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Canadian Drug Establishment Licences: GMP Requirements for API foreign building


Posted: Monday June 26th, 2017

Author: Madhur Jadawala

Canada's Food and Drug Regulations (FDR) were amended to extend the requirements of Division 1A - Establishment Licensing and Division 2 - Good Manufacturing Practices (GMP) to active ingredients used in pharmaceutical drugs for human use only. The amended Regulations came into force on November 08, 2013. This API program was implemented for 3 years and it came into full effect on November 08, 2016. On July 31, 2016, Health Canada did publish a “Notice to Stakeholders - Updates to drug establishment licence applications and good manufacturing practice evidence requirements for active pharmaceutical ingredients” and it can be found here:

https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/notice-stakeholders-updates-drug-establishment-licence-applications-good-manufacturing-practice-evidence-requirements-active-pharmaceutical.html

WHO DOES THIS APPLY TO?

·         All the Canadian establishments (persons) conducting API related activities for APIs used in the manufacture of drugs listed on the Prescription Drug List, Scheduled under the Controlled Drugs and Substances Act (Schedules I, II, III, IV, or V inclusively), or defined as a “narcotic” under the Narcotic Control Regulations:

o   API importers

o   Finished dosage form (FDF) fabricators who import APIs for use in manufacturing

o   FDF importers

WHAT’S NEW

·         As per section C.02.003.3 of the Food and Drug Regulations (FDR), no person shall use an active ingredient in the fabrication of a drug unless it is fabricated, packaged/labelled, tested and stored in accordance with GMP requirements.

·         Effective November 08, 2016, importers are required to update their API Table-A with Health Canada and ensure to keep it comprehensive and consolidated with all the API foreign sites.

·         Importers, along with their most recent API Table-A must also submit section 5.1 attestation of FORM-0033 attesting to maintain API foreign sites Good Manufacturing Practices (GMP) compliance evidence based on inspections by Health Canada or by one of the following recognised regulatory authorities / organizations:

o   Regulatory partners with whom Health Canada has established equivalence under Mutual Recognition Agreements (MRA);

o   Regulatory partners whose inspection system has been assessed and found comparable under the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme (PIC/s);

o   Organizations such as the European Directorate for the Quality of Medicines and Healthcare (EDQM) and the World Health Organization (WHO), which inspect against ICH Q7 guidelines.

·         Consultant or corporate audits, and other GMP evidence should not be used to demonstrate the API foreign site’s compliance with GMP for the drugs listed on the Prescription Drug List, Scheduled under the Controlled Drugs and Substances Act (Schedules I, II, III, IV, or V inclusively), or defined as a “narcotic” under the Narcotic Control Regulations.

·         The GMP evidence must be readily available with the importer and must be supplied to Health Canada when requested.

·         Health Canada will continue to seek clarification with respect to Table A, as applicable, and assess the GMP compliance evidence of foreign buildings during the inspection of an importer, during the off-site paper assessment, or during the foreign on-site inspection.

List of GMP evidence documents:

v  Foreign buildings inspected by the above-noted recognised regulatory authorities and organizations

1.       most recent, available, signed inspection report issued by Health Canada or by a recognised regulatory authority;

2.       copy of the GMP certificate issued by the recognised regulatory authority, stating the outcome of the inspection above (if available);

3.       corrective actions taken, signed by the foreign building’s responsible official (if applicable);

4.       copy of the Site Master File, or a similar document (such as a quality manual); and

5.       copy of the quality/written agreement between the foreign building’s responsible official and the Canadian establishment

v  Foreign buildings which have not been inspected by the above-noted recognised regulatory authorities and organizations

1.       most recent (within last 3 years) corporate or consultant audit, signed and dated by the lead auditor;

2.       justification for using a consultant/corporate audit report (e.g. only available GMP evidence);

3.       qualifications and experience of the auditor(s);

4.       scope of the inspection (including activities being performed, drugs/APIs covered, and specific building address);

5.       evidence that the consultant or corporate audit was conducted against all applicable sections of Part C, Division 2 of the Food and Drug Regulations;

6.       corrective actions taken, signed by the foreign building’s responsible official and assessed by the auditor for adequacy (if applicable);

7.       copy of the Site Master File, or a similar document (such as a quality manual); and

8.       copy of the quality/written agreement between the foreign building’s responsible official and the Canadian establishment

·         If the foreign buildings’ GMP evidence is not based on inspections by recognised regulatory authorities or organizations, in order to meet the required GMP evidence by November 8, 2016, importer should:

1.       Source APIs from an alternate supplier that has the required GMP evidence. It is the importer’s responsibility to advise the DIN holder of any change in suppliers, so that the DIN holder may obtain Health Canada approval, as applicable;

2.       Arrange for a corporate or consultant audit to be conducted as noted in the “Next phase – Beginning November 8, 2016” section of the July 2015 Notice; or

3.       Request a Health Canada inspection using Good Manufacturing Practices − Request for Inspection of a Foreign Site Form (FRM-0213).

Health Canada takes a risk-based approach to inspections. An inspection should be requested as soon as possible for API foreign buildings involved in activities related to prescription and controlled drugs that the importer would deem medically necessary and/or for which there are no alternate suppliers.

References:

1.       “Notice to Stakeholders - Updates to drug establishment licence applications and good manufacturing practice evidence requirements for active pharmaceutical ingredients”:

https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/notice-stakeholders-updates-drug-establishment-licence-applications-good-manufacturing-practice-evidence-requirements-active-pharmaceutical.html

2.       Health Canada issued DEL Bulletin #2 dated August 04, 2016.




A Recap on Vanessa’s Law


Posted: Monday June 19th, 2017

Author: Pinkiy Mazumder

With the evolution of healthcare products and its regulations, today we will recap one of the most significant recent changes in Canadian regulations; Vanessa’s Law. 

Vanessa’s Law, also known as the Protecting Canadians from Unsafe Drugs Act, was launched with the purpose of strengthening the safety of therapeutic products and its regulation (1). Following the death of 15 year old Vanessa Young from a prescription drug in 2000, Bill C-17 Protecting Canadians from Unsafe Drugs Act, was initiated to propose the first amendment to the Food and Drugs Act in 50 years (1,2). With its introduction in December 6th 2013 by the Federal government, Bill C-17 Protecting Canadians from Unsafe Drugs Act received Royal Assent the following year on November 6th 2014 (3).

The Protecting Canadians from Unsafe Drugs Act applies to therapeutic products including prescription drugs, over-the-counter (OTC) drugs, vaccines, medical devices (including combination drug-devices), gene therapies, cells, tissues, organs, however it does not apply to Natural Health Products (1).

The Act brings multiple new changes to the regulation of therapeutic products, to protect patients and the public from unsafe products. For instance, the Act allows the government to mandate the reporting of adverse drug reactions and medical device incidents by healthcare institutions, and recall therapeutic products that are considered unsafe (1). In addition, for enhanced transparency, the amendment allows the Minister of Health to collect additional product information from the sponsor, require new tests/studies, and monitor patient experience for product assessment (4). Moreover, the Minister of Health also has the authority to demand a re-labelling of drug products or a change in drug packaging for safety concerns, and even reveal confidential business information for product safety (4). These changes, among others, form the basis of Vanessa’s Law. For more information on the Protecting Canadians from Unsafe Drugs Act (Vanessa’s Law), please refer to Health Canada’s Overview of Vanessa’s Law, Amendments to the Food and Drugs Act, and Protecting Canadians from Unsafe Drugs Act Questions/Answers.

Thank you for reading Regulated Affairs, the CAPRA Blog. CAPRA is a non-profit organization dedicated to providing networking and professional development opportunities in Regulatory Affairs.

References

1.    Protecting Canadians from Unsafe Drugs Act Questions/Answers: http://www.hc-sc.gc.ca/dhp-mps/legislation/unsafedrugs-droguesdangereuses-faq-eng.php

2.    Vanessa Young’s Legislative Legacy: http://www.macleans.ca/news/canada/vanessa-youngs-legislative-legacy/

3.    Protecting Canadians from Unsafe Drugs Act Amendments to the Food and Drugs Act (Bill C-17): http://www.hc-sc.gc.ca/dhp-mps/legislation/unsafedrugs-droguesdangereuses-eng.php

4.    Overview of Vanessa’s Law: http://www.hc-sc.gc.ca/dhp-mps/legislation/unsafedrugs-droguesdangereuses-overview-ensemble-eng.php




Changes to the Annual Renewal Process of Canadian Drug Establishment Licences


Posted: Monday June 12th, 2017

Author: Author Madhur Jadawala

OVERVIEW

Effective 2017 Annual Licence Renewal (ALR) of Drug Establishment Licences (DEL), Health Canada has added an extra step to the ALR submission process by DEL holders. This change constitutes of an addition of a MS Excel sheet known as “Product List” and it has been provided to all the DEL holders along with the 2017 ALRs packages.

 

WHO DOES THIS APPLY TO?

·         All the Canadian Drug Establishment Licence (DEL) holders who wish to renew their importation DEL and maintain its active status. Although the name of this new sheet is “Product List”, not only it covers the list of drug products (DINs) imported by the importer DEL holder but also the foreign sites and their activities corresponding to these DINs.

 

WHAT’S NEW

·         An accurately completed “Product List” Excel sheet must now be submitted along with the ALR package to Health Canada every year by March 31. Health Canada may issue Screening Deficiencies in case where “Product List” is not provided or is not completed appropriately.

Refer to Figure 1 below for the snapshot of the “Product List” issued by Health Canada:

·         As it is evident from Figure 1 below, Health Canada has already pre-filled the “Product List” with the information they have on their records, and yes, it may not be completely comprehensive. One may find some activities or foreign sites that are actively listed on their DEL but are missing from this “Product List”. This is fine, for Health Canada has provided us with this sheet so that we can add more details and submit the most accurate and comprehensive sheet along with the renewal before March 31st.

 

·         The Excel sheet may seem to be fairly simple at first sight but there is a lot of fact finding and information search involved behind before one can completely fill this sheet with high accuracy. There are clear instructions in cell “H1” for listing only 1 DIN per cell, and this is where it becomes a bit tricky.

 

·         Health Canada wants us to use each row to list each foreign site carrying out each activity for each DIN. As an example, if a foreign site “Foreign Site 1” is involved in Fabrication, Packaging and Labelling of DIN 01234XXX, this needs to be listed in 3 separate rows for each activity as illustrated in Figure 2 below.

 

·         Many times, a single foreign site is involved in carrying out licensable activities for more than 1 DIN product. As an example, “Foreign Site 2” is involved in Fabrication and Packaging of 2 DIN products – 01234XXX and 01234XXY. In this case, both the DINs need to be entered separately in separate rows corresponding to Fabrication and Packaging by “Foreign Site 2” as illustrated in Figure 2 below.

 

·         Health Canada has limited gathering of this information to activities of “Fabrication, Packaging and Labelling” only. Foreign sites involved in “Testing” only need not be listed on this “Product List”.

Figure 1: “Product List issued by Health Canada”

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Figure 2: “Product List issued completed by DEL holder”

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*Different Colours for DINs 01234XXX and 01234XXY have been used to demonstrate that these are two separate unique DINs.




FDA’s eCTD Mandate: Are You Ready?


Posted: Monday June 5th, 2017

Author: Anisah Bipatnath, M.Sc. Project Manager, Regulatory Operations

When FDA posted their eCTD mandate last year, it was more of a whisper than a bang.  It certainly did not wreak havoc in the industry; after all, we were all warned that the time would come sooner rather than later.

The deadlines are quite clear:

After May 5, 2017

The following submission types must be filed in eCTD format:

·         NDAs

·         ANDAs

·         BLAs

·         MFs

After May 5, 2018

The following submission types must be filed in eCTA format:

·         Commercial INDs

Source: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm153574.htm

*Submissions not filed in eCTD format will not be filed or received.

Statistics show that the majority of incoming submissions are already in eCTD format:

[Untitled]

Source: Electronic Submissions Update presentation at RAPS2016: https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/
FormsSubmissionRequirements/ElectronicSubmissions/UCM522105.pdf

Roughly 90 percent of the industry is already filing in eCTD format (DMF filings at least are on the rise) to FDA.  For those of you still holding out, FDA’s eCTD mandate is now forcing your hand to make the switch.  If you’re currently filing paper submissions for IND, you have a year to consider the following:

1. To host or not to host?

eCTD software is expensive.  There exist different cost structures, depending on your decision to host the software in-house or access the software via a remote host.  Hosting eCTD software in-house entails a battery of qualification and validation steps, and can be practical if you already have an IT group with relevant expertise, or can enlist one to manage the installation.  If you’re not in possession of a Computer Science degree, the amount of work and length of time (and the terminology) might be daunting.  Increasingly, eCTD software providers are making cloud based solutions available, which allow you to access the eCTD software remotely.  Your eCTD software vendor can then perform most of the installation and qualification steps, with minimal qualification steps required by you as the end user.

2. Submission compilation – keep in-house or outsource?

This is another key point for consideration.  What would be the utility of having (expensive) eCTD software if you don’t know how to use it to maximize the potential, or compile a submission that meets FDA’s requirements?  Like it or not, FDA has specifications for your PDF files, metadata for submission types that need to be entered correctly or else you run the risk of your submission being rejected.  There are also PDF tools that can facilitate PDF processing at the click of a mouse.  All of these activities require trained professionals and standard operating procedures in order to ensure a consistent and high quality product.

3. Electronic Submissions Gateway (ESG) or Courier?

eCTD and ESG go hand in hand.  Submissions under 10GB should be filed through the Gateway.  Any submissions exceeding 10GB can also be uploaded to the ESG or can be submitted on appropriate physical media and sent by courier to FDA.  You can dispatch your eCTD immediately through ESG once your submission has your internal stamp of approval (no printing, and no more paper cuts!).  Using the ESG also provides an electronic receipt and acknowledgement files, reducing post-filing anxiety (did the courier arrive at FDA? In one piece?), and enabling quicker notification to your submission team that FDA has your submission for review.  However, in order to use the ESG, you must first be qualified by FDA and undergo a sample submission review process and electronic certificate exchange.

4. Health Canada and the Common Electronic Submissions Gateway (CESG)

Health Canada also implemented an eCTD mandate, in order to stay aligned with FDA and the European Medicines Agency (EMA).

Effective January 1, 2018, the following regulatory activity types (as well as all additional information/subsequent regulatory activities) must be filed in eCTD format:

•             New Drug Submission (NDS);

•             Supplement to a New Drug Submission (SNDS);

•             Abbreviated New Drug Submission (ANDS); and,

•             Supplement to an Abbreviated New Drug Submission (SANDS).

Source: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/activit/announce-annonce/ectd-mandatory-notice-avis-obligatoire-eng.php

eCTD filing format for Master Files, Clinical Trial Applications (CTAs), Drug Identification Number (DIN) applications and Post-Authorization Division 1 changes (PDC) is recommended, but not yet mandatory. Medical devices and veterinary drug submissions are currently considered to be out of scope and must follow the non-eCTD electronic only filing format (for details on this guidance, click here: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/ctd/gd_prep_non_ectd_ld-eng.php

Effective January 1, 2017, all eCTD transactions under 10GB in size must be transmitted through the CESG, and sponsors are advised to obtain CESG accounts as soon as possible.

Source: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/activit/announce-annonce/cesg-mand-notice-avis-oblig-pcde-eng.php




Information on the new Access to Cannabis for Medical Purposes Regulations


Posted: Monday May 29th, 2017

Author: Rachelle D’Souza

On August 11, 2016, Health Canada announced the new Access to Cannabis for Medical Purposes Regulations (ACMPR) which came into force on August 24, 2016. These new regulations were intended to replace the Marihuana for Medical Purposes Regulations (MMPR) as of August 24, 2016, and be implemented as a result of the Federal Court ruling in the case of Allard v. Canada. The ACMPR allows for reasonable access to cannabis for medical purposes for Canadians who have been authorized to use cannabis for medical purposes by their healthcare practitioner.

Under the ACMPR, Canadians who have been authorized by their healthcare practitioner to access cannabis for medical purposes, will continue to have the option of purchasing safe and  quality-controlled cannabis from one of the producers licensed by Health Canada. Canadians will also be able to produce a limited amount of cannabis for their own medical purposes, or designate someone to produce it for them.Individuals who have the support of a licensed health care practitioner may consult Accessing Cannabis for Medical Purposes for further information on how to access cannabis for medical purposes under the ACMPR.

Please refer to the statement released by Health Canada and supporting Fact Sheet for additional information.

For more information on the content of the new regulations, please see our guide: Understanding the New Access to Cannabis for Medical Purposes Regulations.

The following information bulletin is also available: Safety and security when producing cannabis for your own medical purposes.

The full text of the new regulations was published in the Canada Gazette, Part II, on August 24, 2016.

Regulations no longer in effect
The Marijuana for Medical Purposes Regulations (MMPR) were repealed on August 24, 2016. The MMPR created conditions for a commercial industry that would be responsible for the production and distribution of marihuana for medical purposes. They also made sure that Canadians with a medical need, could access quality-controlled marihuana grown under secure and sanitary conditions.

In addition, on March 31, 2014, the Marihuana Medical Access Regulations (MMAR) were repealed. However, as a result of a Federal Court Order granted on March 21, 2014, individuals who were previously authorized to possess and/or produce marihuana under the former MMAR and who meet the terms of the Federal Court injunction order may continue to do so until the Court orders otherwise. Individuals covered by the injunction who wish to change the terms of their license, such as a change in address or designated producer, will be able to do so by registering with Health Canada under the new ACMPR.

Reference:

http://www.hc-sc.gc.ca/dhp-mps/marihuana/about-apropos-eng.php




Annual Drug Notification Form


Posted: Tuesday May 23rd, 2017

Article by: Rachelle D’Souza, Regulatory Heights Inc.

The Annual Drug Notification Form (ADNF) is intended to assist manufacturers in complying with section C.01.014.5 of the Food and Drug Regulations which requires that every manufacturer of a drug confirms annually before October that all information previously supplied with regard to that drug is correct.

Health Canada would like to inform manufacturers of changes to the information that is included in the Annual Drug Notification Form (ADNF). These changes are, in part, due to the Regulations Amending the Food and Drug Regulations (Shortages of Drugs and Discontinuation of Sale of Drugs) (the Regulations). These regulations were published in the Canada Gazette, Part II on June 29, 2016 and will come into force on March 14, 2017. Other changes have also been made to the ADNF in an effort to streamline the process.

The significant changes to the information included in the ADNF, and how it will affect manufacturers, are summarized below. These changes will be incorporated in the upcoming ADNF, which will be sent to manufacturers in June of 2017.

The inclusion of these changes to the ADNF will bring the annual notification process into compliance with the Regulations. Furthermore, it will increase the accuracy of the information presented in the Drug Product Database Online Query (DPD).

1.     Drug products which have been assigned a Drug Identification Number (DIN), but have not been marketed (Approved Products), will now be included as a separate list in the ADNF, in an effort to encourage manufacturers to cancel the DINs they do not intend to market in Canada. This will allow the Department to ensure that the drug information provided on the Department's website is accurate and up to date. It will also be beneficial for manufacturers as they will have a complete list of all their DINs in one report on an annual basis. With the implementation of this change, the biennial DIN Assigned Project, which had manufacturers clarify the status of their "Approved Products" in a separate report, will be eliminated.

2.     In accordance with section C.01.014.7 of the Regulations, for drug products that were marketed but are noted as being discontinued on the ADNF, manufacturers will be required to provide the discontinuation date, the lot number and the expiry date of the last lot sold by the manufacturer. This information will be recorded on a separate form that will be provided with the Annual Drug Notification Form.

3.     Drug products which are marketed but have not had sales for 12 consecutive months (Dormant Products) will be included as a separate list in the ADNF. Additionally, in accordance with section C.01.014.12 (1) of the Regulations, there will be an option for manufacturers to note if a marketed product has become a dormant product.

If you have any questions regarding this notice, please contact OSIP, TPD, Email: sipdannual_annuelledppr@hc-sc.gc.ca, Telephone: 613-946-1151, Facsimile: 613-954-3067

 

Regulatory Highlights

Updated: GD207: Guidance on the Content of ISO 13485 Quality Management System Certificates Issued by Health Canada Recognized Registrars




Future Regulatory Initiative for Opioids


Posted: Monday May 15th, 2017

Article by: Pinky Mazumder

If you have been tuning in to recent Canadian news, you will have noticed various critiques and discussions around the use of opioids. In case you are not familiar, opioids are narcotic pain relieving medications and are commonly prescribed in North America for acute and chronic pain1. However, in addition to its therapeutic effects, opioids carry various side effects including increasing tolerance and the potential for dependence and overdose, which can be fatal2. In fact in the year of 2015, there were approximately 2000 deaths in relation to opioid use in Canada1. With such alarming rates of overdoses and deaths across the nation, the need for a change could not be overlooked.

To respond to the opioid crisis, on May 8th, 2017, the Canadian Medical Association Journal published a clinical practice guideline with suggested recommendations on prescribing opioids. The guideline is primarily directed to physicians and relevant policy makers, and includes 10 recommendations for prescribing opioids for cases of chronic pain (non-cancer related)1. For more information, please read the guideline by clicking on this link. In addition to such clinical changes, Health Canada has also released a proposed regulatory initiative for opioid drugs3.

For the Forward Regulatory Plan of 2017-2019, Health Canada proposed a regulatory initiative titled: Amendments to the Food and Drugs Regulations – Labelling and Risk Management Plans for Opioid Drugs. These amendments may bring additional regulatory requirements for opioid drugs such as affixed warning stickers and mandatory risk management plans3. Complete and detailed information on the Forward Regulatory Plan by Health Canada, can be found here. The proposed changes are expected to be released in Canada Gazette Part I in 2017, to allow for public comments and consultations on the matter3. A link to the Canada Gazette Part I: Notices and Proposed Regulations can be found here.


Thank you for reading the CAPRA Blog. If such information is relevant to you, your organization/company, or to someone you know, please feel free to share this blog post with the Share buttons provided. Tune in next time for information on regulatory changes/updates for the industry. However, for implementation of any mentioned regulatory information and other regulatory information, please refer to the information directly released from the appropriate regulatory authorities. CAPRA is not a regulatory authority, nor a regulatory affairs consultation service. Thank you.

References
1.http://www.cmaj.ca/content/189/18/E659

2.https://www.canada.ca/en/health-canada/services/substance-abuse/prescription-drug-abuse/opioids/about.html

3.http://www.hc-sc.gc.ca/ahc-asc/legislation/acts-reg-lois/frp-ppr/2016-2018/opioid-opiode-eng.php




Changes to Submission Filing Requirements - Good Manufacturing Practices (GMP)/Drug Establishment Licences (DEL)


Posted: Monday May 8th, 2017

Article by: Madhur Jadawala, Lead Consultant, Quality & Compliance Services Inc.

Health Canada on February 10, 2017 has issued a notice outlining changes to the submission filing requirements pertaining to Good Manufacturing Practices (GMP)/ Drug Establishment Licences (DEL). These changes are effective immediately for drug submissions filed after the date of this notice (February 10, 2017).

Regulations

Pursuant to Sections C.08.002(2)(e ), C.08.002.01(2)(b), C.08.002.1(2)(a) and C.08.003(2)(e) of the Food and Drug Regulations a new drug submission (NDS), an extraordinary use new drug submission (EUNDS), an abbreviated new drug submission (ANDS), an abbreviated extraordinary use new drug submission (AEUNDS), or a supplement to any of these submissions, shall contain “details of the method of manufacture and the controls to be used in the manufacture, preparation and packaging of the new drug ”. The “controls” include those which ensure GMP, and which are required in order to be in compliance with Division 1A (Establishment Licences) and Division 2 to 4 (Good Manufacturing Practices) of the Regulations.

Background

Historically, the Therapeutic Products Directorate (TPD) of the Health Products and Food Branch (HPFB) of Health Canada has required that buildings performing licensable activities to be GMP compliant. If this requirement was not fulfilled, deficiency letters were issued to the sponsors. As a result, sponsors of drug submissions had to plan strategically when it came to the anticipated drug submission filing date because the DEL Unit’s service standard for processing DEL applications/amendments is 250 calendar days. In the worst-case scenario, the sponsor received a deficiency letter from TPD and had limited time (anywhere between 7 – 45 days) to respond to this deficiency for providing the evidence of GMP compliance. Now as mentioned above, the DEL unit takes about 250 days to process an application or amendment and hence the sponsor, by no means, can respond to this deficiency satisfactorily in the limited time provided by the TPD. Therefore, having appropriate DELs in place prior to submitting the drug submission was imperative and almost a pre-requisite activity.

Revised requirements

Therapeutic Products Directorate (TPD) of the Health Products and Food Branch (HPFB) of Health Canada is revising the process related to the requirements for evidence of Good Manufacturing Practices (GMP) for drug submissions. The goal of this revision is to better align the drug submission screening and review process with the Drug Establishment Licence (DEL) process. This should allow sponsors to make timely drug submissions while still providing adequate assurance of an establishment’s commitment to quality.

As of the date of this Notice (February 10, 2017), and as detailed below, TPD will also accept submissions where a complete application to amend the DEL pursuant to C.01A.006 of the FDR for new buildings and activities not currently listed on the drug submission sponsor’s DEL has been filed with the Minister at least 90 days prior to the time of filing a drug submission.

This requirement will be applicable to all NDS, EUNDS, ANDS, AEUNDS, Supplements, and DIN applications, thereto, submitted to the TPD for review. Eligible submissions are those where

(1) all required buildings and activities are listed on the current DEL,

(2) a site has a GMP compliance rating in Canada for the required activities and dosage form(s), and/or

(3) a complete DEL application has been filed with the Minister for any new buildings and activities.

Please note this notice is applicable ONLY to the drug submissions to TPD referred in this notice, and these are NOT applicable to drug submissions to the BGTD or any other directorate at Health Canada.

Where a DEL application was needed, the sponsor may file the drug submission 90 days after the Acknowledgment of Application Acceptance for the DEL application is issued by the Minister. Drug submissions which do not meet the requirements listed above will be issued a screening rejection letter.

In addition, where any site listed in a drug submission is considered by Health Canada to be non-compliant for GMP, a screening rejection letter will be issued.

The original complete notice published by Health Canada can be found at http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/notice_gmp_el_avis_bpf_le-eng.php

Please refer to the table below that provides a summary of activities that require documentation of a valid DEL and/or DEL application.

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The Journey towards Safe Food for Canadians


Posted: Monday May 1st, 2017

Article by: Carol T Culhane, PHEc, MBA, President, International Food Focus Ltd.

With alarming food safety recalls across the nation, in January 21st 2017, the long-awaited proposed regulations under the Safe Food for Canadians Act (SFCA), which received Royal Assent on November 22nd, 2012, was published in Canada Gazette I. The proposed Safe Food for Canadians Regulations reflects a significant change in the way that the Canadian Food Inspection Agency (CFIA) approaches the regulatory oversight of food safety in Canada.

Pan-Canadian outbreaks of listeriosis and E. coli and Salmonella contaminated food remain in common memory. In 2008, a listeriosis outbreak spanned across five provinces, cost the Canadian economy $242 million, sickened 57 Canadians, and claimed the lives of 23 individuals. Several years later, a nationwide 2012 E.coli contamination of ground beef involved the disposal of 5.5 million kg of product, and revealed that “the CFIA did not possess the power to compel regulated parties to provide adequate documentation in the event of a significant food safety incident.” Moreover in 2014, imported Salmonella-contaminated chia seeds which was incorporated into 24 products sold in Canada and prepared by nine separate Canadian manufacturers. Due to the imported nature of the chia seeds, there was a significant degree of complexity in the recall procedure that needed to be addressed.

Consequent to acceptance of their portion of the responsibility, the CFIA embarked detailed scrutiny, critical analysis, and a comprehensive makeover of their entire operation. The current scope of CFIA inspections are limited to federally-regulated commodities, such as meat and dairy products, while commodities such as spices, snack foods, bakery products, fats and oils, as well infant formula, are not subject to the same scrutinous regulatory requirements. There is also limited oversight on products distributed interprovincially, thus posing possible food safety concerns for Canadians. Moreover, such limiting domestic factors render the containment of food contamination between countries to be increasingly difficult, especially with the ever-growing global scale of food trade.

As a result, the proposed 17 part SFCR is an amalgamation of the Canada Agricultural Products Act, Meat Inspection Act, Fish Inspection Act, Consumer Packaging and Labelling Act, along with food-commodity based Regulations, which will be repealed with the ratification of the SFCR. Therefore, there will be two Acts with enabling regulations pertinent to food sold in Canada – the Food and Drugs Act and the Safe Food for Canadians Act. In addition, the SFCR also uses the legislative instrument, “Incorporated by Reference” (IbR), to include specificities such as Grades and Standards of Identity of food and food commodities. In the view of the CFIA, the SFCA has been designed to “encourage innovation [….], and contains explicit authority to incorporate any document into its regulations, regardless of its source”. An IbR is efficient and practical for all stakeholders by allowing prompt regulatory responses to scientific and innovative improvements without the need for formal and often lengthy regulatory amendments. The Food and Drugs Regulation, administered by Health Canada, carries a provision for IbR since 2012.

With a focus on licensing, trade, Preventive Control Plan (PCP), and traceability, the SFCR introduces new and updated fundamental changes to food safety and requires regulatory compliance by all stakeholders. Food manufacturing, preparing, processing, storing, labelling, importing, exporting, and interprovincial trade among others, would require licensure and a fixed place of business in Canada. With a proposed fee of $250, the license would be valid for a two-year period and would be based on the activity of the establishment. Meat licensure may be subject to additional requirements.

In addition, license applicants would be required to create a PCP to identify the biological, chemical and physical hazards to which the food being prepared is subject to, and, evidence-based, verified procedures specifically designed to control or eliminate these risks. For example, fruit and vegetable producers and processors need to be cognizant of possible contamination by E.coli and Salmonella, and accordingly require documented evidence-based procedures which are proven to be effective in operation and in control of contaminants. Similarly, fish importers and exporters need be aware of histamine levels in fresh fish and have documented procedures to reduce chemicals levels exceeding acceptance. The Regulations further outline the scope of the PCP to include lot numbers on all food products, recall plans, sanitation controls, pest controls, and non-food agents,  conveyances and equipment, conditions respecting establishments, unloading, loading and storing, staff competency, personnel hygiene, communicable diseases and procedures for investigation, and notifications and complaints. The proposed SFCR does however include exemptions for some parties such as businesses with $30,000 or less in annual gross revenue, however such operators will still require preventive control procedures in place.

In addition, the SFCR will also adopt the Codex Alimentarius template of “one step forward, one step back” for every link in the supply chain for enhanced traceability. In the event of a food safety recall, electronic or paper records must be accessible in Canada within 24 hours, which should identify the partner in an immediate forward transaction (e.g. a retailer or another food business), and the immediate backward supplier.  Retailers would not be required to trace forward their sales to consumers.

With such critical initiatives in licensing, PCP, and traceability among others, the SFCR addresses  current concerns and hazards in the food and food-commodity industry. The proposed SFCR in Canada Gazette I, is available HERE and additional information can be found HERE




Natural Health Product Research Society (NHPRS) of Canada hosts 14th annual conference, Beyond Tradition


Posted: Tuesday April 25th, 2017

The Natural Health Product Research Society (NHPRS) of Canada is pleased to host its 14th annual conference, Beyond Tradition, May 8-11, 2017, at the Pinnacle Hotel Waterfront in Vancouver, British Columbia.  With over 250 expected participants, this 4-day event will provide a great opportunity to learn from leaders in the Natural Health Product (NHP) sector, as they discuss key regulatory and quality assurance updates, as well as next innovations in NHP research.  Join the NHPRS as they host speakers from Health Canada, UNPA, USP, AHP, USDA, Chinese Pharmacopoeia, Academia, and key members of the North American health products industry, presenting on current topics in key NHP fields. 

This years’ event will feature focused sessions on Botanical Authentication; Regulatory and Government Affairs; Personalized Nutrition; Industrial Innovations and Emerging Technologies; Ethnobotany, Pharmacology & Traditional Medicine; Modernization of Pharmacopoeial Standards; Gut Health and the Intestinal Microbiome; and Cannabis.  Enjoy a pre-conference workshop, “Frontiers in NHP Research”; participate in the One-to-One Partnering program, and enjoy great social events in Vancouver, including a local Brewery/Distillery Tour and Conference Gala dinner.

Visit the NHPRS website to learn more about this exciting upcoming Canadian NHP industry event! 




Confidential Business Information Disclosure Update


Posted: Monday April 17th, 2017

The Health Minister can disclose confidential business information (CBI) to protect or promote health or safety. A draft guidance document on the disclosure of CBI was published on Mar 10, 2016 and Health Canada underwent a consultation period. Comments received by May 24, 2016 have been incorporated into the revised guidance. A summary of comments received is available on request by email to rmod_stakeholders-intervenants_dgro@hc-sc.gc.ca. This document is intended for health researchers and professionals, patient groups, and pharma and medical device industries. The document includes information on the following.

  • paragraph 21.1(3)(c) of the Food and Drugs Act
  • principals and considerations for Health Canada's exercise of the authority under paragraph 21.1(3)(c) of the Food and Drugs Act
  • protection of personal information and respecting participant's informed consent
  • protection against commercial use
  • maintaining confidentiality of disclosed information
  • process to review requests for disclosure
  • requirements for persons requesting disclosure of confidential business information under paragraph 21.1(3)(c)
  • findings generated from disclosed information
  • forms and additional information:
    • review process flow chart
    • tools for finding regulatory information


Completed CBI disclosure requests under s21.1(3)(c) of the Food and Drugs Act can be found here.




Changes to the Foreign Site Expiry dates on Canadian Drug Establishment Licences


Posted: Monday April 10th, 2017

OVERVIEW

Effective July 21, 2016, Health Canada has changed the expiry date for foreign building GMP renewal evidence to a NERBY (New Evidence Required By) date.

 

WHO DOES THIS APPLY TO?

·       Those who import or are seeking to import drugs from a foreign site listed on the DEL Foreign Annex, including API release testing sites.

 

WHAT’S NEW

·       GMP renewal evidence must now be submitted on or before a NERBY date assigned by Health Canada.

·       Health Canada reviews the submitted GMP renewal evidence, which includes an inspection report. Based on their review, Health Canada calculates a new NERBY date of three to four years from the start date of inspection.

·       Previously GMP renewal evidence had to be submitted 250 calendar days before the expiry date, requiring DEL holders to calculate and track their foreign building expiry dates.

·       Health Canada will not assign a NERBY date for the following (i.e., they must continue to submit GMP evidence 250 calendar days before the expiry date):

o   DELs for API foreign buildings listed on API Annex

o   MRA foreign buildings.

 

KEY POINTS

·       The foreign building expiry date is now a "new evidence required by" (NERBY) date.

·       Health Canada determines the NERBY date using a risk-based approach that takes into account factors such as the drug category and/or a building’s compliance history.

·       If Health Canada receives the application along with complete and updated GMP renewal evidence by the NERBY date, the foreign building will continue to be considered GMP compliant and remain on the DEL Foreign Building Annex during the Health Canada review period.

·       If you do not submit your application package to Health Canada by the NERBY date, the foreign building may be removed from the DEL.

·       If Health Canada deems the renewal evidence unacceptable or incomplete at any time during the assessment process, the foreign building may be removed from the DEL. 

·       You can request an extension 90 or more calendar days prior to the NERBY date or expiry date listed on the DEL.

·       Extension requests must be specific to each foreign building, and must be accompanied by an application form (section 5 of FRM-0033 for each foreign building).

 

References:

1.     Quality & Compliance Services Inc. QuickNote on “Changes to DEL Application Process (NERBY Date) dated January 2017 http://www.qualitycompliance.ca/sites/default/files/QuickNotes/QuickNote_Changes%20to%20DEL%20Application%20Process%20(NERBY)%202017-01-11.pdf

2.     Health Canada DEL Bulletin No. 1 dated July 21, 2016.

3.     Health Canada Guidance on Drug Establishment Licences and Drug Establishment Licensing Fees (GUI-0002) - http://www.hc-sc.gc.ca/dhp-mps/compli-conform/licences/directives/gui-0002-eng.php




Welcome To Regulated Affairs


Posted: Monday April 3rd, 2017

We are excited to be launching a blog for The Canadian Association of Professionals in Regulatory Affairs (CAPRA)!  Your source for timely information on news, events and updates in regulatory affairs in Canada.

CAPRA is the largest and only industry association devoted to individuals working in regulatory affairs in Canada.  We hope that sharing this blog and providing you with updates on Facebook, LinkedIn and Twitter will allow our members to stay connected to the each other and with the various regulators to help build a strong regulatory industry. 

Whether you work in pharmaceuticals, biologics, medical devices, natural health products, food, cosmetics and any other regulated health products, the CAPRA blog will help strengthen your regulatory knowledge and expertise. We will be providing you with informative updates on labelling regulations, Drug Establishment Licensing, the upcoming Safe Food for Canadian’s Regulations, and various other topics to help you keep up with the latest information in the field. Tune in regularly and feel free to share our blog with your colleagues.

We look forward to receiving your feedback  and comments and hope this will be an engaging platform where we can share ideas.

Let's get started!

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