Dec 20

New FDA Guidances for October and November 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 October and November 2017 are posted. Currently, there are no upcoming advisory committee meetings.

Special Interest Guidances/Information Date Posted
Select Updates for Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices – Draft Guidance 29 Nov 2017
Recommendations for Dual 510(k) and CLIA Waiver by Application Studies – Draft Guidance 29 Nov 2017
Pediatric Information for X-ray Imaging Device Premarket Notifications – Final Guidance 28 Nov 2017
Grandfathering Policy for Packages and Homogenous Cases of Product Without a Product Identifier – Draft Guidance 27 Nov 2017
General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products – Final Guidance 21 Nov 2017
Unique Device Identification: Direct Marking of Devices – Final Guidance 17 Nov 2017
Expedited Programs for Regenerative Medicine Therapies for Serious Conditions – Draft Guidance 16 Nov 2017
Evaluation of Devices Used with Regenerative Medicine Advanced Therapies – Draft Guidance 16 Nov 2017
Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception – Final Guidance 16 Nov 2017
Assessing User Fees Under the Biosimilar User Fee Amendments of 2017 – Draft Guidance 15 Nov 2017
S5(R3) Detection of Toxicity to Reproduction – Draft Guidance 09 Nov 2017
Use of a Drug Master File for Shared System REMS Submissions – Draft Guidance 08 Nov 2017
Evaluating Drug Effects on the Ability to Operate a Motor Vehicle – Final Guidance 08 Nov 2017
Recurrent Herpes Labialis: Developing Drugs for Treatment and Prevention – Final Guidance 06 Nov 2017
Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment – Draft Guidance 06 Nov 2017
Recommended Statement for Over-the-Counter Aspirin-Containing Drug Products Labeled With Cardiovascular Related Imagery – Final Guidance 06 Nov 2017
Formal Dispute Resolution: Appeals Above the Division Level – Final Guidance 03 Nov 2017
ANDAs: Pre-Submission of Facility Information Related to Prioritized Generic Drug Applications (Pre-Submission Facility Correspondence) – Draft Guidance 03 Nov 2017
Controlled Correspondence Related to Generic Drug Development – Draft Guidance 02 Nov 2017
Product Labeling for Certain Ultrasonic Surgical Aspirator Devices – Final Guidance 30 Oct 2017
E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials – Draft Guidance 30 Oct 2017
De Novo Classification Process (Evaluation of Automatic Class III Designation) – Final Guidance 30 Oct 2017
Manufacturers Sharing Patient-Specific Information from Medical Devices with Patients Upon Request – Final Guidance 30 Oct 2017
Acceptance Review for De Novo Classification Requests – Draft Guidance 30 Oct 2017
Assessing User Fees Under the Generic Drug User Fee Amendments of 2017 – Draft Guidance 27 Oct 2017
Pediatric Gastroesophageal Reflux Disease: Developing Drugs for Treatment – Draft Guidance 26 Oct 2017
In Vitro Metabolism- and Transporter- Mediated Drug-Drug Interaction Studies – Draft Guidance 25 Oct 2017
Clinical Drug Interaction Studies — Study Design, Data Analysis, and Clinical Implications – Draft Guidance 25 Oct 2017
Breakthrough Devices Program – Draft Guidance 25 Oct 2017
Deciding When to Submit a 510(k) for a Change to an Existing Device – Final Guidance 25 Oct 2017
Deciding When to Submit a 510(k) for a Software Change to an Existing Device – Final Guidance 25 Oct 2017
Salmeterol Xinafoate_020692 – Draft Guidance 18 Oct 2017
Fluticasone propionate_021433 – Draft Guidance 18 Oct 2017
Fluticasone propionate_020833 – Draft Guidance 18 Oct 2017
Post-Complete Response Letter Meetings Between FDA and ANDA Applicants Under GDUFA – Draft Guidance 13 Oct 2017
Assessing User Fees Under the Prescription Drug User Fee Amendments of 2017 – Draft Guidance 12 Oct 2017
Respiratory Syncytial Virus Infection: Developing Antiviral Drugs for Prophylaxis and Treatment – Draft Guidance 11 Oct 2017
Format and Content of a REMS Document – Draft Guidance 11 Oct 2017
Determining Whether to Submit an ANDA or a 505(b)(2) Application – Draft Guidance 11 Oct 2017
Requests for Reconsideration at the Division Level Under GDUFA – Draft Guidance 11 Oct 2017
ANDA Submissions – Prior Approval Supplements Under GDUFA – Final Guidance 04 Oct 2017
Completeness Assessments for Type II API DMFs Under GDUFA – Final Guidance 04 Oct 2017
Individual Patient Expanded Access Applications: Form FDA 3926 – Final Guidance 03 Oct 2017
M4 Organization of the Common Technical Document for the Registration of Pharmaceuticals for Human Use – Final Guidance 03 Oct 2017
Expanded Access to Investigational Drugs for Treatment Use — Qs & As – Final Guidance 03 Oct 2017
Waiver of IRB Requirements for Drug and Biological Product Studies – Information Sheet – Final Guidance 03 Oct 2017
FDA and Industry Actions on De Novo Classification Requests: Effect on FDA Review Clock and Goals – Final Guidance 02 Oct 2017
Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff – Final Guidance 02 Oct 2017
User Fees and Refunds for Premarket Notification Submissions (510(k)s) – Final Guidance 02 Oct 2017
ANDA Submissions — Amendments to Abbreviated New Drug Applications Under GDUFA – Draft Guidance 02 Oct 2017
Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA – Draft Guidance 02 Oct 2017
FDA and Industry Actions on Premarket Approval Applications (PMAs): Effect on FDA Review Clock and Goals – Final Guidance 02 Oct 2017
FDA and Industry Actions on Premarket Notification (510(k)) Submissions: Effect on FDA Review Clock and Goals – Final Guidance 02 Oct 2017
Classification and Requirements for Laser Illuminated Projectors (LIPs) (Laser Notice No. 57) – Draft Guidance 02 Oct 2017
ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin – Draft Guidance 02 Oct 2017
User Fees for 513(g) Requests for Information – Final Guidance 02 Oct 2017
User Fees and Refunds for De Novo Classification Requests – Final Guidance 02 Oct 2017
ANDA Submissions – Refuse-to-Receive Standards: : Questions and Answers – Draft Guidance 02 Oct 2017
Marketing Clearance of Diagnostic Ultrasound Systems and Transducers – Draft Guidance 02 Oct 2017
User Fees and Refunds for Premarket Approval Applications and Device Biologics License Applications – Final Guidance 02 Oct 2017
Special Interest Manual of Policies & Procedures (CDER) Date Posted
Prioritization of the Review of Original ANDAs, Amendments, and Supplements 09 Nov 2017
Developing and Issuing Drug Trial Snapshots 26 Oct 2017
CMC Reviews of Type III DMF’s for Packaging Materials 18 Oct 2017
Communicating Abbreviated New Drug Application Review Status Updates with Industry 06 Oct 2017
Receiving and Processing a Request for Voluntary Withdrawal of an Approved ANDA 04 Oct 2017
Last updated: 15 December 2017  

Dec 07

Toward Compliance 2.0 : When your Pill is Connected to your Smartphone

By: David Hamel, Fellow Scientist Cato Research Canada

The FDA approval of Abilify MyCite (aripiprazole tablets with sensor; by Otsuka) on 13 November 2017 for the treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder and for use as an add-on treatment for depression in adults could mark a new era in patients’ medication adherence technology. The new product combines the antipsychotic aripiprazole in its tablet formulation and a drug ingestion tracking system comprised of an Ingestible Event Marker (IEM) sensor, a wearable patch (MyCite Patch), a mobile application, and a web-based portal, that identifies and relay drug ingestion events to the patient’s smartphone. In addition, the patient can permit their caregivers and physician to access the information through the web-based portal. This is the first drug with a digital tracking system approved in the U.S. Although, Abilify MyCite was not designed to improve patient compliance or modify drug dosage, this technology could eventually be paving the way for a new standard in medication adherence and chronic disease management.

 

The FDA approved aripiprazole in 2002 for the treatment of schizophrenia.[1] Since then, the drug was approved for bipolar I disorder (September 2004) and as an adjunctive treatment of major depressive disorder in adults (November 2007). The FDA approved the ingestible sensor for marketing in 2012.[2] The true innovation of Abilify MyCite resides in its integrated tracking system. At the core of this technology lies a 1-mm sized sensor activated by the reaction between two of its constituents, magnesium and cuprous chloride, in the presence of gastric fluid, which power the sensor. The signal is detected by a wearable sensor (MyCite Patch) located on the patient’s torso, which in turn relays the ingestion event to an application on the patient’s mobile device. In practice, the ingestion events can be detected between 30 minutes and 2 hours after each dose. The patch, which can be worn while showering, swimming or exercising, should be changed at least every week, and be located within 9-foot of the paired smartphone to properly communicate the information. Preclinical studies assessed the safety of ingesting the Event Marker.[3] The safety profile supports the use of the technology in the treatment of chronic diseases.

 

While the approval is an excellent news for individuals suffering from mental disorders, patients affected by other chronic diseases could in theory benefit from the deployment of this technology in other therapeutics areas, such as AIDS, asthma, tuberculosis, hypertension and organ transplant[4], in which medication compliance is also critical. While the stated objective supporting the marketing of the Ingestible Event Marker is to provide better information to healthcare providers, the companies remain in a grey area between simple information and the objective quantification of adherence. Therefore, further studies designed to evaluate the impact of Abilify MyCite on compliance would be required.

 

We should also consider the impact of system defects and improper use on the treatment. Whether a faulty detection or software glitch, the risk of inadequately capturing the ingestion events would prevent healthcare providers from adequately determining if patients are taking their medication. Alternatively, this improper tracking could also lead to patients taking more than the prescribed dose. The Prescribing Information indicates the possibility that the ingestion of the tablet may not be detected. To avoid this, patients should receive adequate training on how to position and pair the patch with the application. Proteus Digital Health, the device developer and manufacturer of the system, reported a detection accuracy of 99.1% during clinical trials. They attributed faulty detections to a combination of stomach environment and receiver-sensor orientation.[5]

 

As with many new technologies, concerns over privacy can be raised. For example, we can consider the security of software and servers necessary to transmit the relevant information to healthcare providers. Will they be sufficiently secured and properly maintained? Who will have access to the information and who will make the choice to grant access to certain individuals or not? What about patients with severe cognitive impairment unable to permit their caregivers and physician to access their information? We can also contemplate a future where insurers could require a “proof of ingestion” before reimbursing the treatment.

 

Abilify MyCite clinical studies demonstrated that the device was safe and that this technology could provide reliable and accurate information with manageable risks to patients. This new combination product could provide physician valuable insight into their patients’ behavior and ultimately guide the discussion on how to improve their treatment.

 

For more information about Abilify MyCite visit:

 

FDA New Release (November 13, 2017): https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm584933.htm?utm_campaign=FDA%20approves%20pill%20with%20sensor%20that%20digitally%20tracks%20if%20patients%20have%20ingested%20their%20medication&utm_medium=email&utm_source=Eloqua

 

Otsuka America Pharmaceutical: https://www.otsuka-us.com/discover/articles-1075

 

Proteus Digital Health: http://www.proteus.com/press-releases/proteus-digital-health-announces-fda-clearance-of-ingestible-sensor-2/

 

[1] FDA Approval Enclosure documentation

[2] Proteus Digital Health, press release 30 July 2012, online at http://www.proteus.com/press-releases/proteus-digital-health-announces-fda-clearance-of-ingestible-sensor-2/

[3] Hafezi H et al., An Ingestible Sensor for Measuring Medication Adherence IEEE Transactions on Biomedical Engineering, vol 62, NO. 1, January 2015

[4] Sabaté E, editor. Adherence to long-term therapies: evidence for action. Geneva: World Health Organization; 2003

[5] Hafezi H et al., An Ingestible Sensor for Measuring Medication Adherence IEEE Transactions on Biomedical Engineering, vol 62, NO. 1, January 2015.

Oct 18

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

 

Oct 11

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

Sep 25

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.

 

Sep 08

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

Aug 16

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

 

Aug 14

New FDA Guidances for July 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 July 2017 are posted. In addition, upcoming advisory committee meetings are listed below with links to more information.

Special Interest Guidances/Information Date Posted
Consumer Antiseptic Wash Final Rule – Questions and Answers– Final Guidance 25 July 2017
M4E(R2): The CTD – Efficacy– Final Guidance 24 July 2017
Maintenance Procedures for Q3C– Final Guidance 24 July 2017
PDE for Triethylamine and Methylisobutylketone– Final Guidance 24 July 2017
Q3C – Tables and List– Final Guidance 24 July 2017
ICH Q3C Maintenance Procedures for the Guidance for Industry Q3C Impurities: Residual Solvents– Final Guidance 24 July 2017
IRB Waiver or Alteration of Informed Consent for Clinical Investigations Involving No More Than Minimal Risk to Human Subjects– Final Guidance 13 July 2017
Bioequivalence Recommendations for Dasabuvir Sodium; Ombitasvir; Paritaprevir; Ritonavir– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Dabigatran Etexilate Mesylate– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Aspirin; Omeprazole– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Tenofovir Alafenamide Fumarate– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Uridine Triacetate– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Obeticholic Acid– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Dorzolamide Hydrochloride– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Brimonidine Tartrate– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Fluphenazine Hydrochloride– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Glycopyrrolate Inhalation Powder– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Aspirin– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Diclofenac Sodium– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Brivaracetam– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Silver Sulfadiazine– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Triamcinolone Acetonide (ointment)– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Cyanocobalamin– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Triamcinolone Acetonide (lotion)– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Tiopronin– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Clocortolone Pivalate– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Gefitinib– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Tipiracil Hydrochloride; Trifluridine– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Dextroamphetamine Sulfate– Draft Guidance 11 July 2017
Bioequivalence Recommendations for Gentamicin Sulfate – Draft Guidance 11 July 2017
Special Interest Manual of Policies & Procedures (CDER) Date Posted
Office of Biotechnology Products and Office of Process and Facilities, Interactions on BLA Assessments 26 July 2017
Communicating Drug Approval Information 17 July 2017
Upcoming Meetings (* = New)
  August 2, 2017: Meeting of the Arthritis Advisory Committee
* August 3, 2017: Meeting of the Arthritis Advisory Committee
* October 11-12, 2017: Meeting of the Patient Engagement Advisory Committee
Last updated: 1 August 2017

 

 

Jul 14

FDA Updates ICH E14 Q&A Modelling in QTc Prolongation Studies

Greg Hileman, Ph.D., Sr. Director and Principle Regulatory Scientist of Cato Research

The International Conference on Harmonization (ICH) last updated its guidance “THE CLINICAL EVALUATION OF QT/QTC INTERVAL PROLONGATION AND PROARRHYTHMIC POTENTIAL FOR NON-ANTIARRHYTHMIC DRUGS (ICH E14 (R3)) in 2005. This month, FDA published the most recent ICH updated list of questions and answers (ICH E14 Q&As ()) related to ICH E14, effectively making it an FDA guidance.  R3 included an updated question on the use of concentration-response modeling in lieu of point estimate and confidence interval calculation at Cmax. Important considerations when using modeling include the possibility of pooling data across multiple studies to explore a wider range of exposures than a single thorough QT prolongation study could explore while maintaining a focus on ECG quality and managing trial heterogeneity.  If data are available to estimate QT effects at sufficiently high multiples of clinically relevant exposures, a separate positive control may not be required.  As always, the focus of the analysis is to exclude a change of 10 ms or more (upper limit of the 90% confidence interval) at relevant concentrations. Significant savings with valid concentration-response modeling may result from predicting results at regimens not studied. A sponsor may be able to avoid certain intrinsic (enzyme induction or inhibition) and extrinsic (DDI) studies by predicting QTc effects.  High quality models may aid in deciding inclusion/exclusion criteria or in predicting dose adjustments needed in phase 3 and 4 studies where such factors are encountered.

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073161.pdf

”ICH guideline E14: the clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs (R3) – questions and answers”

Jul 10

New FDA Guidances for June 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 June 2017 are posted. In addition, upcoming advisory committee meetings are listed below with links to more information.

 

Special Interest Guidances/Information Date Posted
Product Identifier Requirements Under the Drug Supply Chain Security Act – Compliance Policy Guidance for Industry – Draft Guidance 30 June 2017
Current Good Manufacturing Practice for Medical Gases – Draft Guidance 28 June 2017
Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products – Final Guidance 27 June 2017
Use of Electronic Records and Electronic Signatures in Clinical Investigations Under 21 CFR Part 11 – Draft Guidance 20 June 2017
ANDAs: Pre-Submission Facility Correspondence Associated with Priority Submissions – Draft Guidance 19 June 2017
E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs Questions and Answers (R3) – Revision 13 June 2017
Form FDA 3674 – Certifications To Accompany Drug, Biological Product, and Device Applications/Submissions – Final Guidance 07 June 2017
Special Interest Manual of Policies & Procedures (CDER) Date Posted
Acceptance Criteria for Residual Solvents 28 June 2017
Prioritization of the Review of Original ANDAs, Amendments, and Supplements 27 June 2017
Review of Bioequivalence Studies with Clinical Endpoints in ANDAs 22 June 2017
NDAs/BLAs: Financial Disclosure  21 June 2017
Upcoming Meetings (* = New)
* July 11, 2017: Meeting of the Oncologic Drugs Advisory Committee
* July 12, 2017: Meeting of the Oncologic Drugs Advisory Committee
* July 13, 2017: Meeting of the Oncologic Drugs Advisory Committee
  July 28, 2017: Vaccines and Related Biological Products Advisory Committee Meeting
* August 2, 2017: Meeting of the Arthritis Advisory Committee Meeting
Last updated: 3 July 2017

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