New FDA Guidances for July 2016

By Yuka Fukushima, Regulatory Associate & Compliance Specialist at Cato Research

FDA draft and final guidances, released from CDER, CBER, and CDRH from July 2016, are posted.  In addition, upcoming advisory committee meetings to be held are also listed below with a link to more information.

Special Interest Guidances/Information Date Posted
General Wellness: Policy for Low Risk Devices – Final Guidance 7/29/2016
Adaptive Designs for Medical Device Clinical Studies – Final Guidance 7/27/2016
Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices – Draft Guidance 7/27/2016
Unique Device Identification System: Form and Content of the Unique Device Identifier (UDI) – Draft Guidance 7/26/2016
E2C(R2) Periodic Benefit-Risk Evaluation Report (PBRER) – Final Guidance 7/18/2016
E2C(R2) Periodic Benefit-Risk Evaluation Report – Questions and Answers – Final Guidance 7/18/2016
Implementation of Acceptable Full-Length and Abbreviated Donor History Questionnaires and Accompanying Materials for Use in Screening Donors of Source Plasma – Final Guidance 7/17/2016
Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product – Draft Guidance 7/15/2016
Bacterial Vaginosis: Developing Drugs for Treatment – Draft Guidance 7/13/2016
Information to Support a Claim of Electromagnetic Compatibility (EMC) of Electrically-Powered Medical Devices – Final Guidance 7/11/2016
Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics – Draft Guidance 7/8/2016
Updating ANDA Labeling After the Marketing Application for the Reference Listed Drug Has Been Withdrawn – Draft Guidance 7/8/2016
Use of Standards in FDA Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases – Draft Guidance 7/8/2016
Compounded Drug Products That Are Essentially Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act – Draft Guidance 7/7/2016
Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act – Draft Guidance 7/7/2016
Upcoming Meetings (* = New)
* Cellular, Tissue, and Gene Therapies Advisory Committee Meeting; 07 September 2016, Silver Spring, MD
* Oncologic Drugs Advisory Committee Meeting Announcement; 14 September 2016, Silver Spring, MD
* Pediatric Advisory Committee Meeting; 14 September 2016, Bethesda, MD
* National Mammography Quality Assurance Advisory Committee Meeting; 15 September 2016, Gaithersburg, MD
Joint Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee, the Drug Safety and Risk Management Advisory Committee, and the Pediatric Advisory Committee Meeting, 15-16 September, Silver Spring, MD
Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee – 19 October, Silver Spring, MD
* new entry
Last updated: 17 August 2016
Posted in Clinical Trials, Drug Development, FDA, Medical Research, Regulatory Strategy, Regulatory Submissions | Tagged , , , , | Leave a comment

A Brief Overview of the Use of Electronic Informed Consent in Clinical Investigations

by Rachael Gregg, B.A., Cato Research Clinical Research Associate

 

A Brief Overview of the Use of Electronic Informed Consent in Clinical Investigations

The United States Food and Drug Administration (FDA) released a draft guidance “Use of Electronic Informed Consent in Clinical Investigations” in March 2015 that outlines recommendations for clinical investigators, sponsors, and institutional review boards (IRBs) on the use of electronic media and processes to obtain informed consent (and pediatric assent) for FDA-regulated clinical trials. The draft guidance cites that “electronic informed consent refers to using electronic systems and processes that may employ multiple electronic media (e.g., text, graphics, audio, video, podcasts and interactive Web sites, biological recognition devices, and card readers) to convey information related to the study and to obtain and document informed consent.”  This will be a brief summary of some of key considerations discussed in the draft guidance.

How should information in the electronic Informed Consent (eIC) be presented to the subject?

As in a written consent, information must be presented in a language understandable to the subject or the subject’s legally authorized representative (LAR).  Electronic systems used to provide eIC information should be easy to navigate and should be appropriate for the intended audience. The subject should be allowed time to ask questions in person or through electronic media.  Electronic communication tools used (e-mail, telephone calls, videoconferencing or a live chat) should ensure the subject’s privacy as well as the security of the data.

How and where can the eIC process be conducted?

The eIC process can be conducted either at the clinical investigator’s site or remotely.  Should the process be conducted remotely the electronic/computerized system used will need to utilize software that ensures responses cannot be altered and include a method to verify the person signing the informed consent is the subject participating in the research (or their LAR).

What steps may be taken to facilitate the subject’s understanding of the information being presented?

The eIC can utilize an interactive computer-based technology that allows for the use of graphics, images, video and narration that will aid in the subject’s understanding of the information presented. Questions could be included at the end of each section of the eIC to evaluate the subject’s comprehension of the key study elements prior to the subject signing the informed consent.

Does the FDA allow the use of electronic signatures to document eIC?

Use of electronic signatures is permitted.  The FDA does not mandate a specific method but cites that electronic signature must be in compliance with applicable FDA regulations and be considered as “trustworthy, reliable, and generally equivalent to handwritten signatures executed on paper” (see 21 CFR part 11, subpart A).  The electronic system must also be able to capture and record the date that the subject or subject’s LAR provides consent.

Should subjects receive a copy of their eIC and have easy access to the materials and information presented to them in their eIC?

The informed consent must be made available to the subject in a format that can be retained.  The copy, whether an electronic format or paper, should include a transcript of any audiovisual presentations utilized during the eIC process. The subject should be informed of the potential for loss, hacking, or subjection to a search warrant or subpoena should the copy be provided in an electronic format.

As a reminder, the eIC process must follow the requirements cited in FDA 21 CFR part 11 (electronic records/electronic signatures), part 50 (informed consent), and part 56 (IRBs) and any other applicable regulations.

For the full draft guidance:

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM436811.pdf

Additional reference:

“FDA Allows for Electronic Informed Consent, Provides Guidelines for Meeting Regulatory Requirements”. FDA Law Blog, 11Mar2015. http://www.fdalawblog.net/fda_law_blog_hyman_phelps/2015/03/fda-allows-for-electronic-informed-consent-provides-guidelines-for-meeting-regulatory-requirements.html

 

 

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New FDA Guidances for May and June 2016

By Yuka Fukushima, Regulatory Associate & Compliance Specialist at Cato Research
FDA draft and final guidances, released from CDER, CBER, and CDRH from May-June 2016, are posted.  In addition, upcoming advisory committee meetings to be held are also listed below with a link to more information.

Special Interest Guidances/Information Date Posted
Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and Control Information – Final Guidance 6/30/2016
Recurrent Herpes Labialis: Developing Drugs for Treatment and Prevention – Draft Guidance 6/30/2016
Vulvovaginal Candidiasis: Developing Drugs for Treatment – Draft Guidance 6/30/2016
Elemental Impurities in Drug Products – Draft Guidance 6/30/2016
Procedures for Evaluating Appearance Issues and Granting Authorizations for Participation in FDA Advisory Committees – Draft Guidance 6/28/2016
FDA Regional Implementation Specifications for ICH E2B(R3) Reporting to the FDA Adverse Event Reporting System (FAERS) – Technical Specifications Document 6/22/2016
Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices – Final Guidance 6/21/2016
Evaluation and Reporting of Age, Race, and Ethnicity Data in Medical Device Clinical Studies – Draft Guidance for Industry and Food and Drug Administration Staff – Draft Guidance 6/20/2016
Use of International Standard ISO 10993-1, Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process – Final Guidance 6/16/2016
Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions – Draft Guidance 6/16/2016
Quality Attribute Considerations for Chewable Tablets – Draft Guidance 6/16/2016
Osteoporosis: Nonclinical Evaluation of Drugs Intended for Treatment – Draft Guidance 6/13/2016
Dissemination of Patient-Specific Information from Devices by Device Manufacturers – Draft Guidance 6/10/2016
Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act – Final Guidance 6/9/2016
Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance for Industry – Final Guidance 6/9/2016
Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance – Final Guidance 6/9/2016
E18 Genomic Sampling and Management of Genomic Data – Draft Guidance 6/2/2016
Individual Patient Expanded Access Applications: Form FDA 3926 – Final Guidance 6/2/2016
Charging for Investigational Drugs Under an IND — Qs & As – Final Guidance 6/2/2016
Expanded Access to Investigational Drugs for Treatment Use — Qs & As – Final Guidance 6/2/2016
FDA Categorization of Investigational Device Exemption (IDE) Devices to Assist the Centers for Medicare and Medicaid Services (CMS) with Coverage Decisions – Draft Guidance 6/1/2016
Assessing Adhesion with Transdermal Delivery Systems and Topical Patches for ANDAs – Draft Guidance 5/31/2016
Implementation of Acceptable Full-Length and Abbreviated Donor History Questionnaires and Accompanying Materials for Use in Screening Donors of Blood and Blood Components – Final Guidance 5/27/2016
Chronic Obstructive Pulmonary Disease: Developing Drugs for Treatment – Draft Guidance 5/19/2016
Use of Electronic Health Record Data in Clinical Investigations – Draft Guidance 5/16/2016
Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act – Final Guidance 5/16/2016
Considerations for Use of Histopathology and Its Associated Methodologies to Support Biomarker Qualification – Final Guidance 5/13/2016
Infectious Disease Next Generation Sequencing Based Diagnostic Devices: Microbial Identification and Detection of Antimicrobial Resistance and Virulence Markers – Draft Guidance 5/13/2016
Technical Considerations for Additive Manufactured Devices – Draft Guidance 5/10/2016
Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment – Draft Guidance 5/3/2016
Special Protocol Assessment – Draft Guidance 5/3/2016
Upcoming Meetings (* = New)
* Arthritis Advisory Committee Meeting – 12 July, Silver Spring, MD
* Arthritis Advisory Committee Meeting – 13 July, Silver Spring, MD
* Meeting of the Dermatologic and Ophthalmic Drugs Advisory Committee Meeting – 19 July, Silver Spring, MD
* Clinical Chemistry and Clinical Toxicology Devices Panel of the Medical Devices Advisory Committee Meeting – 21-22 July, Gaithersburg, MD
* Cellular, Tissue, and Gene Therapies Advisory Committee Meeting – 26 July, Silver Spring, MD
* Clinical Chemistry and Clinical Toxicology Devices Panel of the Medical Devices Advisory Committee Meeting – 10 August, Gaithersburg, MD
* Microbiology Devices Panel of the Medical Devices Advisory Committee Meeting – 16 August, Silver Spring, MD
Joint Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee, the Drug Safety and Risk Management Advisory Committee, and the Pediatric Advisory Committee Meeting, 15-16 September, Silver Spring, MD
* Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee – 19 October, Silver Spring, MD

* new entry
Last updated: 08 July 2016

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FDA Revises Guidance on Special Protocol Assessments

By Harsh Sancheti, MSPS, MSRS, Ph.D., Medical Writer at Cato Research and
Joanne McNelis, Ph.D., Scientist at Cato Research

 

FDA Revises Guidance on Special Protocol Assessments

What is a Special Protocol Assessment (SPA)?

SPA is a process where a study sponsor and the FDA reach agreement on the critical components of a stability protocol, a pivotal clinical trial, or animal carcinogenicity study to determine if their design and size adequately addresses the specific scientific and regulatory requirements. An FDA agreement on the SPA indicates that the agency agrees with the adequacy and acceptability of specific critical elements of overall protocol design (e.g., entry criteria, dose selection, endpoints, and planned analyses). These elements are critical to ensure that the trial conducted under this protocol has the potential to support the regulatory requirements for a future marketing application.

Importantly, the SPA process is beneficial for the sponsor to gain insight into FDA’s thinking and get agreement with the FDA on critical aspects of the protocol; CDER has issued more than 1000 SPA agreements since the program was established in 1997.

 

What is Included in the May 2016 SPA Draft Guidance?

With the aim of improving the quality and appropriateness of SPA requests, and the resulting interaction with sponsors, FDA addressed several key areas of concern in the new draft guidance to reflect alterations in the regulatory landscape and policy since its 2002 predecessor. The new guidance expanded the protocol eligibility for SPA and provided clarification on the overall submission process. Specifically, the topics addressed include:

  • Clarifying which protocols are eligible for SPA
  • Adding animal rule efficacy protocols intended to support approval of drugs and biological products
  • Adding protocols intended to support approval of biosimilar biological products
  • Providing greater detail about the content of an SPA submission
  • Clarifying the process for rescinding an SPA agreement.

 

What Protocols are Eligible for SPA?

The types of protocols that can be reviewed under an SPA are limited, and according to the 2002 guidance include: (1) Carcinogenicity protocols, (2) Final product stability protocols, or (3) Clinical protocols for Phase 3 trials whose data will form the primary basis for an efficacy claim. Perhaps the most significant revision to the May 2016 draft guidance was the expansion of eligibility for SPA. Consistent with new performance goals for SPA, mandated in the Prescription Drug User Fee Amendments of 2012 (PDUFA V) and with the Biosimilar User Fee Act of 2012 (BsUFA), efficacy protocols that meet the animal rule and protocols intended to support approval of biosimilar biological products will also be eligible, in addition to the previously accepted protocols.

 

Increased Details of the SPA Content and Process

The new draft guidance also describes in greater detail the procedures for submitting a request, the content of the request submission, the FDA assessment process, and the obligations the FDA has in responding to sponsors.

 

Before submitting an SPA Request, the FDA strongly suggests that the sponsor meets with the FDA to discuss the trial for its regulatory context. Under PDUFA V and BsUFA goals, a protocol will qualify for SPA only if the sponsor has had an end-of-phase 2/pre-phase 3 meeting or end-of-phase 1 meeting, as appropriate, or Biosimilar Biological Product Development (BPD) Type 2 or Type 3 meeting, respectively. The guidance states that the complete protocol and statistical analysis plan should be submitted along with “a limited number of specific questions about protocol design and scientific and regulatory requirements.” In particular, the FDA calls on sponsors to “identify unusual or potentially problematic aspects of the protocol” in the SPA request.

 

Typically, the agency reviews an SPA relatively quickly and is within 45 days. There are established procedures and timing for requesting an SPA. Both, CDER and CBER recommends submitting the SPA protocol to the Agency at least 90 days prior to the anticipated study starting date. The protocol should be complete, and enough time should be allowed to discuss and resolve any issues before the study begins. It must be noted that SPA will not be provided by the FDA after a study has begun and if they are evaluated by the FDA, it will not qualify for the 45-day time frame FDA review. The SPA protocol should be submitted as a separate amendment to the sponsor’s IND (with additional filing details listed in the 2002 guidance).

 

After completing the SPA review, FDA issues a letter including an assessment of the protocol, agreement or non-agreement with the proposed protocol and answers to the sponsors initiated questions. The FDA will address the critical elements to the protocol design. For example, the FDA may convey their agreement “with the proposed primary endpoint or sample size estimate, but might not include a detailed review of the case report form”. If a no‑agreement letter is issued, FDA will discuss the specific design parameters with which the FDA does not agree. In addition, the May 2016 draft guidance recommends that a Type A or Type 1 meeting be held to discuss outstanding issues.

 

The Benefits and Risks of an SPA

The SPA can be a very valuable process for a sponsor. It can provide additional assurance, above other regulatory guidance, that innovative clinical trial designs and study endpoints are adequate for marketing approval. When used appropriately, it can promote the use of novel approaches to drug development, potentially reducing the associated time and monetary costs. However, it should be noted that an SPA agreement is not binding in all circumstances. FDA’s guidance states, “an agreement may not be changed by the manufacturer or the agency unless through a written agreement of the two entities, or if FDA determines a substantial scientific issue essential to determining the safety or effectiveness of the drug”. The clause of substantial scientific issue is necessary to prevent the approval of drugs that are realized to have safety and efficacy concerns after new scientific information has come to light. In the past, the FDA has come under fire for changing SPA agreements late in clinical development, and for a lack of transparency of this process. Since the impact of rescinding an SPA agreement is so large — potentially setting a sponsor back years in clinical development and costing millions of dollars — the increased level of detail in the new guidance will be welcomed by drug developers. It is hoped by all stakeholders that the increased clarity of the SPA process provided in this draft guidance will foster a more useful interaction between sponsors and the FDA, and reduce the uncertainty and risk of the drug development process.

Comments on the May 2016 Draft Guidance are due by July 5, 2016 here.

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