Day two of the EIGA Winter Seminar 2019

Whilst day one focused on medical gas safety, regulation and good practice, day two turned its attention to the technologies involved: in particular, medical devices, computerised systems and the introduction of new therapies and equipment. 

Session five – Medical Devices 

Linde Healthcare’s Global Head of Quality, Nils Beyer, set the tone of the fist session with an overview of the new medical device regulation (MDR) and impact assessment for medical devices. 

Beyer said, “We will be looking at where the new regulation is coming from, the timeline, milestones and the impact.”

The EU states that the intention for new MDR is to reflect technical advances in medical science and in law making, to improve safety and create a fair market for manufacturers with reduced risk of discrepancies. 

The MDR entered force in May 2017, it will become applicable in May 2020 and should be present in the Medical Device Directive (MDD) by May 2024.

“We have a lot of new requirements and it’s really important that we look into what this means for us and our organisations. However, we shouldn’t worry, we will be able to handle the new MDR as long as we prepare. A real positive of the MDR is that it will lead to the harmonisation between countries,” Beyer added.

Up next, to give a presentation on the need for more medical device regulation, was Bernd Rieker, Head of Medical Devices at Linde.

He said, “I would like to give you a few examples of how we need to get prepared for MDR. Let’s assume CO₂ becomes a Class 3 medical product.”

The requirements:

• There will be mandatory clinical trials 
• Annual post market updates and post market surveillance 
• A structured approach considering the latest scientific data

“MDR will require distributors to carry out detailed labelling checks before the device is put on the shelf. Full liability amongst the importer will apply if product defects occur,” Rieker added.

“To summarise, the MDR is still pretty close to the MDD however, the details must be considered. In the future, medical device distributors will be closer to medical device manufacturers in terms of responsibility and liability. The new classifications will drastically change the game for some devices,” Rieker concluded.

Dr. Viviana Hoischen, Medical Advisor at Air Products, took to the stage to give an insight into Post-Market Surveillance (PMS) and the Periodic Safety Update Report (PSUR), two fairly new concepts for medical devices. 

He said, “A major change in medical devices has occurred due to two new ‘CRISIS’ products which are now considered medical devices. These are hip replacements and breast implants, which have caused urgent regulatory changes to increase vigilance.”

PMS data can be used to update and improve risk management, it can provide instructions for use, labelling, design and manufacturing, and can be employed in clinical evaluation. PMS can also identify preventative measures and areas of improvement. Finally, it can contribute toward the PMS of other devices and detect and report trends.

The importance of medical device regulation was also reinforced in Dr. Bassil Akra’s presentation. As the Vice-President of TÜV SÜD – technical service provider of testing, product certification, auditing, systems certification, training and knowledge – Akra was able to give a general overview of the Medical Device Regulation (MDR).

He began by saying, “Lawyers tend to write regulation in such a way we can’t understand them. We’re going to see a lot of changes in these guidelines and regulations now that we are entering a new chapter of MDR.” 

Additional documents to be expected include Delegating Acts, Implementing Acts , Common Specification, Harmonised Standards and other guidance documents such as  MEDDEV or similar.  

Akra urged delegates to renew their product certificates and reclassify devices as soon as possible to ensure that they can still place products on the market in 2020 when the new medical regulations are enforced. By the end of the year, helpful guidance documents will be available.  

Session six – Hot Topics and Breaking News 

Following a quick coffee break, Air Products’ Paulo Pereira, resumed the seminar with an introduction to data integrity (D.I.), the guidance document from the MHRA issued in march 2018 D.I. that focuses on the quality of the data generated within the medicinal product life cycle.

Pereira set out to reveal the mindset and philosophy that gas companies, within the British Compressed Gas Association (BCGA), applied in addressing quality data concerns. He addressed the necessary steps required to achieve the goal of identifying possible problematic points in the analytical process of medical gases that could lead to insufficient or poor quality analytical documentation. 

He said, ”The medical gas companies should be responsible for the systems used and the data that is generated, they should enable D.I. controls to be effective, and they should have their data governance policy endorsed at the highest level.” 

Gas companies should look at:

• How analytical data is generated and captured
• What is the potential for the unauthorised deletion and/or correction of this data? 
• What is the inherent criticality of the data that is being generated? 

Pereira  concluded, “Look at your processes, make yours assessments and ask yourself what is the reality of the company.” 

Q-FINITY’s Oliver Herrmann then stepped up to discuss the validation of computerised systems in the light of D.I.

The industry has embraced individual or strategic delegation of activities to internal or external suppliers. Often this leads to a chain of partners and (potential) loss of direct control and oversight that needs to be considered when assessing the risks with regard to D.I.

He said, “We need validation to ensure patient safety. Patients are not healthy and need the medical products and devices. It is a matter of trust. To improve quality we must validate to assure that what you need is what you get.”

‘New Horizons of High Flow Oxygen Therapy (HFOT) in Adults: from Hospital to Home’ was the title of the next presentation given by Dr. Salvador Díaz Lobato, Head of the ‘Noninvasive Ventilation Unit’ at the Hospital UniversityRamón y Cajal. 

Díaz’s HFOT has revolutionised the management of patients suffering a variety of repertory disorders. In Díaz’s presentation, he discussed the rational of HFOT, the main characteristics of this treatment, the available evidence and the challenges of the innovative technique. 

Richard Craig, Technical Director for the Compressed Gas Association (CGA) turned attentions to the medical gas regulatory environment in the US and Canada.

Craig provided a review of CGA activities with the US Food and Drug Administration and Health Canada on revising regulations covering good manufacturing practice, labelling, warehousing, registration and listing, and adverse event reporting for medical gases and devices. 

“What do we have today? We have revised FDA regulations and Unique Device Identifiers,” he stated. 

Session seven – Hot Topics and Breaking News 

After lunch, attendees reconvened for the final session of the EIGA Winter Seminar 2019. Salvatore Velardi of Nippon Gases, Rivoira, took to the stage to discuss new regulatory topics such as cryopreservation. 

Cryobanks for the cryopreservation of cells and tissues have been widely used for many years. In many cases, a fixed liquid nitrogen supply tank and a distribution pipeline system supply the storage containers with samples. However, a recognised standard was missing concerning the criteria of design, installation, commissioning and start-up of such a system.  

The Italian Standardisation Institute (UNI) has developed a new standard that defines the requirements for safe operation of the cryobank.

Velardi said, “In response to the new standard, incorporated into the design of the system is the continuity of supply: automation, energy inlet and a manual bypass. Sample safety: critical parameters monitoring and control, and last but not least, operators safety: ambient monitoring and ventilation.”

ICH Q3D is one of the most complex changes in regulation which advocates the use of a risk-based approach to assessing the potential presence of elemental impurities in drug products. Martin Schöfnagl from the Messer Group, discusses these new guidelines and the ‘EIGA approach’ which he helped to organise as the Chairmen of EIGA’s working group WG-7 on medical and breathing gases.

EIGA’s WG-7 has been working on a document using science and risk-based approaches to evaluate the potential for introduction of elemental impurities into the drug product and to determine if additional controls need to be included in the overall control strategy to ensure product quality and safety. 

Schöfnagl asked the audience, “How do you comply with and make use of this document? You have to ask yourself, are your products within the scope of the document? Do you use the same methods to manufacture your products? And are you using the same APIs, excipients and packaging materials?” 

Georges Caillibotte, Medical R&D Solution Pathways Director at Air Liquide Santé International, approached the subject of numerical simulation of nitrous oxide (N₂O) occupational exposure for healthcare professionals in his presentation. 

The current N₂O/O₂ 50/50 mixture usage guidelines state that the product should be used in airy, well ventilated rooms, for procedures no longer than 59 minutes. 

Caillibotte said, ”If you respect the different guidelines, then you will be ale to do it without risk of over exposure.” 

VIPR drug device combination was next up on the days agenda, presented by Jan Strybol, Regulatory and Quality Manager at Air Products. 

An integrated pressure regulator cylinder valve (VIPR) is a safe and user-friendly medical device. When installed on a medical gas cylinder, it provides a package to the healthcare professional or the patient for direct and easy administration of the required dose of medical gas. 

Requirements for the gas manufacturers:

• Initial qualification of new model
• Incoming checks
• Follow GMP Annex 6 for prefill checks
• First fill checks depend on the detail of flow performance rest records from the valve manufacture
• Based on risk management and documented evidence of field experience, standard post-fill checks are applied

“Although the intended performance of the VIPR is specified in the valve manufacturer’s technical file, the pharmaceutical legislation also requires the gas manufacturer to ensure that the valve is performing correctly each time the cylinder is filled and supplied for patient use over its entire service life,” Strybol concluded.

Mike Ralph, Medical Gas Association Chair and The Linde Group’s Peter Henrys, jointly presented the final session of the 2019 EIGA Winter Seminar, with an introduction to new medical gas cylinder packages. 

Ralph said, “Usability and compliance are key requirements wen developing any new medical gas package designs. These requirements can be achieved by reviewing all of the available valve and cylinder designs by working with manufacturers to produce an efficient, easy to use package. You must ensure that all of the customer ‘user requirements’ are delivered where possible and of course, compliance with standards is essential to meet regulatory requirements.”

Henrys commented, “Going forward, it is still apparent that new requirements can be requested by customers. Often these improvements can lead to a compromise between ease of use and safety regulation requirements. Training is always raised as an issue which indicates it requires improvement.” 

Markus Zacharias, EIGA SOC seminar Chairmen, closed the event by stating,”I think you will all agree we have had two very interesting days. I hope you take home some findings that you can use in the future. Im sure that each of us will have our own personal takeaways. If we have achieved this, I think we will clearly see the improvement of patients safety day-by-day.”