EIGAzette 2023 05 – MGC

CURRENT OVERVIEW

1. Key topics from the last report

-European Medicines Agency (EMA) initiatives: EIGA as key stakeholder

Since Covid-19 pandemic, EIGA is working as a new stakeholder and the presence and influence is being consolidated. Representatives of MGC, WG 7 and WG 15 are actively participating at following working groups:

• The EMA Task Force on availability of authorised medicines. The group works as a "supply and availability Hub" and will track progress on supply and availability activities ongoing under the “Joint Action on Shortages and the European Commission Pharmaceutical Strategy for Europe”, to streamline processes, ensure synergies and avoid duplications.

EIGA proposed that regulatory flexibility adopted during the pandemic could be transformed into permanent regulations just to be reactivated in case of need – currently under revision by EMA

• The Quality Working Party responsible to prepare, review and update of quality guidelines such as EMA Guideline on Medicinal
• The GMP/GDP Inspectors Working Group (GMDP IWG) responsible to prepare, review and update of quality guidelines such as GMP Annex 6 on Medicinal Gases.

For the last two points, EIGA achieved that the revision of both documents has been included on these Working Groups’ work program for the next year. WG7 is currently preparing a proposal for both revisions.

-WG 15 - Medical Device Regulation:

Significant delays with MDR implementation: high risk of interrupted supply of Medical Devices in Europe.

Finally on March 20th EU Commission issued an amendment of MDR:

Certificates issued by notified bodies in accordance with Directives 90/385/EEC and 93/42/EEC that were still valid on 26 May 2021 and that have not been withdrawn afterwards shall remain valid until: 31 December 2028, for class IIb (not implantable), class IIa and class I devices.

Conditions:

1. No significant changes in the design and intended purpose;
2. Do not present an unacceptable risk to the health or safety of patients or public health;
3. No later than 26 May 2024 the manufacturer will:
   1. Put in place a quality management system in accordance with MDR
   2. Formal application with a Notified Body

-Video on VIPRs use

A video was created by WG15 to provide best practices on VIPRs lifetime management to users. This activity was initially requested by the UK Heath Authorities MHRA.

Video is currently available in the E-Learning Section of EIGA website. See Operation of Medical VIPR - EIGA : European Industrial Gases Association

-EU Pharmacopoeia Monographs

The revised Oxygen 98 monograph has just been published in Pharmeuropa 34.4 and was publicly accessible until end 2022. All EIGA’s comments were considered: there are no more calorimetric tubes (except for oil) and for assay, CO, CO2, and moisture there are continuous controls. EDQM is currently reviewing all received comments, mainly coming from France.

AHG-M.8 ISO TC 121 Mirror Group

AHG-M.8 is a small group of experts following up the standardisation activities of ISO/TC 121, Anaesthetic and respiratory equipment with a more specific focus on ISO/TC 121/SC 6, Medical gas supply systems. The goal is to develop an EIGA view on topics related to ISO/TC 121 and coordinate actions, since several members of the AHG are representatives of their country in this subcommittee.

Three AHG members also have a role in the leadership of ISO/TC 121/SC 6, as chairman of the sub-committee or as convenors of working groups (WG 4 - Medical Gas Pipeline Systems, WG 5 - Transportable liquid oxygen systems for medical use and the newly created WG 8 - Pressure regulators).

In their roles, and with the support of AHG members, they have contributed to the development of:

• Drafting of the first edition of ISO 7396-3 on proportioning units, ISO 7396-4 on air compressors and ISO 7396-5 on O2 93 % sources of supply
• Drafting of the revision of ISO 18777-1 & 2 on Transportable Liquid Oxygen Systems
• Drafting of the revision of ISO 10524-3 on medical VIPRs

Industry impact: having International Standards addressing fairly the needs of the Gas Industry and providing the necessary level of safety for the equipment and devices that we operate.

2. Working Groups and Ad Hoc Groups closed

AHG-M.5: N2O Clinical Best Practices

Main objectives of the Clinical Best Practices document are to promote the safe usage of medicinal N2O and raise awareness on the misuse/abuse in order to mitigate the potential safety risks related to human exposure to these products.

In order to promote its dissemination, a communication letter was created by the AHG, which also provided a list of stakeholders that should receive the communication. The communication was also shared with National Gas Associations. Now all companies will distribute the material within their customers.

The AHG has been closed.

AHG-M.16: Cylinder Internal Quality

There are no safety/patient concerns. The MGC mostly prefer to not have a limit set, maybe a range might be acceptable.

MGC members had various viewpoints on the issue, particularly with regard to the possible publication of a limit value. Finally, no consensus could be achieved. Beyond that also the potential risk to publish a document without a threshold was discussed. The conclusion was, that this most likely would sensitize readers on one hand, without providing clear guidance how to handle the particulate issue on the other. It might also trigger issues with Health Authorities.

Accordingly, MGC has decided to close the AHG and archive the Draft Document & Test Results

 

FUTURE OVERVIEW

3. Key objectives and initiatives the coming two years

MGC

The leading objective of MGC has consolidated its position towards European Health Authorities and other EU Regulators, taking advantage of the gas industry’s visibility gained throughout the Covid-19 pandemic. MGC is currently working to:

• Continue actively to act as European Medicines Agency and WHO stakeholder for any impact on Public Health and collaborating in their initiatives
• Promote the collaboration in the industry on Vigilance initiatives regarding medicinal and medical device products, especially considering the strict MDR requirements
• Anticipate and integrate changes in regulations that could impact or significantly modify the medical gases sector; e.g. N2O reclassification and ECHA PFAS proposal and possible impact on the medical business
• Publish white papers on specific areas to spread out our view and best practices in a proactive way
• Continue the publication of documents related to the safe design, manufacturing, operation, and use of medical products
• Ensure a regular communication and synergies between medical and non-medical working groups, ad-hoc groups and with National Associations.

Working Group 7- Medical Gases

-Re-classification of N2O: There are concerns in MGC about the consequential impact of The Netherlands Authority’s decision to include Medicinal N2O within the so called “Opium Act”, meaning stricter traceability requirements, lots of paper administrative work for cross-border transport and more stringent customer requirements.

WG7 created a letter alerting on this situation and distributed to all National Gas Associations. WG7 is also in contact with the Hospital Pharmacist Association to discuss the impact and possible next steps if other authorities take the same position.

Define Standards & Best Practices

-White Paper on Medicinal Oxygen: EIGA’s activity can often be described as “reactive”.  The objective is to create a “proactive” white paper to provide information on production, controls, supply chain, liability and environmental aspects of both ASU and Hospital PSA. Target audience: managers and engineering staff at hospital facilities. The goal of publication has been extended to Q3 2023

- Life cycle of Nitrosamines

The purpose is to provide a comprehensive list the starting materials used for the manufacture of API’s and the medicinal product manufacturing processes and use a standardized risk assessment process to justify no further testing in a consistent manner.

Working Group 10 - Homecare

Define Standards & Best Practices

Key initiative is the extension of the scope of WG 10 to include Sleep Therapy and Ventilation. This will result in a set of documents with best practices regarding these therapies. The work is ongoing, and a publication plan is under preparation.

Working Group 15 - Medical Devices

Define Standards & Best Practices

• Identification of common Rules for the Classification of pipeline systems as Medical Device (priority score 1)
• Substances of concern in medical devices (priority score 1)
• Common General safety and performance requirements for Argon (priority score 2)
• Notified bodies audit on raw material suppliers. Rationale on supplier's qualification (priority score 2)
• Drug Generating devices (priority score 3)

AHG-M.8 ISO TC 121 Mirror Group

Two members of AHG M.8 are participating to the Advisory Group (AG) on Oxygen Supply Source Considerations whose goal is to assess technical and clinical implications of a variable concentration of O2 on the performances of devices covered by ISO/TC 121 (anesthesia workstations, ventilators, medical gas pipeline systems, etc...) and ensure that the works are done in a rigorous way and with data from reliable source.

A new WG on "addressing disconnection of oxygen delivery devices" is about to be created at ISO/TC 121 level. As it concerns, among others, accidental disconnections that may arise between an oxygen cylinder and a patient and that decision made in the WG may have an impact for EIGA members, AHG M-8 members will volunteer to participate in the WG to monitor the works and represent the medical gases industry views and experience.

AHG-M.14 - Pharmacopoeia 9G Mirror group

The key objectives for next year remain as follows:

• Evaluation of different methods for determining water in gases: the proposal is to build a chapter with different analytical procedures adapting to the different gases and different contents of water to be determined. The idea is not to replace the existing method in monographs, but to make alternative procedures available. Validated procedures will be proposed, so that for specific gases the validation work for users could be limited;
• Monograph Air, medicinal: adoption of the PID (Photo Ionization Detector) method for the measurement of oil in gases - in progress at Pharmacopoeia table. The method appears to be a promising alternative to the unreliable detector tubes (e.g. Draeger tubes).
• Revision of Oxygen 93 monograph: risk evaluation and redefinition of the proposed monograph, this once Oxygen 98 monograph will be available.
• Stability of gases at molecular level: Examination of stability, and reactivity of gases, on a molecular level. The goal is to generate a document giving an indication on the stability of gases of different categories (elemental gases, compound gases, mixtures, etc.).

AHG-M.17 - Pharmacovigilance

• Complete review of Doc 203-18 Typical Post-Marketing Pharmacovigilance Cases in the Medical Gases Industry by Q3 2023
• Evaluation of preparation of general 2 minutes animation video for awareness of what Pharmacovigilance in the Gas Industry is (important, risks, raise awareness etc). Examples from Bayer or Roche on YouTube for inspiration
• Prepare communication information of the Pharmacovigilance in the Gas Industry

AHG-M.18 - Unclassified gases used for medical purposes

• The objective of this AHG is to set common rules for the manufacturing of gases that are used for medical purposes but are not defined as drugs or medical devices. This is often due to historical reasons in the different EU countries.
• Some discussions still ongoing. Need to define the minimum requirements for these products. Quality of gases is the main topic; all indications are physicians' responsibility.
• The AHG will produce a Brief as basis for the AHG-M.18 to continue with their work and produce a very short doc. Still ongoing
• Upon receiving of this Brief, the AHG will be re-launched.