Winter Break: November 2019 Regulatory Updates

Join us at weekly Journal Club meetings and connect with students, faculty and staff of Regulatory Science Program. Read the latest Regulatory Updates October 2019. For general information on Education Initiatives, click hereHighlight posted on November 29th, 2019


Digital Submission of Adverse Event Reports for Investigational New Drug Applications Reflects FDA’s Ongoing Modernization Efforts

The U.S. Food and Drug Administration (FDA) is taking steps towards requiring electronic submission of certain safety reports for products being evaluated under an investigational new drug (IND) application into the Adverse Event Reporting System (FAERS). The planned process for submissions is outlined in new draft guidance, and the FDA is also making available supporting technical specification documents. The changes will allow the FDA to access and review both pre- and post-market safety information in the same system and with the same data standard.

FDA’s Proposed Rule on Drug Importation Lands at the Office of Management and Budget

The Office of Management and Budget (OMB) is now reviewing proposed rulemaking from the U.S. Food and Drug Administration (FDA) to allow certain medicines to be imported from Canada and other countries outside the U.S. as a cost-saving measure. According to the FDA plan, the rule, once finalized, will allow Florida and other states, wholesalers or pharmacists to submit plans for demonstration projects to import medicines from Canada.

MHRA Issues Brexit Guidance on Comparator Products for Generics

The United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA) released new guidance on sourcing comparator products for bioequivalence, pharmacokinetic and therapeutic equivalence studies in the event that the UK leaves the European Union without a formal deal. In the case of a no-deal Brexit, comparator products should be sourced from the UK market. If not, the applicant should offer evidence that the comparator is representative of the reference product for the new generic medicine or other abridged marketing authorization application.

FDA Revises Draft Guidance on Implementing GDUFA II

The U.S. Food and Drug Administration (FDA) revised draft guidance from 2017 on the generic drug user fee program (GDUFA II) to explain how the new fee structure works and what types of fees will be assessed. GDUFA II eliminated prior approval supplement fees and added GDUFA program fees. In addition, it clarifies that facilities that manufacture both active pharmaceutical ingredient (APIs) and finished dosage forms (FDFs) will only incur FDFs fees. Also, a facility will no longer incur a fee if it is only referenced in pending generic drug submissions because the facility fee obligation now applies only to facilities referenced in approved generic drug submissions.

FDA Explains Levels of Impurity Found in Recalled Heartburn Drugs

Following a series of recalls for the heartburn drug Zantac and other ranitidine drugs due to a genotoxic impurity, the U.S. Food and Drug Administration (FDA) said that levels of the impurity in ranitidine drugs for heartburn and also in the chemically similar ulcer drug nizatidine are similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats. The FDA is now calling on companies to voluntarily withdraw ranitidine and nizatidine products that do not meet the agency’s N-Nitrosodimethylamine (NDMA) thresholds (96 nanograms per day or 0.32 ppm).


Quality Control
FDA Warns Chinese Drugmaker Over GMP, Data Integrity Violations

The U.S. Food and Drug Administration (FDA) sent a warning letter to Chinese drugmaker Bingbing Pharmaceutical for four violations related to record keeping, ingredient testing (such as the strength of each active ingredient), quality control (such as corrective and preventative action and risk assessment) and complaint handling. In response, Bingbing committed to discontinuing distribution of affected products until it establishes validated analytical methods for testing ingredients.

European Commission Extends Approval for GSK’s Benlysta as Add-On Therapy for Children

The European Commission approved GlaxoSmithKline’s Benlysta (belimumab) as an add-on therapy for children five years and older with active, autoantibody-suppressive lupus with a high degree of disease activity. Benlysta is currently the only medicine approved in Europe as an IV formulation and subcutaneous injection for lupus for adults. In April the U.S. Food and Drug Administration (FDA) approved Benylsta, making it the first approved treatment for pediatric patients with Lupus.

FDA Approves First Therapy to Treat Patients with Rare Blood Disorder

The U.S. Food and Drug Administration (FDA) granted approval to Reblozyl (luspatercept-aamt) for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions. The approval of Reblozyl was based on results of a clinical trial of 336 patients with beta thalassemia who required RBC transfusions, of which 112 received a placebo. Of the patients who received Reblozyl, 21% achieved at least a 33% reduction in transfusions compared to 4.5% of the patients who received a placebo. The transfusion reduction meant that the patient needed fewer transfusions over 12 consecutive weeks while taking Reblozyl.

Merck’s Ervebo, The World’s First Ebola Shot, Wins Inaugural Approval in EU

Merck’s Ervebo cleared European Union regulators, becoming the world’s first Ebola vaccine. Even though the vaccine hadn’t been approved anywhere in the world, it had been deployed in Democratic Republic of the Congo, where an ongoing outbreak has killed nearly 2,200 people. In the U.S., the Food and Drug Administration (FDA) is expected to act on the vaccine in March 2020.

Clinical Trials
International Medical Device Regulators Forum (IMDRF) Guidelines

The International Medical Device Regulators Forum (IMDRF) offered three final clinical guidelines:

  • Clinical Evaluations discusses a range of issues including data sources and documentation, appraising and analyzing clinical data and compiling a clinical evaluation report for Multi-Regional Clinical Trial.
  • Clinical Investigations should be considered when data is needed to demonstrate the safety, clinical performance or benefit/risk profile of a device that cannot be gathered from other sources, including scientific literature and nonclinical testing.
  • Clinical Evidence is defined as “clinical data and its evaluation pertaining to a medical device” and is used to support the marketing of a device and should be reviewed and updated throughout the lifecycle of a device.


FDA Warns Dollar Tree for Importing Unsafe OTC Drugs

The U.S. Food and Drug Administration (FDA) released a warning letter to the owner of Dollar Tree and Family Dollar stores for importing over-the-counter (OTC) drugs from contract manufacturers that had been banned from importing products to the U.S. Donald Ashley, director of FDA’s Office of Compliance in the Center for Drug Evaluation and Research, said: “Dollar Tree has the ultimate responsibility to ensure that it does not sell potentially unsafe drugs and other FDA-regulated products to Americans.”

AstraZeneca Enters Deal to Distribute Sun Pharma Cancer Drugs in China

Sun Pharma has entered into a licensing agreement with AstraZeneca UK to introduce certain novel ready-to-use infusion oncology products in China. The initial duration of the agreement will be 10 years from the first commercial sale of the products in China. Under the deal, Sun Pharma will be responsible for development, regulatory filings and manufacturing the products covered in the agreement while AstraZeneca will exclusively promote and distribute the products.

FDA Seeks to Pull Four NDAs After Companies Failed to Submit Annual Reports 

The U.S. Food and Drug Administration (FDA) proposed to withdraw approval of four NDAs for failure to file required annual reports. The proposal is based on the section 505(e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(e)), withdrawing approval of the applications “on the grounds that the NDA holders have failed to submit reports required under § 314.81”. The NDAs in question are Pan American Laboratories’ Maolate (chlorphenesin carbamate) Tablet, 400 milligrams; Chart Medical’s Chymodiactin (chymopapain) for Injection, 4,000 Units/vial and 10,000 Units/vial; Iomed’s Iontocaine (epinephrine and lidocaine hydrochloride (HCl)) Topical Solution, 0.01 mg/milliliter; 2%; and Vyteris’s Lidosite topical system: LidoSite Patch (lidocaine HCl and epinephrine topical iontophoretic patch) 10%/0.1% and LidoSite Controller.

FDA Approves First Targeted Therapy to Treat Patients with Painful Complication of Sickle Cell Disease

The U.S. Food and Drug Administration (FDA) approved Adakveo (crizanlizumab-tmca), a treatment to reduce the frequency of vaso-occlusive crisis – a common and painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells – for patients age 16 years and older. The Adakveo approval was based on results of a randomized clinical trial enrolling 198 patients with sickle cell disease with a history of vaso-occlusive crisis. Of patients who received Adakveo, 36% did not experience vaso-occlusive crisis during the study, and the time that patients first experienced vaso-occlusive crisis after starting treatment was delayed from 1.4 months to 4.1 months.

FDA Approves Therapy to Treat Patients with Relapsed and Refractory Mantle Cell Lymphoma

The U.S. Food and Drug Administration (FDA) granted accelerated approval to Brukinsa (zanubrutinib) capsules for the treatment of adult patients with mantle cell lymphoma who have received at least one prior therapy based on clinical trial results showing a high response rate of tumor shrinkage. Further clinical trials may be required to verify and describe the clinical benefit of Brukinsa.