Nov 06

New FDA Guidances for October 2018

By Joanne McNelis, Ph.D., RAC (US), Clinical Strategy Scientist II at Cato Research

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

 

Special Interest Guidances/Information Date Posted
Considerations for the Development of Dried Plasma Products Intended for Transfusion – Draft Guidance 30 Oct 2018
M9 Biopharmaceutics Classification System-Based Biowaivers – Draft Guidance 25 Oct 2018
Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs Guidance for Industry – Draft Guidance 25 Oct 2018
Testicular Toxicity: Evaluation During Drug Development Guidance for Industry – Final Guidance 24 Oct 2018
Content of Premarket Submissions for Management of Cybersecurity in Medical Devices – Draft Guidance 18 Oct 2018
Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer Promotional Labeling and Advertisements Guidance for Industry – Draft Guidance 16 Oct 2018
Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment Guidance for Industry – Draft Guidance 15 Oct 2018
Rare Diseases: Early Drug Development and the Role of Pre-IND Meetings Guidance for Industry – Draft Guidance 15 Oct 2018
Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease; Guidance for Industry – Final Guidance 15 Oct 2018
Assessing Adhesion with Transdermal Delivery Systems and Topical Patches for ANDAs Draft Guidance for Industry – Revised Draft Guidance 09 Oct 2018
Assessing the Irritation and Sensitization Potential of Transdermal and Topical Delivery Systems for ANDAs Guidance for Industry – Draft Guidance 09 Oct 2018
Citizen Petitions and Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act – Draft Guidance (revised final) 02 Oct 2018
Selection of the Appropriate Package Type Terms and Recommendations for Labeling Injectable Medical Products Packaged in Multiple-Dose, Single-Dose, and Single-Patient-Use Containers for Human Use – Final Guidance 02 Oct 2018
Atopic Dermatitis: Timing of Pediatric Studies During Development of Systemic Drugs – Final Guidance 02 Oct 2018
Upcoming Meetings (* = New)  
* November 8, 2018: Vaccines and Related Biological Products Advisory Committee Meeting Announcement
* November 14, 2018: Joint Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting Announcement
  November 15, 2018: Patient Engagement Advisory Committee Meeting Announcement
* November 15, 2018: Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee Meeting Announcement
* December 4-5, 2018: Circulatory System Devices Panel of the Medical Devices Advisory Committee Meeting Announcement
* December 4-5, 2018: Science Advisory Board to NCTR Meeting Announcement
* December 17-18, 2018: Joint Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting Announcement
Last updated: 05 November 2018

 

Oct 02

New FDA Guidances for September 2018

By Zachary Swan, Ph.D., Regulatory Scientist at Cato Research

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

 

Special Interest Guidances/Information Date Posted
Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act – Final Guidance

The Special 510(k) Program – Draft Guidance for Industry and Food and Drug Administration Staff – Draft Guidance

Adaptive Design Clinical Trials for Drugs and Biologics – Draft Guidance

Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics Guidance for Industry – Draft Guidance

Contents of a Complete Submission for Threshold Analyses and Human Factors Submissions to Drug and Biologic Applications Guidance for Industry and FDA Staff – Draft Guidance

28 Sep 2018
Public Availability of Lists of Retail Consignees to Effectuate Certain Human and Animal Food Recalls – Draft Guidance 26 Sep 2018
Compounding and Repackaging of Radiopharmaceuticals by State-Licensed Nuclear Pharmacies and Federal Facilities Guidance for Industry – Final Guidance

Compounding and Repackaging of Radiopharmaceuticals By Outsourcing Facilities Guidance for Industry – Final Guidance

Benefit-Risk Factors to Consider When Determining Substantial Equivalence in Premarket Notifications (510(k)) with Different Technological Characteristics – Final Guidance

Guidance for Industry and Food and Drug Administration Staff – Final Guidance

Insanitary Conditions at Compounding Facilities Guidance for Industry – Draft Guidance

25 Sep 2018
Good Review Management Principles and Practices for New Drug Applications and Biologics License Applications – Draft Guidance

ANDA Submissions — Content and Format of Abbreviated New Drug Applications – Final Guidance

24 Sep 2018
Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing – Guidance for Industry and Food and Drug Administration Staff – Final Guidance

Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank – Draft Guidance

20 Sep 2018
Labeling of Nonprescription Human Drug Products Marketed Without an Approved Application as Required by the Dietary Supplement and Nonprescription Drug Consumer Protection Act: Questions and Answers – Final Guidance

Product Identifier Requirements Under the Drug Supply Chain Security Act – Compliance Policy Guidance for Industry – Final Guidance

Product Identifiers under the Drug Supply Chain Security Act – Questions and Answers – Draft Guidance

Grandfathering Policy for Packages and Homogenous Cases of Product Without a Product Identifier – Final Guidance

19 Sep 2018
Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices – Guidance for Industry and Food and Drug Administration Staff – Final Guidance

Recognition and Withdrawal of Voluntary Consensus Standards – Draft Guidance for Industry and Food and Drug Administration Staff – Draft Guidance

510(k) Third Party Review Program – Draft Guidance for Industry, Food and Drug Administration Staff, and Third Party Review Organizations – Draft Guidance

14 Sep 2018
Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions – Draft Guidance for Industry and Food and Drug Administration Staff – Draft Guidance 06 Sep 2018
Nonallergic Rhinitis: Developing Drug Products for Treatment – Final Guidance

Allergic Rhinitis: Developing Drug Products for Treatment Guidance for Industry – Final Guidance

05 Sep 2018
Physiologically Based Pharmacokinetic Analyses — Format and Content Guidance for Industry – Final Guidance 04 Sep 2018
Draft Guidance for Industry: Policy Regarding Quantitative Labeling of Dietary Supplements Containing Live Microbials – Draft Guidance 01 Sep 2018
Upcoming Meetings (* = New)
October 3, 2018: Vaccines and Related Biological Products Advisory Committee
* October 10, 2018: Meeting of the Oncologic Drugs Advisory Committee
* October 11, 2018: Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee Meeting Announcement
* October 12, 2018: Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee Meeting Announcement
* October 17, 2018: Joint Meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting Announcement
* October 18, 2018: Meeting of the Gastrointestinal Drugs Advisory Committee Meeting Announcement
* October 22, 2018: Science Board to the FDA Meeting Announcement
* October 24-25, 2018: Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee Meeting Announcement
* November 1, 2018: Joint Meeting of the Psychopharmacologic Drugs Advisory Committee & Drug Safety and Risk Management Advisory Committee Meeting Announcement
* November 2, 2018: Joint Meeting of the Psychopharmacologic Drugs Advisory Committee & Drug Safety and Risk Management Advisory Committee Meeting Announcement
* November 7, 2018: Allergenic Products Advisory Committee Meeting Announcement
* November 15, 2018: Patient Engagement Advisory Committee Meeting Announcement
Last updated: 01 October 2018

Sep 06

New FDA Guidances for August 2018

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

 

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

 

Special Interest Guidances/Information Date Posted
Hematologic Malignancy and Oncologic Disease: Considerations for Use of Placebos and Blinding in Randomized Controlled Clinical Trials for Drug Product Development– Draft Guidance 23 Aug 2018
Osteoarthritis: Structural Endpoints for the Development of Drugs – Draft Guidance 22 Aug 2018
Quality Attribute Considerations for Chewable Tablets – Final Guidance 20 Aug 2018
Microdose Radiopharmaceutical Diagnostic Drugs: Nonclinical Study Recommendations – Final Guidance 20 Aug 2018
Process to Request a Review of FDA’s Decision Not to Issue Certain Export Certificates for Devices – Draft Guidance 17 Aug 2018
Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics – Draft Guidance 10 Aug 2018
Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances – Final Guidance 08 Aug 2018
Elemental Impurities in Drug Products – Final Guidance 07 Aug 2018
Opioid Use Disorder: Endpoints for Demonstrating Effectiveness of Drugs for Medication-Assisted Treatment – Draft Guidance 06 Aug 2018
Nonclinical Testing of Orally Inhaled Nicotine-Containing Drug Products – Draft Guidance 03 Aug 2018
Medical Device User Fee Small Business Qualification and Certification – Final Guidance 01 Aug 2018
Upcoming Meetings (* = New)
* September 12, 2018: Meeting of the Pharmacy Compounding Advisory Committee
September 20, 2018: Meeting of the Pharmaceutical Science and Clinical Pharmacology Advisory Committee
* September 20, 2018: Pediatric Advisory Committee Meeting
* September 27, 2018: Neurological Devices Panel of the Medical Devices Advisory Committee
* October 3, 2018: Vaccines and Related Biological Products Advisory Committee
Last updated: 05 September 2018

 

Aug 16

New FDA Guidances for June and July 2018

By Joanne McNelis, PhD, RAC (US), Scientist at Cato Research

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

 

Special Interest Guidances/Information Date Posted
Recommendations for Reducing the Risk of Transfusion-Transmitted Babesiosis; Draft Guidance for Industry – Draft Guidance 27 July 2018
Peripheral Vascular Atherectomy Devices – Premarket Notification [510(k)] Submissions – Draft Guidance 27 July 2018
Slowly Progressive, Low-Prevalence Rare Diseases with Substrate Deposition That Results from Single Enzyme Defects: Providing Evidence of Effectiveness for Replacement or Corrective Therapies Guidance for Industry – Draft Guidance 26 July 2018
Use of Liquids and/or Soft Foods as Vehicles for Drug Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments – Draft Guidance 24 July 2018
Inborn Errors of Metabolism That Use Dietary Management: Considerations for Optimizing and Standardizing Diet in Clinical Trials for Drug Product Development: Guidance for Industry – Draft Guidance 23 July 2018
E17 General Principles for Planning and Design of Multi-Regional Clinical Trials – Final Guidance 18 July 2018
Use of Electronic Health Record Data in Clinical Investigations Guidance for Industry – Final Guidance 18 July 2018
Labeling for Biosimilar Products Guidance for Industry – Final Guidance 18 July 2018
Field Alert Report Submission: Questions and Answers Guidance for Industry – Draft Guidance 18 July 2018
Metal Expandable Biliary Stents – Premarket Notification (510(k)) Submissions – Draft Guidance 18 July 2018
Innovative Approaches for Nonprescription Drug Products – Draft Guidance 17 July 2018
Q3D(R1) ELEMENTAL IMPURITIES – Draft Guidance 13 July 2018
Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up; Draft Guidance for Industry – Draft Guidance 11 July 2018
Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs); Draft Guidance for Industry – Draft Guidance 11 July 2018
Long Term Follow-up After Administration of Human Gene Therapy Products; Draft Guidance for Industry – Draft Guidance 11 July 2018
Human Gene Therapy for Hemophilia; Draft Guidance for Industry – Draft Guidance 11 July 2018
Human Gene Therapy for Rare Diseases; Draft Guidance for Industry – Draft Guidance 11 July 2018
Human Gene Therapy for Retinal Disorders; Draft Guidance for Industry – Draft Guidance 11 July 2018
Smallpox (Variola) Infection: Developing Drugs for Treatment or Prevention – Draft Guidance 10 July 2018
Revised Recommendations for Reducing the Risk of Zika Virus Transmission by Blood and Blood Components; Guidance for Industry – Final Guidance 09 July 2018
Indications and Usage Section of Labeling for Human Prescription Drug and Biological Products — Content and Format Guidance for Industry – Draft Guidance 06 July 2018
ANDA Submissions — Amendments to Abbreviated New Drug Applications Under GDUFA – Final Guidance 03 July 2018
Oncology Therapeutic Radiopharmaceuticals: Nonclinical Studies and Labeling Recommendations Guidance for Industry – Draft Guidance 28 Jun 2018
Assessing User Fees Under the Biosimilar User Fee Amendments of 2017 Guidance for Industry – Final Guidance 28 Jun 2018
Major Depressive Disorder: Developing Drugs for Treatment – Draft Guidance 20 Jun 2018
Prescription Drug User Fee Act Waivers, Reductions, and Refunds for Drug and Biological Products Guidance for Industry – Draft Guidance 20 Jun 2018
Logical Observation Identifiers Names and Codes for In Vitro Diagnostic Tests – Guidance for Industry and Food and Drug Administration Staff – Draft Guidance 15 Jun 2018
Coronary, Peripheral, and Neurovascular Guidewires – Performance Tests and Recommended Labeling – Draft Guidance 15 Jun 2018
Intravascular Catheters, Wires, and Delivery Systems with Lubricious Coatings – Labeling Considerations – Draft Guidance 15 Jun 2018
Epidermolysis Bullosa: Developing Drugs for Treatment of Cutaneous Manifestations; Draft Guidance for Industry – Draft Guidance 15 Jun 2018
S9 Nonclinical Evaluation for Anticancer Pharmaceuticals–Questions and Answers – Final Guidance 15 Jun 2018
Humanitarian Device Exemption (HDE) Program – Draft Guidance 15 Jun 2018
Human Immunodeficiency Virus-1 Infection: Developing Systemic Drug Products for Pre-Exposure Prophylaxis – Draft Guidance 13 Jun 2018
Limited Population Pathway for Antibacterial and Antifungal Drugs Guidance for Industry – Draft Guidance 12 Jun 2018
Patient-Focused Drug Development: Collecting Comprehensive and Representative Input – Draft Guidance 12 Jun 2018
Medical Product Communications That Are Consistent With the FDA-Required Labeling — Questions and Answers Guidance for Industry – Final Guidance 12 Jun 2018
Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and Answers Guidance for Industry and Review Staff – Final Guidance 12 Jun 2018
Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program – Draft Guidance 07 Jun 2018
Prescription Drug User Fee Act Waivers for Fixed-Combination Antiretroviral Drugs for the President’s Emergency Plan for AIDS Relief – Draft Guidance 06 Jun 2018
Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA Products Guidance for Industry – Draft Guidance 04 Jun 2018
Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials – Draft Guidance 01 Jun 2018
Complicated Urinary Tract Infections: Developing Drugs for Treatment – Final Guidance 01 Jun 2018
Upcoming Meetings (* = New)  
* September 20, 2018: Meeting of the Pharmaceutical Science and Clinical Pharmacology Advisory Committee Meeting Announcement
Last updated: 15 August 2018

Aug 15

What’s New Health Canada?

 

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

 

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
Notifying Health Canada of Foreign Actions – Guidance Document for Industry – Summary Guidance 12 July 2018

 

Updates from Health Canada (Drugs and Biologics)

 

Type of Update and Link Date Posted
Therapeutic Products Directorate Statistical Report 2017/2018 11 July 2018
Notice: Australia Canada Singapore Switzerland (ACSS) Consortium – Approval of Erleada 13 July 2018

 

 

 

Santé Canada: Quoi de neuf?

 

Par Amélie Rodrigue-Way, Ph.D., RAC (CAN), Directrice associée, Stratégie réglementaire

 

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
Aviser Santé Canada des mesures prises dans les pays étrangers – Document d’orientation à l’intention de l’industrie – Sommaire ligne directrice 12 juillet 2018

 

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

 

Genre de mise à jour et lien Date
Rapport statistique 2017/2018 de la Direction des produits thérapeutiques 11 juillet 2018
Avis : Consortium Australie-Canada-Singapour-Suisse (ACSS)- L’approbation d’Erleada 13 juillet 2018

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Aug 09

Medical Devices: Clinical Trials in South Africa – Part 1

By Nicola Main, Clinical Research Manager I, Clinical Trial Operations – Rest of World Cato Research

 

Medical Device Workshop at MCC – 13/14 July 2017 – Summary for SACRA Members

This workshop provided supporting information and explanation of items contained in the various guidelines regarding medical devices. These guidelines are in the process of being finalized and are posted on the MCC website, either under the Publications / Guidelines tab; or under the Publications / Industry to Comment tab. Most of the discussions related to the licensing of the various local device suppliers, including the application and quality processes. Clinical Trials were discussed very briefly – this information is included first in this summary.

Clinical Trials

General Process

  • Submit in accordance with current clinical trial submission dates
  • Same fees are payable
  • Application will be reviewed by both Clinical Trials Committee and Medical Device Committee before being ratified by MCC (CTC and MD dates don’t line up very well for last 2 submission dates of 2017, this will be sorted out from 2018 onwards)

Medical Device Trial

  • Apply using current CTF1 – mark sections as Not Applicable if truly not applicable to devices(The devices unit are still “piggybacking” onto a number of documents from the medicines section. This is not ideal and these will be revised, but need to be used at the moment due to the focus on getting medical device companies licensed and high-risk products registered)
  • Comply with labelling requirements (9 Dec 2016 Regulations)

Medicine Trial using supporting devices

  • Need to list supporting devices used for a drug trial on the CTF1
  • If not locally sourced devices from licensed company, should be labelled “For clinical trial use only”
  • Supporting devices will be listed on approval letter to facilitate import (still need other import approvals like Department of Radiation for electro-medical devices at this time)

Adverse Event Reporting and Device Recalls

Guideline published and need to comply effective 1 June 2017

Need to report AE to MCC (SAHPRA) if all 3 criteria are met (for registered devices)

  • AE occurred (may also occur in the device operator or other personnel, not limited to the patient)
  • Device / product (of licensed South African manufacturer/distributor) is associated with the AE
  • AE resulted in death or was life-threatening (or is likely to result in death or be life threatening if it occurs again)

(There are 8 sets of exemptions in the guideline which may require reporting even if all 3 criteria are not met)

MCC (SAHPRA) AE reporting timelines vary by event type

  • Serious threat to public health – 48 hours
  • Death/serious deterioration in patient / operator’s health – 10 days
  • May have led to death / serious deterioration in patient / operator’s health – 30 days

Device recalls require consultation with and approval by MCC (SAHPRA)

  • Recall decision is made locally by MCC (SAHPRA) in consultation with local manufacturer/distributor, not by international parent company
  • Various Types and Levels of recall – same as medicines (discussed in same guideline)

Jul 12

FDA Approval of Epidiolex and the Cannabis-Based Drug Pipeline

By: Kristen Biernat, Cato Research

 

The Food and Drug Administration (FDA) granted approval of the cannabis-based drug Epidiolex to GW Research Ltd. (GW) on June 25, 2018.1 The FDA’s approval of Epidiolex represents two major milestones for GW:

First, it is addresses the unmet need for patients with Lennox-Gastaut syndrome and Dravet syndrome, two rare epilepsy disorders. The application received Orphan Drug designation for both indications and Fast-Track Designation for Dravet syndrome. Notably, Epidiolex is the first drug to be approved for the treatment of Dravet syndrome, a genetic disorder that appears during the first year of a child’s life and is associated with severe, fever-related seizures.

Second, it is the first FDA-approved prescription medicine that contains a purified compound derived from marijuana. Epidiolex is an oral solution that contains cannabidiol (CBD), one of over 60 compounds called cannabinoids found in the Cannabis plant.2 Unlike tetrahydrocannabinol (THC), which is also a cannabinoid, CBD does not cause euphoria or a “high”. The exact mechanism by which CBD produces its anticonvulsant effects is still under investigation.3

While Epidiolex is the first FDA-approved drug directly derived from cannabis, it is not the first cannabis-based drug that has been approved in the United States. To better understand how these products relate to each other, three categories may be employed:

  1. Drugs containing cannabinoids derived directly from cannabis
  2. Drugs containing synthetic versions of cannabinoids found in cannabis
  3. Drugs containing compounds that are similar to cannabinoids found in cannabis

As stated above, Epidiolex falls into the first category. However, the commercially available drugs Marinol, Syndros, and Cesamet fall into the second and third categories. Marinol and Syndros contain dronabinol, synthetic THC, and Cesamet contains nabilone, a synthetic analog of THC. All three compounds are indicated in adults for the treatment of nausea and vomiting associated with chemotherapy, while Marinol and Syndros are also indicated for the treatment of anorexia in individuals with AIDS.

The recent Epidiolex decision paves the way for the development of other cannabis-based drugs that fall into all three categories, but in particular, it sets a precedent for the development of drugs derived directly from the cannabis plant. Indeed, GW is also conducting Phase III trials with Sativex for the treatment of multiple sclerosis spasticity. Like Epidiolex, Sativex is an extract of the cannabis plant that contains cannabinoids (THC and CBD in a 1:1 ratio).4

There are also several drugs currently in development that contain synthetic cannabinoids as well as synthetic cannabinoid analogs. Zynerba Pharmaceuticals is conducting Phase II trials with a gel formulation for the transdermal delivery of CBD to treat neuropsychiatric disorders, such as Fragile X Syndrome. A THC pro-drug patch is also undergoing clinical trials for the treatment of Tourette Syndrome. In addition, Corbus Pharmaceuticals is currently conducting Phase II trials with Lenabasum (ajulemic acid), a THC-mimetic drug, for the treatment of rare inflammatory diseases, such as systemic sclerosis, cystic fibrosis, and dermatomyotisis.

Although Epidiolex has been approved by the FDA, it may not be marketed in the U.S. until it is rescheduled by the Drug Enforcement Agency (DEA). The DEA classifies drugs and substances into five schedules based on the drug’s medical use and abuse potential. Schedule I is the most restrictive and consists of drugs with no currently accepted medical use and a high potential for abuse, such as LSD, ecstasy, and cannabis. Schedule V is the least restrictive and consists of drugs with the lowest potential for abuse, such as cough preparations with less than 200 mg of codeine per 100 mL. CBD, a cannabis-derived compound, is currently classified as Schedule I, meaning that it cannot be sold for medical use. Removal of CBD from Schedule I is expected to take place within 90 days of FDA’s approval of Epidiolex, and while it is likely to remain a controlled substance, it is expected to be available for medical use this fall.5 However, removal of Epidiolex from Schedule I does not mean cannabis itself will also be reclassified. Indeed, cannabis was not rescheduled when Cesamet, Marinol, and Syndros, which all contain synthetic versions of THC, were classified as Schedule II, Schedule III, and Schedule II, respectively.6

In summary, the FDA-approval of Epidiolex indicates a promising future for cannabis-based drugs for the treatment of a range of disease states. While there are several products in the cannabis-based drug pipeline, drugs containing compounds derived from the cannabis plant may benefit most from the recent Epidiolex decision.

 

References:

  1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy”. The U.S. Food & Drug Administration. 25 June 2018.
  2. Atakan, Z. (2012) Cannabis, a complex plant: different compound and different effects on individuals”. Therapeutic Advances in Psychopharmacology. 2: 241-254
  3. “Mechanism of Action”. GW Pharmaceuticals.
  4. “Sativex (delta-9-tetrahydrocannibinol and cannabidiol in the EU) (nabiximols in the USA”. GW Pharmaceuticals.
  5. “Biosciences Announce FDA Approval of EPIDIOLEX® (cannabidiol) oral solution – the First Plant-derived Cannabinoid Prescription Medicine”.GW Pharmaceuticals.
  6. “Controlled Substances by DEA Drug Code Number”. 28 March 2018.

 

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Jun 21

What’s New Health Canada?

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

 

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
Cancellation of a Drug Identification Number (DIN) and Notification of Discontinuation of Sales Guidance 12 June 2018
Conduct and Analysis of Comparative Bioavailability Studies & Comparative Bioavailability Standards: Formulations used for Systemic Effects Guidance 16 May 2018
Patented Medicines (Notice of Compliance Regulations) Guidance 11 May 2018

 

Updates from Health Canada (Drugs and Biologics)

 

Type of Update and Link Date Posted
Updated: Patent Register – Frequently Asked Questions 11 May 2018
Consultation for Mandatory Requirements of using Electronic Common Technical Document (eCTD) Format when Submitting Master Files (MFs) 07 May 2018
Notice to Industry: ACSS – New Chemical Entities Work Sharing Trial Phase I 30 April 2018
ICH S3A Questions and Answers: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure – Focus on Microsampling 26 April 2018
ICH M7(R1): Genotoxic Impurities – Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk 26 April 2018
ICH E18: Genomic Sampling and Management of Genomic Data 26 April 2018
What We Heard – Proposals for prescription drug transparency 25 April 2018
Final Notice – Classification of Dental Plaque-disclosing Products as Drugs 18 April 2018
ICH E11(R1) Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population 04 April 2018
ICH Q11: Questions and Answers: Selection and Justification of Starting Materials for the Manufacture of Drug Substances 04 April 2018
ICH Q3C(R6): Impurities: Guidelines for Residual Solvants 04 April 2018
New Master File Applications Fee Form for Human Drugs for filing on or after April 1st, 2018 16 March 2018
New Drug Submission – Application Fee Form for Human and Disinfectant Drugs for submissions filed on or after April 1st, 2018 16 March 2018

 

  

Santé Canada: Quoi de neuf?

 

Par Amélie Rodrigue-Way, Ph.D., RAC (CAN), Directrice associée, Stratégie réglementaire

 

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
Révision de les Lignes directrices : Conduite et analyse des études de biodisponibilité comparatives et Normes en matière d’études de biodisponibilité comparatives : Formes pharmaceutiques de médicaments à effets systémiques ligne directrice 16 mai 2018
Ligne directrice: Règlement sur les médicaments brevetés (avis de conformité) ligne directrice 11 mai 2018

 

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

 

Genre de mise à jour et lien Date
Mise à jour : Registre des brevets – Foire aux questions 11 mai 2018
Consultation concernant les exigences obligatoires relatives à l’utilisation du format Electronic Common Technical Document (eCTD) pour la présentation des fiches maîtresses (FM) 07 mai 2018
Avis à l’industrie : ACSS – Phase I de l’essai de partage du travail concernant les substances chimiques nouvelles 30 avril 2018
ICH S3A Question et réponse : note explicative sur la toxicocinétique : l’évaluation de l’exposition systémique dans les études de toxicité 26 avril 2018
ICH M7(R1) : Évaluation et contrôle des impuretés réactives de l’ADN (mutagènes) dans les produits pharmaceutiques pour limiter les risques de cancérogénicité 26 avril 2018
ICH E18 L’échantillonnage génomique et la gestion des données génomiques 26 avril 2018
Ce que nous avons entendu – Propositions concernant la transparence relative aux médicaments d’ordonnance 25 avril 2018
Avis final – Classification des produits révélateurs de plaque dentaire en tant que médicaments (drogues) 18 avril 2018
Addenda à la ligne directrice E11(R1) de l’ICH : Recherche clinique sur les produits médicinaux dans la population pédiatrique 05 avril 2018
ICH Q11 : Questions et réponses : Mise au point et fabrication de substances pharmaceutiques (entités chimiques et entité biotechnologiques ou biologiques) 04 avril 2018
ICH Q3C(R6): Impuretés : Directive sur les solvants résiduels 04 avril 2018
Nouveau Formulaire sur les frais pour Fiches maîtresse pour les médicaments à usage humain pour les présentations soumises le 1st avril 2018 ou après 16 mars 2018
Nouveau Formulaire concernant les frais de présentation et de demande de drogue pour les médicaments à usage humain et les désinfectants assimilés à drogues pour les présentations soumises le 1st avril 2018 ou après 16 mars 2018

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Jun 13

2018 Changes in the User Fee Program for Prescription Drugs Under PDUFA VI

By Juliati Rahajeng, Ph.D., Scientist at Cato Research

 

The Food and Drug Administration Reauthorization Act (FDARA) was signed into law by the President on August 18, 2017. The law comprises the reauthorization of the Prescription Drug User Fee Act (PDUFA), which gives the Food and Drug Administration (FDA) the resources to sustain a predictable and efficient review process for human drugs and biologics. The current PDUFA (PDUFA VI), which includes the Fiscal Years 2018-2022, generated a new user fee program that contains some significant changes from the one authorized under the PDUFA V. A new FDA guidance document that describes the new fee structure and the type of fees for which industry is responsible was published in May 2018.1

 

Prior to 1992, the pharmaceutical industry, consumers, and the FDA were frustrated with the FDA’s lengthy and unpredictable review process of New Drug Applications (NDAs) and Biologics License Applications (BLAs). The increasing length of the review process led to the delay for patients in accessing the new drugs and for manufacturers in recovering their development costs. In the late 1980s, the reported median time for review process of an NDA was 29 months.2 During the PDUFA I consideration, a one-month delay in a review process roughly cost a manufacturer an average of $10 million.3 The FDA argued that it needed to hire additional scientists for a more efficient and predictable review process of the incoming and backlogged drug applications.

 

The PDUFA law was passed by Congress in 1992. PDUFA I authorized the FDA to collect fees to accelerate the review process of NDA and BLA without compromising product safety and efficacy.4, 5 Based on PDUFA I, the review of priority applications for new drugs, which demonstrated significant improvement in the treatment, diagnosis, or prevention of a disease, was six months, whereas review of standard applications was 12 months. Since the implementation of PDUFA I, patients have faster access to new drugs and the pharmaceutical industry can expect a predictable review process.

 

PDUFA is reauthorized by Congress every five years. PDUFA II broadened the scope of the user fee program by incorporating activities related to the preclinical and clinical phases of a new drug’s development and by increasing FDA communications with the industry and consumer groups.5 Under PDUFA II, the goal of the standard review is to complete 90% of the NDAs and BLAs within 10 months of receipt.6 PDUFA III widened the scope of activities by incorporating a three-year postapproval period.5 PDUFA IV removed the three-year limitation on postapproval activities and focused on new courses of action regarding the postapproval lifetime of a product.4

 

PDUFA V and PDUFA VI maintained the scope of activities of PDUFA IV.1, 5 Under PDUFA V, FDA was authorized to collect human drug application fees and application supplement requiring clinical data fees, prescription drug establishment fees, and prescription drug product fees.1 However, under PDUFA VI, a new user fee structure was created. PDUFA VI removed the prescription drug product and drug establishment fees and added a human prescription drug program fee, which provides 80% of the total fee revenue for the FDA. Although the establishment fee has been eliminated, the establishment registration and drug listing requirements (described below) are still in effect. The human drug application fee, which provides 20% of the total fee revenue, remains, whereas the supplemental application fee is eliminated.1, 5 Additionally, PDUFA VI removes a provision under which the applicant could apply for a waiver or refund of user fees, in which the fee will exceed the anticipated costs incurred in reviewing submissions (also known as “the fees-exceed-costs waiver”).1

 

Under PDUFA VI, a human drug application for which safety and efficacy clinical data (other than bioavailability or bioequivalence studies) are required for approval is assessed a full application fee, whereas an application not requiring clinical data for approval is assessed one-half of a full fee.1 The application fees are due when the application is submitted. Without the submission of the appropriate fee, a human drug application will be deemed as incomplete and the Health and Human Services Secretary will not accept the application for filing until all fees have been paid. The two exceptions to the application fee are orphan drug-designated applications, and resubmissions of previously filed applications that were reviewed but not approved. A full fee is assessed on a resubmitted application that was rejected for filing or withdrawn before a filing action. If an application is refused for filing or withdrawn without a waiver before filing, 75% of the application fee will be refunded. However, if an application is withdrawn after it is filed, the fee or a portion of the fee may be refunded if no significant work was performed.

 

The FDA provides a waiver or a reduction for one or more user fees assessed under section 736(a) of the Food, Drug, and Cosmetic (FD&C) Act when the waiver or reduction is required to protect the public health, the fee would present a major hurdle to innovation, or the applicant is a small business submitting its first human drug application.1 To receive any waiver, reduction, or refund, an applicant must submit a written request to the Secretary no later than 180 days after the fee is due.

 

A human drug application (or any pending application filed after 01 September 1992) is assessed for the annual prescription drug program fee for each prescription drug product that is identified in the application approved as of 01 October of the fiscal year.1 The prescription drug program fee, which is subjected to the original NDA or BLA holder, is determined by each prescription drug product identified in an NDA or BLA. However, a single approved application of multiple drug products may not be assessed for more than five prescription drug program fees for a fiscal year. A prescription drug product is not subject to a program fee if the product falls under one of the conditions in section 505(j)(7) of the FD&C Act (current generic drug) with a potency defined in terms of per 100 milliliters. A prescription drug product is also not subject to the program fee if the product is

  • the same as another product approved under sections 505(b) or 505(j) of the FD&C Act and that other product is not in the list of discontinued products described in section 505(j)(7) of the FD&C Act.
  • an abbreviated application filed under section 507 of the FD&C Act (a Drug Development Tool such as a biomarker or clinical outcomes assessment), or
  • an abbreviated new drug application (generic) approved prior to the execution of the Drug Price Competition and Patent Term Restoration Act of 1984.

 

Prescription drug products eligible for the program fee are on the list of products detailed in section 505(j)(7)(A) of the FD&C Act (often known as the “Orange Book”), or on the list of products with applications approved under section 351(a) of the Public Health Service Act that is generated and maintained by the Secretary.1 Drugs are added to the Orange Book on the day they are approved and not on the date when the next Orange Book is published. If a drug or a biologic is in the discontinued section of the Orange Book or Biologics List on the date fees are assessed, a drug or a biologic product is not subject to a prescription drug fee program for a fiscal year.

 

The FDA will send a notification to applicants with respect to their prescription drug products in preparation for determining the program fees before the program fees due date.1 Therefore, applicants will have the opportunity to review the notice and inform the Agency of any changes regarding the status of their drug products. Based on the information available to the FDA, it issues invoices for the program fees around the end of September. For each fiscal year, payments for the program fees are due either on or after 01 October, or on the first business day after the authorization of an appropriations Act issuing the collection and obligation of fees for the fiscal year, whichever occurs later.

 

In summary, the FDA is authorized to collect human drug application fees at the time the application is submitted and then annually the prescription drug program fees are collected  after the application is approved for certain prescription drug products under PDUFA VI. In addition, PDUFA VI removed fees for application supplement, establishment fees, and the “fees-exceed-costs waiver” that were previously authorized.1

 

References:

  1. Food and Drug Administration (FDA), Assessing User Fees Under the Prescription Drug User Fee Amendments of 2017: Guidance for Industry. May 2018.
  2. Food and Drug Administration (FDA), Third Annual Performance Report: Prescription Drug User Fee Act of 1991, Fiscal Year 1995 Report to Congress (01 December 1995).
  3. Hilts PJ, “Plan to Speed Approval of Drugs: Makers Would Pay Fees to U.S.” The New York Times. 11 August 1992.
  4. Sections 735 and 736 of the FD&C Act.
  5. Congressional Research Service, Prescription Drug User Fee Act (PDUFA): 2017 Reauthorization as PDUFA VI. 16 March 2018.
  6. Food and Drug Administration (FDA), Prescription Drug User Fee Act II (PDUFA II): Five-Year Plan – Fiscal Year 2000 Update. July 2000.

 

Jun 08

New FDA Guidances for May 2018

By Joanne McNelis, PhD, RAC (US), Scientist at Cato Research
FDA draft and final guidances, released from CDER, CBER, and CDRH, in April are posted. In addition, upcoming advisory committee meetings are listed below with links to more information.

 

Special Interest Guidances/Information Date Posted
Development of a Shared System REMS Guidance for Industry – Draft Guidance 31 May 2018
Waivers of the Single, Shared System REMS Requirement; Draft Guidance for Industry – Draft Guidance 31 May 2018
Recommended Content and Format of Complete Test Reports for Non-Clinical Bench Performance Testing in Premarket Submissions – Draft Guidance 31 May 2018
Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Core Guideline Guidance for Industry – Draft Guidance 30 May 2018
Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Annex – Draft Guidance 30 May 2018
Assessment of Pressor Effects of Drugs Guidance for Industry – Draft Guidance 30 May 2018
Complicated Intra-Abdominal Infections: Developing Drugs for Treatment – Final Guidance 29 May 2018
Anthrax: Developing Drugs for Prophylaxis of Inhalational Anthrax Guidance for Industry – Final Guidance 23 May 2018
Maximal Usage Trials for Topical Active Ingredients Being Considered for Inclusion in an Over-The-Counter Monograph: Study Elements and Considerations – Draft Guidance 22 May 2018
Enforcement Policy — OTC Sunscreen Drug Products Marketed Without an Approved Application – Final Guidance 22 May 2018
Bioanalytical Method Validation Guidance for Industry – Final Guidance 21 May 2018
Acne Vulgaris: Establishing Effectiveness of Drugs Intended for Treatment – Final Guidance 21 May 2018
Establishing Effectiveness for Drugs Intended to Treat Male Hypogonadotropic Hypogonadism Attributed to Nonstructural Disorders Guidance for Industry – Final Guidance 18 May 2018
Cytomegalovirus in Transplantation: Developing Drugs to Treat or Prevent Disease – Draft Guidance 18 May 2018
Pediatric HIV Infection: Drug Development for Treatment – Draft Guidance 11 May 2018
Facility Definition Under Section 503B of the Federal Food, Drug, and Cosmetic Act – Final Guidance 10 May 2018
Uncomplicated Urinary Tract Infections: Developing Drugs for Treatment Guidance for Industry – Draft Guidance 09 May 2018
S3A Guidance: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies: Focus on Microsampling – Final Guidance 09 May 2018
Waivers, Exceptions, and Exemptions from the Requirements of Section 582 of the Federal Food, Drug, and Cosmetic Act Guidance for Industry – Draft Guidance 08 May 2018
Assessing User Fees Under the Prescription Drug User Fee Amendments of 2017 Guidance for Industry – Final Guidance 02 May 2018
Donor Screening Recommendations to Reduce the Risk of Transmission of Zika Virus by Human Cells, Tissues, and Cellular and Tissue-Based Products; Guidance for Industry – Draft Guidance 02 May 2018
Upcoming Meetings (* = New)
* June 12, 2018: Circulatory System Devices Panel of the Medical Devices Advisory Committee Meeting Announcement
* June 14, 2018: Anesthesiology and Respiratory Therapy Devices Panel of the Medical Devices Advisory Committee Meeting Announcement
* June 20, 2018: Meeting of the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee
* June 22, 2018: Blood Products Advisory Committee Meeting Announcement
* June 26, 2018: Joint Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting Announcement
* July 18-19, 2018: Blood Products Advisory Committee Meeting Announcement
Last updated: 01 June 2018

 

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