• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Drugs

  • Print
  • Share
  • E-mail

Injection Dosage Form Questions

INTRODUCTION:                           

ANDA Number
Date of Submission
Applicant’s Name
Established Name of the Drug Product
Proprietary Name of the Drug Product (include date proposed)
Labeling Submissions (proposed labeling pieces, e.g., container, carton, FPL, SPL, etc.)
 
QbR Questions:
 
Model Labeling
1.        What model labeling is your product labeling based upon?
 
USP Monograph
2.        Is there a USP Drug Product Monograph and if so, does your product’s labeling meet the USP requirements?
 
Patents and Exclusivities
3.       What are the currently approved patents and exclusivities for the reference listed drug as listed in the Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) and what impact do they have on the labeling submitted? 
 
4.       What are the certifications and labeling impacts for each patent and exclusivity?
 
Inactive Ingredients
5.       Is the listing of inactive ingredients in the DESCRIPTION section of the package insert consistent with the listing of inactive ingredients found in the statement of components and composition and SPL data elements?
 
6.       Are the proposed inactive ingredients consistent with the inactive ingredients of the Reference Listed Drug (RLD)?
 
7.       Do any of your inactive ingredients require special labeling statements or have regulatory requirements?
 
Manufacturing Facility 
8.       Who manufactures the drug product?
 
9.       Who distributes the drug product?
 
Product Description 
10.     How does your product description in the insert labeling compare with the product description in the Finished Product Specifications?
 
11.     Must the product be further diluted prior to administration?  If so, how is this made clear to the health care provider?
 
12.     What diluents are compatible with your drug product? For each diluent listed, have you provided the highest concentration at which each diluent has been shown to be compatible?
 
13.     What warnings or instructions are present in the labeling about the product and how does it compare with the reference product? (e.g., patient instructions for use)
 
14.     Does any text appear on your cap or overseal?
 
Container/Closure System 
15.     How does your container/closure system compare with the container/closure system of the RLD? 
 
16.     Are proposed vial or syringe sizes the same sizes marketed by the RLD? 
 
17.     Does any component of your container/closure system contain natural rubber?
 
Product Line
18.     How do your packaging configurations compare with the packaging configurations of the RLD? (e.g., use of individual cartons)
 
 
Storage Conditions
19.     How does your storage temperature statement, including storage after reconstitution, compare with the storage temperature statement of the RLD?
 
20.     Is this product light sensitive?  If so, do the labeling recommendations and/or special packaging address light sensitivity? 
 
Dispensing Recommendations
21.     How do your dispensing recommendation statements compare with the dispensing recommendation statements of the RLD?
 
SPL Data Elements
22.     Are the SPL Data Elements consistent with information provided in your application and in the insert labeling?
 
Medwatch 
23.     Are the FDA Toll Free Number, MedWatch web address and manufacturer’s phone number present in the labeling?
 
REMS
24.     Is a Risk Evaluation and Mitigation Strategy (REMS) required for the proposed product?
 
25.     Is a non-REMS risk mitigation strategy in place for the RLD, e.g., a Riskmap?
 
Petitions
26.     Is your proposed product subject to any petitions? 
 
Pregnancy Registry 
27.     Does RLD labeling reference a pregnancy registry and if so, do you also propose a pregnancy registry. Please provide your rationale for not including a registry that appears in the labeling of the RLD. 
 
Additional Questions:
 
Controlled Substance Labeling 
1.       Is your product a controlled substance? If yes, does labeling meet regulatory requirements for location and size of symbol?
 
2.       Does the proposed packaging meet requirements for tamper-evident sealing?
 
NDC Codes
1.       Is your drug product registered?
 
2.       Does your product meet the conditions of 21 CFR 207.35(b)(3)(i), regarding the proper placement of the NDC code on labeling?
 
Lot Numbers 
Does a lot number, control number, or batch number appear on the label as described in 21 CFR 201.18?
 
Bar Coding 
How are the conditions of 21 CFR 201.25 met?
                                             
Formatting, wording preferences
 
1.     Does your expression of strength follow the format described below?  If not, how does it deviate and why?
  • For single-use and multiple-dose injection drug products, the strength per total volume should be the primary and prominent expression on the principal display panel of the label followed in close proximity by strength per mL enclosed by parentheses: [e.g. 100 mg/10 mL (10 mg/mL) or 25,000 Units/5 mL (5,000 Units/mL)].
  • The secondary expression of strength should appear with less prominence than the primary expression of strength: [e.g 100 mg/10 mL (10 mg/mL)].
  • For container volumes less than 1 mL, the strength per fraction of an mL should be the only expression of strength.  (i.e. 12.5 mg/0.625 mL).  We refer you to USP General Chapters <1> Injections.
  • “For Injection” products see below.
2.       Is the route of administration prominently displayed on the principal display panel?
 
3.       Does the principal display panel clearly state whether a vial is multiple-dose or single dose? 
 
4.       Do your labels and labeling meet formatting requirements set forth in the regulations? (e.g., font size)
 
Instructions for Use 
1.       How do the instructions for use differ from those of the RLD?
 
2.       If the instructions differ from the RLD, have similar instructions been approved for another of your approved drug products? 
 
Medication Guides
1.       How does the Medication Guide for this product differ from that approved for the RLD?
 
2.       How will the Medication Guide be provided with the product and how many will accompany each package size?
 
3.       Are the conditions of 21 CFR 208.20 met with regard to proper Medication Guide formatting?
 
4.       Do the proposed container labels direct the health care provider to dispense the Medication Guide as required by 21 CFR 208.24(d)?
 
5.       Have requirements for providing a toll-free number for reporting adverse events been met by including the following text with the Medication Guide?
 
Call your doctor for medical advice about side effects.  You may report side effects to FDA at 1-800-FDA 1088.
 
Patient Information Leaflet
1.       How does the Patient Information Leaflet for this product differ from that approved for the RLD?
 
2.       How will the Patient Information Leaflet be provided with the product and how many will accompany each package size?
 
3.       Have requirements for providing a toll-free number for reporting adverse events been met by including the following text with the patient information?
 
Call your doctor for medical advice about side effects.  You may report side effects to FDA at 1-800-FDA 1088.
  
Differentiation 
1.       Are your product strengths sufficiently differentiated to reduce chance of medication errors?
 
2.       Where there is a possibility the products will be stored in close proximity, is there adequate differentiation between your proposed product and your approved products? 
 
3.       Is there sufficient contrast between the expression of strength and background color on container labels and carton labeling? 
 
4.       Are you proposing a product with Tall Man Lettering?
  
 

Product-Specific LABELING QUESTIONS

 
1.       Does your labeling meet the requirements set forth in the regulations?
 
2.       Do you have the proper warning statements set forth in the regulations?  
 
  • “For Injection” Products
1.       Is your product labeled with the volume of diluent required for the target concentration?
 
2.       What is the reconstitution information and where is it described in your labeling?
 
3.       What is the storage temperature and allowable length of time for use after reconstitution? 
 
4.       Are the words "Must be Diluted" on the label?
 
5.       Is the strength displayed in terms of mg per vial, for example, “XXX mg/Vial”?
 
  • Chemotherapeutic Injection Agents
1.       Does your labeling meet labeling and or handling requirements of a USP monograph?
 
2.       Are the words “Cytotoxic Agent" on the main panel?
 
3.       Is your label color the same or similar in color to the reference product to help promote correct product strength selection and to prevent cross product strength mix ups?  Have you provided a list of each strength and corresponding label color?
 
4.       If no preservative is present, does your label include the "discard unused portion" statement?
 
5.       If no preservative is present, does your label include the discard time frame?  (Example:  Reconstituted product should be discarded after 4 hours. )
 
  • Liposomal and Long-acting Formulations
1.       Does labeling for this liposomal product formulation comply with the Guidance for Industry: Liposome Drug Products?
 
2.       What measures have been taken to prevent errors between this product and non-liposomal product(s) employing the same active ingredient?
 
  • Syringes 
1.       Is your product container the same as the reference listed drug?   How have you ensured that your drug product container/carton/ insert will not require additional labeling to prevent route of administration errors? 
 
2.       Have you submitted draft copies of your syringe/needle.
 
3.       Have you included the syringe type and needle gauge size on the carton and in the insert?
 
  • Pharmacy Bulk Packages
 
1.       Does your product follow the labeling guidance for Pharmacy Bulk Packages?
 
2.       Does your product allow for a fluid transfer time of greater than 4 hours?
 
3.       Does your proposed container closure system allow for use with infusion sets?
 
4.       Does the container include graduation/calibration marks?
 
  • Radioactive Drug Products
 

1.       Does your product follow the labeling recommendations for Radioactive Drug Products?

2.       Do you propose auxiliary labeling which accompanies the RLD product?  (e.g., labeling stickers)