Regulatory Alert

Beginning September 20th, June Raine will be the new interim Chief Executive of the MHRA. Raine will replace Ian Hudson, who will step down after 18 years with MHRA, including six years as chief executive. In addition to Hudson, John Wilkinson, director of devices at MHRA, will step down at the end of October. In June, Wilkinson discussed several initiatives that MHRA is working on, including how to deal with Brexit. While working at MHRA's predecessor Medicines Division since 1985 and at MHRA since 2003, Raine has served as MHRA's director of the Vigilance and Risk Management of Medicines (VRMM) division since 2006. Learn More

The US FDA's Center for Drug Evaluation and Research this week announced it will conduct a small pilot project to test the processing and analysis of nonclinical study data provided electronically using an updated standard, known as the SEND 3.1, from the Clinical Data Interchange Standards Consortium (CDISC). CDER is seeking a maximum of five participants for the pilot, which will evaluate the compliance of sample SEND 3.1 datasets submitted to CDER. The FDA notes that studies initiated after December 17th 2016 must be submitted with data according to data standards listed in the FDA Data Standards Catalog for NDA's, BLA's and ANDA's.  Learn More

The EMA and US FDA concur more than 90% of the time in their decisions to approve new drugs, according to a new study from EMA and FDA officials that looked at 107 applications from 2014 to 2016. In just eight of the 107 applications, FDA initially declined to approve a new drug or biologic while EMA approved it, although in all eight of those cases, FDA ended up approving that drug or biologic. And in one case the FDA approved a treatment and the EMA initially did not, but later did. However, the EMA adopted negative opinions for two drugs in 2018 that were approved by FDA in 2017, and one sickle cell drug in 2019 that was also previously approved by FDA. Learn More

The MHRA has confirmed it will accept results from batch testing performed in the United States in the event of a no-deal Brexit. MHRA published the original list of countries authorized to perform batch testing weeks before the UK was due to leave the European Union in March. At that time, MHRA said no batch testing done in the US would be accepted after Brexit because such work was outside the scope of the mutual recognition agreement between America and EU until the assessment of member state equivalence was finished. Under the new guidance, MHRA will allow most medicines that undergo batch testing in the US into the UK if there is a no-deal Brexit. Learn More

While noting that tens of thousands of drug listing records have not been updated in the past year, the US FDA this week announced that it will begin inactivating drug and manufacturing establishment listings that are not current in one month. The announcement is part of FDA's push to encourage drugmakers to ensure that their listed human drugs and any information in their drug listings, including drug establishments, are accurate. FDA Commissioner Ned Sharpless noted in a statement that although there have not been any public health consequences as a result of the outdated listings, "inaccurate information has the potential to compromise the integrity of the FDA's database..." Learn More

As the US FDA explores plans to lower the cost of pharmaceuticals with imports from Canada and elsewhere, Sen. Chuck Grassley is calling on the agency to perform more unannounced inspections of foreign facilities. Moving forward, should the administration's plans to allow certain imports be put into effect, the administration "must require more foreign inspections generally and unannounced inspections specifically, particularly compared to previous administrations," Grassley writes.  Learn More

Sarepta Therapeutics says it has been informed that an adverse event report was erroneously submitted to the U.S. health regulator regarding an ongoing study of the company's gene therapy for Duchenne muscular dystrophy (DMD). Sarepta said its investigation indicated the report was not submitted by its employee or the study's principal investigator. The drug safety monitoring board has recommended the study to continue after a review, the company said in a statement. For its part, the US FDA says that it is looking into the matter but does not have any new information at the time of this writing. Learn More

An FDA advisory panel this week voted in favor of Gilead Sciences combination drug to reduce the risk of sexually acquired HIV infection in men and transgender women who have sex with men. The treatment, Descovy, is a combination of emtricitabine and tenofovir alafenamide, and is already approved to treat chronic HIV. The recommendation is a shot in the arm for Gilead as its third best-selling HIV drug, Truvada, faces exclusivity loss in the United States, beginning 2020. Learn More

In a statement issued this week, Peter Marks, director of the US FDA's CBER, said the agency is investigating data manipulation submitted in the BLA for Novartis' gene therapy Zolgensma, a drug developed by AveXis. Alert readers will recall that AveXis was acquired by Novartis in an $8.7 billion deal in April 2018 and was approved last May. The gene therapy is considered to be the world's most expensive drug at $2.1 million. According to Marks, the FDA was informed by AveXis on June 28th that some of the nonclinical data included in the BLA for Zolgensma was manipulated. Marks also said that AveXis was aware of the data manipulation and warned that the company could be subject to civil or criminal penalties. Learn More

The EMA this week clarified the documentation and declaration requirements for peptones used in the manufacture of active substances in an update to its quality of medicines questions and answers (Q&A) guide. The Q&A covers issues brought to EMA's Joint Committee for Medicinal Products for Human Use/Committee for Medicinal Products for Veterinary Use Quality Working Party and express the harmonized position of European Economic Area competent authorities. Specifically, EMA answered two questions pertaining to peptone use during manufacturing, explaining how manufactures should document its use or notify regulators of any change related to the peptone being used. Learn More

Sunovion has announced that the US FDA has accepted its New Drug Application for dasotraline, a novel dopamine and norepinephrine reuptake inhibitor (DNRI), for the treatment of patients with moderate-to-severe binge eating disorder (BED). The application is based on results from the SEP360-321 study, announced in the latter part of 2018, which showed a statistically-significant decrease in number of binge days per week, at the higher dose. The US Food and Drug Administration earlier rejected an application from the firm to market the drug for the treatment of ADHD. The action date by the FDA under the Prescription Drug User Fee Act is May 14, 2020. Learn More

Last November, officials from the EMA and US FDA met with industry representatives in London to discuss the various quality challenges that arise when the development of investigational products is accelerated. EMA's launch of its priority medicines (PRIME) scheme and FDA's breakthrough therapy designation have enabled companies to speed certain treatments to market, although there have been difficulties in identifying possible scientific and regulatory approaches to facilitate the type of robust quality data packages necessary to ensure that patient safety and product quality and efficacy are not compromised, according to a report released Wednesday on the workshop. Learn More

The US FDA has sent a Form 483 to API manufacturer Dr. Reddy's Bollaram, India site, raising concerns about the company's failure to respond to customer complaints about out-of-specification (OOS) results. According to the FDA, Dr. Reddy's received three complaints related to microbiological failures that did not meet the customer specifications for certain API lots, and Dr. Reddy's testing confirmed the OOS microbiological failures but did not determine a root cause. The site also failed to evaluate whether the finished APIs and retention samples stored in areas where relative humidity is not controlled or monitored were affected by extreme fluctuations in humidity, the FDA says. Learn More

The US FDA has withdrawn a draft guidance originally published back in December 2016 on submitting manufacturing establishment information electronically. Many of the comments on the draft guidance, which was intended to implement section 745A of the Federal Food, Drug, and Cosmetic Act, noted that FDA's approach was not aligned with international work on electronically transmitting registration information. The FDA says that it will publicly announce if any new draft guidance on the submission of manufacturing establishment information is issued. Learn More

US FDA's CDER Director Janet Woodcock said this week that while the NIH has been instrumental to drug discovery and development, she does not think NIH or academics should be in the business of developing new pharmaceuticals. The comments came as part of the first day of a two-day meeting at the National Academies of Sciences, Engineering and Medicine in Washington, DC, on the role of NIH in drug development innovation and the impact on patient access. While noting that NIH research "has served biomedicine very well," Woodcock also explained how NIH's work is heavily geared toward the early stages of development, with a relatively small amount of expertise on bringing drugs to market. Learn More

The World Health Organization (WHO) has revised its guidance on quality system requirements for national good manufacturing practice (GMP) inspectorates to align with international standards and the latest quality management system (QMS) principles and to expand the document's scope. The guidance outlines what a QMS is, what it should do for an inspectorate and how it should help senior management better achieve their targets and quality objectives. "Senior management's commitment and active participation is essential to ensure implementation of the QMS and to support of staff within the inspectorate," the document says. Learn More

The US FDA has approved the first generic versions of Pfizer's blockbuster pain drug Lyrica (pregabalin). The approvals were granted to Alembic Pharmaceuticals, Alkem Laboratories, Amneal Pharmaceuticals, Dr. Reddy's Laboratories, InvaGen Pharmaceuticals, MSN Labs, Rising Pharmaceuticals, Sciegen Pharmaceuticals and Teva Pharmaceuticals. On the market since 2004, Lyrica was singled out by the generic industry's Association of Accessible Medicines (AAM) as an example of patent abuse. AAM said Pfizer filed 118 patent applications and had 68 patents issued, with the drug's price rising more than 163% since 2012. Pfizer pulled in about $5 billion in worldwide revenue from Lyrica in 2018. Learn More

The EU ombudsman has concluded that it believes that the European Medicines Agency (EMA) should not allow the same experts to provide scientific advice to medicine developers prior to an application and evaluate the same medicine, claiming such overlap runs the risk of damaging impartiality or creating the perception of bias. In response to the comments, following a two-year inquiry into EMA's interactions with drug developers, the EMA said Friday: "Early interactions with medicine developers and provision of scientific advice are well-established processes with demonstrated added value in medicines regulation, and contribute positively to public health by helping to bring new, safe and effective medicines to patients..." Learn More


RAPS has just published the updated, 11th edition of Fundamentals of US Regulatory Affairs, the most extensive regulatory affairs textbook available, covering US regulations for pharmaceuticals, medical devices, biologics and related healthcare products. First published 20 years ago, the book has become an important reference for regulatory professionals and others working with healthcare products regulated by the US Food and Drug Administration (FDA) and other US agencies. This edition includes 39 chapters by 54 expert authors, as well as an extensive matrix of regulations across product lines that has been completely revamped. Learn More

The U.S. FDA has warned Strides Pharma over good manufacturing practice (GMP) violations at its Puducherry facility that included uncontrolled shredding of documents and inadequate investigations into out-of-specification (OOS) test results. According to the warning letter, investigators found rampant shredding of uncontrolled documents, including "multiple bags of uncontrolled CGMP documents with color coding indicating they were from drug production, quality and laboratory operations" that were awaiting shredding as well as a binder of batch records that had been tossed in a barrel outdoors. Learn More

Just over two months ago, the U.S. FDA released draft guidance explaining to drugmakers what constitutes real-world data (RWD) and real-world evidence (RWE) and how to submit such data to the agency. But biopharma companies Gilead and Novartis are calling on the FDA to expand on its sources of RWD and the scope of RWE, even as some physicians and experts have cautioned against using RWD and RWE for regulatory decisions or as a replacement for clinical trials. Gilead, for instance, says FDA should include lab data, data from expanded access protocols and data derived from the delivery of health care as sources of RWD. Learn More

The U.S. FDA and Europe's EMA have announced that they have now fully implemented a plan that will allow member state regulators and the FDA to mutually rely on each other's good manufacturing practice (GMP) inspections of drug facilities. In addition to helping reduce redundancies in manufacturing inspections, the implementation of the Mutual Recognition Agreement (MRA) means that biopharma companies can stop import testing for products manufactured in the US. Learn More

The U.S. FDA this week released a revised draft guidance to help keep sponsors informed on the data and model requirements for population pharmacokinetics (PK) analyses submitted as part of new drug applications and biologic license applications. Since the original population PK guidance was published in 1999, the FDA says the number of applications relevant for population PK analysis has increased and, "The sophistication and reliability of population PK analysis methods have improved." Specifically, the revised, 23-page draft guidance includes a description of the types of scientific and regulatory questions appropriate for population PK analysis and outlines FDA's recommendations for data analysis and modeling. Learn More

The U.S. FDA  this week released a draft guidance for public consultation providing recommendations for drugmakers on using the agency's inactive ingredient database (IID) during drug development. The IID is an online repository of information about excipients used in FDA-approved products and serves as a replacement for the inactive ingredient guides the agency began disseminating in the late 1980s. Within the database, the FDA provides information including the various routes of administration, dosage form and maximum potency per unit dose for each inactive ingredient, as well as the chemical abstracts service (CAS) number and unique ingredient identifier (UNII) for each listing. Learn More

The U.S. FDA says it is withdrawing the approval of 31 abbreviated new drug applications (ANDAs) held by Apotex after manufacturing deficiencies were found at two of the company's plants. The FDA action follows Apotex's initial request to withdraw the ANDAs in January 2018. The FDA says it became aware of concerns involving material manufactured at the two Apotex facilities, at least one of which was named in each of the pulled ANDAs. Valsartan, losartan, azithromycin and Viagra generics are among the ANDAs listed. The two facilities involved, according to the FDA, were India-based Apotex Research Private Ltd. and Apotex Pharmachem India Private Ltd. Learn More

Biocon has made public in a filing with the BSE that it has received a Form 483 from the U.S. FDA. In the 483 inspectors from the regulatory agency, which were on-site from June 24thto July 5th, noted no fewer than 12 observations at three of the biopharma company's units in Malaysia. However, as of this writing, details of these observations have not been made public. The units noted in the 483 are insulin glargine drug substance, drug product and device assembly facilities. Learn More

In its warning letter to Aurobindo, the U.S. FDA cites the company for good manufacturing practice (GMP) violations at one of the company's facilities in Srikakulam District, Andhra Pradesh following a six-day inspection in February. While all mention of specific products, APIs and impurities have been redacted from the warning letter, it appears that the warning letter is related to nitrosamine impurities in angiotensin II receptor blockers (ARBs) that have prompted FDA to recall hundreds of lots of the drugs from multiple manufacturers. Shortly after the inspection, Aurobindo expanded its voluntary recall of ARB drugs to include 38 lots of Valsartan tablets due to the presence of an N-nitrosodiethylamine (NDEA) impurity. Learn More

The U.S. FDA is pushing back against assertions made inScience that a decline in the overall number of warning letters during the Trump administration is the result of a politically motivated, deregulatory agenda. The article states that FDA's "compliance and enforcement actions have plummeted since President Donald Trump took office." It reports that the number of warning letters sent by FDA fell by a third from Trump's inauguration through May 2019 compared with the most recent equivalent period in the Obama administration. In a statement provided to BioCentury, the FDA said the presentation of data in Science's story "does not accurately reflect FDA's overarching work to protect the public health." Learn More

The U.S. FDA's Center for Biologics Evaluation and Research (CBER) has updated its list of 2019 guidance and added a new draft on interpreting "sameness" of gene therapy products under the orphan drug regulations. The new draft on sameness, under the category of Tissues and Advanced Therapies, is expected in addition to the finalization of six guidance documents on gene therapies released last July, final guidance from February on expedited programs for regenerative medicines and the evaluation of devices with regenerative medicines, and final guidance from March on CBER's use of standards in regulatory submissions. Learn More

The EMA and European Commission have announced that Germany has joined the mutual recognition agreement for good manufacturing practice (GMP) inspections between the US FDA and EU member states. According to the two agencies, FDA confirmed that Germany's GMP inspections are "at a level equivalent to that of the US." The announcement comes just weeks after Luxembourg and the Netherlands were added to the agreement and two months after Bulgaria and Cyprus joined the pact. With the addition of Germany, the agreement now covers inspections carried out by regulators from all EU member states except Slovakia. Learn More

The US FDA this week proposed a new rule to allow certain biologics, originally approved under a new drug application (NDA), to continue relying on drug master files (DMFs) for certain information even after the NDA is deemed to be a license for a biological product on March 23rd, 2020. This so-called "deemed to be a license" transition next year, the details of which were explained in full last December, will mean that moving forward, follow-on applicants will not be able to rely upon these NDAs and win approval as generics but will have to win approval as biosimilars. Learn More

Akorn has received a warning letter from the U.S. FDA regarding its manufacturing facility in New Jersey, the latest in a string of setbacks for the generic drugmaker. The FDA warning is the second that Akorn has received this year and follows an inspection of the company's Somerset, New Jersey-based plant in July and August 2018. In January, the agency issued a warning letter for Akorn's other manufacturing plant in Decatur, Illinois after the drugmaker did not resolve previously highlighted violations such as failure to follow procedures to prevent contamination of drugs produced at the plant. Learn More

The U.S. FDA has issued a Form 483 to the Sun Pharma site in Halol, India. In it the FDA cites four observations, including one taking the company to task for needing seven years to gain approval for a design plan change associated with its equipment. Alert readers will recall that this practice of cite, fix and repeat has been ongoing for roughly five years with the initial reporting taking place back in 2014. As was the case in a 2015 citation, this latest Form 483 includes observations related to new concerns about data integrity. Learn More

Drugmakers and industry groups are calling for changes to the U.S. FDA's draft guidance on bioavailability (BA) studies submitted as part of an investigational new drug (IND) application or new drug application (NDA). The 27-page draft guidance was released for comment in February and when finalized will replace the agency's 2014 draft guidance Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs - General Considerations. While the comments from drugmakers are largely supportive of the draft guidance, among them are calls for specific changes and additional clarity from FDA. Learn More

The NHS has announced that it is preparing to fast-track 'game changing' cancer drugs that target genetic mutations, targeting tumours according to their genetic make-up rather than where they originate in the body. The revolutionary treatments - known as 'tumour agnostic' drugs - can be used against a wide range of cancers and could offer hope to patients with rare forms of the disease that may previously have been untreatable. Existing cancer drugs need to be approved by NICE for each individual type of cancer they treat such as breast or colon cancer. However, when approved, these cutting edge new tumour agnostic drugs would be available to treat all types of tumour without individual approval. Learn More

The Health Committee of the U.S. Senate plans to vote on a wide-ranging bill with implications for the FDA next week and Janet Woodcock, director of CDER laid out the FDA's views on several proposals at a Senate Aging Committee hearing this week. The bipartisan bill from the committee includes a new section that would give the FDA new authorities to address outdated generic drug labeling because there is no longer a reference product on the market. During her testimony this week, Woodcock offered two proposals to tweak 180-day forfeiture provisions and modify when to start the 180-day clock. Learn More

Roche's push into personalized cancer medicines hit a milestone this week with Japanese approval of a new drug, Rozlytrek, that targets patients who must be identified via genetic profiling. Japan is the first country to give its blessing to Rozlytrek, also known as entrectinib, targeting people with NTRK fusion-positive solid tumors, across 10 different tumor types including breast, colorectal, neuroendocrine, lung and pancreatic cancers. While positive news for Roche, Bayer's Vitrakvi has already won U.S. backing for solid tumors that test positive for NTRK genes. Roche has yet to get U.S. and European approvals.  Learn More

The lengthy preclinical and clinical development necessary to bring a biologic to market has often been cited as one of the central reasons why biologics deserve 12 years of market exclusivity, or about five years more exclusivity than their small molecule counterparts. But a new study published this week in Nature Biotechnology shows that the development time of a new biologic is generally about the same as the development time of a small molecule drug. The study found that of the 275 new drugs approved by the US FDA's CDER between 2007 and 2016, median total development times-from first patent filing to FDA approval-were about 12 years for both types of products. Learn More

Peter Marks, head of the FDA's Center for Biologics Evaluation and Research, said his top concern for gene therapy's future is manufacturing, and how companies will scale up production to match scientific advances. "When the cost of goods are very high, they help justify when people charge astronomical prices," Marks said in a recent interview with BioPharma Dive. "If we can help see cost of goods and ability to manufacture reproducibly improve, I think that'll be a big thing. That's something we're working on but something that keeps me up at night." The FDA aims to finalize six draft guidance documents by the end of 2019 related to gene therapy, including some that will address specific manufacturing issues, Marks said. Learn More

Catalyst has filed a lawsuit against the U.S. FDA claiming the regulator's recent approval of a new drug is illegal and should be thrown out. The lawsuit is the latest chapter in a bizarre competition between Catalyst Pharmaceuticals and Jacobus Pharmaceutical, two small biotechs that both have FDA-approved drugs for a rare disease called Lambert-Eaton Myasthenic Syndrome, or LEMS. At the core of Catalysts lawsuit are two claims, the first being that the labeling of the drug from Jacobus is illegal. The second claim being that the the FDA violated the orphan drug exclusivity period by approving a competitor after just a few months had passed. Learn More

Genentech's blood cancer drug Polivy earned an accelerated approval from the U.S. FDA due to the complete response rate shown during clinical trials. This marks the fifth blood cancer drug approved for Genentech. Polivy, which was also granted Breakthrough Therapy designation, uses ADC technology developed by Seattle Genetics and licensed to Genentech. The FDA's Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition. Polivy was approved two months ahead of its August PDUFA date. However, the FDA noted that further clinical trials are required. Learn More

The US FDA has warned Taipei, Taiwan-based drugmaker Vida International over GMP violations following an inspection of the company's Taoyuan City facility. As a result of the observations made during the inspection, the FDA placed Vida on import alert in March. In the warning letter, the FDA cites Vida for failing to conduct necessary batch testing for one of its products before release. The FDA also says the firm failed to test incoming raw materials, including active ingredients, to determine their identity and whether they conform to written specifications before use. According to the FDA, Vida also prepared an inaccurate batch record for a lot of one of its drugs. Learn More

The U.S. FDA will host a 2-day public workshop on leveraging randomized clinical trials to generate real-world evidence (RWE) for regulatory decisions. The Duke-Margolis Health Policy Center will convene the workshop under a cooperative agreement with FDA to explore how randomized clinical trial designs, including those that incorporate pragmatic design elements, can use real-world data (RWD) to generate RWE in clinical settings. Considerations noted in the discussions will inform the potential usefulness of RWE to support regulatory decision-making. The workshop is part of FDA's ongoing effort to implement the RWE framework unveiled by CDER. Learn More

A draft bill in the U.S. Congress that would overturn a landmark U.S. Supreme Court decision that barred the patenting of human genes and ease other restrictions on patenting software and biomedical inventions is drawing fierce criticism from some scientific societies and patient advocates. This week, the ACLU along with more than 100 other signatories from research institutes and advocacy groups, released a letter to lawmakers arguing the changes would stifle medical research and hinder patients' access to diagnostic tests. The bill aims to address the complaint that recent Supreme Court decisions have created confusing and overly stringent patent eligibility rules. Learn More

The U.S. FDA is "open for business" in considering real-world evidence to clear expanded uses of new cancer drugs, acting agency head Ned Sharpless said this week, but warned industry against relying too heavily on alternative sources of data. Speaking at the BIO conference in Philadelphia, the former National Cancer Institute director acknowledged the rising cost and complexity of clinical trials, and indicated the FDA is aware of how difficult enrolling studies of rare disease subtypes can be. The FDA's willingness to consider alternate sources of data isn't new. Learn More

The UK's Medicines and Health care products Regulatory Agency (MHRA) this week opened a three-month public consultation on its plans to apply analytical quality by design (AQbD) principles to its pharmacopoeial standards. The consultation follows the exploration of AQbD in the International Council for Harmonization's (ICH) recently released concept paper ICH Q14: Analytical Procedure Development and Revision of Q2(R1) Analytical Validation last November. Ahead of the consultation, MHRA conducted a case study that focused on how AQbD principles could be applied to the development of a pharmacopoeial assay procedure for atorvastatin tablets. Learn More

Drugmakers and industry groups are calling for changes to the U.S. FDA's recently released draft guidance, Quality Considerations for Continuous Manufacturing. The 27-page draft guidance was released for comment in February and is part of FDA's effort to encourage the adoption of continuous manufacturing, which the agency believes can improve consistency and reduce the risk of drug shortages. While there is great interest in continuous manufacturing at the FDA, drugmakers have been slow to transition to continuous manufacturing processes. To date only a handful of drugs are manufactured using continuous manufacturing. Learn More

Amarin will get a regulatory decision sooner than expected on an important label expansion for its fish oil-based pill, Vascepa. The company announced this week that the U.S. FDA will decide by September 28th on approving the drug for treating heart risk. The sped-up timeline comes courtesy of a priority review granted by the FDA, setting up a potential approval in late 2019 rather than early 2020. The biotech is still waiting, however, on further word from the agency on whether its application will require an advisory committee review, a critical step in the process that could bring heightened scrutiny on Vascepa.  Learn More

Many people don't believe in evolution. Only one-third of Americans say it occurs through processes like natural selection and no involvement by God. But besides religion, there are several reasons why some reject the fact life evolves, such as not seeing adaptation happening with your own eyes. Scientists have now provided further proof of evolution in action with a video of bacteria evolving resistance to an antibiotic drug. The short film shows the results of a study by microbiologists at the Université Claude Bernard Lyon 1 in France, which reveals how rapidly Escherichia coli can acquire genes that confer the ability to resist the effects of tetracycline. Learn More

The U.S. FDA has approved a new way for cancer drugs to be approved more quickly. The approval for the breast cancer treatment Piqray in combination with fulvestrant and alongside a companion diagnostic - came more than three months ahead of its PDUFA deadline and a little more than five months after it was submitted thanks to FDA's Real-Time Oncology Review (RTOR) pilot and Assessment Aid (AAid) programs. Up until now, the FDA had only approved supplemental new drug applications (sNDAs) and supplemental biologics license applications (sBLAS) under the RTOR pilot. The FDA had never even publicly said that it was expanding the RTOR pilot to NDAs until announcing that Piqray's NDA had been approved. Learn More

The U.S. FDA has approved Zolgensma, the first gene therapy for a type of spinal muscular atrophy. The disease is caused by a defect in a gene that makes SMN, a protein necessary for the survival of motor neurons. Zolgensma uses a re-engineered virus to deliver a functional copy of the defective gene so that SMN protein can be produced. Launching Zolgensma, which at $2.1 million will be the world's most expensive drug, promises to be a big test for Novartis. Alert readers will recall that the biopharma giant spent $8.7 billion to acquire AveXis last spring based in large part on the potential of Zolgensma. Learn More

Scott Gottlieb, who recently stepped down as the head of the U.S. FDA, has rejoined venture capital firm New Enterprise Associates as a full-time investing partner. Gottlieb had been a venture partner with NEA for 10 years before President Trump tapped him to lead the FDA. He's expected to lead investments in life sciences startups and take board seats on behalf of the firm. Gottlieb also recently rejoined the American Enterprise Institute as a resident scholar, and he plans to maintain that position. Alert readers will recall that Mr. Gottlieb resigned abruptly from his leadership position at the FDA just a few months ago. Learn More

A week after finalizing guidance on developing interchangeable biosimilars, the U.S. FDA has drafted guidance for biosimilar developers on the use of comparative analytical studies that can be used to assess whether a proposed product is biosimilar to a reference product. The 28-page draft guidance revises a final guidance from 2015 on quality considerations for demonstrating biosimilarity and serves as a replacement for a 2017 draft guidance on statistical approaches to evaluating biosimilarity that was withdrawn last year after industry questions. Learn More

In line with efforts to assess the impact and sources of the sartan safety scandal, India-based Torrent Pharmaceuticals and Cadila Healthcare separately drew lengthy U.S. FDA Form 483s over, among other issues, failures to thoroughly review unexplained discrepancies. The manufacturing site inspection at Torrent Pharmaceuticals FDA investigators conducted over the course of about a week last month resulted in four inspectional citations, with the 483 largely focusing on that firm's investigations into out-of-specification (OOS) results. The FDA's visit to Cadila Healthcare's site from late April to early May revealed 14 observations of manufacturing deficiencies. Learn More

The U.S. FDA and biopharma industry experts gathered this week in Silver Spring, MD, to discuss how the FDA assesses the benefits and risks of new drugs from the preclinical to post market phases. The meeting was conducted as part of FDA preparations in drafting new guidance in FY 2020 on the benefit-risk assessment of new drugs and biologics. Theresa Mullin, associate director for strategic initiatives at the FDA's CDER, explained how the guidance will be an "articulation of our decision-making context" for benefit-risk assessments "throughout the lifecycle of a medical product." She said the guidance will provide information to help companies communicate and submit data to FDA. Learn More

The U.S. FDA this week released its latest batch of product-specific guidance documents to support the development of generic drugs, with 25 new and nine revised draft guidances. HIV antiretrovirals and antibiotics topped the list of new draft guidances with a total of five, followed by drug products containing active ingredients to treat ophthalmic ailments and cancers. The product-specific guidance is part of the agency's push to spur generic competition. Each guidance provides product-specific recommendations to aid manufacturers in the design of bioequivalence studies in support of abbreviated new drug applications. Learn More

Back in the 1970s and 1980s, the U.S. FDA made clear that at least two adequate and well-controlled studies were necessary to establish a new drug's effectiveness, except in only the rarest of circumstances. Then in 1997, the FDA Modernization Act was passed, and Congress clarified that FDA may consider "data from one adequate and well-controlled clinical investigation and confirmatory evidence" to approve a new drug. However, recently IQVIA released a report finding that 25 of 59 (42%) novel drugs approved in 2018 were approved on the basis of only one trial. And one out of eight approvals relied only on Phase 1 or 2 trials, with no Phase 3 trials. Learn More

In an exclusive interview with NBC News Massoud Motamed, a former inspector with the U.S. FDA, says the regulatory agency struggles to police overseas drug manufacturers who may hide problems in their production lines. Case in point, he cites the valsartan recall and the fact that more than a year before the notices went out, he had tried to sound the alarm on what he flagged as potential systemic problems at two facilities in China and India that produce the active ingredients in generic valsartan and other blood pressure medications. However, the FDA ultimately overruled his recommendation. Learn More

The U.S. FDA has finalized a long-awaited guidance spelling out how biosimilars can achieve an interchangeable status, which means they may be substituted for the reference biologic without a prescriber intervening. No interchangeable biosimilars have been approved in the US yet, and the number of companies seeking approval for an interchangeable has remained at just one, with Boehringer Ingelheim publicly disclosing that it's begun an interchangeability study for its adalimumab biosimilar. But former FDA Commissioner Scott Gottlieb said last month that the final interchangeability guidance will provide sponsors with more certainty on how to develop interchangeable products. Learn More

The U.S. House this week unanimously passed two bills that would increase the utility of the U.S. FDA Orange Book for generic drugmakers and Purple Book for biosimilar developers. The passage of HR 1503, the "Orange Book Transparency Act of 2019," and the passage of HR1520, the "Purple Book Continuity Act of 2019" enables the bills to now proceed to the U.S. Senate. The Orange Book is used as a resource by both brand name and generic drug companies to obtain timely information on medicines. While the more recently created Purple Book includes information on when biosimilars and interchangeable biosimilars were licensed and whether the FDA evaluated the product for reference product exclusivity. Learn More

Acacia Pharma has received a Complete Response Letter from the U.S. FDA regarding its New Drug Application (NDA) for Barhemsys. The letter marks the second for this particular submission and identified continuing deficiencies at the contract manufacturer of amisulpride, the active pharmaceutical ingredient used in Barhemsys. The same issue was raised initially in October 2018 when the company received their first Complete Response Letter from the FDA. Despite the rejection, no concerns were raised by the FDA on any of the clinical or non-clinical data in the NDA and no further studies or data analyses will be required for approval. Learn More

Synthetic CBD from Zynerba Pharma has earned fast track status from the U.S. FDA for its Zygel transdermal CBD lotion to treat symptoms associated with the genetic condition Fragile X. There currently are no drugs to treat the symptoms of Fragile X syndrome, which include developmental problems from learning disabilities to cognitive impairment. Zynerba is in the final stages of a clinical trial of Zygel and hopes to have it on the market by late 2020. The FDA already had granted the gel orphan-drug status, which gives Zynerba a seven-year period to market the drug exclusively in the U.S. as well as granting the company tax credits for clinical research expenses. Learn More

As part of Novartis' new drug application for its recently approved multiple sclerosis drug Mayzent, the U.S. FDA questioned the drugmaker's data practices during a clinical inspection. "During the sponsor inspection, significant data reliability concerns were identified," the FDA said, citing the company with an Official Action Indicated (OAI). The FDA explained how in one study protocol, blinding "was not adequately maintained as specified in the protocol throughout the course of the trial at 62 (21%) of 294 sites. Study personnel were given inappropriate access to the first dose and main databases affecting 285 (17%) out of 1651 total study subjects." Learn More

Manufacturing issues have tripped up two experimental drugs, resulting in the U.S. FDA handing their respective makers Complete Response Letters this week. Heron Therapeutics disclosed this week that the regulator had rejected HTX-011, a non-opioid painkiller for postoperative pain. According to Heron, the FDA wants additional information on chemistry, manufacturing and controls to proceed, along with more non-clinical data. Nabriva Therapeutics, meanwhile, said this week that its drug for complicated urinary tract infections was turned down by the agency. Learn More

A modernization of the way the U.S. FDA reviews NDAs and BLAs will be instituted over the next two years, CDER Director Janet Woodcock told attendees of the Food and Drug Law Institute's annual conference this week. Six active initiatives related to this modernization are ongoing at CDER, including initiatives focused on integrated reviews for marketing applications, IND application review management, post-market safety management, assessing talent, reorganization management and administrative operations. The new integrated reviews, which are currently being phased in, will be used among all CDER divisions beginning in 2020. Learn More

The Seoul Central District Prosecutors' Office has arrested an executive and another employee at Samsung Bioepis, the biosimilar division of Samsung Group, on suspicion of destroying evidence to mask an alleged accounting fraud. The move comes after South Korea's Securities and Future Commission ruled in November that Samsung Biologic violated accounting rules by intentionally inflating the value of Samsung Bioepis and the two employees have said they destroyed evidence on their own but prosecutors are reviewing whether there was an order from management or whether the group's strategic office orchestrated the process. Learn More

The move comes just two months after Bayer, and darolutamide-partner Orion, revealed positive late-stage data for the non-steroidal androgen receptor inhibitor. Known as ARAMIS, the phase 3 program evaluated the safety and efficacy of darolutamide in patients with nmCRPC who are currently being treated with androgen deprivation therapy (ADT) and are at high risk of their cancer metastasising. The drug reduced the risk of this happening, along with risk of death, by 59%, achieving a median metastasis free survival of 40.4 months, versus 18.4 months in the placebo arm. There was also an increase in overall survival of 29% versus placebo. Learn More

Samsung Bioepis has confirmed that the company's biosimilar to Amgen's Enbrel, to be known as Eticovo, has been approved by the US FDA. This is the second US approval of an Enbrel biosimilar, with the first coming in August 2016 for Sandoz's Erelzi, although Erelzi has yet to launch. In the EU, however, both Sandoz and Biogen/Samsung have successfully launched their Enbrel biosimilars. Meanwhile, Amgen and Sandoz are continuing to battle in court over when Erelzi can launch in the US, with analysts predicting anywhere from 2021 to 2029. Learn More

Raising concerns over data collection and quality control, the US FDA has reportedly issued a 10-page Form 483 to Sun Pharma for its Dadra plant. As per published reports, the regulator found deficiencies relating to medicine quality, data collection, maintenance as well as quality control resulting in 11 observations. The observations include lack of written procedures for production and process controls designed to assure that drug products have identity, strength, quality, and purity they are represented to possess. Reportedly, FDA inspectors also made observations specific to shortcomings in data integrity specific to lab records. Learn More

Eli Lilly this week said it is working to pull its cancer medicine Lartruvo from global markets, about three months after the pharma disclosed the drug failed a Phase 3 study. The U.S. FDA conditionally approved Lartruvo in October 2016 as a frontline treatment for certain types of soft tissue sarcoma. However, Lilly's confirmatory trial failed, leading the biopharma to suspend promotion in January. Lilly has set up a program to allow patients already on the drug to carry on with treatment - even after withdrawal - if they've been informed of the study results and risks of continuing therapy. Learn More

AbbVie has announced that the U.S. FDA has approved its Skyrizi drug as a treatment for plaque psoriasis at a time when its blockbuster psoriasis drug, Humira, faces patent pressures. The approval of Skyrizi, an injectable drug, is based on results from AbbVie's global Phase 3 psoriasis program, which assessed the safety and efficacy of the drug in adults with moderate to severe plaque psoriasis. AbbVie said it expects Skyrizi to be available in the United States in early May. Skyrizi, which won regulatory approval in Canada and Japan earlier this year, is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization of the drug. Learn More

The US FDA this week announced it will hold a public meeting on May 16th, 2019 to evaluate ways to apply FDA's benefit-risk framework throughout the human drug lifecycle and best approaches to communicating FDA's benefit-risk assessment. After gathering industry, patient, researcher and other stakeholders' input, the agency said it will draft a guidance document in FY 2020 on benefit-risk assessment for new drugs and biologics. The meeting will be convened by Duke University's Robert J. Margolis Center for Health Policy (Duke-Margolis). The meeting will also discuss how relevant patient experience data may inform the benefit-risk assessments. Learn More

Novartis, which this week announced positive interim trial results for its experimental gene therapy Zolgensma for spinal muscular atrophy, has made public that an investigation is underway into whether a second trial death could be related to the treatment. Novartis has filed for U.S. FDA approval of the gene therapy and a decision is expected within weeks. The FDA submission was based on findings from a trial of 15 babies treated with Zolgensma. During which one patient died from respiratory failure, which was deemed by the investigator and an independent monitor to be unrelated to the gene therapy. Learn More

With more than two dozen companies developing bispecific antibodies, the next frontier of cancer therapy may well involve these genetically engineered, recombinant antibodies, which is why the US FDA this week released a new draft guidance to help developers of these products. Currently, only one bispecific antibody is marketed in the US: Amgen's Blincyto, which brought in $230 million in worldwide sales in 2018, up 31% from 2017. But others are coming, and recent safety concerns, such as a partial clinical hold initiated by FDA after Xencor reported two patient deaths from a Phase 1 study of a bispecific antibody in February, may have triggered the need for more FDA guidance. Learn More

In his first "all hands" speech at the US FDA's White Oak campus this week, Acting Commissioner Ned Sharpless explained how he will pick up where Scott Gottlieb left off, and how next week, the FDA will launch a new and improved website. "The work done over the past year to get us here will provide a more accessible, user-friendly site for the public to learn about recalls, get product safety alerts, and other important information about the work we do to protect the public. This will be important," Sharpless, the former director of the National Cancer Institute (NCI), said. Learn More

Novartis has announced that the US FDA has accepted its BLA for ophthalmology candidate, brolucizumab, for the treatment of wet age-related macular degeneration (AMD). However, competition is stiff in the wet AMD space from the likes of Regeneron's Eylea and Roche's Lucentis, among others. With that in mind, Novartis has optioned a priority review voucher so as to expedite a review by the US FDA. According to the biopharma giant, if approved, brolucizumab could be brought to market in the U.S. by the end of this year. The filing was based on encouraging phase III data from HAWK and HARRIER trials. Learn More

Clovis Oncology has announced that it is halting a mid-stage trial testing its lead drug in bladder cancer patients, sending shares down 12 percent. The company says its decision to discontinue the trial was based on recommendations of an independent committee, which suggested that the treatment may not provide a meaningful benefit to patients. However, Clovis said it would continue to test the drug, Rubraca, in combination with other treatments for bladder cancer. Rubraca belongs to a new class of cancer drugs called PARP-inhibitors, which work by blocking enzymes involved in repairing damaged DNA of cancer cells, thereby helping to kill them. Learn More

In the U.S. and Europe, drug regulators approve new drugs based on whether the benefits of the new product outweigh the risks. But neither of the regulators consider if such new drugs are superior to drugs currently marketed. Now, three senior officials at the European Medicines Agency (EMA) are explaining how an added therapeutic benefit criterion or head-to-head comparisons could help to drive more innovative therapies. "The aim of these proposals is to contain the rising cost of what is often perceived as the nebulous concept of 'innovation,'" EMA's senior medical officer, Hans-Georg Eichler, chair of EMA's human medicines committee Harald Enzmann and EMA's Executive Director Guido Rasi write in a commentary published in Nature Reviews Drug Discovery this week. Learn More

U.S. FDA Commissioner Ned Sharpless "should assess the effectiveness of the foreign offices' contributions," a Government Accountability Office report has recommended. GAO's report called attention this week to priority recommendations on the FDA's parent agency, the U.S. Department of Health and Human Services. As the agency continues testing performance metrics and evaluating the strategic workplan of its Office of International Programs, the FDA's acting commissioner was directed to systematically track data and measure whether OIP's activities are specifically targeting drug safety-related issues, such as inspections, import alerts and warning letters. Learn More

The U.S. FDA this week refused to fully review the marketing application for Zogenix's treatment for seizures associated with Dravet syndrome, a rare form of childhood epilepsy. Zogenix's drug, to be branded as Fintepla, uses a low-dose, liquid solution of fenfluramine, which was used in an obesity drug combination that was withdrawn from the market due to evidence of heart valve damage. The FDA, after a preliminary review, cited a lack of certain non-clinical studies to assess the chronic administration of fenfluramine and due to an incorrect dataset. Learn More

The U.S. FDA this week finalized a guidance from 2016 detailing the factors that the agency uses to determine whether a risk evaluation and mitigation strategy (REMS) is necessary for a drug. As defined by the guidance, a REMS is a required risk management plan that can include one or more elements to ensure that the benefits of a drug outweigh its risks. Such elements can include a medication guide, a package insert or a communication plan. And though the use of a REMS is decided on a case-by-case basis, the 10-page guidance explains how the Amendments Act requires the FDA to consider six factors in deciding whether to require a REMS. Learn More

FDA Commissioner Scott Gottlieb and Center for Biologics Evaluation Research (CBER) Director Peter Marks this week warned that the agency will step up its enforcement efforts against companies illegally marketing stem cell therapies. Gottlieb and Marks also said the agency will look into new ways to "delineate an efficient development path" for low-risk stem cell therapies being developed by firms that have filed investigational new drug applications (INDs) and are engaging in the regulatory process " in a responsible manner." While Gottlieb and Marks said that FDA will continue inspecting stem cell suppliers and clinics to ensure compliance, they emphasized that FDA "will not shy away from taking further steps when sees bad actors taking advantage of patients." Learn More

With the overall goal of reducing the number of complete response letters (CRLs) between tentative approval and final approval for abbreviated new drug applications (ANDAs), Teva and Pfizer are calling on the U.S. FDA to elaborate further on some specifics in a draft guidance on tentatively approved ANDAs. The 12-page draft guidance from last January provides recommendations on the timing and content of amendments to tentatively approved ANDAs to help companies reach final approval on the earliest date by which the ANDA may lawfully be approved. Learn More

Due to significant violations of CGMP regulations, the U.S. FDA sent warning letters to four manufacturers of homeopathic medicines in Florida, North Carolina, Oregon and India. The FDA highlighted how one company-Ashville, NC-based King Bio-"continues to concern us because of the low quality of their operation and the threat their products pose to consumers," FDA Commissioner Scott Gottlieb said. Another company, Oakland Park, FL-based Red Mountain, manufactures finished homeopathic drug products "containing ingredients with potentially toxic effects, including snake venom," without an established Quality Unit, the FDA said. Learn More

Outgoing U.S. FDA Commissioner Scott Gottlieb continued his farewell tour of interviews with a detailed discussion with former FDA Commissioner Mark McClellan at the Pew Charitable Trusts. The wide-ranging conversation covered topics like opioids, the regulation of cell and gene therapies, leveraging electronic health record data and whether the FDA should allow drug importation to bring down costs. As for what Gottlieb thinks might be the most enduring change made during his tenure, he pointed to the Center for Drug Evaluation and Research's evolving application process, which is moving away from a paper-based system to a collaborative, cloud-based document. Learn More

U.S. regulators plan to revamp rules governing how medicines are manufactured, in an effort to ensure the safety of the nation's drug supply as recalls of contaminated imports from developing countries widen. A Bloomberg investigation this year found that manufacturers of generic drugs and their key ingredients in China, India and elsewhere, had in some cases destroyed or hidden testing data revealing quality failures from official records - and showed passing results instead. The FDA wants to force drugmakers to do more rigorous testing to make sure that pills used by millions of Americans meets basic safety and effectiveness standards. Learn More

The U.S. Federal Trade Commission has sought additional information from Bristol-Myers Squibb and Celgene and is focusing on the companies' psoriasis treatments as part of its review of their planned merger. Celgene's psoriasis drug Otezla brought $448 million in sales in the quarter ended Dec. 31st, 2018. However, Alert readers will recall that the FTC review is not the only challenge the companies face. Some Bristol-Myers investors are against the planned $74 billion takeover of Celgene, as they see potential risk associated with Celgene's pipeline, and expect a drop in sales of its flagship multiple myeloma drug, Revlimid, when it loses U.S. exclusivity in 2022. Learn More

Duke University will pay $112.5 million to the federal government to settle allegations that researchers submitted applications and reports containing falsified data to win more than two dozen grants from the National Institutes of Health and the Environmental Protection Agency. The allegations were initially made in a whistle-blower lawsuit brought by Joseph Thomas, a research analyst who worked in Duke's pulmonary division. He claimed that another researcher, Erin Potts-Kant, had fabricated data linked to as much as $200 million in federal research grants. University officials said this week that they discovered the possible research misconduct in 2013, after Ms. Potts-Kant was fired for embezzling funds. Learn More

Congressional Democrats in the U.S. have seized on measures in the United States-Mexico-Canada Agreement that establish protections for drug companies, saying they are a boon to the pharmaceutical industry and could undermine efforts to make American health care more affordable. The new trade pact gives biologic drugmakers 10 years of protections against other products that would rely on the data they used to win approval. But Democrats are objecting to the provision, saying that enshrining the time period in a trade agreement could thwart their future efforts to lower health care costs through legislative changes. Lawmakers also argue that other provisions of the trade pact could hinder the development of generic drugs. Learn More

Beginning March 31st, the U.S. FDA Office of the Commissioner will reorganize and make several changes to various offices within FDA, including the Office of New Drugs (OND). With an eye toward efficiency and better connecting the Office of the Commissioner with center directors and other office leadership. A major change is the creation of the Office of Therapeutic Biologics and Biosimilars (OTBB) within OND. According to an email from Center for Drug Evaluation and Research (CDER) Director Janet Woodcock to staff, the OTBB will house policy and scientific review staff and realign staff from the OND Immediate Office to OTBB. Learn More

Novo Nordisk has submitted its oral semaglutide drug, a pill it hopes will transform the diabetes market, for approval in the United States. The world's biggest maker of diabetes drugs said this week that it had used a so-called priority review voucher to speed up the anticipated review time of the drug to six months. The tablet belongs to a blockbuster class of treatments known as GLP-1s that stimulate insulin production. So far, all have been via injection and a pill would make it quicker and easier for diabetics to take their medication. The semaglutide molecule is the backbone of Novo's future growth hopes amid intensifying pricing pressure in its traditional insulin business. Learn More

AbbVie has announced that the U.S. FDA has placed a partial clinical hold on all trials of its cancer drug Venclexta for multiple myeloma, after a review of data found a higher proportion of deaths in the Venclexta arm of the late-stage study compared to those given a placebo alongside other treatment. Patients who are currently enrolled in studies and receiving the therapy may continue with the treatment, but no new patients should be enrolled in trials testing Venclexta for multiple myeloma until further analysis of the data is completed, the drugmaker said. Venclexta is jointly sold by AbbVie and Roche AG in the United States, while AbbVie sells it in other markets. Learn More

Further modernizing generic drug and new drug reviews and development, improving medical device safety and additional efforts to support the opioid crisis will all see additional funding next year, according to the FY 2020 budget justification from the U.S FDA. The 384-page justification breaks down where all the newly requested funding is expected to go, with $27 million for generic drug reviews and includes a proposal to expand current efforts to streamline and automate the review of the drug quality section of abbreviated new drug applications to include other disciplines engaged in such application assessments. Learn More

Modernizing clinical trials is an agency-wide priority. As more diseases are being redefined based on genomic subtype, researchers have more novel targets and more opportunities to precisely modulate or even repair the basic biological drivers of illness. But these opportunities can be delayed or stymied by a clinical research enterprise that is often extraordinarily complex and expensive. Efforts to streamline medical product development based on advancing science can be frustrated by legacy business models that discourage collaboration and data sharing, and the adoption of disruptive technologies that make clinical research more effective. Learn More

The U.S. Department of Health and Human Services (HHS) announced this week that Dr. Ned Sharpless, current director of the National Cancer Institute (NCI) at the National Institutes of Health, will serve as acting commissioner of the U.S. FDA when Scott Gottlieb steps down next month. Sharpless, who has served as NCI director since October 2017, previously served as director of the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, a position he held since January 2014. No word yet on if he will be nominated by the White House to fill the position permanently and as such be subject to the confirmation process. Learn More

The U.S. FDA, in a warning letter to Pfizer's subsidiary Hospira, says that products made at the company's facility in Tamil Nadu, India are adulterated as a result of data integrity breaches and laboratory testing shortcomings observed during a week-long inspection last spring. According to the FDA, Hospira's microbiology lab did not accurately report microbial growth test results. During the inspection, the FDA requested that Hospira retest multiple batches of its products that were all reported as passing by the company. Each batch was found to be out-of-specification during retesting. Learn More

The U.S. FDA this week approved the 18th biosimilar, Pfizer's Trazimera, which is the fourth approved in the U.S. for Roche's Herceptin. Accoridng to published reports Pfizer is working to make Trazimera available to patients as soon as possible but has not provided a specific launch date. None of the other three approved Herceptin biosimilars have launched in the U.S. Competitors include Merck and Samsung Bioepis' Ontruzant, approved in January; Celltrion's Herzuma, approved in December 2018; and Mylan and Biocon's Ogivri, approved in December 2017. Learn More

In a rare move, the U.S. FDA this month has rescinded two companies' breakthrough therapy designations (BTDs) because of clinical trial data. For Tonix Pharmaceuticals, the FDA informed the company recently that the BTD granted in December 2016 for Tonmya has been rescinded because interim analysis data did not support the continuation of the BTD. Similarly, this week, based on the FDA's review of data from Trevena's Phase 3 studies of oliceridine, the FDA informed Trevena that under the conditions studied, "these data were not sufficient to support the continuation of FDA's previously granted Breakthrough Therapy designation." Learn More

The FDA says it no longer intends to retrospectively modify the names of biologics approved without an agency-designated suffix, according to updated draft guidance on the naming of biologics released this week. Under the naming convention, FDA adds a unique four-letter suffix that is devoid of meaning to non-proprietary names of all biologics, including originators and biosimilars. The draft guidance will revise 2017 final guidance on the topic, in which FDA said the suffix would apply to newly and previously approved biologics. In the draft guidance, the agency says it has decided to assign a unique suffix that distinguishes an interchangeable product from other biologics that share the same core name. Learn More

Teva subsidiary Actavis has received a warning letter from the U.S. FDA regarding quality unit concerns and inconsistencies with its manufacturing processes, among other violations at the company's Davie, Florida site. Of particular concern to FDA inspectors was the sites history of similar cGMP violations in three previous inspections in December 2013, January 2016 and November 2017. "These repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate," the FDA said. Learn More