The Current Implementation of the Drug Supply Chain Security Act (DSCSA) Implementation Plan and Rare Disease Drugs

What is the Drug Supply Chain Security Act (DSCSA)?

In November 2013 the Drug Quality and Security Act (DQSA) was signed into law with the intent to decrease incidence of counterfeit, falsified, or substandard prescription medication.  Title II of this act was the Drug Supply Chain Security Act (DSCSA), which lays the ten-year framework for the implementation of an interoperable system capable of identifying and tracing prescription drugs as they are distributed throughout the United States.  Starting in November 2017 manufacturers will be required to include new identifiers on all drugs products at the package level (serialization); specifically, a national drug code, serial number, and barcode.  Using these identifiers, all drug transactions must be entered into an interoperable record (electronic or paper) which contains the transaction information, transaction history, and transaction statements.  These records will be maintained by the current or new product tracing systems which must meet DSCSA requirements.   Meeting these requirements will require close cooperation between drug manufacturers, dispensers, distributors, logistics, and the FDA itself.

What is Covered by the DSCSA?

The DSCSA covers prescription drugs in their finished dosage form (such as capsules, tablets, lyophilized products before reconstitution, etc.) for administration to a patient.  The Act exempts blood or blood components intended for transfusion, radioactive drugs or radioactive biological, imaging drugs, any medical gas, homeopathic drugs, and drug requiring compounding [DSCSA Section 582. Definitions (13)].

Exemption Waivers

In addition to the exemptions outlines above, the DSCSA outlines the need for the FDA to establish a process by which a waiver from any DSCSA requirement may be obtained [DSCSA Section 582. Requirements (3)(A)(i-iii)].  The process was supposed to go into effect within two years of its enactment (2013), however as of 15 September 2016 the FDA has yet to issue guidance on this topic.  Consideration of exemption waivers, however, is currently scheduled on the regulatory agenda for 2016.  It is therefore unclear under what circumstances waivers are likely to be granted, though the law does specifically mention undue economic hardship or emergency medical reasons, including a public health emergency, as grounds for such a request.

The DSCSA and Rare Disease Drugs

The costs of implementing serialization may hit orphan drugs disproportionately hard as initial costs to serialize a drug are high, and drugs targeting larger markets are likely to benefit from economy of scale.  This is particularly true of drugs targeting small patient populations that are only manufactured sporadically.  One recent survey of pharmaceutical packaging companies carried out at Cato Research Ltd. found small scale serialization costs alone can range up to $185,000 per batch of labeled drug, potentially creating a significant impact on the cost of drugs produced at small scales.  Such drugs seem likely to be good candidates for a DSCSA waiver, though this remains unclear until the FDA issues guidance.

More information about the DSCSA can be found at the FDA:

http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/DrugSupplyChainSecurityAct/ucm20041041.htm

 

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New FDA Guidances for August 2016

By Sheila R. Plant, Ph.D., R.A.C., Regulatory Scientist at Cato Research

FDA draft and final guidances, released from CDER, CBER, and CDRH in August 2016, are posted. One recent CDER Manual of Policies and Procedures (MAPP) regarding a change in hard gelatin capsule shell suppliers is included.  In addition, upcoming advisory committee meetings to be held in the next couple months are listed below with links to more information.

Special Interest Guidances/Information Date Posted
Enforcement Policy on National Health Related Item Code and National Drug Code Numbers Assigned to Devices – Final Guidance 30 Aug 2016
Revised Recommendations for Reducing the Risk of Zika Virus Transmission by Blood and Blood Components – Final Guidance 26 Aug 2016
Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications – Final Guidance 24 Aug 2016
Patient Preference Information – Voluntary Submission, Review in Premarket Approval Applications, Humanitarian Device Exemption Applications, and De Novo Requests, and Inclusion in Decision Summaries and Device Labeling – Final Guidance 24 Aug 2016
Microbiological Data for Systemic Antibacterial Drug Products — Development, Analysis, and Presentation – Final Guidance 24 Aug 2016
ANDA Submissions — Refuse to Receive for Lack of Justification of Impurity Limits – Final Guidance 24 Aug 2016
Use of Nucleic Acid Tests to Reduce the Risk of Transmission of Hepatitis B Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products – Final Guidance 17 Aug 2016
Regulatory Classification of Pharmaceutical Co-Crystals – Draft Guidance 16 Aug 2016
Change in Hard Gelatin Capsule Shell Supplier – CDER MAPP 15 Aug 2016
Deciding When to Submit a 510(k) for a Change to an Existing Device – Draft Guidance 08 Aug 2016
Deciding When to Submit a 510(k) for a Software Change to an Existing Device – Draft Guidance 08 Aug 2016
Ulcerative Colitis: Clinical Trial Endpoints Guidance for Industry – Draft Guidance 05 Aug 2016
Insanitary Conditions at Compounding Facilities Guidance for Industry – Draft Guidance 03 Aug 2016
Medical X-Ray Imaging Devices Conformance with IEC Standards – Draft Guidance 03 Aug 2016
Determining Donor Eligibility for Autologous Donors of Blood and Blood Components Intended Solely for Autologous Use – Compliance Policy – Final Guidance 02 Aug 2016
FY 2017 Medical Device User Fee Small Business Qualification and Certification – Guidance for Industry, Food and Drug Administration Staff and Foreign Governments – Final Guidance 01 Aug 2016
Upcoming Meetings (* = New)
 
Oncologic Drugs Advisory Committee Meeting; 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
 

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Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee; 15 September 2016, Silver Spring, MD
Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee – 19 October 2016, Silver Spring, MD
 

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General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting, Establishment of a Public Docket, Request for Comments; 20-21 September 2016, Gaithersburg, MD
 

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Microbiology Devices Panel of the Medical Devices Advisory Committee Meeting; 5 October 2016, Gaithersburg, MD
* Vaccines and Related Biological Products Advisory Committee Meeting; 13 October 2016, Silver Spring, MD
Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee – 19 October, Silver Spring, MD
* Allergenic Products Advisory Committee Meeting; 27 October 2016, Silver Spring, MD
* new entry

Last updated: 06 September 2016

Posted in Cato Research, Clinical Trials, Drug Development, FDA, Medical Research, Regulatory Strategy, Regulatory Submissions | Tagged , , , , | Leave a comment

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
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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

Posted in Cato Research, Clinical Trials, FDA, Medical Research, Regulatory Strategy, Regulatory Submissions | Tagged , , , , , | Comments Off on New FDA Guidances for May and June 2016