Day one of EIGA’s Winter Seminar 2019

EIGA’s 160 members have been supplying medical gases for more than 100 years. EIGA has always focussed on the quality and efficacy of medical gas products and services to enhance patient safety, as well as the development of good practices and standards to protect workers and users in the supply and handling of medical gases and homecare services.

Today’s sessions provided guidance and perspective on the many aspects of medical gases safety and shared valuable tools and techniques to help both managers and employees navigate the complex medical landscape.

Ivo Bols, EIGA President and Air Products President for Europe and Africa, opened the seminar with, “A warm welcome to all of you. It so great to see so many of you signed up for this seminar, all 206 of you.”

“For the industrial gas industry, medical gases are a group of products and services alongside many other industrial applications, but they have a significant difference, they are used in people which makes them very peculiar and very different,” he added. 

Session one 

Stefania Mariani, MGC Chair and Director of Medical, Scientific and Biotechnology marketing for SOL Group, kicked off the days presentations with a discussion on safety, operational and regulatory challenges in healthcare.

Mariani set out the three segments of EIGA’s mission:

1. To set standards for our industry and users: good manufacturing practice (GMP), risk analysis, plant validation, qualifies person batch release (QP) and good distribution practice (GDP).
2. To provide regulatory agencies and healthcare providers with specialist advice for drugs and medical devices. 
3. To promote our industry in the supply of medical gases and related services, focusing on the quality and efficiency of products and series to enhance patient safety. 

Mariani concluded her presentation with three takeaway messages. She said, “The medical sector is highly regulated; pharmaceutical and medical device legislation needs to be adapted for the gas sector to ensure patient safety. The protective approach of EIGA / MGC is necessary to support the regulations with guidelines, numbers rationales, risk analysis and proposals. Finally, our focus should always be on how to reach the highest level of patients safety and to increase it day by day in our work.”

Next, the Linde Group’s Global Head of Healthcare, Urmi Prasad Richardson, took to the stage to explain how the regulation of medical gases ensures patient safety.

Richardson explained, “Patient safety is a core objective that the medical gases industry must fulfil and that makes us different to other industry segments. To ensure patient safety, a set of regulations for medical gases has been developed over the years. A quality management system must be in place as an integral part of the business.”

Richardson continued, “I believe that we should be empowering and supporting quality as a mindset so that it is a continuous dialogue and not predefining milestones.” 

Fortunately, Richardson added, ”GxP and MDR are developing in the same direction to ensure quality, safety and efficiency of the products.”

Anne-Sophie Fabre, Regulatory Affairs Director at Air Liquide Healthcare International Paris, examined the regulatory status of the Medical Gases and Health Authorities’ Marketing Authorisation Process.

Fabre summarised, “The classification of the different medical gases in the drug category or in the medical device category depends on their mechanism of action and their intended use.”

These uses are:

• Gas as a drug product if it acts through a pharmacological action; usually inhaled
• Gas as a medical device if it acts through a “mechanical” action (without a pharmacological action); usually locally applied or insufflated. 

What are the impacts of the regulations on gas companies?

1. The authorisation granted by the Health Authorities legitimates the use of the medical gas in patient population and covers the company.
2. Deep knowledge of our products and control of our processes
3. The regulations define the framework of the activities around the drug product

This ensures a common objective between Industry and the Health Authorities which aids patient safety. 

Periodic re-evaluation of the products: 

Fabre emphasised the importance of periodic reevaluation of the products, she said, “It is essential that the evolution of the regulations and importance of the relationship between gas associations, Health Authorities and professional trade associations to appropriately implement the requirements in a homogenous way between the different gas companies. 

Consequences on the companies’ organisation:

• On the status of the company / pharmaceutical company
• On the organisation of the company: QP mandatory, pharmacovigilance person mandatory 
• On the processes: Internal procedures and appropriate systems to manage the various activities. 

Gases used for medical purposes in humans can have both statuses, drug or medical device, depending on their mechanism of action and intended use. Several gases are registered through the European procedures. Today flexibility should be given by the Authorities for the national procedure for registration in more than one country. Complex process to get Marketing Authorisations for the medicinal gases and to market drug products. 

Session two – Homecare 

Following a quick coffee break, Harmen van Dijk, Responsible Person GDP at Westfalen Medical, gave a presentation. The objectives of his presentation was to provide an insight on how to provide patients with good homecare practice. He emphasised the importance of acknowledging the vulnerable situation of the patient despite regulatory requirements and for the safe and proper use of products.

He shared three critical elements in homeware practice:

• To listen to the patient and anticipate their capabilities and needs 
• To provide the patient with safe and proper devices
• To provide clear and thorough instructions

Cátia Esteves, Homecare Operations Area Manager at Nippon Gases, considered the safe supply of homecare medical oxygen systems in her presentation. The basic requirements are:

1. Services and supply processes clearly defined
2. Training in the safe usage of the product
3. Risk assessment to relevant service and supply processes 
4. GMPs and GDPs application
5. Containers / equipment used are functioning correctly
6. Continuous improvement of quality management system 

Esteves concluded by stating that, “It is the responsibility of the homeware service provider to ensure that the medical oxygen systems supplied to patients in the home or healthcare facilities provide a safe supply of oxygen breathing therapy.” 

“The adequate training to the patient and / or caregivers is the key to avoid undue risks from the use of oxygen,” he added. 

Martine Labadie, Director of Training and Skills at Air Liquide Healthcare, gave a personal presentation on how oxygen therapy contributes to her father’s quality of life. He had more freedom, a greater tolerance of physical exercise, more energy, better quality of sleep, increased life expectancy and fewer hospitalisations 

Thanks to the professional Homcare Service provider (HSP), Labadie’s farther almost forgot his oxygen dependance and could live a ‘normal’ life. 

The next presentation by Isabel Saraiva, President of the European Lung Foundation, emphasised the importance of improving the travel experience for patients who require oxygen. Saraiva shared a personal experience whereby discriminatory issues occurred at the airport and on her flight to Rome. The oxygen cost more than the fight, staff and airline did not understand her circumstances and Saraiva experienced an uncomfortable sensation caused by the dried cabin and additional dry airflow. Overall, there was a lack of uniform information which caused an unpleasant travel experience. 

A survey found that 79% of oxygen patients found it difficult to choose an airline. Often the airlines policy was not accessible. 63% found it difficult to book a fight as it was not apparent whether you could bring the portable oxygen concentrator (POC) on board and 40% found it difficult to get a medical certificate.

What would make travel easier? 

1. A standard medical certificate 
2. More clear and reliable information by the airline
3. More assistance or fast-track at the airport for people travelling with a lung condition.
4. A standard procedure to provide oxygen on-board.  

Saraiva urged that It is the responsibility of the patients and their organisations to identify the problem, gather data, disseminate information and advocate. 

Session three – Medical Gases 

After a delicious lunch, delegates turned their attentions to the management of medicinal gases in hospitals. Judith Ros, Quality, QP & Regulatory Affairs Manager at Air Products, shared results from a questionnaire performed in a Spanish hospital. 

When hospital personnel were asked if the selection of the gas supplier was done through the pharmacotherapeutic commission, 75% of respondents answered “no” indicating that pharmacy services are not properly involved in the selection of the gas supplier. 

When asked if the pharmacy department is responsible for documents delivered by the supplier, 70% answered “no”, indicating that there is a need to involve the pharmacy department to check batch numbers, expire dates, series numbers etc. 

Finally, when asked if there is a protocol for medicinal gases recall, 49.2% of respondents answered “no”, suggesting that a specific recall protocol is required. 

Ros explained how the handbook, ’Management of medicinal gases procedure: Quality standards of medical gases at hospitals’, approved by the Hospital Engineers Association and Hospital Pharmacists Association, is a good practice to help customers to use gases with efficacy, safety and complying with legislations. 

Medicinal gases inspection

Dr. Ronald Bauer from the Austrian Federal Office for Safety in Healthcare – the agency responsible for assessing the efficacy and safety of medicinal products and medical devices, market surveillance and the inspection of manufacturers – detailed the medicinal gases inspection process. 

Austria has a total of 28 facilities for air separation, filling and distribution of medicinal gases. Produced medicinal gases are mainly oxygen, nitrogen, air and special gas mixtures (liquid or compressed). The GMP compliance of the facilities is inspected periodically and is part of the pharmaceutical surveillance activity. Subject to inspection is the whole chain of manufacturing, from the production of the active pharmaceutical ingredient at the air separation unit, to the filling of the medicinal product and its distribution. 

Inspections cover the regular GMP requirements for the manufacturing and distribution of medicinal gases and are performed risk based. Inspection relevant topics can be maintenance of the air separation unit; separation of technical and medicinal gas production; traceability of the medicinal product to the active pharmaceutical ingredient; connectors to the medicinal containments; refilling of gas cylinders; sampling and validation of analytical procedures, and labelling of the containment of the medical product. 

The authorities 

David Cockburn, Former Principal Scientific Administrator for the European Medicines Agency gave a presentation on working with the authorities.

Cockburn highlighted the importance of dialogue during an inspection in order to influence the authorities. He encouraged delegates to be open and honest, to challenge and engage in scientific debate, ask questions so as to learn from the inspector and finally, to capitalise on the inspectorate’s own Quality Management System. 

“When looking at inspection from an EU level, the European Commission looks after the legislation and policy, and enforces some guidelines such as GMP.”

“The European Medicines Agency (EMA) is responsible for regulatory, procedural and scientific guidance, for example quality. The EMA is also responsible for regulatory expectations, such as Q&As and reflection papers.”

Cockburn concluded by saying that, “Interaction with authorities is a two-way dialogue and competent science and risk management are powerful tools that should be utilised.” 

“Working together is always better than working in isolation,” he added. 

Dr. Viviana Hoischen, Medical Advisor at Air Products provided an overview of the typical pharmacovigilance (PV) cases – the process of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications to ensure that drugs on the market are safe for patients and to identify new hazards associated with the medication.

The EIGA publication: ‘Typical post-marketing PV cases in the medical gases industry’ sets out to harmonise the approach on classification and reporting of PV cases to the Health Authorities. It also provides guidance to differentiate between Materiovigilace (MV) and PV cases. Finally, the document facilitates product safety profile follow-up. 

Some case studies which demonstrate potential issues that can arise during treatment with medical gases are:

• Burning during oxygen therapy
• Rebound effect during nitric oxide treatment
• Blindness caused by exposure to nitrous oxide during ophthalmic surgery 
• No treatment due to package defect 
• Gas mix-ups
• Abuse / misuse
• Occupational exposure

To avoid these instances Hoischen informs attendees that creating awareness within the organisation is key to complying with legal requirements. She explains that Pharmacovigilance is a legal requirement for all pharmaceutical companies, including gas manufacturers. 

A document to align all EIGA members has been issued to agree on the approach on typical PV cases. 

Up next was Messer Group’s Dr.Tobias Dietrich to give a talk on the off-label use of medicinal gases. This is the use of a licensed drug outside the approved labelling, often in paediatrics or cancer treatment. 

In principle, off-label use is not ‘intended use’; thus no liability. However the first exception is if a pharmaceutical entrepreneur expressly points out newly recognised application possibilities, then they are liable for damages. The second exception is if accumulation of side effects reports or indicates serious side effects without risk-reducing measures by the pharmaceutical entrepreneur. 

Session four – The Future for Medical Gases

Professor Olaf Dössel from the Karlsruhe Institute of Technology (KIT) kicked-off session four with a presentation on digital technologies and how they enable major steps in personalised medicine. Personalised medicine means that the patient will get precisely the therapy that solves the patients individual health problem. 

Dössel provided an example whereby new personalised data technology will assist in anaesthesia. 

He said, “ A personalised computer model of the circulation system of the patient will help to control the blood circulation. The computer model can look ahead and help to predict and avoid critical situations by adding the right drugs to the gases at the right times.” 

‘Digital Health – Lost in Legal and Regulatory Challenges?’ was the next presentation to be given by Dr. Marc Oeben, healthcare industry advisor at NOVACOS Rechtsanwälte. 

Oeben’s presentation provided an overview of recent trends and challenges in the healthcare industry related to e-health topics both inside and outside of the gases industry. 

He shared one case study which depicted a patient support programme for medical oxygen that aims to increase therapy compliance and streamline oxygen delivery processes. With this programme, the oxygen cylinder can submit data to the gas suppler, the patient can submit data, and the software can provide recommendations for additional products. 

Digital health is an innovative and fast growing market, although the main hinderance for this type of technical innovation are the legal and regulatory limitations. However, as legalities develop and patient safety and quality of care remain a priority, this market will burgeon. 

Compounding gaseous drug products

Rounding off the days sessions, Christoph Hilker of Westfalen Gas Schweiz, gave a presentation on compounding gaseous drug products.

Rare use of drug products leads to few of them being authorised, as the economic effort does not match the financial benefits. Compounding drug products by pharmaceutical companies has been a solution to that problem. However, for some EU countries, compounding to pharmacies is restricted. Because technologies for gas blends are too complex for pharmacies, this is equal to a ban on compounding gas blends where there is no authorised drug product available.  

“An improvement of quality and compliance could be achieved through enhancement of the regulations controlling the compounding of gaseous drug products. It is demonstrated that a tremendous  benefit for patients, hospital staff and sponsors of the treatments could be achieved by a compounding regulation in harmony to EU-GMP Guide part 1 Annex 6, Manufacture of Medical Gases.”