ARCHIVED - Bilateral Meeting Program with Compressed Gas Association (CGA) - Record of Decisions - October 29, 2009

Agenda

Location: 250 Lanark Avenue, Graham Spry Building, Ottawa (Room 150)

Date: October 29, 2009

Time: 1:30 p.m. to 3:30 p.m.

Participants

Health Canada

• Chad Sheehy - A/Director, CCLD, HPFBI (meeting co-chair)
• Sonya Abgessi - A/Manager, Establishment Licensing Division, HPFBI
• Andrew Sun - HPFBI
• Roy Thaller - A/Manager, Drug GMP Inspection Unit, HPFBI
• Andrew Adams - Director, BPS, TPD
• Suranika Dias - BPSIP, TPD
• Thea Mueller - BPSIP, TPD
• Joyce Pon - BPSIP, TPD
• Daniel Yoon - Medical Devices Bureau, TPD

Compressed Gas Association (CGA)

• Joanne Lekkas - Linde Canada (Chair of CGA's Canadian Medical, Food, and Beverage Gases and Equipment Committee) (meeting co-chair)
• Anne La Ferrière - Air Liquide Canada
• Ken Lum - Praxair Distribution
• Amy Park - Compressed Gas Association
• Danielle Bossack - Praxair Distribution (by phone)
• Alice Chen - VitalAire (by phone)
• Ed Csira - Air Products and Chemicals (by phone)
• Gordon Edwards - Praxair Canada (by phone)
• Patrick Kaigle - Air Liquide Canada (by phone)
• Patrick Litwin - VitalAire (by phone)
• Ron Smart - Medigas (by phone)
• Jim Wallace - Gas Pro (by phone)

1. Welcome and Introductions

Chad Sheehy called the meeting order and welcomed the participants.

Joanne Lekkas thanked Health Canada for this opportunity to meet.

The meeting participants introduced themselves.

2. Review of Agenda

The agenda adopted.

3. Approval of the minutes of October 28, 2008

The comments on the draft minutes of the previous meeting minutes were discussed, and the minutes were amended accordingly and approved.

4. Review of previous action items (from October 28, 2008 meeting minutes)

a) Action items from the meeting on April 13, 2007

Item 4.1: (Approvals for gases in medical applications - drugs versus medical devices)- TPD to develop and to provide guidance to industry as to when a gas is considered a drug, a medical device, or a natural health product.
Update: (See discussion under 5.2 of this meeting.)
Action item is on-going.

Item 4.1: (Approvals for gases in medical applications - drugs versus medical devices) - TPD to meet with CGA to discuss and to resolve the issues pertaining to compounding and approvals for gases in medical applications.
Update: (See discussion under 5.2 of this meeting.)
Action item is on-going.

Item 4.1: (Approvals for gases in medical applications - drugs versus medical devices) - (Additional action item from the meeting on November 14, 2007) Barbara Benning will consider the possibility of a Health Canada presentation on progressive licensing at the next bilateral meeting.
Update: It was agreed to withdraw and to close this action item, as it is no longer applicable; developments in discussions between Health Canada and CGA have taken this issue in other directions.
Action item is withdrawn.

Item 4.2: Foreign site inspections in the U.S. - Chad Sheehy to update the policy document, Conditions for Acceptance of Foreign Inspection Reports for Listing Foreign Sites on Canadian Establishment Licences (POL-0013). (Policy 0013 will be changed to Guide 0080.) The document will reflect the Inspectorate's decision to continue to accept corporate and consultant audit reports for foreign medical gas establishments as evidence of GMP compliance.
Update: Chad Sheehy reported that Guidance on Evidence to Demonstrate Drug GMP Compliance of Foreign Sites (GUI-0080) has been posted on Health Canada's website. Chad Sheehy also noted that, as stated in the cover letter for that guide, HPFBI is soliciting comments on the possible future web-posting of certain information concerning foreign sites that have been approved by Health Canada.
Action item is completed.

Joanne Lekkas enquired if Health Canada sends a letter or document to approved foreign sites. Chad Sheehy responded that a document is not sent to the foreign site and that it is the responsibility of the Canadian importer to provide information to the foreign site. The importer could send a copy of their letter from Health Canada to the foreign site.

b) Action items from the meeting on November 14, 2007

Item 3: HPFBI will follow up with Brenda Lajeunesse regarding the posting on Health Canada's website of the minutes from the bilateral meetings held on October 13, 2006, April 13, 2007, and November 14, 2007.
Update: HPFBI will follow up regarding this action item. The minutes from the previous bilateral meeting on October 28, 2008 will also be posted on the website.
Action item is on-going.

c) Action items from the meeting on October 28, 2008

Item 4.1: Approvals for gases in medical applications - TPD (BPSIP) and CGA will pursue further work regarding approvals for gases in medical applications.
Update: CGA submitted a letter to Brigitte Zirger at TPD (BPSIP) on May 1, 2009, regarding the market authorisation process for gases in medical applications (drugs versus medical devices. TPD (BPSIP) has been in contact with Pat Litwin, on behalf of CGA, to pursue further work. (See also discussion under 5.2 of this meeting.)
Action item is on-going.

Item 4.2: Expiry date requirements for medical gases - The Inspectorate (GMP Unit) will get further updates from the Minister's office about the proposed regulatory amendments, published in Part I of the Canada Gazette on September 30, 2006, addressing the formalisation of the exemption for medical gases from expiry dates.
Update: Suranika Dias reported that more discussion on the issue is needed before finalising the regulations. (See also discussion under 5.1 of this meeting.)
Action item is completed.

Item 4.2: Expiry date requirements for medical gases - CGA to provide rationale and supporting data to TPD (BPS) as to why an expiry date is not required for medical gases. (A scientific literature review will be provided.)
Update: CGA submitted a letter to Alan Viau at TPD (BPS) on May 1, 2009, regarding expiry date requirements for medical gases. (See also discussion under 5.1 of this meeting.)
Action item is completed.

Item 4.5: Transfilling of cylinders with medical gases - Chad Sheehy to follow up with regards to jurisdiction over transfilling by fire departments, ambulances, hospital homecare programmes, and airlines.
Update: Chad Sheehy noted that Wissam Sader had looked into this issue. Chad Sheehy or Roy Thaller will follow up.
Action item is on-going.

Item 5.1: Liquid nitrogen NF in open-top dewars - CGA to provide justification for removing the "small quantities" and "for professional use" limitations from the Q&A.
Update: CGA submitted a letter to Chad Sheehy (HPFBI) on May 1, 2009, regarding the medical gas GMP Q&A on liquid nitrogen NF in open-top dewars. Chad Sheehy sent a letter responding to CGA on June 11, 2009.
Action item is completed.

Action: HPFBI will update the Q&A posted on the Health Canada website to reflect the information in the letter from Chad Sheehy.

Item 5.2: Ethylene oxide mixtures - The Inspectorate (GMP Unit) will update the Q&A on ethylene oxide mixtures to state that the provisions of that Q&A apply to all medical gas mixtures containing ethylene oxide, and not just mixtures of ethylene oxide and carbon dioxide.
Update: Chad Sheehy asked Ken Lum to forward to Roy Thaller the email that Ken Lum had received from Wissam Sader on this issue. Roy Thaller will follow up.
Action item is on-going.

5. Old items for further discussion

5.1 Expiry date requirements for medical gases

Andrew Adams noted that he had reviewed the letter that CGA had submitted on May 1, 2009, to Alan Viau, then Acting Director, Bureau of Pharmaceutical Sciences (BPS), regarding expiry date requirements for medical gases. Andrew Adams stated that some good points had been made, but further discussion was needed.

CGA suggested that a separate meeting be held between Health Canada and CGA representatives to continue discussions on this issue. TPD enquired regarding initial CGA contacts to obtain further technical information or clarification. Joanne Lekkas was identified as a CGA contact, as Chair of CGA's Canadian Medical, Food, and Beverage Gases and Equipment Committee. Pat Litwin was also identified as a CGA contact, as he had conducted the literature review included in the CGA letter. Amy Park was also identified as a CGA contact, for organising a separate meeting or working group.

CGA reviewed some of the history of this issue. Interpretation 3 in the "Records" section (C.02.020 to C.02.024) of Health Canada's Good Manufacturing Practices (GMP) for Medical Gases used to state:

"3. Section C.02.020 (1) (d) does not apply to medical gases. However, if a firm's written procedures call for an expiration date, then a firm will be expected to follow their procedures and apply an expiration date to the product."

This interpretation remained unchanged in the draft revised GMP for Medical Gases, issued for comment in May 2006. However, it was amended as follows, when the final version of revised GMP for Medical Gases was issued in December 2006:

"3. Documentation must be available to support the expiry date of the medical gas. In the case of very stable gases that have been used for a long time and packaged in containers that have also been used for a long time, bibliographic data is sufficient. For gas mixtures, the expiry date should be based on validation studies pertaining to the physical aspects such as the rate of stratification."

As CGA had stated in a previous letter to HPFBI on February 19, 2007, they do not agree with the deletion of the historical interpretation that medical gases do not require an expiration date.

As CGA had also stated in a letter to HPFBI on December 4, 2006, CGA supports the proposed amendment to section C.02.030 of the Food and Drug Regulations, which was published in the Canada Gazette, Part I, on September 30, 2006, to clarify that the expiry date requirements in paragraph C.02.020(1)(d) do not apply to medical gases. As stated in the Regulatory Impact Analysis Statement published in support of the amendment, "Health Canada has historically favoured the interpretation that paragraph C.02.020(1)(d) does not apply to medical gases". This proposed regulatory amendment followed a meeting between Health Canada staff and CGA members that took place on November 7, 2003, at the request of Ms. France Dansereau, then Manager, Inspection Unit, for Health Canada's HPFBI. At this meeting, CGA members had provided information requested by Health Canada, to support the formalisation of certain historical interpretations for medical gases in the regulations, including an exemption with respect to expiry dates.

CGA agreed that, as noted by Health Canada, further consequential amendments would also be needed in C.01 of the Food and Drug Regulations in order to resolve any potential conflicts resulting from the aforementioned proposed regulatory amendment.

TPD enquired regarding expiry date requirements for medical gases in the United States and in European Union.

CGA explained that they have been working with the U.S. Food and Drug Administration (FDA) for many years regarding a citizen's petition filed in 1979 to exempt medical gases from expiration dating. The U.S. FDA has stated that the expiration dating requirements in the U.S. regulations are not being enforced for medical gases pending their formal response to that petition. The U.S. FDA has also stated that stability and degradation of medical gases are not issues and that expiration dates do not apply to cryogenic liquid containers.

CGA also explained that the European requirement is that medical gases must have an expiry date, but no data is required to support the assignment of the expiry date. Enquiries made with medical gas firms in the EU determined that, although it is not entirely a clear process, the assignment of an expiry date appears to be related to the record retention requirements for medical gas products more than anything else.

CGA noted that, in general, expiry dates would typically be based on and supported by stability data. However, under section C.02.030 of the Food and Drug Regulations, the sample requirements in section C.02.025 and the stability requirements in sections C.02.027 and C.02.028 do not apply to medical gases.

TPD asked regarding some medical gases that need an expiry date. CGA stated that, where there are demonstrated concerns that a change in potency, purity, or physical characteristics may occur over time due to the nature of a particular medical gas, an expiry date should be established, and a firm would be expected to follow their procedures and apply an expiry date to the product. However, it should be noted that there are very few such gases in use, e.g. nitric oxide and nitrogen mixtures and sterilant gas mixtures containing ethylene oxide.

Chad Sheehy re-iterated that, while this issue is being resolved, HPFBI will not consider the enforcement of the expiry date requirements in the revised GMP for Medical Gases (GUI-0031) to be a priority. If any observations are noted from an inspector, they should be raised with Chad Sheehy.

Andrew Adams stated that more internal discussions are needed at Health Canada; he also agreed that, as suggested by CGA, a separate meeting or working group with Health Canada and CGA representatives should take place.

Action: By the end of March 2010, Health Canada will provide CGA with a status report and a timeline for further discussions on the issue of expiry date requirements for medical gases.

Chad Sheehy noted that GUI-0031 would be coming up for its three-year review soon, probably in 2010. HPFBI intends on consulting through Drug Establishment Licence holders and CGA. The possibility of a working group for consultation on GUI-0031 revisions was discussed.

5.2 Approvals for gases in medical applications

Prior to this bilateral meeting, Suranika Dias had sent three questions through Pat Litwin to CGA, regarding gases used in medical applications (drugs versus medical devices). CGA distributed initial responses to those three questions, to be discussed further at this meeting.

As stated in the letter from Health Canada on November 2, 1999, "a gas or mixture of gases registered as a drug does not need to be registered as a device". CGA noted that, hence, there are a number of medical gases that have a Drug Identification Number (DIN) but do not currently require a Medical Device Licence (MDL) even if used in a device application. TPD enquired if drugs (medical gases) are actually used for medical devices without an MDL. CGA responded that medical gases (i.e. drugs) could be used for medical devices without an MDL. Companies do not always know for what a gas will actually be used; an end user typically requests an order for a specific medical gas (i.e. drug), and the company would not know if the end user actually uses it for a medical device application. The customer could also order multiple cylinders of a particular gas and use the individual cylinders for different applications.

Suranika Dias and Joyce Pon noted that the letter that CGA had submitted to Brigitte Zirger on May 1, 2009, regarding the market authorisation process for gases in medical applications (drugs versus medical applications), encompassed primarily the following three issues:

1. The compressed gas industry would like to propose that gases in medical applications (drugs or medical devices) be assessed for market authorisation under one scheme.
2. Customised mixtures are often produced in response to requests from healthcare professionals, resulting in low-volume production. Supporting efficacy data for new gas mixtures are not generally available to the compressed gas company supplying the mixture, given they are not formally involved in the use or studies. Since such gas mixtures are produced in low quantities based on unique customer demand, it could be difficult to obtain market authorisation for every foreseeable gas mixture in a reasonable time to meet the end users' needs.
3. Individual components in these gas mixtures may vary in composition by only a few percentage points. Some companies currently have DINs for medical gases that cover ranges of concentrations of component gases. Concentration ranges should be permitted (perhaps through the establishment of class monographs).

CGA explained that the same gas product may be used as a drug (i.e. a medical gas), a medical device, or other uses such as a specialty gas (a non-medical application).

CGA also explained that both medical gases (i.e. drugs) and gases considered medical devices are usually fabricated or packaged in the same facility, often utilising the same equipment and personnel and under the same quality control unit. This entails the necessity to comply with two regulatory schemes and be subject to two separate inspections of the same facility. In the case of gases considered medical devices, under the Medical Devices Regulations, a quality system must be certified to ISO 13485, Medical devices - Quality management systems - Requirements for regulatory purposes; this is not the case for quality systems for medical gases (drugs).

Suranika Dias and Thea Mueller explained that major regulatory changes would be needed to allow for a single scheme for market authorisation for gases in medical applications and that TPD would like to work within the existing regulatory framework.

CGA noted that all gas medical devices are Class I in the U.S. and that the list of gas medical devices provided previously (in March 2006) by Health Canada all seem to be Class II. Daniel Yoon confirmed that, if the gas is used for calibration, it is a Class II medical device in Canada in accordance with classification rule 7(2)(a) of the Medical Devices Regulations.

Suranika Dias noted that TPD issues MDLs for one specific concentration of components and not a range of concentrations.

Joyce Pon stated that TPD could possibly consider the establishment of class monographs for gases to address concentration ranges. Class monographs would simplify the drug identification number (DIN) process because the applicant would not have to show the chemistry again with each application. Joyce Pon stated that, however, DINs should be issued for specific concentrations. CGA noted that, at a previous bilateral meeting on April 13, 2007, Marilyn Schwartz of TPD had stated that component composition ranges have been accepted for DINs for mixture products; in such cases, the name for the DIN includes only a maximum component value, but the ranges are included in the internal notes for that DIN.

CGA expressed concern that, for customised gas mixtures produced in low quantities, it could be difficult to obtain market authorisation in a reasonable time to meet the end users' needs, particularly if any change in concentration would require a new approval. TPD noted that it should take 45 days for a DIN approval. Some CGA members noted that the Special Access Programme had been used, as advised by HPFBI, for approval in some cases, but it was not an ideal solution for medical gases.

Action: By the end of March 2010, TPD and CGA will meet (outside of the bilateral meeting programme) for further discussions on the issue of the market authorisation process for gases in medical applications (drugs versus medical devices).

5.3 Cost Recovery Initiative

CGA members requested an update regarding the status of HPFBI's revised Cost Recovery Initiative proposal with respect to medical gases.

HPFBI provided an update regarding the stakeholder engagement on options for proposed establishment licensing fees for the medical gas industry that took place from August 24 to September 14, 2009. The stakeholder engagement was based on the Human Drug Independent Advisory Panel's recommendation #5 to recognise the unique situation of the medical gas industry. Two options had been proposed:

1. charge the packaging fee once (per year) even where the company has multiple sites performing transfilling activities, and
2. charge the importing/distributing fee once even where the company has multiple sites performing importing/distributing activities.

Andrew Sun reported that, among the responses received, there was near-consensus regarding option 1 being favourable. Only one respondent had stated the option 2 was favourable. A few respondents, particularly those companies with fewer sites, had stated that neither option was beneficial.

Andrew Sun also reported that HPFBI is internally further considering the stakeholder feedback and that more analysis is pending.

HPFBI is developing a user fees proposal to table to Parliament that will encompass all aspects of the Cost Recovery Initiative.

6. New items

6.1 Unique device identifiers & unique product identifiers

Pat Litwin presented this issue on behalf of CGA. CGA enquired regarding Health Canada's position on unique device identifiers and unique product identifiers and any work being done or considered by Health Canada in this area.

CGA noted that they are aware of on-going discussions in the U.S. and elsewhere and that various jurisdictions seem to be requiring or considering unique identifiers (e.g. barcodes) to track pharmaceutical products and medical devices. The purpose of such tracking is reported to be for patient safety, including ensuring that a patient receives the correct treatment as prescribed, preventing harmful drug interactions, and prevention of counterfeiting.

CGA also noted that, under item 16(b) of the Record of Decisions for the MEDEC - Health Canada bilateral meeting on November 17, 2008, Barbara Harrison of HPFBI had informed MEDEC that her office was working on this initiative.

Roy Thaller reported that Health Canada is a member of the Global Harmonization Task Force (GHTF). Both TPD and HPFBI representatives are monitoring and participating in GHTF discussions regarding unique identifiers. The U.S. seems to be going in a direction different from the rest of the world. Health Canada intends to follow the GHTF decision.

Chad Sheehy noted that, for drugs, there is no discussion at the branch level currently to consider unique identifiers.

Amy Park noted that CGA had some comments and concerns regarding implementation of requirements in the U.S.

7. Next meeting and adjournment

The next meeting was tentatively scheduled for April 20, 2010, in the afternoon.

The meeting was adjourned.