What’s New Health Canada?

By Christine Straccini, B.Sc., C.C.R.P., Regulatory Associate II

 

What’s New in:

Therapeutic Products Directorate:

https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/what-new-drug-products-health-canada.html

 

Biologics and Genetic Therapies Directorate:

http://www.hc-sc.gc.ca/dhp-mps/brgtherap/update-miseajour/index-eng.php

Medical Devices: https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/what-new.html

Natural and Non-prescription Health Products Directorate: https://www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription/what-new.html

 

Health Canada New Guidance Documents (Drugs and Biologics)

Health Canada Guidance Type Date Posted
Publication of the Guidance Document: Certificate of Supplementary Protection Regulations Guidance 19 September 2017
Publication of the Health Canada Guidance Document: Use of Certificates of Suitability as supporting information in Drug Submissions Guidance 21 August 2017

 

Updates from Health Canada (Drugs and Biologics)

Type of Update and Link Date Posted
Updated Notice: Interim Policy on Health Canada’s Interpretation of Medicinal Ingredient and Assessment of Identical Medicinal Ingredient 05 October 2017
Consultation: Release of Draft (Step 2) ICH Guidance: E9(R1): Addendum: Statistical Principles for Clinical Trials 05 October 2017
Consultation: Release of Draft (Step 2) ICH Guidance: S5(R3): Revision of S5 Guideline on Detection of Toxicity to Reproduction for Human Pharmaceuticals 05 October 2017
Notice – Patented Medicines (Notice of Compliance) Regulations 19 September 2017
Notice: eCTD Pilot for Clinical Trial Regulatory Activities – Extension 28 August 2017
Notice: Health Canada and United States Food and Drug Administration Joint Public Consultation on International Council for Harmonisation (ICH) 25 August 2017

 

 Santé Canada: Quoi de neuf?

Par Christine Straccini, B.Sc., Associée réglementaire II

 

Quoi de neuf :

Direction des produits thérapeutiques:

https://www.canada.ca/fr/sante-canada/services/medicaments-produits-sante/medicaments/quoi-neuf-medicaments-sante-canada.html

 

Direction des produits biologiques et thérapies génétiques:

http://www.hc-sc.gc.ca/dhp-mps/brgtherap/update-miseajour/index-fra.php

Instruments médicaux: https://www.canada.ca/fr/sante-canada/services/medicaments-produits-sante/instruments-medicaux/quoi-neuf.html

Direction des produits de santé naturels et sans ordonnance:

https://www.canada.ca/fr/sante-canada/services/medicaments-produits-sante/naturels-sans-ordonnance/quoi-de-neuf.html

 

Nouvelles lignes directrices de Santé Canada (Médicaments et Produits biologiques)

 Ligne directrice de Santé Canada

Genre Date
Publication de la ligne directrice : Règlement sur les certificats de protection supplémentaire ligne directrice 19 septembre 2017
Publication de la ligne directrice de Santé Canada : Utilisation de certificats de conformité à titre d’information à l’appui des présentations de drogue ligne directrice 21 août 2017

 

Mises à jour de Santé Canada (Médicaments et Produits biologiques)

 

Genre de mise à jour et lien Date
Avis mis à jour : Politique provisoire sur l’interprétation du terme « ingrédient médicinal » et sur l’évaluation d’un « ingrédient médicinal identique » par Santé Canada 05 octobre 2017
Consultation : Publication de l’ébauche (étape 2) ICH Guidance: E9(R1): Addendum: Statistical Principles for Clinical Trials 05 octobre 2017
Consultation : Publication de l’ébauche (étape 2) ICH Guidance: S5(R3): Revision of S5 Guideline on Detection of Toxicity to Reproduction for Human Pharmaceuticals 05 octobre 2017
Avis : Règlement sur les médicaments brevetés (avis de conformité) 19 septembre 2017
Avis : Projet pilote sur le format eCTD pour les activités de réglementation liées aux études cliniques – Prolongation 28 août 2017
Avis: Santé Canada et États-Unis Food and Drug Administration Consultation publique mixte sur la Conférence internationale sur l’International Council for Harmonisation (ICH) 25 août 2017

 

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New FDA Guidances for September 2017

By Michelle Villasmil, Ph.D., RAC (US), Regulatory Scientist at Cato Research

FDA draft and final guidances released from CDER, CBER, and CDRH and Manual of Policies and Procedures (MAPPs) of interest released from CDER in September 2017 are posted. In addition, upcoming advisory committee meetings are listed below with links to more information.

 

Special Interest Guidances/Information Date Posted
Developing and Responding to Deficiencies in Accordance with the Least Burdensome Provisions – Final Guidance 29 Sep 2017
Center for Devices and Radiological Health Appeals Processes: Questions and Answers About 517A – Final Guidance 29 Sep 2017
Display Devices for Diagnostic Radiology – Final Guidance 29 Sep 2017
Administrative Procedures for CLIA Categorization – Final Guidance 29 Sep 2017
Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations – Draft Guidance 28 Sep 2017
Advancement of Emerging Technology Applications for Pharmaceutical Innovation and Modernization – Final Guidance 28 Sep 2017
Classification of Products as Drugs and Devices and Additional Product Classification Issues – Final Guidance 25 Sep 2017
Expedited Programs for Serious Conditions – Drugs and Biologics – Final Guidance 22 Sep 2017
Statistical Approaches to Evaluate Analytical Similarity – Draft Guidance 21 Sep 2017
Q4B Annex I: Residue on Ignition/Sulphated Ash General Chapter – Final Guidance 18 Sep 2017
Q4B Annex 2: Test for Extractable Volume of Parenteral Preparations General Chapter – Final Guidance 18 Sep 2017
Q4B Annex 3: Test for Particulate Contamination: Subvisible Particles General Chapter – Final Guidance 18 Sep 2017
Q4B Annex 4A: Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests General Chapter – Final Guidance 18 Sep 2017
Q4B Annex 4B: Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms General Chapter – Final Guidance 18 Sep 2017
Q4B Annex 4C: Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use General Chapter – Final Guidance 18 Sep 2017
Q4B Annex 5: Disintegration Test General Chapter – Final Guidance 18 Sep 2017
Q4B Annex 8: Sterility Test General Chapter – Final Guidance 18 Sep 2017
Q4B Annex 9: Tablet Friability General Chapter – Final Guidance 18 Sep 2017
Q4B Annex 10: Polyacrylamide Gel Electrophoresis General Chapter – Final Guidance 18 Sep 2017
Establishing the Performance Characteristics of In Vitro Diagnostic Devices for the Detection or Detection and Differentiation of Human Papillomaviruses – Final Guidance 15 Sep 2017
Regulatory Considerations for Microneedling Devices – Draft Guidance 15 Sep 2017
Utilizing Animal Studies to Evaluate Organ Preservation Devices – Draft Guidance 12 Sep 2017
Microdose Radiopharmaceutical Diagnostic Drugs: Nonclinical Study Recommendations – Draft Guidance 12 Sep 2017
Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device Clinical Studies – Final Guidance 12 Sep 2017
Guidance Agenda: Guidances CDER is Planning… 12 Sep 2017
Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices – Final Guidance 06 Sep 2017
Deviation Reporting for Human Cells, Tissues, and Cellular and Tissue-Based Products Regulated Solely Under Section 361 of the Public Health Service Act and 21 CFR Part 1271 – Final Guidance 06 Sep 2017
Procedures for Meetings of the Medical Devices Advisory Committee – Final Guidance 01 Sep 2017
Requalification of Donors Previously Deferred for a History of Viral Hepatitis after the 11th Birthday – Final Guidance 01 Sep 2017
Providing Regulatory Submissions in Electronic Format – Content of the Risk Evaluation and Mitigation Strategies Document Using Structured Product Labeling – Draft Guidance 01 Sep 2017
Special Interest Manual of Policies & Procedures (CDER) Date Posted
Process for Evaluating Emerging Technologies Related to Quality 28 Sep 2017
Environmental Assessments and Claims of Categorical Exclusion 14 Sep 2017
Filing Review of Abbreviated New Drug Applications 01 Sep 2017
Upcoming Meetings (* = New)
* October 4, 2017: Vaccines and Related Biological Products Advisory Committee
  October 11-12, 2017: Patient Engagement Advisory Committee
* October 12, 2017: Cellular, Tissue and Gene Therapies Advisory Committee
* October 13, 2017: Meeting of the Dermatologic and Ophthalmic Drugs Advisory Committee
* October 31, 2017: Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee
* November 1, 2017: Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee
* November 7, 2017: Vaccines and Related Biological Products Advisory Committee
* November 16, 2017: Meeting of the Antimicrobial Drugs Advisory Committee
  December 7, 2017: Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee
Last updated: 03 October 2017
Posted in Cato Research, FDA, Regulatory Affairs, Regulatory Submissions | Tagged , , | Comments Off on New FDA Guidances for September 2017

Time to Approval and the Metrics of Facilitated Regulatory Pathways

By Dr. Jack Snyder, RAC (US, EU, CA, GS), Asst. Managing Director and Clinical Research Physician at Cato Research

“Early access pathways” for biomedical product marketing approval have attracted substantial attention recently, as Sarepta Therapeutics’ drug Exondys (eteplirsen) gained accelerated approval based on clinical data from just 12 patients.  In the United States, four “expedited” or “conditional” pathways for novel products for serious diseases or unmet medical need are available: Fast Track designation (FT), Breakthrough Therapy designation (BTD), Priority Review designation (PR), and Accelerated Approval pathway (AA).  Characteristics and distinguishing elements of these pathways have been well described by FDA in a 2014 Guidance for Industry: Expedited Programs for Serious Conditions — Drugs and Biologics. Proposed benefits include increased levels of communication and commitment between FDA and product sponsors, greater roles for surrogate endpoints, transfer of burden of evidence generation from pre- to post-authorization phases, and shortened review timelines. None of these programs are exclusive, any combination is permissible, and any designation may be rescinded if products do not continue to meet defined criteria upon periodic reassessment.

Some voices now are clamoring for FDA to adopt the approach of the European Medicines Agency (EMA), which instituted Conditional Marketing Authorization (CMA) procedures in 2006 for products where (a) benefit/risk balance is positive; (b) it is likely that comprehensive clinical data will be provided; (c) unmet medical needs will be fulfilled; and

(d) benefit to public health of immediate availability outweighs risks that additional data are still required.  These EMA-CMA approvals require annual renewal and can be converted to full marketing authorizations upon review of definitive data generated during the conditional approval period.

Do any of these initiatives significantly alter timelines in biomedical product development?  A group of European investigators recently assessed the influence of “Facilitated Regulatory Pathways” (FRP) on review times for 125 new active substances approved by FDA between January 2013 and December 2015.  Metrics for this study included the following:

 

Approved NAS 125
NAS approved using FRP 74 (no use of BTD alone, FT + BTD, or AA ± BTD)
Median development times (IND to NDA submission
Any FRP 2377 days
No FRP 2148 days
BTD + PR + AA 1458 days
FT alone 2620 days
PR alone 3515 days
Median Approval Times
Any FRP 243 days
No FRP 365 days
FT + BTD + PR + AA [a] 145 days
BTD + AA + PR 166 days
FT + BTD + PR 242 days
FT + PR 292 days
PR alone 242 days
Median Developmental + Approval Times (IND to Approval)
Any FRP 2620 days
No FRP 2513 days
BTD + AA + PR 1624 days
BTD + FT + PR 1720 days
FT + PR 2308 days
FT + BTD + AA + PR 2434 days
FT alone 2981 days
PR alone 3757 days

AA = Accelerated Approval; BTD = Breakthrough Therapy Designation; FRP = facilitated regulatory pathways; FT = Fast Track Designation; PR = Priority Review; NAS = new active substances
[a] Four NAS qualified for all four FRPs: ibrutinib, idelalisib, nivolumab, osimertinib mesylate, daratumumab

The authors concluded that combinations of FRPs can shorten review times beyond those provided by PR alone.  The data do not appear, however, to support a general conclusion that various combinations of FRPs reliably shorten the time elapsing between IND submission and marketing approval, or between product conception and marketing approval.

Although FRPs aim to accelerate patient access to medicines, some analyses have in fact shown that development times from first-in-human testing to marketing authorization using FRPs are comparable to development times associated with full (no FRP) marketing authorization, yet are based on less comprehensive data.  Consequently, commentators have raised the possibility that instead of using the FRPs prospectively, sponsors are using them as a backup to full authorization when data packages may not be strong enough to support a full market authorization through conventional pathways.  In any case, more data are needed to determine whether or not implementation of FRPs makes a meaningful difference in terms of conservation of time and/or resources in the biomedical product development plus approval process.

Meanwhile, as of June 2017, the same drug can be eligible for FRPs simultaneously in the U.S., Canada, Europe and Australia.  Since most countries in South America, Africa and Asia grant preferential review to drugs approved by regulators in the U.S., Canada, Europe and Australia, expedited approval in these regions potential translates into world-wide approval of a given drug. With multinational adoption of most expedited approval pathways, it may be tempting for sponsors to simultaneously apply for designations in all regions. However, if any one regulatory agency disagrees with the designation request, it is likely that other regulators will follow suit as well. So, the best strategy is to get successful designation in one region and then try to use that in others.

 

FDA facilitated regulatory pathways: Visualizing their characteristics, development, and authorization timelines. Liberti L, Bujar M, Breckenridge A, Hoekman J, McAuslane N, Stolk P, Leufkens H. Front Pharmacol. 2017 Apr; 8:1-6.

Use of the conditional marketing authorization pathway for oncology medicines in Europe.
Hoekman J, Boon WP, Bouvy JC, Ebbers HC, de Jong JP, De Bruin ML.
Clin Pharmacol Ther. 2015 Nov; 98(5):534-41.

Duchenne muscular dystrophy drugs at the crossroads, as newer agents advance.
Sheridan C.  Nat Biotechnol. 2016 Jul 12; 34(7):675-6.

 

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New FDA Guidances for August 2017

By Michelle Villasmil, Ph.D., RAC (US), Regulatory Scientist at Cato Research

FDA draft and final guidances released from CDER, CBER, and CDRH and Manual of Policies and Procedures (MAPPs) of interest released from CDER in August 2017 are posted. In addition, upcoming advisory committee meetings are listed below with links to more information.

Special Interest Guidances/Information Date Posted
Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices – Final Guidance 31 Aug 2017
Policy Clarification and Premarket Notification [510(k)] Submissions for Ultrasonic Diathermy Devices – Draft Guidance 31 Aug 2017
FY 2018 Medical Device User Fee Small Business Qualification and Certification – Final Guidance 29 Aug 2017
Identifying Trading Partners Under the Drug Supply Chain Security Act Guidance for Industry – Draft Guidance 18 Aug 2017
Qualification of Medical Device Development Tools – Final Guidance 10 Aug 2017
Expiration Dating of Unit-Dose Repackaged Solid Oral Dosage Form Drug Products – Final Guidance 08 Aug 2017
CMC Postapproval Manufacturing Changes for Specified Biological Products To Be Documented in Annual Reports – Draft Guidance 08 Aug 2017
Child-Resistant Packaging Statements in Drug Product Labeling – Draft Guidance 02 Aug 2017
Antibacterial Therapies for Patients With an Unmet Medical Need for the Treatment of Serious Bacterial Diseases – Final Guidance 01 Aug 2017
Special Interest Manual of Policies & Procedures (CDER) Date Posted
Emergency Investigational New Drug Application Process During and After Normal Business Hours 17 Aug 2017
Upcoming Meetings (* = New)
* September 8, 2017: Medical Imaging Drugs Advisory Committee
* September 11, 2017: Pediatric Advisory Committee
* September 12, 2017: Pediatric Advisory Committee
* September 13, 2017: Vaccines and Related Biological Products Advisory Committee
* September 14, 2017: Joint Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee
* September 19, 2017: Oncologic Drugs Advisory Committee
* Meeting of the Peripheral and Central Nervous System Advisory Committee
  October 11-12, 2017: Patient Engagement Advisory Committee
* December 7, 2017: Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee
Last updated: 31 August 2017
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What’s New Health Canada?

By Sandra Salem, Ph.D., Regulatory Scientist I, Cato Research

What’s New in:

Therapeutic Products Directorate:

https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/what-new-drug-products-health-canada.html

Biologics and Genetic Therapies Directorate:

http://www.hc-sc.gc.ca/dhp-mps/brgtherap/update-miseajour/index-eng.php

Medical Devices: https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/what-new.html

Natural and Non-prescription Health Products Directorate: https://www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription/what-new.html

 Health Canada New Guidance Documents (Drugs and Biologics)

Health Canada Guidance Type Date Posted
N/A

 

Updates from Health Canada (Drugs and Biologics) 

Type of Update and Link Date Posted
Updated: Questions and Answers for the Guidance for Industry: Preparation of Drug Submissions in the eCTD Format 29 June 2017
Consultation on Proposed Modification to Bioequivalence Standards for Multiphasic Modified-Release Drug Products 27 July 2017
Notice: Validation rules for regulatory transactions provided to Health Canada in the “non-eCTD electronic-only” format 28 July 2017

 

  

 

Santé Canada: Quoi de neuf?

Par Sandra Salem, Ph.D., Scientifique Règlementaire I 

Quoi de neuf :

Direction des produits thérapeutiques

https://www.canada.ca/fr/sante-canada/services/medicaments-produits-sante/medicaments/quoi-neuf-medicaments-sante-canada.html

Direction des produits biologiques et thérapies génétiques:

http://www.hc-sc.gc.ca/dhp-mps/brgtherap/update-miseajour/index-fra.php

Instruments médicaux: https://www.canada.ca/fr/sante-canada/services/medicaments-produits-sante/instruments-medicaux/quoi-neuf.html

Direction des produits de santé naturels et sans ordonnance:

https://www.canada.ca/fr/sante-canada/services/medicaments-produits-sante/naturels-sans-ordonnance/quoi-de-neuf.html

 Nouvelles lignes directrices de Santé Canada (Médicaments et Produits biologiques) 

Ligne directrice de Santé Canada Genre Date
N/A

 

Mises à jour de Santé Canada (Médicaments et Produits biologiques) 

Genre de mise à jour et lien Date
Mise à jour : Questions et réponses à propos de la ligne directrice à l’intention de l’industrie : Préparation de présentations de drogue en format CTD électronique (eCTD) 29 juin 2017
Consultation Modifications proposes aux norms en matière de bioéquivalence pour les produits pharmaceutiques à libération modifiée multiphasique 27 juillet 2017
Avis : Règles de validation des transactions réglementaires envoyées à Santé Canada en format « électronique autre que le format eCTD » 28 juillet 2017

 

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