Quality versus emergency: How good were ventilation fittings produced by additive manufacturing to address shortages during the COVID19 pandemic?

OBJECTIVE: The coronavirus disease pandemic (COVID-19) increased the risk of shortage in intensive care devices, including fittings with intentional leaks. 3D-printing has been used worldwide to produce missing devices. Here we provide key elements towards better quality control of 3D-printed ventilation fittings in a context of sanitary crisis.
MATERIAL AND METHODS: Five 3D-printed designs were assessed for non-intentional (junctional and parietal) and intentional leaks: 4 fittings 3D-printed in-house using FDeposition Modelling (FDM), 1 FDM 3D-printed fitting provided by an independent maker, and 2 fittings 3D-printed in-house using Polyjet technology. Five industrial models were included as controls. Two values of wall thickness and the use of coating were tested for in-house FDM-printed devices.
RESULTS: Industrial and Polyjet-printed fittings had no parietal and junctional leaks, and satisfactory intentional leaks. In-house FDM-printed fittings had constant parietal leaks without coating, but this post-treatment method was efficient in controlling parietal sealing, even in devices with thinner walls (0.7 mm vs 2.3 mm). Nevertheless, the use of coating systematically induced absent or insufficient intentional leaks. Junctional leaks were constant with FDM-printed fittings but could be controlled using rubber junctions rather than usual rigid junctions. The properties of Polyjet-printed and FDM-printed fittings were stable over a period of 18 months.
CONCLUSIONS: 3D-printing is a valid technology to produce ventilation devices but requires care in the choice of printing methods, raw materials, and post-treatment procedures. Even in a context of sanitary crisis, devices produced outside hospitals should be used only after professional quality control, with precise data available on printing protocols. The mechanical properties of ventilation devices are crucial for efficient ventilation, avoiding rebreathing of CO2, and preventing the dispersion of viral particles that can contaminate health professionals. Specific norms are still required to formalise quality control procedures for ventilation fittings, with the rise of 3D-printing initiatives and the perspective of new pandemics.

Introduction

Non-Invasive Ventilation (NIV) and Continuous Positive Airway Pressure (CPAP) are standards of care for chronic hypercapnia and respiratory failure [1], sleep apnoea, and acute hypoxemia, such as in severe SARS-CoV-2 infections [2]. Several NIV and CPAP devices include fittings with intentional leaks, either on the ventilation mask itself, or between the mask and circuit, to prevent exhaled air to be rebreathed. Since the beginning of the COVID19 pandemic, exhaled particle dissemination has been documented [3] and emerged as an unexpected new problem with contamination risks for the immediate environment of ventilated patients.

To tackle this issue, non-ventilated masks have been proposed as a first-line option with the addition of an expelled expiration port (whisper swivel or similar) [3]. Antibacterial and viral filters interposed between the mask and the exhalation ports have also been proposed [3-6]. Thus, particle dispersion during ventilation could be controlled with sealed mask-interface connections [3].

During the pandemic, shortages in ventilation devices and specifically in fittings with intentional leaks occurred worldwide [7-12]. 3D-printing was extensively used to overcome shortages due to extraordinary needs and interruptions in supply chains, with little focus on quality control and risk management of medical devices requiring compliance to strict ISO standards and CE marking [13,14]. In fact, while 3D printing was successfully used as a versatile emergency solution in many centres in Europe and worldwide, showing its ability to act as a support solution during sanitary crises, the main issue recurrent issue in most reports was the lack of formal certification when medical devices were produced [14].

Within the trust of Greater Paris academic hospitals (Assistance Publique–Hôpitaux de Paris, AP-HP), the largest hospital trust in Europe grouping 39 hospitals, covering an area of over 10 million inhabitants, and employing nearly 100,000 people, a centralized 3D-printing initiative was launched in April 2020 with 60 professional Fused Deposition Modelling (FDM) 3D-printers (F120, F170 and F370, Stratasys, Eden Prairie, USA) and a team of 5 full-time engineers working 24/7 (BONE 3D, Paris). The aim of the project was to provide accelerated design and production services to all AP-HP employees facing various shortages due to the pandemic [15-17]. Over two hundred designs were produced from March to November 2020, with approximately 40,000 pieces printed and distributed within the AP-HP network. Among these designs, the central platform produced various models of ventilation devices, using black Acrylonitrile Butadiene Styrene (ABS) M-30 (№355–02112, Stratasys, Eden Prairie, USA) as a raw material. ABS is a widely used engineering thermoplastic with high durability, and printed ABS has up to 80% of the strength of injection-molded ABS, making it suitable for functional applications. ABS M-30 is characterized by its strength and toughness, while being lightweight and resilient: ultimate tensile strength 32 MPa, Izod impact strength (unnotched) 7%, and elongation at break 300 ohms (data provided by the manufacturer). In parallel, several hospitals within AP-HP had pre-pandemic local 3D-printing platforms and produced significant amounts of ventilation devices during the crisis–notably, Necker–Enfants Malades Hospital contributed to the COVID19 effort by printing ventilation fittings using Polyjet technology (J735, Stratasys, Eden Prairie, USA) with biocompatible transparent MED610 (Stratasys, Eden Prairie, USA) resin as a raw material. Finally, during the first wave of the pandemic, all AP-HP hospitals received generous daily deliveries of ventilation devices printed externally by independent makers owning private 3D-printers, or by various independent manufacturers, with little information on designs and production protocols, and thus insufficient quality control and difficult match with the real needs of clinical departments treating COVID19 patients [14].

The main objective of this study was to assess non-intentional and intentional leaks in a series of ventilation devices produced during the first wave of the pandemic and delivered to AP-HP clinical departments. We considered (1) in-house devices produced by the central AP-HP 3D-printing platform using FDM printing technique for which ABS was a raw material, (2) in-house devices produced by one academic AP-HP hospital using Polyjet printers and MED610 as a raw material, and (3) externally produced devices delivered to AP-HP by independent manufacturers. Our results suggest that in-house and external devices should be used only after professional quality control and that unsupervised 3D-printing of devices with intentional leaks can lead to harmful situations for patients and healthcare professionals. Rigorous approaches to quality control are furthermore mandatory steps to obtain certification for the 3D-printing of medical devices [18-20]. Finally, the rise in the use of 3D-printing and the unfortunate perspective of further pandemics should trigger the formulation of specific international standards dedicated to ventilation fittings.

Material & methods

Five models of 3D-printed ventilation fittings were considered: F22, F22M22, M22M22, M22M22M22T, and F18F20 (Fig 1, Table 1). All designs except M22M22M22T were expected to produce intentional leaks.

Fig 1

Five models of 3D-printed ventilation fittings: F22 (references №1 and №2), F22M22 (references №4, №4, and №10), M22M22 (references №5, №6, and №11), M22M22M22T (references №7 and №8), and F18F20 (references №9).

Table 1

Printing characteristics and quality control for non-intentional leaks.

Reference	Design	Technique	Wall thickness (mm)	Coating (yes/no)	Quality control
					Leak at rigid junction (yes/no)	Leak at rubber junction (yes/no)	Parietal leak (yes/no)
№1	F22	FDM (ABS)	0.7	yes	yes	no	no
№2	F22	FDM (ABS)	2.3	yes	yes	no	no
№3	F22M22	FDM (ABS)	0.7	no	yes	no	yes
№4	F22M22	FDM (ABS)	0.7	yes	yes	no	no
№5	M22M22	FDM (ABS)	0.7	yes	yes	no	no
№6	M22M22	FDM (ABS)	2.3	yes	yes	no	no
№7	M22M22M22T	FDM (ABS)	2.3	no	yes	no	yes
№8	M22M22M22T	FDM (ABS)	2.3	yes	yes	no	no
№9	F18F20	FDM (PLA)	NA	no	yes	yes	yes
№10	F22M22	Polyjet (MED610)	NA	NA	no	no	no
№11	M22M22	Polyjet (MED610)	NA	NA	no	no	no

Three different groups of 3D-printed devices were considered.

Devices manufactured in the central emergency 3D-printing platform of AP-HP using a F120 (Stratasys, Eden Prairie, USA) FDM printer: F22 (references №1–2), F22M22 (references №3–4), M22M22 (references №5–6), and M22M22M22T (references №7–8) produced by designers from BONE 3D (Paris, France) with black ABS-M30 (№355–02112, Stratasys, Eden Prairie, USA) and soluble support SR30 (№311–30200, Stratasys, Eden Prairie, USA);

FDM-printed F18F20 fittings (reference №9 –[6]) provided by Kernel Biomedical (https://3dleak.kernelbiomedical.com), printed with a Raise3D (Irvine, USA) machine using 1.75 mm Polylactic Acid (PLA) and 100 μm layers.

Devices manufactured at Necker–Enfants Malades University Hospital using a J735 Polyjet printer F120 (Stratasys, Eden Prairie, USA): F22M22 (reference №10) and M22M22 (reference №11), produced by designers from BONE 3D (Paris, France) with biocompatible transparent MED610 (Stratasys, Eden Prairie, USA) resin and waterjet removable support SUP705 (Stratasys, Eden Prairie, USA) support.

Two parameters were considered for devices printed at the central AP-HP platform using FDM machines: (1) wall thickness and (2) coating. Thin walls were defined at 0.7 mm (with 0.18 mm layer thickness) and thick walls at 2.3 mm (with 0.33 layer thickness); 100% filling was used for all devices. Coating consisted in impregnating the printed fittings after post-processing using Nano Seal 180W+ (JELN Imprägnierung, Schwalmtal, Germany) to improve wall sealing (Table 1).

Five models of industrial leak valves–providing continuous leak paths in CPAP patient circuits when used with CPAP and bi-level machines–were considered as controls: (1) whisper swivel II exhalation port (№332113, Philips, Amsterdam, Netherlands, reference №12), (2) disposable fixed exhalation port (DEP) with cap single-use (№312149, Philips, Amsterdam, Netherlands, reference №13), (3) leak valve row fixed (№24991, ResMed, San Diego, USA, reference №14), (4) WILAsilent swivel disposable exhalation port (№1139909, WILAmed, Kammerstein, Germany, reference №15), and (5) Silentflow 2 exhalation system (№WM23600, Lowenstein, Hamburg, Germany, reference №16) (Fig 2, Table 2).To screen for non-intentional leaks, we used an Astral 150 ventilator (ResMed, San Diego, USA) in double circuit with an adult profile and assist-control ventilation mode; 22 mm smoothbore tubes (Intersurgical, Wokingham, United Kingdom) were used to connect with the fittings. Rigid junctions when needed corresponded to Hudson RCI universal cuff connectors (№41421 and №41422, TeleFlex Medical, Wayne, USA). Rubber junctions corresponded to F15F22 lipped elastomeric connectors (№1701, Intersurgical, Wokingham, United Kingdom). Terminal obliterations of the fittings were obtained using 22F dust caps (№1978000, Intersurgical, Wokingham, United Kingdom) and smaller caps (inner diameter: 8 mm) from zeolite molecular sieves of Inogen One G3 (Inogen, Goleta, USA) oxygen concentrators. Maximum pressure was set at 85 cmH2O and fittings were immerged into water (see Discussion for the reference to the relevant regulatory texts). Leaks were screened for during five respiratory cycles for each fitting reference, with rigid and rubber junctions (Fig 3). All measures were performed twice: in May 2020, immediately after production, and in November 2021, 18 months after production.

Fig 2

Five models of industrial leak valves: (1) whisper swivel II exhalation port (reference №12), (2) disposable fixed exhalation port (DEP) with cap single-use (reference №13), (3) leak valve row fixed (reference №14), (4) WILAsilent swivel disposable exhalation port (reference №15), and (5) Silentflow 2 exhalation system (reference №16).

Table 2

Industrial leak valves used as controls.

Rendering adapted from images provided by the manufacturers.

Reference	Description	Brand
Reference №12	whisper swivel II exhalation port	Philips
Reference №13	Disposable Fixed Exhalation Port (DEP) with Cap Single-use	Philips
Reference №14	leak valve row fixed	Resmed
Reference №15	WILAsilent swivel disposable exhalation port	WILAmed
Reference №16	Silentflow 2 exhalation system	WILAmed

Fig 3

(a) Astral 150 ventilator (ResMed, San Diego, USA) in double circuit with an adult profile and assist-control ventilation mode used to assess non-intentional leaks; (b) M22M22M22T fitting (reference №7) with rubber junctions before being immerged into water for testing non-intentional leaks; (c) M22M22M22T fitting (reference №7) being tested for non-intentional leaks with rigid junctions, showing massive junctional leaks (red arrow); (d) F18F20 fitting (reference №9) being tested for non-intentional leaks with rigid junctions, showing significant junctional and parietal leaks (red circle indicated parietal leaks).

In order to screen for intentional leaks, we used a Vivo 45 positive pressure generator (Breas Medical, Mölnlycke, Sweden) in constant mode without humidifier (expiratory pressure relief, ramp off) with a slim circuit (№L327148, L3 Medical, Saint-Quentin-Fallavier, France), Hudson RCI universal cuff connectors (№41421, TeleFlex Medical, Wayne, USA) and an air guard filter (№1790000, Intersurgical, Wokingham, United Kingdom). A bacteria filter was connected between the ventilator and the breathing circuit. The leak valve was connected to the breathing circuit and a plug was placed in the mouth of the valve to measure the leakage during ventilation. Measurements were performed at five pressure values: 8, 10, 12, 14, and 16 cmH20 during five respiratory cycles (Figs 3 and 4).

Fig 4

Measurement system designed to assess intentional leaks.

All assessments were performed by ASV Santé (Genevilliers, France) by AML, KL, JPH, GB, RHK and DP. Data on printing time and costs were provided by BONE 3D (Paris, France).

Results

1. Non-intentional leaks (Table 1)

Industrial fittings (references №12–16) and Polyjet-printed fittings (references №10,11) had no leaks at rigid junctions, at rubber junctions, or parietal leaks. All FDM-printed fittings had leaks at rigid junctions (Fig 3), but this issue was tackled for the fittings printed within AP-HP (references №1–8) using rubber junctions. The FDM fitting printed by an external provider (reference №9) had persisting junctional leaks even with rubber junctions. All FDM-printed fittings (printed within AP-HP and from an external provider) had parietal leaks, even with thick walls (2.3 mm, reference №7), but this issue was tackled using coating (references №1,2,4,5,6,8), even for thin walls (0.7 mm, references №1,4,5). Close examination of devices after coating showed irregular junctional surfaces (Fig 5), potentially accounting for leaks when rigid junctions are used. Measures performed in May 2020 and in November 2021 showed identical results, supporting stable properties over time. The devices had been protected from light and stored in a medical office during this 18-months period.

Fig 5

(a) Right panel: effects of coating on intentional leaks. Green arrow: reference №1 –F22 fitting, thin walls (0.7 mm), without coating, showing open perforations designed to allow intentional leaks. Red arrow: reference №1 –F22 fitting, thick walls (2.3 mm), with coating, showing obliterated perforations designed to allow intentional leaks. (b) Left panel: effects of coating on junctions. Green circle: reference №7 –M22M22M22T fitting, thick walls (2.3 mm), without coating showing clean surfaces at junction (green circle). Red circle: reference №8 –M22M22M22T fitting, thick walls (2.3 mm), with coating showing irregular surfaces at junction.

2. Intentional leaks (Tables 2 and 3)

All industrial (references №12–16) and Polyjet-printed (references №10–11) fittings had satisfactory intentional leaks. FDM-printed fittings without coating had acceptable levels of intentional leaks (references №3,9) but knowing that these two models had parietal leaks and should not be used in practice. Coating systematically blocked intentional leaks, due to the presence of coating material into the areas designed to allow leakage (Fig 5). In clear, the technical measures necessary to control unintentional parietal leaks in FDM-printed fittings blocked intentional leaks.

3. Production characteristics (Table 4)

FDM-printed devices were produced faster than Polyjet-printed devices, and were considerably cheaper, for equivalent designs.

Discussion

Here we provide the first quality control assessment of an array of ventilation fittings produced during the first wave of the pandemic, from three different sources representing the suppliers of 3D-printed devices encountered by clinical departments during the crisis: (1) in-house dedicated emergency platforms, (2) in-house academic departments with previous 3D-printing experience, and (3) independent external makers. We show that 3D-printing can be a valuable solution to overcome shortages but only under strict supervision.

Intentional leaks have a significant impact on the effectiveness of non-invasive ventilation as they prevent rebreathing of expired CO2 [21] and should exceed 20 L/min when treating chronic respiratory failure and 22 L/min for acute respiratory failure [21,22]. We found average intentional leakage for all 3D models considered together at 13.5 ± 10.5 L/min, and at 25.8 ±5.0 L/min for control industrial models; this difference most probably reflects the effects of coating on the mechanical properties of FDM-printed devices: while coating seems mandatory to prevent parietal leakage, it interferes with intentional leaks and makes the devices unfit for clinical use (Fig 5).

Using ventilation devices with unintentional or insufficient intentional leaks can have severe clinical consequences, with detrimental effect on the effectiveness of NIV in acute and chronic conditions [23-26]. Similarly, leaks can aggravate nocturnal and diurnal hypoventilation [23-26] and contaminate the environment of the patient by diffusing viral particles [3,4]. This point is particularly relevant knowing that coating for FDM, although mandatory for preventing parietal leaks, leads to irregular surface at junctions, interfering with sealing and leading to unintentional leaks if rubber appliances are not used (Fig 5).

Our results stress the importance of professional 3D-printing protocols for producing critical devices such as ventilation fittings. In usual situations, the manufacture of such devices is subjected to the recent EU regulation 2017/745 (https://eur-lex.europa.eu/eli/reg/2017/745/oj), which limits emergency production due to demanding quality control and risk management protocols. To the best of our knowledge, these regulatory concerns were frequently mentioned but rarely addressed formally by the numerous teams who have produced 3D-printed ventilation fittings and other respiratory-related devices during the first wave of the pandemic [27-30], and few initiatives have been successfully certified by local regulatory authorities [31,32]. If further sanitary crises occur, in potential cases of temporary adaptations of this regulation to overcome shortages, our results strongly suggest that strict quality control assessments should be maintained, managed by teams experienced in medical 3D-printing, to eventually obtain formal certification. Choices in printing methods, such as Polyjet for instance, will depend on financial considerations (Table 4), on the background of the 3D-printing engineering teams, and on the volume of material required, including considerations on the conservation and rate of use of the printed devices [33-39].

Table 4

FDM and Polyjet printing time, requirements in raw materials and price.

Device	Time	Printing technique	Wall thickness (mm)	Resin	Support	Price
F22(design №1)	2h18	FDM	0.7	ABS: 16,41 cm3	SR30: 1,35 cm3	2,25 €
F22(design №2)	2h24	FDM	2.3	ABS: 15,8 cm3	SR30: 1,35 cm3	2,17 €
F22M22(designs №3–4)	3h40	FDM	0.7	ABS: 21,9 cm3	SR30: 4,5 cm3	3,36 €
M22M22(design №5)	3h24	FDM	0.7	ABS: 22,8 cm3	SR30: 1,08 cm3	3,03 €
M22M22(design №6)	3h24	FDM	2.3	ABS: 21,59 cm3	SR30: 1,08 cm3	2,87 €
M22M22M22T(designs №7–8)	4h13	FDM	2.3	ABS: 21,95 cm3	SR30: 9,12 cm3	3,96 €
F22M22(design №10)	4h20	Polyjet	2.0	MED610 (+ purge): 71g	SUP705: 30 g	13,48 €
M22M22(design №11)	4h18	Polyjet	2.0	MED610 (+ purge): 71 g	SUP705: 38 g	14,31 €

Interestingly, the methods for testing leaks of ventilation fittings are not codified by current international standards such as (1) EN 12342:1998+A1:2009 Breathing tubes intended for use with anaesthetic apparatus and ventilators, and (2) EN 13544–2:2002+A1:2009 Respiratory therapy equipment—Part 2: Tubing and connectors. The assessment method we used, although basic, provides clear answers to the clinical issues raised using 3D-printed fittings: occurrence of parietal leaks, occurrence of junctional leaks, and efficiency of intentional leaks. High pressures (85 cmH2O) used to evaluate non-intentional leaks may come out as extreme, especially regarding CPAP standards. However, such pressures may occur in the events such as coughing, and devices should remain sealed in situations with risks of viral particle diffusion. Beyond the current concerns related to the pandemic, our study underlines the need for a standardization of the quality control methods for ventilation tubes, knowing the current rise in the production of 3D-printed devices and specific risks caused by poorly designed and produced fittings.

Conclusion

Additive manufacturing is a valid technique for producing ventilation devices such as fittings with intentional leaks. Our results showed that both FDM with coating and Polyjet allow to obtain devices without parietal leaks. We also demonstrated that these physical properties are stable in time, at least for 18 months without exposition to light, supporting the perspective of the constitution of potential stocks of 3D-printed ventilation devices. FDM with coating nevertheless impaired several of the main properties of the fitting with intentional leaks by creating irregular junctions and obliterating the zones designed to lead intentionally. Based on these findings, our work strongly indicates that professional supervision is mandatory to choose the most relevant production technique, based on technical requirements and local financial constraints. FDM, although cheap and dependable, is not a straightforward approach for producing devices with intentional leaks. Polyjet seems to fulfil most requirements but is not easily available to healthcare professionals and is still expensive. We furthermore suggest that there is a critical need both for (1) defining clear protocols for 3D-printing emergency devices in case of further situations of shortage, and (2) standardizing assessment methods specifically dedicated to the quality control of ventilation fittings. Safety concerns should remain at the forefront, even during sanitary crises: while current regulations are not compatible with fast-track certification for emergency 3D-printing, the use of this technology in extreme situations in the future will only be conceivable based on the formulation of fast-track but reliable assessment methods for ventilation fittings.

STL file for references №1–2 (F22).

(STL)

Click here for additional data file.

STL file for references №3–4 (F22M22).

(STL)

Click here for additional data file.

STL file for references №5–6 (M22M22).

(STL)

Click here for additional data file.

STL file for references №7–8 (M22M22M22).

(STL)

Click here for additional data file.

Assessing leaks in reference №6: FDM-printed M22M22 with thick (2.3 mm) walls and coating, tested using rubber junctions.

Absence of junctional or parietal leaks.

(MOV)

Click here for additional data file.

Assessing leaks in reference №11: Polyjet-printed M22M22, tested using rigid junctions.

Absence of junctional or parietal leaks.

(MOV)

Click here for additional data file.

Assessing leaks in reference №9: FDM-printed F18F20, tested using rigid junctions.

Multiple junctional and parietal leaks.

(MOV)

Click here for additional data file.

4 Mar 2022

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Additional Editor Comments:

About suggested references by the reviewer, you could decide either to cite them or not, if they are not related to your topic. Moreover, all abbreviations need to be defined at first mentioning. The introduction should be extended and the novelty should be highlighted compared to the literature review, if there is any. The conclusion part could be rewritten one by one to highlight the obtained results. The number of references should be extended to 35 articles for a better literature review and also a better discussion. The scale bar should be added on images to know the size of samples. A microscopic image should be added besides Figure 3 to show the quality of samples. In Table 3, what is the dimension of the wall thickness? It is better to add a table for different parameters of 3D-printing for all specimens.

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Tables 1-3 are missing. So, it is not possible to follow the discussions made by the authors.

The reasons for using ABS for this particular application should be described.

The authors employed five models of industrial leak valves as controls. What are their specifications? What are the essential differences? Summarize this information in a table.

Provide a drawing of the ventilation fitting.

Reviewer #2: The additive manufacturing (AM) or 3D printing technique becomes a supplementary manufacturing process to meet the explosive demands of essential medical equipments and to ease the health disaster worldwide during COVID-19 pandemic in the last two years. In this manuscript, authors provide key elements towards a better quality control of 3D-printed ventilation fittings in a context of sanitary crisis using two different 3D techniques. The investigation is timely, worth for investigation, well-structured and easy to follow. Hence, I would recommend its acceptance. However, authors must incorporate some modifications:

1. In page 6, starting the line 'we considered (1) in house devices ..... AP-HP 3D- printing platform using FDM and ABS as a raw material,..", please correct to..... ".... using FDM printing technique in which ABS is used as a raw material".

Similarly, please correct.... "(2) in house devices produced........ using polyjet and MED610 as a raw material,............... to... "".... using PolyJet printing technique whereas MED610 is used as a raw material".

2. PolyJet is a printing technique. Replace polyjet everywhere in the manuscript by "PolyJet'

3. Please note that many 'articles' are missing in the manuscript, e.g. in Page 6... "......MED610 (Stratasys, Eden Prairie, USA) resin as raw material. " will be."......MED610 (Stratasys, Eden Prairie, USA) resin as a raw material. " (a is missing here

4. Finally, I must say that Literature section of the manuscript is very poor. Please note that there are several excellent publications appeared in the last one year in 3D printing and COVID19 crisis. Few more references must be mentioned here, e.g.,

Tareq et al. https://www.sciencedirect.com/science/article/pii/S0278612520302351

Andres et al. https://www.sciencedirect.com/science/article/pii/S0278612521000716

Hannah et al. https://www.sciencedirect.com/science/article/pii/S0278612521001473

Once authors revise the manuscript taking my aforementioned points into account, I will be happy to accept it.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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8 Mar 2022

Dear Editors of PLoS ONE,

Many thanks for your positive comments on our manuscript.

Please find in the following the requirements of the Academic Editor and of the reviewers (in bold characters) followed by our answers (in italics).

We hope that our manuscript, in its present form, will be more suitable for publication.

Thanks in advance for the time you will spend considering our re-submission.

Best regards,

RH Khonsari, for the co-authors

A. Academic editor

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Style requirements have been checked.

2. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files.

Tables have been included into the main manuscript.

3. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager.

ORCID ID has been provided.

4. About suggested references by the reviewer, you could decide either to cite them or not if they are not related to your topic. Moreover, all abbreviations need to be defined at first mentioning. The introduction should be extended, and the novelty should be highlighted compared to the literature review, if there is any. The conclusion part could be rewritten one by one to highlight the obtained results. The number of references should be extended to 35 articles for a better literature review and a better discussion.

These modifications have been performed, and the references have been extended to less that 35 articles, but including most of the recent relevant studies on the subject.

5. The scale bar should be added on images to know the size of samples. A microscopic image should be added besides Figure 3 to show the quality of samples. In Table 3, what is the dimension of the wall thickness? It is better to add a table for different parameters of 3D-printing for all specimens.

Required modifications to figures and tables have been performed. Close views of the devices in Figure 3 have been added.

B. Reviewer №1

1. Tables 1-3 are missing. So, it is not possible to follow the discussions made by the authors.

Tables 1-3 are now inserted into the main text.

2. The reasons for using ABS for this application should be described.

The authors employed five models of industrial leak valves as controls. What are their specifications? What are the essential differences? Summarize this information in a table. Provide a drawing of the ventilation fitting.

All these technical data have been added. The drawings of the ventilation fittings are provided in the tables.

C. Reviewer №2

1. In page 6, starting the line 'we considered (1) in house devices ..... AP-HP 3D- printing platform using FDM and ABS as a raw material,..", please correct to..... ".... using FDM printing technique in which ABS is used as a raw material".

This modification has been performed.

2. Similarly, please correct.... "(2) in house devices produced........ using polyjet and MED610 as a raw material,............... to... "".... using PolyJet printing technique whereas MED610 is used as a raw material".

This modification has been performed.

3. PolyJet is a printing technique. Replace polyjet everywhere in the manuscript by "PolyJet'

This modification has been performed.

4. Please note that many 'articles' are missing in the manuscript, e.g. in Page 6... "......MED610 (Stratasys, Eden Prairie, USA) resin as raw material. " will be."......MED610 (Stratasys, Eden Prairie, USA) resin as a raw material. " (a is missing here

This modification has been performed.

5. Finally, I must say that Literature section of the manuscript is very poor. Please note that there are several excellent publications appeared in the last one year in 3D printing and COVID19 crisis. Few more references must be mentioned here, e.g.,

Tareq et al. https://www.sciencedirect.com/science/article/pii/S0278612520302351

Andres et al. https://www.sciencedirect.com/science/article/pii/S0278612521000716

Hannah et al. https://www.sciencedirect.com/science/article/pii/S0278612521001473

More references (including references provided by Reviewer №2 have been added.

Submitted filename: Reponse to Reviewers.doc

Click here for additional data file.

10 Mar 2022

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Mohammad Azadi

Academic Editor

PLOS ONE

Journal Requirements:

Additional Editor Comments (if provided):

The revised article is not accepted and it should be carefully revised again. All changes should be highlighted in the revised article. Please be careful to address all comments. One example of not addressing the comment is to rewritten the conclusion part, one by one, to show the novelty. This issue was not done in the revision by authors. So please check all comments again, one by one, carefully. Moreover, mentioning "requirement modifications were performed" is not enough. More details should be mentioned and changes should be highlighted in the revised article. In addition, the scale bar in Figure 3 is too small and it could be read. The number of references is not extended and etc.

[Note: HTML markup is below. Please do not edit.]

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

13 Mar 2022

Dear editors of PLoS ONE,

Many thanks on your insightful comments on our manuscript. Please find in the following the list of the modifications required by the academic editor and the reviewers (in bold characters) followed by our answers (in italics).

We hope that our manuscript, in its present form, will be closer to your expectations.

Thanks in advance for the time you will spend considering our revisions.

Best regards,

RH Khonsari, for the co-authors.

A. Academic editor

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

Style requirements have been checked.

2. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files.

Tables have been included into the main manuscript.

3. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager.

ORCID ID has been provided.

4. About suggested references by the reviewer, you could decide either to cite them or not if they are not related to your topic. Moreover, all abbreviations need to be defined at first mentioning. The introduction should be extended, and the novelty should be highlighted compared to the literature review, if there is any. The conclusion part could be rewritten one by one to highlight the obtained results. The number of references should be extended to 35 articles for a better literature review and a better discussion.

All abbreviations (such as FDM for instance) have been defined when first used. The introduction has been extended with the addition of two paragraphs: one on the importance of regulation issues and another one on the technical choices made by our team (choice of FDM, choice of ABS). The conclusion has been also extended and now includes a list of the main points raised by this paper: (1) potentialities of 3D printing in producing ventilation devices during crises, (2) need for technical skills in the production of medical devices, (3) need for support from the regulation bodies, and (4) need for a clarification of assessment panels, especially for fittings with intentional leaks. The references have furthermore been extended to more than 35 articles, and now including most of the recent relevant studies on the subject.

5. The scale bar should be added on images to know the size of samples. A microscopic image should be added besides Figure 3 to show the quality of samples. In Table 3, what is the dimension of the wall thickness? It is better to add a table for different parameters of 3D-printing for all specimens.

Required modifications to figures and tables have been performed. A new table has been added with the characteristics of the commercial devices we included into the assessment. Close views of the devices in Figure 3 have been added and a larger scale bar (1 cm) has been included.

B. Reviewer №1

1. Tables 1-3 are missing. So, it is not possible to follow the discussions made by the authors.

Tables 1-3 are now inserted into the main text.

2. The reasons for using ABS for this application should be described.

The authors employed five models of industrial leak valves as controls. What are their specifications? What are the essential differences? Summarize this information in a table. Provide a drawing of the ventilation fitting.

All these technical data have been added in the introduction. The drawings of the ventilation fittings are provided in a new table dedicated to the commercial fittings we included into the assessment (also following a requirement of the academic editor).

C. Reviewer №2

1. In page 6, starting the line 'we considered (1) in house devices ..... AP-HP 3D- printing platform using FDM and ABS as a raw material,..", please correct to..... ".... using FDM printing technique in which ABS is used as a raw material".

This modification has been performed.

2. Similarly, please correct.... "(2) in house devices produced........ using polyjet and MED610 as a raw material,............... to... "".... using PolyJet printing technique whereas MED610 is used as a raw material".

This modification has been performed.

3. PolyJet is a printing technique. Replace polyjet everywhere in the manuscript by "PolyJet'

This modification has been performed.

4. Please note that many 'articles' are missing in the manuscript, e.g. in Page 6... "......MED610 (Stratasys, Eden Prairie, USA) resin as raw material. " will be."......MED610 (Stratasys, Eden Prairie, USA) resin as a raw material. " (a is missing here

This modification has been performed.

5. Finally, I must say that Literature section of the manuscript is very poor. Please note that there are several excellent publications appeared in the last one year in 3D printing and COVID19 crisis. Few more references must be mentioned here, e.g.,

Tareq et al. https://www.sciencedirect.com/science/article/pii/S0278612520302351

Andres et al. https://www.sciencedirect.com/science/article/pii/S0278612521000716

Hannah et al. https://www.sciencedirect.com/science/article/pii/S0278612521001473

More references, including references above, have been added, also following a requirement of the academic editor.

Submitted filename: response_PLoS.doc

Click here for additional data file.

30 Mar 2022

Quality versus emergency: how good were ventilation fittings produced by additive manufacturing to address shortages during the COVID19 pandemic?

PONE-D-22-02617R2

Dear Dr. Khonsari,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Mohammad Azadi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

It is accepted based on the reviewers' comments. Only please remove the reference in the conclusion part when the proof file will be sent to you. It should be moved to the discussion part.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: Authors took all of my comments into account and improved the manuscript significantly. Hence, I am happy to accept it now.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

13 Apr 2022

PONE-D-22-02617R2

Quality versus emergency: how good were ventilation fittings produced by additive manufacturing to address shortages during the COVID19 pandemic?

Dear Dr. Khonsari:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Mohammad Azadi

Academic Editor

PLOS ONE

Table 3

Quantification of intentional leaks at 5 increasing pressure levels.

References №7–8 have been excluded as T-fittings are not designed to produce intentional leaks. Bold characters: pressure values above 20 cmH2O.

	Design	Technique	Wall thickness (mm)	Coating	Pressure (cmH2O)
					8	10	12	14	16
Reference №1	F22	FDM (ABS)	0.7	yes	0–5	0–5	5–10	5–10	5–10
Reference №2	F22	FDM (ABS)	2.3	yes	0–5	0–5	0–5	0–5	0–5
Reference №3	F22M22	FDM (ABS)	0.7	no	15–20	15–20	20–25	20–25	20–25
Reference №4	F22M22	FDM (ABS)	0.7	yes	0–5	0–5	0–5	0–5	0–5
Reference №5	M22M22	FDM (ABS)	0.7	yes	0–5	0–5	0–5	0–5	0–5
Reference №6	M22M22	FDM (ABS)	2.3	yes	0–5	0–5	0–5	0–5	0–5
Reference №9	F18F20	FDM (PLA)	2.0	no	20–25	25–30	25–30	30–35	30–35
Reference №10	F22M22	Polyjet (MED610)	2.0	NA	15–20	15–20	15–20	20–25	20–25
Reference №11	M22M22	Polyjet (MED610)	2.0	-	5–10	5–10	5–10	5–10	10–15
Reference №12	-	industrial	-	-	15–20	20–25	25–30	25–30	30–35
Reference №13	-	industrial	-	-	15–20	15–20	20–25	20–25	20–25
Reference №14	-	industrial	-	-	20–25	25–30	30–35	30–35	30–35
Reference №15	-	industrial	-	-	15–20	20–25	20–25	25–30	30–35
Reference №16	-	industrial	-	-	15–20	20–25	20–25	25–30	25–30