# Presentation: 541021

## The Office of In Vitro Diagnostics’

**The Office of In Vitro Diagnostics’**
**Annual IVD 510(k) Workshop**
**April 2006**
**Double Tree Hotel**
**Rockville, MD**
**Heather S. Rosecrans**
**Director, 510(k) Staff**
**Center for Devices & Radiological Health**
**U.S. Food & Drug Administration**
**(301) 594-1190 x143**
**Heather.Rosecrans@FDA.HHS.GOV**

## What is a 510(k) 

- Premarket Notification
- Section 510(k) of F,F,D, & C Act
- 21 CFR 807 Subpart E
- Marketing Clearance Submission
- Allows FDA to Determine Substantial Equivalence (SE)
- “The” classification process

## What a 510(k) Is Not

-   A Form
-   Establishment Registration (FDA-2891)
-   Device Listing  (FDA-2892)
-   Premarket Approval  (PMA)
-   Product Development Protocol (PDP)
-   Evaluation of Automatic Class III 	Designation -  (De Novo)

## Premarket Notification (510(k)) Program is meant to:

- Classify new devices that must be placed automatically into class III & undergo premarket approval or reclassification before they are marketed
- Classify new devices. Example:  A Not Substantially Equivalent (NSE) new device is in class III & a Substantially Equivalent (SE) new device is in the same regulatory class as the device to which it is found equivalent

## Principles of Classification

## Classification

- The Federal Food, Drug, and Cosmetic Act
- The Medical Device Amendments of 1976
- Safe Medical Devices Act of 1990
- FDAMA
- MDUFMA
- Classification/Reclassification
- Identification of Risks
- Designation of Controls to Mitigate Risks
- Generic Type of Device
- Intended Use

## “The Poison Squad”

**Harvey Washington Wiley, M.D. **
**(third from right) and the Division of Chemistry Staff in 1883**

## Federal Food and Drug Act  1906 (The “Wiley Act”)

**Notes:**
38 years before devices were recognized to be separate and apart from drugs.

## Federal Food, Drug, and Cosmetic Act

- 1938
- President Roosevelt signed the Food, Drug, and Cosmetic Act which superseded the “Wiley Act”, and introduced “safety” as criterion for premarket approvals of drugs.

- In 1962 “Effectiveness” was added.

## FDA Undercover

- Illegal sales of amphetamines and barbiturates occupied more regulatory concern at FDA than all other drug problems combined from the 1940s to the 1960s. Interdiction in some venues required undercover tactics, as indicated here by these two inspectors posing as truck drivers.

## Medical Device Amendments to F,F,D, & C Act

-  May 28, 1976
-  Defined a device (201(h) of the Act)
-  Required classification of devices
- Led to classification of approximately 1,700 different generic types of devices and grouped them into 19 medical specialties
- Required premarket review of devices

## May 28, 1976

- Preamendments Device* (Pre 1976):
- Exempted (with conditions) from marketing
- clearance
- Postamendments Device (Post 1976):
-    Requires marketing clearance
**Preamendment Status Determinations*
-    _[www.fda.gov/cdrh/comp/preamend.html](http://www.fda.gov/cdrh/comp/preamend.html)_

## Definition of Device (201(h) of the Act)

- The term "device" means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is—
- (1) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,
- (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
- (3) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.

## Preamendments vs. Postamendments Devices

- The act divided the arena of medical devices into either:
- Preamendments Devices (pre-May 28, 1976) or
- Postamendments Devices (post-May 28, 1976)
- Depending on when the devices were introduced into commercial distribution
*Commercial distribution and Preamendment Status are determined by the Office of Compliance (www.fda.gov/cdrh/comp/preamend.html) *

## Safe Medical Devices Act (SMDA)

**1990  **
- 513(i)
- Substantial Equivalence Defined
- 513(a)(1)(B)
- Special Controls

- SMDA

## Food & DrugModernization Act (FDAMA)

**1997 **
- Redefined 510(k) Exemption Criteria for Class I
- Added Class II Exemption Criteria
- De Novo
- SE w/Limitations
- Class II Petitions for Exemption

- FDAMA

## What is Classification?

**It is Premarket Notification (510(k))**
- Meant to:
- Classify postamendment devices
- Find a device substantially equivalent; or
- Find a new device not substantially equivalent (one that must be placed automatically into class III and require PMA, de novo, or reclassification before marketing)

## What is Classification? (cont.) 

**Device Type – 21 CFR 860.3(i) **
*Generic type of device* means a grouping of devices that do not differ significantly in purpose, design, materials, energy source, function, or any other feature related to safety and effectiveness, and for which similar regulatory controls are sufficient to provide reasonable assurance of safety and effectiveness.

## Regulatory Classes

- Three Regulatory Classes (level of control necessary to assure safety and effectiveness)
- Class I – General Controls
- Class II – General Controls & Special Controls
- Class III – General Controls and Premarket Approval

## Regulatory Classes (cont.)

**Class determines type of premarket submission required by FDA**
- Class I or II 510(k) Exempt
- Subject to limitations on exemptions covered under      21 CFR xxx.9 (e.g., 862.9 to 892.9)
- Class I or II 510(k) required
- Class III
- PMA (510(k) for preamendment devices until 515(b) calls for PMA or the device type is reclassified)

## Description of Classes

**Class I****	**1.  Devices for which general controls are sufficient to provide reasonable assurance of the safety and effectiveness of such devices.

## Description of Classes (cont.)

**General controls include:****	**
- prohibition against adulterated or misbranded devices
- premarket notification (510(k)) requirements
- banned devices
- GMPs
- Registration of manufacturing facilities
- listing of device types
- record keeping
- repair, replacement, refund

## Description of Classes (cont.)

- 2.Devices for which general controls and special controls are insufficient to provide reasonable assurance of such devices, but devices:
- are not life-sustaining or life-supporting;
- are not of substantial importance in preventing        impairment of human health; and
- do not present a potential unreasonable risk of illness or injury

## Description of Classes (cont.)

**Class II**
- 1.Devices which cannot be classified into Class I because general controls by themselves are insufficient to provide reasonable assurance of the safety and effectiveness of such devices but
- 2.For which there is sufficient information to establish special controls to provide such assurance:

## Description of Classes (cont.)

**Special Controls include:**
- Performance Standards (discretionary, voluntary national or international standard, recognized by rulemaking);
- Guidance Document;
- Postmarket Surveillance;
- Patient Registries;
- Other

## Description of Classes (cont.)

**Class III**
- 1.  Devices for which insufficient information exists to determine that general and special controls are sufficient to provide reasonable assurance of the safety and effectiveness of such devices; and
- 2.  Such devices are:
- life sustaining or life supporting;
- substantial importance in preventing impairment of human health; or
- present unreasonable risk of illness or injury.

## What is Classification? (cont.) 

- Classification regulations for individual device types found in 21 CFR Parts 862-892
*Example:  *
*Part 866 – Immunology and Microbiology Devices*
*Sec. 866.3210 Endotoxin assay. (a) Identification. An endotoxin assay is a device that uses serological techniques in whole blood. The device is intended for use in conjunction with other laboratory findings and clinical assessment of the patient to aid in the risk assessment of critically ill patients for progression to severe sepsis. (b) Classification. Class II (special controls). The special control for this device is the FDA guidance entitled "Class II Special Controls Guidance Document: Endotoxin Assay." See 866.1(e) for the availability of this guidance document. *

## What is Classification? (cont.) 

- Regulations describe the device type as it existed **prior** to May 28, 1976
- New uses or technologies may be found through the product codes.

## What Is A Product Code?

- 21 CFR 870.1875 – Stethoscope
- DQD
- 	Electronic Stethoscope
- 	Class II Non Exempt
- LDE
- 	Manual Stethoscope
- 	Class I Exempt, subject to the limitations in 870.9
***If more than one class in a regulation, then must have more than one product code ***

## Product Codes

- Ultimately classify the device
- Found on all 510(k) and PMA clearance/approval letters
- Used to Search for a Predicate
- Used in Assigning Inspections
- Used to Search MDRs in public database
- Used to Search Listings in public database
***CDRH only releases product codes for cleared/approved device types or those for export use only***

## What is a Predicate?CFR Part 807.92(a)(3)

- An identification of the legally marketed device to which the submitter claims equivalence. A legally marketed device to which a new device may be compared for a determination regarding substantial equivalence is ***a device that was legally marketed prior to May 28, 1976, or a device which has been reclassified from class III to class II or I (the predicate),*** or a device which has been found to be substantially equivalent through the 510(k) premarket notification process;

## Classified?  Unclassified? Not Classified?

**Classified**
- By classification regulation and may be exempt– (e.g., 21 CFR 878.4800 Manual surgical instruments)
- 510(k) Decision of NSE = Class III
- Approval of PMA = Class III
**Unclassified **
- A preamendments device (pre-May 28, 1976)
**Always requires a 510(k)**
- Classification regulation has not been written
**Not Classified**
- None of the above (a device we have not seen or for which we have not made a final decision)
- Postamendments device (post-May 28, 1976)

## Finished Device 820.3(l) – Quality System Regulation 

- 820.3(l) *Finished device* means any device or accessory to any device that is suitable for use or capable of functioning, whether or not it is packaged, labeled, or sterilized.
- Finished device in final form for sale to an end user is subject to 510(k) requirements

## “Unfinished Device”for purposes of 510(k)

- If not in final form, **or** in final form but ***not*** for sale to an end user, is not subject to the 510(k) requirements

## Accessories and Components

**Component** (820.3(c)) - *Component* means any raw material, substance, piece, part, software, firmware, labeling, or assembly which is intended to be included as part of the finished, packaged, and labeled device.
**Accessory**—”extras” (not defined in the regulations)
**Accessories/components** to a device take on the same classification as the "parent" device unless they are separately classified
- A **finished accessory or finished component** sold to an end user are subject to 510(k) requirements.

## Enforcement Discretion 

- Enforcement Discretion is when FDA makes the decision to ***not***
- enforce ***a***** **regulatory requirement.  Unlike exemption from a
- regulation, enforcement discretion may apply to only one aspect
- of a regulatory requirement:
- 	EXAMPLE:  FDA does not require 510(k) clearance for ***convenience kits*** of a type  consisting of components that have been cleared through the 510(k) process, and where the assembler/manufacturer is able to reasonably conclude that any further processing of the kit and its components does not significantly affect the safety or effectiveness should be noted that while ***FDA exercises enforcement discretion with respect to 510(k) requirements, assemblers/manufacturers of convenience kits are still required to comply with other general controls including registration, listing, prohibition against misbranding, and good manufacturing practices.**** *

## Enforcement Discretion vs. Exemption from 510(k)

**Exempt** – Exempt from 510(k) requirements by regulation or statute
**Enforcement Discretion** – FDA makes decision not to enforce a regulatory requirement, e.g., 510(k) requirements

## Licensing of 510(k)s

- A firm may not **both** manufacture and distribute without their own 510(k)       (21 CFR 807.85(b)(2))

## General Purpose Article807.65(c)

**Sec. 807.65 Exemptions for device establishments. **
- The following classes of persons are exempt from registration in accordance with 807.20 under the provisions of section 510(g)(1), (g)(2), and (g)(3) of the act, or because the Commissioner of Food and Drugs has found, under section 510(g)(5) of the act, that such registration is not necessary for the protection of the public health. The exemptions in paragraphs (d), (e), (f), and (i) of this section are limited to those classes of persons located in any State as defined in section 201(a)(1) of the act. (a) A manufacturer of raw materials or components to be used in the manufacture or assembly of a device who would otherwise not be required to register under the provisions of this part. (b) A manufacturer of devices to be used solely for veterinary purposes. ***(c) A manufacturer of general purpose articles such as chemical reagents or laboratory equipment whose uses are generally known by persons trained in their use and which are not labeled or promoted for medical uses.***

## General Purpose Article807.65(c)

- Exempt from Registration and Listing
- Exempt from premarket requirements i.e., 510(k), PMA
- Subject to enforcement action

## Public Database:  Classification Database

- CDRH has released a new and improved product code database with exciting new features such as:
- Links to standards and guidance documents
- Product code definitions and intended use fields
- User help documents are now available to assist in 	defining fields

## What is a 513(g)?

- Section 513(g) of FD&C Act
- Request for classification information
- Provide device description w/intended use
- Draft labeling
- Guidance under development

## FDA finds the device Substantially Equivalent (SE)?

**NO** ****** **PMA, PDP, HDE Application
-              or De Novo
**YES** **** **To Market**

## Device is Substantially Equivalent (SE) if:

- In Comparison to a legally marketed        device*, it:
- Has the same intended use, and
- Has the same technological characteristics as the predicate device, or:
- **Preamendment Status Determinations*
-   _**www.fda.gov/cdrh/comp/preamend.html**_

## SE (cont.)

- Has the same intended use, and
- Has different technological characteristics and the information in the 510(k):
**Does not raise new questions of safety and effectiveness, and**
**Demonstrates it is at least as safe and effective as the predicate**
**Approximately 80% are found SE**

## Devices with New Technological Features

**Technological differences may include**:
- Modifications in design, materials, or energy sources for example:
- changes in the power levels of electrical surgical instruments, use of new reagents in in vitro diagnostic devices, use of new materials in orthopedic implants, and  use of new battery designs in implanted pacemakers
- The Center finds devices with new  technological features to be NSE, when the new feature could adversely affect safety or effectiveness in a way     that is consequential under the conditions of   intended use

## Device is Not Substantially Equivalent (NSE) if:

- There is no predicate device
- Has a **new** intended use
- Has different technological characteristics compared to the predicate device and raises a **new** type question of safety and effectiveness
- Does not demonstrate that it is **at** **least** as safe and effective as the predicate

## Not Substantially Equivalent (cont.)

- 2 – 3% are found NSE
- Data is looked at last in the 510(k) regulatory process
- Usually asks for additional information at least once prior to determining the device is NSE     for lack of data

## Slide 49

## 510(k) Submission Required When?

- Introducing a device to the market for the first time
- Change in intended use for a marketed device
- Making significant modification to a marketed device

## Modifications 

- Changes in Intended Use
- Modifications that significantly enhance (or decrease) Safety or Effectiveness
- change in design, materials, chemical 	  composition, energy source, or 		  manufacturing process
- Guidance*: ****“Deciding When to Submit a 510(k) for Change to an Existing Device”*** _[www.fda.gov/cdrh/ode/510kmod.html](http://www.fda.gov/cdrh/ode/510kmod.html)__ _

## The 510(k) Paradigm

- Special 510(k)s
- Abbreviated 510(k)s
- Traditional 510(k)s

## 510(k) Content

**Special**

**Admin.**
**Elements**

**Labeling**

**Data**

**Description**

**Traditional**

**Abbreviated**

## “Special 510(k): Device Modification”

- Manufacturer Modifies own Legally Marketed class I, II, or III Device & Determines that a 510(k) is Required
- Modification does _***not***_*** affect intended use or fundamental scientific technology****

## “Special 510(k): Device Modification”

**“****Special 510(k): ****Device Modification”**

- Manufacturer Assesses Modification in Accordance with 21 CFR **§** 820.30
- 510(k) Submitted w/”Declaration of Conformity” to Design Controls
- FDA Processes in less than _**30**_ days

## What Can Be a Special 510(k)?

- Fingertip control to voice activation
- IV catheter, single to double lumen
- Increase in balloon length & diameter, change in manufacturing
- Addition of a radiopaque material
- Change in stent material, used in type device previously

## What Can Be a Special 510(k)? (cont.)

- Manual operating switch to a pressure operating switch
- Reagent reformulated to achieve extended reconstituted stability
- Change in power source
- Etc., etc.

## What Cannot Be a Special?

- Cannot declare conformity with design controls
- Change in intended use
- Change is fundamental scientific technology
- New surfactant, not used in the type device previously
- Addition of a new analyte

## “Abbreviated 510(k)”

- Manufacturer Intends to Market New *“reserved”* Class I/Class II or Select Class III device
- Device is Subject to Special Controls/FDA Guidance or Recognized Standard(s)
- Manufacturer uses Special Controls/FDA Guidance or Conforms
-    to Standard(s)

## Abbreviated 510(k) (cont.)

- Required Elements of 21 CFR 807.87
- 510(k) Submitted w/Summary Information on Special Controls and/or “Declaration of Conformity” with Standard(s)

## Abbreviated 510(k) (cont.)

- Abbreviated form is a required element in the 510k and is available on the WEB.
- Majority of standards being conformed to are cross-cutting.

## Evaluation of Automatic Class III Designation (“de novo” Classification)

_**The Statute**__**	**__**	**__**	**__**	**__**	**__**	**_
- Section 513(f)(2)
- Within 30 days of receipt of NSE
- No predicate
- “Low risk” devices

## Evaluation of Automatic Class III Designation (cont.) 

_**The Statute**_
- 60-day review period final agency action - signed order classifying the device (I, II, or III)
- If approved, new device can immediately be marketed
- New device becomes predicate
- 30 days after the signed approval order, notification is published in FR
- New classification regulation established

## Evaluation of Automatic Class III Designation (cont.)

- _Section 513(f)(2) Contents_
- Coversheet
- “Requests for Evaluation of Automatic Class III Designation”  under 513(f)(2)
- 510(k) number of NSE device
- Statement of Cross Reference to 510k
- Recommended classification

## Evaluation of Automatic Class III Designation (cont.)

- _Section 513(f)(2) Contents - _(cont.)
- Benefit vs. risk discussion
- How to mitigate risks
- Description of controls
- General
- Special
- Any necessary data not included in 510(k)

## Evaluation of Automatic Class III Designation (cont.)

- _Section 513(f)(2) - The 510(k)__	_
- Reviewing may be different from traditional “No predicate” review
- Early division and office level discussion
- If candidate, communicate early to firm
- Perform comprehensive review within 510(k)
- NSE letter should communicate candidacy

## Evaluation of Automatic Class III Designation (cont.)

- _Section 513(f)(2) - Determination of Candidacy_
- “Low risk”
- Contemplate “Similar Technologies” and        risk profiles
- Could risks be controlled with general and/or special controls “available?”

## Evaluation of Automatic Class III Designation (cont.)

- Benefit (safety and effectiveness)
- Is benefit obvious or intuitive?
- Are data available on S & E?
- If not, then a PMA or PDP is likely
**Always discuss with Division or Office ****	**
**management **_**EARLY **_**in 510(k) process!!**

## Evaluation of Automatic Class III Designation (cont.)

- Section 513(f)(2) - Final Decision Pkg.
- Petition
- Reviews
- Controls
- Correspondence
- Approval Order
- FR Notice, within 30 days, of new classification

## Evaluation of Automatic Class III Designation Experience

- 40 received
- 18 classified/approved
- 15 remain class III
- - Inadequate data
- - Already of a type classified
- - Not within statutory time-frame
- 5 withdrawn
- 2 pending

## Doc Band

- (Cranial Technologies, Inc.)
- Intended for use on infants from three to eighteen months of age with moderate to severe non-synostotic positional plagiocephaly, including infants with plagiocephalic-, brachycephalic-, and scaphocephalic-shaped heads.  The device is intended to apply pressure to prominent regions of an infant’s cranium in order to improve cranial symmetry and/or shape.

## Doc Band(cont.)

- 21 CFR 882.5970 - Cranial Orthosis
- Special Controls													1) Prescription					2) Labeling

## Standards Guidance Document	

- Issued March 12, 2000
_***http://www.fda.gov/cdrh/ode/guidance/1131.pdf***_
- Purpose:  To clarify how standards may be used in demonstrating equivalence
- “Level 2” guidance

## Underlying Principles

- FDAMA was intended to:
*Encourage* use of FDA-recognized standards
- Provide a formal option, but not limit past practices
- Statements, like declarations, are legally binding and enforceable
- Use of “least burdensome” approach

## Use of Standards:  3 Alternatives

- FDA-recognized standard, with a declaration
- FDA-recognized standard, without a declaration
- Non-recognized standard

## Use of FDA Recognized Standard With a Declaration

- FDAMA approach  [§ 514(c)]
- Manufacturer elects to conform to recognized standard; includes declaration in 510(k)
- Manufacturer must have supporting data at time of 510(k) submission
- FDA legally bound to accept declaration to meet applicable requirements

## Review Procedures

- Described in previous guidance documents
- Ensure standard is applicable to device
- Determine extent to which standard addresses SE issues; ensure 510(k) contains information for remaining requirements
- Consult supervisor and division director if concerned about adequacy of standard
- Ensure completeness of declaration
- Indicate reliance on declaration in review doc.

## Who Must Submit a 510(k)?

- Manufacturers
- Specifications Developers
- Repackagers who change device or its labeling
- Relabelers who change the labeling- e.g., instructions for use
- Anyone who **both** manufactures & distributes

## Who is Not Required to Submit a 510(k)?

- Private Label Distributor who **only** adds company name & wording such as:
**“****Distributed by ___________” or**
**“****Manufactured for _________”**

## Not Required to Submit (cont.)

- Repackager who does not alter labeling
- Distributor or Importer who furthers marketing of the device and does not alter labeling or change device

## 510(k) Content & Format

**Guidance for Industry and FDA Staff Format for Traditional and Abbreviated 510(k)s **
**	**_[www.fda.gov/cdrh/ode/guidance/1567.html](http://www.fda.gov/cdrh/ode/guidance/1567.html)_
**21 CFR § 807.87 and § 807.90**
**Device Advice website at   **
**     **_[www.fda.gov/cdrh/devadvice](http://www.fda.gov/cdrh/devadvice/)__[/](http://www.fda.gov/cdrh/devadvice/)_
**Device Specific Guidance**
**510(k) Refuse to Accept Checklist**

## The number of 510ks with clinical data is growing...

**Embolic protection devices**

**... ****requiring more in-depth review, including occasional Panel input.**

**Vascular anastomosis devices for CABG**

- Image-guided bronchoscopes

**Barbed sutures**

- Glaucoma shunts

***Daily wear contact lenses***

***CPAP devices for apnea***

## Clinical Data in 510(k)

- 10-15% of all 510(k)s
- Important difference with the predicate device
- Must be collected under IDE
- 	(21 CFR Part 812)

## Relationship to IDE

**Investigational Device Exemption (IDE)**
**Used to gather clinical performance data for research & development, or to support  510(k) or PMA**
**Device exempt from certain requirements, including 510(k)**

## FDA Review Procedure

- Submission Log-in
- Division Acceptance
- Assignment to Reviewer/Review Group
- ODE/OIVD Review
- FDA Issues Decision letter
- SE Decision Made Public Within
-    30 days

## FDA Requests Additional Information-

- Incomplete submissions (Refuse to Accept)
- When testing data is required to demonstrate equivalence

## Request for Additional Data (cont.)

- Reviewer request by telephone, email or letter
- Clock stops by letter only
- Forward to Document Mail Center
- 30 days to submit
- May request extension of time (180 day maximum) from the date of the additional information letter.
- Guidance for Industry and FDA Staff – FDA and Industry Actions on Premarket Notification (510(k)) Submissions: Effect on FDA Review Clock and Performance Assessment
- 	www.fda.gov/cdrh/mdufma/guidance/1219.html

## Confidentiality of Information

**21 CFR § 807.95**

##     Misbranding by Reference to 510(k)

**21 CFR § 807.97**

## 510(k) Exempt Devices

- Preamendments Devices
- Unfinished Devices
- Devices Exempt by Statute or regulation from 510(k)	739 Class I (93%), 74 Class II (8%)
- Finished Devices not Sold in U.S.
- Devices Covered Under Another 510(k), e.g., Private Labeled Device
- Custom Devices
- General Purpose Articles
- Veterinary Devices

##  Class I Exemptions- (Section 510(l) of FD&C Act)

**All Class I Devices are Exempt Except-**
- Those intended for a use which is of substantial importance in preventing
-    impairment of human health, or
- Those that present a potential
-     unreasonable risk of illness or injury

## Class II Exemptions-(Section 510(m) of the FD&C Act) 

- Class II devices that do not require 510(k)s to provide reasonable assurance of safety and effectiveness
- 75 device classifications exempt*
- Final Rule November 3, 1998
- * ***Subject to the Limitations on Exemptions***
**   **_**www.fda.gov/cdrh/modact/frclass2.html**_

## Limitations of Exemption from 510(k) - Class I & II 

- Found in “.9” of Classification Chapters
- Four Limitations:
- If the device has an intended use that is different from the intended use of a legally marketed device in that generic type

## Limitations of Exemptions from 510(k)- Class I & II (cont.)

- Operates using a different fundamental scientific technology than that used by a legally marketed device in that generic type
- Specific limitations for in vitro diagnostic devices
- Device specific limitations as specified in a classification regulation

## Class II Exemption Petition Process

- Beginning 1 day after Class II exemption FR notice of Jan. 20, 1998
- Exemption of Class II devices:
- on our own initiative, or
- by an interested person
- Criteria for exemption
- 510(k) not necessary to assure the safety & effectiveness
- use exemption criteria above

## Class II Exemption Petition Process (cont.)

- Guidance
**	**_**www.fda.gov/cdrh/modact/exemii.html**_
- Public notice, comment period and response
- “The Hammer” 180 days with
-      no response

## Determination of Intended Use(Section 513(i)(l)(E) of F,F,D,&C Act)

- Limits the determination if intended use to the labeling
- Establishes procedures for the Office Director when off-label use may be a concern
- Blue Book K98-1

## Limitations in labeling when there is:
reasonable likelihood that device will be used off label; and
such use could cause harm						

- reasonable likelihood that device will be used off label; and
- such use could cause harm

**Determination of Intended Use****  **

## “SE with Limitations”

- Includes boilerplate language from statute
- Specifies labeling limitations to be added to Precautions, Warnings, or Contraindications
- Indicates that device is SE only if label has these limitations; label cannot be modified w/o new 510(k) (Blue Book Memoranda #K86-3 and K98-1)

## Stent and Delivery System for use in Biliary Ducts

- For Malignant Neoplasms in the 		Biliary Tree
- The safety and effectiveness of this device for use in the vascular systems have not been established [vascular stents require PMA]

## Deciding When to Submit a 510(k) for a Change to an Existing Device

_**(http://www.fda.gov/cdrh/ode/510kmod.html)**_
**Blue Book Memorandum #K97-1**
**Notice of Availability:**
**February 21, 1997   62 FR 8024**

## Hints for Using the Guidance

- Guidance Does Not Establish Regulatory Requirements, i.e., Does Not Bind FDA or Industry
- For Modification Resulting From Recalls, Refer to 510(k) Requirements for Firm-Initiated Recalls” _**(http://www.fda.gov/cdrh/ode/k951.html)**_
- Understand Roles
-    - Industry - Decision-maker				           - FDA - Arbiter

## Hints (cont.)

- Document Does Not Supplant Device/Situation Specific Guidance
- Read the Narrative; Do Not Go Directly to the Flowcharts
- Understand the Definitions; Do Not Make Assumptions
- In Using the Guidance, Comparison Should be to Your Own “Unmodified Device, Whereas 510(k) Submission May Compare to Any Legally Marketed Device

## Hints (cont.)

- Assess Individual Changes; Consider all Reasonably Foreseeable Effects of Each Change
- Do Not Overlook the Cumulative Effect(s) of a Series of Incremental Changes
- Go All the Way Through the Flowcharts, i.e., Don’t Stop at the First Decision Point
- Establish a process for evaluation of modifications
- Document Decision-making

## Modifications to Devices Requiring 510(k) (cont.)

- When is the device new?
- When is the device modified?
- Is the proposed modification “significant?”
- “Could” it significantly affect safety or effectiveness?
- When does FDA say no 510(k) is required?

## Modifications That Do Require a 510(k)

- New Indications for Use
- New Fundamental Scientific Technologies

## Modifications That Do NotRequire a 510(k)

- Addition of a trade name
- Additional sizes within the specifications
- Change from one traditional sterilization to another
- Deleting Indications

## Main Flowchart:

**When to File a 510(k) After **
**a Change to a Legally Marketed Device**

## Slide 109

## FLOWCHART A

**Is It a Labeling Change?**

## Slide 111

## Labeling Changes

**Examples of Labeling Changes that Generally Require a New 510(k) Notice:**
**Expanding the indications for use to a new, distinct patient population;****	**
**Changing the device labeling of a single-use device to permit reuse;**
**Switching from prescription to over-the-counter (OTC) ; or****	****	****	****	**
**Deleting a contraindication.**

## Labeling Changes (cont.)

**Examples of labeling changes that generally do **_**not**_** require a new 510(k) notice:**
- Restricting the indications for use to a subset of the original indications
- Expanding the population with similar
-         diagnosis, prognosis, etc.
- Changing the warnings or precautions; or
- Revising the labeling to clarify the
-    Instructions for use

## FLOWCHART B

**Is It a Technology or **
**Performance Change?**

## Slide 115

## Technology, Engineering, &  Performance Changes	

- Broad span of design activities
- All changes in technology, engineering, and performance are evaluated & validated according to GMP requirements to determine if a new 510(k) notice must be filed.

## Technology, Engineering, &   Performance Changes (cont.)

- Examples of technology, engineering, and performance changes that generally require a new 510(k) notice:
- Changing the control mechanism (i.e., analog to digital control; pneumatic to electronic control, etc.
- Changing the operating principle;
- Changing the energy source;
- Changing the sterilization procedure in a manner that affects performance specifications or
-    reduces the sterility assurance level.

## Technology, Engineering, &   Performance Changes (cont.)

**Other types of design or engineering changes, i.e., changes to the performance specifications, the dimensional specifications, and the software/firmware, may not require a new 510(k) if:****	****	****  **
- They do not affect the indications for use
- They do not require supporting clinical data on
- 	S & E for purposed of determining substantial equivalence; and
- The results of design validation do not raise
-     new issues of S & E.

## FLOWCHART C

**Is It a Materials Change?**

## FLOWCHART C - IS IT A MATERIALS CHANGE?

**an IVD?**

**From**
**Main**
**Chart**

**Documentation**

**New  510(k)**

**Go to Chart D**

**Go to Chart**
**B, B5**

**Go to Chart**
**B, B5**

**Change in**
**material type?**

**Change in**
**material**
**formulation?**

**Change**
**in material**
**supplier?**

**Material**
**ordered to**
**a spec?**

**Is the device**
**an implant?**

**Will the affected**
**part of the**
**device be likely to**
**contact body tissues**
**or fluids?**

**Change in**
** ****device**
** ****performance**
**specifications?**

**Will the**
**affected part**
**of the device be**
**likely to contact**
**body tissues**
**or fluids**
**in vivo?**

**Change in**
** ****device**
**performance**
** ****specifications?**

**Considering the**
**requirements of**
**ISO 10993-1, is**
**additional testing **
**required?**

**New  510(k)**

**Documentation**

**Yes**

- No

- No

- No

- Yes

- Yes

- Yes

- Yes

- No

- No

- Yes

- No

- No

- Yes

- No

- Yes

- No

- Yes

- Yes

- No

- Yes

**C1**

**C2**

**C3**

**C2.1**

**C2.1.1**

**C4**

**C4.1**

**C2.2**

**C2.3**

**C2.2.1**

**C2.1.2**

_**FLOWCHART C - IS IT A MATERIALS CHANGE?**_

## Materials Changes

- A new 510(k) notice may be required for changes in the basic type of material (i.e., metal versus polymer) or the material formulation.
- A new 510(k) notice generally is not required for a change in the raw material supplier, provided that the vendor supplies the material according to the same/similar specification.

## Materials Changes (cont.)

- Standards for determining whether changes in the type of material or the formulation of the material require a new 510(k) differ for implantable devices and non-implantable devices.
- For implantable devices, a new 510(k) should be submitted if the new material is likely to contact body fluids or tissues

## Materials Changes (cont.)

- For non-implantable devices, a new 510(k) generally should be submitted if:
- The new material is likely to contact body fluids or tissues, and
- New biocompatibility testing of the 		  material is required by ISO 10993-1
- In determining whether a new 510(k) must be submitted, manufacturers also should consider whether the change in materials alters the performance specifications for the device

## Slide 124

## When Can a Modification be a Special 510(k)?

- Manufacturer Modifies own Legally Marketed Class I, II, or III Device and Determines that a 510(k) is Required
- Modification Does** **_**not**_ Affect Intended Use or Basic Fundamental Scientific Technology

## When Can a Modification be an Abbreviated 510(k)?

**ALWAYS, if there is a standard or guidance**
**When Can a Modification be **
**Reviewed by a Third Party?****	**
**Always, if the device is eligible and no clinicals are needed**

## What is the Gray Zone?

- Indications vs. Claims?
- Changes in Materials?
- Sterilization Changes?
- Inconsistencies with “The New 510(k) Paradigm?”

## What is the Gray Zone? (cont.)

- What About Implied Indications for Use?
- When Does a Device Exempt from 510(k) Require a New 510(k) for a Modification?
- How/When do you submit a 510(k) for a modification to a Preamendments Device?

## What Should You Do in the Gray Zone?

- Submit a 510(k)?
- Submit an Add-to-File?
- Submit a 513(g)?
- Document Your Files?
- Submit a Special?
- Telephone CDRH?
- Email CDRH?

## 510(k) StatisticsFY’s 02, 03 and O4  

**510(k)s Received:**
- FY02  -  4,322
- FY03  -  4,227
- FY04  -  3,110 (ODE ONLY)
**510(k)s Completed:**
- FY02 -  4,373
- FY03  - 4,123
- FY04  - 3,376 (ODE ONLY)

## 510(k) StatisticsFY’s 02, 03 & 04  

**Average Review Times**
**FY 02 - FDA Days 79  Total Days 100**
**FY 03 - FDA Days 76****	**** Total Days 96**
**FY 04 – FDA Days 74  Total Days 100**

## Average FDA Review Times for 510(k)s(Fiscal Year 2004)

**Average FDA Review Times for 510(k)s**(Fiscal Year 2004)

## MDUFMA and 510(k)

- Goals are defined in letter from DHHS Secretary Thompson to Congress
- Measured in FDA days
- Represent improvements over current clearance/approval times
- FY 2007 FDA 510(k) decision goal (80%) within 90 days) will be re-evaluated to determine whether it is appropriate for FY 2007

## MDUFMA and 510(k)

- Reduced fee for small business began FY 2004 (80% fee)
- No fee for any 510(k) indicated solely for pediatric use
- No fee for any 510(k) reviewed by a Third Party of EU CAB
- No fee for any 510(k) submitted by Federal/State Government if not distributed commercially

## 510(k) MDUFMA Goals

- FY 2007 FDA Decision goal (80% within 90 days) may be re-evaluated in consultation with industry to determine whether it is appropriate for FY2007.

**Notes:**
FY 2007 FDA Decision goal (80% within 90 days) may be re-evaluated in consultation 
With industry to determine whether it is appropriate for FY2007.

- Guidance for Industry and FDA Staff FDA
- & Industry Actions on Premarket
- Notification (510(k)) Submissions: Effect on
- FDA Review Clock and Performance
- Assessment
- 3 Cycles of Review
- 180 Day Maximum Extension
- Refuse to Accept counts as cycle
**    **_[www.fda.gov/cdrh/mdufma/guidance/1219.html](http://www.fda.gov/cdrh/mdufma/guidance/1219.html)_

**New MDUFMA Guidance**

## Meeting the MDUFMA goals- Review Process for Traditional 510ks

**Meeting the MDUFMA goals- ****Review Process for Traditional 510ks**

**Preliminary determination that no additional info needed**

**FDA Initial Review**

**Interactive Review**

***Final Decision ******(***_***<***_***90 total days)***

***Scenario #1***

## Meeting the MDUFMA goals-Review Process for Traditional 510ks

**FDA Initial Review**

**Interactive Review **

**Determination that  additional info needed**

***Hold ***

***Final Decision ******(***_***<***_***90 total days)***

***Scenario #2***

**Preliminary determination that no additional info needed**

## Meeting the MDUFMA Goals-Review Process for Traditional 510ks

**FDA Initial Review**

** ****Review **

**Determination that  additional info needed**

***Hold***

***Final Decision ******(***_***<***_***90 total days)***

***Scenario #3***

***Hold***

** ****Review **

**Determination that  additional info needed**

## New MDUFMA Guidance

- User Fees and Refunds for Premarket Notification Submissions (510(k))
- www.fda.gov/cdrh/mdufma/guidance/1511.html

## 510(k) User Fees and Refunds* Frequently Asked Questions

- Are all 510(k)s subject to user fees?
- Are 510(k)s reviewed by a European Union Conformity Assessment Body 	(EU CAB) subject to user fees?
- *_**www.fda.gov/cdrh/mdufma/guidance/1511.pdf**_

## 510(k) User FeesFrequently Asked Questions (cont.)

- Will the agency assess a fee if FDA determines that my device was not eligible for review by a third party or an EUCAB?
- Will FDA refund the user fee if I submit a 510(k) that is not required?

## 510(k) User FeesFrequently Asked Questions (cont.)

- Are there fees for a new submission if I  previously received a not substantially equivalent (NSE) determination for my device?
- Are there fees assessed if I submit additional information to a pending 	510(k)?

## 510(k) User FeesFrequently Asked Questions (cont.)

- Will FDA refund the user fee if I withdraw my 510(k)?
- If my 510(k) is considered withdrawn because I failed to supply requested information, will FDA require a new user fee if I resubmit my 510(k)?

## Bundling Multiple Devices in a Single Application

- What is it?
- Bundling before MDUFMA
- Effect of MDUFMA
- Stakeholders
- Applies to 510(k)s and PMAs

## Bundling - Specific Issues

- Generic type device
- Multiple indications for use
- 510(k) device with PMA device
- Changes that affect multiple devices
- Reprocessed single use devices
- In Vitro diagnostic devices

## Bundling - Procedures

- How to bundle
- FDA action if inappropriate
- Appeals
- Additions after submission
- Withdrawals & more information

## Bundling - General Principles

- One review
- FDA – won’t cull out
- Submitter – won’t inappropriately bundle

## Dispute Resolution

## Dispute Resolution

- Special Dispute Resolution Panel - April 1999 §404 of FDAMA
- Guidance available on dispute resolution practices, Feb. 1998:
-  _www.fda.gov/cdrh/modact/dispresl.pdf_
- Final agency rule in Nov. 1998 amending                 21 CFR 10.75
- Draft guidance on resolving scientific disputes using

## 21 CFR 10.75

- For any decision					- hold letter					- not equivalent, not approvable		-policy matter
- May request a meeting
- Will receive written response
- Not on public display (other than
- 	dispute resolution process)

## Dispute Resolution Options

-  21 CFR 10.30
- 21 CFR 10.75, includes Dispute Resolution

## 21 CFR 10.30 

- 21 CFR 10.30
- Citizen petition
- Any subject
- Public

## What To Do When You Disagree with CDRH?

- Define the problem, what you’re willing to do, and what you want CDRH to do.
- Try to reach agreement at the lowest level possible
- Document your concerns
- Appeal through the supervisory chain before invoking a more formal process.
- Consider all the options before choosing.

## Appeals Have Their Uses

- Appeals *aren’t* a waste of time.
- Supervisors *want* feedback when you believe we’ve made an incorrect decision.
- Appeals are *routine*.  You won’t be “marked for life” if you appeal a decision.
- CDRH *does not* tolerate retribution.
- Our starting point:  *Any* dispute can be resolved when both sides keep an open mind.

## Appeals Scorecard ---510(k)

- 125 appeals received as of January 1993								-66 decisions upheld				-52 decisions overturned		 		-7 have been withdrawn

## Dispute Resolution

- Dispute Resolution Panel, added to Medical Devices Advisory Committee
- Panel members selected
- CDRH recruited an Ombudsman for the Center
- Dispute Resolution Panel trained October 2000
- Panel meeting scheduled for June 4, 2001

## 510(k) Third Party Review Program

## Topics

- What is third party review?
- Which devices are eligible?
- Volume of submissions
- Organizations accredited
- Acceptability of reviews
- Timeliness
- Steps to strengthen program
- Is third party review right for you?

## Third Party Review Program(a.k.a. “Accredited Persons”)

**Gives manufacturers the option of using accredited, non-Federal organizations to review 510(k)s for low and moderate risk devices, in place of FDA’s review**

## Purpose of Program

- More rapid marketing clearance decisions
- Better allocation of FDA’s resources

## Origin

**1995 -****	****FDA announced 2-year pilot**
**	****	****	****(Reinventing Government)**
**1996 -****	****Pilot began**
**1997 -****	****FDAMA enacted; established**
**	****	****	****§523:  “Accredited Persons”**
**1998 -****	****AP program implemented**
***	******	******	******www.fda.gov/cdrh/thirdparty***

## Key Documentswww.fda.gov/cdrh/thirdparty

- Procedural guidance
- List of eligible devices
- List of Accredited Persons

## Third Party Review Process

**Mfr. may elect to use AP or FDA**
**If AP route is chosen:**
_**Applicant**_** contracts with AP**
_**AP**_** reviews 510(k), makes recom.**
**	**
_**FDA**_** issues final decision (30 days)**

## Statutory Limitation§ 523(a)(3)

**Accredited Persons may not review:**
**Class III devices**
**Class II devices that:**
**are permanently implantable**
**are life sustaining/supporting, or**
**require clinical data in 510(k)s**

## List of Eligible Devices

- Initially:
- Included all Class I devices and selected Class II devices
- Guidance available to ensure timely and consistent reviews

## Expansion Pilot

- Gives Accredited Persons the opportunity to review 510(k)s for Class II devices _**without**_ device-specific guidance documents, to the extent permitted by law

## Class II Device Types (Regs.)Eligible for Third Party Review

**Aug**
**96**

**Nov**
**96**

**Jul**
**97**

**Sep**
**97**

**Feb**
**98**

**Nov**
**98**

**6**

**14**

**23**

**28**

**25**

**104**

**154**

**617**

**Mar**
**01**

**Jun**
**00**

**617**

**Present**

**Expansion Pilot**

## 510(k)s for Class I or II Devices(SE Decisions)

**Pre-FDAMA pilot began**

**FDAMA exemptions**

**AP Program began**

**Expansion pilot**

**Ineligible by law**

## Current Scope

- More than 670 types of Class I and Class II devices are eligible
- Eligible devices account for approximately 65 percent of all 510(k) submissions

## 510(k)s Received by FDA With a Third Party Review 

## Accredited Organizations

- _Accredited for expansion pilot and non-pilot devices_:
- TUV America, Inc.
- Underwriters Laboratories, Inc.
- TUV Rheinland of North America, Inc.
- CITECH
- Entela, Inc.
- California Department of Health Services
- Intertek Testing Services
- KEMA Quality, BV  (Netherlands)
- Regulatory Technology Services, LLC
- _Accredited for non-pilot devices only_:
- Center for Measurement Standards, ITRI  (Taiwan)
- British Standards Institution  (United Kingdom)
- Cheiroon, BV  (Netherlands)
- NIOM Scand. Inst. of Dental Materials  (Norway)
- MedTech Review, LLC

## Steps to Strengthen Program

- Quarterly FDA-AP teleconferences
- Updating July 1996 “Instruction Manual” for third party reviews
- Developing Q&A guidance on eligibility criteria
- Internal training
- Training for AP review personnel

## Why Consider a Third Party?

- Usually more timely
- Accessibility
- Many APs also have standards and foreign regulatory expertise
- No FDA user fee

## When to Think Twice

- “Special” 510(k)s
- Device eligibility uncertain
- 	(e.g., may require clinical data)
- Complex, precedent-setting submissions
- AP lacks relevant experience

## How To Get Started

- Check eligible device list
- Contact AP(s); ask about:
- Review timeframe
- Estimated cost
- Experience
- Obtain quote
- Sign contract/submit 510(k)

## Questions?

- FDA’s third party web page: _**www.fda.gov/cdrh/thirdparty**_
- Eric Rechen,
-    ODE/CDRH
- phone: 301-594-2186, ext. 138
- e-mail:	ejr@cdrh.fda.gov
- DSMICA:
- phone: 800-638-2041
- e-mail:	dsmica@cdrh.fda.gov

## A Strategy For Preparing Successful 510(k) Submissions (cont.)

- Understand and follow the 510(k) decision-making process
- Employ our 510(k) decision-making chart
- Use our 510(k) Format Guidance
- Use and include our “Refuse to Accept” Checklist
- Complete our documentation forms
- Follow applicable guidance documents and device specific checklist

## A Strategy For Preparing Successful 510(k) Submissions (cont.)

- Provide complete information
- Prominently display relevant data and information
- Do not confuse volume with quality when referencing          information include appropriate authorizations and reference with specificity
- Check for contradictions and inconsistencies within the document, e.g., between the indication statements in the 510(k) and the labeling/promotional materials
- Learn from your experiences and the experiences of your competitors

## Recommendations for Greater Success

- Stay abreast of regulatory changes
- 		-Preamendments strategy
- 		-Exemptions from premarket notification		-510(k) modifications document
- 		-Various proposed/final regulations

## Recommendations for Greater Success (cont.)

- Submit Quality Applications
- Understand all applicable regulations
- Become familiar with policies, precedence
-    and procedures related  to subject device
- Rely on valid scientific evidence  (21 CFR 860.7)
- Avoid premature submissions

## Recommendations for Greater Success (cont.)

- Take Advantage of Current Information
- Advisory panel meetings
- FDA sponsored workshops
- CDRH teleconferences
- Division of Small Manufacturers, International and Consumer Assistance
- Freedom of Information
- CDRH Websites
- Guidance Documents

## A Strategy For Preparing Successful 510(k) Submissions

- Present information in an organized manner
- Include a table of contents
- Paginate properly
- Employ tables and graphs where appropriate
- Use visual aids whenever possible
- Highlight basic 510(k) content requirements, e.g.,  510(k) summaries

## 510(k) Guidance Documents

**Guidance on the CDRH Premarket Notification Review Program **
**	**_[www.fda.gov/cdrh/k863.html](http://www.fda.gov/cdrh/k863.html)_
**The New 510(k) Paradigm **_[www.fda.gov/cdrh/ode/parad510.html](http://www.fda.gov/cdrh/ode/parad510.html)_
**Guidance for Industry and FDA Staff Format for Traditional and Abbreviated 510(k)s **
- 	_[www.fda.gov/cdrh/ode/guidance/1567.html](http://www.fda.gov/cdrh/ode/guidance/1567.html)_

## 510(k) Guidance Documents

**Frequently Asked Questions and Answers on Paradigm**
**	**_[www.fda.gov/cdrh/ode/92_a.html](http://www.fda.gov/cdrh/ode/92_a.html)_
**Determination of Intended Use for 510(k) Devices**
**	**_[www.fda.gov/cdrh/ode/guidance/857.html](http://www.fda.gov/cdrh/ode/guidance/857.html)_

## 510(k) Guidance Documents

**Deciding when to Submit a 510(k) for a Change to an Existing Device**
**   **_[www.fda.gov/cdrh/ode/510kmod.html](http://www.fda.gov/cdrh/ode/510kmod.html)_
**Use of Standards in Substantial Equivalence Determinations **_**www.fda.gov/cdrh/ode/guidance/1131.html**__** **_

## 510(k) Guidance Documents

**Convenience Kit Interim Regulatory Guidance****	**_[www.fda.gov/cdrh/ode/convkit.html](http://www.fda.gov/cdrh/ode/convkit.html)_
**	**
**Evaluation of Automatic Class III Designation****	**_[www.fda.gov/cdrh/modact/classiii.html](http://www.fda.gov/cdrh/modact/classiii.html)_

## 510(k) Guidance Documents

**Expedited Review****	**
- 	_[www.fda.gov/cdrh/modact/expedite.html](http://www.fda.gov/cdrh/modact/expedite.html)_
**Procedures for Class II Device Exemptions from 510(k)****	**
-     _[www.fda.gov/cdrh/modact/exemii.html](http://www.fda.gov/cdrh/modact/exemii.html)_

## 510(k) Guidance Documents

**Updated Sterility Review Guidance**
- 	_[www.fda.gov/cdrh/ode/guidance/361.html](http://www.fda.gov/cdrh/ode/guidance/361.html)_
**Resolving Scientific Disputes Concerning the Regulation of Medical Devices****	**
- 	_[www.fda.gov/cdrh/resolvingdisputes/1121.html](http://www.fda.gov/cdrh/resolvingdisputes/1121.html)_

## 510(k) Guidance Documents

**Medical Device Appeals and Complaints**
- 		_[www.fda.gov/cdrh/modact/dispresl.pdf](http://www.fda.gov/cdrh/modact/dispresl.pdf)_
**General/Specific Intended Use****	****	****	**_[www.fda.gov/cdrh/modact/genspec.html](http://www.fda.gov/cdrh/modact/genspec.html)_
**	**

## New 510(k) Guidance Documents

**FDA and Industry Actions on Premarket Notification (510(k)) Submissions:  Effect on FDA Review Clock and Performance Assessment**
**   **_**w**__[ww.fda.gov/cdrh/mdufma/guidance/1219.html](http://www.fda.gov/cdrh/mdufma/guidance/1219.html)_
**User Fees and Refunds for Premarket Notification Submissions (510(k))**
**   ****www.fda.gov/cdrh/mdufma/guidance/1511.html**

## Related Websites 

**Medical Device User Fee Modernization Act**
-    _[www.fda.gov/cdrh/mdufma/index.html](http://www.fda.gov/cdrh/mdufma/index.html)_
**Combination Products**
-     _[www.fda.gov/oc/combination.html](http://www.fda.gov/oc/combination.html)_
**Preamendment Status Determination**
-    _[www.fda.gov/cdrh/comp/preamend.html](http://www.fda.gov/cdrh/comp/preamend.html)_

## More Related Websites

**CDRH Device Advice**					_[www.fda.gov/cdrh/devadvice](http://www.fda.gov/cdrh/devadvice)_
**CDRH Standards Program**
- 		_[www.fda.gov/cdrh/stdsprog.html](http://www.fda.gov/cdrh/stdsprog.html)_
**Good Guidance Practices****	**			_[www.fda.gov/cdrh/ggpmain.html](http://www.fda.gov/cdrh/ggpmain.html)_

## Additional Resources

- Facts-on-Demand:
-   1-800-899-0381 (Index is #919)
-   301-827-0111
- Division of Small Manufacturers, International and Consumer Assistance (DSMICA)
- 	1-800-638-2041 or 301-443-6597

## Additional Resources

**Blue Book Memo: Fax & E-mail Communication** _[http://www.fda.gov/cdrh/ode/a02-01.html](http://www.fda.gov/cdrh/ode/a02-01.html)_
**CDRH website**
- 	_[http://www.fda.gov/cdrh](http://www.fda.gov/cdrh)_

## Additional Resources

**You can subscribe to the CDRHNEW list by going to:**
- _[http://](http://list.nih.gov/archives/cdrhnew.html)__[list.nih.gov/archives/cdrhnew.html](http://list.nih.gov/archives/cdrhnew.html)_