SlideShare a Scribd company logo
1 of 60
Download to read offline
Harvard-MIT Division of Health Sciences and Technology
HST.535: Principles and Practice of Tissue Engineering
Instructors: Myron Spector

                           Massachusetts Institute of Technology
                                Harvard Medical School
                             Brigham and Women’s Hospital
                              VA Boston Healthcare System




                                             HST535

                  FEDERAL REGULATORY ISSUES:
                   US Food and Drug Administration
                     Medical Device Amendments



                                       M. Spector, Ph.D.
FEDERAL AGENCIES THAT REGULATE
MEDICAL DEVICES AND TISSUE ENGINEERED
             PRODUCTS

 US       Food and Drug Administration
 China    Chinese FDA
 Europe   Various agencies; “CE mark”
 India    None yet
US FDA ORGANIZATION
Center for Biologics Evaluation and Research (CBER)
Center for Devices and Radiological Health (CDRH)
Center for Drug Evaluation and Research (CDER)
Center for Food Safety and Applied Nutrition
 (CFSAN)
Center for Veterinary Medicine (CVM)
National Center for Toxicological Research (NCTR)
Office of the Commissioner (OC)
Office of Regulatory Affairs (ORA)
                  Which center to review your application?
FDA

      Center for Devices and
        Radiological Health
      http://www.fda.gov/cdr
            h/index.html
FDA APPROVAL PROCESS
          Classification of Product as I, II, or III
                                               TE products
 I. General        II. Special         III. Premarket
    Controls           Controls             Approval (PMA)




Good Manuf.
  Practice
   GMP
FDA APPROVAL PROCESS
          Classification of Product as I, II, or III
                                               TE products
 I. General        II. Special         III. Premarket
    Controls           Controls             Approval (PMA)
No approval of
 FDA prior to
 selling the
 product.

Good Manuf.
  Practice
   GMP
FDA APPROVAL PROCESS
          Classification of Product as I, II, or III
                                               TE products
 I. General        II. Special          III. Premarket
    Controls           Controls              Approval (PMA)
No approval of Equivalent to Marketed
 FDA prior to         Device?;
 selling the   Premarket Notification
 product.
                      510 (k)
Good Manuf.
  Practice
   GMP
FDA APPROVAL PROCESS
          Classification of Product as I, II, or III
                                                     TE products
 I. General          II. Special              III. Premarket
    Controls             Controls                  Approval (PMA)
No approval of Equivalent to Marketed
 FDA prior to         Device?;
 selling the   Premarket Notification
 product.
                        510 (k)
Good Manuf.
  Practice      Analysis of composition
               and properties, and in vitro
   GMP             and in vivo studies          Good Lab Pract.   GLP
FDA APPROVAL PROCESS
          Classification of Product as I, II, or III
                                                     TE products
 I. General          II. Special              III. Premarket
    Controls             Controls                  Approval (PMA)
No approval of Equivalent to Marketed             Human Trial
 FDA prior to         Device?;                   Investigational
 selling the   Premarket Notification                Device
 product.                                          Exemption IDE
                        510 (k)
Good Manuf.
  Practice      Analysis of composition               PMA
               and properties, and in vitro
   GMP             and in vivo studies          Good Lab Pract.   GLP
FDA History
http://www.fda.gov/oc/opacom/fda101/sld017.html
• In 1906, President Theodore Roosevelt signed into law the Food and Drugs
  Act. The 1906 law's relevant background in America starts with colonial food
  statutes concerned with bread and meat. The first national law came in 1848
  during the Mexican War. It banned the importation of adulterated drugs, a
  chronic public health problem.
• In 1937, a public health disaster demonstrated the need for a stronger federal
  law. Sulfanilamide, the first quot;wonder drugquot; and a popular and effective
  treatment for diseases like strep throat and gonorrhea, was formulated into an
  Elixir of Sulfanilamide and marketed for use in children. But the liquid
  formulation contained a poison, the same chemical used in antifreeze, and it
  killed 107 people, most of them children. The earlier law did not require the
  drug's manufacturer to test the formulation for safety before it was sold.
• Congress corrected this weakness in the law the next year when it passed the
  Federal Food, Drug, and Cosmetic Act. This law, for the first time, required
  companies to prove the safety of new drugs before putting them on the
  market. The new act also added the regulation of cosmetics and therapeutic
  devices, and generally updated the law to improve consumer protection.
• Congress has continued to give FDA new responsibilities over the years,
  including the requirement that drugs and medical devices be proven effective
  as well as safe before they can be sold (Medical Devices Amendment of 1976).
CDRH Advisory Committees
•   The Center for Devices and Radiological Health has
    established advisory committees to provide independent,
    professional expertise and technical assistance on the
    development, safety and effectiveness, and regulation of
    medical devices and electronic products that produce
    radiation. Each committee consists of experts with
    recognized expertise and judgment in a specific field. The
    committees are advisory -- they provide their expertise and
    recommendations -- but final decisions are made by FDA.
•   The Center has four advisory committees, including a
    Medical Devices Advisory Committee which consists of 18
    panels that cover the medical specialty areas. These advisory
    committee meetings are open to the public, and time is
    provided for public comment on the topic under
    consideration.
CDRH
               Overview of Regulations
• The CDRH is responsible for regulating firms who
  manufacture, repackage, relabel, and/or import
  medical devices sold in the United States.
• Medical devices are classified into Class I, II, and III.
  A description of device classification and a link to the
  Product Classification Database can be found at:
  ttp://www.fda.gov/cdrh/devadvice/313.html.
  Regulatory control increases from Class I to Class III.
  The device classification regulation defines the
  regulatory requirements for a general device type.
   – Most Class I devices are exempt from Premarket
     Notification 510(k)
   – Most Class II devices require Premarket Notification
     510(k);
   – Most Class III devices require Premarket Approval.
CDRH
           Overview of Regulations

• The basic regulatory requirements that
  manufacturers of medical devices distributed in
  the U.S. must comply with are:
  – Premarket Notification 510(k), unless exempt, or
    Premarket Approval (PMA),
  – Establishment registration on form FDA-2891,
  – Medical Device Listing on form FDA-2892,
  – Quality System (QS) regulation,
  – Labeling requirements, and
  – Medical Device Reporting (MDR)
Is My Product Regulated by FDA's Center
        for Devices and Radiological Health?
• The FDA regulates medical devices to assure their safety and effectiveness.
  The CDRH is the component within the FDA that is responsible for this
  program. To fulfill the provisions of the FD&C Act that apply to medical
  devices and radiation-emitting products, the FDA develops, publishes and
  implements regulations. These regulations are initially published in the
  Federal Register (FR) for public comment. The FR is a compilation of the
  daily government activities including proposed and final regulations. Final
  regulations are subsequently placed or codified into the Code of Federal
  Regulations (CFR) on an annual basis.
• One of the most important aspects of getting a medical device to market is to
  know where to begin. The starting point is determining whether the product
  you plan to market is a medical device, as defined in section 201(h) of the
  FD&C Act. If your product meets the definitions, it will be subject to the
  provisions of the FD&C Act, that is, there are FDA regulatory requirements
  that must be met before a product can be marketed in the U.S. The purpose
  of Device Advice is to help you decide whether your product is subject to
  FDA regulations, and if so, to identify what these regulatory requirements
  are and help you comply with them.
Medical Device Definition
• Medical devices range from simple tongue depressors and bedpans to
  complex programmable pacemakers with micro-chip technology and laser
  surgical devices. If a product is labeled, promoted or used in a manner that
  meets the following definition in section 201(h) of the Federal Food Drug &
  Cosmetic (FD&C) Act it will be regulated by the FDA as a medical device
  and is subject to premarketing and postmarketing regulatory controls.
• A device is:quot;an instrument, apparatus, implement, machine, contrivance,
  implant, in vitro reagent, or other similar or related article, including a
  component part, or accessory which is:
    – recognized in the official National Formulary, or the United States
      Pharmacopoeia, or any supplement to them,
    – 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
    – intended to affect the structure or any function of the body of man or other
      animals, and which does not achieve any of it's 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 any of its
      primary intended purposes.quot;
Medical Device Definition
• The definition provides a clear distinction between a medical
  device and other FDA regulated products such as drugs. If the
  primary intended use of the product is achieved through
  chemical action or by being metabolized by the body, the
  product is usually a drug. Human drugs are regulated by
  FDA's Center for Drug Evaluation and Research (CDER).
  Biological products which include blood and blood products,
  and blood banking equipment are regulated by FDA's Center
  for Biologics Evaluation and Research (CBER).
• FDA's Center for Veterinary Medicine (CVM) regulates
  products used with animals.
• If your product is not a medical device but regulated by
  another Center in the FDA, each component of the FDA has an
  office to assist with questions about the products they regulate.
• In cases where it is not clear whether a product is a medical
  device there are procedures in place to use DSMICA Staff
  Directory to assist you in making a determination.
FDA DEVICE CLASSIFICATION
• The FDA has established classifications for approximately 1,700
  different generic types of devices and grouped them into 16
  medical specialties referred to as panels. Each of these generic
  types of devices is assigned to one of three regulatory classes
  based on the level of control necessary to assure the safety and
  effectiveness of the device:
  – Class I General Controls
  – Class II General Controls and Special Controls
  – Class III General Controls and Premarket Approval
• The class to which your device is assigned determines, among
  other things, the type of premarketing submission/application
  required for FDA clearance to market.
  – If your device is classified as Class I or II a 510k will be required for
    marketing.
  – For Class III devices, a premarket approval application (PMA) will be
    required.
FDA DEVICE CLASSIFICATION

• Device classification depends on the intended use of the device
  and also upon indications for use. For example, a scalpel's
  intended use is to cut tissue. A subset of intended use arises when
  a more specialized indication is added in the device's labeling
  such as, quot;for making incisions in the cornea.quot; Indications for use
  can be found in the device's labeling, but may also be conveyed
  orally during sale of the product.
• In addition, classification is risk based, that is, the risk the device
  poses to the patient and/or the user is a major factor in the class
  it is assigned. Class I includes devices with the lowest risk and
  Class III includes those with the greatest risk.
• As indicated above all classes of devices as subject to General
  Controls. General Controls are the baseline requirements of the
  Food, Drug and Cosmetic (FD&C) Act that apply to all medical
  devices, Class I, II, and III.
How to Determine Classification
• To find the classification of your device you need to find the regulation
  number that is the classification regulation for your device. There are two
  methods for accomplishing this: go directly to the classification database and
  search for a part of the device name, or, if you know the device panel
  (medical specialty) to which your device belongs, go directly to the listing for
  that panel and identify your device and the corresponding regulation.
• If you already know the appropriate panel you can go directly to the CFR
  and find the classification for your device by reading through the list of
  classified devices, or if you're not sure, you can use the keyword directory in
  the PRODUCT CODE CLASSIFICATION DATABASE. In most cases this
  database will identify the classification regulation in the CFR. You can also
  check the classification regulations below and the Precedent Correspondence
  for information on various products and how they are regulated by CDRH.
• Once you have identified the correct classification regulation go to What are
  the Classification Panels below and click on the correct classification
  regulation or go to the CFR Search page. Some Class I devices are exempt
  from the premarket notification and/or parts of the good manufacturing
  practices regulations. Approximately 572 or 74% of the Class I devices are
  exempt from the premarket notification process. These exemptions are listed
  in the classification regulations of 21 CFR and also has been collected
  together in the Medical Device Exemptions document.
DEVICE CLASSES


Class I - General Controls
Class II - Special Controls
Class III - Premarket Approval
DEVICE CLASSES
                  Class I - General Controls
• Class I devices are subject to the least regulatory control. They
  present minimal potential for harm to the user and are often
  simpler in design than Class II or Class III devices. Class I devices
  are subject to quot;General Controlsquot; as are Class II and Class III
  devices.
• General controls include:
  – Establishment Registration of companies which are required to register
    under 21 CFR Part 807.20, such as manufacturers, distributors, repackages
    and relabelers.
  – Medical Device Listing (use FDA Form 2892) with FDA of devices to be
    marketed.
  – Manufacturing devices in accordance with Good Manufacturing Practices
    (GMP).
  – Labeling devices in accordance with labeling regulations.
  – Submission of a premarket notification [510(k)] before marketing a device.
• Examples of Class I devices include elastic bandages, examination
  gloves, and hand-held surgical instruments.
DEVICE CLASSES
            Class II - Special Controls

• Class II devices are those for which general
  controls alone are insufficient to assure safety and
  effectiveness, and existing methods are available to
  provide such assurances. In addition to complying
  with general controls, Class II devices are also
  subject to special controls.
• Special controls may include special labeling
  requirements, mandatory performance standards
  and postmarket surveillance.
• Examples of Class II devices include powered
  wheelchairs, infusion pumps, and surgical drapes,
  and also some joint replacement prostheses and
  bone graft substitute materials.
DEVICE CLASSES
             Class III - Premarket Approval
• Class III is the most stringent regulatory category for devices. Class III
  devices are those for which insufficient information exists to assure safety
  and effectiveness solely through general or special controls.
• Class III devices are usually those that support or sustain human life, are
  of substantial importance in preventing impairment of human health, or
  which present a potential, unreasonable risk of illness or injury.
• Premarket approval is the required process of scientific review to ensure
  the safety and effectiveness of Class III devices. Not all Class III devices
  require an approved premarket approval application to be marketed.
  Class III devices which are equivalent to devices legally marketed before
  May 28, 1976 may be marketed through the premarket notification
  [510(k)] process until FDA has published a requirement for manufacturers
  of that generic type of device to submit PMA data.
• Class III devices which require an approved premarket approval
  application to be marketed are those:
   – regulated as new drugs prior to May 28, 1976, also called transitional devices.
   – devices found not substantially equivalent to devices marketed prior to May 28,
     1976.
   – Class III preamendment devices which, by regulation in 21 CFR, require a
     premarket approval application.
DEVICE CLASSES
           Class III - Premarket Approval

• Examples of Class III devices which require a premarket
  approval include replacement heart valves, silicone gel-filled
  breast implants, and implanted cerebella stimulators.
• Class III devices which can be marketed with a premarket
  notification 510(k) are those:
  – postamendment (i.e., introduced to the U.S. market after May 28, 1976)
    Class III devices which are substantially equivalent to preamendment
    (i.e., introduced to the U.S. market before May 28, 1976) Class III
    devices and for which the regulation calling for the premarket approval
    application has not been published in 21 CFR.
• Examples of Class III devices which currently require a
  premarket notification include implantable pacemaker pulse
  generators and endosseous implants.
What is Premarket Notification [510(k)]

• Each person who wants to market Class I, II and some
  III devices intended for human use in the U.S. must
  submit a 510(k) to FDA at least 90 days before
  marketing unless the device is exempt from 510(k)
  requirements.
• A 510(k) is a premarketing submission made to FDA to
  demonstrate that the device to be marketed is as safe
  and effective, that is, substantially equivalent (SE), to a
  legally marketed device that is not subject to premarket
  approval (PMA). Applicants must compare their 510(k)
  device to one or more similar devices currently on the
  U.S. market and make and support their substantial
  equivalency claims.
What is Premarket Notification [510(k)]

• A legally marketed device is
   – a device that was legally marketed prior to May 28, 1976
     (preamendments device), or
   – a device which has been reclassified from Class III to Class II
     or I,
   – a device which has been found to be substantially equivalent
     to such a device through the 510(k) process.
• The legally marketed device(s) to which equivalence is
  drawn is known as the quot;predicatequot; device(s).
What is Premarket Notification [510(k)]

• Applicants must submit descriptive data and,
  when necessary, performance data to
  establish that their device is SE to a predicate
  device. Again, the data in a 510(k) is to show
  comparability, that is, substantial equivalency
  (SE) of a new device to a predicate device.
What is Substantial Equivalence

• Unlike PMA, which requires demonstration of
  reasonable safety and effectiveness, 510(k) requires
  demonstration of substantial equivalence. SE means
  that the new device is as safe and effective as the
  predicate device(s).
• A device is SE if, in comparison to a predicate device it:
   – has the same intended use as the predicate device; and
   – has the same technological characteristics as the predicate
     device; or
   – has different technological characteristics, that do not raise
     new questions of safety and effectiveness, and the sponsor
     demonstrates that the device is as safe and effective as the
     legally marketed device.
IDE Overview
• An investigational device exemption (IDE) allows the investigational device
  to be used in a clinical study in order to collect safety and effectiveness data
  required to support a Premarket Approval (PMA) application or a
  Premarket Notification [510(k)] submission to FDA.
• Clinical studies are most often conducted to support a PMA.
• Only a small percentage of 510(k)’s require clinical data to support the
  application.
• All clinical evaluations of investigational devices, unless exempt, must have
  an approved IDE before the study is initiated.
• Clinical evaluation of devices that have not been cleared for marketing
  requires:
  – an IDE approved by an institutional review board (IRB). If the study involves a
    significant risk device, the IDE must also be approved by FDA;
  – informed consent from all patients;
  – labeling for investigational use only
  – monitoring of the study and;
  – required records and reports.
Premarket Approval (PMA)

• PMA is the FDA process of scientific and regulatory review to evaluate the
  safety and effectiveness of Class III medical devices.
    – Class III devices are those that support or sustain human life, are of substantial
      importance in preventing impairment of human health, or which present a
      potential, unreasonable risk of illness or injury.
    – Due to the level of risk associated with Class III devices, FDA has determined
      that general and special controls alone are insufficient to assure the safety and
      effectiveness of class III devices.
    – Therefore, these devices require a premarket approval (PMA) application
      under section 515 of the FD&C Act in order to obtain marketing clearance.
• PMA is the most stringent type of device marketing application required by
  FDA. The applicant must receive FDA approval of its PMA application
  prior to marketing the device. PMA approval is based on a determination
  by FDA that the PMA contains sufficient valid scientific evidence to assure
  that the device is safe and effective for its intended use(s). An approved
  PMA is, in effect, a private license granting the applicant (or owner)
  permission to market the device. The PMA owner, however, can authorize
  use of its data by another.
PMA Data Requirements
• A PMA application is a scientific, regulatory documentation to FDA to
  demonstrate the safety and effectiveness of the class III device. Good science
  and scientific writing is a key to the approval of PMA application. If a PMA
  application lacks valid clinical information and scientific analysis on sound
  scientific reasoning, it will delay FDA’s review and approval. PMA
  applications that are incomplete, inaccurate, inconsistent, omit critical
  information, and poorly organized have resulted in delays in approval or
  denial of PMA applications. Manufacturers should perform a quality control
  audit of a PMA application before sending it to FDA to assure that it is
  scientifically sound and presented in a well organized format.
• Technical Sections: The technical sections containing data and information
  should allow FDA to determine whether to approve or disapprove the
  application. These sections are usually divided into non-clinical laboratory
  studies and clinical investigations.
• Non-clinical Laboratory Studies’ Section: Non-clinical laboratory studies’
  section includes information on microbiology, toxicology, immunology,
  biocompatibility, stress, wear, shelf life, and other laboratory or animal tests.
  Non-clinical studies for safety evaluation must be conducted in compliance
  with 21CFR Part 58 (Good Laboratory Practice for Nonclinical Laboratory
  Studies).
PMA Data Requirements

• Clinical Investigations’ Section: Clinical investigations’ section
  includes study protocols, safety and effectiveness data, adverse
  reactions and complications, device failures and replacements,
  patient information, patient complaints, tabulations of data
  from all individual subjects, results of statistical analyses, and
  any other information from the clinical investigations. Any
  investigation conducted under an Investigational Device
  Exemption (IDE) must be identified as such.
• Like other scientific reports, FDA has observed problems with
  study designs, study conduct, data analyses, presentations, and
  conclusions. Investigators should always consult all applicable
  FDA guidance documents
  (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfGGP/Sear
  ch.cfm).
FEDERAL REGULATORY ISSUES


Recommended Biocompatibility Testing
        and Clinical Trials
Required Biocompatibility Training and
Toxicology Profiles for Evaluation of Medical
                   Devices
              http://www.fda.gov/cdrh/g951.html
• FDA-modified matrix that designates the type of testing
  needed for various medical devices.
• It also includes a flow chart entitled quot;Biocompatibility
  Flow Chart for the Selection of Toxicity Tests for
  510(k)s.“
• The guidance will be effective for all submissions that will
  be received on or after July 1, 1995. The former guidance,
  #G87- 1 entitled quot;Tripartite Biocompatibility Guidance,quot;
  may continue to be applied until a final decision is reached
  on each submission received prior to July 1, 1995.
Required Biocompatibility Training and
Toxicology Profiles for Evaluation of Medical
                   Devices
• Biological evaluation of medical devices is performed to
  determine the potential toxicity resulting from contact of
  the component materials of the device with the body.
• The device materials should not, either directly or through
  the release of their material constituents:
   –   (i) produce adverse local or systemic effects;
   –   (ii) be carcinogenic; or
   –   (iii) produce adverse reproductive and developmental effects.
• Therefore, evaluation of any new device intended for
  human use requires data from systematic testing to ensure
  that the benefits provided by the final product will exceed
  any potential risks produced by device materials.
Required Biocompatibility Training and
  Toxicology Profiles for Evaluation of Medical
                     Devices
• When selecting the appropriate tests for biological evaluation of a medical
  device, one must consider the chemical characteristics of device materials and
  the nature, degree, frequency and duration of its exposure to the body.
• In general, the tests include:
  – acute, sub- chronic and chronic toxicity;
  – irritation to skin, eyes and mucosal surfaces;
  – sensitization;
  – hemocompatibility;
  – genotoxicity;
  – carcinogenicity; and
  – effects on reproduction including developmental effects.
• Additional tests for specific target organ toxicity, such as neurotoxicity and
  immunotoxicity may be necessary for some devices.
  – For example, a neurological device with direct contact with brain parenchyma and
    cerebrospinal fluid (CSF) may require an animal implant test to evaluate its effects
    on the brain parenchyma, susceptibility to seizure, and effects on the functional
    mechanism of choroid plexus and arachnoid villi to secrete and absorb (CSF).
• The specific clinical application and the materials used in the manufacture of
  the new device determines which tests are appropriate.
International Organization for Standards, ISO
http://www.iso.ch/iso/en/CatalogueListPage.CatalogueList?ICS1=11&ICS2=100
                                   &ICS3=

  ISO 10993-1:1997Biological evaluation of medical devices --
                                                           --
    Part 1: Evaluation and testing
  ISO 10993-2:1992Biological evaluation of medical devices --
                                                           --
    Part 2: Animal welfare requirements
  ISO 10993-3:1992Biological evaluation of medical devices --
                                                           --
    Part 3: Tests for genotoxicity, carcinogenicity and
    reproductive toxicity
  ISO 10993-4:2002Biological evaluation of medical devices --
                                                           --
    Part 4: Selection of tests for interactions with blood
  ISO 10993-5:1999Biological evaluation of medical devices --
                                                           --
    Part 5: Tests for in vitro cytotoxicity
  ISO 10993-6:1994Biological evaluation of medical devices --
                                                           --
    Part 6: Tests for local effects after implantation
International Organization for Standards, ISO
http://www.iso.ch/iso/en/CatalogueListPage.CatalogueList?ICS1=11&ICS2=100
                                   &ICS3=

 ISO 10993-7:1995Biological evaluation of medical devices ----
   Part 7: Ethylene oxide sterilization residuals
 ISO 10993-8:2000Biological evaluation of medical devices ----
   Part 8: Selection and qualification of reference materials for
   biological tests
 ISO 10993-9:1999Biological evaluation of medical devices ----
   Part 9: Framework for identification and quantification of
   potential degradation products
 ISO 10993-10:2002Biological evaluation of medical devices --  --
   Part 10: Tests for irritation and delayed-type hypersensitivity
 ISO 10993-11:1993Biological evaluation of medical devices --  --
   Part 11: Tests for systemic toxicity
 ISO 10993-12:2002Biological evaluation of medical devices --  --
   Part 12: Sample preparation and reference materials
International Organization for Standards, ISO
http://www.iso.ch/iso/en/CatalogueListPage.CatalogueList?ICS1=11&ICS2=100
                                   &ICS3=

  ISO 10993-13:1998Biological evaluation of medical devices ----
    Part 13: Identification and quantification of degradation
    products from polymeric medical devices
  ISO 10993-14:2001Biological evaluation of medical devices ----
    Part 14: Identification and quantification of degradation
    products from ceramics
  ISO 10993-15:2000Biological evaluation of medical devices ----
    Part 15: Identification and quantification of degradation
    products from metals and alloys
  ISO 10993-16:1997Biological evaluation of medical devices ----
    Part 16: Toxicokinetic study design for degradation products
    and leachables
  ISO 10993-17:2002Biological evaluation of medical devices ----
    Part 17: Establishment of allowable limits for leachable
    substances
American Society for Testing and Materials

          http://www.astm.org
        Search “Biocompatibility”
FDA
  TISSUE ENGINEERING PRODUCTS

   FDA's Tissue Reference Group Workshop
      August 29, 2001 - Slide Presentation
 Human Cells, Tissues, and Cellular and Tissue-
  Based Products (HCT/Ps) Regulated as Devices
Mark N. Melkerson
 CDRH / FDA
 Tissue Reference Group (TRG)
 “FDA’s TRG Process”

 http://www.fda.gov/cber/summaries/melkersontrg.htm
Premarket Review of Biological Products &
            Medical Devices


     •   Biological Products
     •   Medical Devices
     •   Combination Products
Definition of a Medical Device

• “...apparatus,…, implant, in vitro reagent,
  including any component…or accessory...
• intended for the diagnosis, mitigation, treatment,
  or prevention of disease...
• or intended to affect the structure or function of
  the body...
• and does not achieve its primary intended
  purposes through chemical action within or on
  the body…and which is not dependent upon
  being metabolized…”
Examples of Medical Devices &
          Combination Products

• Medical Devices - collagen, hyaluronic acid
  and synthetic implants
  – FocalSeal-L - aqueous PEG solutions modified
    to photo-polymerize in situ
  – Emdogain - porcine enamel matrix proteins
• Combination Products -
                       -
  – Apligraf - cells on bovine collagen
Marketing Applications

• Premarket Notification (Class II Devices)
  Section 510(k) of the FD&C Act (21 CFR 807)
• Premarket Approval Application (Class III
  Devices)
  Section 515 of the FD&C Act (21 CFR 814)
• Humanitarian Device Exemption (requires HUD
  Designation)
  Section 520(m) of the FD&C Act (21 CFR
  814.100)
Premarket Notification Review

• Case-by-case approach, except if can
  demonstrate “equivalent” to predicate device
• Basic elements:
  – Same Intended Use(s)
  – Preclinical equivalence of Product Manufacture, In
    vitro and/or in vivo testing
  – May need to demonstrate equivalence of Clinical
    Performance, if seeking specific indication(s) for use
    under general intended use(s) or differences in
    technological characteristics
Food and Drug Administration
        Modernization Act of 1997

• Gave CDRH authority to recognize
  national and international standards in
  product reviews
  – Allows for “Declaration of Conformity”
  – Somewhat mirrors device marketing
    authorities used in Europe
CDRH Standards Program

      www.fda.gov/cdrh/stdsprog.html
• Standards Participation
  – ASTM F04
   • Division IV - Tissue Engineered Medical Products
     (TEMPS)
  – ISO TC 150
   • Working Group 11 - Tissue Engineered Implants
     (Reviewing Other Standards Development
     Activities)
Premarket Approval Review
• Case-by-case approach
• Both safety and effectiveness evaluations
• Basic elements:
  – Product Manufacture
  – In vitro and in vivo testing
  – Clinical Performance
  – Product Labeling
• Product Manufacture
  – Cell, tissue & biomaterial sourcing
  – Product Processing
  – In-process and final product tests
  – Adventitious agents & co-purifying impurities
  – Lot - to - lot consistency
  – Quality control procedures
Premarket Approval Review
• In vitro and in vivo testing
  – Toxicity / Genotoxicity
  – Biomaterials biocompatibility
  – Immunogenicity /inflammatory responses
  – Models of product effectiveness
  – Product resorption/decomposition
• Investigating product safety and clinical
  benefit:
  – Patient population
  – Investigational and control treatments
  – Study endpoints
  – Study conduct
  – Data analysis
  – Labeling claims
Investigational Human Studies

• An exemption from marketing approval is
  required when unapproved products are
  studied in humans.
  – Investigational Device Exemption (IDE) 21
    CFR 812
• For significant risk medical devices:
  – FDA approval of IDE
  – IRB approval
Humanitarian Device Exemption
• Requires HUD (maximum of 4000 cases/per
  year) and requires no alternatives be
  marketed
• Case-by-case approach
• Both safety and probable benefit
  evaluations
 – Product Manufacture
 – In vitro and in vivo testing
 – Clinical Perfor
 – Product Labeling
Internet Access to FDA Documents

• Proposed Approach to Regulation of Cellular and
  Tissue-Based Products - 2/28/97 -
  http://www.fda.gov/cber/gdlns/CELLTISSUE.txt
• Tissue Action Plan -
  http://www.fda.gov/cber/tissue/tissue.htm
• Intercenter Agreement Between The Center for Biologics
  Evaluation and Research and The Center for Devices
  and Radiological Health -
  http://www.fda.gov/oc/ombudsman/bio-dev.htm
• Guidance on Applications for Products Comprised of
  Living Autologous Cells Manipulated Ex Vivo and
  Intended for Structural Repair or Reconstruction (5/96)
  - http://www.fda.gov/cber/gdlns/GDEXV.TXT
Internet Access to FDA Documents

• Guidance For the Submission of Chemistry,
  Manufacturing and Controls Information and
  Establishment Description for Autologous Somatic Cell
  Therapy Products - 1/10/97 -
  http://www.fda.gov/cber/gdlns/xvcmc.txt
• Required Biocompatibility Training and Toxicology
  Profiles for Evaluation of Medical Devices 5/1/95 (G95-1)
  - http://www.fda.gov/cdrh/g951.html
• Public Health Service Guideline on Infectious Disease
  Issues in Xenotransplantation
  http://www.fda.gov/cber/gdlns/xenophs0101.htm
• FDA PMA Database Search Engine
  http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPM
  A/pma.cfm
Tissue Related Documents
          http://www.fda.gov/cber/tissue/docs.htm
• Guidance for Industry: Availability of Licensed Donor
  Screening Tests Labeled for Use with Cadaveric Blood
  Specimens - 6/23/2000
• Suitability Determination for Donors of Human Cellular
  and Tissue-Based Products; Proposed Rule; reopening of
  comment period - 4/18/2000
• Establishment Registration and Listing for
  Manufacturers of Human Cellular and Tissue-Based
  Products - 5/14/98
• Guidance for Industry - Screening and Testing of Donors
  of Human Tissue Intended for Transplantation - 7/29/97
• Guidance for the Preparation of a Premarket Notification
  Application for Processed Human Dura Mater -
  http://www.fda.gov/cdrh/ode/054.html
Specific Product Information

• FocalSeal-L Sealant- Focal - SSE
  – http://www.fda.gov/cdrh/pdf/p990028b.pdf
• Apligraf - Organogenesis - SSE
  – http://www.fda.gov/cdrh/pdf/p950032.pdf
• CCS - Ortec, Inc. - SSPB (H990013)
  – http://www.fda.gov/cdrh/pdf/h990013b.pdf
Multi-Agency Tissue Engineering Science
         (MATES) Working Group

The Multi-Agency Tissue Engineering Science
 (MATES) Working Group is proposed as a
 means for the various federal agencies
 involved in Tissue Engineering to stay
 informed of each other’s activities and better
 coordinate their efforts.




                           http://www.tissueengineering.gov
Multi-Agency Tissue Engineering Science
              (MATES) Working Group
          Five Year Plan; Subcommittee on Biotechnology
The term “Tissue Engineering” was coined at an NSF-sponsored
  meeting in 1987(1). At a subsequent NSF sponsored workshop,
  Tissue Engineering was defined as “the application of principles
  and methods of engineering and life sciences toward fundamental
  understanding of structure-function relationships in normal and
  pathological function” (2). This multidisciplinary technology
  involves the development of biological substitutes for the repair or
  regeneration of tissue or organ function and has led to a broad
  range of products.
1. Heineken FG and Skalak R. Tissue Engineering: A Brief
  Overview, Journal of Biomechanical Engineering 113, 111 (1991).
2. Skalak R and Fox CF, eds. Tissue Engineering, Proceedings for a
  Workshop held at Granlibakken, Lake Tahoe, California,
  February 26-29, 1988, Alan Liss, New York.
                                        http://www.tissueengineering.gov
Multi-Agency Tissue Engineering Science
              (MATES) Working Group
To date, some of these products have been approved by the U.S.
  Food and Drug Administration while many are under either
  preclinical investigation or regulatory evaluation (3, 4). Since
  1990, the Tissue Engineering industry has grown to become more
  than a $3.5 billion worldwide R&D effort by over seventy
  biotechnology start-ups and business units (5, 6). Less than ten
  percent of this effort is funded by the U.S. government, but this
  contribution is rapidly increasing.
3. Hellman KB, Knight E, and Durfor CN. Tissue Engineering: Product
   Applications and Regulatory Issues, pp. 341-366, Frontiers in Tissue
   Engineering, Charles W. Patrick, Antonio G. Mikos, and Larry V. McIntire
   (eds.), Amsterdam, Elsevier Science (1998).
4. Hellman KB., Solomon RR, Gaffey C, Durfor C and Bishop JG, III.
   Tissue Engineering: Regulatory Considerations, Principles of Tissue
   Engineering, 2nd Edition, Robert Lanza, Robert Langer, and Joseph P.
   Vacanti (eds.), Academic Press, San Diego, California (in press).
5. Lysaght MJ, Nguy AS, and Sullivan K. An Economic Survey of the Emerging
   Tissue    Engineering Industry, Tissue Engineering: 4, 231 (1998).
6. Lysaght MJ, and Reyes J. The Growth of Tissue Engineering, Tissue Engr.
FDA APPROVAL PROCESS
          Classification of Product as I, II, or III
                                                     TE products
 I. General          II. Special              III. Premarket
    Controls             Controls                  Approval (PMA)
No approval of Equivalent to Marketed             Human Trial
 FDA prior to         Device?;                   Investigational
 selling the   Premarket Notification                Device
 product.                                          Exemption IDE
                        510 (k)
Good Manuf.
  Practice      Analysis of composition               PMA
               and properties, and in vitro
   GMP             and in vivo studies          Good Lab Pract.   GLP

More Related Content

What's hot

Regulatory approval process for invitro diagnostics in us
Regulatory approval process for invitro diagnostics in usRegulatory approval process for invitro diagnostics in us
Regulatory approval process for invitro diagnostics in usVinod Raj
 
FDA Regulation of Medical Devices
FDA Regulation of Medical DevicesFDA Regulation of Medical Devices
FDA Regulation of Medical DevicesDr Dev Kambhampati
 
Regulatory requirements for CE CERTIFICATION of Medical Devices in European U...
Regulatory requirements for CE CERTIFICATION of Medical Devices in European U...Regulatory requirements for CE CERTIFICATION of Medical Devices in European U...
Regulatory requirements for CE CERTIFICATION of Medical Devices in European U...Pallavi Christeen
 
CE marking and CE certification
CE marking and CE certificationCE marking and CE certification
CE marking and CE certificationmeddevicemarking
 
Regulatory Approval Process for Medical Devices in EU - Presentation by Aksha...
Regulatory Approval Process for Medical Devices in EU - Presentation by Aksha...Regulatory Approval Process for Medical Devices in EU - Presentation by Aksha...
Regulatory Approval Process for Medical Devices in EU - Presentation by Aksha...Akshay Anand
 
Clinical Research Regulation in European Union
Clinical Research Regulation in European Union Clinical Research Regulation in European Union
Clinical Research Regulation in European Union ShantanuThakre3
 
Regulations of medical devices in india
Regulations of medical devices in indiaRegulations of medical devices in india
Regulations of medical devices in indiasuspandanachowdary
 
International Medical Device Regulators Forum
International Medical Device Regulators ForumInternational Medical Device Regulators Forum
International Medical Device Regulators ForumSanthiNori1
 
Ce marking of medical devices
Ce marking of medical devicesCe marking of medical devices
Ce marking of medical devicesPallavi Christeen
 
Regulatory aspects of Biologics in India
Regulatory aspects of Biologics in India Regulatory aspects of Biologics in India
Regulatory aspects of Biologics in India RichaTrivedi16
 
overview of Japan pharmaceutical regulatory authority - PMDA
overview of Japan  pharmaceutical regulatory authority - PMDAoverview of Japan  pharmaceutical regulatory authority - PMDA
overview of Japan pharmaceutical regulatory authority - PMDANandhanan
 
Food Safety Modernization Act (FSMA) regulatory requirements by FDA
Food Safety Modernization Act (FSMA) regulatory requirements by FDAFood Safety Modernization Act (FSMA) regulatory requirements by FDA
Food Safety Modernization Act (FSMA) regulatory requirements by FDABrian Thomas
 
Plasma drug file and TSE/ BSE evaluation
Plasma drug file and TSE/ BSE evaluationPlasma drug file and TSE/ BSE evaluation
Plasma drug file and TSE/ BSE evaluationShoba Elangovan
 
Combination product
Combination productCombination product
Combination productRicha Patel
 
Regulatory Affairs by Chandra Mohan
Regulatory Affairs by Chandra MohanRegulatory Affairs by Chandra Mohan
Regulatory Affairs by Chandra MohanChandra Mohan
 
Premarket Notification 510(k) for Biologics [Autosaved].pptx
Premarket Notification 510(k) for Biologics [Autosaved].pptxPremarket Notification 510(k) for Biologics [Autosaved].pptx
Premarket Notification 510(k) for Biologics [Autosaved].pptxSusmithaTella2
 
ACTIVE SUBSTANCE MSTER FILE (ASMF) eMA
ACTIVE SUBSTANCE MSTER FILE (ASMF) eMA ACTIVE SUBSTANCE MSTER FILE (ASMF) eMA
ACTIVE SUBSTANCE MSTER FILE (ASMF) eMA sandeep bansal
 

What's hot (20)

Regulatory approval process for invitro diagnostics in us
Regulatory approval process for invitro diagnostics in usRegulatory approval process for invitro diagnostics in us
Regulatory approval process for invitro diagnostics in us
 
FDA Regulation of Medical Devices
FDA Regulation of Medical DevicesFDA Regulation of Medical Devices
FDA Regulation of Medical Devices
 
Regulatory requirements for CE CERTIFICATION of Medical Devices in European U...
Regulatory requirements for CE CERTIFICATION of Medical Devices in European U...Regulatory requirements for CE CERTIFICATION of Medical Devices in European U...
Regulatory requirements for CE CERTIFICATION of Medical Devices in European U...
 
CE marking and CE certification
CE marking and CE certificationCE marking and CE certification
CE marking and CE certification
 
Regulatory Approval Process for Medical Devices in EU - Presentation by Aksha...
Regulatory Approval Process for Medical Devices in EU - Presentation by Aksha...Regulatory Approval Process for Medical Devices in EU - Presentation by Aksha...
Regulatory Approval Process for Medical Devices in EU - Presentation by Aksha...
 
Clinical Research Regulation in European Union
Clinical Research Regulation in European Union Clinical Research Regulation in European Union
Clinical Research Regulation in European Union
 
GHTF
GHTFGHTF
GHTF
 
Regulations of medical devices in india
Regulations of medical devices in indiaRegulations of medical devices in india
Regulations of medical devices in india
 
Guidelines gdp
Guidelines gdpGuidelines gdp
Guidelines gdp
 
International Medical Device Regulators Forum
International Medical Device Regulators ForumInternational Medical Device Regulators Forum
International Medical Device Regulators Forum
 
Ce marking of medical devices
Ce marking of medical devicesCe marking of medical devices
Ce marking of medical devices
 
Regulatory aspects of Biologics in India
Regulatory aspects of Biologics in India Regulatory aspects of Biologics in India
Regulatory aspects of Biologics in India
 
overview of Japan pharmaceutical regulatory authority - PMDA
overview of Japan  pharmaceutical regulatory authority - PMDAoverview of Japan  pharmaceutical regulatory authority - PMDA
overview of Japan pharmaceutical regulatory authority - PMDA
 
Food Safety Modernization Act (FSMA) regulatory requirements by FDA
Food Safety Modernization Act (FSMA) regulatory requirements by FDAFood Safety Modernization Act (FSMA) regulatory requirements by FDA
Food Safety Modernization Act (FSMA) regulatory requirements by FDA
 
Plasma drug file and TSE/ BSE evaluation
Plasma drug file and TSE/ BSE evaluationPlasma drug file and TSE/ BSE evaluation
Plasma drug file and TSE/ BSE evaluation
 
Combination product
Combination productCombination product
Combination product
 
Regulatory Affairs by Chandra Mohan
Regulatory Affairs by Chandra MohanRegulatory Affairs by Chandra Mohan
Regulatory Affairs by Chandra Mohan
 
Premarket Notification 510(k) for Biologics [Autosaved].pptx
Premarket Notification 510(k) for Biologics [Autosaved].pptxPremarket Notification 510(k) for Biologics [Autosaved].pptx
Premarket Notification 510(k) for Biologics [Autosaved].pptx
 
ACTIVE SUBSTANCE MSTER FILE (ASMF) eMA
ACTIVE SUBSTANCE MSTER FILE (ASMF) eMA ACTIVE SUBSTANCE MSTER FILE (ASMF) eMA
ACTIVE SUBSTANCE MSTER FILE (ASMF) eMA
 
Medical Device Regulations - 510(k) Process
Medical Device Regulations - 510(k) ProcessMedical Device Regulations - 510(k) Process
Medical Device Regulations - 510(k) Process
 

Viewers also liked

Emc–Safety Weee–Ro Hs Compliance Overview
Emc–Safety Weee–Ro Hs Compliance OverviewEmc–Safety Weee–Ro Hs Compliance Overview
Emc–Safety Weee–Ro Hs Compliance OverviewJacobe2008
 
Impacts of the Affordable Care Act
Impacts of the Affordable Care ActImpacts of the Affordable Care Act
Impacts of the Affordable Care ActFlorida Blue
 
Healthcare Reform 2011: The Good, the bad and the ugly (Part 2)
Healthcare Reform 2011: The Good, the bad and the ugly (Part 2)Healthcare Reform 2011: The Good, the bad and the ugly (Part 2)
Healthcare Reform 2011: The Good, the bad and the ugly (Part 2)David Goldstein
 
The Affordable Care Act And Its Effect On American Healthcare (3)
The Affordable Care Act And Its Effect On American Healthcare (3)The Affordable Care Act And Its Effect On American Healthcare (3)
The Affordable Care Act And Its Effect On American Healthcare (3)amande1
 
psychiatry and mental health issues in the emergency room - EMTALA and State ...
psychiatry and mental health issues in the emergency room - EMTALA and State ...psychiatry and mental health issues in the emergency room - EMTALA and State ...
psychiatry and mental health issues in the emergency room - EMTALA and State ...Conrad Meyer JD MHA FACHE
 
US Healthcare Reform and Impact On Pharma and Healthcare IT Companies
US Healthcare Reform and Impact On Pharma and Healthcare IT CompaniesUS Healthcare Reform and Impact On Pharma and Healthcare IT Companies
US Healthcare Reform and Impact On Pharma and Healthcare IT CompaniesDr. Susan Dorfman
 
Fellow Ais 4 Laws Regs & Ethics (Revised)
Fellow Ais 4 Laws Regs & Ethics (Revised)Fellow Ais 4 Laws Regs & Ethics (Revised)
Fellow Ais 4 Laws Regs & Ethics (Revised)William Copeland
 
EU General Data Protection Regulation top 8 operational impacts in personal c...
EU General Data Protection Regulation top 8 operational impacts in personal c...EU General Data Protection Regulation top 8 operational impacts in personal c...
EU General Data Protection Regulation top 8 operational impacts in personal c...Erik Vollebregt
 
Understanding FDA Requirements Medical Devices
Understanding FDA Requirements Medical DevicesUnderstanding FDA Requirements Medical Devices
Understanding FDA Requirements Medical Devicesmarchell
 
Overview of FDA Regulation of Medical Devices
Overview of FDA Regulation of Medical DevicesOverview of FDA Regulation of Medical Devices
Overview of FDA Regulation of Medical DevicesMichael Swit
 

Viewers also liked (12)

Emc–Safety Weee–Ro Hs Compliance Overview
Emc–Safety Weee–Ro Hs Compliance OverviewEmc–Safety Weee–Ro Hs Compliance Overview
Emc–Safety Weee–Ro Hs Compliance Overview
 
Tissue Engineering slides
Tissue Engineering slidesTissue Engineering slides
Tissue Engineering slides
 
Impacts of the Affordable Care Act
Impacts of the Affordable Care ActImpacts of the Affordable Care Act
Impacts of the Affordable Care Act
 
Healthcare Reform 2011: The Good, the bad and the ugly (Part 2)
Healthcare Reform 2011: The Good, the bad and the ugly (Part 2)Healthcare Reform 2011: The Good, the bad and the ugly (Part 2)
Healthcare Reform 2011: The Good, the bad and the ugly (Part 2)
 
The Affordable Care Act And Its Effect On American Healthcare (3)
The Affordable Care Act And Its Effect On American Healthcare (3)The Affordable Care Act And Its Effect On American Healthcare (3)
The Affordable Care Act And Its Effect On American Healthcare (3)
 
psychiatry and mental health issues in the emergency room - EMTALA and State ...
psychiatry and mental health issues in the emergency room - EMTALA and State ...psychiatry and mental health issues in the emergency room - EMTALA and State ...
psychiatry and mental health issues in the emergency room - EMTALA and State ...
 
US Healthcare Reform and Impact On Pharma and Healthcare IT Companies
US Healthcare Reform and Impact On Pharma and Healthcare IT CompaniesUS Healthcare Reform and Impact On Pharma and Healthcare IT Companies
US Healthcare Reform and Impact On Pharma and Healthcare IT Companies
 
Fellow Ais 4 Laws Regs & Ethics (Revised)
Fellow Ais 4 Laws Regs & Ethics (Revised)Fellow Ais 4 Laws Regs & Ethics (Revised)
Fellow Ais 4 Laws Regs & Ethics (Revised)
 
EU General Data Protection Regulation top 8 operational impacts in personal c...
EU General Data Protection Regulation top 8 operational impacts in personal c...EU General Data Protection Regulation top 8 operational impacts in personal c...
EU General Data Protection Regulation top 8 operational impacts in personal c...
 
Understanding FDA Requirements Medical Devices
Understanding FDA Requirements Medical DevicesUnderstanding FDA Requirements Medical Devices
Understanding FDA Requirements Medical Devices
 
Triage
TriageTriage
Triage
 
Overview of FDA Regulation of Medical Devices
Overview of FDA Regulation of Medical DevicesOverview of FDA Regulation of Medical Devices
Overview of FDA Regulation of Medical Devices
 

Similar to Federal Regulatory Issues Us Food And Drug Administration Medical Device Amendments

regulation for combination product and medical devices
regulation for combination product and medical devicesregulation for combination product and medical devices
regulation for combination product and medical devicesSNEHADAS123
 
medical device regulatory approval in USA
medical device regulatory approval in USAmedical device regulatory approval in USA
medical device regulatory approval in USASuraj Pamadi
 
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICESREGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICESArunpandiyan59
 
USFDA GUIDLINES
USFDA GUIDLINESUSFDA GUIDLINES
USFDA GUIDLINESRaj Tiwari
 
ANDA FDA APPLICATION
ANDA FDA APPLICATIONANDA FDA APPLICATION
ANDA FDA APPLICATIONRoshan Bodhe
 
5. Unit-V- Regulatory Concepts.
5. Unit-V- Regulatory Concepts.5. Unit-V- Regulatory Concepts.
5. Unit-V- Regulatory Concepts.Audumbar Mali
 
Drug Delivery -- Perspectives on the FDA Regulatory Environment
Drug Delivery -- Perspectives on the FDA Regulatory EnvironmentDrug Delivery -- Perspectives on the FDA Regulatory Environment
Drug Delivery -- Perspectives on the FDA Regulatory EnvironmentMichael Swit
 
Understanding FDA Regulations
Understanding  FDA RegulationsUnderstanding  FDA Regulations
Understanding FDA RegulationsBeth Friedland
 
FDA Regulations and Medical Device Pathways to Market
FDA Regulations and Medical Device Pathways to MarketFDA Regulations and Medical Device Pathways to Market
FDA Regulations and Medical Device Pathways to MarketMethodSense, Inc.
 
FDA Regulations and Medical Device Pathways to Market
FDA Regulations and Medical Device Pathways to MarketFDA Regulations and Medical Device Pathways to Market
FDA Regulations and Medical Device Pathways to MarketMethodSense, Inc.
 
Fda gmp compliance for the Life Science Industry
Fda gmp compliance for the Life Science IndustryFda gmp compliance for the Life Science Industry
Fda gmp compliance for the Life Science Industrydmanalan
 
Regulation for combination product
Regulation for combination productRegulation for combination product
Regulation for combination productAkashYadav283
 
FDA classify Medical Devices and how to report device problems A Systematic R...
FDA classify Medical Devices and how to report device problems A Systematic R...FDA classify Medical Devices and how to report device problems A Systematic R...
FDA classify Medical Devices and how to report device problems A Systematic R...Pubrica
 
FDA classify Medical Devices and how to report device problems A Systematic R...
FDA classify Medical Devices and how to report device problems A Systematic R...FDA classify Medical Devices and how to report device problems A Systematic R...
FDA classify Medical Devices and how to report device problems A Systematic R...Pubrica
 
Kobridge medical devices registration in South Korea
Kobridge medical devices registration in South KoreaKobridge medical devices registration in South Korea
Kobridge medical devices registration in South KoreaKobridge Consulting Ltd.
 

Similar to Federal Regulatory Issues Us Food And Drug Administration Medical Device Amendments (20)

regulation for combination product and medical devices
regulation for combination product and medical devicesregulation for combination product and medical devices
regulation for combination product and medical devices
 
medical device regulatory approval in USA
medical device regulatory approval in USAmedical device regulatory approval in USA
medical device regulatory approval in USA
 
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICESREGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
 
USFDA GUIDLINES
USFDA GUIDLINESUSFDA GUIDLINES
USFDA GUIDLINES
 
Medical devices
Medical devicesMedical devices
Medical devices
 
CLINICAL TRIALS OF MEDICAL DEVICES
CLINICAL TRIALS OF MEDICAL DEVICESCLINICAL TRIALS OF MEDICAL DEVICES
CLINICAL TRIALS OF MEDICAL DEVICES
 
ANDA FDA APPLICATION
ANDA FDA APPLICATIONANDA FDA APPLICATION
ANDA FDA APPLICATION
 
5. Unit-V- Regulatory Concepts.
5. Unit-V- Regulatory Concepts.5. Unit-V- Regulatory Concepts.
5. Unit-V- Regulatory Concepts.
 
Drug Delivery -- Perspectives on the FDA Regulatory Environment
Drug Delivery -- Perspectives on the FDA Regulatory EnvironmentDrug Delivery -- Perspectives on the FDA Regulatory Environment
Drug Delivery -- Perspectives on the FDA Regulatory Environment
 
Understanding FDA Regulations
Understanding  FDA RegulationsUnderstanding  FDA Regulations
Understanding FDA Regulations
 
FDA Regulations and Medical Device Pathways to Market
FDA Regulations and Medical Device Pathways to MarketFDA Regulations and Medical Device Pathways to Market
FDA Regulations and Medical Device Pathways to Market
 
FDA Regulations and Medical Device Pathways to Market
FDA Regulations and Medical Device Pathways to MarketFDA Regulations and Medical Device Pathways to Market
FDA Regulations and Medical Device Pathways to Market
 
Fda gmp compliance for the Life Science Industry
Fda gmp compliance for the Life Science IndustryFda gmp compliance for the Life Science Industry
Fda gmp compliance for the Life Science Industry
 
Regulation for combination product
Regulation for combination productRegulation for combination product
Regulation for combination product
 
USFDA
USFDAUSFDA
USFDA
 
USFDA Over View
USFDA  Over ViewUSFDA  Over View
USFDA Over View
 
FDA classify Medical Devices and how to report device problems A Systematic R...
FDA classify Medical Devices and how to report device problems A Systematic R...FDA classify Medical Devices and how to report device problems A Systematic R...
FDA classify Medical Devices and how to report device problems A Systematic R...
 
FDA classify Medical Devices and how to report device problems A Systematic R...
FDA classify Medical Devices and how to report device problems A Systematic R...FDA classify Medical Devices and how to report device problems A Systematic R...
FDA classify Medical Devices and how to report device problems A Systematic R...
 
Medical devices
Medical devicesMedical devices
Medical devices
 
Kobridge medical devices registration in South Korea
Kobridge medical devices registration in South KoreaKobridge medical devices registration in South Korea
Kobridge medical devices registration in South Korea
 

More from Jacobe2008

數位學院:快樂經濟學
數位學院:快樂經濟學數位學院:快樂經濟學
數位學院:快樂經濟學Jacobe2008
 
答案,在你心中
答案,在你心中答案,在你心中
答案,在你心中Jacobe2008
 
這一生都是你的機會
這一生都是你的機會這一生都是你的機會
這一生都是你的機會Jacobe2008
 
這一生,你為何而來?
這一生,你為何而來?這一生,你為何而來?
這一生,你為何而來?Jacobe2008
 
很棒的文章【偶爾】
很棒的文章【偶爾】很棒的文章【偶爾】
很棒的文章【偶爾】Jacobe2008
 
多點思考更能放鬆
多點思考更能放鬆多點思考更能放鬆
多點思考更能放鬆Jacobe2008
 
先別急著吃棉花糖
先別急著吃棉花糖先別急著吃棉花糖
先別急著吃棉花糖Jacobe2008
 
正面思考的威力
正面思考的威力正面思考的威力
正面思考的威力Jacobe2008
 
China Compulsory Certification Requirement And Procedures Of Medical Device
China Compulsory Certification Requirement And Procedures Of Medical DeviceChina Compulsory Certification Requirement And Procedures Of Medical Device
China Compulsory Certification Requirement And Procedures Of Medical DeviceJacobe2008
 
Risk Management
Risk ManagementRisk Management
Risk ManagementJacobe2008
 
Medical Device Administration In China
Medical Device Administration In ChinaMedical Device Administration In China
Medical Device Administration In ChinaJacobe2008
 
China Compulsory Certification Requirement And Procedures Of Medical Device
China Compulsory Certification Requirement And Procedures Of Medical DeviceChina Compulsory Certification Requirement And Procedures Of Medical Device
China Compulsory Certification Requirement And Procedures Of Medical DeviceJacobe2008
 
Medical Device Regulations Global Overview And Guiding Principles
Medical Device Regulations   Global Overview And Guiding PrinciplesMedical Device Regulations   Global Overview And Guiding Principles
Medical Device Regulations Global Overview And Guiding PrinciplesJacobe2008
 
Japan Medical Devices Market
Japan Medical Devices MarketJapan Medical Devices Market
Japan Medical Devices MarketJacobe2008
 
Statistical Issues In Medical Device Trials
Statistical Issues In Medical Device TrialsStatistical Issues In Medical Device Trials
Statistical Issues In Medical Device TrialsJacobe2008
 
Postmarket Surveillance Medical Devices
Postmarket Surveillance   Medical DevicesPostmarket Surveillance   Medical Devices
Postmarket Surveillance Medical DevicesJacobe2008
 
The Regulation Of Medical Device In China
The Regulation Of Medical Device In ChinaThe Regulation Of Medical Device In China
The Regulation Of Medical Device In ChinaJacobe2008
 

More from Jacobe2008 (18)

數位學院:快樂經濟學
數位學院:快樂經濟學數位學院:快樂經濟學
數位學院:快樂經濟學
 
答案,在你心中
答案,在你心中答案,在你心中
答案,在你心中
 
這一生都是你的機會
這一生都是你的機會這一生都是你的機會
這一生都是你的機會
 
這一生,你為何而來?
這一生,你為何而來?這一生,你為何而來?
這一生,你為何而來?
 
深思考
深思考深思考
深思考
 
很棒的文章【偶爾】
很棒的文章【偶爾】很棒的文章【偶爾】
很棒的文章【偶爾】
 
多點思考更能放鬆
多點思考更能放鬆多點思考更能放鬆
多點思考更能放鬆
 
先別急著吃棉花糖
先別急著吃棉花糖先別急著吃棉花糖
先別急著吃棉花糖
 
正面思考的威力
正面思考的威力正面思考的威力
正面思考的威力
 
China Compulsory Certification Requirement And Procedures Of Medical Device
China Compulsory Certification Requirement And Procedures Of Medical DeviceChina Compulsory Certification Requirement And Procedures Of Medical Device
China Compulsory Certification Requirement And Procedures Of Medical Device
 
Risk Management
Risk ManagementRisk Management
Risk Management
 
Medical Device Administration In China
Medical Device Administration In ChinaMedical Device Administration In China
Medical Device Administration In China
 
China Compulsory Certification Requirement And Procedures Of Medical Device
China Compulsory Certification Requirement And Procedures Of Medical DeviceChina Compulsory Certification Requirement And Procedures Of Medical Device
China Compulsory Certification Requirement And Procedures Of Medical Device
 
Medical Device Regulations Global Overview And Guiding Principles
Medical Device Regulations   Global Overview And Guiding PrinciplesMedical Device Regulations   Global Overview And Guiding Principles
Medical Device Regulations Global Overview And Guiding Principles
 
Japan Medical Devices Market
Japan Medical Devices MarketJapan Medical Devices Market
Japan Medical Devices Market
 
Statistical Issues In Medical Device Trials
Statistical Issues In Medical Device TrialsStatistical Issues In Medical Device Trials
Statistical Issues In Medical Device Trials
 
Postmarket Surveillance Medical Devices
Postmarket Surveillance   Medical DevicesPostmarket Surveillance   Medical Devices
Postmarket Surveillance Medical Devices
 
The Regulation Of Medical Device In China
The Regulation Of Medical Device In ChinaThe Regulation Of Medical Device In China
The Regulation Of Medical Device In China
 

Recently uploaded

Challenging Factors of Rural Women Entrepreneurs in West Bengal
Challenging Factors of Rural Women Entrepreneurs in West  BengalChallenging Factors of Rural Women Entrepreneurs in West  Bengal
Challenging Factors of Rural Women Entrepreneurs in West BengalNabarun Chakraborty
 
First, Second, and Third Generation Islamic Economicss
First, Second, and Third Generation Islamic EconomicssFirst, Second, and Third Generation Islamic Economicss
First, Second, and Third Generation Islamic EconomicssAsad Zaman
 
Mytilineos (OW, TP_ €46.0_sh)_ Strong organic progress 14-03-2024.pdf
Mytilineos (OW, TP_ €46.0_sh)_ Strong organic progress 14-03-2024.pdfMytilineos (OW, TP_ €46.0_sh)_ Strong organic progress 14-03-2024.pdf
Mytilineos (OW, TP_ €46.0_sh)_ Strong organic progress 14-03-2024.pdfNewsroom8
 
Swift_Maintaining Critical Standards(...).pptx.pdf
Swift_Maintaining Critical Standards(...).pptx.pdfSwift_Maintaining Critical Standards(...).pptx.pdf
Swift_Maintaining Critical Standards(...).pptx.pdfNeo4j
 
AUDITING FRAUDS OF AN ENGLISH COMPANY.PPTX
AUDITING FRAUDS OF AN ENGLISH COMPANY.PPTXAUDITING FRAUDS OF AN ENGLISH COMPANY.PPTX
AUDITING FRAUDS OF AN ENGLISH COMPANY.PPTXkamikazekujoh
 
Stock Market Brief Deck FOR 3142024..pdf
Stock Market Brief Deck FOR 3142024..pdfStock Market Brief Deck FOR 3142024..pdf
Stock Market Brief Deck FOR 3142024..pdfMichael Silva
 
Economic Risk Factor Update: March 2024 [SlideShare]
Economic Risk Factor Update: March 2024 [SlideShare]Economic Risk Factor Update: March 2024 [SlideShare]
Economic Risk Factor Update: March 2024 [SlideShare]Commonwealth
 
2024.03 Strategic Resources_Pub presentation
2024.03 Strategic Resources_Pub presentation2024.03 Strategic Resources_Pub presentation
2024.03 Strategic Resources_Pub presentationAdnet Communications
 
ANALYSIS OF BANK MANDIRI S HEALTH LEVEL BASED ON RISK PROFILE, GOOD CORPORATE...
ANALYSIS OF BANK MANDIRI S HEALTH LEVEL BASED ON RISK PROFILE, GOOD CORPORATE...ANALYSIS OF BANK MANDIRI S HEALTH LEVEL BASED ON RISK PROFILE, GOOD CORPORATE...
ANALYSIS OF BANK MANDIRI S HEALTH LEVEL BASED ON RISK PROFILE, GOOD CORPORATE...indexPub
 
Buy-Side Leaps Into Gen AI Era by Jasper Colin
Buy-Side Leaps Into Gen AI Era by Jasper ColinBuy-Side Leaps Into Gen AI Era by Jasper Colin
Buy-Side Leaps Into Gen AI Era by Jasper ColinJasper Colin
 
2024.03 Strategic Resources_Pub (1). pdf
2024.03 Strategic Resources_Pub (1). pdf2024.03 Strategic Resources_Pub (1). pdf
2024.03 Strategic Resources_Pub (1). pdfAdnet Communications
 
Pros and Cons of Interest-Only DSCR Loans
Pros and Cons of Interest-Only DSCR LoansPros and Cons of Interest-Only DSCR Loans
Pros and Cons of Interest-Only DSCR LoansPark Place Finance LLC
 
Islamic banking in Afghanistan from start until now
Islamic banking in Afghanistan from start until nowIslamic banking in Afghanistan from start until now
Islamic banking in Afghanistan from start until nowhamidzafar6
 
powerpoint presentation about asian regioonalism
powerpoint presentation about asian regioonalismpowerpoint presentation about asian regioonalism
powerpoint presentation about asian regioonalismrezeraaisla
 
Stock Market Brief Deck FOR 31124 yt.pdf
Stock Market Brief Deck FOR 31124 yt.pdfStock Market Brief Deck FOR 31124 yt.pdf
Stock Market Brief Deck FOR 31124 yt.pdfMichael Silva
 
Planning of societal re/production in a commonist society
Planning of societal re/production in a commonist societyPlanning of societal re/production in a commonist society
Planning of societal re/production in a commonist societyStefanMz
 
BIHC Briefing Greece March 2024, with Crédit Agricole CIB
BIHC Briefing Greece March 2024, with Crédit Agricole CIBBIHC Briefing Greece March 2024, with Crédit Agricole CIB
BIHC Briefing Greece March 2024, with Crédit Agricole CIBNeil Day
 
renaltumors upasana sahu Group 50.pptxism
renaltumors upasana sahu Group 50.pptxismrenaltumors upasana sahu Group 50.pptxism
renaltumors upasana sahu Group 50.pptxismthxz2fdqxw
 
The Role of Non-Banking Financial Companies (NBFCs).pdf
The Role of Non-Banking Financial Companies (NBFCs).pdfThe Role of Non-Banking Financial Companies (NBFCs).pdf
The Role of Non-Banking Financial Companies (NBFCs).pdfChampak Jhagmag
 

Recently uploaded (20)

Closing Remarks International Women's Day 2024
Closing Remarks International Women's Day 2024Closing Remarks International Women's Day 2024
Closing Remarks International Women's Day 2024
 
Challenging Factors of Rural Women Entrepreneurs in West Bengal
Challenging Factors of Rural Women Entrepreneurs in West  BengalChallenging Factors of Rural Women Entrepreneurs in West  Bengal
Challenging Factors of Rural Women Entrepreneurs in West Bengal
 
First, Second, and Third Generation Islamic Economicss
First, Second, and Third Generation Islamic EconomicssFirst, Second, and Third Generation Islamic Economicss
First, Second, and Third Generation Islamic Economicss
 
Mytilineos (OW, TP_ €46.0_sh)_ Strong organic progress 14-03-2024.pdf
Mytilineos (OW, TP_ €46.0_sh)_ Strong organic progress 14-03-2024.pdfMytilineos (OW, TP_ €46.0_sh)_ Strong organic progress 14-03-2024.pdf
Mytilineos (OW, TP_ €46.0_sh)_ Strong organic progress 14-03-2024.pdf
 
Swift_Maintaining Critical Standards(...).pptx.pdf
Swift_Maintaining Critical Standards(...).pptx.pdfSwift_Maintaining Critical Standards(...).pptx.pdf
Swift_Maintaining Critical Standards(...).pptx.pdf
 
AUDITING FRAUDS OF AN ENGLISH COMPANY.PPTX
AUDITING FRAUDS OF AN ENGLISH COMPANY.PPTXAUDITING FRAUDS OF AN ENGLISH COMPANY.PPTX
AUDITING FRAUDS OF AN ENGLISH COMPANY.PPTX
 
Stock Market Brief Deck FOR 3142024..pdf
Stock Market Brief Deck FOR 3142024..pdfStock Market Brief Deck FOR 3142024..pdf
Stock Market Brief Deck FOR 3142024..pdf
 
Economic Risk Factor Update: March 2024 [SlideShare]
Economic Risk Factor Update: March 2024 [SlideShare]Economic Risk Factor Update: March 2024 [SlideShare]
Economic Risk Factor Update: March 2024 [SlideShare]
 
2024.03 Strategic Resources_Pub presentation
2024.03 Strategic Resources_Pub presentation2024.03 Strategic Resources_Pub presentation
2024.03 Strategic Resources_Pub presentation
 
ANALYSIS OF BANK MANDIRI S HEALTH LEVEL BASED ON RISK PROFILE, GOOD CORPORATE...
ANALYSIS OF BANK MANDIRI S HEALTH LEVEL BASED ON RISK PROFILE, GOOD CORPORATE...ANALYSIS OF BANK MANDIRI S HEALTH LEVEL BASED ON RISK PROFILE, GOOD CORPORATE...
ANALYSIS OF BANK MANDIRI S HEALTH LEVEL BASED ON RISK PROFILE, GOOD CORPORATE...
 
Buy-Side Leaps Into Gen AI Era by Jasper Colin
Buy-Side Leaps Into Gen AI Era by Jasper ColinBuy-Side Leaps Into Gen AI Era by Jasper Colin
Buy-Side Leaps Into Gen AI Era by Jasper Colin
 
2024.03 Strategic Resources_Pub (1). pdf
2024.03 Strategic Resources_Pub (1). pdf2024.03 Strategic Resources_Pub (1). pdf
2024.03 Strategic Resources_Pub (1). pdf
 
Pros and Cons of Interest-Only DSCR Loans
Pros and Cons of Interest-Only DSCR LoansPros and Cons of Interest-Only DSCR Loans
Pros and Cons of Interest-Only DSCR Loans
 
Islamic banking in Afghanistan from start until now
Islamic banking in Afghanistan from start until nowIslamic banking in Afghanistan from start until now
Islamic banking in Afghanistan from start until now
 
powerpoint presentation about asian regioonalism
powerpoint presentation about asian regioonalismpowerpoint presentation about asian regioonalism
powerpoint presentation about asian regioonalism
 
Stock Market Brief Deck FOR 31124 yt.pdf
Stock Market Brief Deck FOR 31124 yt.pdfStock Market Brief Deck FOR 31124 yt.pdf
Stock Market Brief Deck FOR 31124 yt.pdf
 
Planning of societal re/production in a commonist society
Planning of societal re/production in a commonist societyPlanning of societal re/production in a commonist society
Planning of societal re/production in a commonist society
 
BIHC Briefing Greece March 2024, with Crédit Agricole CIB
BIHC Briefing Greece March 2024, with Crédit Agricole CIBBIHC Briefing Greece March 2024, with Crédit Agricole CIB
BIHC Briefing Greece March 2024, with Crédit Agricole CIB
 
renaltumors upasana sahu Group 50.pptxism
renaltumors upasana sahu Group 50.pptxismrenaltumors upasana sahu Group 50.pptxism
renaltumors upasana sahu Group 50.pptxism
 
The Role of Non-Banking Financial Companies (NBFCs).pdf
The Role of Non-Banking Financial Companies (NBFCs).pdfThe Role of Non-Banking Financial Companies (NBFCs).pdf
The Role of Non-Banking Financial Companies (NBFCs).pdf
 

Federal Regulatory Issues Us Food And Drug Administration Medical Device Amendments

  • 1. Harvard-MIT Division of Health Sciences and Technology HST.535: Principles and Practice of Tissue Engineering Instructors: Myron Spector Massachusetts Institute of Technology Harvard Medical School Brigham and Women’s Hospital VA Boston Healthcare System HST535 FEDERAL REGULATORY ISSUES: US Food and Drug Administration Medical Device Amendments M. Spector, Ph.D.
  • 2. FEDERAL AGENCIES THAT REGULATE MEDICAL DEVICES AND TISSUE ENGINEERED PRODUCTS US Food and Drug Administration China Chinese FDA Europe Various agencies; “CE mark” India None yet
  • 3. US FDA ORGANIZATION Center for Biologics Evaluation and Research (CBER) Center for Devices and Radiological Health (CDRH) Center for Drug Evaluation and Research (CDER) Center for Food Safety and Applied Nutrition (CFSAN) Center for Veterinary Medicine (CVM) National Center for Toxicological Research (NCTR) Office of the Commissioner (OC) Office of Regulatory Affairs (ORA) Which center to review your application?
  • 4. FDA Center for Devices and Radiological Health http://www.fda.gov/cdr h/index.html
  • 5. FDA APPROVAL PROCESS Classification of Product as I, II, or III TE products I. General II. Special III. Premarket Controls Controls Approval (PMA) Good Manuf. Practice GMP
  • 6. FDA APPROVAL PROCESS Classification of Product as I, II, or III TE products I. General II. Special III. Premarket Controls Controls Approval (PMA) No approval of FDA prior to selling the product. Good Manuf. Practice GMP
  • 7. FDA APPROVAL PROCESS Classification of Product as I, II, or III TE products I. General II. Special III. Premarket Controls Controls Approval (PMA) No approval of Equivalent to Marketed FDA prior to Device?; selling the Premarket Notification product. 510 (k) Good Manuf. Practice GMP
  • 8. FDA APPROVAL PROCESS Classification of Product as I, II, or III TE products I. General II. Special III. Premarket Controls Controls Approval (PMA) No approval of Equivalent to Marketed FDA prior to Device?; selling the Premarket Notification product. 510 (k) Good Manuf. Practice Analysis of composition and properties, and in vitro GMP and in vivo studies Good Lab Pract. GLP
  • 9. FDA APPROVAL PROCESS Classification of Product as I, II, or III TE products I. General II. Special III. Premarket Controls Controls Approval (PMA) No approval of Equivalent to Marketed Human Trial FDA prior to Device?; Investigational selling the Premarket Notification Device product. Exemption IDE 510 (k) Good Manuf. Practice Analysis of composition PMA and properties, and in vitro GMP and in vivo studies Good Lab Pract. GLP
  • 10. FDA History http://www.fda.gov/oc/opacom/fda101/sld017.html • In 1906, President Theodore Roosevelt signed into law the Food and Drugs Act. The 1906 law's relevant background in America starts with colonial food statutes concerned with bread and meat. The first national law came in 1848 during the Mexican War. It banned the importation of adulterated drugs, a chronic public health problem. • In 1937, a public health disaster demonstrated the need for a stronger federal law. Sulfanilamide, the first quot;wonder drugquot; and a popular and effective treatment for diseases like strep throat and gonorrhea, was formulated into an Elixir of Sulfanilamide and marketed for use in children. But the liquid formulation contained a poison, the same chemical used in antifreeze, and it killed 107 people, most of them children. The earlier law did not require the drug's manufacturer to test the formulation for safety before it was sold. • Congress corrected this weakness in the law the next year when it passed the Federal Food, Drug, and Cosmetic Act. This law, for the first time, required companies to prove the safety of new drugs before putting them on the market. The new act also added the regulation of cosmetics and therapeutic devices, and generally updated the law to improve consumer protection. • Congress has continued to give FDA new responsibilities over the years, including the requirement that drugs and medical devices be proven effective as well as safe before they can be sold (Medical Devices Amendment of 1976).
  • 11. CDRH Advisory Committees • The Center for Devices and Radiological Health has established advisory committees to provide independent, professional expertise and technical assistance on the development, safety and effectiveness, and regulation of medical devices and electronic products that produce radiation. Each committee consists of experts with recognized expertise and judgment in a specific field. The committees are advisory -- they provide their expertise and recommendations -- but final decisions are made by FDA. • The Center has four advisory committees, including a Medical Devices Advisory Committee which consists of 18 panels that cover the medical specialty areas. These advisory committee meetings are open to the public, and time is provided for public comment on the topic under consideration.
  • 12. CDRH Overview of Regulations • The CDRH is responsible for regulating firms who manufacture, repackage, relabel, and/or import medical devices sold in the United States. • Medical devices are classified into Class I, II, and III. A description of device classification and a link to the Product Classification Database can be found at: ttp://www.fda.gov/cdrh/devadvice/313.html. Regulatory control increases from Class I to Class III. The device classification regulation defines the regulatory requirements for a general device type. – Most Class I devices are exempt from Premarket Notification 510(k) – Most Class II devices require Premarket Notification 510(k); – Most Class III devices require Premarket Approval.
  • 13. CDRH Overview of Regulations • The basic regulatory requirements that manufacturers of medical devices distributed in the U.S. must comply with are: – Premarket Notification 510(k), unless exempt, or Premarket Approval (PMA), – Establishment registration on form FDA-2891, – Medical Device Listing on form FDA-2892, – Quality System (QS) regulation, – Labeling requirements, and – Medical Device Reporting (MDR)
  • 14. Is My Product Regulated by FDA's Center for Devices and Radiological Health? • The FDA regulates medical devices to assure their safety and effectiveness. The CDRH is the component within the FDA that is responsible for this program. To fulfill the provisions of the FD&C Act that apply to medical devices and radiation-emitting products, the FDA develops, publishes and implements regulations. These regulations are initially published in the Federal Register (FR) for public comment. The FR is a compilation of the daily government activities including proposed and final regulations. Final regulations are subsequently placed or codified into the Code of Federal Regulations (CFR) on an annual basis. • One of the most important aspects of getting a medical device to market is to know where to begin. The starting point is determining whether the product you plan to market is a medical device, as defined in section 201(h) of the FD&C Act. If your product meets the definitions, it will be subject to the provisions of the FD&C Act, that is, there are FDA regulatory requirements that must be met before a product can be marketed in the U.S. The purpose of Device Advice is to help you decide whether your product is subject to FDA regulations, and if so, to identify what these regulatory requirements are and help you comply with them.
  • 15. Medical Device Definition • Medical devices range from simple tongue depressors and bedpans to complex programmable pacemakers with micro-chip technology and laser surgical devices. If a product is labeled, promoted or used in a manner that meets the following definition in section 201(h) of the Federal Food Drug & Cosmetic (FD&C) Act it will be regulated by the FDA as a medical device and is subject to premarketing and postmarketing regulatory controls. • A device is:quot;an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: – recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, – 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 – intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of it's 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 any of its primary intended purposes.quot;
  • 16. Medical Device Definition • The definition provides a clear distinction between a medical device and other FDA regulated products such as drugs. If the primary intended use of the product is achieved through chemical action or by being metabolized by the body, the product is usually a drug. Human drugs are regulated by FDA's Center for Drug Evaluation and Research (CDER). Biological products which include blood and blood products, and blood banking equipment are regulated by FDA's Center for Biologics Evaluation and Research (CBER). • FDA's Center for Veterinary Medicine (CVM) regulates products used with animals. • If your product is not a medical device but regulated by another Center in the FDA, each component of the FDA has an office to assist with questions about the products they regulate. • In cases where it is not clear whether a product is a medical device there are procedures in place to use DSMICA Staff Directory to assist you in making a determination.
  • 17. FDA DEVICE CLASSIFICATION • The FDA has established classifications for approximately 1,700 different generic types of devices and grouped them into 16 medical specialties referred to as panels. Each of these generic types of devices is assigned to one of three regulatory classes based on the level of control necessary to assure the safety and effectiveness of the device: – Class I General Controls – Class II General Controls and Special Controls – Class III General Controls and Premarket Approval • The class to which your device is assigned determines, among other things, the type of premarketing submission/application required for FDA clearance to market. – If your device is classified as Class I or II a 510k will be required for marketing. – For Class III devices, a premarket approval application (PMA) will be required.
  • 18. FDA DEVICE CLASSIFICATION • Device classification depends on the intended use of the device and also upon indications for use. For example, a scalpel's intended use is to cut tissue. A subset of intended use arises when a more specialized indication is added in the device's labeling such as, quot;for making incisions in the cornea.quot; Indications for use can be found in the device's labeling, but may also be conveyed orally during sale of the product. • In addition, classification is risk based, that is, the risk the device poses to the patient and/or the user is a major factor in the class it is assigned. Class I includes devices with the lowest risk and Class III includes those with the greatest risk. • As indicated above all classes of devices as subject to General Controls. General Controls are the baseline requirements of the Food, Drug and Cosmetic (FD&C) Act that apply to all medical devices, Class I, II, and III.
  • 19. How to Determine Classification • To find the classification of your device you need to find the regulation number that is the classification regulation for your device. There are two methods for accomplishing this: go directly to the classification database and search for a part of the device name, or, if you know the device panel (medical specialty) to which your device belongs, go directly to the listing for that panel and identify your device and the corresponding regulation. • If you already know the appropriate panel you can go directly to the CFR and find the classification for your device by reading through the list of classified devices, or if you're not sure, you can use the keyword directory in the PRODUCT CODE CLASSIFICATION DATABASE. In most cases this database will identify the classification regulation in the CFR. You can also check the classification regulations below and the Precedent Correspondence for information on various products and how they are regulated by CDRH. • Once you have identified the correct classification regulation go to What are the Classification Panels below and click on the correct classification regulation or go to the CFR Search page. Some Class I devices are exempt from the premarket notification and/or parts of the good manufacturing practices regulations. Approximately 572 or 74% of the Class I devices are exempt from the premarket notification process. These exemptions are listed in the classification regulations of 21 CFR and also has been collected together in the Medical Device Exemptions document.
  • 20. DEVICE CLASSES Class I - General Controls Class II - Special Controls Class III - Premarket Approval
  • 21. DEVICE CLASSES Class I - General Controls • Class I devices are subject to the least regulatory control. They present minimal potential for harm to the user and are often simpler in design than Class II or Class III devices. Class I devices are subject to quot;General Controlsquot; as are Class II and Class III devices. • General controls include: – Establishment Registration of companies which are required to register under 21 CFR Part 807.20, such as manufacturers, distributors, repackages and relabelers. – Medical Device Listing (use FDA Form 2892) with FDA of devices to be marketed. – Manufacturing devices in accordance with Good Manufacturing Practices (GMP). – Labeling devices in accordance with labeling regulations. – Submission of a premarket notification [510(k)] before marketing a device. • Examples of Class I devices include elastic bandages, examination gloves, and hand-held surgical instruments.
  • 22. DEVICE CLASSES Class II - Special Controls • Class II devices are those for which general controls alone are insufficient to assure safety and effectiveness, and existing methods are available to provide such assurances. In addition to complying with general controls, Class II devices are also subject to special controls. • Special controls may include special labeling requirements, mandatory performance standards and postmarket surveillance. • Examples of Class II devices include powered wheelchairs, infusion pumps, and surgical drapes, and also some joint replacement prostheses and bone graft substitute materials.
  • 23. DEVICE CLASSES Class III - Premarket Approval • Class III is the most stringent regulatory category for devices. Class III devices are those for which insufficient information exists to assure safety and effectiveness solely through general or special controls. • Class III devices are usually those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. • Premarket approval is the required process of scientific review to ensure the safety and effectiveness of Class III devices. Not all Class III devices require an approved premarket approval application to be marketed. Class III devices which are equivalent to devices legally marketed before May 28, 1976 may be marketed through the premarket notification [510(k)] process until FDA has published a requirement for manufacturers of that generic type of device to submit PMA data. • Class III devices which require an approved premarket approval application to be marketed are those: – regulated as new drugs prior to May 28, 1976, also called transitional devices. – devices found not substantially equivalent to devices marketed prior to May 28, 1976. – Class III preamendment devices which, by regulation in 21 CFR, require a premarket approval application.
  • 24. DEVICE CLASSES Class III - Premarket Approval • Examples of Class III devices which require a premarket approval include replacement heart valves, silicone gel-filled breast implants, and implanted cerebella stimulators. • Class III devices which can be marketed with a premarket notification 510(k) are those: – postamendment (i.e., introduced to the U.S. market after May 28, 1976) Class III devices which are substantially equivalent to preamendment (i.e., introduced to the U.S. market before May 28, 1976) Class III devices and for which the regulation calling for the premarket approval application has not been published in 21 CFR. • Examples of Class III devices which currently require a premarket notification include implantable pacemaker pulse generators and endosseous implants.
  • 25. What is Premarket Notification [510(k)] • Each person who wants to market Class I, II and some III devices intended for human use in the U.S. must submit a 510(k) to FDA at least 90 days before marketing unless the device is exempt from 510(k) requirements. • A 510(k) is a premarketing submission made to FDA to demonstrate that the device to be marketed is as safe and effective, that is, substantially equivalent (SE), to a legally marketed device that is not subject to premarket approval (PMA). Applicants must compare their 510(k) device to one or more similar devices currently on the U.S. market and make and support their substantial equivalency claims.
  • 26. What is Premarket Notification [510(k)] • A legally marketed device is – a device that was legally marketed prior to May 28, 1976 (preamendments device), or – a device which has been reclassified from Class III to Class II or I, – a device which has been found to be substantially equivalent to such a device through the 510(k) process. • The legally marketed device(s) to which equivalence is drawn is known as the quot;predicatequot; device(s).
  • 27. What is Premarket Notification [510(k)] • Applicants must submit descriptive data and, when necessary, performance data to establish that their device is SE to a predicate device. Again, the data in a 510(k) is to show comparability, that is, substantial equivalency (SE) of a new device to a predicate device.
  • 28. What is Substantial Equivalence • Unlike PMA, which requires demonstration of reasonable safety and effectiveness, 510(k) requires demonstration of substantial equivalence. SE means that the new device is as safe and effective as the predicate device(s). • A device is SE if, in comparison to a predicate device it: – has the same intended use as the predicate device; and – has the same technological characteristics as the predicate device; or – has different technological characteristics, that do not raise new questions of safety and effectiveness, and the sponsor demonstrates that the device is as safe and effective as the legally marketed device.
  • 29. IDE Overview • An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification [510(k)] submission to FDA. • Clinical studies are most often conducted to support a PMA. • Only a small percentage of 510(k)’s require clinical data to support the application. • All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated. • Clinical evaluation of devices that have not been cleared for marketing requires: – an IDE approved by an institutional review board (IRB). If the study involves a significant risk device, the IDE must also be approved by FDA; – informed consent from all patients; – labeling for investigational use only – monitoring of the study and; – required records and reports.
  • 30. Premarket Approval (PMA) • PMA is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. – Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. – Due to the level of risk associated with Class III devices, FDA has determined that general and special controls alone are insufficient to assure the safety and effectiveness of class III devices. – Therefore, these devices require a premarket approval (PMA) application under section 515 of the FD&C Act in order to obtain marketing clearance. • PMA is the most stringent type of device marketing application required by FDA. The applicant must receive FDA approval of its PMA application prior to marketing the device. PMA approval is based on a determination by FDA that the PMA contains sufficient valid scientific evidence to assure that the device is safe and effective for its intended use(s). An approved PMA is, in effect, a private license granting the applicant (or owner) permission to market the device. The PMA owner, however, can authorize use of its data by another.
  • 31. PMA Data Requirements • A PMA application is a scientific, regulatory documentation to FDA to demonstrate the safety and effectiveness of the class III device. Good science and scientific writing is a key to the approval of PMA application. If a PMA application lacks valid clinical information and scientific analysis on sound scientific reasoning, it will delay FDA’s review and approval. PMA applications that are incomplete, inaccurate, inconsistent, omit critical information, and poorly organized have resulted in delays in approval or denial of PMA applications. Manufacturers should perform a quality control audit of a PMA application before sending it to FDA to assure that it is scientifically sound and presented in a well organized format. • Technical Sections: The technical sections containing data and information should allow FDA to determine whether to approve or disapprove the application. These sections are usually divided into non-clinical laboratory studies and clinical investigations. • Non-clinical Laboratory Studies’ Section: Non-clinical laboratory studies’ section includes information on microbiology, toxicology, immunology, biocompatibility, stress, wear, shelf life, and other laboratory or animal tests. Non-clinical studies for safety evaluation must be conducted in compliance with 21CFR Part 58 (Good Laboratory Practice for Nonclinical Laboratory Studies).
  • 32. PMA Data Requirements • Clinical Investigations’ Section: Clinical investigations’ section includes study protocols, safety and effectiveness data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, tabulations of data from all individual subjects, results of statistical analyses, and any other information from the clinical investigations. Any investigation conducted under an Investigational Device Exemption (IDE) must be identified as such. • Like other scientific reports, FDA has observed problems with study designs, study conduct, data analyses, presentations, and conclusions. Investigators should always consult all applicable FDA guidance documents (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfGGP/Sear ch.cfm).
  • 33. FEDERAL REGULATORY ISSUES Recommended Biocompatibility Testing and Clinical Trials
  • 34. Required Biocompatibility Training and Toxicology Profiles for Evaluation of Medical Devices http://www.fda.gov/cdrh/g951.html • FDA-modified matrix that designates the type of testing needed for various medical devices. • It also includes a flow chart entitled quot;Biocompatibility Flow Chart for the Selection of Toxicity Tests for 510(k)s.“ • The guidance will be effective for all submissions that will be received on or after July 1, 1995. The former guidance, #G87- 1 entitled quot;Tripartite Biocompatibility Guidance,quot; may continue to be applied until a final decision is reached on each submission received prior to July 1, 1995.
  • 35. Required Biocompatibility Training and Toxicology Profiles for Evaluation of Medical Devices • Biological evaluation of medical devices is performed to determine the potential toxicity resulting from contact of the component materials of the device with the body. • The device materials should not, either directly or through the release of their material constituents: – (i) produce adverse local or systemic effects; – (ii) be carcinogenic; or – (iii) produce adverse reproductive and developmental effects. • Therefore, evaluation of any new device intended for human use requires data from systematic testing to ensure that the benefits provided by the final product will exceed any potential risks produced by device materials.
  • 36. Required Biocompatibility Training and Toxicology Profiles for Evaluation of Medical Devices • When selecting the appropriate tests for biological evaluation of a medical device, one must consider the chemical characteristics of device materials and the nature, degree, frequency and duration of its exposure to the body. • In general, the tests include: – acute, sub- chronic and chronic toxicity; – irritation to skin, eyes and mucosal surfaces; – sensitization; – hemocompatibility; – genotoxicity; – carcinogenicity; and – effects on reproduction including developmental effects. • Additional tests for specific target organ toxicity, such as neurotoxicity and immunotoxicity may be necessary for some devices. – For example, a neurological device with direct contact with brain parenchyma and cerebrospinal fluid (CSF) may require an animal implant test to evaluate its effects on the brain parenchyma, susceptibility to seizure, and effects on the functional mechanism of choroid plexus and arachnoid villi to secrete and absorb (CSF). • The specific clinical application and the materials used in the manufacture of the new device determines which tests are appropriate.
  • 37. International Organization for Standards, ISO http://www.iso.ch/iso/en/CatalogueListPage.CatalogueList?ICS1=11&ICS2=100 &ICS3= ISO 10993-1:1997Biological evaluation of medical devices -- -- Part 1: Evaluation and testing ISO 10993-2:1992Biological evaluation of medical devices -- -- Part 2: Animal welfare requirements ISO 10993-3:1992Biological evaluation of medical devices -- -- Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity ISO 10993-4:2002Biological evaluation of medical devices -- -- Part 4: Selection of tests for interactions with blood ISO 10993-5:1999Biological evaluation of medical devices -- -- Part 5: Tests for in vitro cytotoxicity ISO 10993-6:1994Biological evaluation of medical devices -- -- Part 6: Tests for local effects after implantation
  • 38. International Organization for Standards, ISO http://www.iso.ch/iso/en/CatalogueListPage.CatalogueList?ICS1=11&ICS2=100 &ICS3= ISO 10993-7:1995Biological evaluation of medical devices ---- Part 7: Ethylene oxide sterilization residuals ISO 10993-8:2000Biological evaluation of medical devices ---- Part 8: Selection and qualification of reference materials for biological tests ISO 10993-9:1999Biological evaluation of medical devices ---- Part 9: Framework for identification and quantification of potential degradation products ISO 10993-10:2002Biological evaluation of medical devices -- -- Part 10: Tests for irritation and delayed-type hypersensitivity ISO 10993-11:1993Biological evaluation of medical devices -- -- Part 11: Tests for systemic toxicity ISO 10993-12:2002Biological evaluation of medical devices -- -- Part 12: Sample preparation and reference materials
  • 39. International Organization for Standards, ISO http://www.iso.ch/iso/en/CatalogueListPage.CatalogueList?ICS1=11&ICS2=100 &ICS3= ISO 10993-13:1998Biological evaluation of medical devices ---- Part 13: Identification and quantification of degradation products from polymeric medical devices ISO 10993-14:2001Biological evaluation of medical devices ---- Part 14: Identification and quantification of degradation products from ceramics ISO 10993-15:2000Biological evaluation of medical devices ---- Part 15: Identification and quantification of degradation products from metals and alloys ISO 10993-16:1997Biological evaluation of medical devices ---- Part 16: Toxicokinetic study design for degradation products and leachables ISO 10993-17:2002Biological evaluation of medical devices ---- Part 17: Establishment of allowable limits for leachable substances
  • 40. American Society for Testing and Materials http://www.astm.org Search “Biocompatibility”
  • 41. FDA TISSUE ENGINEERING PRODUCTS FDA's Tissue Reference Group Workshop August 29, 2001 - Slide Presentation Human Cells, Tissues, and Cellular and Tissue- Based Products (HCT/Ps) Regulated as Devices Mark N. Melkerson CDRH / FDA Tissue Reference Group (TRG) “FDA’s TRG Process” http://www.fda.gov/cber/summaries/melkersontrg.htm
  • 42. Premarket Review of Biological Products & Medical Devices • Biological Products • Medical Devices • Combination Products
  • 43. Definition of a Medical Device • “...apparatus,…, implant, in vitro reagent, including any component…or accessory... • intended for the diagnosis, mitigation, treatment, or prevention of disease... • or intended to affect the structure or function of the body... • and does not achieve its primary intended purposes through chemical action within or on the body…and which is not dependent upon being metabolized…”
  • 44. Examples of Medical Devices & Combination Products • Medical Devices - collagen, hyaluronic acid and synthetic implants – FocalSeal-L - aqueous PEG solutions modified to photo-polymerize in situ – Emdogain - porcine enamel matrix proteins • Combination Products - - – Apligraf - cells on bovine collagen
  • 45. Marketing Applications • Premarket Notification (Class II Devices) Section 510(k) of the FD&C Act (21 CFR 807) • Premarket Approval Application (Class III Devices) Section 515 of the FD&C Act (21 CFR 814) • Humanitarian Device Exemption (requires HUD Designation) Section 520(m) of the FD&C Act (21 CFR 814.100)
  • 46. Premarket Notification Review • Case-by-case approach, except if can demonstrate “equivalent” to predicate device • Basic elements: – Same Intended Use(s) – Preclinical equivalence of Product Manufacture, In vitro and/or in vivo testing – May need to demonstrate equivalence of Clinical Performance, if seeking specific indication(s) for use under general intended use(s) or differences in technological characteristics
  • 47. Food and Drug Administration Modernization Act of 1997 • Gave CDRH authority to recognize national and international standards in product reviews – Allows for “Declaration of Conformity” – Somewhat mirrors device marketing authorities used in Europe
  • 48. CDRH Standards Program www.fda.gov/cdrh/stdsprog.html • Standards Participation – ASTM F04 • Division IV - Tissue Engineered Medical Products (TEMPS) – ISO TC 150 • Working Group 11 - Tissue Engineered Implants (Reviewing Other Standards Development Activities)
  • 49. Premarket Approval Review • Case-by-case approach • Both safety and effectiveness evaluations • Basic elements: – Product Manufacture – In vitro and in vivo testing – Clinical Performance – Product Labeling • Product Manufacture – Cell, tissue & biomaterial sourcing – Product Processing – In-process and final product tests – Adventitious agents & co-purifying impurities – Lot - to - lot consistency – Quality control procedures
  • 50. Premarket Approval Review • In vitro and in vivo testing – Toxicity / Genotoxicity – Biomaterials biocompatibility – Immunogenicity /inflammatory responses – Models of product effectiveness – Product resorption/decomposition • Investigating product safety and clinical benefit: – Patient population – Investigational and control treatments – Study endpoints – Study conduct – Data analysis – Labeling claims
  • 51. Investigational Human Studies • An exemption from marketing approval is required when unapproved products are studied in humans. – Investigational Device Exemption (IDE) 21 CFR 812 • For significant risk medical devices: – FDA approval of IDE – IRB approval
  • 52. Humanitarian Device Exemption • Requires HUD (maximum of 4000 cases/per year) and requires no alternatives be marketed • Case-by-case approach • Both safety and probable benefit evaluations – Product Manufacture – In vitro and in vivo testing – Clinical Perfor – Product Labeling
  • 53. Internet Access to FDA Documents • Proposed Approach to Regulation of Cellular and Tissue-Based Products - 2/28/97 - http://www.fda.gov/cber/gdlns/CELLTISSUE.txt • Tissue Action Plan - http://www.fda.gov/cber/tissue/tissue.htm • Intercenter Agreement Between The Center for Biologics Evaluation and Research and The Center for Devices and Radiological Health - http://www.fda.gov/oc/ombudsman/bio-dev.htm • Guidance on Applications for Products Comprised of Living Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair or Reconstruction (5/96) - http://www.fda.gov/cber/gdlns/GDEXV.TXT
  • 54. Internet Access to FDA Documents • Guidance For the Submission of Chemistry, Manufacturing and Controls Information and Establishment Description for Autologous Somatic Cell Therapy Products - 1/10/97 - http://www.fda.gov/cber/gdlns/xvcmc.txt • Required Biocompatibility Training and Toxicology Profiles for Evaluation of Medical Devices 5/1/95 (G95-1) - http://www.fda.gov/cdrh/g951.html • Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation http://www.fda.gov/cber/gdlns/xenophs0101.htm • FDA PMA Database Search Engine http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPM A/pma.cfm
  • 55. Tissue Related Documents http://www.fda.gov/cber/tissue/docs.htm • Guidance for Industry: Availability of Licensed Donor Screening Tests Labeled for Use with Cadaveric Blood Specimens - 6/23/2000 • Suitability Determination for Donors of Human Cellular and Tissue-Based Products; Proposed Rule; reopening of comment period - 4/18/2000 • Establishment Registration and Listing for Manufacturers of Human Cellular and Tissue-Based Products - 5/14/98 • Guidance for Industry - Screening and Testing of Donors of Human Tissue Intended for Transplantation - 7/29/97 • Guidance for the Preparation of a Premarket Notification Application for Processed Human Dura Mater - http://www.fda.gov/cdrh/ode/054.html
  • 56. Specific Product Information • FocalSeal-L Sealant- Focal - SSE – http://www.fda.gov/cdrh/pdf/p990028b.pdf • Apligraf - Organogenesis - SSE – http://www.fda.gov/cdrh/pdf/p950032.pdf • CCS - Ortec, Inc. - SSPB (H990013) – http://www.fda.gov/cdrh/pdf/h990013b.pdf
  • 57. Multi-Agency Tissue Engineering Science (MATES) Working Group The Multi-Agency Tissue Engineering Science (MATES) Working Group is proposed as a means for the various federal agencies involved in Tissue Engineering to stay informed of each other’s activities and better coordinate their efforts. http://www.tissueengineering.gov
  • 58. Multi-Agency Tissue Engineering Science (MATES) Working Group Five Year Plan; Subcommittee on Biotechnology The term “Tissue Engineering” was coined at an NSF-sponsored meeting in 1987(1). At a subsequent NSF sponsored workshop, Tissue Engineering was defined as “the application of principles and methods of engineering and life sciences toward fundamental understanding of structure-function relationships in normal and pathological function” (2). This multidisciplinary technology involves the development of biological substitutes for the repair or regeneration of tissue or organ function and has led to a broad range of products. 1. Heineken FG and Skalak R. Tissue Engineering: A Brief Overview, Journal of Biomechanical Engineering 113, 111 (1991). 2. Skalak R and Fox CF, eds. Tissue Engineering, Proceedings for a Workshop held at Granlibakken, Lake Tahoe, California, February 26-29, 1988, Alan Liss, New York. http://www.tissueengineering.gov
  • 59. Multi-Agency Tissue Engineering Science (MATES) Working Group To date, some of these products have been approved by the U.S. Food and Drug Administration while many are under either preclinical investigation or regulatory evaluation (3, 4). Since 1990, the Tissue Engineering industry has grown to become more than a $3.5 billion worldwide R&D effort by over seventy biotechnology start-ups and business units (5, 6). Less than ten percent of this effort is funded by the U.S. government, but this contribution is rapidly increasing. 3. Hellman KB, Knight E, and Durfor CN. Tissue Engineering: Product Applications and Regulatory Issues, pp. 341-366, Frontiers in Tissue Engineering, Charles W. Patrick, Antonio G. Mikos, and Larry V. McIntire (eds.), Amsterdam, Elsevier Science (1998). 4. Hellman KB., Solomon RR, Gaffey C, Durfor C and Bishop JG, III. Tissue Engineering: Regulatory Considerations, Principles of Tissue Engineering, 2nd Edition, Robert Lanza, Robert Langer, and Joseph P. Vacanti (eds.), Academic Press, San Diego, California (in press). 5. Lysaght MJ, Nguy AS, and Sullivan K. An Economic Survey of the Emerging Tissue Engineering Industry, Tissue Engineering: 4, 231 (1998). 6. Lysaght MJ, and Reyes J. The Growth of Tissue Engineering, Tissue Engr.
  • 60. FDA APPROVAL PROCESS Classification of Product as I, II, or III TE products I. General II. Special III. Premarket Controls Controls Approval (PMA) No approval of Equivalent to Marketed Human Trial FDA prior to Device?; Investigational selling the Premarket Notification Device product. Exemption IDE 510 (k) Good Manuf. Practice Analysis of composition PMA and properties, and in vitro GMP and in vivo studies Good Lab Pract. GLP