Bilateral Meeting Program with Compressed Gas Association (CGA) - Record of Decisions - July 26, 2011

Agenda

• Location: 250 Lanark Avenue, Graham Spry Building, room 150, Ottawa, Ontario
• Date: July 26, 2011
• Time: 1:30 p.m. to 3:30 p.m.

Participants

• Health Canada
  • Stephanie Reid - Acting Manager, Drug Good Manufacturing Practices (GMP) Unit, Health Product and Food Branch Inspectorate (HPFBI) (meeting co-chair)
  • Duarte Rodrigues - HPFBI
  • Valerie Watier - HPFBI
• Compressed Gas Association (CGA)
  • Gordon Edwards - Praxair Canada (Chair of CGA's Canadian Medical, Food and Beverage Gases and Equipment Committee) (meeting co-chair)
  • Bill Beckett - Medigas
  • Daniel Bizier - Air Liquide Canada
  • Alice Chen - VitalAire
  • Robert Crabtree - Linde Canada
  • Patrick Kaigle - Air Liquide Canada
  • Patrick Litwin - VitalAire
  • Ken Lum - Praxair Distribution
  • Amy Park - Compressed Gas Association

1. Welcome and Introductions

Stephanie Reid and Gordon Edwards called the meeting order.

The meeting participants introduced themselves.

The CGA participants thanked Health Canada for this opportunity to meet.

Stephanie Reid relayed apologies from the Therapeutic Products Directorate (TPD) whose representatives were not able to attend this meeting.

2. Review of Agenda

Amy Park noted that two additional new items proposed by CGA had not been included in the final agenda for this meeting. These two items followed up from a meeting with TPD on November 26, 2010. The first item, "Comparison of requirements in the GMP for Medical Gases and ISO 13485", had been requested by TPD, and CGA would like an opportunity to present and to explain it to TPD. The second item, "Modern regulations framework and gases in medical applications", had been at the invitation of TPD, and CGA would like some feedback from TPD. It was noted that CGA intended to propose these items again for the next bilateral meeting.

Stephanie Reid reported that their new Assistant Deputy Minister, Paul Glover, was in the process of reviewing the priorities of the Health Products and Food Branch, including the regulatory modernisation project. She noted that the Office of Legislative and Regulatory Modernization should be able to provide an update at the next bilateral meeting.

The agenda was adopted.

3. Approval of the minutes of the meeting on November 25, 2010

There were no comments received from the Health Canada participants regarding the draft minutes of the previous meeting that had been prepared by CGA. The minutes were approved in principle.

ACTION: Stephanie Reid will confirm with Basanti Ghosh that there were no comments from the Health Canada participants regarding the draft minutes of the meeting held on November 25, 2010 and let Amy Park know.

4. Review of previous action items (from the November 25, 2010 meeting minutes)

1. Action items from the meeting on April 13, 2007
   • Item 4.1: (Approvals for gases in medical applications - drugs versus medical devices) - Therapeutic Products Directorate (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: Discussions on this issue continued at a meeting between CGA and TPD representatives on November 26, 2010. As follow-up to that meeting, Brigitte Zirger of TPD sent a letter to CGA on December 9, 2010, regarding this issue.
       Action item is completed.
   • 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: Discussions on this issue continued at a meeting between CGA and TPD representatives on November 26, 2010. As confirmed at that meeting by Satish Mallya of TPD, the issue of ranges and market authorisations for medical gas mixtures could not be addressed under "compounding", since the mixtures are not made by a pharmacist nor for a specific patient.
       Action item is completed.
2. 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: The minutes from the bilateral meetings held on October 13, 2006 and April 13, 2007 have now been posted on the Health Canada website. The minutes from the bilateral meetings on November 14, 2007, as well as on October 28, 2008, October 29, 2009, and April 20, 2010 and November 25, 2011 will also be posted on the website; Stephanie Reid anticipated this to be completed by the next bilateral meeting.
       Action item is on-going.
3. Action items from the meeting on October 28, 2008
   • Item 4.1: Approvals for gases in medical applications - TPD, (Bureau of Policy, Science and International Programs (BPSIP) & Bureau of Policy and Sciences (BPS)) and CGA will pursue further work regarding approvals for gases in medical applications and expiry date requirements for medical gases.
     • Update: Discussions on these issues continued at a meeting between CGA and TPD representatives on November 26, 2010. At that meeting, TPD indicated that it would be difficult to address these issues (including drugs versus medical devices, ranges for mixtures, and expiry date requirements) within the current regulatory framework; TPD recognised that gases do not fit well in the current framework and suggested that these issues were appropriate to address under the regulatory modernisation framework. Based on this, CGA's desired outcome would be by regulatory reform, working with TPD and the Office of Legislative and Regulatory Modernization.
       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.
     
     Following-up action: HPFBI will update the Q&A posted on the Health Canada website to reflect the information in the letter from Chad Sheehy.
     • Update: The Q&A posted on the Health Canada website was updated in November 2010.
       Action item is completed.
   • 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: The Q&A posted on the Health Canada website was updated in November 2010.
       Action item is completed.
4. Action items from the meeting on October 29, 2009
   • Item 5.1: Expiry date requirements for medical gases - 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.
     • Update: Discussions on this issue continued at a meeting between CGA and TPD representatives on November 26, 2010; at that meeting, TPD indicated that expiry date requirements for medical gases should be addressed in the modern regulations framework. It was agreed to include and to continue to track this issue under the on-going action item regarding "approvals for gases in medical applications", under item 4 c) above.
       Action item is completed.
5. Action items from the meeting on April 20, 2010
   • Item 5.1: Expiry date requirements for medical gases - Joyce Pon (TPD) will go back to Bureau of Policy Science (BPS)/TPD to identify TPD representatives for a meeting to discuss this topic with CGA representatives, and Joanne Lekkas will follow up with Joyce in a month to ensure a meeting is scheduled.
     • Update: On November 26, 2010, CGA representatives met with Joyce Pon (BPSIP), Brigitte Zirger (BPSIP), Eric Ormsby (BPSIP), Satish Mallya (BPS), Lisa Lange (BPSIP), and Sarah Chandler (Medical Devices Bureau), of TPD.
       Action item is completed.
   • Item 5.2: Market authorisation process for gases in medical applications (drugs versus medical devices) - Joyce Pon (TPD) will go back to BPS/TPD to identify TPD representatives for a meeting to discuss this issue with CGA representatives, and Joanne Lekkas will follow up with Joyce in a month to ensure a meeting is scheduled.
     • Update: On November 26, 2010, CGA representatives met with Joyce Pon (BPSIP), Brigitte Zirger (BPSIP), Eric Ormsby (BPSIP), Satish Mallya (BPS), Lisa Lange (BPSIP), and Sarah Chandler (Medical Devices Bureau), of TPD.
       Action item is completed.
   • Item 5.2: Market authorisation process for gases in medical applications - Joyce Pon will go back to TPD to determine why the range of gas concentrations for a DIN is not on the annual notification.
     • Update: At a meeting between CGA and TPD representatives on November 26, 2010, Joyce Pon explained that the range is not on the annual notification because the annual notification is pulled from the drug product database (DPD), and the DPD does not currently have a field for the range. However, it is intended for that field to be added to the DPD in the future.
       Action item is completed.
6. Action items from the meeting on November 25, 2010
   • Item 6.4: Review of Good Manufacturing Practices (GMP) for Medical Gases (GUI-0031) - Johanne Veenstra will address with the GMP Committee CGA's enquiry regarding the possibility of having discussions with the GMP Committee concerning the revision of GUI-0031.
     • Update: The review of GUI-0031 is included in the agenda for this meeting; see the discussion under item 5.1.
       Action item is completed.

5. Old items for further discussion

5.1 Review of Good Manufacturing Practices (GMP) for Medical Gases (GUI-0031)

CGA requested an update regarding the status of the review of the Good Manufacturing Practices (GMP) for Medical Gases (GUI-0031).

Stephanie Reid reported that the GMP Committee looked at GUI-0031, as well as related PIC/S documents. The Q&As posted on the Health Canada website were also reviewed for incorporating into GUI-0031. The GMP Committee last met in June 2011 and finalised the draft revision of GUI-0031. The draft revised GUI-0031 has not yet been posted on Health Canada's website; HPFBI will send the document to Amy Park when it is officially published for consultation.

Valerie Watier and Stephanie Reid presented the significant changes and minor changes to be included in the draft revised GUI-0031. CGA members provided some comments.

Stephanie Reid noted that the draft revised GUI-0031 has been approved by the GMP Committee and is pending approval by their Management Committee. It is anticipated that the document will be distributed for comment by the end of summer 2011, for a 90-day comment period. The GMP Committee will discuss the comments at their meeting in January 2012, and depending on the number of comments received, it is anticipated that the revised GUI-0031 will be finalised by the end of this fiscal year (i.e. March 2012).

CGA noted that the issue concerning expiry date requirements for medical gases is still pending resolution with TPD. It was noted that, at previous bilateral meetings including the one held on October 29, 2009, Chad Sheehy, then Acting Director, Compliance and Coordination Licensing Division, Health Products and Food Branch Inspectorate (HPFBI), had 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 were noted from an inspector, they should be raised with Chad Sheehy. Stephanie Reid stated that she would discuss this with the GMP Committee to ensure that the inspectors were all on the same page.

6. New items

6.1 Evidence of GMP compliance for foreign sites in the U.S.

Ken Lum introduced this item on behalf of CGA.

A CGA member company submitted an application for approval of a foreign site located in the U.S. and was told that a U.S. FDA 483 report was not acceptable as evidence of drug GMP compliance and that only a U.S. FDA Establishment Inspection Report (EIR) would be accepted. FDA 483 reports (along with corrective actions taken) were previously acceptable to Health Canada, as evidence of drug GMP compliance for a foreign site located in the U.S.

In 3.2.1.2 of Health Canada's GUI-0080, Guidance on Evidence to Demonstrate Drug GMP Compliance of Foreign Sites, a U.S. FDA EIR is listed as an example ("e.g.") of acceptable documentation. As this is an example, other types of documentation would seem also to be acceptable.

EIRs are not readily available, as they are not consistently issued by the U.S. FDA following each inspection. If an EIR is issued, it may take months. In many cases, EIRs are never issued, and a facility will only receive an FDA 483 or 482 report.

CGA suggested that, for a foreign site located in the U.S., other types of documentation (other than an FDA EIR) should be acceptable for evidence of GMP compliance, such as registration of the facility with the U.S. FDA.

Duarte Rodrigues and Stephanie Reid stated that specific situations are considered on a case-by-case basis. An FDA 483 report, along with corrective actions taken, may be considered in some cases, but they may not have all the information needed. It was clarified that the documents listed as examples ("e.g.") in GUI-0080 are the preferred documents, but the list of documents is not absolute.

Duarte Rodrigues reported on the revision of GUI-0080. HPFBI is committed to updating its guidance documents as per the three-year document review cycle set out in its Quality System Framework. GUI-0080 is scheduled for revision during the second half of the 2012 calendar year.

HPFBI is currently working on an updated version of GUI-0080. It is anticipated that the draft revision will be available for comment by the end of this fiscal year.

Some of the updates will include clarification on the risk-based approach to be used by HPFBI when assigning an expiry date (e.g. not all sites will expire after the same period of time). The risk-based approach will take into consideration a number of factors such as, but not necessarily limited to, the category of drug (e.g. gases, disinfectants), the activities occurring at the foreign site, the compliance history of the foreign site, etc. Further guidance on what is considered acceptable evidence of drug GMP compliance will also be provided. The revised version of the guidance document will also contain tools to assist regulated parties in submitting acceptable GMP evidence, with clear examples in appendices, tables, and a checklist.

The revised version of the guidance document will take into consideration the comments received by HPFBI over the last few years, as well as the comments, including the completed surveys, that were received during the spring 2010 GMP-EL cross-Canada road show. Furthermore, the updated version of GUI-0080 will be in line with Health Canada's commitment to seek harmonisation with Mutual Recognition Agreement (MRA) countries and other international partners, wherever possible.

CGA members are welcome to continue contacting HPFBI's Drug GMP Inspection Unit (Ottawa) to discuss specific issues pertaining to the interpretation of GUI-0080 and sections of the document that may be unclear.

7. Next meeting and adjournment

The next meeting was tentatively scheduled for the end of November 2011, with the subsequent meeting to be held in late spring 2012.

Stephanie Reid noted that Chantal Ricard-Lacroix will contact Amy Park to schedule the November 2011 meeting. It is intended for CGA to present comments on the draft revised Good Manufacturing Practices (GMP) for Medical Gases (GUI-0031), at that meeting. It is also anticipated that the Office of Legislative and Regulatory Modernization will provide an update, at that meeting.

It is also anticipated that the two new agenda items previously mentioned under item 2, "Comparison of requirements in the GMP for Medical Gases and ISO 13485" and "Modern regulations framework and gases in medical applications", will be included in the agenda for the next meeting, unless CGA has an opportunity before then to discuss these directly with TPD.

The meeting was adjourned.