integrating additive manufacturing into the …...model output, i.e., compute a qualified guess of...

THE WINSTON CHURCHILL MEMORIAL TRUST OF AUSTRALIA

Report by - CHRISTOPHER PAUL CARTY - 2017 Churchill Fellow

Integrating additive manufacturing into the treatment

pathway for children with bone deformities

Keywords

3D Printing

Additive Manufacturing

Surgery Planning

Orthopaedic Paediatrics

Deformity Correction

Patient Specific Surgical Guides

Musculoskeletal Modelling

Predictive Simulation

31st August 2018

I understand that the Churchill Trust may publish this Report, either in hard copy or on the

internet or both, and consent to such publication.

I indemnify the Churchill Trust against any loss, costs or damages it may suffer arising out of

any claim or proceedings made against the Trust in respect of or arising out of the publication

of any Report submitted to the Trust and which the Trust places on a website for access over

the internet.

I also warrant that my Final Report is original and does not infringe the copyright of any

person, or contain anything which is, or the incorporation of which into the Final Report is,

actionable for defamation, a breach of any privacy law or obligation, breach of confidence,

contempt of court, passing-off or contravention of any other private right or of any law.

Christopher Paul Carty, PhD

Clinical Research Manager (Orthopaedics), Division of Surgery & Perioperative Services

Clinical Motion Analysis Consultant, Queensland Children’s Motion Analysis Service

Children’s Health Queensland Hospital & Health Service

Advance Queensland Fellow, Griffith University

Level 5, Centre for Children’s Health Research

62 Graham Street, South Brisbane Qld 4101

T: 3069 7194 ׀ F: 3069 7929 ׀ E: [email protected]

mailto:[email protected]

Acknowledgements

I would like to thank the Winston Churchill Memorial Trust and Griffith University for the

ongoing support during my Churchill Fellowship. In particular, I would like to thank Professor

David Lloyd for his mentorship and his passion for disruptive technologies that will transform

the medical device industry, and Daniel Martinez-Marquez for sharing his extensive

knowledge on Quality by Design methodologies and collaborating with me during the

European phase of my travels. Furthermore, I would like to thank Martina Barzan (pictured

below left), Dr Sheanna Maine (pictured below right) and Dr David Bade for their continued

support on innovative projects that aim to improve surgery for children with bony

deformities. Finally, I would like to thank my wife Michelle and our four children Sophie,

Joshua, Isabella and Jessica for bravely supporting my absence during my travels and cheering

me up with video calls every evening from half way across the world.

Executive Summary

The purpose of my Churchill Fellowship was to determine the potential for additive

manufacturing (i.e., 3D printing) to be integrated into the management pathway for children

with bony deformities. The great advantage of additive manufacturing is that is capable of

fabricating complex shapes, and manipulating material properties that are impossible with

traditional manufacturing methods and for these reasons show immense potential. The major

conclusions from my fellowship are as follows:

1. Equal time and effort should be invested in the quality processes that inform pre-

operative planning of surgery for complex lower limb deformities. More research on

advanced patient specific computational simulations is required to enable a more

objective surgical prescription process, and better understanding of actual loads

experienced by bones and implants during human movement.

2. The relationship between the orthopaedic surgeon and the design, or clinical, engineer is

crucial during the design phase of any custom 3D printed patient specific product. The

surgeon should be actively involved in the design phase of the product and be provided

an opportunity to gather hands on experience with any new surgical guide concepts.

3. Effective collaborative pre-planning and additive manufacturing will allow the surgeon to

execute the surgical plan in theatre in an accurate, precise and efficient manner.

Nonetheless, it recommended that more research be conducted on the efficacy of

patient specific surgical guides, as there remains a paucity of research in this area.

4. Industry and research institutions need to collaborate with regulatory authorities in the

near future to ensure product quality and safety, whilst not overburdening the quality

control process with redundant methodologies.

Fellowship Programme

Dates Location Organisation Individuals visited

29th June – 5th July Leuven. Belgium Materialise Dr Sebastian De Boodt Dr Pieter Slagmolen Dr Sjoerd Kolk Dr Maria-Elvira Zeman Dr Roel Wirix- Speetjens Sharifah Fareena Aljunid

KU Leuven Professor Ilse Jonkers Professor Friedl De Groote Dr Hans Kainz Dr Hoa Hoang

5th July – 7th July Hamburg, Germany implantcast Marcus Junge Peter Scheinemann Klemens Terhaer Lia Schenk Gregor Besser

7th July – 14th July Dublin, Ireland World Congress of Biomechanics

Conference attendance

VU Amsterdam Prof Jaap Harlaar Dr Marjolein van der krogt

Imperial College London

Dr Luca Modenese

14th July – 22nd July Warsaw, USA OrthoPediatrics Dr Mallory Trusty Dr Peter Armstrong Joe Hauser David Daniels Fred Hite David Bailey

Zimmer Biomed Aaron Smits Josh Catanzarite Troy Hershberger

22nd July – 28th July Vancouver, Canada BC Children’s Hospital

Dr Emily Schaeffer Dr Liam Johnson Eva Habib

Centre for Hip Health and Mobility

Dr Sima Zakani Prof David Wilson

Definition of terms

3D: Three-dimensional

4D: Four-dimensional

Accuracy: Accuracy is used to describe the closeness of a measurement to the true value (ISO 5725)

Additive Manufacturing: The process of joining materials to make objects from 3D model data,

usually layer upon layer, as opposed to subtractive manufacturing methodologies

Avascular necrosis: The death of bone tissue due to a lack of blood supply

Biomechanics: The study of the mechanical laws relating to the movement or structure of

living organisms

Bone implant: Use of natural or artificial materials for osseous reconstruction

Bony scaffold: A medical process used to regrow bone tissue. Damaged cells grip to the scaffold and

begin to rebuild missing bone and tissue through tiny holes in the scaffold

CAD: Computer-aided design. The use of computer systems to aid in the creation, modification,

analysis, or optimization of a design

Cerebral Palsy: A condition marked by impaired muscle coordination and bony deformity resulting

from damage to the brain before or at birth

CT: Computed tomography. The CT scan can reveal anatomic details of internal organs that cannot

be seen in conventional X-rays

Digital twin: A digital replica of physical assets (physical twin), processes and systems that can be

used for various computational modelling purposes

FDA: Food and Drug Administration (USA)

Neuromusculoskeletal modelling: Modelling the movements produced by the muscular and skeletal

systems as controlled by the nervous system

Machine learning: A field of computer science that uses statistical techniques to give computer

systems the ability to "learn" with data, without being explicitly programmed

Medical device: An instrument, apparatus, implement, machine, contrivance, implant, in vitro

reagent, or other similar or related article, including a component part, or accessory

MRI: Magnetic resonance imaging. A medical imaging technique that uses a magnetic field and radio

waves to create detailed images of organs and tissues

Osteotomy: The surgical cutting of a bone, especially to allow realignment.

PMI: Patient matched implant

Precision: The closeness of agreement among a set of results (ISO 5725)

Predictive simulation: In musculoskeletal modelling predictive simulations can be used to predict

model output, i.e., compute a qualified guess of future output values based on past observations of

system’s inputs and outputs

QbD: Quality by Design. The approach is composed of eight main steps that follow in

a systematic way they can provide a deep understanding of the product and its manufacturing

process, including the identification and control of all variables to ensure desired quality

Saw bone: An artificial bone produced for the practice surgical techniques

SCFE: Slipped capital femoral epiphysis. A medical term referring to a fracture through the growth

plate (physis), which results in slippage of the overlying end of the femur (metaphysis)

Selective laser sintering: An additive manufacturing technique that uses a laser as the power source

to sinter powdered material (typically nylon/polyamide), aiming the laser automatically at points in

space defined by a 3D model, binding the material together to create a solid structure

Surgical guide: A medical device that is 3D printed based on patient specific medical imaging. It is

used to accurately assist in placement of surgical tools or devices bone

TGA: Therapeutic Goods Administration (Australia)

Virtual Surgery: Computational technique of simulating surgery procedure, which help Surgeons

improve surgery plans and practice surgery process on 3D models

Integrating additive manufacturing into the treatment

pathway for children with bone deformities

Background

Paediatric bone deformities can result from congenital conditions or acute injuries and often

require orthopaedic intervention. For example, a femoral de-rotation osteotomy can address

the in-toeing gait of a child with cerebral palsy [1], or correct the out-toeing gait subsequent

to a slipped capital femoral epiphysis fracture (SCFE) [2]. Corrective osteotomies for

paediatric bone deformities are highly complex and require meticulous surgical pre-planning

and precise surgical execution. There have been a number of procedures described to correct

proximal femoral geometry in children with deformity subsequent to SCFE [3], which can be

broadly classified by anatomical region including subcapital, base of the femoral neck or

intertrochanteric, with the latter being preferred due to reduced risk of avascular necrosis.

For this reason, the present report will focus on utilising additive manufacturing to assist with

an intertrochanteric osteotomy.

The typical patient management pathway for paediatric deformity correction is depicted in

figure 1. First, the patient presents to the orthopaedic surgeon for an initial consultation.

During the consultation, the surgeon will gather the patient’s medical history and will perform

a physical evaluation. When indicated, the surgeon will refer the patient for medical imaging

(x-ray, CT or MRI) to visualise the deformity and/or three dimensional (3D) gait analysis to

determine the consequence of the deformity on the patients walking gait. The results from

medical imaging and 3D gait analysis are viewed independently and interpreted by the

orthopaedic surgeon. Once the surgeon has determined the preferred intervention the

surgery is planned from the static medical imaging and is executed in theatre. Depending on

the preference of the surgeon, they may mark the angle of the osteotomy wedge directly on

the bone or insert a guide wire at the desired angle. Following the osteotomy, the distal

segment is aligned and fixation is achieved using a dynamic compression plate, blade plate or

dynamic hip screw and plate device. Post-operatively patients are encouraged to participate

in a rehabilitation program and are evaluated for progress. At approximately 12 months post-

surgery medical imaging and/or 3D gait analysis is conducted to evaluate outcomes.

Figure 1. Typical patient management pathway for paediatric deformity correction

Additive manufacturing also known as 3D printing is an emerging manufacturing technology

in the biomedical field. The great advantage of this technology is that is capable of fabricating

complex shapes, and manipulating material properties that are impossible with traditional

manufacturing methods. The printers are supported by software to build three-dimensional

Surgeon consult

Medical imaging

+/- gait analysis

Surgery

planning

Surgical execution

Rehabilation

physical models from a series of cross sections, which are automatically joined together to

create the final shape [4]. A number of different additive manufacturing methods are

currently being implemented in the biomedical field and include stereolithography, selective

laser sintering, Inkjet 3D printing, electron beam melting, polyjet photopolymer and fused

deposition [5, 6]. Furthermore, there are a variety of materials that can be used by these

additive manufacturing methods, which may include plastics, ceramics and metals [4, 7]. For

complex surgical procedures, such as the intertrochanteric osteotomy, there exists an

opportunity to use additive manufacturing technology to assist surgical planning (e.g. 3D

printed anatomical models), aid surgical guidance (e.g. patient specific cutting guides) and/or

develop custom surgical fixation devices (e.g. bone implants).

Custom 3D printed orthopaedic solutions for paediatric deformity correction, including bone

implants, scaffolds or surgical guides have to overcome several barriers from a quality control

perspective, Firstly, medical devices are strictly regulated by organizations such as FDA (USA),

EMA (European Union), and TGA (Australia), in order to ensure their compliance to medical

specifications and consistency in manufacturing practices. Moreover, current standardization

methods applied to traditional manufacturing methods are not suitable for 3D printing

technology [8]. As a result, there is a lack of standardization and defined quality control

processes. Furthermore, additive manufacturing incorporates new technologies in the

biomedical field, and the design and fabrication of custom medical devices requires many

steps that might lead to imperceptible errors, affecting the performance and consequently,

patient safety. Successful industry transformation to this new design and manufacturing

approach requires technology integration, concurrent multi-disciplinary collaboration, and a

robust quality management framework.

Fellowship aims

To determine the potential for additive manufacturing to be integrated into the management

of children with bone deformities. Specifically, this report will investigate:

I. The potential of 4D medical image simulation for surgical-pre planning

II. The engineer to orthopaedic surgeon relationship

III. Additive manufacturing of patient specific cutting guides

IV. Quality assurance and regulatory approval

The potential of four dimensional (4D) medical image simulation for

surgical-pre planning

During the second week of my fellowship, I attended the 8th World Congress of Biomechanics

in Dublin, Ireland. This congress represents the premier meeting worldwide in the field of

Biomechanics. In brief, biomechanics is the study of the mechanical laws relating to the

movement or structure of living organisms. Human research in this field sits at the interface

of engineering and medicine and has revolutionised medical device technologies. The World

Congress of Biomechanics was attended by over 3,000 delegates and comprised of 15 parallel

sessions for most timeslots across the conference programme. Consequently, I focussed my

attendance on advances in medical imaging, neuromusculoskeletal modelling, paediatric

biomechanics, cerebral palsy, predictive simulation and medical devices. A major theme that

emerged from the conference was the pursuit of a simulation framework to allow accurate

predictive modelling following surgical intervention (e.g. muscle lengthening, bone

osteotomy) or musculoskeletal adaptation (e.g. muscle strengthening, robotic devices). The

two research groups at the forefront of this pursuit were led by Professor Benjamin J Fregly

in the Department of Mechanical Engineering, Rice University, Houston, TX, USA, and,

Professors Ilsa Jonkers and Friedl De Groote in the Human Movement Biomechanics Research

Group, KU Leuven, Leuven, Belgium. Furthermore, I had the opportunity to meet with some

of my international collaborators to discuss the current state of technology in predictive

modelling. It was clear the advances in the field of biomechanics could be used to improve

the typical patient management pathway described in figure 1. Based on the many

presentations and discussions on this topic a new framework for objective surgical

prescription is proposed (see Figure 2).

Figure 2. A new framework for objective surgical prescription and execution

Similar to the typical patient management pathway the patient presents to the orthopaedic

surgeon for an initial consultation, however, rather than an independent evaluation of

medical imaging and 3D gait analysis this data is merged to create a neuromuscuoskeletal

model, or ‘digital twin’. The digital twin is then calibrated to ensure that the simulation can

match the experimental data [9, 10]. The calibrated model can then be virtually adjusted (see

figure 3) and a predictive simulation could be used to determine the potential consequence

of the chosen surgical intervention. Virtual surgery planning is an innovative solution and will

allow the identification of the limitations, constraints, and risks of the surgery [11].

Furthermore, virtual planning improves technical performance, gives confidence, and pays

dividends on the day of the actual procedure [11]. Once an optimal surgical intervention is

determined, an appropriate implant can be selected from those available on the market, or

could be 3D printed. To assist the surgeon in executing in their pre-operative surgical plan,

patient specific surgical guides could also be 3D printed.

Figure 3. Virtual surgical adjustment to simulate an osteotomy.

Following surgery, a rehabilitation program is provided to the patient, however, in this

framework the rehabilitation program is specifically targeted to the expected post-surgical

impairments as predicted by the simulation [12]. A targeted rehabilitation program could

particularly be helpful for children with limited capacity and/or energy in the months

following surgery (e.g. patients following bone tumour resection). Finally, at 12 months post-

surgery the patient is assessed with medical imaging and 3D gait analysis, but this time the

information is not lost, rather it feeds back into the workflow using machine-learning methods

[13], thereby enabling process to be adapted in future to reduce discrepancies.

In summary, advances in biomechanics will allow a more objective surgical prescription

process and 3D printing technology will play an important part in aiding the surgeon with

custom devices and also tools to executive the surgical plan. Nonetheless, it is important to

state that without an effective pre-operative surgical plan, 3D printed solutions will not

enhance surgical outcomes because the precise execution of a sub-optimal surgery will still

lead to suboptimal outcomes.

The engineer to orthopaedic surgeon relationship

A common theme that emerged from discussions with orthopaedic companies who offered

patient specific solutions was the need for a strong collaborative relationship between the

orthopaedic surgeon and the design engineer. In this section, I will briefly describe the

collaborative engineer-surgeon process implemented by the companies that I visited.

Materialise

In Leuven, I met with the osteotomy team at

Materialise, headed by Maria-Elvira Zeman. Maria

took me through the history of the company’s

methods in collaborating with hospitals to provide

patient specific solutions for complex deformities.

In total, their team had provided virtual surgical

pre-planning and/or the manufacture of cutting

guides via 3D printing for over 2,000 cases, with

the demand growing each year. The portfolio

included deformity correction for upper and lower

limb deformities. In their workflow, the

orthopaedic surgeon sends medical images to

Materialise and a clinical engineer segments the

medical images and subsequently creates a preliminary virtual design for the deformity

correction. The proposed implant may be informed by the surgeon’s preference or might be

sourced from those available on the market. The preliminary design is presented to the

surgeon who subsequently makes suggestions based on clinical experience and the virtual

plan is adjusted accordingly. Once the plan is decided, a single guide is manufactured from a

regulatory approved polyacetylene base powder with selective laser sintering. The guides are

typically produced with cutting slits for the wedge resection, drill holes for the guide wire

placement, and drill holes for pre-drilling of the tunnels for plate fixation. Furthermore,

should an appropriate corrective device not be available on the market the Materialise team

also has the capacity to 3D print their own custom fixation devices (see Figure 4).

Figure 4. Example 3D printed fixation devices at developed by the Materialise osteotomy team.

Zimmer Biomed

In Warsaw, “The Orthopaedic

Capital”, I met with the Patient

Matched Implants (PMI) team at

Zimmer Biomed comprising of

Aaron Smits (Technical Graphics

Manager, PMI), Josh Catanzarite

(Engineering Manager, PMI), and Troy Hershberger (Director, PMI). The team informed me of

the two separate departments at Zimmer Biomed that use 3D printing in designing patient

specific solutions. The PMI department typically deals with lower incident unique cases where

standards products are not available and therefore patient matched solutions are requested.

Interestingly, the demand for the PMI service is growing and the team is expanding. An

example of a PMI request might be to provide a solution to reconstruct the hip at the pelvis

and femur subsequent to tumour resection. The other department focuses on production of

personalised surgical guides for mass produced knee, hip and shoulder implants. I was

particularly interested in discovering how the team conveys to the surgeon the benefit of

patient matched solutions. Together we agreed that evidence for the benefit of cutting

guides, for example, could be provided by citing research on the superior outcomes shown

for guides that are used in knee replacement surgery to restore the mechanical or anatomical

axis [14-17]. However, the evidence for the benefit of customised solutions for complex

deformity is less clear and not yet available in the literature, partially due to the difficulty in

designing such a study and longitudinally tracking economic benefits. To overcome this lack

of scientific evidence the team conducts hands on workshops with orthopaedic surgeons

using saw-bones. The team recently conducted a study with a group of surgeons where a

guide wire was to be inserted in the glenoid fossa and oriented towards a specific notch on

the scapula. This process was then repeated with the use of 3D printed surgical guides. Follow

up investigations with CT revealed the variability in guide wire placement using a manual

approach, whereas the guided approach was accurate, precise and efficient. The experiment

allowed the surgeons to visualise the benefit of the guides and they are now strong advocates

for the use of surgical guides in clinical practice.

OrthoPediatrics

In Warsaw, I also met with

the team at OrthoPediatrics,

who are an orthopaedic

company solely focused on

products for the paediatric

orthopaedic market. The

founders of the company saw

that paediatric surgeons

were forced to modify adult size implants in the operating theatre to fit the implant to the

child. OrthoPediatrics was founded with the vision to address the problem of off-label use of

adult implants. The company now has an extensive number of products that are designed to

cater specifically for the paediatric patient. OrthoPediatrics are not currently producing

patient specific implants but do collaborate with an external company (MightyOak Medical -

https://mightyoakmedical.com/) who design surgical navigation guides for their spinal

deformity implants. I did not have the opportunity to visit the team at Mighty Oak medical in

Denver, Colorado, but was able to connect with the President of the company and the Chief

Operating Officer via a phone interview prior to my departure. The company echoed the need

for a close relationship between the design engineer and the surgeon. They also shared

feedback from paediatric spinal surgeons who reported that the surgical navigation guides

were particularly helpful when performing complex scoliosis surgeries in paediatric patients.

https://mightyoakmedical.com/

Implantcast

In Hamburg, I met with the team at Implantcast who also had a well-established process for

digital, pre-operative planning, which was similar to the process implemented at Materialise

and can be reviewed in detail at the following website (https://www.implantcast.de/en/for-

medical-professionals/products/individual-prosthetics/c-fitr-3d/). Implandcast produces

approximately 10

patient-specific implants

per week with a total of

500 implants per year. I

had the opportunity to

sit down with design

engineers Lia Schenk

and Gregor Besser and

was able to ask a

number of questions related to medical imaging segmentation and the virtual surgery design

process. Furthermore, I had a hands-on experience on a number of de-identified patient case

studies whereby segmentation and virtual design of surgery was conducted. The complexity

of each case highlighted the difficulty confronted by many orthopaedic surgeons in planning

and executing surgery for complex deformities. Furthermore, the precision required by Lia

and Gregor to segment the images and create a virtual plan underlined their high level of

specialised skill in design engineering and the important role they play in treating the patient.

The case studies highlighted the potential of additive manufacturing for virtual surgery,

surgical guides and metal implants and covered many body regions including pelvis, distal

tibia / calcaneus, distal radius, proximal radius / ulna, shoulder /scapula and femur.

https://www.implantcast.de/en/for-medical-professionals/products/individual-prosthetics/c-fitr-3d/

https://www.implantcast.de/en/for-medical-professionals/products/individual-prosthetics/c-fitr-3d/

Summary

In summary, the relationship between design, or clinical, engineer and the orthopaedic

surgeon is crucial during the design phase of any patient specific product. Providing an

opportunity for the surgeons to test any surgical guides on saw bones, and/or providing 3D

printed models of the deformity aids the surgeon in planning complex deformity corrective

surgeries. The combination of effective collaborative pre-planning and additive

manufacturing allows the surgeon to execute the surgical plan in theatre in an accurate,

precise and efficient manner. There appears to be a growing demand from orthopaedic

surgeons who would like to utilise custom patient specific solutions for their patients. In the

next section, I will discuss the design and additive manufacturing process of patient specific

surgical guides for an intertrochanteric osteotomy.

Additive manufacturing of patient specific surgical guides

Following the collaborative development of a 3D virtual surgical plan, the surgeon may

request manufacture of patient specific instrumentation to accommodate accurate, precise

and efficient execution of the pre-operative plan in the operating theatre. The four companies

that I visited all had the capacity to provide 3D printed custom surgical guides to assist with

deformity corrective surgery. The guides were either designed and manufactured on site

(Materialise, implantcast), designed onsite with manufacturing outsourced (Zimmer Biomed)

or designed and manufactured via collaboration with external partners (OrthoPediatrics).

Should a hospital department buy a printer and print custom medical devices in a hospital?

A common misconception with 3D printing is that a hospital department can simply buy a 3D

printer and start printing custom medical devices. Although this may be partially true for

external devices (e.g. custom orthotics), it is certainly not recommended for custom medical

devices that are intended for use in an operating theatre. Indeed, medical device companies

are anticipating regulatory changes in the custom medical device market and consequently

are developing comprehensive quality control procedures. The workflow to produce a patient

specific surgical guide for a proximal femoral osteotomy using a blade plate can be

summarised as follows:

Segmentation of external femoral geometry from CT or MRI

Design of a base plate for the surgical guide considering the surgical approach and the

anatomy the will be exposed in surgery. In addition, the design for the inner surface

needs to allow intuitive and secure positioning to be achieved during surgery.

Integration of the CAD model of the desired implant to determine the orientation of

the blade plate into the post-osteotomy proximal segment geometry, and the positon

of the fixation screws in post-osteotomy distal segment.

The outer surface of the base plate can then be designed to incorporate the

specifications of the medical tool dimensions and guide their orientation during

surgery. This includes the dimensions of the guide wires, drill bits, chisel and saw

blade.

Once the design of the medical tool placement is incorporated into the outer surface

of the base plate, labelling of hole/plane dimension should be incorporated into the

surface.

The final CAD model design of the surgical guide is then converted to an STL file for

printing. Note - prior to 3D printing any medical devices the manufacturer needs to

ensure validation of the print for all proposed print materials. This includes verification

of the external shape and verification that the material properties meet ISO standards

for all proposed print orientations.

During the initial prototyping stages, low quality materials and printers can be used to

create ‘proof of concept’ models. For example, Materialise used fused deposition

modelling for prototypes and functional testing.

Printing the surgical guide requires higher accuracy printing using materials that are

biocompatible with regulatory approval. Many of the companies use laser-sintering

technology and print with polyamide powder. In brief, the process produces 3D

printed parts by selectively fusing individual layers of powdered material using a laser.

Following the printing process, the powder bed and parts contained within are

allowed to cool before being removed from the build chamber. The 3D printed surgical

guide needs to be extracted from the powder and all surface powder needs to be

removed.

Removal of the power is important given the intricate holes and slits that guide the

medical tools. The surfaces first need to be brushed, which removes the major part of

the powder, and then sandblasted to remove what the brush may have missed.

The part should have dimensional accuracy assessed and each guide hole/slit should

be inspected and trailed to ensure the intended medical tool fits into the respective

parts. Many companies will fulfil this requirement with manual measurement,

however optical and scanning probing systems are recommended because they

collect much more data in the same or less time, resulting in more correct handling of

geometrical imperfections [18]. These methods also allow a complete automation of

the measurements process [19], improve the representation of the real geometrical

feature, and provide a higher degree of flexibility in measurement settings [20].

The labelling of the guide also needs to be inspected for accuracy.

The guide then needs to be sterilised, labelled and packaged for patient use in theatre.

Summary

In summary, the process from design to manufacture of a surgical guide that can be used by

an orthopaedic surgeon in theatre is complex and requires specialised software, equipment,

and team of trained professional to ensure quality control at each step of the workflow

described above. In the next section, I will overview regulations regarding custom 3D printed

orthopaedics devices in the USA, Europe and Australia, and the quality control methods that

medical device companies are adopting to ensure they meet current regulatory requirement

and anticipate future requirement.

Quality assurance and regulatory approval

The integration of 3D printed anatomical models, surgical guides and/or bony implants into

clinical practice in Australia will revolutionise the medical industry. However, this technology

introduces a new layer of complexity and variability in product characteristics and is currently

posing a serious challenge to regulatory bodies tasked with managing and assuring product

quality and safety. Traditional quality frameworks that have ensured the fabrication of

reliable medical devices in the past are limited to standardized manufacturing methods,

which base their quality control activities on lot sampling and statistical quality control

techniques. Such approaches are limited for customized products where the manufacturing

environment is reduced to a fraction of traditional manufacturing activities.

According to the Australian Therapeutic Good Administration (TGA), mass produced 3D

printed devices are governed by the same regulatory requirements as conventionally

manufactured devices. However, devices that meet the definition for ‘custom-made’,

whether 3D printed or otherwise manufactured, have different requirements and are exempt

from being included in the Australian Register of Therapeutic Goods (ARTG). They must

however, meet the requirements under the conformity assessment procedures for custom-

made medical devices specified in the regulations. At present, the TGA is considering changes

to current medical device regulatory frameworks for custom medical devices to mitigate risks

to patients, and to meet requirements for health care providers and manufacturers. In

November 2017, the TGA released a consultation paper proposing regulatory changes related

to personalised and 3D printed medical devices [21]. The consultation covered topics

including: new definitions for personalised devices, changes to the custom-made conformity

assessment procedure, changes to the definition of manufacturer (including a potential

exception for health care practitioners and hospitals), a new classification for anatomical

models and digital 3D print files and regulating scaffolds that contain human origin material

under the devices framework rather than the biologicals framework. In May 2018, the TGA

released the feedback form the consultation process [22]. In general, the submissions from

industry, health care and government organisations indicated that there is still need for more

clarity. The need for clarification was especially evident regarding the boundary between the

proposed ‘custom-made’ and the proposed ‘patient-specific’ definitions. There were also

several submissions indicating uncertainty, and requesting further explanation of what

exactly would be seen as a medical device production system. Furthermore, the exemptions

for health care practitioners and hospitals were not fully supported, which fits well with above

recommendation regarding the difficulty of printing medical devices in a hospital facility with

hospital staff alone. There is still work to be done in Australia and the TGA is currently leading

an international harmonisation initiative for definitions for personalised medical devices

through chairing an International Medical Device Regulators Forum working group on this

topic.

During this transition phase, where regulatory bodies are updating procedures, the quality

assurance of custom 3D printed medical devices has been carried out in the medical device

industry without any specific standard for this technology [23]. Indeed, the companies that I

visited who used additive manufacturing conveyed that there was a lack of clarity in

regulatory requirements for 3D printed medical devices. Therefore, to ensure compliance

these companies follow the same regulatory requirements and submission expectations as

traditional manufactured medical devices. However, the sharing of quality control resources

such as staff and technologies between the standard implants and the patient-specific

products can be counterproductive in the long term when the production of customised

products is increased. This strategy leads to the creation of more inspection activities that are

not necessarily required and/or appropriate for additive manufacturing, and these resources

could be better allocated to future innovative research and development activities. A

framework for quality control of 3D printed surgical guides is proposed below (see figure 5).

Currently I am working with Daniel Martinez Marquez, a colleague at Griffith University who

is working on a project investigating the use of the Quality by Design (QbD) system for custom

3D printed bone prostheses and scaffolds [24] with the aim of industry translation [25]. In

brief, the QbD system was created by the US Food and Drug Administration in 2004, which

aims to carefully design products, services and processes considering all aspects of their life

cycle [26]. The result is a flexible regulatory framework designed to improve pharmaceutical

manufacturing processes and enhance product quality [26]. QbD focuses on acquiring process

control through a deep understanding of products and processes using science, engineering

and quality risk management [27]. Moreover, QbD accelerates research timelines and reduces

development costs, by avoiding trial-and-error studies, and focusing on testing methods

towards product development [28-30]. As a result, the implementation of QbD can help to

reduce a regulatory burden that forces many product engineers to purposely design their

products to fit within existing approved thresholds in order to avoid seeking further time-

consuming approvals for minor variations [31].

The purpose our current work is to develop a robust new design framework for the

development of custom 3D printed surgical guides, bone implants and scaffolds, through the

QbD approach, and using quality risk management tools to help industry and research to

optimize resources and accelerate product development time frames. Such adaptation of the

QbD approach should facilitate product understanding to support innovation and efficiency

by reducing of costs and waste. The next stage of this project is for Daniel to conduct follow

up interviews with the companies visited during my Churchill Fellowship in addition to other

world-leading orthopaedic manufacturing companies to develop a list of the most critical risks

on product quality, including preventive and corrective actions to mitigate these risks from

an industry and research perspective. The findings will be presented to the TGA.

Figure 5. Workflow of additive manufacturing process for surgical cutting guides including main

quality control activities (adapted from [24])

Recommendations and Conclusions

The purpose of my Churchill Fellowship was to determine the potential for additive

manufacturing to be integrated into the management of children with bone deformities.

1. Equal time and effort should be invested in the quality processes that inform pre-

operative planning of surgery for complex lower limb deformities. More research on

advanced patient specific computational simulations is required to enable a more

objective surgical prescription process, and better understanding of actual loads

experienced by bones and implants during human movement.

2. The relationship between the orthopaedic surgeon and the design, or clinical, engineer is

crucial during the design phase of any custom 3D printed patient specific product. The

surgeon should be actively involved in the design phase of the product and be provided

an opportunity to gather hands on experience with any new surgical guide concepts using

anatomical models, and if possible, patient-specific saw bones.

3. The combination of effective collaborative pre-planning and additive manufacturing will

allow the surgeon to execute the surgical plan in theatre in an accurate, precise and

efficient manner. Nonetheless, it recommended that more research be conducted on the

efficacy of patient specific surgical guides, as there remains a paucity of research in this

area.

4. Design to manufacture of a 3D printed surgical guide should be a collaborative process

and include a team of trained professional to ensure quality control. Industry and

research institutions need to collaborate with regulatory authorities in the near future to

ensure product quality and safety, whilst not overburdening the quality control process

with redundant methodologies.

Future work and dissemination strategies

Since my return to Australia, I have engaged in follow up discussions with the companies I

visited during my fellowship, local Australian distributors of medical devices, university

researchers and medical professionals. I have also progressed a number of research projects

aimed at providing evidence for the application of 3D printing for medical devices in Australia.

Finally, I have been active in securing partnership funding to further research in this space.

Dissemination though presentation

I have been invited to provide presentations on my fellowship topics at the Queensland

Orthopaedic Physiotherapy Network conference on the 14th September 2018, the Australia and

New Zealand Paediatric Imaging conference on the 7th October 2018 and the Australian and

New Zealand Society of Biomechanics Conference on the 14th of December 2018. My colleagues

and I at Griffith University are assisting the Engineers Australia Biomedical College in developing

an event on the topic of 3D printing and the changes to the regulations of custom made medical

devices proposed by the TGA.

Research to address gaps in the literature

Prior to my Churchill Fellowship, I was successful in obtaining an Advance Queensland Mid-

Career Fellowship for the project ‘The Personalised Digital Patient: helping children with lower

limb deformities’. In brief, I will collaborate with an international medical device company,

Griffith University and Children's Health Queensland to apply digitally-enabled technology and

advanced manufacturing to create solutions for better health outcomes for children, and

generate commercial opportunities for the Australian medical device market. This project aims

to address a number of the abovementioned recommendations. At present, the project has

ethical approval to be conducted as a clinical trial in the Lady Cilento Children’s Hospital,

Brisbane. The clinical trial is registered as a phase one clinical trial with the Australian and New

Zealand Clinical Trials Registry. A collaborative clinical trials research agreement has been

established between Griffith University (manufacture of cutting guides) and Children’s Health

Queensland Hospital and Health Service. Finally, manufacture and use of the custom medical

device (i.e., the patient specific cutting guides) in the clinical trial has been acknowledged by

the TGA according to the Clinical Trial Notification Scheme.

Partnership funding

In August 2018, I was part of a team of chief investigators from Melbourne University, Flinders

University and Griffith University who successfully obtained $4M funding from the Australian

Research Council to lead an Industrial Training Transformation Centre over the next four years.

This Centre, focused on Medical Implant Technologies, will train a new generation of

interdisciplinary engineers and transform the orthopaedic and maxillofacial implant industry in

Australia into international leaders. While meeting the research and development needs of

local companies, it will build strong networks with hospitals and international collaborations.

Industry benefits include informed industry standards, more support for clinical research and

expansion into new markets. Australians will have improved procedures and assessments for

more reliable surgery with safer and successful outcomes. Faster recoveries and higher patient

satisfaction will increase demand. Advances in materials and savings in time for procedures and

translation will reduce costs.

Prototyping facility

My current and future projects will be facilitated by the support of Griffith University’s

Advanced Design and Prototyping Technologies Institute (ADaPT)

https://www.griffith.edu.au/advanced-design-prototyping-technologies-institute. ADaPT

brings together multi-disciplinary expertise across Griffith University in collaboration with

leading industry partners to push the boundaries in advanced design, prototyping and new

materials, in what is called the ‘next industrial revolution’ or Industry 4.0. Combining expertise

in micro and nano science, with big data analytics, artificial intelligence, complex medical

imaging and functional modelling and the latest in 3D printing and bioengineering, ADaPT will

be the flagship institute within the Gold Coast Health and Knowledge Precinct.

https://www.griffith.edu.au/advanced-design-prototyping-technologies-institute

References

1. Carty, C.P., et al., The effect of femoral derotation osteotomy on transverse plane hip

and pelvic kinematics in children with cerebral palsy: a systematic review and meta-

analysis. Gait Posture, 2014. 40(3): p. 333-40.

2. Caskey, P.M., et al., Gait outcomes of patients with severe slipped capital femoral

epiphysis after treatment by flexion-rotation osteotomy. J Pediatr Orthop, 2014. 34(7):

p. 668-73.

3. Abu Amara, S., J. Leroux, and J. Lechevallier, Surgery for slipped capital femoral

epiphysis in adolescents. Orthop Traumatol Surg Res, 2014. 100(1 Suppl): p. S157-67.

4. Prince, J.D., 3D Printing: An industrial revolution. Journal of Electronic Resources in

Medical Libraries, 2014. 11(1): p. 39-45.

5. Ho, C., et al., Laser resurfacing in pigmented skin. Dermatol Surg, 1995. 21(12): p.

1035-7.

6. Mazzoli, A., Selective laser sintering in biomedical engineering. Med Biol Eng Comput,

2013. 51(3): p. 245-56.

7. Bhatia, S.K. and S. Sharma, 3D-Printed prosthetics roll off the presses. Chemical

Engineering Progress, 2014. 110(5): p. 28-33.

8. Monzón, M., et al., Standardization in additive manufacturing: activities carried out by

international organizations and projects. Int. J. Adv. Manuf. Technol, 2015. 76(5-8): p.

1111-21.

9. Jackson, J.N., C.J. Hass, and B.J. Fregly, Development of a Subject-Specific Foot-Ground

Contact Model for Walking. J Biomech Eng, 2016. 138(9).

10. Pizzolato, C., et al., CEINMS: A toolbox to investigate the influence of different neural

control solutions on the prediction of muscle excitation and joint moments during

dynamic motor tasks. J Biomech, 2015. 48(14): p. 3929-36.

11. Tetsworth, K., S. Block, and V. Glatt, Putting 3D modelling and 3D printing into

practice: virtual surgery and preoperative planning to reconstruct complex post-

traumatic skeletal deformities and defects. SICOT J, 2017. 3(16).

12. Jonkers, I., et al. Towards a simulation-based understanding of musculoskeletal

deformity and their therapeutic remediation in children with cerebral palsy. in 8th

World Congress of Biomechanics. 2018. Dublin, Ireland.

13. Fregly, B.J. Generating Subject-specific Predictions of Human Movement. in 8th World

Congress of Biomechanics. 2018. Dublin, Ireland.

14. Lombardi, A.V., Jr., K.R. Berend, and J.B. Adams, Patient-specific approach in total knee

arthroplasty. Orthopedics, 2008. 31(9): p. 927-30.

15. Ng, V.Y., et al., Comparison of custom to standard TKA instrumentation with computed

tomography. Knee Surg Sports Traumatol Arthrosc, 2014. 22(8): p. 1833-42.

16. Schotanus, M.G., B. Boonen, and N.P. Kort, Patient specific guides for total knee

arthroplasty are ready for primetime. World J Orthop, 2016. 7(1): p. 61-8.

17. Silva, A., R. Sampaio, and E. Pinto, Patient-specific instrumentation improves tibial

component rotation in TKA. Knee Surg Sports Traumatol Arthrosc, 2014. 22(3): p. 636-

42.

18. Liu, X., et al., Evaluation of uit on titanium alloy residual stress eliminating by ultrasonic

residual stress measurement system Rev. Adv. Mater. Sci, 2013. 33: p. 266-269.

19. Savio, E., L. De Chiffre, and R. Schmitt, Metrology of freeform shaped parts. CIRP

annals, 2007. 56(2): p. 810-835.

20. Chen, F., G.M. Brown, and M. Song, Overview of 3-D shape measurement using optical

methods. Optical Engineering, 2000. 39(1): p. 10-23.

21. TGA, Consultation paper: Proposed regulatory changes related to personalised and 3D

printed medical devices, M.D. Brance, Editor. 2017.

22. TGA. Submissions received: Proposed regulatory changes related to personalised and

3D printed medical devices. 2018 [cited 2018 28/07/2018]; Available from:

https://www.tga.gov.au/node/842868.

23. Ituarte, I.F., et al., Additive manufacturing in production: a study case applying

technical requirements. Physics Procedia, 2015. 78: p. 357-366.

24. Martinez-Marquez, D., et al., Application of quality by design for 3D printed bone

prostheses and scaffolds. PLOS ONE, 2018. 13(4): p. e0195291.

25. Martinez-Marquez, D., et al. Quality by Design towards Standardization of 3D Printed

Bone Implants and scaffolds for Industry Translation. in 4th World Congress on

Electrical Engineering and Computer Systems and Sciences. 2018. Madrid, Spain.

26. Fahmy, R., et al., Quality by design I: application of failure mode effect analysis (FMEA)

and Plackett–Burman design of experiments in the identification of “main factors” in

the formulation and process design space for roller-compacted ciprofloxacin

hydrochloride immediate-release tablets. AAPS PharmSciTech, 2012. 13(4): p. 1243-

1254.

27. Vogt, F.G. and A.S. Kord, Development of quality‐by‐design analytical methods. Journal

of pharmaceutical sciences, 2011. 100(3): p. 797-812.

28. Krucoff, M.W., et al., Medical device innovation: prospective solutions for an

ecosystem in crisis. Adding a professional society perspective. JACC Cardiovascular

interventions 2012. 5(7): p. 790.

https://www.tga.gov.au/node/842868

29. Lawrence, X.Y., Pharmaceutical quality by design: product and process development,

understanding, and control. Pharmaceutical research, 2008. 25(4): p. 781-791.

30. Naidu, N.V.R., et al., Total quality management. Vol. 1. 2006, New Delhi: New Age

International (P) Ltd., Publishers.

31. Sangshetti, J.N., et al., Quality by design approach: Regulatory need. Arabian Journal

of Chemistry, 2014.

integrating additive manufacturing into the …...model output, i.e., compute a qualified guess of...

Documents