www.hcltech.com

DRIVING INNOVATION IN DIAGNOSTIC INSTRUMENTSA DEEP DIVE INTO CHANGING IVD LANDSCAPE

THE CHANGING LANDSCAPE OF IN VITRO DIAGNOSTIC DEVICES

The author:

PARTHA MARELLA is a Senior Vice President and Heads the Medical Devices & IVD Business for HCL Technologies globally.

Global Healthcare Industry today is focusing on meeting the increasing demand for healthcare services and reducing the rising cost of those services. The industry is being driven by the health needs of aging and growing populations, rising prevalence of chronic diseases, emerging-market expansion, treatment and technology advances, and building connected solutions. Innovations transforming the landscape of healthcare Industry are bringing the Patient at the Center of healthcare ecosystem. However, the industry continues to face a growing number of challenges such as cost pressure, competition, globalization and volatility.

The $68 Bn global In Vitro Diagnostics (IVD) market is growing at a rapid pace. The rising demand for early and accurate disease diagnosis, increasing prevalence of infectious diseases, adoption of fully-automated instruments & automation in laboratories and increasing adoption of point-of-care testing are the key factors driving the growth of this market.

The global IVD market has a highly competitive and consolidated vendor landscape. The market is expected to witness a steady growth in the coming years owing to increasing new product innovations and investments in R&D activities. Mergers & Acquisitions and partnerships has been and continue to be a key growth strategy for most of the prominent players in the industry. Also, Connected Digital Health Ecosystem has become a manufacturer’s ammunition to fuel-diff erentiated value creation.

However, these are challenging times for IVD companies as well. Despite the factors for growth, lack of important reimbursement policies are restraining the growth of global IVD market. In addition, the lack of regulations for clinical laboratory in numerous countries is also hampering the growth. The new and stringent requirements related to clinical evidence has already created chaos in the industry. It necessitates the manufacturer to go through the existing evidence and ensure that it is in compliance with the new defi nitions and performance evaluation requirements set by IVDR.

The mounting need to sustain the momentum of business growth and innovate amidst increasing regulations and competition, is creating a lot of pressure on the top line as well as the bottom line.

Modern IVD companies must rethink their existing business blueprints in-line with evolving market dynamics and defi ne a strategy that addresses the following challenges:

• Stringent regulatory norms and scrutiny model• Demand for fl exible healthcare services delivery• Organizational dissonance arising from

mergers/ acquisitions• The need to embrace evidence-based care• Expansion in emerging markets

We believe that a robust vendor ecosystem is vital for a sustainable and reliable healthcare organization. In addition, partner experience and skillsets must encompass diverse industry requirements such as R&D, engineering, regulatory, manufacturing and so on. Finally, business transformation should go beyond driving value and improving patient outcomes. As a partner of choice of 6 out of Top 10 IVD companies and 9 out of Top 10 Medical Devices companies, HCL has delivered innovation at predictable costs and expertise in New Product Development, Product Sustenance, Regulatory and Compliance, New Technology Adoption (IoT, Medical Mobile Apps, Cloud Enablement) and more.

With that as the backdrop, our global team of diagnostic devices specialists & subject matter experts (SMEs) at HCL and regulatory leaders from IVD industry have authored this collection of articles sharing their perspective on the challenges faced by OEM’s and how they have been able to manoeuvre those challenges put forth in front of them.

We welcome your feedback and stand ready to meet with you to discuss these perspectives, our experience, and potential impacts to your organization. Contact information of our key leaders are provided at the end of this handbook. Please feel free to write to us.

[ 3 ]

FEATURED ARTICLES

05

16

11

2008

18

14

21

27

Pg

Pg

Pg

PgPg

Pg

Pg

Pg

Pg

THE AUTHOR:

ANUPAM TALAPATRAis a part of Regulatory COE at HCL Technologies, with over 14 years of experience in Top Global IVD companies

THE AUTHOR:

HILDE VIROUX is an AVP for Regulatory at HCL Technologies, with 26 years experience in Industry

THE AUTHOR:

KISHOR KUMAR GOPI is a part of Mechanical division at HCL Technologies with over 10 years of Industry experience

THE AUTHOR:

JYOTIKA is a part of Regulatory COE at HCL Technologies

THE AUTHOR:

MIRNA DIPANO is Regulatory Aff airs Global Head at Abbott Hematology

THE AUTHOR:

NISHANT PALIWAL is a part of Regulatory COE at HCL Technologies

THE AUTHOR:

DR. PADMA PRIYA PUTREVU is a part of Clinical COE at HCL Technologies with over 12 years of industry experience

THE AUTHOR:

HILDE VIROUX is an AVP for Regulatory at HCL Technologies, with 26 years experience in Industry

THE AUTHOR:

SUBRAHMANYA KRISHNABHAT is a part of the Mechanical team at HCL Technologies, with over 18 years of industry experience

MARKET INFLUENCE ON DEFINING IVD PRODUCT STRATEGY

IMPACT OF MDR AND IVDR ON PRIVATE LABEL MANUFACTURING AND KITS

IMPERATIVES OF IVDR MATERIALS/REAGENTS COMPLIANCE: “FROM ALERT TO ACTION PLAN TO IVD COMPLIANCE”

APPROACH TO CONTROLLING THE COMPLEX PMS PROCESS

TRACKING GLOBAL REGULATIONS – AN IVD MEDICAL DEVICE PERSPECTIVE

QMS PROCESS DEFINITION: COMPLIANCE TO APPLICABLE STANDARDS & REGULATIONS

HOW MEDICAL LITERATURE CAN SAVE TIME AND CLINICAL VALIDATION EXPENSES

FINDING THE RIGHT NOTIFIED BODY TO KEEP IVDS ON THE MARKET AFTER MAY 2022

CHANGE MANAGEMENT BEST PRACTICES TO MAINTAIN AND IMPROVE PRODUCT HEALTH

[ 4 ]

MARKET INFLUENCE ON DEFINING IVD PRODUCT STRATEGY

THE AUTHOR:

ANUPAM TALAPATRA is a Program Director for IVD/IVDR Services, and is an Associate General Manager in Regulatory Centre of Excellence at HCL Technologies. He has over 14+ Years of experience in various lead technical & managerial positions in Product Development, Program & Product Management in global IVD companies, including Roche Molecular, Thermo Fisher, Hologic and BD. He has ISO 13485 Lead Auditor Certification from BSI, extensive experience in Design Control and Quality System as per FDA 21 CFR 820 and in Regulatory submission (510k, PMA, BLA and CE-Mark)

Customer-perceived quality is the leading driver of business success. An effective VoC serves as a multi-source insight platform whose capabilities provide an outside-in view of customer experience and expectations towards a company’s products or services, that enables a deeper understanding and engagement at key points of the customer journey, quantification of customer sentiments and perceptions, and identification of product improvement opportunities.

VoC research is about answering those burning questions such as ‘should I enter the market’, ‘what sort of product should I develop’, ‘how do I price my product’, ‘what regulatory path should I take’ and ‘what is the most effective sales and marketing strategy’ for me. A well thought-out and comprehensive VoC initiative requires one to be part detective and part psychologist – trying to solve a puzzle through questions and observations that will help inform and guide product direction,

regulatory strategy and commercialization path. It should enable the IVD manufacturer to:• Continually monitor the voice of customers (via

surveys, focus groups and customer interviews)• Integrate information from multiple customer

voices • Identify and prioritize voiced as well as implicit

needs and wants

HCL has a dedicated Center of Excellence - STRIDE, which is a global network of multi-disciplinary design studios of HCL

STRIDE is a creative Studio with design capabilities in Industrial Design and Communication Design under one roof.

[ 5 ]

• Categorize customer needs in different buckets, e.g., needs related to:

specimens such as specimen type, specimen handling and processing, specimen volume, specimen stability

assay workflow, such as throughput, automation, and convenience

analytical performance, such as analytical sensitivity, specificity, precision, accuracy, measuring range, etc.

clinical performance: clinical utility and correlation to specific clinical end points (intended use), clinical sensitivity and specificity, PPV, NPV

data: data analysis/management/integrity

reagent stability

assay controls

labelling and information provided

product risk

technical support and services

assay configuration

pricing vs. new features

• Prioritize customer needs based on understanding of the market, competitive landscape and business needs

• Translate customer needs to product requirements (avoid taking raw data and dropping it directly into a requirements document…instead, analyze the enabling features in the products)

• Provide input to new product development/product modification/feature enhancements for next generation products or services

• Customize products, services, add-ons and features to meet the evolving needs and wants of customers

• Solicit and evaluate new product concepts and possible solutions

Build an Effective Voice of Customer program At the onset of a VoC program, there needs to be a clear understanding of the business issues involved to ensure the program will support overall business objectives. To engage internal cross-functional stakeholders, the VoC program needs to be aligned with their business goals. If relevant business drivers are identified, a program can be built that provides actionable insights to support those objectives (such as, increased revenue, reduced costs, increased cross-sell, increased customer centricity, etc.).

While the amount of customer data collected, directly or indirectly, in the age of social media is rising at an exponential rate, for many organizations, this feedback is not delivering business results or impacting the ROI in a positive way. If implemented effectively, the Voice of the Customer program has the potential of becoming a real catalyst for change across the manufacturer’s organization.

“Organizations often have multiple touch points with the customer across various functions, including product management, sales, field applications, technical support, warranty and accounting. These and other adjacent customer-facing functions need to be fully engaged and leveraged to achieve the long-lasting benefits of a VoC program”

The needs for different testing environments may be quite different. A high volume high throughput, low cost site may want streamlined workflow and minimize provisions of error. Hence, the VoC program should span the regions and types of environment that the product will be sold into, e.g. small boutique labs to the high-volume testing labs (reference labs, core labs, large hospital labs, community hospital labs, physician’s office or patient’s bedside for near-patient testing or self-testing).

In some instances, it may be useful to interview people who operate upstream and downstream of the target user to help identify interfaces and/or reveal alternate decision makers. For example, a lab director may be the key purchaser and user of a new diagnostic test; however, it is the referring clinician that will drive the adoption of that test into the laboratory, based on clinical data

Key areas to consider when building an effective Voice of Customer program:

• Capture: identify customer listening posts both internally and externally. Surveys are the most common way to establish listening posts across all customer touch-points.

HCL has worked on Product concept & Requirements definition for more than 25 Medical & Diagnostic devices

[ 6 ]

• Analyze: Analyze feedback in real-time. It’s important to deliver clear and actionable insight to the appropriate internal functions and key stakeholders.

• Act: Knowing the challenge or improvement areas allows the appropriate internal cross-functional team to take measures or corrective actions in a variety of ways.

• Monitor: Having a real-time pulse on customers can help determine the effectiveness of improvements executed across the enterprise.

While conducting a VoC study, it helps if the researchers and/or marketers have prior knowledge of the various players in the target diagnostics marketplace (i.e., patients, clinicians & medical providers, payers, customer segments and testing labs), a critical understanding of the market gaps, market trends, the competitive landscape and the regulations. This insight can provide that extra edge and a head start to the VoC process, help in focusing on the key issues and in asking the right questions, to unveil both explicit and implicit needs. For the IVD products, a VOC can be very effective if conducted by someone who is able to sense the real needs, not just gather a bunch of requested features or functionalities, someone who is familiar with the clinical space, the state-of-the-art in medical practice, the algorithms used by clinicians for triaging patients (as applicable), the patient pathway mapping, workflow of the end users (e.g., lab technicians) and takes the regional, regulatory and reimbursement implications into perspective. It is a huge benefit if the VoC team understands that there are different drivers for different players, i.e., usability and convenience may be key for the direct users, workflow improvements and cost savings

may be critical for the insurance administrators, while the clinicians are primarily interested in patient outcome

VOC methods and tools

There are a range of options including online survey, focus groups or one-on-one interviews. Simple questions may be suitable for preliminary data gathering, however following up with more structured tools can quickly get to what is critical. Conjoint analysis is a great example of such a tool, particularly where product pricing is concerned, as it allows the product development team to run trade off decisions, evaluating cost versus feature set.

Include regulatory aspects in the VoC program

For companies developing IVD products which will enter a regulated market, it is recommended that a regulatory component be included in the VoC program. Market and regulatory considerations can be closely related. Market may inform developing a product with specific claims. The regulatory environment may drive the manufacturer to position the product differently. For example, diluting product claims may ease out regulatory hurdles and in turn, reduce the scope of verification and validation studies – the question is if such reduced claims will hold similar marketing benefit.

Conclusions

With the intense pressure from competition, and the volume and impact of customer feedback through social media building up, organizations have shifted from inside-out models of operation, to more outside-in, to gain sustainable competitive advantage. Businesses are keen to listen to the thoughts and opinions of their customers more than ever before.

However, while organizations have become adept at feedback collection, the challenge is to translate the customer data into actionable insights. Organizations need to revisit the way that insights are operationalized in a cross-functional manner to support change.

HCL STRIDE works on User Research & Design Research, product conceptualization, usability engineering & User design experience primarily

[ 7 ]

TRACKING GLOBAL REGULATIONS – AN IVD MEDICAL DEVICE PERSPECTIVE

THE AUTHOR:

MIRNA DIPANO is Regulatory Affairs Global Head at Abbott Hematology

Manufacturers that want to sell their products in the global markets must comply with global regulations. There is no dearth of regulatory changes and related deadlines are popping up all the time around the world. Gone are the days when you got your FDA approval or clearance and you could basically sell your products anywhere in the world. Manufacturers in general had a rude awakening when the European Union (EU) came up with the CE mark concept and the directives: The Active Implantable Medical Device Directive (AIMDD), the Medical Devices Directive (MDD), and the In Vitro Medical Device Directive (IVDD). The International Organization for Standards (ISO) released ISO 13485 in 1996, that lays out the requirements for a comprehensive quality management system to enable the design and manufacture of medical devices, including IVD devices. In 1998, ISO 14971 was introduced to address application of risk management to medical

HCL Regulatory CoE has a team size of 600+ trained resources deployed in MDR and IVDR Programs

[ 8 ]

January 1, 2018 marked the enforcement of India’s Medical Device Rules, 2017. This is India’s first device specific regulatory framework. Compliance is mandatory. The regulations are driven by risk-based principles developed by the Global Harmonization Task Force (now IMDRF, International Medical Device Regulators Forum), under which all medical devices are categorized in four groups based on their risk level. This is a big change from how devices were regulated in India; previously only certain types of device products were regulated as drugs, while all other types of devices were not regulated. Under the new Medical Device Rules as per India’s Regulatory Authority, Central Drugs Standard Control Organization (CDSCO), Quality Systems of device manufacturers must comply with ISO 13485.

January 1, 2019: MDSAP was created by the IMDRF, allowing firms to undergo one audit by an accredited third party to satisfy quality regulations in the US, Canada, Brazil, Japan, and Australia. On January 1, 2019, the Medical Device Single Audit Program (MDSAP) became mandatory in Canada. The program is voluntary for the other four regions, but Canada has mandated that manufacturers who sell medical devices (Class 2 or higher) in Canada after 1st January 2019 must have a QMS that has been approved through the MDSAP program. MDSAP replaces Health Canada’s Canadian Medical Device Conformity Assessment System (CMDCAS). Starting 2019, MDSAP is the only mechanism available to demonstrate compliance with Canadian quality management system requirements.

March 1, 2019, compliance date for ISO 13485:2016: Five years in the making, revision to ISO 13485 was released on March 1, 2016. Device companies use ISO 13485 as road map to ensure quality systems compliance with regulators in different countries, including Canada, Japan, Australia, and the 27-member states of the European Union. Companies must pay attention to ISO 13485:2016, as it includes substantial changes. Manufacturers have until March 1, 2019, to comply with its requirements or risk enforcement actions.

January 1, 2020: The ten-member states that make up the Association of Southeast Asian Nation (ASEAN) must be fully compliant with ASEAN Medical Device Directive (AMDD) by Jan 1, 2020. Under AMDD there is a greater convergence of the medical device regulatory systems in these 10 ASEAN nations: Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar/Burma, the Philippines, Singapore, Thailand, and Vietnam. AMDD requires those countries to implement standardized medical

devices and expanded in scope in the subsequent releases (latest version ISO 14971:2012). These were big adjustments for device manufactures. That was just the beginning. Since then, many other countries came up with their own regulations and their own standards. Some of them are being revised and some others are new formulations. The clock is ticking to comply with the changes in global regulatory landscape, from compliance with ISO 13485:2016 to the required use of the Medical Device Singe Audit Program (MDSAP) in Canada, new medical device regulations in the EU, India, the Association of Southeast Asian Nation (ASEAN), the Eurasian Economic Union (EAEU), etc.

JAN 2018

India’s Medical Device Rules

MAR 2019

ISO 13485MAY 2020

EU MDRMAY 2022

EU IVDR

JAN 2019

MDSAP in Canada

JAN 2020

ASEAN AMDD

JAN 2022

EURASIAN (EAEU)

HCL is supporting 14 different Medical Devices OEM’s in their MDR/ IVDR compliance journey

HCL is presently working executing 11 MDR and 5 IVDR Programs for leading Medical Device/ IVD customers

[ 9 ]

device classification criteria and device placement systems, and to establish post market surveillance systems. The ASEAN AMDD agreement became effective in January 2015 but will be enforced in January 2020.

May 26, 2020: European Medical Devices Regulations (MDR) was published in the Official Journal of the European Union on May 5, 2017 and took effect 20 days later. The MDR will become fully enforced as of May 26, 2020; after this date, notified bodies will no longer assess products against the European (EU) Medical Device Directives. There will be no grandfathering. After this date all products must comply with the new Regulations. The new regulations will replace the Active Implantable Medical Device Directive (AIMDD) and the Medical Devices Directive (MDD). The changes are substantial, and impacts technical files, product labeling, post-market surveillance, supply chain, etc. Even after MDR takes full effect, CE marking Certificates issued by Notified Bodies under MDD and AIMDD will remain valid until the end of the period indicated on the Certificate in most instances. MDD Certificates issued prior to final implementation of the MDR (around Q2 2020) have a maximum validity of five years. However, all MDD Certifications will automatically expire four years after the new Regulation comes into effect.

January 1, 2022 EURASIAN Economic Union (EAEU) Regulation, compliance is mandatory: The current regulations of the five-member countries will be replaced with a single, decentralized system for the region. The countries that make up the EAEU are Russia, Belarus, Kazakhstan, Kyrgyzstan, and Armenia. After December 31, 2021, local regulatory processes will no longer be recognized. Nevertheless, implementing the new umbrella EAEU regulatory system could prove challenging because there are strident differences among its members when it comes to regulating devices. Some member countries have light regulatory structures in place while Russia has more developed regulatory agencies. The implementation of this new regulatory structure may be delayed. This will mean the device industry will have to use the national systems longer.

This was only a snap-shot of the current state of some regulations in the global market. By the time you read this, there may be more regulations and more challenges for medical device manufacturers to overcome. The clock is ticking, device manufacturers must comply.

“May 26, 2022 EU In Vitro Diagnostics Regulations (IVDR), compliance mandatory. The IVDR regulations were published on the same day that MDR was published. The difference with MDR is that IVD manufacturers have two extra years to comply with IVDR, which will be completely enforceable on May 26, 2022. The new regulation will replace the In Vitro Medical Device Directive (IVDD). As with MDR, the changes for IVDR are extensive; from the technical files, labeling, post-market surveillance, product traceability, supply chain, economic operators, etc. and will take time to be fully implemented”

HCL regulatory CoE provides End to End support from regulatory feasibility assessment till sustenance support covering different aspects such as regulatory planning, review and preparation of Dossier

[ 10 ]

IMPERATIVES OF IVDR MATERIALS/REAGENTS COMPLIANCE : “FROM ALERT TO ACTION PLAN TO IVD COMPLIANCE”

THE AUTHOR:

KISHOR KUMAR GOPI is a part of Mechanical division at HCL Technologies with over 10 years of Industry experience

Any hazardous substance or Material of Concern, present as an ingredient/component in a reagent formulation of an IVD medical device, needs to be assessed per European Union (EU) Regulations and labelled appropriately.

A substance of very high concern (SVHC) is a chemical substance (or part of a group of chemical substances) whose use within the European Union is subjected to authorization under the REACH (Registration, Evaluation, Authorization and

Restriction of Chemicals) Regulation. Listing of a substance as an SVHC by the European Chemicals Agency (ECHA) is the first step in the process for restriction of use of that entity. The first list of SVHCs was published on 28-Oct-2008 and the list has been updated several times to include new candidates. The most recent update occurred on 27-June-2018 to include a total 191 SVHC.

The criteria are stated in Article 57 of the REACH Regulation. A substance may be proposed as

[ 11 ]

an SVHC if it meets one or more of the following criteria:

• it is carcinogenic

• it is mutagenic

• it is toxic for reproduction

• it is Persistent, Bio-accumulative and Toxic (PBT substances) according to the criteria set out in Annex XIII to the REACH Regulation

During the development of an IVD device, product stewardship should be one of the key aspects that needs to be built into the design element.

1. Special attention needs to be paid to physical and/or chemical incompatibility, if any, between the materials/reagent components used and the human specimens (e.g., biological tissues, cells, blood and other bodily fluids), based on the intended purpose of the device.

2. Devices shall be designed and manufactured in such a way as to reduce, to a level as low as reasonably practicable, the risks posed by hazardous substances, with special emphasis on

• substances that are carcinogenic, mutagenic or toxic to reproduction (‘CMR’), in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the European Parliament and of the Council

• substances that are having endocrine disrupting properties per Article 59 of Regulation (EC) No 1907/2006 of the European Parliament and of the Council (taken from Annex I, Chapter II, 10.3)

“Information on any hazardous substance or Material of Concern (CMR substances, Endocrine Disruptors, etc.) shall be explicitly stated under Warnings or Precautions in product labels and in the IFU/package insert”

There are challenges while ensuring compliance to Regulations, when it comes to hazardous substances:

- Gaps in the product Bill of Materials (BOM) due to reasons such as system migration, components outsourced to contract manufacturers, etc…it is imperative for companies to have the latest Bill of Materials (BOM), exploded to the lowest level possible, and Certificate of Analysis of incoming raw materials from various vendors, to get accurate information on the formulations used in product manufacturing. It is also important to determine if a part or component is considered “off the shelf” or has been developed as a custom effort, to decide on the source of information related to its formulation or composition.

- Major dependencies on suppliers, and third-party manufacturers (TPMs) to collect material specifications and assess for hazardous substance compliance…in several instances, it is the level of an active ingredient or substance that determines toxicity. A known hazardous substance, if present below a critical and validated threshold in an IVD medical device, can be considered safe.

[ 11 ]

HCL has partnership with external labs to perform

Biocompatibility evaluation as per ISO 10993-1 : 2018 & Testing as per ISO 10993-1: 2018

Exhaustive Extractable and Leachability tests of the Medical Devices Products per ISO 10993-18 and 17

Toxicology Risk assessment per ISO 10993-17

Hazardous substance assessment for CMR substances (Carcinogenic, Mutagenic and Toxic to Reproduction), ED’s substances (Endocrine disrupting) and Phthalate per EU MDR, Annex I, 10.4.1

Testing of Hazardous substances ( CMR/ED’s / Phthalate) per EU MDR , Annex I, 10.4.1.

HCL has executed Toxicology assessment and Hazardous substance testing per EU MDR , Annex I, 10.4.1 for two large global medical device companies successfully for 42 products

[ 12 ]

* Example: Triton X-100 is a commonly used detergent in buffer formulations, used to lyse cells to extract protein or organelles, or to permeabilize the membranes of living cells. Triton X-100 is also used as a viral inactivation agent in the production of mammalian culture-based biopharmaceuticals, that is essential for patient safety. Recently, Triton X-100 (concentration 10–20%) was included in the Candidate List of Substances of Very High Concern (SVHC) according to Regulation (EC) No 1907/2006 (REACH). The level of Triton X-100 in assay buffers is usually much lower than the levels in the danger zone as indicated here (10 – 20%). Hence, the presence of Triton X-100 at a trace level in buffer formulations may not suggest a non-compliance to REACH Regulation. IVD manufacturers are however making a conscious effort to steer away from Triton X-100 and are adopting other alternative non-ionic detergents such as Tween-20.

- Considering the huge amount of material data received from multiple sources under some situations, it may be necessary to assess the level of automation needed to enable timely processing

of compliance requests and requirements. This was one of the challenges faced by medical device companies implementing regulations such as European Union’s RoHS and REACH, or the Dodd-Frank Act rule on Conflict Minerals in the US. Compliance to IVDR may generate similar challenges when rolling up data to the product level for thousands of components/ingredients and suppliers, which can be resource-intensive and prone to error.

- Companies expect that all parts and products must meet compliance requirements but often there are exceptions. Non-compliant parts should be managed, and there must be a process in place, within the QMS framework, to work with suppliers to replace or remove the parts or products in question. Non-compliance may be the result of a supplier who has not provided adequate data on a part or a product. This process requires that outside sources of data be used, or a new sourcing requirement is implemented

There are certain dependencies that an IVD manufacturer needs to be aware of for generating sufficient objective evidence to establish materials/reagents compliance under IVDR and for sustaining the competitive advantage through proactive product stewardship:

- Dependencies on SMEs and Analytical Labs to assess the hazardous materials in question, verify material specifications and conduct material characterization, chemical compatibility and toxicological risk assessments, as needed.

- Dependencies on European Commission in finalizing the CMR and Endocrine Disrupting substance list.

HCL has executed biocompatibility & toxicology test as per 10993 for two large global medical device companies and has successfully validated 6 product family of disposables for sterilization for a leading medical device customer

[ 13 ]

HOW MEDICAL LITERATURE CAN SAVE TIME AND CLINICAL VALIDATION EXPENSES

THE AUTHOR:

DR. PADMA PRIYA PUTREVU is a part of Clinical COE at HCL Technologies with over 12 years of industry experience

Clinical evidence includes clinical and analytical performance evaluation data pertaining to IVD devices. The amount and quality of the data enables a qualified assessment of whether the device achieves the intended clinical benefit(s) and safety, when used as intended by the manufacturer (Annex XIII, Part A, 1.3.1).

Clinical evidence generation & evaluation is a continuous process which requires routine on-market monitoring and impact analysis (driven by changes in medical practice guidelines, adverse event reporting, outcome of ongoing performance studies, new published literature, etc.) by the manufacturer to ensure continued clinical utility

and favorable risk-benefit analysis throughout the lifecycle of the device (considering relative risks to patient management as well as to end users/lab personnel).

Generation of clinical evidence of an IVD device could be impacted by:

• Accuracy of laboratory test results

• Assay technology

• Degree of variation in the disease profile and in the patient population

• Intended use and user(s) of the device.

HCL has done 100+ Clinical Evaluation Reports as per MED DEV 2.7.1/R4; Scientific Validity and Clinical Performance (IVDR) reports

[ 14 ]

Demonstrating Clinical Evidence by Scientific Literature Review

Literature search can be used to identify external validated clinical data that may support the manufacturer’s effort to establish acceptable performance and safety of an IVD medical device.

Scientific Literature search helps to:

- validate the analyte or biomarker being assayed (detected or measured) for its intended purpose

- identify published data which may support a clinical performance or clinical evidence claim for an IVD medical device.

Figure 1: Key elements of Literature search

HCL has an extensive network of clinicians throughout India and USA supporting clinical evaluation & assessment

HCL has extensive experience in preparation of PEP, APR, CPR & SVR’s for multiple medical device customers

There should be a search strategy generated with close attention to the scope of the clinical evaluation. A specific protocol needs to be developed to retrieve selected and highly relevant publications which address the carefully constructed questions around clinical evidence. The involvement of information retrieval experts in this process will help maximize targeted information retrieval.

As illustrated in Figure 1, the main elements of a literature search protocol include:• search strategy• data sources (scientific literature databases) to

be used, including a justification for their choice• selection criteria to be applied to retrieved

literature and justification for inclusion/exclusion• strategies for addressing the potential for

duplication of data during the search process

The data generated through literature search should directly relate to the IVD medical device in question or earlier versions of the product with justification of why the data from earlier versions is still relevant.

Validation studies performed, in order to assess gaps or compliance to clinical evidence requirements. Where no testing has been undertaken by a manufacturer or where there have been deviations from procedures, the Notified Body reviewer shall critically examine the literature-based justification presented by the manufacturer.

In situations where IVD device manufacturers have limited clinical data (esp. for some of the legacy products) or have conducted limited clinical investigations due to incremental changes in device design, function or clinical application, there can be an increased dependency on scientific literature and experience data from routine testing to demonstrate clinical validity. It is critical to dive deep into the study design, confounding factors and appropriate study controls, clinical trial conduct and execution approach, data integrity, statistical methods used in the analysis, the primary and or secondary end points, reference methods and success criteria, when trying to re-purpose, re-analyse or recycle external clinical data, in order to establish and/or reinforce clinical evidence in support of the claims made for an IVD medical device.

Once the literature search is executed, a report is prepared compiling the results of the search. It is important that the literature search is documented in sufficient detail, so that the search strategy and procedure can be appraised critically, the results can be verified, and the search reproduced if necessary.

“It is recognized that in cases where manufacturers source clinical performance data reported in the scientific literature (i.e. studies on the relevant IVD conducted by a third party, published articles on clinical investigations and adverse event reports for the IVD device in question or for comparable devices), the documentation (typically, the

published paper) is readily available to the manufacturer for inclusion in the clinical evidence report”

The Notified bodies assess the output of and conclusions from the literature search along with the Analytical Verification & Clinical

Develop search strategy, generate

search strings

Comprehensive search

Relevant Citations

Summary Report

Scientific and Medical Literature database (Ovid Medline,

Embase) clinical trial registers, advere event databases

Inclusion and Exclusion criteria to enrich for relevant

citations

[ 15 ]

IMPACT OF MDR AND IVDR ON PRIVATE LABEL MANUFACTURING AND KITS

THE AUTHOR:

HILDE VIROUX is Associate Vice President for Regulatory at HCL Technologies, with over 26 years of experience in the Medical devices Industry. During the development of the medical devices regulations she was vice-chair of the MedTech Europe Regulatory Affairs Committee, and chair of the Euromcontact Regulatory Affairs Focus Group, representing Euromcontact at EU Commission meetings. She is a Fellow of TOPRA4 and has published several articles in Regulatory Rapporteur

Article 16 of the Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) specifies the conditions under which the distributor of a device becomes the legal manufacturer of that device.

This means that it is not possible anymore to buy a device from a third party, and put your own name and CE mark on the label.

HCL has a dedicated “Centre of Excellence” in Packaging, Biocompatibility, Labelling & Sterilization

“Article 16.1:

A distributor, importer or other natural or legal person shall assume the obligations incumbent on manufacturers if it does any of the following:

(a) Makes available on the market a device under its own name, registered trade name or registered trade mark, except in cases where a distributor or importer enters into an agreement with a manufacturer whereby the manufacturer is identified as such on the label and is responsible for meeting the requirements placed on the manufacturers in this Regulation

(b) Changes the intended purpose of a device already placed on the market or put into service

(c) Modifies a device already placed on the market or put into service in such a way that compliance with the applicable requirements may be affected.”

[ 16 ]

Why is it not possible anymore?Commission Recommendation 2013/473/EU already restricted the possibility of Private Label activities as the Private Label manufacturer needed to have the technical file continuously at the disposal of the Notified Body in case of unannounced inspections.

IVDR requires the Private Label manufacturer not only to have the full technical documentation available, but also to meet all the requirements of Article 10 of the IVDR ‘General obligations of manufacturers’. This includes having a risk management system, conducting performance evaluation, assigning the UDI, having a Quality Management System, a Post Market Surveillance System, all including the device in question. In addition, the Person Responsible for Regulatory Compliance must be able to demonstrate that he/she has the authority and responsibility for this device.

Manufacturers need to assess their product portfolio, identify all Private Label devices and develop the strategy either to continue selling these products as a distributor, discontinue or move to a contract manufacturing situation.

IVD manufacturers therefore need to pay attention to the devices they put in kits. When it is 3rd party devices, the kit label need to reflect the original manufacturer’s name, authorised representative (where applicable) and CE marking to avoid becoming the legal manufacturer of the third party device in the kit.

The IVDR does not mention kits, but the Regulation 2017/745 on medical devices (MDR) does. Article 22 of that Regulation governs systems and procedure packs of devices, IVDs or combinations. A procedure pack is defined as ‘a combination of products packed together and placed on the market with the purpose of being used for a specific medical purpose’. This meets the definition of a kit.

In all cases, the labelling of the kit must reflect original manufacturer’s data, to avoid becoming the legal manufacturer of the devices in the pack.

In addition, the manufacturer of the kit has to issue a declaration that:

- The mutual compatibility of the devices in the kit has been verified

- They packaged the kit and supplied relevant information to users incorporating the information supplied by the manufacturer of the devices

- The activity of combining the devices in the kit was subject to appropriate methods of internal monitoring verification and validation.

It seems a bit strange that this article is not repeated in the IVDR, and as a consequence may be overlooked by IVD manufacturers, but the scope is both medical devices and IVDs.

HCL has implemented UDI across 10000+ labels, executed 5000+ graphics/labels for line extension

[ 17 ]

QMS PROCESS DEFINITION: COMPLIANCE TO APPLICABLE STANDARDS & REGULATIONS

THE AUTHOR:

NISHANT PALIWAL is a part of Regulatory COE at HCL Technologies

Medical device is an innovation driven industry. Innovations concern both new products as incremental improvements to the existing products in the market. Acquisitions are another means of expanding the product portfolio. The strategy of mergers and acquisition creates a few challenges as it leads to multiple Quality Management Systems (QMS) within the overall organization. The quality systems of medical device manufacturers are designed in line with EU requirements or on the basis of the US federal regulations. Global companies QMS will meet both. The quality system of the acquired organizations, although based on the same requirements, may differ for the type of templates followed, ways of applying design controls, recording feedback from the market and risk management. The verification and validations to assess the performance requirements is frequently carried out by the testing laboratories using the region specific standards.

“There are 2 common approaches to these different QMSs. Most common is that manufacturers keep the multiple QMS in place, allowing each business unit their own QMS. The other, more burdensome approach is to align the different QMS under one global QMS. The latter may be initially more burdensome, but makes it easier to implement changes”

HCL has Best in Class Medical Quality Management Systems and Processes, compliant to ISO 13485 ISO 14971, IEC 62304, 21 CFR Part 820 and ISO27001

[ 18 ]

The strategy for QMS remediation and harmonization starts with an assessment to identify the common elements and differences. The equivalency of the different region specific standards used for verification to the global harmonised standards requires to be established

The continuous evolvement of medical devices and new technologies has led to new challenges related to safety evaluation. The state or art approach for the safety and performance evaluation is defined in ISO standards. Not all standards are internationally recognized though, local requirements may apply. A structured harmonised QMS will address global and local requirements.

A consulting support can help in remediating and harmonizing QMS for medical device manufacturers. Considering all the economic operators and factors, a consultant team can perform a thorough assessment of the quality systems against the latest regional and harmonised requirements in major regulated countries/areas like United states, European Union, Japan, Australia and Canada as well as it can identify the processes which are followed in the semi regulated countries. Consulting team assesses the templates and Standard Operating Procedure and after discussing with the client takes a call either to follow and remediate the process and templates supplied by client or to freshly create them. The decision of adapting a process for further improvement will be based on the maturity level of the existing process against the industries state of art. Assimilation of the quality systems, its harmonization and adaption to the best practice can help medical device manufacturers to cut short unnecessary expenditure and direct it in right direction.

Fig.1: Approach for QMS Remediation

HCL has done QMS Process Definition for 7 Medical Device manufacturers

• Defining of all vital key process to cover the entire lifecycle of the products

• Understanding of the differences to define training, transition approach

• Identifying the State of Art and regional harmonized standards in each area

• Gap assessment to bring the most matured process to the desired level

• Understanding of the common factors to judge the priorities for remediation and harmonization

• A weighted approach to judge the maturity level of QMS for different manufacturing locations leads to selection of best fit for the remediation

Defining QMS Key Elements

Commo Factors Differences

Judging QMS

maturity

State of Art

[ 19 ]

APPROACH TO CONTROLLING THE COMPLEX PMS PROCESS

THE AUTHOR:

JYOTIKA is a Product Regulatory Lead, at HCL Technologies and has 10+ Years of experience in MD/IVD Product Realization and Regulatory compliance in Healthcare Industry. She is experienced in QMS Processes as per ISO 13485 and FDA 21 CFR 820 and Risk Management as per ISO 14971

Post-Market activities are geared towards collecting, trending, analysing, managing and reporting, as needed, any product quality, usability, safety and performance related information in the post-production phase of IVD device lifecycle.

Processing of the PMS Input, which may be derived from numerous sources, shall pass through the PDCA cycle during the periodic review, as per defined PMS process, and can potentially impact various functional areas connected to the output of PMS process. Please refer to Figure 1:

Figure 1: PMS Process Flow (PMS Input and PMS Output)

Technical documenta-

tion

Serious incidents (Adverse Events)

DHF/ DMR

Non- reportable incidents

Device Design

Scientific and Medical

Literature

Includes: Decision and Traceability Tools

Risk Man-agement

documents

Device databases

and/or registers

Labelling, IFU

Customer Complaints/

Feedback

CAPA

FSCA

PMPF, PER, Periodic Safety Update Report/

PMS-Report

Trend reports

Summary of Safety and

Perfor-mance, SSP (If applica-

ble)

Publicly avail-able informa-

tion about similar IVD

devices

PMS of related devices

QMS

PMS Input

PMS Process

PMS Output

Periodic Review

Plan Do Check Act

[ 20 ]

PMS Plan (Article 79)

All Classes unless justified All Classes

PMPF Report (Annex XIII, Part B)

Performance Evaluation Report (Annex XIII, Part A)

Updated with the PMPF outcome

Update, Only Class C and D

Update Annually based on PMS data (if indicated)

PSUR(Article 81)

Update at least AnnuallyClass C – Make available to

NB and on request to CA Class D – submit to NB

by electronic system

PMS Report (Article 80)

Update when necessary and made available to NB and the

CA upon request

Class A and B Class C and D

Summary of Safety Performance

(Article 29)NB Validates and Publish

in EUDAMED and publicly available

Figure 2: Relationship between various PMS related documents (mandated by IVDR)

PMS documentation ecosystem based on IVD Risk Classification:

The Post-market surveillance requirements are located in Chapter VII of IVDR (EU IVDR 2017/746). Annex III of IVDR states the PMS information that needs to be included as a part of the Technical Documentation.

“The PMS Plan shall specify relevant indicators and threshold values to be used in the continuous reassessment of the risk- benefit analysis, as a part of Risk Management program. The Plan should specify effective methods, protocols and tools to investigate complaints, analyse market-related experience collected from the field, identify malfunctioning devices, initiate appropriate response measures including Corrective and Preventive Actions, communicate effectively with Competent Authorities (CAs), Notified Bodies, Economic Operators and Users”

The implementation of the PMS plan can lead to two different types of reports based on the class of the device (please refer to Figure 2):

- Post-Market Surveillance Report (PMSR): This would apply to class A and B devices for IVDR. The PMSR shall present results and conclusions from data gathered from the PMS activities and shall include rationale and description of CAPA tasks, if applicable. This report shall be updated as necessary and made available to the Competent Authorities and/or Notified Body upon request.

- Periodic Safety Update Report (PSUR): For IVDs in Class C and D, the Manufacturer shall prepare a PSUR. The PSUR shall also present results and conclusions from data gathered from the PMS activities and shall include rationale and description of CAPA tasks, if applicable. However, the Regulations adds items to be included in PSUR: the conclusions of the Benefit/Risk determination, the main findings of PMPF, the sales volume, an estimation of the user population characteristics and usage frequency. The PSUR, which shall be a part of the Technical Documentation, will need to be updated and submitted to Notified Body annually for class D IVD devices => IVDR introduces a new type of annual review of Class D PSURs by the Notified Bodies.

Reusable PMPF checklist and templates can save you significant time in your IVDR compliance journey

HCL’s PMS program is helping multiple OEM’s in expediting their IVDR compliance journey. The program includes creation of PMS SOPs and templates (such as PMS Plan, PSURs, PMS-R, PMPF Plan and Report, and SSP)

[ 21 ]

HCL is guiding Medical device manufacturers in various research methods/ strategic initiatives for proactive PMS approach, based on the type/ Class of Device

Based on the device’s risk-based classification, the PMS documentation needs to be updated periodically throughout the lifetime of the IVD device. Table 1 presents the PMS documentation requirement for different IVD classifications.

Table 1: PMS documentation requirement for each IVD Device’s Class (Based on Risk categories under IVDR)

Title of Document IVDR Refer-ence Class A Class B Class C Class D

Post market surveil-lance plan (PMS-P)

Article 79 and Section 1 of Annex III

Required Required Required Required

Post market Perfor-mance Follow up Plan (PMPF plan)

Annex XIII-PART B / Article 56

Required Required Required Required

Post-market surveil-lance report (PMS Report)

Article 80 Required Required Not Required Not Required

Periodic Safety Up-date Report (PSUR) Article 81 Not Re-

quiredNot Re-quired

To be updated at least annually

To be updated at least annually

Post-Market Perfor-mance Follow up Report (PMPF)

Article 56 & Annex XIII

Part BRequired Required To be updated at

least annuallyTo be updated

at least annually

Summary of Safety and Performance (SSP)

Article 29 / Article 56

Not Re-quired

Not Required

Required (shall be updated

as soon as possible, where necessary)

Required (shall be updat-ed as soon as

possible, where necessary)

Performance Evalua-tion Plan (PEP)

Article 56 Annex XIII-PART A-1.1

Required Required Required Required

Performance Evalua-tion Report (PER)

Article 56 Annex XIII-

PART A-1.3.2Required Required To be updated at

least annuallyTo be updated

at least annually

[ 22 ]

IVDR emphasizes a transition towards a Proactive approach to Post-Market Surveillance, rather than just being Reactive (following an event or a trigger).

A cross-functional initiative is key to fostering and sustaining a successful Proactive PMS approach:

• Enable and leverage organization’s existing functions such as PMO, Field Applications, Tech Support, Product Management and Marketing, Technical Operations, Product Development (PD), Clinical Operations, Medical Aff airs

• Generate a RACI Matrix for each of the Proactive PMS related activities and/or deliverables such as Customer Surveys, Focus Group feedback, etc. (refer to Table 2)

Vigilance Activities:

• Reporting of serious incidents and fi eld safety corrective actions (Art 82, IVDR)

• Trend reporting (Art 83, IVDR)

• Analysis of serious incidents and fi eld safety corrective actions (Art 84, IVDR)

• EUDAMED (Art 87, IVDR)

PMS ACTIVITIES e.g.

• Customer complaints and warranty claims

• User feedback other than complaints

• Retrieval of information from Social media and Medical Literature

• Regulatory bodies database scanning

• Maintenance/service Reports

• Spontaneous feedback report

• Failure analysis

PMPF ACTIVITIES e.g.

• Customer surveys/ Focus Groups

• Device tracking

• Feedback during training programs

• Remote Monitoring System

• Online Surveys

• Routine Monitoring of Relevant Medical Literature

PMPF STUDY e.g.:

• Customer surveys/ Focus Groups

• Device tracking

• Feedback during training programs

• Remote Monitoring System

• Online Surveys

• Routine Monitoring of Relevant Medical Literature

Post-Market Surveillance (PMS) and Vigilance, Chapter VII (IVDR)

Reactive Proactive

HCL has a large dedicated complaint management team, to support complaint categorisation & analysis

[ 23 ]

In summary, the IVD Regulations are more prescriptive than the Directives with regard to Post-Market Surveillance. The new regulations also provide more details about what to document and how to do so. There are more requirements for the Manufacturer in this area and also a much greater involvement of the Notified Bodies.

Table 2: Example of a RACI Matrix for conducting a Customer Survey

Step Description Responsible Account-able Consulted Informed

Execution of Proactive Feedback

1Prepare a Survey based on the objectives identified in Periodic Review

PMS-Global PDCross-

functional Team

Marketing, PMS Group

2 Generate and issue the Survey link to Marketing and Tech Support PMS-Global PD Marketing,

PMS Group

3 Disseminate the survey link to the customer

Marketing, Sales, Tech

SupportPD Marketing,

PMS Group

4Monitor and provide analysis of the survey responses throughout the sur-vey period for new complaints.

PMS-Global PD Marketing, PMS Group

5Summarize the survey results as an input into the scheduled period review.

PD PD Marketing, PMS Group

HCL has rich expertise in risk management and performance evaluation processes, which are impacted by PMS findings and activities.

[ 24 ]

FINDING THE RIGHT NOTIFIED BODY TO KEEP IVDS ON THE MARKET AFTER MAY 2022

THE AUTHOR:

HILDE VIROUX is Associate Vice President for Regulatory at HCL Technologies. She has held various leadership positions at Alcon and has worked closely with the European trade associations and the European Commission on the development of the new Medical Device Regulations

Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) was published on April 5, 2017 in the Offi cial Journal of the European Union. Per Article 113, the IVDR entered into force May 25, 2017 and will fully apply by May 26, 2022. This gives manufacturers a transition period of 5 years to bring all their in vitro diagnostic devices (IVDs) in compliance with the new regulation. There is an additional ‘grace’ period during which IVDs covered by a valid IVD certifi cate can continue to be sold. See also fi gure 1 for a schematic representation of the transition period and grace period.

“The IVDR does not only apply to manufacturers and their IVDs, but also applies to the Notifi ed Bodies dealing with IVDs. As from May 26, 2022, all Notifi ed Bodies designation under the IVD Directive will become void. This means that Notifi ed Bodies have to apply for designation under the IVDR in order to continue operating.”

Under the IVDR, the requirements for both manufacturers and Notifi ed Bodies increased. It is mentioned that 7 Notifi ed Bodies have applied for IVDR designation, but the designation process is not transparent, and little is known beyond that. It is not known which Notifi ed Bodies have applied, and how far they are in the designation process. It is rumoured that priority is given to Notifi ed Body designation under the MDR, as the transition period for MDR is only 3 years, until May 2020.

HCL has Working relationship with Global Notifi ed Bodies including TUV, UL, BSI

[ 24 ]

[ 25 ]

Compared to the MDR, the manufacturers of IVDs face 2 additional challenges when it comes to IVDR implementation.

The fi rst challenge is that not many IVDs are currently covered under an IVD certifi cate, only the IVDs listed in Annex ll of the IVD directive. This means that for most IVDs, the technical fi le and related documents such as Performance Evaluation Report (PER), Periodic Safety Update Report (PSUR) and Summary of Safety and Performance (SSP) have to be fully compliant to IVDR by May 2022. The IVDs from Annex ll of the IVD Directive and devices for self-testing can continue to be sold after May 26, 2022 as long as the EC type examination certifi cate is still valid. Extending these certifi cates to make maximum use of the grace period is a strategy an IVD manufacturer can apply to spread out the cost and resources for IVDR implementation

The second challenge is that many more IVDs require some form of Notifi ed Body intervention as

part of the conformity assessment process under IVDR compared to the directive. This is related to the risk classifi cation of IVDs and the new conformity assessment procedures in the IVDR. Only non-sterile devices class A (the lowest risk class) can be placed on the market after May 2022 without Notifi ed Body intervention. The amount of Notifi ed Body involvement increases with the risk associated to the IVD. It includes the assessment of the Quality Management System (QMS) and review of technical documentation for classes A sterile, B, C and D, and batch release for the highest risk class of IVDs. The sample size for technical documentation assessment depends on the risk class of the IVD, with a review of all fi les for class D devices, devices for self-testing and near-patient testing.

In combination with the small number of IVDR Notifi ed Bodies, there is the risk that the Notifi ed Body assessment of the QMS and the technical fi les may become a bottleneck for IVD manufacturers. Even when they have the QMS and the technical documentation in compliance with IVDR, they will depend on the Notifi ed Body being able to perform the assessments. It is therefore important for IVD manufacturers to start the dialogue with the Notifi ed Body and start planning for the IVD certifi cate renewals where possible, and the IVDR QMS audits and technical fi le assessments in order to continue selling their IVDs in Europe after May 26, 2022.

Fig 1: IVDR transition period, important dates

HCL IVDR resources are working in 4 Geos, interacting with 25+ sites, Multilingual like English, Japanese, German, French

Manufacturer’s QMS has to be fully IVDR compliant

May 27, 2024All IVD certifi cates become void

Entry into force May 25, 2017

Date of application May 26, 2022

May 27, 2025Supply chain has to be emply of IVD devices

2017 2018 2019 2020 2021 2022 2023 2024 2025

[ 26 ]

CHANGE MANAGEMENT BEST PRACTICES TO MAINTAIN AND IMPROVE PRODUCT HEALTH

THE AUTHOR:

SUBRAHMANYA KRISHNABHAT is a part of the Mechanical team at HCL Technologies, with over 18 years of industry experience

There is a constant need to bring in relevant changes to products after releasing them to the market to maintain high product competitiveness and upkeep the product health at all times. This has become more significant for Medical devices and in Vitro Diagnostic (IVD) devices since these have direct impact on human life.

Engineering Changes could be due to part obsolescence, frequent part failure, service issues, cost improvement, technology changes, competitive pressure, changes in interfacing

devices, increased demand for product efficiency, CAPAs, changes in regulatory norms and more.

However, one should be cautious while introducing these changes due to possible regulatory and safety consequences, unique needs of specific user bases, usability considerations and many other associated factors that could potentially be impacted by the change. Some changes can be managed internally with proper change review documentation, other significant changes may require notification to regulatory body, while some others may require

[ 27 ]

review and approval by notifying body before releasing the change.

Many IVD equipment manufacturers face challenges in managing these changes due to the lack of best practice in managing such changes, insufficient regulatory knowledge, inadequate documentation and ineffective change review method.

Approach to IVD Engineering Change Management:To tackle change management, we need a holistic approach that considers all possible risks and guidance document in order to mitigate or eliminate potential risks. Below are some recommendations for effective change management:

Develop a comprehensive Engineering Change (EC) process:A good process gives good profit. Comprehensive Engineering Change process needs to be designed by quality department in consultation with other functions such as R&D, Regulatory, Product Management/Marketing, Manufacturing, Supply Chain/Logistics and Technical Support. A comprehensive process flow diagram should clearly map out the paths for various types of changes, including next steps, as well as paths for all possible situations that may arise during the execution of the changes. Guidance documents need to be in place for various steps in the EC process, e.g., for assessing a need for change, raising a Change Request, reviewing change, implementing document update, conducting technical review, determining the composition of Change Review Board (CRB), conducting change review before change and after change, developing verification plan and protocol, conducting verification, generating a test report, providing regulatory notification to notifying body if the change requires notification, releasing parts in the system, and for dealing with old parts in market/stock etc.

Select good PLM tool to manage change:A good PLM tool is a must to effectively manage engineering changes. Management of parts and the product in question with all associated design documents (DHFs), test reports, supplier details, previous changes, if applicable, BOM, relevant part and product history documents with relevant objective evidence, should be organized in one folder/location. Integrating multiple systems into one system, such as NX Polarion tool, may also help in effective maintenance of product.

Generate a compréhensive change management questionnaire/ Template :A comprehensive change management questionnaire/template is essential for a high quality change management. For IVD equipment, extensive knowledge on Regulations and Standards is a must prior to generating a questionnaire. The template should have fields to fill in details such as product information, part description, description of change, function of part being changed, functional groups affected, impact on design input requirements, impact on essential design output, performance specifications, required verification & validation during change implementation, impact on intended use & functionality, impact on safety/regulatory/user needs/product claims, impact on any interfacing software, interfacing parts & devices and more. An effective questionnaire and change management template supports documentation needed to complete the engineering change efficiently. The template should also have questions to address if the change is really required or can be avoided. Minimizing change is always recommended, since even a small change has the potential to trigger a large failure on the field, or manufacturer may receive a letter from regulatory body listing a barrage of questions related to the change that may have far-reaching consequences.

Test to verify change is robust:

Some changes can be implemented without testing, just by documentation updates, part-to-part analysis, design reviews, receiving letters from supplier or subject matter experts confirming that the change will not have any negative impact on product quality, safety and performance. However, it is recommended to perform sample part testing in a lab. A well thought-out, statistically robust, comprehensive test plan that considers the test environment, sample size, test severity, step-by-step procedure and highlights methods to capture objective evidence, supports the overall test execution and verification process. Whenever possible, testing is recommended for change impact review to minimize field risk.

Initiate the change process early and stay proactive:

Advance identification and planning of any upcoming change will avoid last minute rush. Periodic review of all the parts of product, part obsolescence, technology change and field failures, support advance planning for any upcoming

[ 28 ]

change. There is a pressing need of field issues/complaints management to be able to trace back into redesign considerations and field corrective actions, which poses a major challenge for some IVD manufacturers. Install base management can include accessory hardware and upgrade compatibility issues, which helps in field retrofits and in recommending upgrades to customers. Frequent meetings with suppliers may help enhance product health and competitiveness by enabling timely adoption of the latest technology, build performance quality and efficiency or reduce cost of production. Additionally, initiating a change process in advance offers a buffer time for an alternate approach to be pursued, as needed, in case the original proposed change ends up in test failure or triggers additional risk.

Don’t finalize on regulatory pathway right in the beginning:

The IVD manufacturer needs to complete a change-driven full impact analysis and conduct the testing to determine whether the planned change has any deleterious effect on the device’s

safety, efficacy, or performance. Once testing and analysis is completed, the regulatory path that was initially proposed for the applicable change will need to be revisited. If the objective evidence from testing/V&V studies shows impact on safety, efficacy, usability or brings to surface a potential new risk, the Regulatory function may need to take appropriate decision on next steps. A Regulatory oversight throughout the change process is recommended for minimizing risk.

Proper tracking system to manage after effect:

There needs to be a tracking system in the PLM to track the parts changed and to closely monitor the after effect of such changes. This will help in traceability of any change consequences in the field, including any new field performance issues or failures, and in expediting any follow-up action, before significant loss occurs.

“Following proper process to perform engineering change is a must for IVD equipment manufacturers, as it has direct impact on medical decisions. Although there is Regulatory guidance available for change management, it is always advantageous to have company specific or product specific engineering change process, in order to minimize high risks such as life loss or product recall. If a company can manage its engineering changes efficiently by following best practice, it can gain good reputation in the market for after sales support and product reliability, that can boost customer experience and market share”

HCL supports 9 of the Top 10 Medical Device and 6 of the Top 10 IVD companies in sustaining the on market products

[ 29 ]

HCL MEDICAL DEVICES

PRACTICE

Work with 10 of the top 15 Global

Pharmaceutical Companies

40+ years of engineering heritage and several complex mission-critical electro-mechanical products developed from concept to launch

Mature and robust quality management systems compliant to ISO 13485, 21 CFR Part 820, CMMi Level 5, ISO 9001, ISO 27001, ISO 20000, ISO / IEC 17025 and Compliant to ISO-14971, IEC 62304, 21 CFR Part 11, IEC 60601x, SHA, FMEA, HL7 & DICOM

Work with 9 of the top 10 Global Medical

Devices companies

HCL has worked on 150+ Medical Devices

Work with 6 of the top 10

IVD manufacturers

17+ years of experience in medical devices

ELECTRICAL ENGINEERING

MECHANICAL ENGINEERING

SYSTEM ENGINEERING / REGULATORY

HCL INVESTMENTS/ SOLUTION ACCELERATORS

SOFTWARE ENGINEERING

INTEGRATED DESIGN

SERVICES

HCL’s presence in Medical & IVD Space?

HCL’s Integrated Design services to IVD device manufacturers

Hello there! I am an Ideapreneur. I believe that sustainable business outcomes are driven by relationships nurtured through values like trust, transparency and flexibility. I respect the contract, but believe in going beyond through collaboration, applied innovation and new generation partnership models that put your interest above everything else. Right now 137,000 Ideapreneurs are in a Relationship Beyond the Contract™ with 500 customers in 44 countries. How can I help you?

PRADEEP MATHAPATIDIRECTOR & HEAD, MEDICAL DEVICES & IVD BUSINESS – EUROPEE-MAIL: PRADEEP.MATHAPATI@HCL.COMMOBILE: +49 170 99 68 207

Contact: