ML20344A423
| ML20344A423 | |
| Person / Time | |
|---|---|
| Issue date: | 12/10/2020 |
| From: | Di Prima M NRC/NRR/DNRL/NVIB, US Dept of Health & Human Services, Food & Drug Admin (FDA) |
| To: | |
| Anchondo I | |
| Shared Package | |
| ML20344A421 | List: |
| References | |
| Download: ML20344A423 (30) | |
Text
FDA REGULATORY APPROACH FOR ADDITIVE MANUFACTURING Matthew Di Prima, PhD Division of Applied Mechanics Office of Science and Engineering Laboratories Center for Devices and Radiological Health U.S. Food and Drug Administration 10 December 2020 OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Disclaimer The mention of commercial products, their sources, or their use in connection with materials reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.
OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Speaker Bio Dr. Matthew Di Prima is a Materials Scientist in the US Food and Drug Administrations Office of Science and Engineering Laboratories, housed in the Center for Devices and Radiological Health. His areas of research are investigating how the additive manufacturing process can alter material properties, the interplay between corrosion and durability testing, and explant analysis. Along with his research duties, he is the head of the Additive Manufacturing Working Group which is spearheading efforts across the Agency to address how this technology affects medical devices and other regulate medical products OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Outline
- FDA and Medical Device Regulations
- Device Classification
- Regulatory Controls
- Submission Types
- How this is applied to AM
- Cleared AM Medical Devices
- Patient Matched Devices
- Anatomical Models OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
FDAs Mission
- Protecting the public health by assuring that foods (except for meat from livestock, poultry and some egg products which are regulated by the U.S. Department of Agriculture) are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drugs, and vaccines and other biological products and medical devices intended for human use are safe and effective
- Protecting the public from electronic product radiation
- Assuring cosmetics and dietary supplements are safe and properly labeled
- Regulating tobacco products
- Advancing the public health by helping to speed product innovations This equals ~25% of consumer spending in the US www.fda.gov/AboutFDA/Transparency/Basics/ucm194877.htm OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
CDRHs Role
- Regulates medical devices and radiation-emitting products
- Evaluate safety and effectiveness of medical devices
- Before and after reaching market
- Assure patients and providers have timely, continued access to safe, effective, and high-quality medical devices OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
CDRH Snapshot 1900 EMPLOYEES 18k Medical Device Manufacturers 183k Medical Devices On the U.S. Market 22k /year 570k Proprietary Brands 1.4 MILLION Reports on
/year Premarket Submissions medical device including supplements and amendments 25k adverse events and Medical Device Facilities malfunctions Worldwide OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Medical Device, defined
- Instrument, apparatus, machine, implant, in vitro reagent, including component, part, or accessory
- Diagnoses, cures, mitigates, treats, or prevents disease or condition
- Affects structure or function of body
- Doesnt achieve purpose as a drug
- Excludes certain software functions
- data storage, administrative support, electronic patient records Section 201(h) of FD&C Act OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Device Regulations
- 21 Code of Federal Regulations (CFR): Parts 800-1050
- 800-861: cross-cutting device requirements
- Example: 812 - Investigational Device Exemption
- 862-1050: device-specific requirements
- Example: 876 - Gastroenterology and Urology Devices
- 21 CFR: Parts 1-99
- general medical requirements that also apply to medical devices OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Device Classification
- Based on device description and intended use
- Determines extent of regulatory control
- Class I, II, or III
- increases with degree of risk
- Product Codes: three-letter coding to group similar devices and intended use OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
How to determine classification
- Classification is defined under Code of Federal Regulations (e.g. 21 CFR 888.3350)
(a) Identification: A hip joint metal/polymer semi-constrained cemented prosthesis is a device intended to be implanted to replace a hip joint. The device limits translation and rotation in one or more planes via the geometry of its articulating surfaces. It has no linkage across-the-joint. This generic type of device includes prostheses that have a femoral component made of alloys, such as cobalt-chromium-molybdenum, and an acetabular resurfacing component made of ultra-high molecular weight polyethylene and is limited to those prostheses intended for use with bone cement (888.3027).
(b)Classification. Class II.
- This language is specific, slight changes in device design/function can change the regulation and therefore the classification
- If your device is not in the CFR, you have to request a designation and classification from the FDA, 513(g)
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Classes of Medical Devices Class Risk Controls Submission I Lowest General
- Exempt*
- 510(k)
II Moderate General and
- 510(k)*
Special (if available)
- Exempt III Highest General and
- PMA PMA
- More common submission requirement of this Class OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
General Controls: Examples Control Regulation Brief Description (21 CFR Part)
Labeling 801 provide information for users Medical Device Reporting 803 report device-related injuries and deaths Establishment Registration 807 register business with FDA Device Listing 807 identify devices Quality System 820 ensure safe, effective finished devices Adulteration FD&C Act 501 provide device not proper for use Misbranding FD&C Act 502 provide false or misleading labeling FD&C Act = Federal Food Drug, and Cosmetic Act OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Special Control
- Specific to Class II devices
- Usually for well-established device types
- Found in (b) Classification of regulation
-example: 21 CFR 876.5860(b)
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21 CFR 876.5860 High permeability hemodialysis system
- (a) Identification. A high permeability hemodialysis system is a device intended for use as an artificial kidney system for the treatment of patients with renal failure, ...
- (b) Classification. Class II. The special controls for this device are FDA's:
- (1) "Use of International Standard ISO 10993 'Biological Evaluation of Medical Device - Part I:
Evaluation and Testing,' "
- (2) "Guidance for the Content of 510(k)s for Conventional and High Permeability Hemodialyzers,"
- (3) "Guidance for Industry and CDRH Reviewers on the Content of Premarket Notifications for Hemodialysis Delivery Systems,"
- (4) "Guidance for the Content of Premarket Notifications for Water Purification Components and Systems for Hemodialysis," and
- (5) "Guidance for Hemodialyzer Reuse Labeling."
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Special Controls: Examples
- Design, Characteristics or Specifications
- Testing
- Special Labeling
- Guidance Documents OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Premarket Submission Types
- Investigational Device Exemption (IDE)
- Premarket Notification (510(k))
- Premarket Approval Application (PMA)
- De Novo
- Humanitarian Device Exemption (HDE)
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AM and Device Manufacturing
- Generally, manufacturing method does not change regulatory classification or regulatory controls
- This allows AM products to use existing regulatory pathways
- The majority of AM devices have been cleared through the 510(k) pathway to date
- Predicate devices can be AM or non-AM
- Generally, we dont expect the technological characteristics of the devices [to] raise different questions of safety and effectiveness1
- I.E., a spine cage is a spine cage and a bone plate is a bone plate 1 FDA Guidance Benefit Risk Factors to Consider When Determining Substantial Equivalence in Premarket Notifications (510(k)) with Different Technological Characteristics OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
AM 510(k) Submissions
- FDA Guidance Technical Considerations for Additively Manufactured Medical Devices details pre-market submission expectations
- For a 510(k) submission, we are looking for the worst case AM condition to be determined in order to ensure subject device performance is substantially equivalent to the predicate
- This is different from most non-AM submissions as material performance can be assessed separately from the manufacturing process
- In most cases purchasing controls and an understanding of tooling/post-processing effects are sufficient to address material performance
- For AM controlling only the feedstock and understanding the tooling/post-processing effects are not generally sufficient to address material performance OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
AM 510(k) Submissions - Establishing Worst Case Build Conditions
- Build location
- Establish the worst case build location or that all build locations have comparable mechanical properties
- Build orientation
- If multiple build orientations are used, which will have the worst mechanical properties
- Feedstock re-use
- For AM processes that re-use feedstock, what is the re-use scheme and is there a worst-case feedstock condition in terms of performance and variability
- Residual feedstock in lattice/porous structures
- How residual feedstock material is removed from lattice/porous structures and what is the worst case for residual feedstock in final device OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Evidence of this working: 510(k) Cleared 3D Printed Devices
- Patient matched implants
- Orthopedic devices
- Skull plate - Hip Cups
- Maxillofacial - Spinal Cages K121818 implants OsteoFab by OPM - Knee trays K102975 http://www.accessdata.fda.gov/c drh_docs/pdf12/K121818.pdf Novation Crown by Exatech http://www.accessdata.fda.gov/cdrh_docs
- Patient matched surgical guides
- Dental /pdf10/K102975.pdf
- Craniofacial - Temporary bridges
- Knee - Reconstructive surgery support
- Ankle K120956 VSP by Medical K102776 Modeling e-DENT Temporary Resin http://www.accessdata.fda.gov/cd rh_docs/pdf12/K120956.pdf by DeltaMed GmbH http://www.accessdata.fda.gov/c drh_docs/pdf10/K102776.pdf OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Cleared 510(k) AM Products (2010 - 2016)
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AM Device Adverse Events 2014 59 product-related adverse events for additive manufactured devices based on 836 reports to the Manufacturer and User Facility Device Experience (MAUDE) database in 2014 OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Patient Matched Devices
- Implants
- Anatomical models
- Incorporating virtual surgical software allows for personalized cutting guide and tools
- Regulatory challenge is that there is no longer a discrete device to assess, instead we are looking at a design envelope OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Examples of Patient Matched Devices K133809: K121818: K122870:
http://www.oxfordpm.com/news/articl http://www.oxfordpm.com/news/article/2 http://www.conformis.com/c e/2014 013 ustomized-knee-19_oxford_performance_materials_rec 18_osteofab_patient_specific_cranial_devi implants/products/itotal/
eives_fda_clearance_for_3d_printed_os ce_receives_510k_approval_-
teofab_patient- _osteofab_implants_ready_for_us_market http://www.accessdata.fda.go specific_facial_device.php _and_beyond.php v/cdrh_docs/pdf12/K122870.
pdf http://www.accessdata.fda.gov/cdrh_d http://www.accessdata.fda.gov/cdrh_d ocs/pdf13/K133809.pdf ocs/pdf12/K121818.pdf OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Patient Matched Regulatory Approach
- Not Custom Devices
- Devices meeting the regulatory definition of custom devices are exempt from pre-market review
- §V.E of FDA Custom Device Exemption Guidance explains why patient matched device generally dont meet the custom device requirements
- Treating the design envelope as the device design requirements
- Design envelope needs to be validated for the intended use
- For 510(k)-eligible devices, substantial equivalence needs to be shown for the worst cases OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
AM Anatomic Models
- Intended Use of the Anatomic model is key to determine if they are considered medical devices
- Diagnostic Use makes a model a medical device (i.e., the model will affect diagnosis, patient management, or patient treatment)
- Models used to make a diagnosis based on examination or a physical measurement of structural changes from the 3D model
- Using the model to size and/or select a device or surgical instrument based on a comparison, fitting, or measurements with the model
- Using the model to determine whether a specific surgical procedure may be viable OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
AM Anatomic Model Regulatory Approach
- A 3D printed patient-specific anatomic model that is intended for diagnostic use is, in essence, a physical representation of a digital 3D model that is produced by medical image analysis software.
- The software used to generate the 3D printed models based on medical images, will be regulated. There needs to be evidence that the 3D printed models are of equivalent accuracy to the digital 3D models (segmented volumes).
- The goal is not to have to clear every individual 3D printed model, or the 3D printers.
Instead, FDA will clear software capable of generating diagnostic quality 3D printed anatomic models that has been tested and validated on a set of 3D printers based on the performance needed for the intended use and anatomy (i.e., orthopedic, cardiovascular, neurological, etc.).
OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science
Summary of AM Regulatory Approach
- Existing FDA regulatory pathways and controls have been sufficient to handle the AM medical devices that we have reviewed
- Existing product performance requirements/predicate comparisons have generally been sufficient to ensure safety and efficacy
- One product specific test standards has been developed to address fatigue concerns in AM acetabular (hip) cups
- Ongoing research to evaluate adequacy of lattice/porous standards for AM Products
- Currently working to develop a framework to handle the adoption of AM technologies by hospitals and other points of care.
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Thank You For Your Attention Questions?
AdditiveManufacturing@fda.hhs.gov 30 OSEL Accelerating patient access to innovative, safe, and effective medical devices through best-in-the-world regulatory science