Record of Decisions - June 27, 2012, Groupement provincial de l'industrie du médicament (GPIM)

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Health Canada - Health Products and Food Branch (HPFB) - Bilateral Meeting Program

• Record of Decisions: Groupement provincial de l'industrie du médicament (GPIM)
• Location: 1600 Scott Street, Holland Cross, Tower B, 2^nd Floor, Boardroom 2048, Ottawa, Ontario
• Date: Wednesday, June 27^th, 2012
• Start Time: 1:30 p.m.
• End Time: 3:30 p.m.

GPIM Participants

Viken Afarian, Lernapharm, Co-Chair

François Angers, Laboratoires Omega Ltd.

Obayda Debs, Laboratoires Omega Ltd.

Marco Hamel, Laboratoires Omega Ltd.

Stéphane Lévesque, 3M

Sabrina Defnoun, Europharm

Pierre Morin, GPIM

Suzanne Spagnoli, Jamp Pharma

Esther Tremblay, ERFA Canada Inc.

Nathalie Toutant, Jamp Pharma

Health Canada Participants

John Patrick Stewart, Acting Senior Executive Director, Therapeutic Products Directorate (TPD), Co-Chair

Andrew Adams, Bureau of Pharmaceutical Sciences (BPS), TPD

Ratna Bose, Nonprescription Drug Evaluation Division, Bureau of Gastroenterology, Infection and Viral Diseases (BGIVD), TPD

Jacques Bouchard, BGIVD, TPD

Janet Brunette, Office of Business Transformation (OBT), TPD

Louise Déry, Policy, Planning and International Affairs Directorate (PPIAD)

Françoise Gagnon, Office of Controlled Substances (OCS), Healthy Environments and Consumer Safety Branch (HECSB)

Erica Harnett, OBT, TPD

Véronique Lalonde, Submission Information Policy Division (SIPD), TPD

Lisa Lange, Bureau of Policy, Science and International Programs (BPSIP), TPD

Paul Litowitz, Bureau of Metabolism, Oncology and Reproductive Sciences (BMORS), TPD

Kwasi Nyarko, Biologics and Genetic Therapies Directorate (BGTD)

Sonia Roussel, BGIVD, TPD

Via Teleconference

Stephanie Reid, HPFB Inspectorate

Observers

Marilena Bassi, OBT, TPD

Denise Denicourt, BGIVD, TPD

Bruce Randall, OBT, TPD

Susan Robertson, Office of Risk Management (ORM), TPD

Regrets

Louis Lafontaine, Président Groupement provincial de l'industrie de médicament (GPIM)

Katie Greenwood, BPS, TPD

Wissam Sader, OCS, HECSB

1. Welcome and Introductions

Dr. John Patrick Stewart Acting Senior Executive Director, TPD, Co-Chair, welcomed all attendees. He then introduced himself and began roundtable introductions for all those in attendance.

Organization Update

Dr. Stewart provided the following staffing updates at the Directorate level:

• Dr. John Patrick Stewart joined the Director General's Office as the new Acting Senior Executive Director.
• Dr. Barbara Rotter has retired from her position as Director of BMORS. Kelly Robinson has replaced Dr. Rotter as the Acting Director of BMORS.
• Paul Litowitz has also joined BMORS as the Associate Director.
• Andy Hua is the new Associate Director at the Bureau of Cardiology, Allergy and Neurological Sciences.
• Marilena Bassi is the new Director of the Office of Business Transformation.
• Heather L. MacDonald has replaced Mandy Collier as the Acting Associate Director of BPSIP.

Budget Impact

Dr. Stewart summarized the impact of the 2012 Federal Budget on the TPD. The Deficit Reduction Action Plan was implemented by the Department, which required that 5% and 10% cut-backs be identified. Since the TPD relies on Cost Recovery, our services were largely spared. Ultimately, some policy projects were centralized and internal efficiencies were created such that only 15 positions and 10 staff were affected by the job cuts. Despite these changes, Health Canada expects to continue to provide the same levels of service to stakeholders.

2. Review of Agenda

No changes to agenda were suggested.

3. Review/Update from November 16^th, 2011 meeting notes/action items

The following action items from the last meeting were mentioned at this time:

1. Guidance Document on Human Use Antiseptic: It was discussed previously that a working group would be formed to discuss this guidance document. However, it was not clear who should be invited to participate on this working group. GPIM provided a list of potential industry participants to Janet Brunette and Jacques Bouchard. As well, GPIM plans to provide a rationale for Category IV products not covered by this guidance document. It is anticipated that this will be provided by September 2012. Jacques Bouchard will meet with Pierre Morin from GPIM to discuss this rationale and plans for moving it forward.

4. The Ongoing Drug Shortage and TPD's response

Pierre Morin, GPIM, commended Health Canada and the TPD, in particular, on their response to the most recent drug shortage issues. As industry is involved in supplying medicines to the Canadian market, GPIM members were all surprised by the sudden drug shortage that started in earnest last February, 2012. Some of the GPIM members were more directly involved and acted to alleviate the shortage. Representatives from GPIM met with both Andrew Adams and Katie Greenwood of BPS, who indicated that a dedicated approach would be taken to rectify the drug shortage issues. The TPD and other HPFB management and staff should be praised for their outstanding management of the issues by taking the means, both usual and unusual, to grant safe authorization for new products to reach the market.

Dr. Stewart on behalf of Katie Greenwood, BPS, expressed his thanks to GPIM member companies for stepping forward to help alleviate the shortage of parenteral medications. Dr. Stewart further reported that the recent drug shortage problem was of a scope not previously experienced. An internal working group will be established to review Health Canada's response to the drug shortage and to outline what can be learned from this experience.

5. The Use of Foreign Reviews by Health Canada

François Angers, Laboratoires Omega Ltd., reported that GPIM is very supportive of the proposed measure for the Use of Foreign Reviews by Health Canada. In fact, a few of the member companies have joined the pilot program. The notice introducing the Guidance document states: "Recognizing that market authorization holders currently provide foreign reviews to Health Canada, the principles and practices described in this draft document may currently be used, and will serve to formalize the existing practices until such time as the guidance is finalized." This, of course, applies to authorization holders that submit primarily in other jurisdictions. However, for most of GPIM's member companies, participating in the program involves acquiring a complete dossier including the reviews from the foreign authorization holder of a drug product. Since GPIM member companies are not multinational and, thus, do not already have the foreign dossiers, they will be required to acquire these dossiers. Thus, GPIM is seeking advice from Health Canada on the elements that should be sought or avoided when acquiring these foreign dossiers (reviews). Further, GPIM suggests that the draft guidance document be enriched with information specifically designed for sponsors that will be acquiring foreign products and their accompanying authorization documents.

Andrew Adams, Director BPS and Louise Déry, Director, International Affairs Division, PPIAD reported that the response to the pilot project included 60 submissions. Of these only 40 submissions were accepted. These submissions were required to provide review reports from foreign jurisdictions, which were un-redacted.

To address GPIM's query regarding elements that should be sought or avoided when acquiring foreign review reports, Dr. Adams indicated the following:

• Completely un-redacted reports are required.
• Reports generated within the last five years should be sought. Newer reports are ideal since they will be based on the latest scientific developments.
• Gap analyses, which summarize the quality of differences, should be sought.
• The entire foreign submission is not required. Instead, only the review report should be provided
• Older files that were addressed through drug shortage issues should be avoided.
• Solid oral dosage forms require bioavailability studies using the Canadian reference product (CRP).
• While some jurisdictions will allow aseptic sterilization techniques for injectable drugs, this is not preferred by Health Canada.
• The inclusion of a foreign review report as part of a new drug submission is desirable.

The pilot for generic drugs was expected to end in June 2012. However, it is currently under evaluation. The larger project regarding the use of foreign reviews is still underway.

GPIM explained that bioavailability studies are expensive and wondered whether these could be leveraged with those done in a foreign jurisdiction. Dr. Adams replied by indicated that, currently, this is not possible. While there is considerable work being conducted with foreign reviews and generic drugs, the issue of the use of the CRP remains, such that a bioavailability study must be conducted using the CRP.

Of note, Louise Déry also reported that foreign review reports cannot be rejected based on their origin. Rather, decisions are made based on the quality of the report.

The Draft Guidance Document on the Use of Foreign Reviews is posted on Health Canada Website. Comments can be provided to Health Canada during the pilot period which will end on March 31^st, 2013.

6. Manning a Narcotics Vault

Esther Tremblay, ERFA Canada, reported on a specific issue related to a controlled substances vault and the presence or absence of the responsible person. In this case the Controlled Substances Vault is not located on the premises of the owner but rather, is located on the premises of a supplier such that the Qualified Person in Charge (QPIC) of the vault may not be on the premises at all times. Instead, one or two other persons authorized for limited access to the vault may be present. However, at the last Health Canada inspection, the inspector indicated that the responsible person should be on the premises at all times in the event there is an inspection. GPIM believes that, provided the vault is securely managed with little activity related to the vault, the QPIC should not be required to be on the premises at all times. GPIM desires a more relaxed interpretation of the Narcotic Regulation 8.3(1)a) such that flexibility may be permitted in the QPIC's schedule which would more accurately reflect market requirements.

Françoise Gagnon, Office of Controlled Substances, Healthy Environments and Consumer Safety Branch reported that a responsible person (QPIC) must be onsite. However, this role may be shared by more than one person (alternate QPIC (A/QPIC)). Thus, the QPIC or alternate QPIC (A/QPIC) must be physically on the premises to manage any transactions with a controlled substance that take place. The QPIC is responsible for ensuring compliance with the Controlled Drugs and Substances Act and its Regulations on behalf of the narcotic and controlled drug licensed dealer and supervises the activities with respect to controlled substances. Paragraphs 8.3 (1) (a) and (b) of the Narcotic Control Regulations states the following regarding a licensed dealer:

(a) shall designate one qualified person in charge, who may be the licensed dealer if the licensed dealer is an individual, who must work at the premises specified in the license, have responsibility for supervising activities with respect to narcotics specified in the license and for ensuring, on behalf of the licensed dealer, that those activities comply with these Regulations; and

(b) may designate an alternate qualified person in charge who must work at the premises specified in the license and have authority to replace the qualified person in charge when that person is absent.

Thus, the QPIC is responsible for supervising all activities related to narcotics, controlled drugs and benzodiazepines specified in the license and to ensure that all transactions comply with the regulations. The QPIC function is related to the licensed site and the QPIC must work on the premises of the licensed site at all times. The regulations, however, provide some flexibility as to the replacement of a QPIC as a licensed dealer may also designated a A/QPIC who can replace the QPIC when that person is absent. The A/QPIC must work at the licensed site at all times. The duties of the QPIC and A/QPIC are essentially the same. However, the QPIC is also responsible for all transactions approved by the A/QPIC.

The regulatory requirements for the presence of the QPIC and A/QPIC on the premises during approved working house to fulfill their duties are clear. The requirement for the QPIC to be on-site at all times was revised to allow for an A/QPIC to be designated back in May of 1982. Upon confirmation with the Office of Controlled Substances, the QPIC or A/QPIC must be onsite during all transactions and when accessing the vault. They must be present during the hours negotiated with the above mentioned office.

ACTION: Health Canada (F. Gagnon/S. Reid) to contact GPIM to resolve any further issues in regard to manning a narcotics vault.

7. Gelatin and BSE

Pierre Morin, GPIM, reported that some years ago, TPD was concerned about obtaining information on products containing beef or animal tissues either as an active ingredient or as an excipient. The source of concern was Bovine spongiform encephalopathy (BSE). It was done and GPIM assumed that TPD had a database of sources of animal tissues. Members of GPIM were surprised when a request was received recently for member companies to supply information on sources of gelatin in their products. Members of GPIM expected that Health Canada would already have a database of this information given that this type of detail is generally provided at the time of a drug submission. However, GPIM has learned that only about 58% of drugs have provided this information and, in fact, the provision of this information is not mandatory. Since the United States Food and Drug Administration (FDA) already maintains a database on inactive ingredients, which is publicly available, GPIM suggests that Health Canada attempt to link into this database rather than building their own.

Véronique Lalonde, Drug Identification Number (DIN) Management and Cost Recovery, Submission and Information Policy Division, reported that the process of the collection of information on animal and/or human sourced materials has been in place since 2004. In October 2004, Health Canada started collecting, DIN holders, a current listing of their product formulation, including medicinal and non-medicinal ingredients, and information concerning their sources (such as animal species, age, country of origin, tissues and fluids). Health Canada also collected information on animal and/or human sourced material(s) used in the manufacturing/processing of all these ingredients in the final dosage form. In November, 2005, Health Canada also started to request from new Drug Master File (DMF) owners/agents an attestation regarding the use of materials and reagents from animal or human origin at risk for BSE. However, information regarding the product formulation is being provided on a voluntary basis and not all companies have complied with this request. Health Canada has information on approximately 58% of all marketed drugs (DIN) in Canada and 33% of all DMF's.

Health Canada is maintaining this information in the Drug product Database (DPD) and the DMF Database, both of which are searchable databases to facilitate retrieval of information in the event that it is required (example: public health emergency, crisis, emerging issues). Health Canada maintains the confidentiality of all proprietary information.

As of May 2012, there are 12,685 DINs currently being market notified in Canada. DIN owners have voluntarily declared bovine or cattle non-medicinal ingredient or active ingredients in 2,914 products out of the 12,685 marketed DINs. This represents 23% of the marketed products in Canada.

As of June 2012, there are 5,719 DMFs including types I-IV. Of of these, 94 have voluntarily declared that they contain material from bovine or cattle origin, which represents 1.6% of all the DMF.

8. Proposed Regulatory Framework for Allergenic Substances of Biological Origin

Francois Angers, Laboratoires Omega Ltd, reported that Item 6 of the Record of Decisions from the last GPIM bilateral meeting stated that the Biologics and Genetic Therapies Directorate (BGTD) would review all comments received and make final decisions regarding the Proposed Regulatory Framework for Allergenic Substances of Biological Origin. GPIM's understanding, however, was that further contacts would take place with industry to gain a better understanding of the market in Canada and its status. Members of GPIM are not aware of any contacts have taken place as no communication has occurred since spring 2011. Members of GPIM would like some feedback to ease the uncertainties this has created regarding the outcome of the proposed regulatory framework.

Kwasi Nyarko, Office of Policy and International Collaboration, BGTD reported that the Directorate is completing their review of the comments received from stakeholders in response to the draft Guidance Document Regulatory Framework for Allergenic Products of Biological Origin used for the diagnosis or treatment of allergenic diseases. A final decision is pending.

A revised draft guidance document, which will clarify the scope of the document as applicable only to new allergenic products, will be released for additional comments (consultation) once completed. Other issues with existing products such as the standardization of the non-standardized allergenic products and the use of the same DIN for multiple products will be addressed separately.

The guidance document clarifies the current regulations. No new regulations have been developed or implemented. If a pharmaceutical company makes a change to an existing product the new interpretation will not be enforced for this change. Exceptions, however, do exist such that a DIN may be requested for each allergen.

9. Roundtable

Three items were discussed during the roundtable session:

1. Forward Planning Initiatives for TPD: Lisa Lange, BPSIP, TPD provided a summary of the forward planning initiatives for TPD and a handout was distributed.
2. Generic Timely labeling Initiative: Paul Litowitz, BMORS, TPD, reported on the Generic Timely Labeling Initiative. In the pharmaceutical chapter of the 2011 fall report to Parliament the Auditor General recommended that Health Canada improve the timeliness of safety assessments, the implementation of related recommendations to update labels and to issue risk communications such that Canadians and health care professionals can be informed of new drug safety information in a timely manner. Health Canada agreed with this recommendation and now intends to post a chart acknowledging affected sections of the Product Monograph following safety label updates so as to alert the public, healthcare professionals and manufacturers about revisions. Health Canada aims to begin posting this chart on its website in early 2013.

   GPIM members recommended that this chart be posted to MedEffect website, which advises manufacturers and others when specific changes to Product Monographs are required. While Health Canada does acknowledge this suggestion, Paul Litowitz will work with the Marketed Health Products Directorate to determine the best website to post this document. The decision will be made based on transparency and the best use of resources.

3. French Language Bilateral Meetings: GPIM expressed their gratitude to Health Canada for their efforts in conducting bilateral meetings in French. GPIM very much appreciates these efforts and indicated that, in future, Agenda Item Summaries are likely to be submitted in French as well.

10. Adjournment

Meeting adjourned at 3:50 p.m.

11. Next Meeting

Wednesday, November 7^th, at 1:30 p.m.

Original signed by
Barbara J. Sabourin
Director General
Therapeutic Products Directorate