ARCHIVED - Bilateral Meeting Program with Compressed Gas Association (CGA) - Record of Decisions - October 13, 2006

Agenda

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

Date: October 13, 2006

Time: 10:00 a.m. to 12:00 p.m.

Participants

Health Canada

Kim Dix, A/Associate Director General, Health Products and Food Branch (HPFB) Inspectorate, Chair
Louise Jodoin - HPFB Inspectorate
Johanne Veenstra - HPFB Inspectorate
Marylee Dean - HPFB Inspectorate
Preetham Natarajan - HPFB Inspectorate
Jo Roulston - HPFB Inspectorate

Compressed Gas Association (CGA)

Patrick Litwin (VitalAire) - Chair, CGA Canadian Medical, Food, and Beverage Gases and Equipment Committee
Serge Bellehumeur (Air Liquide Canada)
Alice Chen (VitalAire)
Kim Greenwood (Praxair Canada)
Anne La Ferrière (Air Liquide Canada)
Joanne Lekkas (BOC Canada Ltd.)
Ken Lum (Praxair Canada Inc.)
Amy Park (Compressed Gas Association)

1. Welcome and Introductions

Kim Dix, Co-Chair, called the meeting order and welcomed the participants.

Patrick Litwin thanked the HPFB Inspectorate for providing this opportunity to meet, to provide input on the Good Manufacturing Practices (GMP) for Medical Gases (GUI-0031), and resolve other pending issues.

Kim Dix presented the Therapeutic Products Directorate (TPD) document entitled "Bilateral Meeting Program". This document provides an overview of the system used (e.g., responsibilities, timelines, scope and purpose of meetings, tools, etc.) to organize and carry out bilateral meetings between TPD and Associations. Kim Dix invited CGA to take a look at this document, and proposed to adopt a similar system for these bilateral meetings if CGA is in agreement.
Action: Kim Dix to send the TPD document entitled "Bilateral Meeting Program" to Amy Park.

Update: Kim Dix sent the TPD document to Amy Park on October 13, 2006.
Action item is completed.

2. Review of Agenda

No new items were added to the agenda. The second last agenda item number was corrected to 4.5.

The agenda was approved.

3. Review of action items and approval of the Meeting Minutes of February 15, 2006

Minutes were approved as presented.

Action Items

Item 3. Approval of the Meeting Notes of May 25, 2005 - Health Canada will be checking to see if other committee meeting minutes are posted on Health Canada's Website.

Update: Louise Jodoin confirmed that the meeting notes of the October 13, 2006 meeting, and subsequent meeting notes, will be posted on the Health Canada Website. Louise Jodoin also confirmed that HPFB Inspectorate agreed with the contents of the minutes of the May 25, 2005 meeting that were sent by Amy Park.
Action item is completed.

Item 4.1 Dispensing Liquid Oxygen United States Pharmacopeia (USP) in homecare units at a facility site - HPFB Inspectorate will provide rationale for finished product testing being required for each homecare vessel filled at a facility, which would not be required for curbside delivery, when a certificate of analysis is available for the tank from which the homecare vessels are filled in both situations.

Update: Louise Jodoin indicated that a medical gas expert will attend the next bilateral meeting in order to address CGA's concern regarding the finished product testing requirement for homecare vessels filled at a facility.
Action item is ongoing.

Item 4.1 Dispensing Liquid Oxygen USP in homecare units at a facility site - HPFB will send correspondence when the policy discussion pieces for each building block of the External Charging Initiative Framework are posted for comment on Health Canada's Website. (Heather Throop)

Update: Kim Dix explained that there will be two parts to the policy discussions regarding the External Charging Initiative Framework: 1) the Approach, and 2) the actual changes. At this time, HPFB Inspectorate doesn't know the timeframe for the consultation on each policy discussion. However, all the individuals that participated in the consultation meeting, including CGA, will be included in the stakeholder list. In addition, Patrick Litwin suggested that the Canadian Homecare Association be included in the stakeholder list.
Action item is completed.

Item 4.2 Curbside Filling - CGA would like to request HPFB Inspectorate to include their response and a rationale with respect to the Drug GMP Committee's decision pertaining to curbside filling in the medical gases Q&A document (GMP Interpretation Decision Records for Medical Gas (GUI-0062)).

Update: Louise Jodoin explained that the GMP Interpretation Decision Records for Medical Gas (GUI-0062) will be revised after the GMP for Medical Gases (GUI-0031) is finalized. The general Q&As have been integrated in GUI-0031 but the specific Q&As will remain in GUI-0062. Furthermore, the format of the Q&A document will change.
Action item is on-going (awaiting revision of the Q&A document).

Item 4.3 GMP Guidelines for Medical Gases - CGA would like to enquire if it is possible to receive a copy of the French translation of the medical gas industry presentation. (Item identified after meeting.)

Update: Louise Jodoin's Administrative Assistant gave a copy of the French translation of the medical gas industry presentation to Amy Park on October 13, 2006.
Action item is completed.

Item 4.4 Liquid Nitrogen NF - HPFB Inspectorate will relay that Liquid Nitrogen NF, filled on site in open-top dewars, is exempt from analysis, since it is not physically possible to be performed, to their Inspection Subcommittee.

Update: Louise Jodoin presented the text that will be sent via a GMP Bulletin to the Inspectorate inspectors. CGA provided comments and the text was revised to the following: "When a fabricator/distributor supplies liquid nitrogen NF in an open-top dewar, no additional testing is required provided that the source container has been tested, met appropriate specifications and has been released by authorized people."
Action item is completed.

Item 4.4 Liquid Nitrogen NF - HPFB Inspectorate to add this exemption to the medical gases Q&A document (GMP Interpretation Decision Records for Medical Gas (GUI-0062)).

Update: The GMP Interpretation Decision Records for Medical Gas (GUI-0062) will be revised after the GMP for Medical Gases (GUI-0031) is finalized. This exemption regarding finished product testing of Liquid Nitrogen NF filled on site in open-top dewars will be added to GUI-0062.
Action item is on-going (awaiting revision of the Q&A document).

Item 4.5 Natural Health Products Regulations and medical gases - Company contacted CGA concerning this issue (Natural Health Products Regulations and medical gases). CGA will give the company an update concerning this meeting.

Update: Patrick Litwin indicated that some companies are currently treating medical gases as natural health products. Therefore, what action should CGA members follow regarding these companies? Louise Jodoin stated that CGA members should submit a trade complaint. Further information can be found in the document entitled "How to Submit a Trade Complaint", available on the Health Canada Website.
Action item is completed.

Item 4.6 Drug versus medical devices - HPFB Inspectorate will provide CGA with the name of the head of the Classification Committee.

Update: Kim Dix indicated that the head of the Classification Committee is Brigitte Zirger, Director of the Bureau of Policy, Science and International Programs within TPD.
Action item is completed.

Item 4.6 Drug versus medical devices - CGA should request a meeting again with TPD, noting that the discussion at February 15, 2006 bilateral meeting did not resolve the issues surrounding the approval of gases and gas mixtures used in medical applications, as well as summarising the information regarding medical devices provided by Nancy Shadeed and requesting clarification regarding the process for DINs and marketing authorisations.

Update: CGA is drafting a letter to TPD.
Action item is ongoing.

Item 4.6 Drug versus medical devices - Roy Thaller will send a copy of the Compounding presentation and current draft of the document to Amy Park.

Update: Roy Thaller sent a copy of the presentation to Amy Park. Louise Jodoin explained that the draft policy document entitled Manufacturing and Compounding Drug Products in Canada (POL-0051) is almost ready to be posted for comment. Therefore, a copy of the February 2006 version of the document will not be sent to Amy Park.
Action item is completed.

Item 4.6 Drug versus medical devices - HPFB Inspectorate and CGA will discuss compounding issues with respect to medical gases at the next bilateral meeting.

Update: The compounding issue with respect to medical gases is item 4.1 of the October 13, 2006 bilateral meeting.
Action item is completed.

Item 5.1 Ethylene oxide / carbon dioxide mixtures - HPFB Inspectorate to add this exemption to the medical gases Q&A document (GMP Interpretation Decision Records for Medical Gas (GUI-0062)).

Update: This exemption regarding identity testing for ethylene oxide/carbon dioxide mixtures will be added to GUI-0062. Louise Jodoin also presented the following text that will be sent via a GMP Bulletin to the Inspectorate inspectors: "Due to the carcinogenic nature of ethylene oxide, an identity test is not required to be performed on mixtures of ethylene oxide/carbon dioxide by the importer if the importer sells the gas mixture "as is in the same container" and does not perform any additional fabricating and/or packaging operations for this gas mixture. A certificate of analysis will be required from the fabricator of the gas mixture." CGA agreed with the proposed wording.
Action item is on-going (awaiting revision of the Q&A document).

Item 5.2 Drug Establishment licence activity - fabricate vs. package - Merry Bujaki will address the Inspectors inconsistencies at the All-Staff.

Update: Merry Bujaki did address the Inspectors inconsistencies at the All-Staff meeting in April 2006. Louise Jodoin is also in constant communication with the Operational Centre Managers and inspectors.
Action item is completed.

Item 5.2 Drug Establishment licence activity - fabricate vs. package - HPFB Inspectorate will include this in an internal "GMP Bulletin" to the inspectors.

Update: Louise Jodoin presented the following text that will be sent via a GMP Bulletin to the Inspectorate inspectors:

The following operations are considered a "fabricate" activity:

  1. medical gases produced via air liquefaction (i.e., air separation plants) and/or
  2. medical gas mixtures made by filling into cylinders (i.e., packaged gases).

Transfilling of medical gases either at the facility or curbside is considered a "package" activity.

Facilities should have establishment licences that reflect what activity they are conducting."

CGA agreed with the proposed wording.
Action item is completed.

Item 5.2 Drug Establishment licence activity - fabricate vs. package - CGA would like to request that this clarification also be provided in a document that is available externally. (Item identified after meeting.) (Louise Jodoin)

Update: This clarification regarding fabricate vs package with respect to medical gases will be added to GUI-0062.
Action item is on-going (awaiting revision of the Q&A document).

DECISION: It was agreed that GMP Bulletins that pertain to medical gases will be shared with CGA.

4. New Issues

4.1 Compounding issues with respect to medical gases

Louise Jodoin explained that for medical gas mixtures, gases must be mixed prior to obtaining a DIN. Some mixtures need to be prepared for specific circumstances and because of a specific patient's need and cannot wait for DIN approval. These mixtures could be candidates for compounding. CGA is encouraged to complete and submit an Agenda Item Summary, requesting the attendance of a TPD representative to address this issue, for the next bilateral meeting. Furthermore, the policy document entitled Manufacturing and Compounding Drug Products in Canada (POL-0051) will be posted on Health Canada's Compliance and Enforcement Website for a 75 day comment period. CGA is invited to participate in this public consultation to ensure that the medical gas industry needs are met.
Action: CGA to complete and submit an Agenda Item Summary for our next bilateral meeting.

4.2 Drug Establishment Licence requirements for foreign sites

Kim Greenwood presented the issue. CGA is seeking clarification regarding foreign inspection reports in support of listing a foreign site on a Drug Establishment Licence.

As noted in item 5.4 of the meeting notes from the bilateral meeting held on May 25, 2005, a report from a corporate Quality Assurance group performing a GMP audit would be acceptable.

However, a Health Canada (Drug GMP Inspection Unit) staff member has informed a CGA member that a corporate self-assessment would no longer be acceptable as evidence of GMP compliance when registering a foreign site.

Louise Jodoin explained that a corporate or a consultant audit report for medical gases may be acceptable as GMP evidence where no recent (less than 3 years old) inspection report from the Inspectorate, a Regulatory Authority (MRA), or a Qualified Authority is available. In order to be accepted for review by the Inspectorate, the requirements outlined in section 5.4 of the policy document Conditions for Acceptance of Foreign Inspection Reports for Listing Foreign Sites on Canadian Establishment Licences (POL-0013) must be met.

If one of the requirements outlined in section 5.4 is not met (i.e., audit not conducted against Canadian GMPs, audit report in the format of a checklist instead of written observations, no corrective measures provided), the GMP evidence provided is considered unacceptable. As a result, a letter is sent to the Canadian importer indicating why the report was not acceptable.

The HPFB Inspectorate is aware that U.S. medical gas establishments are not inspected frequently by the U.S. FDA, and consequently, Canadian importers of medical gases might be in a difficult situation. In the mean time, the HPFB Inspectorate will be conducting inspections of nine (9) medical gas establishments located in the U.S. to obtain a snapshot of the current situation with the medical gas industry in the USA. During that period, no corporate audit report will be accepted as evidence of GMP compliance. Once this blitz of inspections will be completed (end of January 2007), the policy document will be revised as required and relevance of corporate audit reports as GMP evidence will be evaluated.

CGA members are invited and encouraged to send requests to the Inspectorate as soon as possible in order to perform foreign site inspections of medical gas establishments for which GMP evidence is expiring at the end of 2006.

Action: CGA members to send requests to the Inspectorate as soon as possible in order to perform foreign site inspections of medical gas establishments for which GMP evidence is expiring at the end of 2006.

4.3 CGA publication P-8.2, Guideline for Validation of Air Separation Unit and Cargo Tank Filling for Oxygen USP and Nitrogen NF

Kim Greenwood presented the issue. A Health Canada Inspector in Thunder Bay has suggested strongly that the GMP for Medical Gases (GUI-0031) should include a reference to CGA's method of validation described in CGA publication P-8.2, Guideline for Validation of Air Separation Unit and Cargo Tank Filling for Oxygen USP and Nitrogen NF.

CGA would like to introduce P-8.2, have a discussion with Health Canada to determine if CGA's approach is acceptable, and in which case, CGA would like to request that it be considered for reference in the GMP for Medical Gases (GUI-0031).

Louise Jodoin indicated that the Health Canada practice is to reference international guidelines, such as International Conference on Harmonisation (ICH) or Pharmaceutical Inspection Co-operation Scheme (PIC/S) documents. Therefore, the Inspectorate respectfully declines CGA's request to add a reference to CGA P-8.2 in the GMP for Medical Gases (GUI-0031). The Inspector was most likely not aware of this Health Canada practice.

Ken Lum pointed out that other federal departments, such as Transport Canada, do include references to CGA documents.

CGA's method of validation described in CGA publication P-8.2 may be acceptable as long as it does not contradict Health Canada validation guidelines.

4.4 Schedule Ethical

Patrick Litwin presented the issue. Medical gases are drugs classified under Schedule E to the Food and Drugs Act. CGA is seeking clarification concerning how Schedule E drugs are defined and what specific regulatory references or requirements exist for Schedule E drugs.

Kim Dix confirmed that Schedule E of the Food and Drugs Act has nothing to do with Ethical Drugs. Medical gases are considered to be ethical drugs. An ethical drug is defined on Health Canada's Website as "a drug that in accordance with Federal Legislation does not require a prescription, but that is generally prescribed by a medical practitioner, eg. Nitroglycerine". This definition is available online on the Drug Product Database (DPD) under Terminology. A decision is made by the Therapeutic Products Directorate (TPD) during the review of the drug submission, whether the gas will be classified as an ethical drug or not.

Furthermore, Kim Dix confirmed that the definition for "distribute" does apply to medical gases, since the definition also includes a non-Schedule-specific reference to "a distributor of a drug for which that distributor holds the drug identification number". However, the definition for "wholesale" does not apply to medical gases.

Action: Kim Dix to send the link to the Health Canada Website that defines the term "ethical drug" to Amy Park.

Update: Kim Dix sent the link to the Health Canada Website that defines the term "ethical drug" to Amy Park on October 13, 2006.
Action item is completed.

4.5 Discussion of CGA comments on GUI-0031

Hard-copies of the revised GMP for Medical Gases (GUI-0031) as well as responses to CGA comments were distributed to the participants. Louise Jodoin thanked CGA for providing comments. She presented a summary table of the comments that were accepted and rejected for each section. Overall, 27 comments out of 38 from CGA lead to modifications to the document in order to improve the guideline. Due to time constraints, Louise Jodoin proposed to review only the comments that were rejected. Everyone agreed with this approach.

With respect to the comment on the Introduction section (p.1 of the table of industry's comments), Patrick Litwin expressed concerns regarding the safety of the product due to the fact that ambulances and fire departments are not subject to GMP and EL requirements. He has personally met with some of these services and they are willing to comply with these regulatory requirements. Kim Dix explained that these services are regulated by the provincial authorities. For the time being, the guideline will not be modified. CGA requested that Health Canada discuss this issue with provincial authorities.

Action: Patrick Litwin to forward incident reports pertaining to safety and quality deficiencies of medical gases that were handled by ambulances and fire departments to Louise Jodoin.

With respect to the comment on the definition of the term "package" (p.5), Patrick Litwin suggested to include the definition of the term "immediate container" from the Food and Drug Regulations to the glossary of GUI-0031. Louise Jodoin agreed with this suggestion.

Action: Johanne Veenstra to add the definition of the term "immediate container" from the Food and Drug Regulations to the glossary of GUI-0031.

With respect to the comment on interpretation 6 under the Equipment section (p.8), Ken Lum expressed a concern that Inspectors would apply this interpretation to the letter, including the example. However, it might not be possible to follow the example in some cases. CGA suggested removing the example of protective caps. Louise Jodoin agreed with this suggestion.

Action: Johanne Veenstra to remove the example of protective caps in interpretation 6 under the Equipment section of GUI-0031.

After reviewing the rationale for the rejected comments, Patrick Litwin inquired about the next steps for finalizing the guideline. Louise Jodoin explained that after incorporating the above modifications, the document will be approved internally and then posted on Health Canada's Website within a couple of weeks.

Ken Lum inquired about the implementation date of the guideline. Louise Jodoin confirmed that the implementation date would be the same as the posting date. Several CGA members argued that time is required to implement changes, modify SOPs, etc. CGA suggested an implementation date of January 1, 2007. Louise Jodoin confirmed that the implementation date would not be modified due to the fact that there are no major changes to the guidelines.

5. Next meeting & Adjournment

The next bilateral meeting will be held on April 13, 2007.

Kim Greenwood expressed a concern that some individuals confirm attendance to bilateral meetings but are absent during the meeting. She suggested that an invitation to the next bilateral meeting should be sent as soon as possible in order to ensure full attendance to the April 2007 meeting.

Kim Dix strongly recommends that CGA request the attendance of appropriate representatives to address their issues when completing Agenda Item Summaries for the next or subsequent bilateral meetings.

The meeting was adjourned at 12:15 pm.

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