Bilateral Meeting Program with Compressed Gas Association (CGA) - Record of Decisions - November 25, 2010

Agenda

  • Location: 250 Lanark Avenue, Graham Spry Building, Room 150, Ottawa, Ontario
  • Date: November 25, 2010
  • Time: 1:30 p.m. to 3:30 p.m.

Participants

  • Health Canada
    • Basanti Ghosh - Director, Coordination & Licensing Division, Health Products and Food Branch Inspectorate (HPFBI) (meeting co-chair)
    • Andrew Sun - HPFBI
    • Ranjeet Massey - Good Manufacturing Practices (GMP), HPFBI
    • Preetham Natarajan - GMP, HPFBI
    • Johanne Veenstra - GMP, HPFBI
  • Compressed Gas Association (CGA)
    • Gordon Edwards - Praxair Canada (Vice Chair of CGA's Canadian Medical, Food and Beverage Gases and Equipment Committee) (meeting co-chair)
    • Danielle Bossack - Praxair Canada
    • Patrick Daigle - Air Liquide Canada
    • Patrick Litwin - VitalAire
    • Ken Lum - Praxair Distribution
    • Ron Smart - Medigas
    • Amy Park - Compressed Gas Association

1. Welcome and Introductions

Basanti Ghosh called the meeting order and welcomed the participants.

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

The meeting participants introduced themselves.

2. Review of Agenda

Andrew Sun noted that the agenda item proposed by CGA regarding unique identifiers had not been included in the final agenda because there was no update to provide. As stated at the previous bilateral meeting, Andrew Sun reminded the CGA participants that any comments regarding unique identifiers could be sent to him through Amy Park.

The agenda was adopted.

3. Approval of the minutes of the meeting on April 20, 2010

CGA had provided comments on the draft minutes of the previous meeting. These comments were discussed, and the minutes were amended accordingly and approved.

4. Review of previous action items (from the April 20, 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: CGA will be meeting with TPD on November 26, 2010, to continue discussions on this issue
        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: CGA will be meeting with TPD on November 26, 2010, to continue discussions on this issue.
        Action item is on-going.
  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 will also be posted on the website; Basanti Ghosh anticipated this to be completed in the next four to six weeks.
        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) and CGA will pursue further work regarding approvals for gases in medical applications.
      • Update: CGA will be meeting with TPD on November 26, 2010, to continue the discussions on this issue.
        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: Ranjeet Massey reported that this update to the Q&A should be posted on the Health Canada website in the next several days.
        Action item is on-going.
    • 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: Ranjeet Massey reported that this update to the Q&A should be posted on the Health Canada website in the next several days.
        Action item is on-going.
  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: CGA will be meeting with TPD on November 26, 2010 to continue discussions on this issue.
        Action item is on-going.
    • Item 5.2: Approvals for gases in medical applications - 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).
      • Update: CGA will be meeting with TPD on November 26, 2010, to continue discussions on this issue.
        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: CGA will be meeting with TPD on November 26, 2010, to continue discussions on this issue.
        Action item is on-going.
    • 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: CGA will be meeting with TPD on November 26, 2010, to continue discussions on this issue.
        Action item is on-going.
    • 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: CGA will be meeting with TPD on November 26, 2010, to continue discussions on this issue.
        Action item is on-going.
    • Item 5.3: Cost Recovery Initiative - Health Canada (Etienne Ouimette and Andrew Sun) to come back to the CGA to discuss a regulatory fee mitigation strategy for companies with multiple transfilling sites.
      • Update: See discussion under 5.1 of this meeting.
        Action item is completed.

5. Old items for further discussion

5.1 Cost Recovery Initiative

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

Andrew Sun noted that, as discussed at the previous bilateral meeting, fees are to be increased. Health Canada had proposed some fee mitigation or relief with respect to medical gas companies, but there was difficulty in addressing this within the context of the regulations. This has now been resolved in the proposed fee regulations. In subsection 19(3) of the proposed Fees in Respect of Drugs and Medical Devices Regulations, medical gases are specifically addressed. As specified in paragraph 19(3)(a), for a company packaging/labelling medical gas at multiple sites, fees would be required to be paid as if the company had only one building. For other activities, fees would be as specified in paragraph 19(3)(b). If a site was conducting more than one activity (e.g. fabrication and packaging/labelling), the company would be expected to pay the more-expensive fee; in the example of fabrication and packaging/labelling, the company would pay for the activity of fabrication.

The proposed regulations were published for comment in Part I of the Canada Gazette, on November 13, 2010, with a 75-day consultation period. Andrew Sun noted that Etienne Ouimette had emailed information to Amy Park, including links to the proposed regulations.

6. New items

6.1 GMP Review implementation

Johanne Veenstra provided information to CGA regarding the implementation of the Good Manufacturing Practices (GMP) Review recommendations.

Currently, there are two pre-determined inspection cycles based only on activity, and therefore, establishments of many different risk levels are being inspected using much the same approach. Furthermore, there is a lack of flexibility in inspecting new establishments. In light of these challenges and others, HPFBI launched in 2008 a review of its GMP inspection program for drug establishments. The goal of the project was to create an inspection model that will integrate the changing needs of industry, the effective use of resources, and international expectations. The outcome will be to have an inspection scheduling model where risk determines cycles based on a variety of factors, and to have a variety of inspection models to allow for an approach that is commensurate with risk in any given situation.

During the first year, the GMP Review team examined each component of the current program, including how inspections are scheduled and conducted. This involved meeting with the inspector community, management, and Health Canada partners, to discuss challenges facing the program and what can be done to address those challenges. The team has also spent time reviewing what international and domestic regulators have done to renew inspection programs.

During the second year, the issue-identification and options-development phases of the project were completed. In the fall of 2009, the Inspectorate planned and carried out stakeholder consultations related to the GMP Review. This included the launch of an online workbook, a meeting with industry associations, and face-to-face consultations across the country with industry stakeholders and patient and consumer groups.

As a result of internal and external consultations, a list of over 25 recommendations has been compiled and covers a broad array of areas such as scheduling, conduct of inspections, training, quality oversight, performance measurement, and evaluation. The recommendations have been organized according to the duration of the implementation (short-term, medium-term, and long-term) as well as the priority of implementation (high, medium, and lower).

Three recommendations are being suggested as pilots:

  1. Implement a new model for risk-based inspection scheduling, which will allow for more flexibility, whereby establishments representing a higher risk could be inspected more frequently and establishments representing lower risk less frequently. This is currently targeted to start in January 2011.
  2. For establishments with many sites, all covered under a single corporate quality system, inspect a sample of sites each inspection cycle, covering all sites within a set period. This could be useful for lower-risk and compliant establishments with many sites, such as medical gas establishments.
    • This pilot will apply to medical gas fabricators, packagers/labellers, distributors, and importers located in Ontario.
    • This pilot should start in early December 2010 and last for one year.
    • At the end of the pilot, the data will be analysed. Adjustments and recommendations will be made with the intent of national implementation.
    • A general communication piece will be sent shortly to CGA for distribution to their members, and a detailed communication piece will be sent to medical gas sites that meet inclusion criteria for the pilot.
  3. Evaluate effectiveness of focussed inspections. A focussed inspection is a regular type of inspection, which takes less time to complete, and allows for targeting known problem areas. This is currently targeted for implementation in Quebec in 2013.

The next and final phase of the review, the implementation, has started. Johanne Veenstra is managing the implementation. An implementation plan and a detailed project plan have been developed but will also be evolving throughout this phase.

In terms of next steps, the stakeholder consultation summary report will be emailed to stakeholders that participated in the consultation workshops and will be posted on the Health Canada website shortly.

With respect to the medical gas pilot described in the second recommendation above, the target is to inspect 15% of a company's sites per cycle. The goal is to inspect 15% of a company's sites during the one-year pilot, but the cycle might be extended to two or three years if it is decided to go forward following the pilot. There are two conditions for a company to be included in the pilot: 1. the company must have a corporate-wide quality programme, and 2. the company must have a good compliance history (i.e. a C rating for the last two years and no repeat observations).

CGA members welcomed the opportunity to participate in the pilot.

It was clarified that the GMP Review is a domestic review, but foreign sites might be addressed in the future.

It was also clarified that each pilot is being applied separately, but amalgamation of the different pilot programmes might be considered after their results are evaluated.

Any questions regarding the GMP Review may be sent to Johanne Veenstra.

6.2 Timing of foreign site approvals

Patrick Kaigle introduced this item on behalf of CGA.

In accordance with section 3.3.2 of Health Canada's GUI-0080, Guidance on Evidence to Demonstrate Drug GMP Compliance of Foreign Sites, for foreign sites in non-MRA countries or for non-MRA products and activities, the period of validity of the submitted audit reports is either two years or three years, depending on if the report is dated on or before June 30 or if the report is dated on or after July 1, respectively.

Companies schedule and perform audits at frequencies based on risk. For many foreign sites, a three-year period may be appropriate for audits as specified in GUI-0080. Therefore, they will target to perform these audits on or after July 1 in order to be granted a three-year expiry date for the audit report. However, with Drug Establishment Licence (DEL) renewal applications now due in early August, this would seem to allow only one month for an audit to be performed at a foreign site, including any corrective actions to be addressed, and to prepare the DEL renewal package. CGA members suggested that an extended period of time be allowed for submission of foreign site audit documentation, beyond the DEL renewal application deadline in August, such as in October. CGA members wanted to ensure that a mechanism was in place for a DEL renewal application to be submitted, with some supporting documentation submitted at a later date.

Preetham Natarajan noted that section 3.2.2 of GUI-0080 states: "The information in sections 3.2.1.2 and/or 3.2.1.3 should be normally submitted to the Inspectorate in the DEL Renewal package. However, should the DEL holder or sponsor wish to submit the information at any other time...". The importer being aware that the GMP compliance information for a foreign site is required (e.g. by the foreign site annex listing an expiry date, letter sent to the applicant when evidence is submitted, etc.) should help all importers determine when it is the best time to submit evidence. The instructions in the DEL renewal package are merely guidelines. The information and dates (e.g. August 1, 2010) indicated in the DEL renewal documents are a friendly reminder that, if the applicant has yet to submit evidence to extend the expiry date of a foreign site, they should take the next month to submit. This should provide sufficient time for Health Canada to screen, review, and evaluate submitted GMP evidence in hopes of issuing a DEL before the start of the next calendar year.

Preetham Natarajan clarified that specific information regarding a foreign site only has to be submitted once; for example, if a foreign site is compliant for a three-year period, an applicant does not have to re-submit the same information for that foreign site each year when renewing the DEL for a domestic site, until such time as the foreign site's compliance has been re-evaluated or called into question. Furthermore, any person may submit compliance information, whether they hold a DEL or not, and that compliance information may be applied to one or more domestic DEL applications.

6.3 Supporting documentation for foreign site approvals

Gordon Edwards introduced this item on behalf of CGA.

Section 3.2.1.2 of Health Canada's GUI-0080 outlines the documentation to be submitted in order to assess GMP compliance of a foreign site in a non-MRA country, such as the U.S. Section 3.2.1.3 of GUI-0080 outlines the information that is required, if the information described in A and B of 3.2.1.2 is not available, for certain cases including medical gases.

Much of the information described in sections 3.2.1.2 and 3.2.1.3 of GUI-0080 would be subject to business confidentiality, and companies would not be able to share this information with competitor companies. The supporting documentation that is requested to be supplied with foreign site applications may not be available to a DEL applicant when foreign sites are owned by competitor companies.

CGA suggested that it should possible for documents from foreign sites to be submitted directly to Health Canada's DEL office, referencing the DEL applicant's importing site, and not necessarily submitted via the DEL applicant. Furthermore, once submitted, it would be helpful if Health Canada sent notification (e.g. an acknowledgment letter of receipt) to the foreign site and the applicant, which could be cross-referenced for use by other applicants also adding that foreign site to their DEL application. That is, Health Canada could reference certain documentation for a particular foreign site for multiple approvals without sharing information between importing sites.

Preetham Natarajan reported that, for many years now, Health Canada has acknowledged receipt of the GMP evidence that has been submitted to its offices for the review and assessment of GMP compliance of foreign sites. This evidence includes all parts described in Parts A to G of section 3.2.1.2 of GUI-0080. Furthermore, if an importer or foreign site contacted the Drug GMP Inspection Unit, they would be provided upon request an update regarding the status of their submission (e.g. screened, reviewed, awaiting final review and sign off, etc.). As previously explained under 6.2, any person may submit compliance information to Health Canada, whether they hold a DEL or not. Health Canada has been accepting information directly from foreign sites for many years.

Preetham Natarajan explained that, if a foreign site has been deemed GMP compliant, the GMP compliance rating would apply to all Canadian importers who wish to have their drugs fabricated, packaged/labelled, and tested at that foreign site. Although it is the Canadian importer's responsibility to ensure that the foreign site meets Canadian GMP requirements, Health Canada would not require multiple submissions for the same foreign site when dealing with the same categories of drugs, licensable activities, and dosage forms, if they are already approved. As a long-term goal, Health Canada is considering the creation of a web connection that would allow applicants to securely access this form of GMP compliance information.

Challenges were noted regarding documentation for foreign sites in U.S., as the U.S. is a non-MRA country.

Preetham Natarajan reported that the U.S. FDA would be joining PIC/S in January 2011.

Any further questions may be sent to Preetham Natarajan.

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

CGA enquired regarding the review of Health Canada's guidance document, Good Manufacturing Practices (GMP) for Medical Gases (GUI-0031).

Johanne Veenstra reported that the GMP Committee had done a first review of GUI-0031 at their last meeting. It was anticipated that the revised draft would be finalised at the next GMP Committee meeting in February 2011 and then posted for consultation around the spring of 2011.

CGA enquired regarding the possibility of having discussions with the GMP Committee concerning the revision of GUI-0031. This could perhaps take place in conjunction with the next bilateral meeting. Johanne Veenstra stated that she would address this with the GMP Committee.

ACTION: 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.

7. Next meeting and adjournment

The next meeting was tentatively scheduled for the spring of 2011.

Johanne Veenstra will contact Amy Park after the GMP Committee meeting in February 2011, to determine the scheduling of the next bilateral or perhaps informal meeting, to facilitate discussion of the review of GUI-0031.

The meeting was adjourned.

Report a problem or mistake on this page
Please select all that apply:

Thank you for your help!

You will not receive a reply. For enquiries, contact us.

Date modified: