October 2019 Drug and Device Corner

Posted on October 29, 2019October 29, 2019

REMINDER: we are currently in the renewal period (1 Oct – 31 Dec) for medical device & drug establishment registrations, as well as drug listing certifications.

The FDA, in their commitment to assisting industry in the development of affordable, available, generic drugs, and as part of the Drug Competition Action Plan, is working toward addressing and improving transparency with regard to potential generic applicants obtaining brand RLD samples for generic drug development. The significant issue of industry’s inability to obtain certain RLDs for generic drug development, those that are in limited distribution, is being addressed by the agency in part by posting a list identifying all drug products for which the FDA has received an RLD access inquiry related to limited distribution. Further information is available on the website.

In the October 25, 2019 issue of the Federal Register, FDA announced that it was withdrawing Compliance Policy Guide Sec. 400.400 “Conditions under Which Homeopathic Drug Products May be Marketed”, effective immediately. This CPG was issued in 1988 and has served as the mechanism by which the regulation of homeopathic drug products was enforced.

However, due to ongoing concerns about the safety of homeopathic drug products, the FDA determined that the CPG did not prevent unsafe products from reaching the market nor did it reflect the agency’s current thinking with regard to its risk-based approach to regulatory and enforcement action.

In addition to withdrawing the CPG, the FDA also revised the draft guidance Drug Products Labeled as Homeopathic Guidance for FDA Staff and Industry that had been issued in 2017. The revised draft adds a definition for “homeopathic drug product”, incorporates additional information regarding safety issues that contributed to the development of the guidance and clarifies the agency’s intent to use risk-based factors to prioritize enforcement and regulatory actions involving homeopathic drug products.

In an effort to assist Applicants with supplying correct and complete facility information to the FDA for NDAs, ANDAs, BLAs and submissions associated to these applications, the FDA has published the Guidance Document Identification of Manufacturing Establishments in Applications Submitted to CBER and CDER Q & A. This guidance is intended to clarify Agency expectations regarding facility information that should be included in original NDAs; ANDAs; original BLAs; amendments; supplements; CMC supplements; and resubmissions to these submission types. It is the FDAs hope that this guidance document will reduce the frequency of IRs, RTFs and RTRs as well as increase the efficiency of the application assessment process. The document addresses form 356h, Module 3 and referenced DMF details.

Federal Register Vol 84, No 207, Medical Devices; Exemptions from Premarket Notification: Class II Devices; Request for Comments. FDA is announcing a publication containing modifications the Agency is making to the list of standards FDA recognizes for use in premarket reviews (FDA Recognized Consensus Standards). FR Vol 84, No 206, entitled “Modifications to the List of Recognized Standards, Recognition List Number: 052” (Recognition List Number: 052), will assist manufacturers who elect to declare conformity with consensus standards to meet certain requirements for medical devices.

Quarterly Inactive Ingredient Database (IID) Change Log

Guidance Document updates on the FDA website:

ALL DIVISIONS:

Investigational In Vitro Diagnostics in Oncology Trials: Streamlined Submission Process for Study Risk Determination The purpose of this guidance is to describe an optional streamlined submission process for determining whether use of an investigational in vitro diagnostic (IVD) in a clinical trial for an oncology therapeutic is considered significant risk (SR), nonsignificant risk (NSR), or exempt from investigational device exemption (IDE) requirements.

CDER:

Type V DMFs for CDER-Led Combination Products Using Device Constituent Parts With Electronics or Software A Type V DMF is intended for the submission of FDA-accepted reference information and supporting data that are not covered by DMF Types II–IV.
Human Immunodeficiency Virus-1 Infection: Developing Systemic Drug Products for Pre-Exposure Prophylaxis Specifically, this guidance addresses the FDA’s current thinking regarding the overall development program and clinical trial designs to support the development of systemic drug products for the prevention of HIV-1 infection.
Investigational Enzyme Replacement Therapy Products: Nonclinical Assessment The purpose of this guidance is to help sponsors design and conduct nonclinical studies during development of investigational enzyme replacement therapy (ERT) products.

CDER & CBER:

Electronic Submission of IND Safety Reports Technical Conformance Guide This document represents the Food and Drug Administration’s (FDA’s or Agency’s) current thinking on this topic.
Providing Regulatory Submissions in Electronic Format: IND Safety Reports This draft guidance describes the electronic format sponsors will be required to use when they electronically submit to the FDA investigational new drug application (IND) safety reports for serious and unexpected suspected adverse reactions.
Postmarketing Studies and Clinical Trials – Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act This guidance provides information on the implementation of section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act, which authorizes FDA to require certain postmarketing studies and clinical trials for prescription drugs approved under section 505(c) of the FD&C Act and biological products approved under section 351 of the Public Health Service Act.
Drug Master Files Guidance for Industry This guidance provides FDA’s current thinking on drug master files (DMFs), which are submissions to FDA that may be used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products. DMFs can contain other types of information as well (e.g., toxicology information, shared system REMS (risk evaluation and mitigation strategy)).
Prescription Drug User Fee Act Waivers, Reductions, and Refunds for Drug and Biological Products This guidance provides recommendations to applicants regarding requests for waivers, refunds, and reductions of user fees assessed under sections 735 and 736 of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) for drugs, including biological products.
Patient-Focused Drug Development: Methods to Identify What Is Important to Patients Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders This guidance (Guidance 2) is the second in a series of four methodological patient-focused drug development (PFDD) guidance documents that FDA is developing to describe in a stepwise manner how stakeholders (patients, researchers, medical product developers and others) can collect and submit patient experience data and other relevant information from patients and caregivers to be used for medical product development and regulatory decision-making.

CDRH:

Breast Implants – Certain Labeling Recommendations to Improve Patient Communication This draft guidance contains recommendations concerning the content and format for certain labeling information for saline and silicone gel-filled breast implants.
Coronary, Peripheral, and Neurovascular Guidewires – Performance Tests and Recommended Labeling This guidance document provides recommendations for premarket notification (510(k)) submissions for guidewires intended for use in the coronary vasculature, peripheral vasculature, and neurovasculature.
Intravascular Catheters, Wires, and Delivery Systems with Lubricious Coatings – Labeling Considerations This guidance document addresses labeling considerations for devices containing lubricious coatings used in the vasculature.

CBER:

Submitting Study Datasets for Vaccines to the Office of Vaccines Research and Review This technical specifications document provides you, sponsor/applicant detailed information and specifications for the content of datasets submitted to FDA’s Center for Biologics Evaluation and Research (CBER) Office of Vaccines Research and Review (OVRR) and is designed to aid clinical and statistical reviewers in the review of vaccine applications, e.g., biologics license applications.
Further Testing of Donations that are Reactive on a Licensed Donor Screening Test for Antibodies to Hepatitis C Virus The FDA is providing blood establishments that collect Whole Blood and blood components, including Source Plasma, with recommendations for further testing of donations that are reactive on a licensed donor screening test for antibodies to hepatitis C virus (anti-HCV), as required under 21 CFR 610.40(e).
Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion The FDA is issuing this guidance document to provide blood collection establishments and transfusion services, with recommendations to control the risk of bacterial contamination of room temperature stored platelets intended for transfusion.

CVM:

CVM GFI #171 – Demonstrating Bioequivalence for Soluble Powder Oral Dosage Form Products or Type A Medicated Articles Manufactured from Active Pharmaceutical Ingredients This document describes how CVM intends to evaluate requests for waiving the requirement for performing in vivo bioequivalence studies (biowaivers) for animal drugs administered orally as soluble powders or as Type A medicated articles manufactured from active pharmaceutical ingredients considered to be soluble in aqueous media (water soluble APIs).
CVM GFI #261 – Eligibility Criteria for Expanded Conditional Approval of New Animal Drugs This guidance is intended for sponsors and potential sponsors interested in pursuing conditional approval of new animal drugs for certain major uses in major species.

September 2019 Drug and Device Corner

Posted on October 1, 2019October 1, 2019

The FDA has announced the Reorganization of the Office of New Drugs with Corresponding Changes to the Office of Translational Sciences and the Office of Pharmaceutical Quality. This move is one critical component of the agency’s initiative to modernize the New Drugs Regulatory Program. The FDA expects these changes to not only enable greater efficiency, but to also better understand the diseases intended to be treated by the drugs being evaluated for approval. The OND will also create cross-functional support offices of New Drug Policy, Drug Evaluation Sciences, Regulatory Operations, Operations, and Administrative Operations.

On 9 September 2019, the FDA published the Acceptance Review for De Novo Classification Requests

Final Guidance Document. The purpose of this document is to explain the procedures and criteria FDA intends to use in assessing whether a request for an evaluation of automatic class III designation (De Novo classification request or De Novo request) meets a minimum threshold of acceptability and should be accepted for substantive review. The guidance includes 2 appendices similar in form to a ‘check list’. Appendix A includes information regarding the acceptance criteria which will ensure the DeNovo classification request includes sufficient information for substantive review. This checklist will determine whether the request is accepted or whether an RTA will be issued. Appendix B is a recommended content checklist. The FDA is observing a 60-day transition period between 8 September – 7 November, 2019 during which applications will be accepted per existing process. RTA reviews will begin on 8 November 2019. Please see the guidance document for further information.

The FDA committed to developing “electronic submission templates that will serve as guided submission preparation tools for industry to improve submission consistency and enhance efficiency in the review process” and “[by] FY [fiscal year] 2020, the Agency will issue a draft guidance document on the use of the electronic submission templates.” Providing Regulatory Submissions for Medical Devices in Electronic Format — Submissions Under Section 745A(b) of the Federal Food, Drug, and Cosmetic Act

Draft Guidance Document, is intended to satisfy the draft guidance documents referenced in section 745A(b)(3) and the MDUFA IV Commitment Letter. This draft guidance is not final nor is it in effect at this time. The agency has concluded that it is not feasible to provide and implement an electronic format that would apply to all submissions covered by section 745A(b) of the FD&C Act in one guidance document. Therefore, the published draft document describes the FDA’s plan to develop individual guidances specific to submission type with corresponding timetables for implementation, as well as criteria for waivers of and exemptions from the requirements.

With FDA’s commitment to facilitate generic drug product availability and to assist the generic pharmaceutical industry with development, 53 Product-Specific Guidances for Generic Drug Development have recently been published. Of these guidances – 34 are new and 19 are revised. Five of the new draft guidances and 11 of the revised draft guidances are for complex drug products. Nearly half of these 53 PSGs (8 complex and 18 non-complex) are for products with no approved Abbreviated New Drug Application (ANDA).

On 20 September 2019, the FDA announced limits on packaging for the anti-diarrhea medicine loperamide (Imodium) to encourage safe use. This link will bring you to the agency’s webpage where you may find more information on the FDA’s approved changes to the packaging.

Guidance Document updates on the FDA website

ALL DIVISIONS

Clinical Decision Support Software

The Food and Drug Administration (FDA) has long regulated software that meets the definition of a device in section 201(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including software that is intended to provide decision support for the diagnosis, treatment, prevention, cure, or mitigation of diseases or other conditions (often referred to as clinical decision support software). This guidance provides clarity on the scope of FDA’s oversight of clinical decision support software intended for health care professionals, patients, or caregivers.

CDER

Citizen Petitions and Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act

This draft guidance updates the November 2014 guidance to account for recent regulatory changes and describes a change in FDA’s current thinking on what constitutes a 505(q) petition. In addition, FDA is revising this guidance to describe some of the considerations FDA will take into account in determining whether a petition is submitted with the primary purpose of delaying the approval of an application.

Drugs for Treatment of Partial Onset Seizures: Full Extrapolation of Efficacy from Adults to Pediatric Patients 2 Years of Age and Older

This guidance provides recommendations to sponsors on the clinical development of drugs for the treatment of partial onset seizures (POS) in pediatric patients.

Evaluation of Internal Standard Responses During Chromatographic Bioanalysis: Q & A

This guidance provides recommendations to sponsors, applicants, and contract research organizations regarding internal standard (IS) response variability in chromatographic analytical data submitted in investigational new drug applications, new drug applications, abbreviated new drug applications, biologics license applications, and supplements.

CDER & CBER

Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment

The purpose of this guidance is to assist sponsors in the clinical development of drugs and biological products for the treatment of amyotrophic lateral sclerosis (ALS).

Wholesale Distributor Verification Requirement for Saleable Returned Drug Product—Compliance Policy

This guidance is intended for wholesale distributors who must verify the product identifier upon receipt of a returned product that the wholesale distributor intends to further distribute as required under section 582(c)(4)(D) of the Federal Food, Drug, and Cosmetic Act.

Interacting with the FDA on Complex Innovative Trial Designs for Drugs and Biological Products

This document provides guidance to sponsors and applicants on interacting with the FDA on complex innovative trial design (CID) proposals for drugs or biological products. FDA is issuing this guidance to satisfy, in part, a mandate under section 3021 of the 21st Century Cures Act (Cures Act).

Placebos and Blinding in Randomized Controlled Cancer Clinical Trials for Drug and Biological Products

This guidance provides recommendations to industry about the use of placebos and blinding in randomized controlled clinical trials in development programs for drug or biological products to treat hematologic malignancies and oncologic diseases.

CDRH & CBER

Changes to Existing Medical Software Policies Resulting from Section 3060 of the 21st Century Cures Act

Section 3060(a) of the 21st Century Cures Act (Cures Act) amended section 520 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) on December 13, 2016, removing certain software functions from the definition of device in section 201(h) of the FD&C Act. This guidance provides FDA’s current thinking regarding the amended device definition and the resulting effect the amended definition has on FDA’s guidances related to medical device software.

Medical Device Data Systems, Medical Image Storage Devices, and Medical Image Communications Devices

FDA’s current thinking on the definition of MDDS is reflected in this guidance.

Policy for Device Software Functions and Mobile Medical Applications

The FDA is issuing this guidance document to inform manufacturers, distributors, and other entities about how the FDA intends to apply its regulatory authorities to select software applications intended for use on mobile platforms (mobile applications or “mobile apps”) or on general-purpose computing platforms.

The Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program

In accordance with amendments made to section 514 by the FDA Reauthorization Act of 2017 (FDARA), and as part of the enactment of the Medical Device User Fee Amendments of 2017 (MDUFA IV), FDA was directed to issue a draft guidance regarding the goals and implementation of the ASCA Pilot. This draft guidance refers to voluntary consensus standards.

Safety and Performance Based Pathway

This guidance provides FDA’s current thinking on expanding the concept of the Abbreviated 510(k) Program for demonstrating substantial equivalence for premarket notification (510(k)) submissions.

Safer Technologies Program for Medical Devices

The FDA is introducing a new, voluntary program for certain medical devices and device-led combination products that are reasonably expected to significantly improve the safety of currently available treatments or diagnostics that target an underlying disease or condition associated with morbidities and mortalities less serious than those eligible for the Breakthrough Devices Program. Devices and device-led combination products are eligible for this program if they are subject to review under a premarket approval application (PMA), De Novo classification request (“De Novo request”), or premarket notification (510(k)).

Format for Traditional and Abbreviated 510(k)s

The main focus of this document is to provide guidance on how to format an original submission for a Traditional or Abbreviated premarket notification (510(k)) submission.

The Abbreviated 510(k) Program

This guidance provides recommendations on an optional approach that may be used to demonstrate substantial equivalence in premarket notifications (510(k)s).

The Special 510(k) Program

This guidance provides the Food and Drug Administration’s (FDA) current thinking on premarket notifications (510(k)s) appropriate for review as a Special 510(k).

Refuse to Accept Policy for 510(k)s

The purpose of this document is to explain the procedures and criteria FDA intends to use in assessing whether a premarket notification (510(k)) submission meets a minimum threshold of acceptability and should be accepted for substantive review.

FDA and Industry Actions on De Novo Classification Requests: Effect on FDA Review Clock and Goals

Performance goals were negotiated and agreed to under MDUFA IV for De Novo requests received in FY 2018-2022. These performance goals and process improvements are outlined in the MDUFA IV Commitment Letter from the Secretary of Health and Human Services (the Secretary) to Congress and are further described in the document.

User Fees and Refunds for De Novo Classification Requests

The purpose of this guidance document is to identify: 1) the types of De Novo requests subject to user fees; 2) exceptions to user fees; and 3) the actions that may result in refunds of user fees that have been paid. This document incorporates the impact of process improvements from MDUFA IV.

Humanitarian Device Exemption (HDE) Program

FDA developed this guidance document to provide clarity to industry and FDA staff about the current review practices for the Humanitarian Device Exemption (HDE) Program.

Humanitarian Use Device (HUD) Designations

This guidance document is intended to assist applicants in the preparation and submission of Humanitarian Use Device (HUD) designation requests to the U.S. Food and Drug Administration’s (FDA or Agency) Office of Orphan Products Development (OOPD).

Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications

FDA has developed this guidance document to provide greater clarity for FDA reviewers and industry regarding the principal factors FDA considers when making benefit-risk determinations during the premarket review process for certain medical devices.

Patient Engagement in the Design and Conduct of Medical Device Clinical Investigations

This draft guidance is intended to: 1) help sponsors understand how they can use patient engagement to elicit experience, perspectives, and other relevant information from patient advisors (see definition in Section IV) to improve the design and conduct of medical device clinical investigations; 2) highlight the benefits of engaging with patient advisors early in the medical device development process; 3) illustrate which patient engagement activities are generally not considered by FDA to constitute research or an activity subject to FDA’s regulations, including regulations regarding institutional review boards (IRBs); and 4) address common questions and misconceptions about collecting and submitting to FDA patient engagement information regarding the design and conduct of a medical device clinical investigation.

CDRH

General Wellness: Policy for Low Risk Devices

The Food and Drug Administration (FDA) is issuing this guidance document to provide clarity to industry and FDA staff on the Center for Devices and Radiological Health’s (CDRH’s) compliance policy for low risk products that promote a healthy lifestyle (general wellness products). This guidance does not apply to products (e.g., drugs, biologics, dietary supplements, foods, or cosmetics) regulated by other FDA Centers or to combination products.

Off-The-Shelf Software Use in Medical Devices

This guidance document was developed to address the many questions asked by medical device manufacturers regarding what they need to provide in a premarket submission to the FDA when they use OTS Software.

Conventional Foley Catheters – Performance Criteria for Safety and Performance Based Pathway

This draft guidance provides performance criteria for conventional Foley catheters in support of the Safety and Performance Based Pathway.

Cutaneous Electrodes for Recording Purposes – Performance Criteria for Safety and Performance Based Pathway

This draft guidance provides performance criteria for cutaneous electrodes in support of the Safety and Performance Based Pathway.

Orthopedic Non-Spinal Metallic Bone Screws and Washers – Performance Criteria for Safety and Performance Based Pathway

This draft guidance provides performance criteria for non-spinal metallic bone screws and their associated washers in support of the Safety and Performance Based Pathway.

Spinal Plating Systems – Performance Criteria for Safety and Performance Based Pathway

This draft guidance provides performance criteria for spinal plating systems in support of the Safety and Performance Based Pathway.

Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions

This guidance document describes the Food and Drug Administration’s (FDA or Agency) current approach to considering uncertainty in making benefit-risk determinations to support FDA premarket decisions for medical device premarket approval applications (PMAs), De Novo requests, and humanitarian device exemption (HDE) applications.

CVM

#171 Demonstrating Bioequivalence for Soluble Powder Oral Dosage Form Products or Type A Medicated Articles Manufactured from Active Pharmaceutical Ingredients Considered to be Soluble in Aqueous Media

This document describes how the Center for Veterinary Medicine (CVM) intends to evaluate requests for waiving the requirement for performing in vivo bioequivalence studies (biowaivers) for animal drugs administered orally as soluble powders or as Type A medicated articles manufactured from active pharmaceutical ingredients (APIs) considered to be soluble in aqueous media (water soluble APIs).

#261 Eligibility Criteria for Expanded Conditional Approval of New Animal Drugs

This guidance is intended for sponsors and potential sponsors interested in pursuing conditional approval of new animal drugs for certain major uses in major species.

#263 Recommendations for Sponsors of Medically Important Antimicrobial Drugs Approved for Use in Animals to Voluntarily Bring Under Veterinary Oversight All Products That Continue to be Available Over-the-Counter

This guidance is intended for sponsors of approved applications and abbreviated applications for new animal drugs containing medically important antimicrobials for use in non-food (companion), food-producing animals, or both, that are currently approved with over-the-counter marketing status.

August 2019 Drug and Device Corner

Posted on September 1, 2019September 3, 2019

The FDA has announced FY2020 User fees, please scroll down for further information.

EAS recently sent an email update regarding FDA’s intention to begin inactivating drug listing records, effective 13 Sept 2019. The FDA has found that tens of thousands of drug listing records contain errors. The agency announced their intentions in the Federal Register on 14 August 2019. The main concern with these non-compliant listings is their lack of certification as being active and up-to-date, or the listings are associated with a drug establishment no longer duly registered with the FDA. The notification also points out that some companies have simply opted to not renew registrations / certify listings and have considered this sufficient notification to the FDA. However, this practice is not compliant with the regulations. To appropriately close files, a de-registration SPL file must be submitted to the FDA for an establishment registration and a ‘Marketing Complete’ file (which includes the expiration date of the last batch of product introduced into U.S. commerce) must be submitted for a drug listing.

If the FDA does inactivate a listing, the listing record will note this and it will be removed from all public drug listing databases maintained by FDA. This includes the NDC Directory and the NDC SPL Data Elements (NSDE) file. Any such drug that is still marketed will be deemed misbranded and the company involved will be subject to FDA enforcement action. This would be particularly problematic for foreign companies when importing products into the U.S.

The agency also notes in their announcement that manufacturers and repackagers of products subject to the new product identification requirement, must submit the updated labeling to their product listings. This update will satisfy the annual certification requirement and therefore such products will not need the “blanket no changes” submission to maintain the listings’ active status.

While on the topic, labeler codes should also be current and reflect accurate contact information for the labeler. If you have any questions or concerns regarding your company’s status, EAS is here to assist.

A message was communicated recently from the FDA re approved (A)NADA labeling. By 30 September 2023 the following statements (as applicable) must be included on approved (A)NADA labeling: Approved by FDA under NADA# xxx-xxx OR Approved by FDA under ANADA# xxx-xxx. This requirement applies to all approved animal drugs currently on the market. If you need further information on this topic, please contact EAS.

The FDA, in their ongoing effort to update the IID Database, has announced their most recent changes. Information about FDA’s plans for upcoming changes to the IID can be found on the IID web page. The web page will be continually updated as FDA makes changes to the IID over the coming year.

The FDA has published the following user fee rates for their FY2020, which runs from 1 Oct 2019 – 30 Sept 2020:

Annual Establishment facility fee rates effective 1 October 2019 are as follows:

Medical Device: $5,236

GDUFA

Domestic API facility: $44,400
Foreign API facility: $59,400
Domestic FDF facility: $195,662
Foreign FDF facility: $210,662
Domestic CMO facility: $65,221
Foreign CMO facility: $80,221

Guidance Document updates on the FDA website:

ALL DIVISIONS

Pathology Peer Review in Nonclinical Toxicology Studies: Q & A This guidance provides information to sponsors and nonclinical laboratory staff regarding the management and conduct of pathology peer review performed during good laboratory practice (GLP)-compliant toxicology studies.

CDER

Osteoporosis: Nonclinical Evaluation of Drugs Intended for Treatment The purpose of this guidance is to provide recommendations to industry for designing nonclinical bone quality studies to support the approval of drugs and biologics intended for the treatment of osteoporosis.
Gastroparesis: Clinical Evaluation of Drugs for Treatment This guidance addresses FDA’s current recommendations regarding clinical trial designs and clinical endpoint assessments to support developing gastroparesis drugs for treating idiopathic and diabetic gastroparesis.
Oncology Therapeutic Radiopharmaceuticals: Nonclinical Studies and Labeling Recommendations The purpose of this guidance is to provide information to assist sponsors in the design of an appropriate nonclinical program for the development of radiopharmaceuticals to treat cancer — also known as oncology therapeutic radiopharmaceuticals — and to provide recommendations for certain aspects of product labeling.
E8(R1) GENERAL CONSIDERATIONS FOR CLINICAL STUDIES This document focuses on designing quality into clinical studies, considering the diversity of clinical study designs and data sources used to support regulatory and other health policy decisions.
Uncomplicated Urinary Tract Infections: Developing Drugs for Treatment This guidance addresses the FDA’s current thinking regarding the overall development program and clinical trial designs for drugs to support an indication for the treatment of uUTIs.
Vulvovaginal Candidiasis: Developing Drugs for Treatment The purpose of this guidance is to assist sponsors in the overall clinical development program and clinical trial designs to support drugs for treating vulvovaginal candidiasis (VVC).

CDER & CBER

Male Breast Cancer: Developing Drugs for Treatment This guidance provides recommendations to sponsors regarding the development and labeling of cancer drugs, including biological products, regulated by the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) for the treatment of male patients with breast cancer.
Child-Resistant Packaging Statements in Drug Product Labeling The guidance discusses what information should be included to support CRP statements in labeling for new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and supplements to these applications.
Fabry Disease: Developing Drugs for Treatment The purpose of this guidance is to provide recommendations to sponsors regarding clinical trial design features that can support approval of drugs and biological products intended for the treatment of Fabry disease (FD).
Bacterial Vaginosis: Developing Drugs for Treatment The purpose of this guidance is to assist sponsors in the overall development program and clinical trial designs to support development of topical and systemic drugs and biological products for the treatment of bacterial vaginosis (BV).
General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products This draft guidance is intended to assist sponsors of new drug applications (NDAs), biologics license applications (BLAs), and supplements who are planning to conduct clinical studies in neonatal populations.
Rare Pediatric Disease Priority Review Vouchers This guidance provides information on the implementation of section 908 of the Food and Drug Administration Safety and Innovation Act (FDASIA), which added section 529 to the Federal Food, Drug, and Cosmetic Act (the FD&C Act). Under section 529, FDA will award priority review vouchers to sponsors of certain rare pediatric disease product applications that meet the criteria specified in that section.
Delayed Graft Function in Kidney Transplantation: Developing Drugs for Prevention This guidance addresses the FDA’s current thinking regarding the overall development program and clinical trial designs for systemic drugs administered to the kidney transplant recipient to support an indication of prevention of DGF.

CDRH

Testing and Labeling Medical Devices for Safety in the Magnetic Resonance (MR) Environment This draft guidance document provides Food and Drug Administration’s recommendations on testing to assess the safety and compatibility of medical devices in the Magnetic Resonance (MR) Environment and the recommended format for Magnetic Resonance Imaging (MRI) Safety Information in medical device labeling.
Metal Expandable Biliary Stents – Premarket Notification (510(k)) Submissions This guidance document provides recommendations for 510(k) submissions for metal expandable biliary stents and their associated delivery systems.

CVM

CVM GFI #257 (VICH GL57) The objective of this guidance is to provide study design recommendations that will facilitate the universal acceptance of the generated residue depletion data to fulfill the national/regional requirements for drugs intended for using in aquatic food-producing species.

July 2019 Drug and Device Corner

Posted on August 1, 2019August 5, 2019

The FDA recently issued a warning letter to a company for inaccurate information in one of their drug listings. Section 510(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act and 21 CFR Part 207) outlines the requirements for registration and listing of drug products. EAS would like to remind our clients of the importance of ensuring not only that your drug listings are current, but also correct with regard to both product and label information. Failure to fulfill your listing obligations renders your product misbranded. If you have questions or would like further information, please contact EAS.

The Office of Global Policy and Strategy (OGPS) has launched its own Twitter account, https://twitter.com/FDA_Global. The FDA invites all to follow their new Twitter handle for day-to-day information on FDA’s global regulatory work, foreign offices and international arrangements. Have questions? Contact: FDA_Global@fda.hhs.gov.

Guidance Document updates on the FDA website

All Divisions

Postmarketing Safety Reporting for Combination Products

This guidance addresses how to comply with the final rule on postmarketing safety reporting (PMSR) requirements for combination products that FDA issued on December 20, 2016 (81 FR 92603, hereafter the “combination product PMSR final rule,” “final rule,” or “rule”).

CDER

Federal Register Generic Drug User Fee Rates for Fiscal Year 2020
The FDA has published the FY2020 GDUFA fee rates.

07-22-2019 FDA is announcing the withdrawal of the draft guidance for industry Providing Regulatory Submissions in Electronic Format—Submission of Manufacturing Establishment Information, issued in December 2016.

Establishing Effectiveness and Safety for Hormonal Drug Products Intended to Prevent Pregnancy

This guidance provides recommendations for clinical trials designed to establish clinical effectiveness and safety for hormonal drug products intended to prevent pregnancy.

Harmonizing Compendial Standards With Drug Application Approval Using the USP Pending Monograph Process

This guidance describes the process that allows for the revision of compendial standards that are harmonized with the approved quality and labeling requirements for a drug product application.

Using the Inactive Ingredient Database

This guidance describes the Food and Drug Administration’s (FDA’s) Inactive Ingredient Database (IID) and provides recommendations for how to use the IID in the development of drug products.

Compliance Policy for Certain Compounding of Oral Oxitriptan (5-HTP) Drug Products for Patients With Tetrahydrobiopterin (BH4) Deficiency Immediately in Effect

This guidance describes the Food and Drug Administration’s policy concerning the conditions under which the Agency does not generally intend to take regulatory action against a licensed pharmacist in a State-licensed pharmacy or Federal facility or a licensed physician using the bulk drug substance oxitriptan to compound oral drug products for patients with tetrahydrobiopterin (BH4) deficiency.

E19 Optimisation of Safety Data Collection

This Guideline is intended to provide internationally harmonised guidance on when it would be appropriate to use a selective approach to safety data collection in some late-stage pre-marketing or post-marketing studies, and how such an approach would be implemented.

Advanced Prostate Cancer: Developing Gonadotropin-Releasing Hormone Analogues

This guidance describes the Food and Drug Administration’s (FDA’s) current recommendations regarding the overall development program to establish the effectiveness and safety of gonadotropin-releasing hormone (GnRH) analogues for treating advanced prostate cancer.

Submitting Next Generation Sequencing Data to the Division of Antiviral Products Guidance for Industry Technical Specifications Document

The purpose of this technical specifications document is to provide the current thinking of FDA’s Division of Antiviral Products (the Division) in regard to the submission of next generation nucleotide sequence analysis procedures and data in support of resistance assessments for the development of antiviral drug products.

CDER & CBER

Population Pharmacokinetics

This guidance is intended to assist sponsors of new drug applications (NDAs) and biologics license applications (BLAs) in the application of population pharmacokinetic (population PK) analysis.

Risk Evaluation and Mitigation Strategies: Modifications and Revisions

This guidance provides information on how the FDA defines the types of changes to approved risk evaluation and mitigation strategies (REMS), how application holders should submit changes to an approved REMS, and how the FDA will process submissions from application holders for changes to REMS.

Drug Abuse and Dependence Section of Labeling for Human Prescription Drug and Biological Products — Content and Format

This guidance is intended to assist applicants in writing the DRUG ABUSE AND DEPENDENCE section of labeling, as described in the regulations for the content and format of labeling for human prescription drug and biological products.

Instructions for Use — Patient Labeling for Human Prescription Drug and Biological Products and Drug-Device and Biologic-Device Combination Products — Content and Format

This guidance provides recommendations for developing the content and format of an Instructions for Use (IFU) document for human prescription drug and biological products and drug-device or biologic-device combination products submitted under a new drug application (NDA) or a biologics license application (BLA).

Epidermolysis Bullosa: Developing Drugs for Treatment of Cutaneous Manifestations

The purpose of this guidance is to assist sponsors with the development of drugs for treatment or prevention of the serious cutaneous manifestations of the heterogeneous group of disorders collectively known as epidermolysis bullosa (EB).

Treatment for Heart Failure: Endpoints for Drug Development

This guidance has two purposes: 1) to make it clear that an effect on symptoms or physical function, without a favorable effect on survival or risk of hospitalization, can be a basis for approving drugs to treat heart failure; and 2) to provide recommendations to sponsors on the need to assess mortality effects of drugs under development to treat heart failure.

M10 Bioanalytical Method Validation

This guideline is intended to provide recommendations for the validation of bioanalytical assays for chemical and biological drug quantification and their application in the analysis of study samples.

Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications

This guidance describes how sponsors and applicants must organize the content that they submit to the Agency electronically for all submission types under section 745A(a) of the FD&C Act.

CDRH

Live Case Presentations During Investigational Device Exemption (IDE) Clinical Trials

This document provides guidance on important information about a live case presentation that should be provided as part of an original IDE application or a supplement to an IDE application when requesting inclusion of a live case presentation during a clinical investigation.

Center for Devices and Radiological Health (CDRH) Appeals Processes

This guidance document describes the processes available to outside stakeholders to request additional review of decisions or actions by Center for Devices and Radiological Health (CDRH or the Center) employees.

Center for Devices and Radiological Health (CDRH) Appeals Processes: Questions and Answers About 517A

This guidance document provides the Center for Devices and Radiological Health of key provisions set forth in section 517A of the Federal Food, Drug, and Cosmetic Act, as those provisions pertain to requests for appeals of significant decisions under 21 CFR 10.75, as well as for the timeframes and procedures of regulatory decisions and actions taken by CDRH under 21 CFR 800.75.

Marketing Clearance of Diagnostic Ultrasound Systems and Transducers

In addition to outlining regulatory approaches for certain diagnostic ultrasound devices, this guidance document describes the types of modifications to a diagnostic ultrasound device for which FDA does not intend to enforce the requirement for a new premarket notification (510(k)).

Clinical Investigations for Prostate Tissue Ablation Devices

This draft guidance document, when finalized, will provide recommendations for (1) complying with the clinical testing special control under 21 CFR 876.4340(b)(8) for premarket notifications (510(k)s) for high intensity ultrasound systems for prostate tissue ablation, and (2) collecting clinical data to support marketing submissions for new types of prostatic tissue ablation devices.

Metal Expandable Biliary Stents – Premarket Notification (510(k)) Submissions

This guidance document provides recommendations for 510(k) submissions for metal expandable biliary stents and their associated delivery systems.

CVM

CVM GFI #181 Blue Bird Medicated Feed Labels

The purpose of this guidance is to provide NADA sponsors of Type A medicated articles with FDA’s current thinking on the recommended content and format of Blue Bird labels.

June 2019 Drug and Device Corner

Posted on July 2, 2019July 8, 2019

As part of the FDA’s ongoing efforts in their goal of more ANDA approvals in order to increase access to high-quality lower cost generic drugs, the agency began on 18 June 2019 to publish additional data in the existing Paragraph IV Patent Certifications list. The FDA hopes to assist ANDA applicants in their business decisions to pursue generic drug development. The list will now include, on a prospective basis, the following information:

Number of potential first applicants
180-day decision status
Date of first “first applicant” approval
Date of first commercial marketing
Expiration date of last qualifying patent

For further information, please see the FDA’s Patent Certifications and Suitability Petitions website.

The FDA has posted a website regarding products containing cannabis or cannabis-derived compounds, and particularly cannabidiol (CBD), articulating their current position and 4 specific points they are working to learn more about. The webpage includes a link to a public docket the FDA is using to gather information and data. The docket is available for comment until 16 July 2019. The agency has consistently stated, however, that it believes that CBD is not a legal ingredient in a food or a dietary supplement because it has been investigated as a Investigational New Drug (IND) and has been approved for use in the drug Epidiolex.

Effective 17 June 2019, the FDA is making pre-assigned ANDA number requests available via the CDER NextGen Portal.

Guidance Document updates on the FDA website

CDER

Opioid Analgesic Drugs: Considerations for Benefit-Risk Assessment Framework
The purpose of this guidance is to describe the benefit-risk assessment framework that the Agency uses in evaluating whether applications for opioid analgesic drugs meet the standard for approval under section 505 of the Federal Food, Drug, and Cosmetic Act.
Nonalcoholic Steatohepatitis with Compensated Cirrhosis: Developing Drugs for Treatment
This guidance describes the Food and Drug Administration’s (FDA’s) current recommendations regarding the important components of a drug development program for compensated NASH cirrhosis.

CDER & CBER

ANDA Submissions — Content and Format of Abbreviated New Drug Applications
This guidance details the information that should be provided in each section of the common technical document (CTD) format for human pharmaceutical product applications and identifies supporting guidance documents and recommendations issued by FDA to assist applicants in preparing their ANDA submission.
Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs
This guidance recommends approaches that sponsors of clinical trials to support a new drug application or a biologics license application can take to broaden eligibility criteria, when scientifically and clinically appropriate, and increase enrollment of underrepresented populations in their clinical trials.
Providing Regulatory Submissions in Electronic and Non-Electronic Format—Promotional Labeling and Advertising Materials for Human Prescription Drugs
This guidance pertains to submissions made to the Office of Prescription Drug Promotion (OPDP) in the Center for Drug Evaluation and Research (CDER) and the Advertising and Promotional Labeling Branch (APLB) in the Center for Biologics Evaluation and Research (CBER).
Formal Dispute Resolution: Sponsor Appeals Above the Division Level
This guidance describes the formal dispute resolution (FDR) procedures for sponsors that wish to appeal4 a scientific and/or medical issue to the office or center level and provides a structured process for resolving disputes.

CDRH

Mouse Embryo Assay for Assisted Reproduction Technology Devices
FDA is issuing this draft guidance to outline draft recommendations on conducting the mouse embryo assay (MEA) to support premarket submissions and lot release of assisted reproduction technology (ART) devices.

CDRH & CBER

Testing for Biotin Interference in In Vitro Diagnostic Devices
This guidance is intended to help device developers and clinicians understand how FDA recommends biotin interference testing be performed, and how the results of the testing should be communicated to end-users, including clinical laboratories and clinicians.

CVM

Guidance for Industry: Determining the Number of Employees for Purposes of the “Small Business” Definition in Parts 117 and 507
The purpose of this guidance is to help industry subject to Title 21 of the Code of Federal Regulations (21 CFR) part 117 (part 117) or 21 CFR part 507 (part 507) determine the number of employees for purposes of the “small business” definition under parts 117 and 507.
CPG Sec. 651.100 Ethylenediamine Dihydroiodide (EDDI)
This guidance document represents the Agency’s current thinking on animal products containing ethylenediamine dihydroiodide (EDDI) or feeds containing unapproved new drugs under the provisions of the Federal Food, Drug, and Cosmetic Act (the FD&C Act).

May 2019 Drug and Device Corner

Posted on June 1, 2019July 2, 2019

Guidance Document updates on the FDA website

CDER

CDER & CBER

CBER

Recommendations for Reducing the Risk of Transfusion-Transmitted Babesiosis

CDRH

April 2019 Drug and Device Corner

Posted on May 1, 2019May 5, 2019

It has come to EAS’s attention that there is significant confusion regarding the exemption of Class 1 Medical Device products to comply with the 21 CFR 801.20 requirement for the label of a medical device to bear a unique device identifier. Per 21 CFR 801.30 A class I device that FDA has by regulation exempted from the good manufacturing practice requirements found at 21 CFR 801.20 is not required to comply with the UDI label requirement. You can check the FDA’s Medical Device Exemptions 510(k) and GMP Requirements webpage for more specific information to determine if your product is indeed exempt. All other Class I devices will be required to bear the UDI number on the packaging/device beginning no later than September 24, 2020. If you have questions on UDI requirements, please contact EAS.

Guidance Document updates on the FDA website

Immediately in effect Guidance Document

Compliance Policy for Combination Product Postmarketing Safety Reporting: This guidance document is intended to assist Combination Product Applicants who are subject to the Combination Product Postmarketing Safety Reporting Final Rule issued on December 20, 2016, and codified in 21 CFR Part 4, Subpart B. This guidance document discusses FDA’s compliance policy for the rule. The Federal Registernotification can be found at this link.

CDER & CBER

Bispecific Antibody Development Programs: This guidance provides recommendations to assist industry and other parties involved in the development of bispecific antibodies. This guidance does not discuss development considerations for other multitarget therapies that are combinations of monoclonal antibodies or are antibody cocktails or polyclonal antibodies. Although this guidance is specific to bispecific antibodies, the principles discussed in this guidance may also be applicable to the development of other types of bispecific protein products.

This guidance focuses on general regulatory and scientific considerations for bispecific antibodies, not on development of a particular bispecific antibody. Industry and other stakeholders are encouraged to engage FDA to discuss their individual bispecific antibody development program.

REMS: FDA’s Application of Statutory Factors in Determining When a REMS Is Necessary: This guidance is intended to clarify how the FDA applies the factors set forth in section 505-1 of the FD&C Act (21 U.S.C. 355-1) in determining whether a risk evaluation and mitigation strategy (REMS) is necessary to ensure that the benefits of a drug outweigh its risks.

CDER, CDRH & CBER

Guidance for Industry Pharmacogenomic Data Submissions: This guidance is intended to facilitate scientific progress in the field of pharmacogenomics and to facilitate the use of pharmacogenomic data in drug development.

CDRH

Technical Considerations for Non-Clinical Assessment of Medical Devices containing Nitinol: The 25 purpose of this draft guidance is to outline technical considerations associated with medical devices that have at least one patient contacting component comprised of nitinol. Due to the unique properties of nitinol, the Agency has developed this draft guidance to provide FDA’s current thinking on technical considerations specific to devices using nitinol. These recommendations are intended to be general and not product-specific and should be evaluated in conjunction with the intended use and technological characteristics of your device and any relevant device-specific guidances.

Technical Performance Assessment of Quantitative Imaging in Device Premarket Submissions: This draft guidance document is applicable to all devices that generate quantitative imaging values across the information, a wide range of imaging modalities, intended uses, levels of automation, and complexity of algorithms. This guidance document provides FDA’s recommendations on technical performance assessment, and user information that should be included in a premarket submission for devices that include quantitative imaging functions.

Class II Special Controls Guideline: In Vitro Diagnostic Devices for Bacillus spp. Detection: Guideline for Industry and FDA staff. This special controls guideline was developed to establish special controls for in vitro diagnostic devices for Bacillus species (spp.) detection. This guideline identifies measures that FDA believes are necessary to mitigate the risks to health associated with devices of this type and provide a reasonable assurance of safety and effectiveness. Following the effective date of the final rule classifying the device,1 manufacturers of in vitro diagnostic devices for Bacillusspp. detection2 will need either to (1) comply with the particular mitigation measures set forth in the special controls guideline or (2) use alternative mitigation measures, which demonstrate to the Agency’s satisfaction that those alternative measures identified by the firm will provide at least an equivalent assurance of safety and effectiveness.

Surgical Staplers and Staples for Internal Use – Labeling Recommendations: The Food and Drug Administration (FDA) is issuing this guidance to provide labeling recommendations for surgical staplers and staples for internal use. These labeling recommendations are being issued because malfunctions and misuse associated with these devices have resulted in serious adverse events, including deaths.

DCRH & CBER

Review and Update of Device Establishment Inspection Processes and Standards: FDA is issuing this draft guidance to comply with section 702(b)(1) of the FDA Reauthorization 77 Act of 2017 (FDARA) (Public Law 115-52), which directs FDA to issue draft guidance that specifies how the Agency will implement uniform processes and standards that are applicable to inspections (other than for-cause) of foreign and domestic medical device establishments. FDA updated processes and standards as needed, to address the new provisions in section 704(h)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) that were added by FDARA section 702(a), and to establish a standard timeframe for inspections. This draft guidance also describes standardized methods of communication during the inspection process, and identifies practices for investigators and device establishments to facilitate the continuity of inspections of such establishments.

CVM

#120 Veterinary Feed Directive Regulation Questions and Answers (Revised)

March 2019 Drug and Device Corner

Posted on April 1, 2019April 24, 2019

Implementation of reorganization to begin for CDRH

In order to create a smart and quick-moving infrastructure that can adapt to the needs of future organizational, regulatory and scientific requirements, the Center for Devices and Radiological Health (CDRH) is beginning the implementation of a reorganization.

The reorganization will integrate CDRH’s premarket and post-market program functions along product lines, allowing their experts to leverage their knowledge to optimize decision-making across the product life cycle. This type of approach blends many of the current aspects of product review, quality, surveillance and enforcement into a new, team-based approach. With the implementation of reorganization, the FDA aims to enhance information-sharing across the Center, increase collective decision-making, improve work-life balance and increase professional opportunities for employees.

The implementation is set to begin March 2019 and is expected to be completed by September 2019. FDA says the implementation will take place in a phased approach, and timelines for implementation will vary by office. Each office within the current CDRH structure is undergoing some change in order to better support and advance CDRH’s public health mission and vision.

More information can be found here.

CDER:

Human Immunodeficiency Virus-1 Infection: Developing Systemic Drug Products for Pre-Exposure Prophylaxis

Severely Debilitating or Life- Threatening Hematologic Disorders: Nonclinical Development of Pharmaceuticals

Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act

Quality Considerations for Continuous Manufacturing

Bioavailability Studies Submitted in NDAs or INDs — General Considerations

Assessing the Effects of Food on Drugs in INDs and NDAs — Clinical Pharmacology Considerations

Smoking Cessation and Related Indications: Developing Nicotine Replacement Therapy Drug Products

CDER & CBER:

Pediatric Information Incorporated Into Human Prescription Drug and Biological Product Labeling

Rare Diseases: Natural History Studies for Drug Development

Pediatric HIV Infection: Drug Product Development for Treatment

Enrichment Strategies for Clinical Trials to Support Determination of Effectiveness of Human Drugs and Biological Products

Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials

Cancer Clinical Trial Eligibility Criteria: Patients with Organ Dysfunction or Prior or Concurrent Malignancies

Cancer Clinical Trial Eligibility Criteria: Minimum Age for Pediatric Patients

Cancer Clinical Trial Eligibility Criteria: Brain Metastases

Nonproprietary Naming of Biological Products: Update

CDRH & CBER:

Acceptance and Filing Reviews for Premarket Approval Applications (PMAs)

Refuse to Accept Policy for 510(k)s

CDRH:

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices)

Implanted Brain-Computer Interface (BCI) Devices for Patients with Paralysis or Amputation – Non-clinical Testing and Clinical Considerations

CBER:

Standards Development and the Use of Standards in Regulatory Submissions Reviewed in the Center for Biologics Evaluation and Research

Providing Lot Release Protocol Submissions to the Center for Biologics Evaluation and Research (CBER) in Electronic Format

All Centers:

A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers

February 2019 Drug and Device Corner

Posted on March 1, 2019March 5, 2019

Sunscreen Innovation Act to Enhance Product Safety Requirements

On February 21, 2019 FDA issued a proposed rule that would update regulatory requirements for most sunscreen products in the United States. Aimed at bringing nonprescription, over-the-counter (OTC) sunscreens that are marketed without FDA-approved applications up to date with the latest science, the provisions address sunscreen active ingredient safety, dosage forms, and sun protection factor (SPF) and broad-spectrum requirements. It also proposes updates to how products are labeled to make it easier for consumers to identify key product information.

Per FDA, the agency is issuing this proposed rule to put into effect final monograph regulations for OTC sunscreen drug products as required by the Sunscreen Innovation Act. OTC monographs establish conditions under which the FDA permits certain OTC drugs to be marketed without approved new drug applications because they are generally recognized as safe and effective (GRASE) and not misbranded. Over the last twenty years, new scientific evidence has helped to shape the FDA’s perspective on the conditions, including active ingredients and dosage forms, under which sunscreens could be considered GRASE. For more information, please visit: Sunscreen Proposed Rule.

You may also be interested in EAS complimentary webinar series on OTCs which includes a discussion of monograph reform expectations, labeling, registrations and lists and more. For more information please visit the upcoming webinars page on the EAS website or view our many on-demand webinars on a variety of topics pertinent to the industry.

Federal court enters consent decree against compound manufacturer

The FDA is continuing to see concerning activity when it comes to some compounded drugs, including problems related to the conditions under which compounded sterile medicines are made. As a result, the FDA continues intense focus in this area. The FDA will take enforcement actions against compounders who fail to produce sterile drugs in compliance with FDA regulations.

A consent decree of permanent injunction was filed against a company and its owner. The consent decree prohibits the company and its owner from, among other things, manufacturing, holding, or distributing human or animal sterile drugs compounded at their facility until they comply with the Federal FD&C Act and FDA regulations.

The complaint was filed by the U.S. Department of Justice on behalf of the FDA. Further information can be found on the FDA website.

Medical Device Classification Procedures

The FDA issued a final rule on the classification procedures for medical devices on 17^th December, 2018 entitled “Medical Device Classification Procedures: Incorporating Food and Drug Administration Safety and Innovation Act Procedures”. The rule will be effective from March 18^th, 2019.

The purpose of this final rule is to incorporate the amendments by Food and Drug Administration Safety and Innovation Act (FDASIA) to the FD&C Act which governs the classification and reclassification of medical devices. Also, additional changes have been made by the FDA independent of the FDASIA in efforts to update its regulations governing classification and reclassification of medical devices. The rule will enhance consistency and uniformity across reclassification processes and will also help to reduce regulatory and economic burden.

Summary of the major provisions of the final rule include the provisions for reclassification of devices and for requiring PMA applications for preamendments class III devices to change from a rulemaking proceeding to an administrative order process. Prior to publication of a final order reclassifying a device or requiring a PMA application for a preamendments class III device, FDA must publish a proposed order in the Federal Register, consider any comments submitted on the proposed order, and hold a device classification panel meeting. This final rule also clarifies the process where reclassification of a postamendments device or a transitional device is initiated by FDA, rather than in response to a petition. The final rule also removes the requirement for a hearing under part 16 (21 CFR part 16) for reclassifying transitional devices.

More information can be found at regulations.gov

Guidance Document updates on the FDA website

Guidance Document highlight

In order to improve communications regarding corrective actions in response to inspectional observations with medical device companies, the FDA issued a draft guidance titled “Nonbinding Feedback After Certain FDA Inspections of Device Establishments”, a requirement under the FDA Reauthorization Act of 2017 (FDARA). The document was issued on February 19th, 2019.

Earlier, companies could ask for a feedback on proposed corrective actions but there was no standardized process in place for provision of nonbinding feedback. The draft guidance proposes to standardize the process of communicating and submitting nonbinding feedback for companies on certain kinds of documented inspectional observations that are issued on a Form 483, during either premarket or postmarket inspections of device establishments. It also describes how the FDA evaluates and responds to such requests.

The proposed guidance has outlined steps on the process of requesting a nonbinding feedback.

These include timely submission of request, eligibility criteria, justification of request, proposed responsive actions and how the FDA will respond with a nonbinding feedback. More detailed description can be found here.

CDER

Eosinophilic Esophagitis: Developing Drugs for Treatment Guidance for Industry Draft guidance document for sponsors who are developing drugs and therapeutic biologics for Eosinophilic Esophagitis (EoE) stating FDA’s current recommendations regarding clinical trials for EoE drugs.

Opioid Use Disorder: Developing Depot Buprenorphine Products for Treatment Guidance on FDA’s current thinking about drug product development and designing of trials relevant to study of depot buprenorphine products for Opioid Use Disorder treatment through 505(b)2 pathway for a new drug application (NDA) submission

Marketing Status Notifications Under Section 506I of the Federal Food, Drug, and Cosmetic Act; Content and Format Guidance for Industry Draft guidance document intended to assist holders of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) approved under section 505(c) and 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(c) and (j)), respectively with identifying required contents for marketing status notification and format to submit these notifications required under section 506I of the FD&C Act (21 U.S.C. 356i)

Planning for the Effects of High Absenteeism to Ensure Availability of Medically Necessary Drug Product This guidance is intended to encourage manufacturers of medically necessary drug products (MNPs) and any components of those products to develop contingency production plans to use during emergencies that result in high absenteeism at production facilities.

CDER’s Program for the Recognition of Voluntary Consensus Standards Related to Pharmaceutical Quality This guidance describes a proposed program at FDA’s Center for Drug Evaluation and Research (CDER) to make public a comprehensive listing of informally recognized voluntary consensus standards related to pharmaceutical quality. CDER is issuing this draft guidance to obtain public comments on the proposed program.

Competitive Generic Therapies This guidanceprovides a description of the process that applicantsshould follow to request designation of a drug as a CGT and the criteria for designating a drug as a CGT. This guidance also includes information on the actions FDA may take to expedite the development and review of ANDAs for drugs designated as CGTs. This guidance also provides information on how FDA implements the statutory provision for a 180-day exclusivity period for certain first approved applicants that submit ANDAs for CGTs.

Smoking Cessation and Related Indications: Developing Nicotine Replacement Therapy Drug Products The purpose of this guidance is to assist sponsors in the clinical development of nicotine replacement therapy (NRT) drug products, including but not limited to those intended to help cigarette smokers stop smoking. This guidance reflects the FDA’s current recommendations regarding overall development programs to support NRT drug products for smoking cessation and related chronic indications.

CDER & CBER

Safety and Performance Based Pathway – Guidance for Industry and Food and Drug Administration This guidance provides FDA’s current thinking on expanding the concept of the Abbreviated 510(k) Program for demonstrating substantial equivalence for premarket notification (510(k)) submissions

The Least Burdensome Provisions: Concept and Principles – Guidance for Industry and FDA Staff

Rare Diseases: Common Issues in Drug Development Guidance for Industry Rev. 1 Draft guidance is to assist sponsors of drug and biological products for the treatment or prevention of rare diseases in conducting more efficient and successful drug development programs.

Providing Regulatory Submissions in Electronic Format – Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications The purpose of this document is to explain the procedures and criteria FDA intends to use in assessing whether a 510(k) submission meets a minimum threshold of acceptability and should be accepted for substantive review.

Acceptance and Filing Reviews for Premarket Approval Applications (PMAs) The PMA regulation (21 CFR 814.42(e)) identifies the criteria that, if not met, may serve as a basis for refusing to file a PMA. This guidance is intended to be used by FDA staff and the device industry to help elucidate the broad preclinical and clinical issues that need to be addressed in a PMA and the key decisions to be made during the filing process.

CDRH & CBER

Evaluation of Devices Used with Regenerative Medicine Advanced Therapies This guidance provides manufacturers, applicants, and sponsors engaged in the development of regenerative medicine therapies, with FDA’s current thinking regarding evaluation of devices used in the recovery, isolation, or delivery of regenerative medicine advanced therapies.

Refuse to Accept Policy for 510(k)s The purpose of this document is to explain the procedures and criteria FDA intends to use in assessing whether a 510(k) submission meets a minimum threshold of acceptability and should be accepted for substantive review.

CDRH & CDER

Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Test Devices – Guidance for Industry and Food and Drug Administration Staff This guidance is intended to assist drug sponsors and device manufacturers who are planning to develop new antimicrobial drugs and antimicrobial susceptibility test (AST).

CDRH

Intent to Exempt Certain Unclassified, Class II, and Class I Reserved Medical Devices from Premarket Notification Requirements † This guidance describes the Food and Drug Administration’s (FDA) intent to exempt certain unclassified medical devices, certain Class II medical devices, and certain Class I medical devices that are subject to the reserved criteria of section 510(l) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 360(l), from premarket notification requirements.

CBER

Expedited Programs for Regenerative Medicine Therapies for Serious Conditions This guidance addresses regenerative medicine therapies which are defined in section 506(g)(8) of the FD&C Act as including cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, except for those regulated solely under section 361 of the Public Health Service Act (PHS Act) (42 U.S.C. 264) and Title 21 of the Code of Federal Regulations Part 1271 (21 CFR Part 1271).

†The 21st Century Cures Act (Cures), signed into law on December 13, 2016, amended several sections of the Federal Food, Drug, and Cosmetic Act. This guidance was developed and issued prior to the enactment of Cures, and certain sections of this guidance may no longer be current as a result. FDA is assessing how to revise this guidance to represent our current thinking on this topic. For more information please contact DICE@fda.hhs.gov.

January 2019 Drug and Device Corner

Posted on February 1, 2019February 1, 2019

With the Federal Register (FR) publication unavailable, the FDA has published Safety and Performance-Based Pathway on the Guidance Document webpage. Full details will be available in the Federal Register once that site is again functioning. The existing Docket Number for this document is

FDA-2018-D-1387. For questions about this document regarding CDRH-regulated devices, contact the 510(k) Staff at 301-796-5640. For questions about this document regarding CBER-regulated devices, contact the Office of Communication, Outreach, and Development (OCOD) at 1-800-835-4709 or 240-402-8010.

Guidance Document updates on the FDA website

FDA’s CDRH recently released a Safety and Performance-Based Pathway Guidance Document describing a new abbreviated submission process for 510(k)s which aims to simplify submissions for devices which meet performance standards developed by FDA rather than showing outright equivalence in safety/efficacy to the predicate device. This new pathway has the potential for reducing the administrative burden of building a lengthy clearance dossier as well as be a slightly faster way to gain review and clearance. More information will be forthcoming as FDA issues future guidance on the application of this Safety and Performance-Based Pathway to certain types of devices with corresponding FDA-identified performance criteria. Industry may suggest device types for which FDA should consider identifying performance criteria.

Drug and Device January 2019

Posted on January 2, 2019January 2, 2019

Guidance Document updates on the FDA website

All centers:

Developing and Labeling In vitro Companion Diagnostic Devices for a Specific Group or Class of Oncology Therapeutic Products

CDER:

Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment

Post-Complete Response Letter Meetings Between FDA and ANDA Applicants

Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act

CDER & CBER:

New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 2)

Questions and Answers on Biosimilar Development and the BPCI Act

The “Deemed to be a License” Provision of the BPCI Act Questions and Answers Guidance for Industry

Interpretation of the “Deemed to be a License” Provision of the Biologics Price Competition and Innovation Act of 2009

Biomarker Qualification: Evidentiary Framework

Data Integrity and Compliance With Drug CGMP Questions and Answers

Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics

Developing and Submitting Proposed Draft Guidance Relating to Patient Experience Data

CDRH & CBER:

User Fees and Refunds for Premarket Approval Applications and Device Biologics License Applications

CDRH:

Recommendations for Dual 510(k) and CLIA Waiver by Application Studies

Select Updates for Recommendations Select Updates for Recommendations Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices

Self-Monitoring Blood Glucose Test Systems for Over-the-Counter Use

Blood Glucose Monitoring Test Systems for Prescription Point-of-Care Use

Clarification of Radiation Control Regulations For Manufacturers of Diagnostic X-Ray Equipment

Breakthrough Devices Program

CBER:

Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion

Labeling of Red Blood Cell Units with Historical Antigen Typing Results

CVM:

Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-Producing Species: Study Design Recommendations for Residue Studies in Honey for Establishing MRLs and Withdrawal Periods

Drug and Device Corner 2018 December

Posted on December 1, 2018December 3, 2018

Guidance Document updates on the FDA website:

All centers:

Post-Complete Response Letter Meetings Between FDA and ANDA Applicants Under GDUFA Guidance for IndustryOn December 3, 2018, the U.S. Food and Drug Administration (FDA) published the guidance for industry entitled “Post-Complete Response Letter Meetings Between FDA and ANDA Applicants Under GDUFA.” The final guidance provides recommendations to industry on Post-complete response letter (CRL) meetings between the FDA and abbreviated new drug application (ANDA) applicants to clarify deficiencies identified in a CRL to an ANDA submitted under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

CDER:

CDER & CBER:

CDRH & CBER:

CBER:

Considerations for the Development of Dried Plasma Products Intended for Transfusion

Drug and Device Corner 2018 October

Posted on November 1, 2018October 29, 2018

The FDA has announced their FY 2019 Animal Drug User Fee Rates for ADUFA and AGDUFA, please follow link for full information.

Please see the FDA webpage for updates on valsartan recalls.

Guidance Document updates on the FDA website:

All centers:

CDER:

CDER & CBER:

CDRH:

CBER:

Considerations for the Development of Dried Plasma Products Intended for Transfusion

Remember to keep up with CDER Product – Specific Guidances for Generic Drug Development. October had 2 new guidances and 23 revisions.

Drug and Device Corner 2018 September

Posted on October 1, 2018October 1, 2018

EAS would like to remind clients, the FDA FY 2019 establishment registration renewal period begins this month. With reference to Drug Establishments, please make sure you are aware of your obligations under the Drug Supply Chain Security Act (DSCSA) during this drug listing certification period. The FDA has released several guidance documents to assist.

In the event you not already seen the Statement from FDA Commissioner Scott Gottlieb, M.D, EAS highly recommends you read this to understand the FDA’s global efforts to help assure product quality and transparency at foreign drug manufacturing facilities. The statement includes a link to the FDA’s published internal policy for how manufacturing facilities are prioritized and scheduled for surveillance inspections.

In addition, FDA recently announced a Special 510(k) Program Pilot, which aims to expand upon the types of changes eligible for the Special 510(k) Program to improve the efficiency of 510(k) review. FDA is working to simplify the review of certain 510(k)s for industry and FDA staff using efficient practices consistent with least burdensome principles. As part of this pilot, certain design or labeling changes that previously were reviewed as a Traditional 510(k) may be eligible to be reviewed through the Special 510(k) pathway instead. The Agency believes that the reliance on design control requirements and previous Agency review of detailed information can reduce review times and still protect the public health. This pilot is part of ongoing efforts to simplify the 510(k) process and help promote timely access to safe, effective, and high-quality medical devices. EAS offer 510(k) review and submission assistance. Please contact us for more information.

Guidance Document updates on the FDA website:

All centers:

Postapproval Changes to Drug Substances

Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank

CDER:

Product Identifiers Under the Drug Supply Chain Security Act Questions and Answers

Product Identifier Requirements Under the Drug Supply Chain Security Act – Compliance Policy

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

Allergic Rhinitis: Developing Drug Products for Treatment

Nonallergic Rhinitis: Developing Drug Products for Treatment

Physiologically Based Pharmacokinetic Analyses — Format and Content

Hematologic Malignancy and Oncologic Disease: Considerations for Use of Placebos and Blinding in Randomized Controlled Clinical Trials for Drug Product Development

Technical Specifications—Comparative Clinical Endpoint Bioequivalence Study Analysis Datasets for Abbreviated New Drug Applications

FDA Product-Specific Guidances for Generic Drug Development webpage

FDA in Brief: FDA issues 54 product-specific guidances to promote generic drug access and drug price competition

CDER & CBER:

Hematologic Malignancy and Oncologic Disease: Considerations for User of Placebos and Blinding in Randomized Controlled Clinical Trials for Drug Product Development

Indications and Usage Section of Labeling for Human Prescription Drug and Biological Products – Content and Format

CDRH:

Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing

Recognition and Withdrawal of Voluntary Consensus Standards

510(k) Third Party Review Program

Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices

Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions

Drug and Device Corner 2018 August

Posted on September 1, 2018September 26, 2018

The FDA recently sent a reminder email to registered drug establishments regarding the Drug Supply Chain Security Act’s (DSCSA) impending requirements. Production of a prescription drug that meets the definition of “product” (see section 581(13) of the FD&C Act noted below), now requires manufacturers to affix or imprint a product identifier to each package and homogenous case of a product intended to be introduced into commerce by November 28, 2018. A product identifier should include the product’s NDC, unique serial number, lot number and expiration date (see section 581(14) of the FD7C Act) in human- and machine-readable formats. The machine-readable format shall be a 2-dimensional (2D) data matrix barcode when affixed to or imprinted on a package or a linear or 2D data matrix barcode when affixed to or imprinted onto a homogeneous case of the product (see section 582(a)(9) of the FD&C Act).

Section 581(13): “(13) Product.–The term ‘product’ means a prescription drug in a finished dosage form for administration to a patient without substantial further manufacturing (such as capsules, tablets, and lyophilized products before reconstitution), but for purposes of section 582, does not include blood or blood components intended for transfusion, radioactive drugs or radioactive biological products (as defined in section 600.3(ee) of title 21, Code of Federal Regulations) that are regulated by the Nuclear Regulatory Commission or by a State pursuant to an agreement with such Commission under section 274 of the Atomic Energy Act of 1954 (42 U.S.C. 2021), imaging drugs, an intravenous product described in clause (xiv), (xv), or (xvi) of paragraph (24)(B), any medical gas (as defined in section 575), homeopathic drugs marketed in accordance with applicable guidance under this Act, or a drug compounded in compliance with section 503A or 503B.”

More information about the DSCSA can be found on FDA’s website.

We would like to remind our clients, that beginning 1 October 2018, VMF sponsors will be required to use eSubmitter to submit all animal drug applications to the agency. The FDA has been hosting webinars to teach interested parties on the process. You can download the eSubmitter program from the FDA website and find recordings of the instructional webinars, when available, here.

Manufacturers of sunscreen products have an opportunity to offer FDA comments on SPF testing and drug facts labeling through 18 October 2018, please see instructions at the Federal Register notice docket# FDA-2011-N-0449.

On 10 August 2018, the FDA published a revision to the Manual of Policies and Procedures (MAPP 5240.5), ANDA Suitability Petitions – link will bring you to the document for review.

The FDA has announced via the Federal Register Vol 83, No. 163, their determination that Danocrine (danazol) capsules, 50 mg, 100 mg and 200 mg were not withdrawn from sale for reasons of safety or effectiveness, except with respect to the indication of fibrocystic breast disease that was withdrawn for reasons of safety or effectiveness. As a result, the FDA will not be suspending approval of ANDAs that refer to this drug product as long as the applications have removed the indication for fibrocystic breast disease. This determination will also allow the FDA to continue to approve ANDAs that refer to this drug as long as they meet relevant legal and regulatory requirements.

Per the FDA Reauthorization Act of 2017, the FDA has identified a list of Medical Device accessories proposed to be classified as class I, and distinct from other devices. The FDA welcomes public comment until 16 October 2018 on their proposal. Full details and information on how to comment can be found by following this link to the Federal Register notification.

The FDA has announced several public meetings that may be of interest to our readers, please see details below.

The FDA will hold a public hearing with an opportunity for public comment on the future format of the National Drug Code (NDC). With the availability of 5-digit labeler codes nearing capacity, the FDA is open to input from stakeholders on their perspectives regarding the impact of any future changes made to the length and format of the NDC. The hearing is to be held 5 November 2018 from 8:30 am to 5:00 pm EST. Registration for online attendance is available. If you wish to attend in person or present at the public hearing, you must register no later than 15 October 2018. Further information and a registration link can be found here.

Public Meeting of the Pharmaceutical Science and Clinical Pharmacology Advisory Committee will be held 20 September 2018, at FDA’s White Oak Campus, in Silver Spring, MD. The FDA plans to provide a live webcast of this meeting. The morning session will focus on the modernization of assessing drug applications through a Knowledge-Aided Assessment and Structured Application (KASA) initiative. The afternoon session will focus on in-vitro/in-vivo relationship standards and will seek input on establishing patient-focused dissolution standards for oral solid modified-release dosage forms. Complete details can be found at the Federal Register Vol. 83, No. 158.

There will be a public meeting entitled “Standardized Data for Pharmaceutical Quality / Chemistry Manufacturing and Control (PQ/CMC)” on 19 October 2018 from 9 am to 4 pm EDT. The purpose is to provide members of the pharmaceutical industry, and other interested parties, an opportunity to discuss with FDA and provide input on related topics and issues. Please see the Federal Register Notice for complete details.

The FDA has published the following user fee rates for their FY2019 which runs from 1 Oct 2018 – 30 Sept 2019:

Generic Drug User Fee Rates for Fiscal Year 2019

Medical Device User Fee Rates for Fiscal Year 2019

Prescription Drug User Fee Rates for Fiscal Year 2019

Outsourcing Facility Fee Rates for Fiscal Year 2019

Guidance Document updates on the FDA website:

All centers:

Osteoarthritis: Structural Endpoints for the Development of Drugs, Devices and Biological Products for Treatment

CDER:

Fluticasone Propionate Draft Guidance

Nonclinical Testing of Orally Inhaled Nicotine – Containing Drug Products

Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances

Opioid Use Disorder: Endpoints for Demonstrating Effectiveness of drugs for Medication – Assisted Treatment

Quality Attribute Considerations for Chewable Tablets

Microdose Radiopharmaceutical Diagnostic Drugs: Nonclinical Study Recommendations

CDER & CBER:

Elemental Impurities in Drug Products

Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics

CDRH:

Peripheral Vascular Atherectomy Devices – Premarket Notification [510(k)] Submissions

Medical Device User Fee Small Business Qualification and Certification

Process to Request a Review of FDA’s Decision Not to Issue Certain Export Certificates for Devices

CBER:

Recommendations for Reducing the Risk of Transfusion-Transmitted Babesiosis

OOPD: (office of orphan products development)

Clarification of Orphan Designation of Drugs and Biologics for Pediatric Subpopulations of Common Diseases

Drug and Device Corner 2018 July

Posted on August 1, 2018September 26, 2018

EAS would like to bring to your attention the Draft Guidance released by the FDA for ANDA Submissions – Amendments to Abbreviated New Drug Applications Under GDUFA. This guidance describes the significant difference between GDUFA I and GDUFA II Amendments and the timelines associated with their review. The FDA considers all submissions to an ANDA to be an amendment, they will be classified based on the content and issued a goal date consistent with that classification. Please review the guidance for further details.

In the FDA’s ongoing effort to make generic affordable drugs available to the public, they have published product-specific guidances describing the Agency’s current thinking and expectations on how to develop generic drug products therapeutically equivalent to specific reference listed drugs. These guidances are hoped to assist the generic pharmaceutical industry with identifying the most appropriate methodology for developing drugs and generating the evidence needed to support ANDA approval. Please see the FDA’s Product-Specific Guidances for Generic Drug Development webpage for more details.

The FDA issued a press release regarding its recent actions on bulk drug substances used for compounding. Their Bulk Drug Substances Nominated for Use in Compounding lists for 503A Category drugs and 503B Category drugs have been updated as of 23 July 2018. Included in the update are the changes to the lists and when the changes became effective. Please see the press release for full details.

The Food and Drug Administration (FDA) announced a public hearing to solicit input from the public on how to facilitate greater availability of biosimilar and interchangeable products while retaining the balance between competition and innovation. The hearing will be held on Tuesday 4 September 2018, from 9 a.m. to 5 p.m. at the Food and Drug Administration’s White Oak Conference Center. If you would like to participate and weigh in on this hearing, more information on how to register for the meeting or the live webcast can be found in the Federal Register Notice.

Guidance Document updates on the FDA website

All centers

Use of Electronic Health Record Data in Clinical Investigations

CDER

Oncology Therapeutic Radiopharmaceuticals: Nonclinical Studies and Labeling Recommendations

Smallpox (Variola Virus) Infection: Developing Drugs for Treatment or Prevention

Q3D(R1) Elemental Impurities

Hypertension: Conducting Studies of Drugs to Treat Patients on a Background of Multiple Antihypertensive Drugs

Innovative Approaches for Nonprescription Drug Products

Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products – Quality Considerations

Use of Liquids and / or Soft Foods as Vehicles for Drug Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments

Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products – Quality Considerations

CDER & CBER

Assessing User Fees Under the Biosimilar User Fee Amendments of 2017

Indications and Usage Section of Labeling for Human Prescription Drug and Biological Products – Content and Format

E17 General Principles for Planning and Design of Multiregional Clinical Trials

Field Alert Report Submission Q & A

Labeling for Biosimilar Products

Inborn Errors of Metabolism That use Dietary Management: Considerations for Optimizing and Standardizing Diet in Clinical Trials for Drug Product Development

Slowly Progressive, Low-Prevalence Rare Diseases with Substrate Deposition That Results from Single Enzyme Defects: Providing Evidence of Effectiveness for Replacement or Corrective Therapies

E17 General Principles for Planning and Design of Multiregional Clinical Trials

CDRH

Metal Expandable Biliary Stents – Premarket Notification (510(k)) Submissions

CBER

Human Gene Therapy for Retinal Disorders

Long-Term Follow-Up After Administration of Human Gene Therapy Products

Human Gene Therapy for Rare Diseases

Chemistry, Manufacturing and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

Human Gene Therapy for Hemophilia

Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up

Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

CVM

Antimicrobial Animal Drug Sales and Distribution Reporting

#257 Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-Producing Species: Marker Residue Depletion Studies to Establish Product Withdrawal Periods in Aquatic Species

June 2018 Drug and Device Corner

Posted on July 1, 2018September 6, 2018

Federal Register Notice Vol 83, No. 108

FDA is publishing an order to exempt a list of class II devices from premarket notification (510(k)) requirements, subject to certain limitations. This exemption from 510(k), subject to certain limitations, is immediately in effect for the listed class II devices. This exemption will decrease regulatory burdens on the medical device industry and will eliminate private costs and expenditures required to comply with certain Federal regulations. FDA is also amending the codified language for the listed class II devices to reflect this final determination. FDA is publishing this order in accordance with the section of the FD&C Act permitting the exemption of a device from the requirement to submit a 510(k).

FDA Withdraws Draft Guidance for Industry: Statistical Approaches to Evaluate Analytical Similarity

[6/21/2018] The Food and Drug Administration (FDA or Agency) is announcing the withdrawal of a draft guidance for industry entitled “Statistical Approaches to Evaluate Analytical Similarity,” issued in September 2017. The draft guidance, if finalized as written, was intended to provide advice for sponsors developing biosimilar products regarding the evaluation of analytical similarity between a proposed biosimilar product and the reference product. After considering public comments that the agency received about the draft guidance, the FDA determined it would withdraw the draft guidance as it gives further consideration to the scientific and regulatory issues involved. Comments submitted to the docket addressed a range of issues that could impact the cost and efficiency of biosimilar development, including the number of reference product lots the draft guidance would recommend biosimilar developers sample in their evaluation of high similarity and the statistical methods for this evaluation. The FDA believes that in better addressing these issues in the future, the agency can advance principles that can promote a more efficient pathway for the development of biosimilar products.

The agency intends to issue future draft guidance that will reflect state-of-the-art techniques in the evaluation of analytical data to support a demonstration that a proposed biosimilar product is highly similar to a reference product.

Guidance Document updates on the FDA website

All Centers

Medical Product Communications That Are Consistent With the FDA-Required Labeling – Q & A

CDER

Human Immunodeficiency Virus-1 Infection: Developing Systemic Drug Products for Pre-Exposure Prophylaxis

Prescription Drug User Fee Act Waivers for Fixed-Combination Antiretroviral Drugs for the President’s Emergency Plan for AIDS Relief

Complicated Urinary Tract Infections: Developing Drugs for Treatment

Assessment of Pressor Effects of Drugs

Complicated Intra-Abdominal Infections: Developing Drugs for Treatment

Major Depressive Disorder: Developing Drugs for Treatment

CDER & CBER

Limited Population Pathway for Antibacterial and Antifungal Drugs

Patient-Focused Drug Development: Collecting Comprehensive and Representative Input

Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials

Development of a Shared System REMS

Waivers of the Single, Shared System REMS

Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management – Core Guideline

Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management – Annex

Prescription Drug User Fee Act Waivers, Reductions, and Refunds for Drug and Biological Products

CDRH

Logical Observation Identifiers Names and Codes for In Vitro Diagnostic Tests

Intravascular Catheters, Wires and Delivery Systems with Lubricious Coatings – Labeling Considerations

Coronary, Peripheral and Neurovascular Guidewires – Performance Tests and Recommended Labeling

Humanitarian Device Exemption (HDE) Program

CDER & CDRH

Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities Q & A

CDER & CBER

S9 Nonclinical Evaluation for Anticancer Pharmaceuticals Q & A

Epidermolysis Bullosa: Developing Drugs for Treatment of Cutaneous Manifestations

Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program

CVM

General Principles for Evaluating the Human Food Safety of New Animal Drugs Used in Food-Producing Animals

May Drug and Device Corner

Posted on June 1, 2018September 6, 2018

In the ongoing effort to make more affordable drugs available to the public, FDA Commissioner Scott Gottlieb, MD issued a statement on the FDA’s efforts to assist in this process. Of particular note is the FDA’s commitment to ensuring generic drug developers have access to brand drug samples for their development process. You can read the commissioners statement here.

The U.S. House Energy and Commerce Committee has progressed with legislation to reform and modernize the OTC Monograph System. Included in this reform is a discussion of an OTC user fee program similar to that of PDUFA, GDUFA, and BsUFA. The FDA sees an OTC monograph user fee program as a means of resources that would encourage innovation and fund the necessary regulatory system update. Currently, each ingredient-specific monograph must be finalized through a multi-step public rulemaking process. This new legislation is proposing an administrative order process to replace the current procedures. EAS will keep you updated as this legislation evolves.

We want to bring to your attention the recently released Enforcement Policy – OTC Sunscreen Drug Products Marketed Without an Approved Application Guidance Document. In this guidance, the FDA articulates its enforcement approach for OTC sunscreen drug products that are being marketed without an approved application as well as those included in the final monograph (for which the effective date has indefinitely stayed.) We highly recommend reviewing this document to find out where your sunscreen products fall in regard to the formulation, testing, and labeling requirements and how this new enforcement policy may affect their continued marketing. To read FDA Commissioner Scott Gottlieb, MD’s statement regarding sun exposure and sunscreens, please follow this link.

The FDA has announced in the Federal Register Vol 83, No. 87 their final order regarding the General Hospital and Personal Use Needle Destruction Device. Effective 4 June 2018, this device will be renamed “sharps needle destruction device” and reclassified from a class III device (regulated under product code MTV) into class II (special controls) which will make it subject to premarket notification. The reclassification will lessen the burden on industry for marketing such devices while still ensuring reasonable safety and effectiveness for users.

The FDA has published in the Federal Register Vol 83, No 94 a proposed amendment to regulations concerning the classification of products as biological products, devices, drugs or combination products. The agency will be accepting e-comments on their proposed amendment until midnight ET 16 July 2018.

The FDA has a webpage dedicated to Drug Supply Chain Security Act readiness, please follow the link for further information. There have also been 3 draft guidance documents released in 2018 regarding the Drug Supply Chain Security Act. The link will bring you to the FDA page listing each of these documents.

Guidance Document updates on the FDA website

CDER

CDER & CBER

CVM

April 2018 FDA Drug / Medical Device Activity

Posted on May 1, 2018September 14, 2018

Reminder! 5 May 2018 is the date for DMF (Drug Master File) and IND (Investigational New Drug) applications to comply with eCTD format submission. There has been a delay for Type III DMF files to comply. The FDA announced in April via their Guidance Document Providing Regulatory Submissions in Electronic Format – Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications that Type III DMF files will have until 5 May 2019 in order to comply with the eCTD format requirements. With the exception of Type III DMFs, all files not submitted in eCTD beginning 5 May 2018 will be rejected. Please see the FDA Drug Master File Tip Sheet for further information. If you have any questions, please do not hesitate to contact EAS.

We would like to bring to your attention the FDA draft Guidance Expansion of the Abbreviated 510(k) Program: Demonstrating Substantial Equivalence through Performance Criteria. Please note, comments on this draft are due to the FDA no later than 90 days after publication in the Federal Register(which was 12 April 2018). This draft guidance proposes to provide an optional pathway for certain well-understood device types which the FDA would identify on a list maintained on the FDA website. Rather than a direct comparison to the predicate device for a 510(k) submission, the FDA proposes to provide alternate objective performance criteria that would satisfy demonstrating substantial equivalence for performance relevant to safety and effectiveness. This will comply with the new congressional amendment to the FD & C Act for the “least burdensome” provisions for medical devices.

Guidance Document updates on the FDA website: CDER:

CBER:

Submitting Study Datasets for Vaccines to the Office of Vaccines Research and Review

CDHR:

CVM:

The Index of Legally Marketed Unapproved New Animal Drugs for Minor Species

CDER & CBER:

CDRH & CBER:

March 2018 FDA Drug / Medical Device Activity

Posted on April 1, 2018September 14, 2018

EAS would like to bring to your attention, the Statement from FDA Commissioner Scott Gottlieb, MD regarding drug compounding outsourcing facilities. The Drug Quality and Security Act (DQSA) was enacted by Congress in 2013 in response to a significant safety issue experienced by the public as the result of poor drug compounding practices. As seen with recently issued warning letters, the FDA is also prioritizing enforcement of section 503B of the Federal Food, Drug and Cosmetic Act which allows for compounded drugs which are not FDA-approved and do not undergo premarket review by the FDA for safety, effectiveness, and quality. In the FDA’s ongoing efforts to enact measures to ensure this allowance is exercised only when necessary and appropriate, and in a safe manner with assured product quality, they have released the Draft Guidance Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug and Cosmetic Act. In this guidance, the FDA addresses their plan to formulate the “503B bulks list”, a list of bulk drug substances determined by the FDA as clinically necessary for outsourcing facilities to use for compounding drugs. Follow the links for further information.

Now that the dust has settled with the 2017 FDA requirement to certify all drug listings annually, we would like to bring to your attention the necessity to complete expired listings. Under 21 CFR 207.57(b), registrants must submit updated listing information at each June and December if there is change since the previous listing and they must submit this information to the FDA via electronic format. These changes include any drug recently introduced into U.S. commercial distribution which was not previously listed, any drug which commercial distribution has been ceased, any drug reintroduced in commercial distribution and any material changes in any drug listing information previously submitted. The FDA has communicated that although listings that were not certified by 31 December 2017 have been changed to an expired status, it is still required to ‘complete’ the marketing status and input an ‘end marketing date’ in order to delist the product. EAS is here to assist with any listing issues you may need to be resolved. Please let us know if we can help.

Guidance Document updates on the FDA website:

OC: Immediately in Effect Guidance for Industry and Food & Drug Administration Staff

Compliance Policy for Combination Product Postmarketing Safety Reporting

CDER:

CDHR:

Acceptance of Clinical Data to Support Medical Device Applications and Submissions FAQ

CVM:

OC: Distributed for Comment Purposes Only

Postmarketing Safety Reporting for Combination Products

February 2018 FDA Drug / Medical Device Activity

Posted on March 1, 2018September 14, 2018

Medical Device manufacturers and importers, please make note of the upcoming FDA Adverse Event codes update. Per the FDA eMDR System Enhancements website, the list of FDA Adverse Event codes accepted in F10 and H6 will be updated to harmonize with the IMDRF Adverse Event Reporting Terminologies. This update will affect the Device Problem Codes and Manufacturer Evaluation Codes, which correspond to IMDRF Annexes A through D. Future updates will harmonize all remaining FDA adverse event codes with IMDRF as more annexes are published. IMDRF codes are not currently accepted by eMDR, but the new hierarchies posted on FDA.gov include a one-to-one mapping of IMDRF codes to FDA codes. FDA codes that are being retired during this update will be rejected by eMDR once this update is deployed. The current non-harmonized hierarchies and the future IMDRF-harmonized hierarchies are currently posted at MDR Adverse Event Codes. The scheduled date of this production update is 6 April 2018.

Senior Director for Pharmaceuticals and Medical Devices, Bryan J. Coleman has summarized a new agency guidance on Refuse to Accept (RTA)’s for 510(k) Medical Device applications. In this summary, Bryan discusses FDA’s newly produced checklists enabling submitters to ensure all required data is complete prior to submission. This should better facilitate FDA’s ability to complete a substantive review by assuring all preliminary information is included. EAS offers services with 510(k) submissions including the review of data and assistance with compiling submissions to the process of submitting to FDA. Please contact Bryan at bcoleman@easconsultinggroup.com

Guidance Document updates on the FDA website:

CDER:

CDRH:

January 2018 FDA Drug / Medical Device Activity

Posted on February 1, 2018September 14, 2018

EAS would like to remind all DMF holders that the FDA DEADLINE for eCTD submissions is fast approaching. As of 5 May 2018, the FDA will only accept eCTD submissions to ALL DMF files. If you have not already made plans for conversion, you should do so immediately. If you have any questions, feel free to contact EAS. While on the topic of DMFs Albert Yehaskel, EAS Independent Advisor for Pharmaceutical Submissions, has written a very informative white paper, “An Overview of Drug Master Files”. This has been slightly updated and added to our website, please use this link to access this valuable resource.

The Food and Drug Administration is reopening the comment period for the document published in the Federal Register on September 26, 2017, announcing a public hearing on a potential approach for device sponsors who seek to obtain marketing authorization for their products that are intended for a new use with an approved, marketed drug when the sponsor for the approved, marketed drug does not wish to pursue or collaborate on the new use. Submit either electronic or written comment by February 21, 2018.

In the event you missed the FDA announcement, the agency has created a new platform to request pre-ANDA meetings. This platform, CDER Direct NextGen Collaboration Portal, was designed to help the FDA minimize manual data entry and support the agency’s GDUFA II performance goals. The new technology platform, which will allow the industry to request pre-ANDA meetings for complex generic drug products with the FDA. In just a few steps, potential applicants of abbreviated new drug applications (ANDAs) will be able to initiate requests by uploading a meeting request package. The portal also allows the industry to submit supporting documents, such as meeting presentation materials, requests for additional information made by the FDA, and post-meeting comments. For additional information about the portal, please visit the FDA Pre-ANDA Program webpage.

FDA (or Agency) is announcing the timetable for updates to the FDA Data Standards Catalog for study data submitted electronically in NDAs, ANDAs, BLAs, and certain INDs to CBER and CDER. The initial implementation timetable for submitting standardized study data in electronic format was 24 months for NDAs, ANDAs, and applications, and 36 months for certain INDs after the publication of the final guidance “Providing Regulatory Submissions in Electronic Format–Standardized Study” in December 2014. When future updates to study data standards listed in the FDA Data Standards Catalog (Catalog) occur, these updated standards will be required in studies with a start date no earlier than 12 months after a Federal Register notice announcing such updates is published. When future new study data standards are listed in the Catalog, these new standards will be required in studies with a start date no earlier than 24 months after a Federal Register notice announcing such new standards is published. Please see the FDA Study Data Standards Resources webpage for further information.

Guidance Document updates on the FDA website: CDER:

CDHR:

CBER:

Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV) – Testing, Product Disposition, and Donor Deferral and Reentry

December 2017 FDA Drug / Medical Device Activity

Posted on January 1, 2018September 14, 2018

We would like to highlight one of the Draft Guidance issued by the FDA this month.^**The U.S. Food and Drug Administration proposed a new, risk-based enforcement approach to drug products labeled as homeopathic. This proposed new approach would update the FDA’s existing policy to better address situations where homeopathic treatments are being marketed for serious diseases and/or conditions but where the products have not been shown to offer clinical benefits. It also covers situations where products labeled as homeopathic contain potentially harmful ingredients or do not meet current good manufacturing practices. Under the law, homeopathic drug products are subject to the same requirements related to approval, adulteration and misbranding as any other drug product.

With the new drug listing regulation, all companies have been given a renewed opportunity to ensure their listings are complete and accurate. This includes the label uploaded to the drug listing. The FDA recently issued a warning letter to a company whose listing did not match the product in commercial distribution. Do keep in mind that the FDA requires all changes to a drug listing to be reported as soon as possible but no later than the June or December following the change. As of FDA FY 2018, all drug listings must be certified as accurate by 31 December of each year. Any listing that has not been updated or certified as accurate according to the regulation will be considered expired by the FDA in January of the following year.