United States: 3D Printing Meets Medical Devices: FDA Weighs In On Additive Manufacturing

Last Updated: January 17 2018
Article by Erin M. Bosman, Julie Y. Park and Austin Marsh

In December, the U.S. Food and Drug Administration (FDA) issued guidance on Technical Considerations for Additive Manufactured Medical Devices. The guidance represents FDA's efforts to provide regulatory direction about additive manufacturing (AM)—the broad field of 3D printing—of medical devices. Specifically, AM makes objects by sequentially building 2-dimensional layers and joining each to the layer below. AM enables diverse design models without the need to retool or create complex manufacturing machines to build components. The FDA guidance focuses on technical aspects of AM, and is organized into two topics: (1) design and manufacturing considerations; and (2) device testing considerations. The guidance notes that FDA "does not comprehensively address all considerations or regulatory requirements to establish a quality system for the manufacturing" of AM devices. Instead, FDA recommends testing and characterization for devices that include at least one additively manufactured component or additively fabricated step. The guidance also reflects the agency's current thinking on AM for medical devices.1

AM is a rapidly growing technology with numerous applications in medical devices. Representing a step toward personalized medicine, AM can facilitate anatomically matched devices and surgical instrumentation by using the patient's own medical imaging (these are referred to as "patient-matched devices"). AM can create complex geometric structures that would otherwise be impossible to manufacture, or too costly to manufacture under traditional manufacturing approaches. These technologies can prove life-saving. For example, in 2012, after receiving emergency clearance from FDA, medical staff at the University of Michigan used AM processes to create a bioresorbable tracheal splint that they used to rescue an infant suffering from a collapsed bronchus due to severe tracheobronchomalacia.2 The splint was implanted in the infant's airway, expanding the bronchus and allowing for future proper growth. Within weeks, the infant was off ventilator support and breathing normally. AM saved the baby's life.

Recognizing the benefits of AM, FDA is preparing for "a significant wave of new technologies that are nearly certain to transform medical practice." The FDA Commissioner does recognize that novel aspects of the AM process lack substantial clinical histories and experimentation.3 Accordingly, use of AM techniques in sensitive medical contexts poses challenges, and FDA anticipates that manufacturers may struggle in "determining optimal characterization and assessment methods for the final finished device, as well as optimal process validation and acceptance methods for these devices."

So far, FDA has reviewed more than 100 medical devices that were manufactured using AM techniques. FDA also recently approved a drug for seizures that was 3D-printed to create a more porous matrix than the drug would have had if manufactured using traditional means. This allowed the drug to dissolve more rapidly in the mouth. FDA further anticipates that AM can lead to treatments for burn wounds and even artificial replacement organs.4

Design and Manufacturing Process Considerations

FDA anticipates that its standard premarket submission process will apply in equal force to AM devices as it does to traditionally-manufactured devices. Accordingly, for Class II and III devices (and select Class I devices), manufacturers "must establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met per 21 CFR 820.30 Design Controls." The FDA further expects manufacturers to "establish procedures including validation of the manufacturing process of AM devices to ensure that the device can perform as intended." Especially where the final result of a process cannot be fully verified by subsequent inspection and testing, the process must be "validated with a high degree of assurance and approved according to established procedures."

Because several AM technologies and processing steps can be used in medical devices, the guidance urges manufacturers to "clearly identify each step in the printing process." In this vein, FDA recommends use of production flow diagrams coupled with high-level summaries of each critical step to help ensure product quality. Each described process step should include "a description of the process, and identification of the process parameters and output specifications." Delineated, step-by-step descriptions of each process should be well documented to allow the manufacturer to identify and remedy any root causes of failures from manufacturing defects; absent such detailed process instructions, defects can be difficult to pinpoint and correct. Because AM processes can be quickly modified and adapted to specific use-scenarios, dimensional specifications for the final device or component, as well as manufacturing tolerances of the manufacturing machine, should be properly documented.

Additional considerations come with patient-matched devices, which may not have a "standard sized template" (since they are contoured to individual patients) and may be modified by clinical staff, the device manufacturer, or third parties in response to clinical inputs. Because of this customizability, manufacturers "should clearly identify clinically relevant design parameters, the pre-determined range (min/max) for these parameters, and which of these parameters can be modified for patient-matching." The guidance specifically recommends, to the extent applicable, that manufacturers address: (1) effects and necessity of imaging; (2) clinical and patient interactions with design models; (3) maintenance of data integrity of complex design files; and (4) the (cyber)security of personally identifiable information.

FDA provides that "AM typically involves interaction between several software packages, often from different manufacturers[.]" As a result, errors in file conversions and software interactions can negatively impact the quality of the AM process and final device. For this reason, FDA recommends that manufacturers "verify the critical attributes and performance criteria of [their] final products as part of the software workflow validation to ensure expected performance, especially for patient-matched devices."

Further, once a device design is complete, manufacturers should consider additional preparatory processes, including:

  • placement, orientation, and packing density of devices or components within the build volume;
  • use of additional support material or structures for certain design features;
  • layer thickness of each "slice" created by the AM machine as related to the layer-by-layer printing process;
  • the build path, or path traced by the energy or material delivery system (e.g., laser or extruder);
  • required machine parameters and calibrations (e.g., build speed, total energy density, and focal point or nozzle diameter); and
  • environmental conditions within the build volume (e.g., temperature, pressure, and atmospheric compositions).

FDA recommends that materials used in AM processes should be well documented and chosen based on the AM technology used, the intended use of the final medical product, and any other information available. Reuse of certain materials (something possible when using AM technologies) is allowed but should be scrupulously documented. Evidence should be provided that reuse will not adversely affect the final device. Any post-processing steps of AM (manufacturing steps occurring after the printing process) that may affect device performance and material properties should also be well documented and include analysis of any effects such steps may have.

As noted above, when a final result of a process cannot be fully verified by subsequent inspection and testing, the process must be validated with a high degree of assurance. For such validation processes, monitoring and control methods of data must be documented. Such methods may include monitoring and documenting parameters such as:

  • temperature at the beam focus;
  • melt pool data;
  • build-space environmental conditions;
  • location in the build volume where a device or component was built; and
  • power of the energy delivery system.

These same methods may also be helpful for processes that are not required to be validated.

Device Testing Considerations

Generally, FDA advises that AM product performance testing should be implemented in the same manner as if the device were manufactured using traditional manufacturing methods. Depending on the device type, these testing methods may include: "material property testing such as modulus, yield strength, ultimate strength, creep/viscoelasticity, fatigue, or abrasive wear." Further, performance testing should be conducted on all finished devices following post-processing, cleaning, and sterilization steps. Manufacturers should also conduct tests targeting the "worst-case combinations" of dimensions, features, orientations of the materials, and locations in the build space to ensure adequate product performance. These tests should include a discussion of how the combinations were selected and why each test was conducted. Manufacturers should create and maintain "test coupons" (a representative test sample of the device or component) when evaluating AM products.

Recognizing that AM processes may lead to a wider variance in end products than traditional manufacturing methods, FDA recommends that manufacturers specify and adhere to pre-set dimensional tolerances by measuring representative product samples. Manufacturers should address any variability due to orientation and build location if studies show variance based on these parameters. In order to maintain consistency, product measurements should be made on samples from multiple build cycles and manufacturers are expected to provide justification for the sampling scheme used. Finally, process validation information may help demonstrate negligible variability between products in different build cycles or batches.

Because of the iterative nature of AM, starting materials may be exposed to partial re-melting and solidifications multiple times. This may result in unexpected or undesired material compositions. Because many AM medical devices will be used in sensitive medical contexts (often surgically implanted into a patient), manufacturers should conduct biocompatibility testing and incorporate guidance proffered in "Use of International Standard ISO 10993-1, 'Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process'" if necessary. Specific testing (e.g., in vitro degradation testing) may be necessary if the AM device uses an absorbable material.

One of the greatest advantages of AM devices is the ability to make highly complex components and end products. With that advantage comes an inherent disadvantage—AM devices may be exceptionally hard to clean and sterilize. AM also allows porous structures to be produced earlier in the manufacturing process than traditional methods, which may result in greater soiling by subsequent exposure to other AM materials. Accordingly, manufacturers should create work-flows and be able to validate that any remaining material residue will not adversely affect the device's quality. A summary of this information should be included in premarket submissions to the agency. Additionally, the guidance warns that many end-use facilities will not have access to the equipment or materials needed to implement on-site cleaning procedures designed to remove residual manufacturing materials. Accordingly, only devices that are sufficiently cleaned should be provided to the end user.

Labeling

Finally, the guidance provides that AM device labeling "should be developed in accordance with applicable regulations, device-specific guidance documents, and consensus standards." Additional labeling is recommended for AM devices that are patient-matched. FDA recommends that such labeling identify (1) the patient; (2) the products used (e.g., left distal femoral surgical guide); and (3) final design iteration or version used to produce the device. Expiration dates for patient-matched devices should also be included. Because it is possible that a patient may experience an event between imaging and surgery, FDA also recommends that manufacturers include a precaution in their labeling that the patient should be evaluated for potential anatomical changes prior to the procedure.

Conclusion

Though not binding, manufacturers should consider adopting the recommendations included in the FDA's guidance on AM. As with other FDA guidance documents, future regulations are likely to incorporate and expand on these existing guidelines.

Footnotes

1 The FDA categorized this document as "leap-frog" guidance because "it helps bridge where we are today with innovations of tomorrow."

2 Moore, Nicole, 3D Printed Splint Saves the Life of a Baby, Michigan Engineer News Center (May 22, 2013), https://news.engin.umich.edu/2013/05/3d-printed-splint-saves-the-life-of-a-baby/.

3 Statement of FDA Commissioner Scott Gottlieb, M.D., on FDA ushering in new era of 3D printing of medical products (Dec. 4, 2017), https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm587547.htm.

4 Id.

Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

© Morrison & Foerster LLP. All rights reserved

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Authors
Erin M. Bosman
Julie Y. Park
Similar Articles
Relevancy Powered by MondaqAI
 
In association with
Related Topics
 
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
 
Related Video
Up-coming Events Search
Tools
Print
Font Size:
Translation
Channels
Mondaq on Twitter
 
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
 
Email Address
Company Name
Password
Confirm Password
Position
Mondaq Topics -- Select your Interests
 Accounting
 Anti-trust
 Commercial
 Compliance
 Consumer
 Criminal
 Employment
 Energy
 Environment
 Family
 Finance
 Government
 Healthcare
 Immigration
 Insolvency
 Insurance
 International
 IP
 Law Performance
 Law Practice
 Litigation
 Media & IT
 Privacy
 Real Estate
 Strategy
 Tax
 Technology
 Transport
 Wealth Mgt
Regions
Africa
Asia
Asia Pacific
Australasia
Canada
Caribbean
Europe
European Union
Latin America
Middle East
U.K.
United States
Worldwide Updates
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.

Disclaimer

The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.

General

Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions