Draft Guidance for 

Industry and FDA Staff: 

Technical Considerations for 

Pen, Jet, and Related Injectors 

Intended for Use with 

Drugs and Biological Products 

DRAFT GUIDANCE 

This guidance document is for comment purposes only. 

Written comments and suggestions regarding this draft document should be submitted within 90 

days of publication in the Federal Register of the notice announcing the availability of the draft 

guidance. Submit comments to Division of Dockets Management (HFA-305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be 

identified with the docket number listed in the notice of availability that publishes in the Federal 

Register. 

Additional copies are available from the Office of Combination Product, HFG-3; Office of the 

Commissioner; Food and Drug Administration; 15800 Crabbs Branch Way, Suite 200; Rockville, 

MD 20855; (Tel) 301-427-1934; (Fax) 301-427-1935; or http://www.fda.gov/oc/combination. 

For questions regarding this document, contact Patricia Y. Love, MD, 

Office of Combination Products, at 301-427-1934 or patricia.love@fda.hhs.gov.

U.S. Department of Health and Human Services 

Food and Drug Administration

Center for Devices and Radiological Health, 

Center for Drug Evaluation Research, 

Center for Biologics Evaluation and Research, and 

Office of Combination Products in the Office of the Commissioner. 

April 2009 
Contains Nonbinding Recommendations 

Draft - Not for Implementation 

2

Draft Guidance for 

Industry and FDA Staff: 

Technical Considerations for Pen, Jet, 

and Related Injectors Intended for Use 

with 

Drugs and Biological Products 

Additional copies are available from: 

Office of Combination Products, HFG-3 

Office of the Commissioner 

Food and Drug Administration 

15800 Crabbs Branch Way, Suite 200 

Rockville, MD 20855 

(Tel) 301-427-1934 

(Fax) 301-427-1935 

http://www.fda.gov/oc/combination 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Devices and Radiological Health, 

Center for Drug Evaluation Research, 

Center for Biologics Evaluation and Research, and 

Office of Combination Products in the Office of the Commissioner. 

April 2009 
Contains Nonbinding Recommendations 

Draft - Not for Implementation 

3

Table of Contents 

INTRODUCTION.....................................................................................................................4 

The Least Burdensome Approach.....................................................................................5

BACKGROUND .......................................................................................................................5 

SECTION I: SCIENTIFIC AND TECHNICAL CONSIDERATIONS..............................6 

A. Injector Description......................................................................................................6 

B. Design Features ...........................................................................................................10 

C. Injector Materials of Construction and Manufacture.............................................14 

D. Performance Testing: General Use Injector Considerations..................................15 

E. Performance Testing: Injector and Drug/Biological 

Product Considerations..............................................................................................18 

F. Performance Testing – Clinical Considerations.......................................................21 

G. Sterilization and Sterility Assurance.........................................................................22 

H. Labeling .......................................................................................................................24 

SECTION II: THE CONTENT AND FORMAT CONSIDERATIONS...........................25 

A. Preliminary Format Considerations for an Injector in an NDA or BLA 

Submission...................................................................................................................25 

B. Abbreviated 510(k) Submission Considerations .......................................................25 

SECTION III. WHERE CAN I FIND ADDITIONAL INFORMATION?.....................26 
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Draft Guidance for Industry and FDA Staff 

Technical Considerations for Pen, Jet, and Related 

Injectors for Use with 

Drugs and Biological Products 

This draft guidance represents the Food and Drug Administration's (FDA's) current 

thinking on this topic. It does not create or confer any rights for or on any person and 

does not operate to bind FDA or the public. You can use an alternative approach if the 

approach satisfies the requirements of the applicable statutes and regulations. If you 

want to discuss an alternative approach, contact the FDA staff responsible for 

implementing this guidance. If you cannot identify the appropriate FDA staff, call the 

appropriate number listed on the title page of this guidance. 

Introduction 

FDA is providing this draft guidance document to assist industry in developing technical 

and scientific information to support a marketing application for a pen, jet, or related 

injector device intended for use with drugs and biological products.1 The marketing 

application would typically be a premarket notification submission (510(k)) or a 

premarket approval (PMA) application for the injector alone. For a combination product 

that includes the injector, the marketing application would typically be a New Drug 

Application (NDA) or a Biological Licensing Application (BLA).2

 

For purposes of this guidance, the term injector includes, but is not limited to: jet 

injectors, pen injectors, piston syringes, needle-free injectors, mechanically operated 

injectors, and injectors with computerized or electronic elements. 

This guidance does not apply to devices the sole purpose of which is to aid in the 

insertion of a syringe or infusion set. Also, this guidance does not apply to dental surgery 

gas-powered jet injectors (product code EGQ under 21 CFR 872.4465) or dental surgery 

spring-powered jet injectors (product code EGM under 21 CFR 872.4475). 

 

1 This guidance was prepared by the Office of Combination Products in the Office of the Commissioner in 

conjunction with the Center for Devices and Radiological Health, the Center for Drug Evaluation and 

Research, and the Center for Biologics Evaluation and Research. 

2

 Throughout this guidance, we use the terms "marketing application" and "submission" interchangeably to 

reference whichever type may be appropriate for your product. 

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This draft guidance supplements other FDA guidance documents that may apply 

regarding specific content requirements of a marketing application and any electronic and 

software components of your product. See Section III for a list of some additional 

guidance documents that may be useful when developing pen, jet, or related injectors for 

use with drugs and biological products. 

The Least Burdensome Approach 

This draft guidance document reflects our careful review of what we believe are the 

relevant technical and scientific development considerations for injectors and what we 

believe would be the least burdensome way of addressing these issues. If you have 

comments on whether there is a less burdensome approach, however, please submit your 

comments as indicated on the cover of this document. 

FDA's guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe the Agency's current thinking on a topic and 

should be viewed only as recommendations, unless specific regulatory or statutory 

requirements are cited. The use of the word should in Agency guidances means that 

something is suggested or recommended, but not required. 

Background 

Pen, jet, and related injectors may provide an innovative approach to deliver drugs or 

biological products and may enhance safety, improve dosing accuracy, and increase 

patient compliance, particularly in self-administration settings. There are three basic 

groups of injectors. First, some injectors are intended for general use with a wide range 

of currently marketed drugs/biological products. Second, some injectors are intended for 

use with a certain class of drugs/biological products or with a specific product line. 

Third, some injectors are intended for use with a specific drug/biological product. 

Depending upon the technology, an injector may be pre-filled with a drug/biological 

product for single or repeat dosing. For example, a given injector may be for single use 

only in acute intervention for treatment or prevention while another injector may be for 

repeat dosing as part of a long term treatment regimen. Other injectors may be available 

in a co-package with the drug or biological product for assembly by the patient or health 

care provider. 

Pen, jet, and related injectors provide a method of accurately injecting a dose of 

drug/biological product3

 from a cartridge, reservoir, or syringe through an automatically 

or manually inserted single lumen hypodermic needle or through a high velocity jet. 

3

 For purposes of this guidance, the phrase "dose of a drug/biological product" refers to a liquid, semi-solid, 

or solid form for injection by the device.

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They may be intended for use by a health professional or for self-administration by a 

patient, as appropriate, in the diagnosis, cure, mitigation, treatment, or prevention of 

disease. 

Injectors may be subject to different regulatory provisions depending on their intended 

use, technological characteristics, proposed labeling, and packaging. For example, most 

injectors are intended for general use with a wide range of drugs/biological products and 

are marketed alone. Typically, general use injectors have marketing clearance as devices 

under a pre-market notification (510(k)). Other injectors are intended for use with a 

specific drug/biological product and may be pre-filled with that product, co-packaged 

with that product, or separately provided with mutually conforming labeling. These 

injectors are typically combination products under 21 CFR 3.2(e). For most combination 

products, one marketing application is sufficient for the injector and the drug/biological 

product; this application is usually an NDA/BLA. When appropriate, however, FDA 

may determine that two applications are necessary (i.e., an NDA/BLA along with a 

device submission that is usually a 510(k)). Considerations for determining the 

appropriate type of marketing application are beyond the scope of this draft guidance. 

 

This draft guidance focuses on the scientific and technical considerations that may be 

relevant when developing a pen, jet, or related injector regardless of the regulatory 

provisions that apply (i.e., device, drug, or biological product provisions). It provides 

considerations applicable to a general use injector and to an injector intended for a 

product class, product line, or a specifically named drug/biological product. It also 

provides general content and format information for injectors to be reviewed under 

510(k) submissions and for review as part of an NDA/BLA submission. It focuses 

specifically on scientific and technical information for the injector, which would be part 

of any marketing application. Overall, this draft guidance is intended to promote 

efficient premarket review and ensure consistent and appropriate postmarket regulation of 

injector delivery systems. 

SECTION I: SCIENTIFIC AND TECHNICAL 

CONSIDERATIONS 

A. Injector Description 

 

Given the spectrum of use for injectors, we recommend that your submission 

comprehensively describe the product, its indication(s), and its conditions of use. 

Typically this information would include elements such as the following: 

1. Identification 

• Trade name or proprietary name of the injector 

• Device regulatory classification and product code (see Section II for 

additional information if you are submitting a 510(k) submission) 

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2. Indication Information 

Proposed indication statement including the following items: 

• Patient population (e.g., medical disorder, demographics) 

• Injection site (area on the body where the drug/biological product is 

injected) 

• Target tissue/required tissue characteristics 

• Type-of-use (e.g., single, disposable, repeat dose, refillable) 

• Identification of general use or indication of use with a product class, 

product line, or a specifically named drug or biological product 

3. Description of Conditions of Use4

• Discussion of principles by which the injector operates 

• Performance specifications 

• Drug/biological product(s) of intended delivery 

• Drug/biological product dose capability (e.g., single dose, multiple dose, 

adjustable dose) 

• Description of how the injector is supplied to the end-user (e.g., as a prefilled injector-drug/biological product, as a co-package containing the 

injector and drug/biological product for assembly, or as a separately 

distributed injector) 

• Type-of-use and description of the intended user (if applicable), for 

example as arrayed in the following table: 

Personal For self-administration or by a non-professional caregiver 

Professional For use by a health care provider in a health care or 

institutional setting 

Single-use Entire injector and drug cartridge is discarded after a single use

Injector can be used more than once with the same drug 

cartridge in place and is discarded after the cartridge is empty 

Reusable 

Injector can be used more than once with replaceable drug 

cartridge 

Other Describe any unique type-of-use characteristics 

4. Description of Drug/Biological Product for Injection 

As noted above, there are three groups of injectors: (a) injectors intended for use 

with a wide range of currently marketed drugs/biological products (general use), 

(b) injectors intended for use with a specific class or product-line of 

 

4

 Information in the "Conditions of Use" section may also be part of the "Labeling Indications" section or 

the "Use and Handling" section, as appropriate depending on the type of marketing application submitted 

(e.g., Structured Product Labeling in an NDA/BLA). 

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drugs/biological products, and (c) injectors intended for use with only a specific 

drug/biological product. Overall, the descriptive information should reflect the 

following development considerations: 

a) General use: Typically, general use injectors would be marketed under a 

510(k) premarket notification submission. A general use indication 

assumes the availability of at least one approved injectable product that is 

compatible with the injector.5 Further, it assumes that the injector will not 

change the characteristics of the marketed drug/biological product. For 

general use indications, the description section of your application should 

provide the following information on the drug/biological product to be used 

with your injector, in addition to the information recommended by other 

applicable guidance. As part of the review, FDA intends to consider how 

this information will be used in labeling to help ensure appropriate 

selection of a drug/biological product for the general use injector. (For 

additional information on labeling, see Section I.H.) 

• Identify the drugs/biologic products that are currently approved and 

marketed for the dose, rate, and route of administration proposed for 

the general use injector. Your submission should include a copy or 

copies of the most recently approved labeling for representative 

drug/biological product(s) currently approved in a configuration 

(container-closure) that is compatible with your injector. (For 

additional information on performance testing for general use 

injectors, see Section I.D.) 

• Identify the drug/biological product characteristics, such as pH and 

viscosity, that are compatible with your injector materials and 

performance characteristics. You should also identify characteristics 

that would not be compatible with your injector materials and 

performance characteristics and/or provide a rationale for why certain 

characteristics were not tested. 

• If a compatible drug/biological product configuration is in 

development and/or pending approval, or if there are other 

compatibility concerns, we recommend that you contact the CDRH 

review branch or the Office of Combination Products for additional 

information. 

b) Injectors intended for use with a class or product line or with a specific 

drug/biological product: If the injector is intended to deliver a specific 

 

5

 In cases where only one marketed injectable product is available, FDA recommends that you discuss with 

the CDRH review branch or the Office of Combination Products whether to develop the injector as a 

general use device or as a device intended for use with that one approved product. 

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drug/biological product, a certain product line, or a class of products, your 

submission should include the following. 

• Identify the product(s) for injection by brand and/or generic name and 

their labeled indication(s) for administration. In these circumstances, 

FDA intends to consider whether the target product, product line, or 

class of products is currently approved for the dose, rate, and route of 

injection proposed for the injector. We also recommend that you 

provide copies of the most recently approved product labeling of the 

target drug/biological product(s). For some very narrow or internally 

consistent product lines, it may be acceptable to provide a copy of the 

labeling for one representative product within the product line. (For 

additional information on performance testing for these products, see 

Section I.E.) 

• Indicate whether the to-be-injected drug/biological product is already 

marketed in the necessary configuration in the injector. 

• If you are proposing a new route, dose, or rate of administration for the 

drug or biological product, FDA expects that a CDER - CDRH 

collaboration will be necessary, as appropriate for the type of 

submission. We recommend that you contact the CDRH review 

branch or the Office of Combination Products for additional 

information. 

• For pre-filled injectors and for injectors co-packaged with the 

drug/biological product, identify which application 

holder/manufacturer/supplier will perform the pre-filling, copackaging, and other manufacturing steps. 

• If you are providing injectors to pharmaceutical firms (or entities such 

as holders of other marketing applications) for further manufacture, 

pre-filling, or co-packaging, and if you wish to maintain certain 

confidential information, you can provide FDA with proprietary 

information about these injectors in a device master file. When doing 

so, you should also provide letters of authorization to the other 

firms/application holders who are performing the additional 

manufacturing steps or are relying on your information.6

 These other 

entities could then reference the information in your device master file 

when they provide their own marketing submissions (i.e., NDA/BLA). 

In such circumstances, we recommend discussions with the Agency on 

what and how to provide information in the device master file and/or 

6

 For more information on master files (MAFs) and authorized references, see 

http://www.fda.gov/cdrh/dsma/pmaman/appdxc.html#P7_2. 

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marketing application. 

B. Design Features 

Design features encompass the technical specifics of the injector, technical considerations 

for the injectable product, and the human factors to consider to ensure safety and 

effectiveness of the product. 

1. Comparison to an Existing Delivery Method 

To facilitate the regulatory review of the injector, developers may compare various 

design features to features in similar legally marketed products. The goal of this 

comparison may differ depending on the type of marketing application and 

development approach. For example, in a 510(k) submission, the comparison would 

be to a legally marketed predicate injector to demonstrate substantial equivalence. 

When submitting a 510(k) submission, you should provide a comprehensive summary 

comparing and contrasting your injector with the predicate injector cleared under a 

different 510(k). In some instances, it may be appropriate to provide multiple 

comparisons. The following are examples of information and comparisons that FDA 

considers important in a 510(k) submission: 

• 510(k) number of the predicate 

• Indications for use, listing similarities and differences between the new 

injector and the predicate injector 

• Conditions of use 

• Injection sites 

• Depth of needle insertion 

• Injector life 

• Compatible cartridges 

• Compatible needles 

• Dose, dose accuracy, and precision (including mechanisms to determine the 

dose) 

• Power source 

• Overall dimensions 

• Weight 

• Design features 

• Materials 

• Performance specifications and profile (e.g., force, pressure) 

• Needle lumen and jet injector nozzle orifice size 

• Drug/biological product(s) intended for use with the predicate injector, if 

applicable 

When submitting an NDA/BLA for approval of the injector, similar information 

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may be useful.7 The NDA/BLA should also include either the specific 

information on the injector or a letter of authorization to reference information in 

a 510(k) or device master file that is necessary for review of the NDA/BLA.8

 

Note, however, that the referenced information may not be sufficient to address 

the safety or effectiveness (risk) of the device in the context of the use submitted 

in the NDA/BLA (i.e., use with a specific drug/biological product or products). 

2. Engineering Drawings and Photographs 

We recommend that you provide engineering component and assembly drawings for 

the injector and each of the following key functional components: 

• Fluid path and reservoir 

• Power supply 

• Dose-setting mechanism, such as a dial, used to set the desired dose

In addition, you should provide the following:

• Exploded views and photographs of the injector and illustrations showing the 

drug product delivery stages 

• Drawings with critical dimensions and tolerances 

• List of the components incorporated in the injector 

3. Dose Setting and Administering an Injection 

In order to assess the ability of the injector to reliably and reproducibly deliver the 

necessary injection volume for the target drug/biological product(s), and to compare 

the reliability and reproducibility to those of the predicate injector or other delivery 

method as applicable, we recommend you provide a description of the mechanism for 

setting and administering the dose, including (if applicable): 

• Assembly of an injector at the point of clinical use 

• Loading the drug/biological product 

• Priming the injector 

• Pre-setting the dose 

• Inspecting the drug/biological product 

• Preparing and positioning for an injection 

• Dose adjustment mechanism 

• Resetting after use 

• Needle change and disposal 

We also recommend that you include: 

• The source of power for the injector 

7

 Unlike in a 510(k) submission, the purpose of this information in an NDA/BLA would not be to establish 

substantial equivalence. 

8

 See footnote 6, above. 

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• A description of the controls, such as dose indicators, activation status, and 

reservoir volume 

• The method and mechanism for ensuring that the drug/biological product in 

the chamber or cartridge is sufficient for the desired volume of delivery 

• A discussion of incomplete or partial dosing or overdosing events and the 

actions necessary to remedy these events 

• The time required for delivery of the drug/biological product 

• If the injector has a retractable fixed needle, a discussion for how the design 

ensures that the full dose will be delivered prior to needle retraction 

• For jet injectors, a description of the nozzle design (e.g., single orifice, 

multiple nozzles/orifices of different sizes) 

• A description of all of the attachments that are necessary for the proper 

operation of the jet injector, even if they are not part of the injector proposed 

for marketing or part of a cleared or approved product being referenced (e.g., 

a regulator for compressed air) 

• If assembly by the user is required, details on how the injector is assembled; if 

the injector is pre-filled, details on how the drug/biological product is 

contained in the injector 

4. Graduation Marks and Fill Lines 

Graduation marks and fill lines may be used to aid the user in setting the correct dose 

or for verifying the set dose. We recommend that these markings be provided to aid 

proper dosing if: 

• The injector is intended to deliver multiple doses of a drug/biological product 

• The dose can be adjusted by the user 

• The injector is intended to deliver a single dose of a specific drug/biological 

product and the risks associated with under- and over-dosing are critical as 

determined by a risk analysis 

When using graduation marks or fill lines, the submission should include validation 

of the accuracy of these markings. 

5. Visual Inspection of the Drug/Biological Product

In some circumstances, the drug/biological product for delivery has labeling 

instructions requiring visual inspection of the product before injection. In such cases, 

the injector design should allow for appropriate inspection. For example, for a prefilled injector, an injector that holds a cartridge for future use that cannot be removed 

once it is placed in the injector, or a repeat dose injector that uses the same drug 

cartridge after placement in the injector, the injector design should permit the full 

visual inspection of the injection material once it is placed in the injector pending 

later injection. 

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In addition, some injectors are intended for use with high-risk drugs/biological 

products. When applicable, the injector design should address safety issues aimed at 

preventing confusion among different injectable products. Such design 

considerations may include, but are not limited to, special injector-cartridge design 

features that restrict use of a given cartridge to a specific injector, or injector-cartridge 

designs that allow a visual confirmation of the cartridge label to ensure the presence 

of the correct drug/biological product after placement in the injector. 

6. Safety Features 

Injectors may have a variety of safety features to ensure accurate dosing and to 

prevent sharps injury. In addition to graduation/fill marks and visual inspection, these 

features may include audible, visual, and tactile notifications as well as switches and 

mechanical protections. We recommend that you describe all the safety features of 

the injector, their purposes, and their procedures for use. Also, the submission should 

include details on all alarms, warnings, or switches and expected user responses to 

these features. If the injector has a sharps injury prevention feature (e.g., retractable 

needle), we recommend that you address the issues discussed in the guidance 

document Supplementary Guidance on Premarket Notifications for Medical Devices 

with Sharps Injury Prevention Features (Aug. 2005), available at 

http://www.fda.gov/cdrh/ode/guidance/934.pdf. 

We also recommend that you conduct a risk analysis that considers the overall 

product and includes both the injector and injected material components. 

Specifically, you should assess the risk of use of the intended drugs/biological 

products delivered via a dedicated system. Furthermore, you should provide labeling 

information about conditions associated with the characteristics of the patient 

population using the intended drugs/biological products. 

7. Human Factor Design Considerations

Depending on the characteristics of the intended use population or on the 

environmental conditions, the injector design may need to consider human factors 

that would affect the safety or effectiveness of the injector. These factors may 

include age, gender, range of tissue characteristics in the intended use population, 

medical disorders common to the end-user population, or environmental or other 

conditions associated with the intended use population.9

 For example, injectors 

intended for use at high altitudes may necessitate special design features. Injectors 

intended for use in treating disorders associated with visual impairment or in treating 

arthritis may need design features that accommodate the visual impairment or manual 

 

9

 See Guidance for Industry and FDA Premarket and Design Control Reviewers, Medical Device Use 

Safety: Incorporating Human Factors Engineering into Risk Management (July 2000), available at 

http://www.fda.gov/cdrh/humfac/1497.pdf.

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dexterity, respectively, of the intended use population. Injectors intended for use by 

the military may need to accommodate special environmental conditions under which 

the products will be stored and possibly used (e.g., desert and tropical climates, frigid 

conditions, at various altitudes, in aircraft, and in submarines below sea level). (See 

also Section I.F for further discussion of human factors.) 

C. Injector Materials of Construction and Manufacture 

Your marketing application should identify all known materials that comprise the injector 

for use as well as the manufacturing materials used in construction of the injector. 

Specifically, for each material or component, the submission should provide the 

chemical, grade, and brand name and indicate which materials are in or will affect the 

fluid path.10 It should also identify any components that are not identical to those of the 

predicate injector or other delivery mode, for example, plastic stoppers instead of glass 

stoppers. (See Section I.B.1 for more on such comparisons.) For any new component, 

the submission should include the methods and results of biocompatibility tests. 

Certain drugs/biological products have different responses to metals and manufacturing 

materials that may be components of an injector (e.g., silica, steel, carbon, polymers). 

Furthermore, some products such as lyophilized drugs may be more sensitive to moisture, 

and other products (e.g., solutions) may be more sensitive to oxygen. The submission 

should therefore include the results of tests that examine the interaction of the 

drug/biological product with the injector. These tests should explore how the injectordrug/biological product interactions affect each other’s performance. They should 

include the entire product use cycle, ranging from materials that interact with the 

drug/biological product within the cartridge or injector to the injection process itself. 

The following list describes specific issues FDA intends to consider in reviewing the 

submission: 

• Analysis of potential leachables arising from the interaction between the 

drug/biological product and injector (see Section 1.E.3) 

• Analysis of extractables from the injector components using solvents under 

laboratory conditions and providing the extraction profiles (see Section 1.E.3) 

• Effect of adsorption of drugs/biological products (including preservatives) on 

injector components 

• Effect of head-space volatile compounds and impurities on the drug/biological 

product and/or injector components 

• Effect of drug-injector interaction over time for re-useable injectors 

• Analysis of functional materials corrosion from the drug/biological product 

10 For purposes of this guidance, materials that are in or will affect the fluid path are components and 

accessories of the injector that contact the drug/biological product, including the needle, dose chamber, 

cartridge, plungers and stoppers, and reservoirs for the drug/biological product. 

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• Analysis of seal integrity (e.g., lubricity breach of sealing) 

• Introduction of particulates 

D. Performance Testing: General Use Injector Considerations

Performance testing for general use injectors should consider the characteristics of 

drugs/biological products and diluents with which your injector is intended to be used. 

For example, these tests should study a range of drugs/biological products for appropriate 

reconstitution with a range of diluents (e.g., aqueous, non-aqueous, or oil based). For 

each injectable product and delivery vehicle used for reconstitution, the submission 

should include a copy of the approved labeling of the diluent and the approved labeling 

of the drug/biological product proposed for reconstitution. FDA recognizes that in some 

general use circumstances it may be acceptable to conduct testing with a range of 

alternative substances. If such testing is proposed, the submission should provide a 

detailed justification for why it is appropriate and why the chosen substance or range of 

substances is acceptable. When conducting performance testing, we recommend that you 

follow the standards identified below and available at 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm: 

• ISO 7886-1:1993, Sterile Hypodermic Syringes for Single Use - Part 1: Syringes 

for Manual Use 

• ISO 10993-1:1997, Biological Evaluation of Medical Devices - Part 1: 

Evaluation and Testing 

• ISO 11608:2000, Pen-Injectors for Medical Use

• ISO 21649:2006, Needle-Free Injectors for Medical Use - Requirements and Test 

Methods. 

• ASTM D4169:1999, Standard Practice for Performance Testing of Shipping 

Containers and Systems

• ASTM F647, Testing to Assess Durability of Devices Following Interaction with 

Drugs 

FDA also recommends that you conduct software and electromagnetic compatibility 

testing as appropriate for your injector. Guidance on these aspects is available from 

FDA.11

FDA recommends that your submission include results from the performance tests 

identified below. Your submission should include not only the results of each test, but 

also a diagram of each test set-up (with labels to identify the test instruments) and an 

explanation of how each test was conducted. 

1. Biocompatibility 

 

11 See General Principles of Software Validation; Final Guidance for Industry and FDA Staff (Jan. 2002), 

available at http://www.fda.gov/cdrh/comp/guidance/938.pdf; see also http://www.fda.gov/cdrh/emc/.

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For general use injectors, FDA recommends that you conduct biocompatibility testing 

as described in the guidance, Use of International Standard ISO-10993, Biological 

Evaluation of Medical Devices Part-1: Evaluation and Testing (May 1995), available 

at http://www.fda.gov/cdrh/g951.html. The testing should consider components or 

materials in contact with the patient, including components or materials that are in the 

fluid path that externally communicates with the patient's blood/bodily fluids. The 

selected biocompatibility tests should be appropriate for the type and duration of 

contact with your device. Summaries of biocompatibility testing should include: 

• The specific tests you conducted 

• The details of extraction testing (e.g., whether the entire injector or only a 

small piece of the injector was extracted, whether all the components were 

included in the extraction, whether the extraction was performed on the 

finished injector subject to all processing methods and sterilization) 

• The extracts tested and justification for the choice of extracts (e.g., polar, 

non-polar) 

• The animal model or cell line 

• The extract conditions (e.g., time, temperature, area- or mass-to-volume ratio 

compared to in-use conditions) 

• The test and controls used 

• The end points used 

• As appropriate, toxicity testing of extracts described in the United States 

Pharmacopeia USP<87> and USP<88>12 as well as systemic toxicity, delayed 

dermal contact sensitization studies, non-pyrogenicity testing, cytotoxicity 

testing using red blood cells and mouse fibroblasts, and Ames assays.

2. Shelf-Life Stability and Expiration Dating 

For stability and expiration dating, the testing should consider the injector alone and 

the injector with the drug/biological product. For the injector alone, the data should 

demonstrate that the injector can be reliably and reproducibly used for the labeled 

number of injections. FDA recommends that shelf life-testing endpoints include: 

• Freedom from defects (e.g., displaced parts, cracking, leaking) 

• Dose accuracy (see Section I.E.1) 

• Replacement needles and cartridges 

The submission should include an analysis and discussion of the physical degradation 

and changes to the injector due to the conditions the injector is exposed to before use 

(i.e., shelf life, expiration date) and during use (in-use life expiration dating). For 

additional information relating to the life of an injector, see Section I.E.1. 

 

12 United States Pharmacopeia information is accessible at http://www.usp.org.

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When determining the stability and shelf life, expiration date, and in-use life 

expiration date, you should submit data to verify that the injector performance is not 

adversely affected by environmental conditions, such as the following: 

• Sterilization 

• Extreme operating temperature environments 

• Extreme storage temperature environments 

• Extreme conditions of use testing, when applicable 

• Packaging 

• Shipping 

In addition, for jet injectors, the extent of “wear and tear” on the nozzle and fluid path 

is of concern. The high jet stream velocity and pressure may have deleterious effects 

on the fluid path and the nozzle, including erosion, component deformation, and 

structural failure. These effects should be assessed in relationship to the injector and 

component service life, servicing, or replacement intervals. 

3. Functional Testing 

Depending on the injector design, it may be appropriate to conduct additional bench 

testing to demonstrate the functionality of the injector. Testing to assess the 

reliability of your injector may include: 

• Flow rate 

• Injection time (i.e., time required to deliver the drug/biological product) 

• Reliability of the mechanism to deliver the drug/biological product 

• Depth of injection (see Section I.E.2) 

• Functionality of the safety mechanism 

• Verification for absence of leakage 

• Verification of non-coring needle (e.g., if the needle is used to puncture a 

septum)

• Needle dwell time (i.e., amount of time that the needle is in the body)

• Chemical resistance (i.e., data to ensure that injector and injector labeling are 

not adversely affected by the recommended cleaning agents)

• Structural testing at extreme pressure and temperature conditions 

Testing to assess the mechanical features of your injector may include: 

• Force required for assembly 

• Force required to actuate the injector 

• Force required to defeat the needle shield or other safety mechanism 

• Load testing on individual components 

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• Needle bond strength (i.e., force required to pull the needle off the injector) 

• Needle penetration force (i.e., force available for needle insertion)

• Needle deflection angle that causes injector failure (note: this is important if 

the needle retracts after insertion) 

The above tests should include testing of safety features to ensure their intended 

performance. Also, for multiple use injectors, the testing should establish the 

duration of repeated use. 

For a general use injector, we further recommend performance testing for dose 

accuracy and route of injection (see Section I.E.1-2). 

E. Performance Testing: Injector and Drug/Biological Product 

Considerations 

In developing your plan for performance testing of injectors intended for use with a 

certain class/product line or with a specific drug/biological product, you should begin 

with the considerations described in Section I.D and should then focus on the unique 

injectable product. Depending upon the specific materials in the product, FDA may 

request additional pharmacology-toxicology testing. 

When conducting performance testing for your injectable product, you should use the 

actual drug/biological product(s) intended for injection. For example, for an injector 

intended for use with a specific drug, you should perform biocompatibility testing with 

that drug (see Section I.D.1). When conducting performance testing for a class of 

products, you should consider the type of testing necessary to evaluate the expected 

injector-drug/biological product interactions. For example, if the injector materials are 

coated with a polymer, then the submission should identify which types of 

drug/biological product characteristics were tested to demonstrate absence of leachable 

material into the drug/biological product. This testing should include testing for 

extractables (more below). In addition, you should identify which drug/biological 

product characteristics were tested and the methods used to demonstrate absence of 

adherence to the injector materials. 

Specifically, we recommend that your submission include results from the following 

performance tests, in addition to the tests identified in Section 1.D: 

1. Dose Accuracy 

FDA recommends completion of the following dose accuracy testing. 

• Testing to demonstrate that the volume/weight of drug/biological product 

expelled through the injector is the same as the set dose 

• Testing to ensure that multi-dose cartridge injectors satisfy the requirement 

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that each successive dose is the same as the first set dose 

• Testing to ensure that dose settings/markings correlate with the volume of 

drug/biological product delivered 

Because diluents may affect the drug/biological product and the injector, the above 

testing should ensure that the delivery volume meets the dose accuracy specification 

for the specific drug/biological product when reconstituted according to its approved 

or proposed labeling, as applicable. 

We recommend, where appropriate, that injectors include a mechanism or feature that 

notifies the user that an incorrect dose has been delivered. Performance testing 

should include testing of such mechanism(s). Product labeling should also include 

information instructing the user on what action should be taken in the event of 

incorrect dosage. 

2. Depth and Route of Injection 

Testing should demonstrate that the depth of needle penetration and/or dispersion of 

the injectate are consistent. The model chosen for testing should simulate human skin 

and any specific tissue layers as closely as possible. The application should include 

an explanation to justify the model chosen for testing.13 

Where applicable, the submission should include the results of studies to compare the 

depth of penetration and dispersion testing of the subject injector with similar 

injectors or other methods of delivery. It should also include a statistical comparison 

and a discussion of, and justification for, any differences between the measurements 

for the subject injector and those for similar injectors or other methods of delivery. 

Certain drugs or biological products require delivery to a precise tissue plane (e.g., 

intradermal, subcutaneous, intramuscular). Where applicable, the submission should 

include test results demonstrating reliable and reproducible depth of delivery (e.g., 

amount delivered subcutaneously, amount delivered epidermally, amount delivered 

intramuscularly). 

For injectors that involve the mechanical actuation and insertion of the hypodermic 

needle, we recommend that you perform additional testing. Testing should examine 

the following parameters: 

• Reliability for the specified depth of insertion throughout the expected injector 

life cycle 

13 Submissions for previously cleared or approved injectors have included depth of penetration testing 

performed on human, porcine, and cadaver models. 

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• Injector performance such as the amount of pressure needed to administer an 

injection and the permissible areas of body that may receive successful 

injections 

• How population-specific issues, such as gender, body weight, age, and skin 

disorders, may affect injection safety or effectiveness 

• The presence of blood vessels (if applicable) 

For jet injectors, testing should also characterize the fluid dispersion from the 

injection to indicate the percentage of fluid in or at the surface of the muscle and at 

various depth ranges in the subcutaneous region. The submission should include 

images of injections depicting the distribution of the injected drug/biological product. 

3. Special Testing Considerations 

If the injector materials also comprise the container closure system for the specific 

drug/biological product, then you should perform the following in-vitro testing to 

support the performance of your injector with the drug/biological product. In some 

circumstances, similar testing may be appropriate for injectors intended for use with a 

class/product line. 

• Extractability/Leachability 

In addition to the studies identified in Section I.C, you should provide studies 

that evaluate head space volatiles in the cartridge. Specifically, you should 

demonstrate that any seals or o-rings have the ability to contact different types 

of injection media without sloughing or leaching material. Testing should 

also demonstrate seal integrity. Other testing that may be applicable to 

identify interaction with the injector and the injector manufacturing materials 

include: 

- Extractant analysis: pH shift, turbidity, heavy metals, non-volatile 

residue, residue on ignition, UV absorption, silicone content, etc. 

- Chromatography: nucleating agents, cross-linking agents, curing agents, 

antioxidants, acid scavengers, plasticizers, etc. 

- Impurities and degradation products 

- Endotoxins 

• Adsorptivity 

Testing should ensure that there is no tendency for gases, liquids, or solutes to 

accumulate on a surface of the drug/biological product. 

• Drug/Biological Product Container and Closure Integrity 

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When the injector is in direct contact with the drug/biological product, we 

recommend consideration of the principles in the FDA guidance, Container 

Closure Systems for Packaging Human Drugs and Biologics: Chemistry, 

Manufacturing and Controls Documentation (May 1999), available at 

http://www.fda.gov/cber/gdlns/cntanr.htm. 

• Shelf-life and Expiration Dating: Injector-Drug/Biological Product

 Applications for injectors intended for use with a specific drug/biologic 

product or for a drug/biological class or product line should include stability 

data to establish the shelf-life and expiration dating of the relevant fully 

assembled injector-drug/biological product. For example, as appropriate, tests 

may assess the shelf life of the assembled product in storage conditions before 

use. They may also assess stability and expiration dating of the final to-bemarketed configuration under expected in-use conditions (e.g., rugged use, 

different environmental conditions). Where applicable, the tests should 

evaluate the product after reconstitution. They should assess any injectate that 

remains in the fluid path after injection and that may degrade and contribute to 

the denaturing of the drug/biological product. 

Further, when conducting stability and expiration dating tests, the entire 

injector system should be tested, i.e., the drug/biological product in its direct 

container closure (cartridge) plus any surrounding injector and packaging. 

Bench testing for container closure and packaging ruggedness should include, 

but is not limited to, mechanical reliability (release specifications), accelerated 

testing, temperature cycling, temperature extremes, pressure changes, 

vibration, etc. (For information on testing the injector alone, see Section 

I.D.2.) 

F. Performance Testing: Clinical Considerations 

Specific considerations for clinical trial design are beyond the scope of this guidance. In 

general, however, clinical trials for some injectors may focus on the injector itself. 

Typically, these trials would evaluate the design features and whether the intended use 

population can use the injector as proposed. 

1. Human Factors 

In some instances, depending upon the characteristics of the injector, studies may be 

appropriate to demonstrate that providers or patients can use the injector properly. 

Sometimes these studies may focus on general use performance, for example the 

ability of users to read and follow instructions for set-up and use. In other instances, 

the studies may focus on specific factors, characteristics, and demographics of the 

intended use population. These factors may include age, gender, range of tissue 

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characteristics in the intended use population, disorders commonly seen in the 

intended use population, or environmental or concomitant conditions associated with 

the intended use population.14 For example, for an injector intended for use with a 

drug for treatment of arthritis, studies should test whether the design accommodates 

the manual dexterity of the target patient population. 

2. Additional Considerations 

FDA may request additional in-use information for critical features of injectors 

intended for use with a specific drug/biological product. For example, additional 

information may be appropriate for certain lock-out injectors or complex doseadjustment methods. For such products, we recommend that you contact the lead 

review division to discuss the pre-clinical and clinical development plan. 

G. Sterilization and Sterility Assurance 

1. Sterilization 

Sterilization incorporates two aspects: the sterility assurance necessary for the 

injector itself and the sterility assurance necessary for the injector-drug/biological 

product as a whole. For general use injectors intended for use with a wide range of 

marketed drugs/biological products, the submission should include sterilization 

information for the injector in accordance with the FDA guidance, Updated 510(k) 

Sterility Review Guidance K90-1; Final Guidance for Industry and FDA (August 

2002), available at http://www.fda.gov/cdrh/ode/guidance/361.html. If the injector is 

provided as sterile, the data should demonstrate a probability of a non-sterile unit not 

greater than 1 x 10-6. The components comprising the fluid pathway should be shown 

to be non-pyrogenic. For all sterile components, the submission should contain a 

description of the injector packaging, including a list of packaging materials. 

FDA recognizes that the following standards may be useful for determining 

sterilization requirements and test methods. These standards are available at 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. 

 

• ANSI/AAMI/ISO 11134:1993, Sterilization of Health Care Products – 

Requirements for Validation and Routine Control – Industrial Moist Heat 

Sterilization

• ANSI/AAMI/ISO 11135:1994, Medical Devices - Validation and Routine Control 

of Ethylene Oxide Sterilization 

• USP 27:2004, Sterility, Biocompatibility, Biological Tests and Assays, Bacterial 

 

14 See Guidance for Industry and FDA Premarket and Design Control Reviewers, Medical Device Use 

Safety: Incorporating Human Factors Engineering into Risk Management (July 2000), available at 

http://www.fda.gov/cdrh/humfac/1497.pdf.

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Endotoxin Test (LAL), Pyrogen Test (USP Rabbit Test), or other applicable tests 

related to the drug/biological product and delivery of the drug/biological product 

• AAMI/ANSI/ISO 11737-1:1995, Sterilization of medical devices-microbiological 

methods-Part 1: Estimation of the population of microorganisms on product 

• ANSI/AAMI/ISO 11607:2000, Packaging for terminally sterilized medical 

devices

For an injector that will be in a co-package or will be pre-filled with a specific 

drug/biological product, the submission should address the possible effects of the 

method of co-package sterilization on the combination product (i.e., effects specific to 

the drug/biological product concerning, for example, light stability or oxygen 

sensitivity). For an injector cartridge that will be in direct contact with a 

drug/biological product, we recommend that you select an appropriate method of 

sterilization for the product and primary packaging material, and that you justify your 

choice of method in your submission. For example, if you do not use aseptic 

methods, you should justify this choice. 

2. Cross-Contamination Testing 

Disease transmission may result from cross-contamination in reusable needle-free 

injectors, e.g., Multi-Use-Nozzle Jet Injectors (MUNJIs). There is a potential for 

disease transmission when blood contamination of the fluid path or injectable product 

occurs during a previous injection. Contamination can occur on the skin-contacting 

surface of the injector or inside the injector from splash-back. It is also possible that 

the replaceable cap may become contaminated. 

Given these risks of contamination, submissions for MUNJI injectors should provide 

cross-contamination testing results and should quantify the residual contaminant for 

subsequent injections. The submission should identify the test method chosen for 

quantifying the residual contaminant, indicate the accuracy of this method, and 

include a thorough discussion and justification of the test method selection. In 

general, the most sensitive test method available should be used. The discussion of 

test method selection should include assumptions, limitations, and weaknesses of the 

test method. Also, the bench testing for blood cross-contamination should include 

testing for hepatitis B virus (HBV), using the most sensitive detection method 

available.15 

In addition, FDA generally recommends against developing injectors that require 

between-use cleaning of any component in or around the fluid path. If such cleaning 

is necessary, the review division should be contacted for additional guidance. 

 

15 For more information on cross-contamination risks and detection of HBV, see the transcript for the FDA 

General Hospital and Personal Use Devices Panel (August 9, 2005), available at 

http://www.fda.gov/ohrms/dockets/ac/05/transcripts/2005-4172t1.htm. 

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H. Labeling 

Pen, jet, and related injectors may be intended for use by health care professionals or for 

self-administration by the patient. Overall, the submission should include clear and 

concise instructions that delineate the technological features of the specific injector and 

how the injector is to be used. We recommend developing labeling that carefully 

considers the user. In some circumstances, it may be appropriate to provide a patient 

package insert or labeling for the patient or caregiver.16 Additional instructions may be 

appropriate for in-service training programs to familiarize users with the features of the 

injector and how to use the injector in a safe and effective manner. The following 

examples illustrate the elements that may be appropriate for labeling.17 

• Injector description, including name 

• Intended use and indications for use 

• Type-of-use for the injector (e.g., personal, professional, public health, single-use, 

reusable, DCJI, MUNJI, labeled and sold for only one patient) 

• Intended patient population

• Name, type, and characteristics of drug/biological product that is compatible with 

the injector, the dose range for the injector, and number of doses the injector 

delivers

• Drug/biological product approval status (FDA or USP)

• Drug/biological product capability (e.g., single-dose-disposable, repeat dose 

disposable, repeat dose refillable, adjustable dose) 

• Directions for use, user instructions, and diagrams

• Areas of the body appropriate for injection, including diagrams, and appropriate 

skin preparation prior to injection 

• Target tissue and injection sites, including appropriate warnings for intravenous 

injection of drugs/biological products intended for intramuscular or subcutaneous 

injection 

• Warnings, limitations, and precautions, including incomplete dosing, overdosing, 

misdosing (injection into wrong tissue), and cross-contamination 

• Contraindications 

• Identification of any drug/biological product(s) that are not compatible with the 

injector 

• Assembly instructions and diagrams (e.g., how the drug/biological product is 

contained in the injector and the method for inserting the drug/biological product 

into the injector) 

• Maintaining sterility during injector assembly 

• Dose setting and administering an injection 

• How to ensure that the full dose is delivered 

16 See, e.g., 21 CFR 208.20.

17 The labeling format may vary depending upon the type of marketing application submitted.

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• Prevention of or remedy for incomplete or partial dosing or overdosing events 

• The correct amount of pressure needed for an injection 

• Information about injection depth including validation methods 

• Labeling recommendations for sharps injury prevention features 

• Environmental conditions of use and storage 

• Reuse, cleaning, servicing, and disposal instructions 

• Troubleshooting 

• Life of the injector and critical components 

For certain injectors intended for use with a specific drug/biological product or for a class 

or product line, FDA may request additional labeling information (e.g., expiration dating 

after insertion into the injector and/or reconstitution of a drug cartridge, or use of 

nomenclature consistent with that of the drug/biological product). 

SECTION II: CONTENT AND FORMAT 

CONSIDERATIONS 

A. Preliminary Format Considerations for an Injector in an NDA or 

BLA Submission 

Some applicants who have included injector information in an NDA/BLA have included 

the injector information under the Common Technical Document (CTD) as a subsection 

in module 3. Other applicants have included the information in the container closure 

section. FDA recommends a pre-submission meeting with the lead center to discuss how 

you propose to organize the NDA/BLA submission. Similar meetings should be 

requested when an NDA/BLA submission is planned along with a 510(k). 

It should be noted that product codes are applicable to devices marketed under 

device regulatory provisions only. When you include a pen, jet, or related 

injector in an NDA/BLA submission, you may reference the product code of a 

previously cleared or approved injector and any associated information. This 

referenced information may not be sufficient, however, to address the safety and 

effectiveness (risk) of the device in the context of the use being proposed in the 

NDA/BLA submission (i.e., its use with a specific drug/biological product(s)). 

B. Abbreviated 510(k) Submission Considerations 

When a 510(k) is appropriate for a pen, jet, or related injector, you have the option of 

submitting a Traditional 510(k), an Abbreviated 510(k), or a Special 510(k).18 For the 

general use injectors discussed in this document, FDA believes that an Abbreviated 

18 FDA has published several guidances on 510(k) submission methods, available at

http://www.fda.gov/cdrh/ode/parad510.html and http://www.fda.gov/cdrh/ode/92_a.html. 

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510(k) is generally acceptable and provides the least burdensome means of demonstrating 

substantial equivalence. 

Pen injectors are generally regulated as class II devices under 21 CFR 880.5860 (product 

code NSC) and 21 CFR 880.6920 (product code KZH).19 Jet injectors, which include 

needle-free or needless injectors, are generally regulated as class II devices under 21 

C.F.R. 880.5430 (product code KZE). 

 

For 510(k) format and content information, you should refer to the following: 

• 21 CFR 807.87 

• The New 510(k) Paradigm - Alternate Approaches to Demonstrating Substantial 

Equivalence in Premarket Notifications; Final Guidance (March 1998), available 

at http://www.fda.gov/cdrh/ode/parad510.html

• Guidance for Industry and FDA Staff: Format for Traditional and Abbreviated 

510(k)s (August 2005), available at 

http://www.fda.gov/cdrh/ode/guidance/1567.pdf

If you are a manufacturer considering modifying your own cleared device, it may be 

possible to lessen the regulatory burden by submitting a Special 510(k). If so, then FDA 

recommends that you include the technical information, as applicable, in the Special 

510(k) submission using the format recommended in the preceding guidance documents. 

The Special 510(k) should describe the risk analysis method used and the results of this 

analysis. If you elect to use an alternative approach to address a particular risk identified 

in this draft guidance, or if you have identified and addressed risks additional to those 

identified in this draft guidance, your Special 510(k) should provide sufficient detail to 

support review of the risk analysis method chosen. 

SECTION III. WHERE CAN I FIND ADDITIONAL 

INFORMATION? 

We recommend that you have early discussions with FDA if you are developing an 

injector described in this draft guidance and if you are uncertain about the type of 

technical and scientific information that may be appropriate or necessary in your 

submission. Such product-specific advice may be useful for complex delivery systems, 

for associated drugs/biological products, or for technical aspects of the device. Where 

appropriate, you may request a pre-submission meeting for more detailed discussion. 

Additional guidance information is available from the CDRH, General Hospital Devices 

Branch at 301-240-276-3707 or from the Office of Combination Products by email to 

combination@fda.gov. General guidance information and links to the different center 

 

19 In identifying injectors, FDA distinguishes pen injectors from piston syringes and pen injectors with 

manually-inserted needles from pen injectors with automatically-inserted needles. 

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27

documents are also accessible at http://www.fda.gov/oc/combination/. For an injector 

intended for use with a specific drug/biological product, additional information is 

available from the CDER or CBER review division. 

The following FDA guidance and informational documents may be useful when 

developing injectors intended for use with drugs and biological products. 

• Guidance for Industry and FDA Premarket and Design Control Reviewers, 

Medical Device Use Safety: Incorporating Human Factors Engineering into Risk 

Management (July 2000), available at http://www.fda.gov/cdrh/humfac/1497.pdf

• Guidance for Industry and FDA Staff: Early Development Considerations for 

Innovative Combination Products (Sept. 2006), available at 

http://www.fda.gov/oc/combination/innovative.pdf

• Draft Guidance to Industry and FDA Staff: Current Good Manufacturing 

Practice for Combination Products (Sept. 2004), available at 

http://www.fda.gov/oc/combination/OCLove1dft.pdf

• Guidance for Industry and FDA Staff: Format for Traditional and Abbreviated 

510(k)s (August 2005), available at 

http://www.fda.gov/cdrh/ode/guidance/1567.pdf 

• The New 510(k) Paradigm - Alternate Approaches to Demonstrating Substantial 

Equivalence in Premarket Notifications - Final Guidance (March 1998), available 

at http://www.fda.gov/cdrh/ode/parad510.html

• Guidance for Industry, Formal Meetings with Sponsors and Applicants for 

PDUFA Products (Feb. 2000), available at

http://www.fda.gov/cder/guidance/2125fnl.pdf

• IND Meetings for Human Drugs and Biologics: Chemistry and Manufacturing 

Controls Information (May 2001), available at 

http://www.fda.gov/cder/guidance/3683fnl.pdf

• Early Collaboration Meetings under FDAMA; Final Guidance for Industry and 

CDRH Staff (Feb. 2001), available at 

http://www.fda.gov/cdrh/ode/guidance/310.pdf

• International Conference on Harmonization Q8 Pharmaceutical Development

(May 2006), available at http://www.fda.gov/cder/guidance/6746fnl.pdf