February 2020 Drug and Device Corner

The FDA has published a revision to Manual of Policies and Procedures 5240.3, Prioritization of the Review of Original ANDAs, Amendments, and Supplements. This update is designed to efficiently allocate limited agency resources to areas where priority review is most likely to meaningfully increase generic drug access and ensure fairness to applicants. Details can be found on the FDA webpage. Additionally, the agency has a prerecorded webinar describing the revisions.

The FDA published a Guidance Document, Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications, which 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. Of note, this guidance also describes the addition of exemptions and waivers from complying with eCTD requirements. Exempted from the eCTD Requirements are all Type III DMF submissions. Although these specific submissions will be exempt from filing in eCTD format as described in this guidance, FDA still encourages applicants to send submissions in an alternative electronic format (e.g., PDF files following the CTD structure). See the Guidance Document for further exemptions and waivers.

Below noted CDER Product-Specific Guidances have been withdrawn as of 22 January 2020:

Active IngredientType of GuidanceRoute & Dosage FormRLD
Butenafine HydrochlorideDraftTopical dream21408
LevonorgestrelDraftIUD203159
SelexipagDraftOral Tablet207947

The Agency has launched The Compilation of Center for Drug Evaluation and Research (CDER) New Molecular Entity (NME) Drug and New Biologic Approvals, a new resource designed to assist external and agency researchers collecting historical information about FDA’s drug approvals. This .csv file with curated data regarding drug products approved by CDER since 1985, will be available on the agency’s website.

The FDA is requesting voluntary withdrawal of bacitracin for injection from the market. In April 2019, the Antimicrobial Drugs Advisory Committee met and discussed the safety and effectiveness of bacitracin for injection. The advisory committee voted almost unanimously, with one abstention, that the risks outweigh the benefits for the drug’s only approved indication. Based on FDA’s review of currently available data, FDA believes that the potential problems associated with bacitracin for injection are sufficiently serious to remove the drug from the market. This requested voluntary withdrawal does not impact approved topical or ophthalmic drugs that contain bacitracin.

The FDA is hosting a Public Meeting regarding Communications about the Safety of Medical Devices. During this public meeting the FDA hopes to hear from all stakeholders, including patients and caregivers, healthcare providers, regulated industry, and media. The FDA is looking for feedback on how the agency can improve their safety communications to assure stakeholders receive the information they need in a timely, clear, and consistent manner. A preliminary agenda has been published. Details can be found on the website for participation.

CVM Broadcast #39 notice was issued 7 February 2020. The OSC DER eSubmitter Program will soon require digital signatures on electronic submissions to be registered with the CVM Electronic Submission System (ESS). We expect this requirement to be implemented as early as mid-March 2020. If you have questions, please contact CVM at cvmesubmitter@fda.hhs.gov.

CVM Broadcast #40 notice was issued 13 February 2020. CVM is updating their CVM Submission Type list of values in response to feedback from stakeholders when submitting Manage Forms to CVM. This change will occur on February 22, 2020 in FDA ESG Pre-Production and February 29, 2020 for FDA ESG Production. This update will modify the Submission Type list of values for CVM: 1] Submission Type “Electronic_Submissions” will be changed to “Manage_Form”. Stakeholders should use this folder when submitting Manage Form submissions to CVM. 2] Submission Type “eSubmitter” should be used for any eSubmitter submission to CVM 3] Submission Type “Adverse_Events_Reports” should be used for any electronic adverse event report submission to CVM.

Guidance Document updates on the FDA website

CDER

Hypertension Indication: Drug Labeling for Cardiovascular Outcome Claims – This guidance is intended to assist applicants in developing labeling for cardiovascular outcome claims for drugs that are indicated to treat hypertension.

CDER & CBER

Promotional Labeling and Advertising Reference and Biosimilar Products Questions and Answers – This guidance addresses questions firms may have when developing FDA-regulated promotional labeling and advertisements (promotional materials), for prescription reference products licensed under 351(a) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(a))

Mucopolysaccharidosis Type III (Sanfilippo Syndrome): Developing Drugs for Treatment – The purpose of this guidance is to provide recommendations to sponsors regarding eligibility criteria, trial design considerations, and efficacy endpoints to enhance clinical trial data quality and foster greater efficiency in development programs for drugs to treat mucopolysaccharidosis type III (MPS III; also called Sanfilippo syndrome).

Biosimilars and Interchangeable Biosimilars: Licensure for Fewer Than All Conditions of Use for Which the Reference Product Has Been Licensed – This guidance provides recommendations to applicants seeking licensure under section 351(k) of the Public Health Service (PHS) Act of a proposed biosimilar or proposed interchangeable biosimilar for fewer than all of the reference product’s licensed conditions of use.

Specifications for Preparing and Submitting Electronic ICSRs and ICSR Attachments – This document provides current specifications for submitting individual case safety reports (ICSRs) and ICSR attachments in electronic form.

CDRH

Arthroscopy Pump Tubing Sets Intended for (510(k)) Submissions – This draft guidance document provides recommendations for 510(k) submissions for arthroscopy pump tubing sets intended for multiple patient use. These devices are designed to deliver irrigation fluid to the surgical site, such as knee, shoulder, hip, elbow, ankle, and wrist joint cavities, during arthroscopic procedures.

Peripheral Vascular Atherectomy Devices – Premarket Notification [510(k)] Submissions – This guidance document provides recommendations for 510(k) submissions for peripheral vascular atherectomy devices. The recommendations reflect current review practices and are intended to promote consistency and facilitate efficient review of peripheral vascular atherectomy submissions.

CBER

Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations – This guidance provides FDA’s current thinking on determining sameness of human gene therapy products under FDA’s orphan drug regulations for the purpose of orphan-drug designation and orphan-drug exclusivity.

Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up – FDA is providing sponsors of retroviral vector-based human gene therapy products, recommendations regarding the testing for RCR during the manufacture of retroviral vector based gene therapy products, and during follow-up monitoring of patients who have received retroviral vector-based gene therapy products.

Long Term Follow-up After Administration of Human Gene Therapy Products – FDA is providing sponsors who are developing a human gene therapy product (GT Product), recommendations regarding the design of long term follow-up studies (LTFU observations) for the collection of data on delayed adverse events following administration of a GT product.

Human Gene Therapy for Retinal Disorders – This guidance provides recommendations to sponsors developing human gene therapy (GT) products for retinal disorders affecting adult and pediatric patients.

Human Gene Therapy for Rare Diseases – This guidance provides recommendations to sponsors developing human gene therapy (GT) products intended to treat a rare disease in adult and/or pediatric patients regarding the manufacturing, preclinical, and clinical trial design issues for all phases of the clinical development program.

Human Gene Therapy for Hemophilia – This guidance provides recommendations to sponsors developing human gene therapy (GT) products for the treatment of hemophilia including clinical trial design and related development of coagulation factor VIII (hemophilia A) and IX (hemophilia B) activity assays, including how to address discrepancies in factor VIII and factor IX activity assays.

Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs) – FDA is providing sponsors of human gene therapy Investigational New Drug Applications (INDs), recommendations regarding chemistry, manufacturing, and control (CMC) information submitted in an IND.

Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components – FDA is issuing this guidance document to provide blood establishments that collect blood and blood components, with revised recommendations intended to reduce the possible risk of transmission of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) by blood and blood components.

Use of Serological Tests to Reduce the Risk of Transfusion-Transmitted Human T-Lymphotropic Virus Types I and II (HTLV-I/II) – We, FDA, are providing you, blood collection establishments, with recommendations regarding the use of serological tests to reduce the risk of transmission of human T-lymphotropic virus type I (HTLV-I) and type II (HTLV-II), collectively referred to as HTLV-I/II, by blood and blood components. These recommendations apply to the collection of Whole blood and blood components, except Source Plasma.

CVM

CVM GFI #108 Registering with CVM’s Electronic Submission System – This guidance provides general standards which should be used to register with the Center for Veterinary Medicine (CVM or the Center) Electronic Submission System (ESS).

CVM GFI #191 Changes to Approved NADAs – New NADAs vs. Category II Supplemental NADAs – This guidance is intended to assist sponsors who wish to apply for approval of changes to approved new animal drugs that require FDA to reevaluate safety and/or effectiveness data.

Draft Guidance for comment purposes only

Nonclinical Safety Evaluation of the Immunotoxic Potential of Drugs and Biologics – The purpose of this guidance is to assist sponsors in their nonclinical evaluation of the immunotoxic potential of drugs and biologics by supplementing the recommendations on nonclinical immune system assessments provided across the following guidance documents: 1] International Council for Harmonisation (ICH) guidances for industry, 2] S8 Immunotoxicity Studies for Human Pharmaceuticals (April 2006), 3] M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (January 2010), 4] S6(R1) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (May 2012) and 5] S5(R3) Detection of Toxicity to Reproduction for Human Pharmaceuticals (November 2017)

Posted in 2020, 2020 March, Drug and Device Corner, EASeNews.