What’s New Health Canada? Jan 2017

By Amelie Rodrigue-Way, Ph.D., RAC (CAN), Associate Director, Regulatory Strategy, and Christine Straccini, B.Sc., Regulatory Associate; Cato Research Canada

What’s New in:

Therapeutic Products Directorate:


Biologics and Genetic Therapies Directorate:


Medical Devices:


Natural and Non-prescription Health Products Directorate:



Health Canada New Guidance Documents

(Drugs and Biologics):
October – December 2016

Health Canada Guidance/Notice Type Date Posted
Updated – Guidance Document: Preparation of Regulatory Activities in the “Non-eCTD Electronic-Only” Format


Guidance 14 Dec 2016
Guidance Document: Information and Submission Requirements for Biosimilar Biologic Drugs


Guidance 02 Dec 2016
Patented Medicines (Notice of Compliance) Regulations


Draft Guidance 27 Oct 2016
How to Pay Fees to Health Products and Food Branch (HPFB)


Guidance 19 Oct 2016
Post-Notice of Compliance (NOC) Changes: Quality Document


Guidance 14 Oct 2016
Consultation on the Health Canada Draft Guidance Document: Quality (Chemistry and Manufacturing) Guidance: New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDSs)





This consultation was open for comment until December 4, 2016

Draft Guidance


05 Oct 2016


Updates from Health Canada

(Drugs and Biologics)

Type of Update and Link Date
Notice: Mandatory Requirements for using the Common Electronic Submissions Gateway (CESG)


28 Dec 2016
Notice: Final Release: Part I – Health Professional Information and Part II – Scientific Information of the Guidance Document – Product Monograph


09 Dec 2016
Fact Sheet: Biosimilars


07 Dec 2016
Register of Innovative drugs


02 Dec 2016
Notice – Validation rules for regulatory transactions submitted to Health Canada in the electronic Common Technical Document (eCTD) format


01 Dec 2016
Notice: Release of Draft (Step 2) International Council for Harmonisation (ICH) Guidance: E11(R1): Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population



04 Nov 2016
Notice: Release of the revised Post-Notice of Compliance (NOC) Changes – Quality Guidance



03 Nov 2016
Notice – Post-Notice of Compliance (NOC) Changes: Notices of Change (Level III) Form


03 Nov 2016
Product Monograph Brand Safety Updates


19 Oct 2016
Posted in Cato Research, Drug Development, Health Canada, Medical Research, Regulatory Strategy, Regulatory Submissions | Tagged , , , | Leave a comment

New FDA Guidances for December 2016

By Joanne McNelis, Ph.D., Clinical Strategy Scientist at Cato Research

FDA draft and final guidances, released from CDER, CBER, and CDRH in December 2016 are posted. In addition, upcoming advisory committee meetings are listed below with links to more information.

Special Interest Guidances/Information Date Posted
Electronic Drug Product Reporting for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act. – Final Guidance 30 Dec 2016
Medical Device Accessories – Describing Accessories and Classification Pathway for New Accessory Types – Guidance for Industry and Food and Drug Administration Staff – Final Guidance 30 Dec 2016
Prescription Requirement Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance for Industry – Final Guidance 28 Dec 2016
Compounding and Repackaging of Radiopharmaceuticals by State-Licensed Nuclear Pharmacies and Federal Facilities Guidance for Industry – Draft Guidance 28 Dec 2016
Compounding and Repackaging of Radiopharmaceuticals By Outsourcing Facilities Guidance for Industry – Draft Guidance 28 Dec 2016
Providing Regulatory Submissions in Electronic Format–Submission of Manufacturing Establishment Information Guidance for Industry – Draft Guidance 28 Dec 2016
Botanical Drug Development: Guidance for Industry – Final Guidance 28 Dec 2016
Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product – Final Guidance 28 Dec 2016
Postmarket Management of Cybersecurity in Medical Devices; Guidance for Industry and Food and Drug Administration Staff – Final Guidance 28 Dec 2016
ANDA Submissions — Refuse-to-Receive Standards Rev.2 -Final Guidance 21 Dec 2016
Use of Electronic Informed Consent in Clinical Investigations – Questions and Answers – Final Guidance 14 Dec 2016
Public Notification of Emerging Postmarket Medical Device Signals (“Emerging Signals”) – Guidance for Industry and Food and Drug Administration Staff – Final Guidance 14 Dec 2016
Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans; Guidance for Industry – Final Guidance 12 Dec 2016
Immediately in Effect Guidance Document: Conditions for Sale for Air-Conduction Hearing Aids – Guidance for Industry and Food and Drug Administration Staff – Final Guidance 12 Dec 2016
Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification Guidance for Industry – Final Guidance 08 Dec 2016
Clinical Pharmacology Labeling for Human Prescription Drug and Biological Products — Content and Format – Final Guidance 02 Dec 2016
Physiologically Based Pharmacokinetic Analyses — Format and Content Guidance for Industry – Draft Guidance 01 Dec 2016
Upcoming Meetings (* = New)
* March 15, 2017: Pharmaceutical Science and Clinical Pharmacology Advisory Committee Meeting Announcement
* 2017 Advisory Committee Tentative Meetings
* new entry
Last updated: 06 January 2017
Posted in Cato Research, Clinical Trials, FDA, Regulatory Strategy, Regulatory Submissions, Uncategorized | Tagged , , | Leave a comment

Transparency Initiatives at Health Canada

By Amelie Rodrigue-Way, Ph.D., RAC (CAN), Associate Director, Regulatory Strategy for Cato Research Canada.

As part of the Regulatory Transparency and Openness Framework (http://www.hc-sc.gc.ca/home-accueil/rto-tor/index-eng.php), Health Canada has committed to provide greater transparency and openness to further strengthen trust in their regulatory decisions.

The Framework will:

  • Help Canadians to better understand how and why decisions are made. Canadians will be able to use this information to make well-informed decisions on their health and the health of their families.
  • Assist industry to be better positioned to comply with current regulatory requirements and plan for upcoming regulatory changes.


Since 2012, Summary Basis of Decision (SBD) documents are published for ‘novel’ drugs and devices: New Drug Submissions for New Active Substances and a subset of Class IV medical device applications. The SBD documents explain why Health Canada authorized certain drugs for sale in Canada. The documents include regulatory, safety, effectiveness and quality (chemistry and manufacturing) considerations.

Under the transparency initiatives, the Health Products and Food Branch (HPFB) proceeded since May 2016 with Phase II of the Regulatory Decision Summary (RDS) and Submissions Under Review (SUR) List initiatives.


Submissions Under Review (SUR)

Canadians can access the list of certain drug submissions currently under review. These submissions include new drug submissions (NDSs) containing new active substances, pharmaceuticals and biologics with an active ingredient not approved in Canada. This applies to submissions whose review started on or after 01 April 1 2015.

The following are now included on the SUR List as part of Phase II of the Transparency Initiatives:

– Medicinal ingredient and therapeutic class for all NDSs and SNDSs for new indications for pharmaceuticals and biologics accepted into review on or after 01 May 2016

The entry for each submission includes its medicinal ingredient(s) and therapeutic area but not the manufacturer. The list is updated monthly.

A substance is removed from these lists:

  • once a final decision is made and the submission is no longer under review
  • if the submission is cancelled

Canadians can see if a submission has been approved in the Notice of Compliance Database. In addition, an explanation of the decision (positive or negative) or cancellation in the Regulatory Decision Summary (RDS) will be available. If applicable, a more detailed explanation is also contained in a Summary Basis of Decision document.


Regulatory Decision Summary (RDS)

The regulatory decision summaries (RDSs) provide Canadians with an understanding of the decisions to approve or not approve the sale of drugs and medical devices in Canada.

RDSs for positive decisions issued after 01 April 2015, are provided for:

  • new drug submissions (NDSs) for prescription pharmaceuticals and biologics
  • supplemental new drug submissions (SNDSs) for new uses of prescription pharmaceuticals and biologics
  • new class IV licence applications for medical devices

Summaries are also posted for negative decisions and cancellations for NDSs accepted into review after 01 April 2015. These submissions are for drugs containing new active substances, pharmaceuticals and biologics with an active ingredient not approved in Canada.

The following RDSs for negative decisions and cancellations are now published as part of Phase II of the Transparency Initiatives for submissions accepted into review after 01 May 2016:

  • NDSs
  • SNDSs for new uses
  • new class IV licence applications for medical devices

The following information may be listed on the RDS:

  • What was the purpose of this submission?
  • Why was the decision issued?
  • What did the company submit to support its submission?
  • Decision issued
  • What was the status of the submission when it was cancelled? What was Health Canada’s assessment of the submission at the time of cancellation?
  • Date of decision or cancellation
  • What consequences does the cancellation have for patients accessing the drug under the Special Access Programme (SAP), or via clinical trials?
  • Manufacturer
  • Drug Identification Number(s) if issued
  • Prescription status
  • Type of submission
  • Date filed
  • Control number




Summary Under Review:



Regulatory Decision Summaries (RDSs), Medical Devices and Drugs: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/rds-sdr/index-eng.php


Summary Basis of Decision (SBD), Medical Devices and Drugs: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/index-eng.php




Posted in Canadian Regulatory Affairs, Cato Research, Clinical Trials, Drug Development, Health Canada | Tagged , , | Leave a comment

New FDA Guidances for October and November 2016

By Michelle Villasmil, Ph.D., Regulatory Scientist at Cato Research

FDA draft and final guidances, released from CDER, CBER, and CDRH in October and November 2016 are posted. In addition, upcoming advisory committee meetings to be held in the next month are listed below with links to more information.


Special Interest Guidances/Information Date Posted
Mitigating the Risk of Cross-Contamination from Valves and Accessories Used for Irrigation Through Flexible Gastrointestinal Endoscopes – Final Guidance 29 Nov 2016
Providing Postmarket Periodic Safety Reports in the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report) – Final Guidance 28 Nov 2016
Submission of Quality Metrics Data Guidance for Industry – Draft Guidance 23 Nov 2016
Nonprescription Sunscreen Drug Products – Format and Content of Data Submissions – Final Guidance 22 Nov 2016
Contract Manufacturing Arrangements for Drugs: Quality Agreements – Final Guidance 22 Nov 2016
Nonprescription Sunscreen Drug Products – Safety and Effectiveness Data – Final Guidance 22 Nov 2016
Safety Testing of Drug Metabolites – Final Guidance 22 Nov 2016
Generic Drug User Fee Amendments of 2012: Questions and Answers Related to User Fee Assessments – Final Guidance 21 Nov 2016
Submission of Premarket Notifications for Magnetic Resonance Diagnostic Devices – Final Guidance 18 Nov 2016
BCG-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment – Draft Guidance 17 Nov 2016
Product Labeling for Certain Ultrasonic Surgical Aspirator Devices – Draft Guidance 10 Nov 2016
Medical Device Reporting for Manufacturers – Final Guidance 08 Nov 2016
Clinical Considerations for Investigational Device Exemptions (IDEs) for Neurological Devices Targeting Disease Progression and Clinical Outcomes – Final Guidance 07 Nov 2016
Non-Inferiority Clinical Trials – Final Guidance 07 Nov 2016
Revised Recommendations for Determining Eligibility of Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products Who Have Received Human-Derived Clotting Factor Concentrates – Final Guidance 01 Nov 2016
Labeling for Permanent Hysteroscopically-Placed Tubal Implants Intended for Sterilization – Guidance for Industry and Food and Drug Administration Staff – Final Guidance 31 Oct 2016
Collection of Race and Ethnicity Data in Clinical Trials – Guidance for Industry and FDA Staff – Final Guidance 26 Oct 2016
Low Sexual Interest, Desire, and/or Arousal in Women: Developing Drugs for Treatment Guidance for Industry – Draft Guidance 25 Oct 2016
Software as a Medical Device (SaMD): Clinical Evaluation – Draft Guidance 14 Oct 2016
ANDA Submissions – Prior Approval Supplements Under GDUFA – Final Guidance 14 Oct 2016
Blood Glucose Monitoring Test Systems for Prescription Point-of-Care Use – Guidance for Industry and Food and Drug Administration Staff – Final Guidance 11 Oct 2016
Self-Monitoring Blood Glucose Test Systems for Over-the-Counter Use – Guidance for Industry and Food and Drug Administration Staff – Final Guidance 11 Oct 2016
Sunscreen Innovation Act: Withdrawal of a 586A Request or Pending Request Guidance for Industry – Final Guidance 07 Oct 2016
Sunscreen Innovation Act: Section 586C(c) Advisory Committee Process – Final Guidance 07 Oct 2016
Head Lice Infestation: Developing Drugs for Topical Treatment Guidance for Industry – Final Guidance 05 Oct 2016
Tropical Disease Priority Review Vouchers – Final Guidance 05 Oct 2016
Acetaminophen; Oxycodone hydrochloride_204031 – Draft Guidance 04 Oct 2016
Upcoming Meetings (* = New)
* Bone, Reproductive and Urologic Drugs Advisory Committee; 06 December 2016; Silver Spring, MD
* 2017 Advisory Committee Tentative Meetings
* new entry

Last updated: 30 November 2016



Posted in Cato Research, Drug Development, FDA, Medical Research, Regulatory Strategy, Regulatory Submissions | Tagged , , | Comments Off on New FDA Guidances for October and November 2016

NORD Summit 2016 Highlights

By Kimberley Cummings, Ph.D., RAC (US), Vice President, Scientific & Regulatory Strategy and Operations Cato Research


The National Organization for Rare Disorders (NORD) held their annual Rare Diseases and Orphan Products Breakthrough Summit in Arlington, VA on October 17th and 18th.  If you have never been to this meeting before, it is the most unique and interesting mix of FDA representatives (and we are talking BIG names, too!), pharmaceutical/industry representatives, policy analysts, and patient advocacy groups along with several patients themselves.  That combination of individuals will certainly lead to some thought-provoking discussions, and if you follow any other industry blogs, then you have likely already seen some interesting highlights from this conference.

At last year’s Summit, the biggest news regarding Patient-Focused Drug Development and patient advocacy was that patients were, in fact, helping forge a path to approval as evidenced by the development and subsequent release of the FDA’s Guidance for Industry: Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment, a guidance largely drafted by the Duchenne advocacy community.  So, it was no surprise that this year, the discussion continued around potential drugs for Duchenne’s Muscular Dystrophy, but mostly on the recent somewhat controversial approval of Sarepta’s Exondys 51 (eteplirsen).  Not once or even twice, but at least three during the various sessions I attended, did an FDA or industry representative express their opinions on the approval of Exondys 51 only to result in an emotional rebuttal comment from a parent and/or advocate.  Clearly, charged conversations occurred during the approval process, and are still lingering today.

Rest assured, there were many other informative discussions that took place over the course of the 2-day summit.  Session topics included genetic innovation, advancing diagnoses, challenges of access and reimbursement, progress through policy, and understanding the pipeline and investment landscape for rare diseases and orphan products.  Presented here are some of the important take‑away messages from these various discussions:

  1. Rigorous data exploration has been and must remain the driver for drug development. Orphan drugs tend to be innovative (ie, first in class) and take advantage of FDA’s special programs, but development and approval must be based on strong science.  Furthermore, the development programs need to keep up with the ever-evolving science including innovations in telemedicine, genetic phenotyping, biosimilars, and advancements in CRISPR (clustered regularly interspaced palindromic repeat) technology, just to name a few.  In response to some of these advancing technologies, FDA has even reorganized to provide better oversight of gene therapy products; the office formerly known as the Office of Cellular, Tissue and Gene Therapies (OCTGT) has now become the Office of Tissues and Advanced Therapies (OTAT).  The formation of OTAT involves the transfer of the Office of Blood Research and Review’s Division of Hematology Clinical Review and Division of Hematology Research and Review, along with appropriate support staff, to OCTGT to constitute the new office.  The products now regulated by OTAT include all purified and recombinant versions of therapeutic proteins for hematology.


  1. Collaboration must continue between patient advocacy groups and the FDA, as well as among researchers through consortia. No one can hold all the knowledge.  This thinking is also supported by the Final Rule for the registering of studies and posting of results on Clinicaltrials.gov.  A panel discussion on collaboration across borders identified the increased interactions between FDA and EMA in regards to rare disease programs and suggested more international patient advocacy groups.  Furthermore, this panel confirmed the need for patient-driven registries, by disease, not by company, to collect natural history data and suggested a global depository system with standardized terms.  Progress in global outreach was substantiated by the establishment of the United Nations Committee for Rare Diseases.  This Committee will serve as an advocacy platform uniting around the issue of rare diseases a diversity of constituents which need to be more closely connected and collaborating with each other, including: the international non-governmental (NGO) community, major UN agencies, national governments, the academic and scientific world as well as the private sector.  The formal inauguration of the Committee is currently scheduled for November 11, 2016 at the United Nations headquarters in New York.


  1. In regards to patient advocacy collaboration, FDA continues to conduct the Patient Focused Drug Development (PFDD) meetings per the PDUFA V goals. A total of 24 PFDD meetings were planed from FY 2013-2017, and include the publication of a “Voice of the Patient” upon completion of the meeting.  To date, 20 meetings have been conducted, and only 4 remain.  These final 4 meetings will examine sarcopenia, autism, alopecia areata, and hereditary angioedema.  Upon completion of this PDUFA V goal, externally led PFDD meetings are expected to continue.  Meetings will be attended, but not organized by FDA; rather, a patient advocacy group or consortia would submit a letter of intent to the FDA 1 year in advance of the anticipated meeting date outlining the time, location, goal, objectives, outreach effort, and expected collaboration for the meeting.  Meeting organizers would also be expected to produce a “Voice of the Patient” report on their own website.


  1. FDA speakers confirmed for their audience that randomized clinical trials are the fastest way to determine clinical effectiveness. Especially in rare disease populations, every subject is critical, so valuable resources – either the subject themselves or a subject’s samples, should not be misused or wasted on poorly designed clinical trials.  To that end, the paradigm of early open-label studies shifted to randomizing subjects with rare diseases as early as possible and minimize time on placebo.  Emphasis was placed on the use of validated biomarkers and the need to report trial results early and accurately to obtain input from the FDA in regards to the clinical relevance of the biomarker and the plan for accelerated approval.  The audience was reminded that accelerated approval is NOT a rescue for a failed program, and that “any” effect of a drug on a biomarker does not equate to accelerated approval. Only a clearly defined and clinically relevant effect would suffice for accelerated approval.  Finally, post-hoc analyses should be used to design the next clinical trial, not as a basis for approval.


  1. As Natural History studies remain a critical component of rare disease and orphan product development, all stakeholders need to understand the natural history of a disease, and prospectively identify any natural history external controls. In regards to understanding the natural history of a disease, the Office of Orphan Product Development launched the Orphan Products Natural History Grants Program in 2016.  The goal of the grants program is to support studies that advance rare disease medical product development through characterization of the natural history of rare diseases/conditions, identification of genotypic and phenotypic subpopulations, and development and/or validation of clinical outcome measures, biomarkers and/or companion diagnostics.


  1. Officials at FDA working with rare diseases and orphan indications remain committed and VERY busy. Over the past 6 years, OOPD has seen a doubling of the number of orphan designations requests and will likely see a record number of designation requests this year.  To keep up with this demand, OOPD has had to expand the review time of a designation request from 90 days to 120 days.


Paul Melmeyer, NORD’s Associate Director of Public Policy, said it best when he said, “If you have a drug in the FDA process in the next 6 years, you should be involved with PDUVA VI.”  Given the timing of this meeting so close to a Presidential election, there was a particularly strong policy component to this year’s summit.  With the upcoming authorization of PDUFA VI, proposed bills already in review in Congress (including 21st Century Cures), and potential major healthcare changes with the approaching election, the next few months and years to come should bring about some small, and some not so small, changes in drug development, particularly for rare diseases and orphan indications.


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