was created for pharmaceutical companies as a recommendation for the submission of proposed proprietary names for their new products to the US Food and Drug Administration (FDA) for review

Definition of Terms Used in this Guidance:

Applicant or sponsor: The organization that submits a proposed proprietary name (trademark or brand name) submission for prescription drug products (including biologics) and nonprescription drug products. For example, GlaxoSmithKline (GSK) could be an applicant or a sponsor.

Complete submission: This is the information identified by the FDA that is needed by them to perform a complete review of a proposed proprietary name.

Established name: This is the official name of the drug. It is often the generic or common name and can usually be found in the United States Pharmacopeia (USP). For example, topotecan hydrochloride is the established name (generic name or common name) for Hycamtin®.

Label: A display of written, printed, or illustrated matter upon the immediate container of any drug.

Labeling: Labeling includes all labels and other written, printed, or illustrated matter that is found upon any drug or any of its containers or wrappers or that accompanies the drug. Labeling includes outside containers, wrappers, and package liners.

Medical error: The Institute of Medicine (IOM) defines medical error as “the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim.”[1] Types of medical errors include diagnostic, treatment, preventive and other (such as communication, equipment, or system failure).[2]

Medication error: Any preventable situation that may cause or result in inappropriate medication use or harm to the patient while the medication is in the control of the health care professional, patient, or consumer. These preventable situations may be related to professional practice, health care products, procedures, and systems. These situations include prescribing; order communication; product labeling, packaging, and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use.[3]

Medication-use system: This is the system that includes (1) prescribing by the clinician (or self-prescribing), followed by transcribing; (2) preparing and dispensing by the pharmacist; (3) administering by the provider or consumer (self-care); and (4) monitoring for therapeutic and adverse effects (by nurse, surrogate, or self). Each of these four steps includes critical control points at which decisions and actions can contribute to safety or errors.[4]

Product characteristics: The physical characteristics of the product itself and those of the environment in which the product is used. Characteristics of the product include dosage form, strength, and active ingredient. Characteristics of the environment in which the product is used include the facility, storage conditions, the person who prescribes and administers the product, and patient population.

Proprietary name: The trademark or brand name.

Laws and Regulations Referenced:
1. 21 CFR 201: Labeling
2. 21 CFR 201.6(b): Drugs; misleading statements
3. 21 CFR 201.10(c)(3): Drugs; statement of ingredients
4. 21 CFR 202.1(a)(3), (e)(5)(i), and (e)(6)(i): Prescription-drug advertisements
5. 21 CFR 299.4: Established names for drugs
6. 21 CFR 312.3: Investigational New Drug application – Definitions and interpretations
7. 21 CFR 314.105(c): Approval of an application and an abbreviated application
8. 21 CFR 314.125(b)(6) and (b)(8): Refusal to approve an application
9. 21 CFR 314.3: Applications for FDA approval to market a new drug - Definitions
10. 21 CFR 314.50: Content and format of a New Drug Application
11. 21 CFR 314.92: Drug products for which abbreviated applications may be submitted
12. 21 CFR 601.2: Applications for biologics licenses; procedures for filing
13. 21 CFR 601.4(b): Issuance and denial of [a biologics] license
14. 21 USC 321(n), 352(a) and (n): Definitions (misbranded) and Misbranded drugs and devices
15. 21 USC 352(e)(3): Designation of drugs or devices by established names
16. 21 USC 355(d)(7): Grounds for refusing application; approval of application; “substantial evidence” defined
17. 42 USC 262(a)(1)(B)(ii): Biologics license
18. 42 USC 262(b): Falsely labeling or marking a package or container; altering a label or mark of a biological product
19. Public Law 110-85 Stat 823: The Food and Drug Administration Amendments Act of 2007 (September 27, 2007; 121 Stat. 823; 156 pages) also known as an act to amend the Federal Food, Drug, and Cosmetic Act to revise and extend the user-fee programs for prescription drugs and for medical devices, to enhance the postmarket authorities of the Food and Drug Administration with respect to the safety of drugs, and for other purposes

Summary: This guidance provides US pharmaceutical companies with the information the FDA considers essential to be enabled to conduct a complete review of a proposed proprietary name. A proprietary name is a trademark or brand name. For example, Tylenol® is McNeil Consumer Healthcare’s brand name for acetaminophen. All proprietary names that are proposed for new drugs (both prescription and nonprescription) and new biologics must be evaluated by the FDA before a product is allowed to be sold on the US market.

Rationale: The FDA is committed to the efficient development of safe and effective new medications for the American public. One goal of the FDA is to reduce medication errors by ensuring that all products have clearly understandable labels. The FDA hopes to reduce medication errors by eliminating look-alike and sound-alike proprietary names, unclear label abbreviations, unclear acronyms, confusing dose designations, and poor packaging designs. As part of this goal to reduce medication errors that are related to unclear labeling, the FDA agreed to publish guidance on the contents of a complete submission package for a proposed proprietary name for a drug or biological product. Resulting Recommendations:

1. Applicants (drug/biologic manufacturers) must submit, and FDA must review, proposed proprietary names as part of New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), and Biologic License Applications (BLAs).

2. When possible, applicants may have the FDA evaluate a proposed proprietary name even earlier in the drug development process; however, the product must have successfully completed phase 2 trials prior to submission. This time period is referred to as the end of phase 2 of the Investigational New Drug (IND) process.

3. A complete submission for evaluation of proposed proprietary names includes the following:

3.1. General Information
Each submission should be identified as one of the following:
REQUEST FOR PROPRIETERY NAME REVIEW, or
AMENDMENT TO REQUEST FOR PROPRIETARY NAME REVIEW, or
REQUEST FOR RECONSIDERATION OF PROPRIETERY NAME, as appropriate.
Either FDA Form 1571 (for all products that are the subject of an IND) or FDA Form 356h (for all products that are the subject of an NDA, ANDA, or BLA) should be submitted and include:
-Proposed first choice of proprietary name
-Application number (BLA/NDA/ANDA/IND)
-Applicant or sponsor contact information
-Identification of the submission as mentioned above (in bold under Section 3.1.)
-A list of the contents of the submission

3.2. Proposed Proprietary Name
All submissions should include the following information about the proposed proprietary name:
-Primary and alternate proposed proprietary name
-Intended pronunciation of the proposed proprietary name
-Derivation of proprietary name
-Intended meaning of proprietary name modifiers (for example, the meaning of a prefix or suffix such as “ER” means extended-release)
-Pharmacologic/therapeutic category

3.3. Additional Information about the Product
Submissions should include the following depending on whether they already have proposed labels and labeling or not:
3.3.1. Submission for a product that has proposed labels and labeling is to include:
-Proposed labeling (also known as the package insert, prescribing information, or physician labeling)
-Proposed container labels and labeling (external labeling and packaging)
3.3.2. Submission for a product without proposed labeling is to include (this information is normally contained in professional labeling):
-Established name
-Prescription status
-Dosage form(s)
-Product strength(s)
-Proposed indication(s) for use
-Route(s) of administration
-Usual dosage, frequency of administration, dosing interval, maximum daily dose
-Dosing in specific populations
-Instructions for use
-Storage requirement
-How supplied and packaging configuration

3.4. Information about product dispensing and delivery
-Likely care environment(s) for dispensing and use
-Delivery system
-Measuring device

3.5 Applicant’s assessments of proprietary name, packaging, and/or labeling

Impact:
This guidance will help improve patient safety and decrease preventable adverse drug events in the US. Although an applicant (a pharmaceutical company, for example) may perform their own assessment of the proprietary name they have chosen for one of their new drug/biologic products, it is an added safety step to have the FDA evaluate proposed proprietary names. In the US, 44,000 to 98,000 deaths each year are the direct result of medical errors.[5] This statistic makes medical errors the eighth leading cause of death in the US.[6] Of these deaths due to medical errors, 7,000 deaths annually were attributed to medication errors.[7] Labeling and packaging issues are the cause of 33 percent of medication errors and 30 percent of the fatalities associated with medication errors.[8] It is no surprise that the IOM recommended that the FDA 1) develop and enforce standards for the design of drug packaging and labeling that will maximize safety in use and 2) require pharmaceutical companies to test proposed drug names to identify and remedy potential sound-alike and look-alike confusion with existing drug names. The IOM is an unbiased, independent, nonprofit organization that works outside of government to advise the nation how to improve national health.



[1] Kohn LT, Corrigan JM, Donaldson MS, eds. To Err is Human: Building a Safer Health System. Institute of Medicine, National Academies Press: Washington DC, 2000. Chapter 1, p. 1.
[2] Leape L, Lawthers AG, Brennan TA, et al. Preventing Medical Injury. Qual Rev Bull. 19(5):144-149, 1993, cited in To Err is Human, p. 1.
[3] National Coordinating Council for Medication Error Reporting and Prevention Web site, http://www.nccmerp.org/aboutMedErrors.html.
[4] Aspden P, Wolcott JA, Bootman JL, Cronenwett LR, eds. Overview of the Drug Development, Regulation, Distribution, and Use System. Preventing Medication Errors, Institute of Medicine, The National Academies Press: Washington DC, 2006. Chapter 2, p. 67.
[5] Kohn LT, Corrigan JM, Donaldson MS, eds. To Err is Human: Building a Safer Health System. Institute of Medicine, National Academies Press: Washington DC, 2000.
[6] American Hospital Association. Hospital Statistics. Chicago, 1999.
[7] Phillips, DP, Christenfeld, N, and Glynn, LM. Increase in US Medication-Error Deaths between 1983 and 1993. The Lancet. 351:643-644, 1998.
[8] Aspden P, Wolcott JA, Bootman JL, Cronenwett LR, eds. Preventing Medication Errors. Institute of Medicine, The National Academies Press: Washington DC, 2006.