ibim tariah ph.d technical director, healthcare solutions · technical director, healthcare...

$: Ibim Tariah Ph.D Technical Director, Healthcare Solutions · Technical Director, Healthcare Solutions ... by Directive 2007/47 ... to help identify potential gaps\ഠtoward CE Marking$
Copyright © 2014 BSI. All rights reserved. 1

Ibim Tariah Ph.D Technical Director, Healthcare Solutions

BSI 2014 Medical Device Mini-Roadshow

Understanding Clinical Equivalence


• Review Requirements from Directives on Medical Devices

• Examine Definition of Medical Devices • Review EU Commission Guidelines on:

• Clinical Evaluation of Medical Devices (MEDDEV 2.7.1) • Post Market Clinical Follow-up (PMCF) Studies (MEDDEV

2.12/2) • Practical Example

Understanding Clinical Equivalence


EU Directives on Medical Devices

Copyright © 2014 BSI. All rights reserved. 4 Copyright © 2014 BSI. All rights reserved.

EU Directives on Medical Devices

MDD & AIMD modified by Directive 2007/47/EC, effective 21 Mar 2010 • MDD: ER 6a – Demonstration of conformity with the

essential requirements must include a clinical evaluation in accordance with Annex X

• AIMD: ER 5a - Demonstration of conformity with the essential requirements must include a clinical evaluation in accordance with Annex 7

Presenter

Presentation Notes

As part of the Mar 2010 revisions to the MDD and the AIMD, it was emphasized that a Clinical Evaluation was necessary for all classes of devices to demonstrate conformity with the ERs.


Annex X (MDD) / Annex 7 (AIMD) • As a general rule, confirmation of conformity with the

requirements concerning the characteristics and performances … must be based on clinical data.

• The clinical evaluation: 1.1.1 either a critical evaluation of the relevant scientific

literature currently available relating to the safety, performance, the design characteristics and the intended purpose of the device, where: o there is demonstration of equivalence of the device with that to which

the data relates and, o the data adequately demonstrate compliance with the relevant

Essential Requirements;

1.1.2 or a critical evaluation of the results of all clinical investigations made;

1.1.3 or a critical evaluation of the combined clinical data provided in 1.1.1 and 1.1.2 above.

Presenter

Presentation Notes

The requirements detailing this were also clarified in Annex X / 7. Bottom line, conformity must be based on clinical data. Can come from relevant scientific literature (as detailed through the clinical evaluation), or Clinical investigation on the device, or Both Clinical Evaluation and Clinical Investigation.


Annex X (MDD) / Annex 7 (AIMD)

Clinical Investigations: •MDD: In the case of implantable devices and devices in Class III clinical investigations shall be performed unless it is duly justified to rely on existing clinical data.

•AIMD: Clinical investigations shall be performed unless it is duly justified to rely on existing clinical data.

Presenter

Presentation Notes

It should be emphasized that clinical investigations are expected for all AIMD devices and implantable / class III MDD devices unless it is duly justified to rely on existing data. If a Mfr. is unsure whether they need to do a Clinical Investigation or not, they should discuss this with their Notified Body. Many notified bodies provide services to help identify potential gaps toward CE Marking in a prepared Clinical Evaluation Plan prior to execution.


Clinical Evaluations: • Many devices developed by incremental innovation, so they are not completely novel • Often possible to draw on the clinical experience and literature reports of the safety and

performance of equivalent devices to establish the clinical evidence • Requires comprehensive analysis of pre- and post-market clinical data relevant to the intended

use • data specific to the device in question • data relating to devices claimed as equivalent

2013 Medical Device Roadshow

Annex X (MDD) / Annex 7 (AIMD)

Presenter

Presentation Notes

Since many devices are developed incrementally and are not completely novel, it is often possible to draw on the clinical experience of equivalent devices. The CER requires comprehensive analysis of data relevant to the intended use that pertains either to the device in question, or to devices claimed to be equivalent.


Annex X, Sec 1.1c (MDD) / Annex 7, Sec. 1.2 (AIMD)

CER Updates: •CER must be actively updated with data obtained from the post-market surveillance.

•Where post-market clinical follow-up (PMCF) as part of the post-market surveillance (PMS) plan for the device is not deemed necessary, this must be duly justified and documented.

Presenter

Presentation Notes

Annex X / 7 go on to sat that the CER must be actively updated with data from PMS. In addition, if post-market clinical f/u (or PMCF) is not deemed necessary, this must be duly justified. It is not sufficient just to say “PMCF does not need to be done”, the reason must be duly justified.


Where demonstration of conformity with ERs based on clinical data is not deemed appropriate:

• Adequate justification for any such exclusion has to be given based on risk management output and under consideration of the specifics of the device/body interaction, the clinical performances intended, and the claims of the manufacturer.

• Adequacy of demonstration of conformity with the essential requirements by performance evaluation, bench testing and pre-clinical evaluation alone has to be duly substantiated.

Annex X, Sec 1.1d (MDD) / Annex 7, Sec. 1.5 (AIMD)

Presenter

Presentation Notes

This clause is really only applicable to the lowest risk devices. Whenever a NB audits a technical file, even for a low-risk Class IIa, they will be looking for a clinical evaluation, even if it is just a review of the literature that shows the device is so safe and so well known that no one is publishing anything on it any more. And would then expect reference to the risk evaluation and the objective evidence available to demonstrate that the risks are adequately mitigated. This is still a clinical evaluation – it is still necessary to demonstrate how you know that the device will perform safely and effectively.


Definition of a Medical Device


Definition of “Medical Devices”

MDD/AIMD – Article 1 • Formal definition

MEDDEV 2.1/1 • Medical devices are defined as articles which are intended to

be used for a medical purpose • Products intended to have a toiletry or cosmetic purpose are

not medical devices even though they may be used for prevention of a disease.

• Products with a multiple purpose which may be used occasionally in a medical environment are normally not medical devices, unless a specific medical intended purpose is assigned to them.

Presenter

Presentation Notes

Article 1 (MDD & AIMD) discusses that a medical device includes any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination . . . used for human beings for the purpose of: diagnosis, prevention, monitoring, treatment or alleviation of disease diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap investigation, replacement or modification of the anatomy or of a physiological process control of conception and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means MEDDEV 2.1/1 goes on to say that MEDICAL DEVICES are intended to have a MEDICAL PURPOSE. Therefore, devices intended to have a toiletry or cosmetic purpose are not medical devices. Products w/ multiple purposes are not normally considered MEDICAL DEVICES unless a specific intended purpose is assigne\d.


EU Commission Guidelines on the Clinical Evaluation of Medical Devices


Presenter

Presentation Notes

MEDDEV 2.7.1 is the Key guidance to consider when constructing the CER. This was created based on the GHTF guidance and provides guidance for both the MFR. and the NB.


MEDDEV 2.7.1

• Reflects positions taken in particular by representatives of National Competent Authorities and Commission Services, Notified Bodies, industry and other interested parties in the MEDICAL DEVICEs sector

• Guidelines not legally binding . . . alternative approach may be possible or appropriate to comply with requirements

• It is anticipated that the guidelines will be followed within the Member States

Presenter

Presentation Notes

The forward discusses that this document reflects the position of the Competent Authorities, the Commission, NBs, Industry, and others and while it is not legally binding, it is anticipated that it will be followed.


Sections: 5. General principles of Clinical Evaluation 6. Sources of data / documentation (Stage 1) 7. Appraisal of clinical data (Stage 2) 8. Analysis of clinical data (Stage 3) 9. The CER 10. Role of the Notified Body (NB)

Appendices: A – E: Sample formats / methodologies F: NB Clinical Evaluation Checklist

MEDDEV 2.7.1 – Key Contents

Presenter

Presentation Notes

There are 6 sections in the body of the document which provide guidance for the Mfr. and 6 Appendices which provide guidance for the NBs. The MFR. should review ALL parts of the MEDDEV. The sections in red contain key contents on Equivalence. It is also worth noting that Sec. 5 includes the requirements of WHO should perform / evaluate the CER. This could include indiviuals internal or external to the organization including independent clinicians if warranted. It is up to the Mfr. to justify appropriate competencies are involved.


Section 5.1 – Scope of CER: • Devices should have the same intended use and will need to be

compared with respect to their technical and biological characteristics. • Intended use relates to the clinical condition being treated, the

severity and stage of disease, the site of application to/in the body and the patient population

• Technical characteristics relate to the design, specifications, physiochemical properties including energy intensity, deployment methods, critical performance requirements, principles of operation and conditions of use

• Biological characteristics relate to biocompatibility of materials in contact with the same body fluids/tissues.

• Characteristics should be similar to extent that there would be no clinically significant difference in the performance and safety of the device.

MEDDEV 2.7.1 – “Equivalent Devices”

Presenter

Presentation Notes

Sec. 5.1 states that EQUIVALENT DEVICES should have the same intended use and need to be compared relative to technical and biological characteristics. The section provides detail on what is expected for each of these comparisons for the devices to be considered equivalent.


Appx. E, Sec. 4 – Possible format for CER • Clearly state if the clinical data used in the evaluation are

for an equivalent device. • Identify the equivalent device(s) and provide a

justification of the equivalency, cross-referenced to the relevant non-clinical documentation that supports the claim.

Appx. F, Sec. 3.2.3 – NB Checklist • If differences are identified, an assessment must be done

to demonstrate potential significance of differences on safety & performance


Presenter

Presentation Notes

Although no single format is required, some Mfrs may develop a template for easier compilation and consistency. Appx. E provides an example. A key take-home point is that the CER must clearly state if the clinical data are for an EQUIVALENT device and that data should be provided to support this claim. Appx. F contains a very critical part of the evaluation. It sates that if differences are noted between the subject and comparable devices, an assessment must be done to demonstrate the potential significance of the differences on safety and performance in order to judge the relevancy of the clinical data presented. Unfortunately, this is frequently NOT done.


Appx. F, Sec. 3.2.3 (Footnote) – Meaning of Equivalence • Clinical:

• C1 - same clinical condition or purpose • C2 - same site in the body • C3 - similar population (including age, anatomy, physiology) • C4 - similar relevant critical performance for specific intended use

• Technical: • T1 - similar conditions of use • T2 - similar specifications and properties • T3 - similar design • T4 - similar principles of operation

• Biological: • S1 - same materials in contact with the same tissues or body fluids


Presenter

Presentation Notes

Furthermore, Appx. provides a very detailed definition of how equivalence should be judged. Note that some characteristics say same, some say similar. This is not to say that if the characteristic says “the same” and it is not “the same”, it cannot be considered equivalent. However, the discussion on the clinical impact of the differences needs to be robust in order to draw equivalence.


FDA Predicate Device ≠ MEDDEV 2.7.1 equivalent device

Substantially equivalent predicate device (per FDA): • Device has the same intended use as the predicate; and • Device has the same technological characteristics as the

predicate;

OR

• Device has the same intended use as the predicate; and • Device has different technological characteristics and the

information submitted to FDA; • does not raise new questions of safety and effectiveness; and • demonstrates that the device is at least as safe and effective as

the legally marketed device.

FDA – “Predicate Devices”

Presenter

Presentation Notes

It should be empasized that FDA Predicate Device substantial equivalence MEDDEV 2.7.1 equivalent device The FDA states that a device is substantially equivalent if, in comparison to a predicate it: has the same intended use as the predicate; and has the same technological characteristics as the predicate; �or has the same intended use as the predicate; and has different technological characteristics and the information submitted to FDA; does not raise new questions of safety and effectiveness; and demonstrates that the device is at least as safe and effective as the legally marketed device. These are different concepts.


• Equivalence should be substantiated based on a detailed assessment.

• Focus should be on discussing the DIFFERENCES rather than highlighting the SIMILARITIES.

• Some devices have very narrow clinical purposes (such as hip replacements) but others have multiple purposes (such as meshes or dressings or fillers). In these cases, equivalent devices should have the same purposes.


Presenter

Presentation Notes

The literature for the equivalent devices should have the same purpose as that of the subject device.


Device Equivalence Example

• Are devices which are “EQUIVALENT” to your device available on the market?

• Are clinical data available for these devices?

21

Presenter

Presentation Notes

These are the fundamental questions. The answer to both must be YES to utilize the Equivalent Device pathway.


Clearly Not Equivalent

22

Not equivalent Both fruits but different types

– shape, consistency, taste, edible vs. inedible skin Differences clearly impact function and use


Clearly Equivalent

Equivalent Same variety, colour, etc.

Can use data from one to assume performance will be the same.


Equivalence Must be Justified

Both apples Different varieties

– colour, taste, crunch, dessert or cooking? How do the differences impact their function or use?


Stage 1* Identify clinical data from: • Literature searching & / or • Clinical experience & / or • Clinical Investigation

Stage 2 Appraisal of individual data sets: • Suitability • Contribution of results to demonstration

of performance and safety

Stage 3 Analysis of relevant data: • Strength of overall evidence • Conclusion about performance

and safety

Generate new or add’l clinical data

Produce CER

Is clinical evidence sufficient to be able to

declare conformity with relevant

ERs?

Yes

No

* Conformity to harmonized performance standard may be sufficient to demonstrate compliance to ERs

Figure 1:

http://ec.europa.eu/enterprise/policies/european-standards/harmonised-standards/medical-devices/index_en.htm

MEDDEV 2.7.1 – CER Construction

Presenter

Presentation Notes

3 Stages: Identify Appraise Analyze the relevant data Decide if information is sufficient. If not, GENERATE MORE. Red shaded boxes frequently not done or conclusions reached are not supported by data. Conformity to ERs must be demonstrated for ALL INDICATIONS.




Stepwise Approach • Identify potential “equivalent devices” for search strategy

MEDDEV 2.7.1 – “Equivalent Devices” Example:

A C B E D F Subject G • Identify data (CER Stage 1) – Discover clinical data on A, B, C, F, and

unknown device G • Appraise data (CER Stage 2) – Determine device C is not equivalent and data for F is weak (small sample size) • Analyze data (CER Stage 3) – Data from A, B, & G supports safety & performance but gap identified

• Repeat as warranted – Search again on device G • Write CER

• Justify Equivalence on Devices A, B, and G • Write PMS Plan (to include PMCF for subject device)

Presenter

Presentation Notes

Quick example showing stepwise approach for using data from equivalent devices.


• For devices cited in literature

Demonstration of equivalence Example:

Parameter Subject Device

Comparative Devices Potential Clinical Impact of Differences Device A Device B Device G

Picture

Indications

Contraindications

Material

Sizes

Design

Lifetime

Etc.

Key Parameters

Based on expert analysis Source of data should be cited

EQUIVALENT

EQUIVALENT

EQUIVALENT

EQUIVALENT?

Presenter

Presentation Notes

The Demonstration of equivalence might look like this. Comparison devices included in equivalence demonstration may be subset of devices included in search criteria. Key parameters should include parameters that impact technical and biological characteristics or are associated with complications Potential clinical impact section should address whether subject device is expected to encounter complications / performance demonstrated by comparative devices. There is a presumption that each comparative device is equivalent in total. If key design features come from multiple devices and safety and performance is not known when all features are brought together, equivalence may be challenged by the Notified Body.

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=jT-lmrodOgKpuM&tbnid=5gfLQ3_DAutRbM:&ved=0CAUQjRw&url=http://www.mynamesnotmommy.com/yes-there-are-dumb-questions/question-mark/&ei=yLILUp_kDOL-iwKPmICACg&bvm=bv.50723672,d.aWc&psig=AFQjCNHE3N6f6_5cGuRtQGczNXsqagmRUA&ust=1376584701726718


Equivalent Devices – Watch-Outs • Equivalent devices not identified • Equivalent devices not EU medical devices • Improper equivalent devices identified – not equivalent for clinical,

technical, and biological • Piecing equivalent features out of multiple devices • Gaps in demonstration of equivalence – insufficient data / information

• Not all information in public domain • Preclinical data can be used to fill in gaps

• Equivalence argument does not cover key parameters that may impact safety or performance

• Differences from subject device not characterized • Potential clinical impact of differences not discussed • Citations do not identify devices used or other key information

• Manufacturer must demonstrate (i.e. justify) equivalence with the device

Presenter

Presentation Notes

Lack of documentation of devices used in studies tends to be more problematic the lower the device class. Nevertheless, the manufacturer must demonstrate equivalence with the device used (somehow). Alternatively, consider whether it can be justified that clinical data are not required to demonstrate conformity with the ERs (MDD Annex X, Sec. 1.1d / AIMD Annex 7, Sec. 1.5).

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=r96KWTUYdH1l4M&tbnid=dCmU40XP-M5cyM:&ved=0CAUQjRw&url=http://learningorganizations.wordpress.com/2010/12/05/watch-out-do-not-mix-up/&ei=5RABUqBHgYWIAoGMgJgI&bvm=bv.50310824,d.cGE&psig=AFQjCNFoyLpdKUDUkU8rRaUDSYvjFl1reA&ust=1375887860463447


BSI Examples Where Equivalence Argument Has Been Rejected • Devices are judged to be alternate treatments

• Composed of different materials in contact with tissues resulting in different biological response (e.g. biologic vs. synthetic)

• Dissimilar material form (e.g. sheets vs. granules vs. foam) • Dissimilar principles of operation (e.g. stop bleeding by pressure

vs. natural hemostasis vs. included medicinal agent) • Vastly different absorption profiles (e.g. non-absorbable devices

claimed to be equivalent to absorbable ones) • Different clinical uses (e.g. hemostasis vs. aid to wound healing)

• Only clinical data available for equivalent device is for off-label use


CER Stage 2: Data Appraisal – Merits/Limitations • Suitability – appraise quality and relevance

• characterize merits / limitations • document reasons for exclusions

• Contribution – weigh value by considering confounding influences • underlying medical conditions • concomitant treatment(s) • bias


Presenter

Presentation Notes

Must have method in place to judge the Suitability and Contribution of the citation This is done in Stage 2.


• CER Stage 2: Data Appraisal – Suitability Appx D Example:


? Weight

?

Presenter

Presentation Notes

Example from Appx. D After suitability is assessed, then there should be a judgment about the relative weight that should be given to each article. For example, should clinical data for other (non-equivalent) devices used in different patient groups or data for equivalent devices with major deviations in device application even be considered?



• CER Stage 3: Data Analysis – Sufficiency • If clinical literature is presented for equivalent devices,

• is this clinical data when taken together with the available preclinical data sufficient to demonstrate conformity with ERs covering safety and performance of the device in question under normal conditions of use?

• are there gaps in either the demonstration of compliance with each relevant essential requirement or in the demonstration of equivalence that needs addressing through the means of a specifically designed clinical investigation(s)?

• is the data sufficient to address the clinical hazards identified in the risk analysis?

• If no, a clinical investigation(s) will be needed. The objectives of the clinical investigation(s) should focus on those aspects not sufficiently addressed by the available data.

Presenter

Presentation Notes

Stage 3 covers the analysis to determine sufficiency. The questions shown here must be answered.


EU Commission Guidelines on Post-Market Clinical Follow-up (PMCF) Studies


MEDDEV 2.12/2 - PMCF Studies

Circumstances that may justify PMCF studies include: • Innovation, unanswered questions on long-term safety and performance,

emergence of new information on safety and performance • High risk design, materials, components, invasiveness, clinical procedures,

anatomical locations, target populations • Severity of disease, unstudied subpopulations, interaction with other

medical products or treatments • Generalizability of pre-market clinical data • Verification of safety and performance when exposed to a larger and more

varied population of users • Risks identified from literature, adverse events, clinical investigations or

PMS • Where CE marking was based on equivalence.

Focus of PMCF Subject Device

Presenter

Presentation Notes

I’ve listed some of the reasons why PMCF may be warranted but relative to this talk, one of the key reasons PMCF is warranted is when CE marking was based on equivalence. The focus of PMCF is the subject device!


Clinical data from PMCF Studies: • Not intended to replace the pre-market data necessary to demonstrate

conformity with the provisions of the legislation. • Critical to update the clinical evaluation throughout the life-cycle of the

medical device and to ensure the long term safety and performance of devices after their placing on the market.

• The objective is to confirm clinical performance and safety, the acceptability of identified risks, and to detect emerging risks on the basis of factual evidence.

• Provides real world experience obtained in larger, heterogeneous and more complex populations, with a broader (and potentially less experienced) range of end-users than is usually the case with clinical investigations.



Clinical data from PMCF Studies: • Most useful for identifying less common but serious device-related

adverse events; providing long term information about safety and performance, including durability data and information about failure modes; and elucidating the end-user “learning curve”.

• Particularly useful source of clinical data for low risk devices that are based on long standing, well-characterised technology and, therefore, unlikely to be the subject of either reporting in the scientific literature or clinical investigation.



Practical Example


Subject Device – Mesh A • Absorbable PLLA knitted mesh • Intended Use: For the repair of hernia, uterovaginal prolapse, and other

fascial deficiencies that require the addition of a reinforcing or bridging material to obtain the desired surgical result.

• 4 Sizes (10 x 15 cm, 15 x 20 cm, 30 x 35 cm, 30 x 50 cm) • Absorption time: 3 years

Assessing Device Equivalence

Potential Equivalent Device – Mesh B • 2 Layer co-knitted Mesh composed of non-absorbable polypropylene (top)

and co-knit of absorbable PLA/PGA copolymer (bottom) • Intended Use: For tissue reinforcement and long-lasting stabilization of

fascial structures of the abdominal wall during open and laparoscopic inguinal hernia repair.

• 4 sizes (10 x 10 cm, 10 x 15 cm, 20 x 20 cm, 20 x 30 cm) • Absorption time (absorbable component): 4 months



Justification for Device Equivalence: • Meshes A and B have been used successfully in the US for the repair of soft

tissue deficiencies and have been judged to be substantially equivalent. The materials used all have a long history of implant use and biocompatibility per ISO 10993 and the devices are offered in similar size ranges. Each can be fixated with sutures or tacks and maintain sufficient strength past 12 weeks to allow healing to occur. After this time, the presence of the mesh is no longer necessary.

• Adverse event (AE) rates associated with the subject device (per the cited literature) are low (0 – 2%) compared to that for Mesh B (2 – 6%). The AE rates of both meshes compare favorably to non-absorbable Polypropylene meshes (10 – 20%) which have been considered the gold standard for decades. The primary complications include infection, pain, adhesions, recurrence, contracture, erosion, and extrusion.

Did justification substantiate device equivalence?

Presenter

Presentation Notes

Does the justification as presented substantiate equivalence of devices A & B? If not, why not? The following should be considered: Reference made to devices being “substantially equivalent” (per FDA) rather than “equivalent” per MEDDEV 2.7.1 Does not expressly discuss clinical, technical, and biological characteristics that are important to device or discuss the potential clinical impact of the differences. Clinical Uses that May be Important: Device A used in uterovaginal prolapse whereas Device B is not – if data are only available on Device B, this indication would not be covered Technical Characteristics that May be Important: Device A is fully absorbable whereas Device B is only partially absorbable - there are likely to be differences in performance Device A is available in much larger sizes than Device B – there might be issues related to size There is no information on key characteristics such as strength/strength retention, stiffness, pore size, method of application, etc. No data (e.g. preclinical studies, risk analyses) were presented to substantiate equivalence Biological Characteristics that May be Important: Device A is not the same material as Device B and is not used in the same tissues. While the justification states that both materials are compatible to ISO 10993, there is no justification for equivalence. It is unlikely that absorbable and partially absorbable materials could be considered equivalent.



Device Equivalence Not Substantiated: • Reference made to devices being “substantially equivalent” (per FDA) rather than

“equivalent” per MEDDEV 2.7.1 • Does not expressly discuss clinical, technical, and biological characteristics that are

important to device or discuss the potential clinical impact of differences. • Clinical Uses that May be Important:

o Device A used in uterovaginal prolapse whereas Device B is not – if data are only available on Device B, this indication would not be covered

• Technical Characteristics that May be Important: o Device A is fully absorbable whereas Device B is only partially absorbable - there are likely to be

differences in performance o Device A is available in much larger sizes than Device B – there might be issues related to size o There is no information on key characteristics such as strength/strength retention, stiffness, pore

size, method of application, etc. o No data (e.g. preclinical studies, risk analyses) were presented to substantiate equivalence

• Biological Characteristics that May be Important: o Device A is not the same material as Device B and is not used in the same tissues. While the

justification states that both materials are compatible to ISO 10993, there is no justification for equivalence. It is unlikely that absorbable and partially absorbable materials could be considered equivalent.


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ibim tariah ph.d technical director, healthcare solutions · technical director, healthcare...

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