Regulatory Alert

In a move that could help the US better understand who has already had COVID-19, the US FDA this week provided the first Emergency Use Authorization (EUA) for a serology test to North Carolina-based Cellex Inc. The test can detect SARS-CoV-2 antibodies, immunoglobulin M (IgM) and immunoglobulin G (IgG) that are generated as part of the human immune response to the virus. Although FDA recommends that results from serology testing should not be used as the sole basis to diagnose or exclude a coronavirus infection, the test can help detect how many people have had SARS-CoV-2, even if they did not show symptoms. Learn More

The US FDA has requested that all manufacturers of drugs containing ranitidine remove all prescription and over-the-counter versions from the market because the carcinogen N-Nitrosodimethylamine (NDMA) has now been found to increase significantly in samples stored at higher temperatures. This comes amid new FDA testing and evaluation prompted by information from third-party laboratories "confirmed that NDMA levels increase in ranitidine even under normal storage conditions, and NDMA has been found to increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers," the FDA said. Learn More

Following an inspection last August and September, the US FDA sent a warning letter to Pfizer's injectable product manufacturing site in Visakhapatnam, India. The letter, dated March 25th and released this week, explains how the site did not adequately investigate root causes and implement corrective and preventive action (CAPA) to address deficiencies with its sterility testing. The FDA also notes microbial contamination and how the site "did not adequately investigate serious deficiencies in microbiology laboratory conditions and practices." In addition, the site invalidated microbial results without adequate scientific justification. Learn More

Opening the door to the wider use of unapproved but potential COVID-19 treatments, the US FDA has issued an emergency use authorization (EUA) to allow BARDA to distribute donated hydroxychloroquine sulfate and chloroquine phosphate products to doctors, who can decide whether to prescribe them to hospitalized teen and adult patients with COVID-19 when a clinical trial is not available or feasible. This is FDA's first EUA for a therapeutic product to potentially treat COVID-19. The donations to be distributed include 30 million doses of hydroxychloroquine sulfate from Sandoz and one million doses of chloroquine phosphate from Bayer. Learn More

The US FDA has published a new guidance on how manufacturers should notify the FDA of permanent halts or interruptions to manufacturing certain products that are likely to lead to a meaningful disruption in supply. So far, only one firm is reporting a shortage of one human drug. The FDA previously declined to name the firm or the drug, citing confidential commercial information. FDA staff also have been proactively reaching out to manufacturers to identify potential disruptions or shortages of drugs. And although the shutdown of certain areas in China heightened concerns because the US relies heavily on products and active ingredients manufactured there, Chinese manufacturers seem to be coming back online now. Learn More

The US FDA this week officially ended a fledgling pilot program that was part of an effort to provide more transparency on the drug approval process. The agency said it's working on a new approach to disclosing study reports. Last June, the agency was already pushing away from the clinical study report (CSR) pilot because of lackluster participation, Janssen was the only sponsor that agreed to participate,  and said it would focus its efforts to better communicate the basis for drug approvals on the development of new integrated review documents. Janet Woodcock, director of CDER, said in a statement that the FDA has learned some useful information from the CSR pilot. Learn More

To increase the availability of personal protective equipment (PPE) and other medical devices amid the coronavirus disease (COVID-19) pandemic, the US FDA this week eased import requirements for certain products. Typically, companies importing FDA-regulated products are required to submit entry information to the agency for the products. However, to ease burdens on importers and speed up the entry process for PPE and certain devices intended for emergency use or covered by an enforcement discretion policy, FDA is reducing the amount of information that needs to be submitted. Learn More

As Gilead begins to streamline the process for COVID-19 patients to receive its experimental antiviral remdesivir on a wider basis, the company also raised some eyebrows this week by obtaining an orphan drug designation for the potential COVID-19 treatment. Orphan designations are meant to help companies developing treatments for limited populations and they provide incentives like tax credits for research and seven years of exclusivity for the sponsors of such drugs. Although the number of COVID-19 cases is currently below 200,000, some have begun to criticize this designation as just the latest in a series of orphan drug abuses. Learn More

The law that opened up the approval pathway for biosimilars, known as the Biologics Price Competition and Innovation Act (BPCIA), turned 10 years old this week and nearly 100 drugs officially became biologics under what's known as the "deemed to be a license" provision of the BPCIA. As anticipated, the shift for these nearly 100 products will mean insulin and treatments for respiratory distress syndrome, fertility conditions, Cushing's syndrome, deep vein thrombosis, Gaucher disease and others will be marketed under biologics license applications (BLAs) and see biosimilar competition moving forward. Earlier this month, the FDA finalized guidance on what this transition means for sponsors of these products. Learn More

As the US FDA re-gears to respond to the coronavirus disease (COVID-19) pandemic, the agency's Center for Biologics Evaluation and Research (CBER) says it will "significantly scale back" lot release activities. In a letter to biological product manufacturers, CBER's Office of Compliance and Biologics Quality (OCBQ) advises that it will no longer accept biological product samples or lot release protocols in physical form (paper or CD-ROM) at the agency's headquarters in Silver Spring, MD until further notice. Despite the pause in other lot release activities, CBER says it will continue to prepare reagents for the 2020/2021 influenza season. Learn More

The Health Products Regulatory Authority (HPRA) of Ireland has joined the US FDA in canceling what it terms "routine compliance inspections". These initial cancelations are scheduled to last through March 29th. However, with the rate of new daily cases in Ireland still increasing, it is being speculated that the cancellations may continue well beyond this date. No word as of this writing what, if any, changes might be coming to the site inspection plans of other European regulators such as the United Kingdom's MHRA. Learn More

The US FDA has formally announced that it has temporarily postponed all domestic routine surveillance facility inspections. The decision, which FDA said is for "the health and well-being of our staff and those who conduct inspections for the agency under contract at the state level, and because of industry concerns about visitors". FDA Commissioner Stephen Hahn said in a statement: "I want to assure the American public that we have full confidence in the safety and quality of the products we all use every day and that the FDA will continue to leverage all available authorities to continue to ensure the integrity of the products we regulate." Learn More

The US FDA this week released a warning letter sent to a Goa, India-based manufacturing site of pharmaceutical company Cipla. Following a more than week-long inspection last September, the FDA uncovered cross-contamination of products, noting, "Your testing confirmed the presence of active ingredients from a previous product in batches of the next product." And the firm's "lack of a clear root cause casts doubt on whether you have fully resolved a serious cross-contamination problem," the FDA said. The agency acknowledged that the site has suspended production in several sterile units. Learn More

The US FDA unleashed the private sector over the weekend, granting Emergency Use Authorizations (EUA) to Thermo Fisher Scientific in vitro diagnostics. The company says it currently has 1.5 million tests available to ship under its EUA and expects to quickly ramp up to reach 2 million tests per week. Two other lab testing companies - Quest Diagnostics and LabCorp - are also pursuing EUAs and ramping up testing. Quest said on Saturday that it expects to have capacity to perform approximately 10,000 tests a day by the end of next week and approximately 20,000 tests a day by the end of the month. Learn More

The U.S. FDA has granted Roche's Cobas SARS-CoV-2 Test Emergency Use Authorization. Hospitals and laboratories will be able to run the test on Roche's fully automated Cobas 6800 and Cobas 8800 Systems, which are already in wide use in the U.S. and internationally. This test is for the coronavirus that causes COVID-19, which was classified a pandemic by the World Health Organization. The new test can give results in about three-and-a-half hours and can run up to 4,128 test results per day. The Emergency Use Authorization allows the test to be conducted in the U.S. and in countries that accept the CE mark showing they conform to European standards. Learn More

The US FDA this week offered advice to healthcare providers to conserve their supply of personal protective equipment (PPE), such as surgical masks and gowns, as fears of supply constraints mount amid the global coronavirus disease (COVID-19) pandemic. FDA's recommendations are tiered based on the situation within individual healthcare organizations and the level of supply of PPE available to them. The FDA notes that these strategies do not apply to N95 respirators but do apply broadly to patient care beyond those being treated for COVID-19. Learn More

The World Health Organization this week declared the ongoing coronavirus (COVID-19) outbreak to be a global pandemic, marking the first time since the 2009 H1N1 influenza outbreak the agency has used the designation. Hours before the announcement, the European Medicines Agency (EMA) said it will be holding all its committee and working party meetings virtually through April in response to the ongoing coronavirus (COVID-19) outbreak. EMA also said it will postpone or virtually host all meetings and events with stakeholders originally scheduled to take place in March and April. Learn More

As a precaution amid the global coronavirus outbreak, the US FDA this week canceled all foreign travel by agency officials and said it is limiting domestic travel to "mission critical only" through April. FDA Commissioner Stephen Hahn also said the agency will postpone most foreign inspections, though some "will still be considered on a case-by-case basis." Last month, the FDA stopped conducting inspections in China while the outbreak was mostly contained within the country. For her part, CDER Director Janet Woodcock said that CDER-organized meetings, conferences and workshops will be postponed or canceled through April. Learn More

In a draft guidance issued this week, the US FDA proposed a new, broader approach to conducting safety evaluations for new drugs to treat type 2 diabetes that looks beyond assessing cardiovascular (CV) risk. The new four-page draft guidance replaces the agency's 2008 guidance on evaluating cardiovascular risk in type 2 diabetes drugs, as well as the agency's 2008 draft guidance on developing drugs to treat or prevent diabetes. Unlike the agency's previous guidance, the new draft guidance does not recommend sponsors "uniformly rule out a specific degree of risk for ischemic cardiovascular adverse outcomes." Learn More

Since 1971, Annex 1 of the EU's good manufacturing practice (GMP) guide has helped with the manufacture of sterile medicinal products, but now the European Commission, European Medicines Agency, PIC/S and WHO are launching a second consultation on fully revising the annex and introducing the principles of Quality Risk Management (QRM). A first consultation on the guideline was previously conducted from December 2017 to March 2018 and about 140 companies and/or organizations commented. The joint PIC/S-EMA drafting group (with WHO participation) said they processed more than 6200 lines of comments. Learn More

The UK government has detailed what it hopes to get out of its Brexit trade deal talks with the EU. United Kingdom officials are seeking multiple provisions intended to facilitate trade in medicinal products, for example by proposing for each side to recognize GMP certificates issued by the other. Unlike the European Commission, which provided scant details of its thinking about medicines and medical devices in its negotiating guidelines, the UK government detailed multiple specific objectives related to the industry in a document outlining its approach to the talks. The UK government wants an annex on medicinal products designed to facilitate cross-border trade. Learn More

In preparation for certain NDAs to be converted to BLAs on March 23rd, the US FDA this week finalized a questions and answers (Q&A) guidance on the transition. The Q&A has been updated to reflect the recent change from the latest appropriations bill, enacted in December, which further amended the definition of "biological product" to include chemically synthesized polypeptides. The change in the definition effectively means that three additional products will make the transition (in addition to the almost 100 others listed last year). But other companies, like Teva, have requested that FDA include their products in the transition. Learn More

The US FDA's Center for Biologics Evaluation and Research (CBER) is looking for ways to facilitate the development of more products intended to treat individual or small groups of patients, including cell and gene therapies, antisense oligonucleotides and phage therapies. At a workshop at the FDA's headquarters in Silver Spring, MD this week, CBER Director Peter Marks addressed some of the barriers to developing individualized therapies such as "customized products" with a single indication and a mode of action that are tailored to individual patients, or "created products" that could target different indications via different modes of action. Learn More

The US FDA this week released a batch of 43 new and revised draft product-specific guidance's to support the development of generic drugs. The guidance's, when finalized, are intended to promote generic competition by clarifying FDA's expectations for the studies required to demonstrate that a generic drug is equivalent to a reference listed drug. So far, FDA has issued a total of 1,832 product-specific guidance's. This latest batch features 33 new and 10 revised draft product-specific guidance's and comes more than three months after the agency's last batch. Among the revised draft guidance's are five that provide recommendations for complex generics. Learn More

At its recent meeting the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended one new and one generic medicine for authorization and launched a review of medicines supported by an Indian contract research organization (CRO) citing data integrity concerns. Specifically, CHMP recommended the authorization of Shionogi's Fetroja (cefiderocol) to treat Gram-negative bacterial infections and Accord Healthcare's generic version of the antibiotic tigecycline. The recommendation for Fetroja comes after the US FDA approved the drug to treat certain complicated urinary tract infections caused by Gram-negative bacteria last November. Learn More

Acacia Pharma announced this week that the US FDA has approved BARHEMSYS® (amisulpride injection) for the prevention and treatment of PONV in adult patients. The Company owns global rights to BARHEMSYS and intends to directly commercialize the product in the US through its own sales channel, having built critical sales, marketing, medical, and operational infrastructure and capabilities over the past two years. The Company plans to launch BARHEMSYS in 2H 2020. Learn More

The US FDA has identified 20 drugs that are made in or produced solely from active pharmaceutical ingredients (APIs) sourced from China. In a statement, FDA spokesperson Stephanie Caccomo said the agency has been in contact with the companies that make the 20 products and that "none of these firms has reported any shortage to date." Caccomo also said that FDA has been in contact with more than 180 manufacturers to remind them of their responsibility to notify the agency of anticipated supply disruptions and ask that they review their supply chains for API and other components sourced from China. Learn More

The US FDA this week released three warning letters sent earlier this month. One to Yibin Lihao noted that the company told FDA inspectors that they had not produced crude heparin "for months," but inspectors found "two batches of crude heparin manufactured just a few days before the FDA inspection." The FDA's warning letter to India's JHS Svendgaard Hygiene Products notes how the firm lacked adequate testing for incoming API and thus relied on its suppliers' certificates of analyses (COA). While for India CMO Essnd, the FDA said the firm released drug product without adequate testing, including identity and strength testing of the active ingredient. Learn More

The US FDA this week unveiled the first version of its searchable online database of biological product information, known as the Purple Book. Building off the previous PDF lists of biological products, the database now allows for easier searches and includes information on product names, the type of biologics license application (BLA) that was submitted, strength of the biologic, dosage form, product presentation, license status, BLA number and approval date. Biopharma companies previously requested that FDA include exclusivity information in the Purple Book, similar to what's offered in the Orange Book, and FDA says that a later iteration of the database will include such dates. Learn More

A month before the long-anticipated transition of applications for certain biological products to be deemed to be licensed as biologics, the US FDA has issued a final rule amending its definition of "biological product." Effectively, on March 23rd, 2020, some 100 products approved under new drug applications (NDAs) will transition to biologics license applications (BLAs). Under the rule, the FDA is amending its definition of "biological product" in line with the statutory definition set by the BPCIA. As such, the FDA now interprets the term "protein" to mean "any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size." Learn More

The U.S. FDA and the Federal Trade Commission today signed a joint statement regarding enhanced collaboration in support of a robust marketplace for biological products, including the critical adoption of biosimilars and interchangeable products. This joint statement describes key steps the agencies will take to address false or misleading promotion about biosimilars within their respective authorities and deter anti-competitive behavior in this space. Learn More

The US FDA this week issued a new draft guidance consolidating its recommendations on nonclinical safety evaluations for immunotoxicity and withdrew an earlier 2002 guidance on the topic. The FDA says the guidance addresses issues related to evaluating immunotoxicity including immune suppression, modulation and stimulation and provides recommendations for carcinogenicity assessments, dermal sensitization, adjuvanted vaccine development and developmental and juvenile animal studies. The 10-page draft guidance consolidates and supplements recommendations from various guidances, including the ICH S8 and the FDA's 2006 guidance. Learn More

The UK will not act as a "leading authority" for medicines during the one-year Brexit transition, although UK and EU negotiators are still trying to fine-tune what that means in practice. The meaning of "leading authority" depends on interpreting Article 123 of the draft withdrawal agreement. Regardless, the MHRA's role will change immediately. For instance, the UK will no longer have voting rights in the European Medicines Agency (EMA) and EU committees, but the UK will continue to respect their drug approval decisions. As for biopharma companies, the MHRA says they will be able to continue UK batch release testing and Qualified Person certification in the UK, which are recognized by the EU and vice versa. Learn More

The FDA's CBER has unveiled its 2020 guidance list, with new drafts coming on several increasingly crowded areas for drug development. Three new drafts this year will likely draw lots of comments from industry and other stakeholders. They deal with considerations for the development of CAR T-cell therapies, considerations for the development of human gene therapies incorporating genome editing, and one on human gene therapies for neurodegenerative diseases. Final guidance expected this year will deal with a draft from last September on interacting with the FDA on complex and innovative trial designs for biologics and a draft from December 2017 on chemistry, manufacturing, and controls changes to an approved biologic. Learn More

A series of partially redacted internal emails from the US FDA, released as part of a lawsuit filed by Catalyst, attempt to show how price and Sen. Bernie Sanders's pressure played a role in the FDA's approval of a competitor. Specifically, approval of the drug Ruzurgi developed by Jacobus Pharmaceuticals. According to the arguments being made by Catalyst, the US FDA unfairly took into consideration drug pricing when determining its approval and did so based in no small part on the political pressure being asserted by the Vermont Senator. Learn More

The US FDA this week announced it has requested the withdrawal of Eisai's weight-loss drug Belviq and the extended release version Belviq XR after a large postmarketing study found increased rates of pancreatic, colorectal and lung cancer among patients taking the drug. The announcement comes one month after the agency issued a safety communication warning about a possible increased risk of cancer with the drug. In a statement, Eisai says it is complying with the FDA's request and will withdraw both versions of the drug from the US market, though the company says it disagrees with the FDA's assessment of the study. Learn More

About two years after first opening a consultation on the guideline, the EMA said this week that on July 30th, the International Council for Harmonisation's (ICH) M9 guideline on biopharmaceutics classification system-based biowaivers will take effect. The M9 guideline has been in the works at ICH since at least 2016, and may help to avoid unnecessary in vivo bioequivalence studies. BCS-based biowaivers are applicable to drug products where the drug substance(s) exhibit high aqueous solubility and, either high intestinal permeability (BCS Class I) or low permeability (BCS Class III). Learn More

LogicBio has announced that the U.S. FDA has placed a clinical hold on its proposed gene therapy treatment for methylmalonic academia (MMA). In January, LogicBio submitted an Investigational New Drug Application to initiate a Phase I/II trial of LB-001, a recombinant adeno-associated viral vector with human methylmalonyl-COA mutase (MMUT) gene for the treatment of MMA. But, before that trial could ever receive the green light, the FDA has demanded answers to a few undisclosed clinical and nonclinical questions. While the concerns raised by the FDA have not been made public, in the past, there have been some questions over potential downstream side effects from gene-editing treatments. Learn More

The World Health Organization (WHO) is seeking comments on a draft policy to help guide national regulators seeking to use international harmonized standards for creating systems to track and trace pharmaceuticals and vaccines through their supply chains. The policy is part of efforts to help already stretched regulators minimize the risk of substandard and falsified (SF) medical products, shortages and expired products. The draft also discusses what constitutes an appropriate regulation for traceability, noting that establishing voluntary pilots to test draft regulations before finalizing them can help to expose unexpected complexities, missing requirements and unnecessary steps. Learn More

The US Embassy in the Netherlands is calling attention to efforts on the part of the Dutch government to reduce drug prices by legalizing the violation of intellectual property rights by producing patented drugs. As evidence of this intention, the embassy is citing recent legislation by the government which permits pharmacists to prepare patented medicines despite the presence of intellectual property protections and plans to further implement policies to expand compulsory licensing and compounding of pharmaceuticals. However, attempts to take advantage of these emerging policies to date have proven difficult with one hospital having to stop making a drug amid quality concerns. Learn More

The US FDA this week published a new draft guidance explaining how it will speed its review of biosimilar or interchangeable application supplements, which can be used to update the initial biosimilar approval when it is for fewer than all the reference product's licensed conditions of use. The 9-page draft details how the FDA cannot license a biosimilar or interchangeable product for an indication protected by orphan-drug exclusivity or pediatric exclusivity until the expiration of that exclusivity. But after that exclusivity or patent expires, an applicant may decide to submit a supplement to the licensed 351(k) biologics license application (BLA) for the previously protected indication. Learn More

As the US FDA continues to approve new drugs and biologics more quickly, more often and with less data than ever before, the number of new application filings in the first quarter of FY 2020 (to 12/31/2019) has increased dramatically when compared to FY 2019 and 2018. This latest quarter saw 74 NDA filings and 32 BLA filings, which compares with a total of only 26 BLA filings in all four quarters of 2019, and a high of 51 NDA filings in Q1 of 2019. By comparison, the FDA saw an average of 35 quarterly NDA filings across FY 2019 and 34.25 across FY 2018, while quarterly BLA filings averaged 6.5 in FY 2019 and 5.25 in FY 2018. Learn More

Biopharma companies Regeneron, Janssen and AstraZeneca, as well as the US Pharmacopeia (USP) and the International Pharmaceutical Excipients Council of the Americas (IPEC-Americas) all pledged their support for a new US FDA pilot program to review novel excipients. The term "excipient" is defined by the FDA as any ingredient intentionally added to a drug or biologic that is not intended to have a therapeutic effect but may improve product delivery. In December, the FDA explained how it's interested in creating a pilot program to evaluate certain novel excipients to obviate the need for another review of the excipient in the context of an IND. Learn More

At its first meeting in 2020, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended the authorization of eight new medicines, six generic and hybrid applications and a biosimilar. The CHMP also said that two marketing authorization applications were withdrawn from consideration ahead of the meeting, Merck's application to extend the use of Keytruda to treat esophageal cancer and Celgene and Agios' application for Idhifa to treat acute myeloid leukemia. Separately, Bristol-Myers Squibb said it had withdrawn its application for Opdivo plus Yervoy for first-line treatment of advanced non-small cell lung cancer. Learn More

US FDA Commissioner Stephen Hahn addressed FDA staffers in an all-hands meeting for the first time, explaining how he wants to do more with real-world evidence (RWE), which has been a controversial subject. While noting that the FDA is operating in a time of "unsurpassed scientific and technological innovation," Hahn called to unleash the power of data and "to attain more and better data," according to a transcript of his speech. The comments build upon the agency's technology modernization plan unveiled last September. Hahn also continued to push the related agenda of his predecessor, Scott Gottlieb. Learn More

With the official beginning of Brexit starting soon, the UK government this week offered further information on supplementary protection certificates (SPCs) in a post-Brexit world. The guidance explains how after the transition period that runs until the end of 2020, medicine authorizations from the European Medicines Agency will be converted into equivalent UK authorizations on January 1st, 2021. SPCs, which extend the protection of patented active ingredients in pharmaceuticals by six months if pediatric testing has been done, will then be overseen by the UK. Learn More

The House Energy & Commerce Committee of the US Congress this week considered a bill, supported by members on both sides of the aisle, that focuses on encouraging continuous drug manufacturing. As currently written, the bill, known as HR 4866, would allow the FDA to designate institutions of higher education as a National Center of Excellence in Continuous Pharmaceutical Manufacturing. This comes amid an ongoing 7 year push by the FDA's CDER Director Janet Woodcock for the increased adoption of continuous manufacturing practices by the biopharma community. Learn More

The US FDA this week finalized six guidance documents on gene therapy development and released a new draft guidance on interpreting the sameness of gene therapies under the orphan drug regulations. The guidance release comes as more than 900 investigational new drug applications are ongoing for gene and cell therapy clinical studies, and as the FDA has struggled to hire enough experts to tackle the related challenges. The release of the six final guidances and the new draft were expected as FDA's list of guidance documents from last July explained. Learn More

The Federal Trade Commission (FTC) and New York Attorney General this week filed a lawsuit against Vyera Pharmaceuticals, which was previously known as Turing and was run by the infamous "Pharma Bro" Martin Shkreli. The FTC and New York lawsuit explains how Vyera withheld samples of the drug so that generic competitors could not conduct bioequivalence testing and enter the market. For instance, in August 2015, Vyera and a Daraprim distributor agreed that the distributor would not sell more than five bottles to a single customer without Vyera's express approval. Learn More

Alert readers will recall that late last year the US Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada. Now Gilead has filed its retort, making clear that it does not believe it has infringed on the CDC's Truvada patents because they are invalid. The defense echoes what Gilead CEO Daniel O'Day said before the House Oversight Committee in May 2019, when he noted that the patents are invalid "because the use of Truvada as prophylaxis was widely known at the time the CDC sought these patents." Learn More

New details on the US FDA's tussle with Sarepta over the approval of golodirsen, a drug that treats Duchenne muscular dystrophy, are raising worries over the fate of another drug for the same disease that Sarepta is seeking approval for. Alert readers will recall that the FDA rejected Sarepta's application for golodirsen in August then changed its mind in December and granted approval. Now, with the FDA's release of the text of the original rejection letter, industry observers are concerned that the scathing nature of the rejection could adversely effect another Sarepta drug for Duchenne muscular dystrophy called eteplirsen. Learn More

The Court of Justice of the EU this week ruled that the European Medicines Agency (EMA) acted lawfully when it released certain toxicology reports and a clinical study report from two sponsors that wanted to keep that information confidential. The cases centered around PTC Therapeutics and MSD Animal Health, which claimed that EMA's disclosure of a clinical study report, in the case of PTC, and five toxicology reports from MSD Animal Health would undermine their commercial interests. But the Court of Justice concluded, siding with the General Court ruling from February 2018. Learn More

Later this month, the US FDA will formally launch its Drug Risk Management Board (DRMB) to coordinate safety activities among offices, Center for Drug Evaluation and Research (CDER) Director Janet Woodcock said in an email to staff. Woodcock says the DRMB is a center-level body that will also rapidly analyze and resolve drug safety issues by facilitating decision making across CDER on major clinical and quality-related safety issues with marketed products. The board is also expected to help foster better communications across the center. Learn More

As part of efforts to better align scientific advice across the EU, beginning February 1st, a dozen national competent authorities (NCAs) will participate in a pilot project to allow drug developers to obtain two NCA opinions simultaneously. The multi-national discussions aim to provide two NCA opinions within one application, in addition to earlier opinions, better explanations for possibly conflicting opinions, increased interactions between NCAs and the potential for further alignment or clarification among NCAs on different regulatory positions and/or requirements. Learn More

The US FDA last month offered a new Manual of Policies and Procedures (MAPP) to explain how the Center for Drug Evaluation and Research (CDER) reviews risk evaluation and mitigation strategy (REMS) assessment reports submitted to the agency. Although the statute does not specifically describe how companies should conduct their assessments, the agency has released two draft guidances (one on survey methodologies and another on planning and reporting REMS assessments, both from last January) and now, this new MAPP, effective December 2019, for further explanation. Learn More

Industry groups, the Mayo Clinic, Regeneron and others are seeking more clarity from the US FDA's revised draft guidance on clinical decision support (CDS) software. The 27-page draft from September builds on a previous draft from 2017, with which industry also raised concerns. The latest draft clarifies the categories of CDS software subject to FDA oversight, as well as the low-risk categories of CDS software for which FDA does not intend to enforce regulatory requirements and CDS categories that do not meet the definition of a device. Weighing in on the draft, industry group AdvaMed praised its discussions of what types of software are, or are not, subject to FDA's oversight. Learn More

As some insulin, human growth hormone and other products transition on March 23rd from new drug applications (NDAs) to biologics license applications (BLAs), the recently passed government spending bill included a further tweak to add new proteins to the transition. The NDA to BLA change effectively means that any follow-on products for these NDAs will need to win approval as biosimilars after March. The transition was created by the Biologics Price Competition and Innovation Act of 2009, which clarified the statutory authority under which certain protein products will be regulated by amending the definition of a "biological product" to include a "protein". Learn More

The FDA this week released two warning letters recently sent to China-based contract manufacturer Huaian Zongheng Bio-Tech and New Jersey-based drug manufacturer Health Pharma for GMP violations. For Huaian Zongheng FDA inspectors said the firm released over-the-counter drugs without conducting identity or strength testing for each active ingredient. The firm also failed to test incoming components used to manufacture its drug products to determine their identity. While for Health Pharma, FDA inspectors, following a visit to the Rahway, New Jersey site last May and June, said the firm's quality unit (QU) lacked the appropriate oversight of its drug manufacturing operations. Learn More

As API quality concerns linger, China's National Medical Products Administration (NMPA) has agreed to work with the European Commission's DG Sante, the European Medicines Agency (EMA) and others to identify similarities and differences between the Chinese and EU regulatory systems for APIs. The commission says it has created a budget to conduct a gap analysis, which would be used to identify Chinese training needs in the API space. EU experts will also conduct a fact-finding visit to China to assess the regulatory, control and enforcement system governing the implementation of GMP standards, according to the agreement forged at a bilateral EU/China meeting in October 2019. Learn More

The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended 30 new active substances (NAS) for marketing authorization in 2019, down from 42 the previous year. The agency also recommended just six new orphan medicines for authorization, the fewest in recent years and a drop from the 17 new orphan medicines recommended in 2018. In comparison, the US FDA (FDA) Center for Drug Evaluation and Research (CDER) approved 48 novel drugs in 2019, down from 59 in 2018, 21 of which were orphan products. While most of the products EMA recommended in 2019 have also been approved by FDA, four have not been approved in the US. Learn More

The US FDA this week said it plans to withdraw the approval of 249 abbreviated new drug applications (ANDAs) after their manufacturers repeatedly failed to submit annual reports for the generic drugs. The FDA says the manufacturers will have the opportunity to request a hearing to appeal the decision by filing a written request and providing the agency with a rationale for why the ANDA should not be withdrawn. Some of the companies impacted include major drugmakers and their subsidiaries, including Pfizer Laboratories, Novartis' Sandoz and Fresenius USA, although the vast majority of the companies are smaller manufacturers. Learn More

As the use of complex innovative design (CID) trials for new cancer treatments continues, a group of UK professors from the University of Oxford, Birmingham and others, as well as representatives from the UK's Medicines and Healthcare products Regulatory Agency and Pfizer have offered a series of recommendations on the flexible trials. Published this week in the British Journal of Cancer, the consensus statement explains how unlike conventional trials in which patients are recruited by tumor of origin, patients enrolled in one kind of CID trial, known as "master protocol" trials, incorporate molecular biomarkers. Learn More

The Pharmaceutical Inspection Co-operation Scheme (PIC/S) this week released a new guideline explaining its pre-accession procedure for competent authorities wishing to join the inspection scheme. Membership in PIC/S is open to any competent authority "having the arrangements necessary to apply an inspection system comparable to that enforced by" existing members. "The scheme is primarily based on mutual confidence between participating authorities (PA). Such confidence can only be achieved on the basis of a thorough knowledge of each other's inspection systems and inspection practice and standards," PIC/S writes. Learn More

The US FDA has issued a draft guidance on requesting feedback from the agency on scientific and regulatory questions during the development of a combination product. The 18-page draft guidance fulfills an obligation under the 21st Century Cures Act to publish guidance on best practices when seeking feedback on combination products and to explain how combination product agreement meetings (CPAMs) work. The guidance also details the submission process and what information should be included in CPAM requests and outlines how the agency will respond to such requests. Learn More

Following its Brexit-related departure from London, the European Medicines Agency's (EMA) staff has been reduced from 897 staffers to 775 as noted in an update from a board meeting in its new home in Amsterdam. At the same meeting, the EMA board also agreed to the mandatory use of the ISO standard for individual case safety reports for the reporting of suspected side effects of medicines. The board also signed off on the EMA's budget for 2020, which is $399 (€358) million. And for the new clinical trial regulation, the EMA is moving forward with a proposal to begin an audit of its Clinical Trial Information System in December 2020. Learn More

The US FDA this week issued a draft guidance explaining how drug-device and biologic-device combination product sponsors can bridge data from earlier stages or development or other development programs to support an application. In the 14-page draft guidance, the FDA describes how sponsors can develop an analytical framework for identifying information gaps that could be addressed with bridging. The draft provides three examples of bridging scenarios for different drug-device combination products. The draft guidance comes just after the deadline set in the FDA's Prescription Drug User Fee Act goal letter to issue guidance on the topic by the end of FY2019. Learn More

The European Medicines Agency (EMA) this week announced the launch of a two-year pilot that will allow regulators across the EU, US, UK, Australia and Canada to share information from good manufacturing practice (GMP) inspections of sterile medicines manufacturing sites. Specifically, the pilot will enable information sharing from GMP inspections of manufacturers located in countries that are not participating in the pilot and allow participants to organize joint inspections. The pilot, which EMA says will last for a minimum of two years, is modeled after an earlier joint inspection program for active pharmaceutical ingredients (APIs), which was piloted in 2008 and fully implemented in 2012. Learn More

After years of criticism from the FDA, Sun's Halol plant still can't get through an FDA inspection without the agency finding some deficiency. In June, it was just one observation, but a just completed inspection ended with a Form 483 for Halol with significantly more. The Indian drugmaker has recently reported that an inspection which took place from December 3rd through December 13th had resulted in the FDA citing the key facility with eight observations. It didn't say what issues were uncovered but insisted it was committed to working with the FDA to fix these problems as well as to improve its manufacturing systemwide. Learn More

The US FDA has issued a draft guidance explaining its qualification process for drug development tools (DDTs) in line with the 21st Century Cures Act. The 20-page draft guidance comes just ahead of the deadline set in the Cures Act and fulfills some of FDA's Prescription Drug User Fee Act (PDUFA VI) commitments to enhance its DDT qualification pathway for biomarkers. Once qualified, the FDA says a DDT can be used within its context of use (COU) to support regulatory submissions, including investigational new drug applications (INDs), new drug applications (NDAs) and biologics license applications (BLAs) for any drug or biologic. Learn More

The full US Senate voted this week 72-18 to confirm Stephen Hahn, chief medical executive of the MD Anderson Cancer Center in Houston, to be the next commissioner of the US FDA. The vote came just over a month since he was nominated, although in that time little information has come to light about how he plans to direct the FDA. Still, senators on both sides of the aisle seemed convinced that he'll be able to handle the job. Learn More

The US reliance on imported pharmaceuticals and ingredients is rising as foreign drug facility inspections decreased by about 10% from 2016 to 2018. Part of the reason for the decline: The US FDA said it's still struggling to hire new inspectors. Testifying under oath before the House Subcommittee on Oversight and Investigations of the Committee on Energy & Commerce this week, Janet Woodcock, director of FDA's Center for Drug Evaluation and Research, defended the FDA's approach and discussed some of the vulnerabilities of the agency's foreign inspection program. She said the FDA is looking to hire 50 new inspectors, but there are difficulties. Learn More

The US FDA recently warned two US-based drugmakers, Teligent Pharma in Buena, NJ, and OHM Pharma in Mineral Wells, TX, for good manufacturing practice (GMP) violations at their respective facilities. In its warning letter to Teligent Pharma, the FDA cites the company for failing to thoroughly investigate out-of-specification (OOS) test results. While the FDA's warning letter to OHM Pharma comes after a 10-day inspection in May that uncovered issues with the company's cleaning practices, laboratory controls and manufacturing practices. Learn More

Regulators including the US FDA, EMA, Health Canada and the UK's MHRA are looking into whether formulations of the diabetes drug metformin contain N-nitrosodimethylamine (NDMA) impurities. The announcements come after Singapore's Health Sciences Authority (HSA) recalled three out of 46 locally marketed metformin medicines after determining they contained NDMA "above the internationally acceptable level." The three drugs were marketed by Singapore-based Glorious Dexa Singapore and Pharmazen Medicals Pte Ltd. According to HSA, the risk posed by three medicines is low as they "have only been supplied locally for a short period of time since last year." Learn More

Ipsen has announced that the U.S. FDA has placed a partial clinical hold effective immediately for studies conducted under IND120181 and IND135403 evaluating the investigational drug candidate. The partial clinical hold was issued following recent safety reports submitted by the company to the FDA of cases of early growth plate closure in pediatric patients with FOP treated with palovarotene. The FDA has placed the studies on partial clinical hold pending review of additional details regarding these events and plans to issue additional requests for information within the next 30 days. Learn More

As manufacturers of popular heartburn drugs, like Zantac, continue to pull their products from shelves, the US FDA is now telling the companies to test their drugs for an impurity, known as N-nitrosodimethylamine (NDMA), before making them available. The new requirement comes as earlier last month the FDA noted that although many of these NDMA levels observed via FDA testing are much lower than the levels some third-party scientists first claimed, "some levels still exceed what the FDA considers acceptable for these medicines," said Janet Woodcock, director of FDA's Center for Drug Evaluation and Research. Learn More

The US FDA this week sought comments on whether it should run a voluntary pilot program to evaluate the toxicology and quality of novel excipients. While the agency does currently review new excipients as part of an investigational new drug application (IND) or a marketing application (NDA or BLA), FDA explains how certain novel excipients may provide public health benefits, such as improved drug delivery or utility in abuse-deterrent opioid formulations. The term "excipient" is defined by FDA as any ingredient intentionally added to a drug or biologic that is not intended to have a therapeutic effect but may improve product delivery. Learn More

The US FDA has finalized the guidance on adaptive clinical trial designs for drugs and biologics. The 33-page guidance, which finalizes a draft version released for comment in September 2018 and replaces an earlier guidance from 2010, sets out the FDA's recommendations on adaptive trial design principles and the information the FDA will review from adaptive studies submitted as part of investigational new drug applications (INDs), new drug applications (NDAs), biologics license applications (BLAs) and supplemental applications. While the final guidance is largely the same as the draft version, the FDA says it has revised the guidance to clarify its recommendations for Bayesian adaptive designs... Learn More

PIC/S last week published a draft recommendation offering guidance for GMP inspectors seeking to evaluate the effectiveness of a company's pharmaceutical quality system (PQS) in relation to risk-based change management. The 8-page draft recommendation, which is not open for comments, will be applied on a 6-month trial basis by PIC/S participating authorities, which include the US FDA, and other regulators across Europe, Australia, Canada, South Africa, Turkey, Iran, Argentina and more. The document was created in recognition of the fact that the PIC/S GMP Guide requires companies to demonstrate the effectiveness of their PQS and to apply quality risk management (QRM) principles to change control activities. Learn More

The U.S. FDA has approved an expanded indication for Sanofi's Toujeo for blood sugar control in adult and pediatric patients who are ages six years and older. Previously, Toujeo was approved only for adults aged 18 years and older. The company announced the results of the clinical trial earlier in the month. It was the first randomized, controlled trial to compare Toujeo to Gla-100 in this patient population. The trial met its primary endpoint, demonstrating comparable decreases in average blood sugar over six months with both treatments and similar risk of low blood sugar events. Based on the data, the EMA's Committee for Medicinal Products for Human Use recommended the expanded label in Europe. Learn More

AstraZeneca has announced that the U.S. FDA has given its go ahead for the company's Calquence drug to treat chronic lymphocytic leukemia (CLL), one of the most common types of leukemia in adults. The drug was approved roughly two months after being granted a Breakthrough Therapy Designation by the U.S. FDA in collaboration with drug watchdogs in Canada and Australia. The decision to also approve Calquence for the treatment of small lymphocytic lymphoma, a similar disease, will pit the AstraZeneca drug against AbbVie and Johnson & Johnson's established CLL treatment Imbruvica. Learn More

The UK's MHRA has announced the fifth recent recall of the heartburn medicine ranitidine due to possible contamination with the carcinogen NDMA. The recall, which affects 13 over-the-counter ranitidine medicines marketed by four different companies, follows four previous recalls in October and November and comes as international regulators including the US FDA and EMA investigate the source of the impurities. The FDA previously said the 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." Learn More

The US FDA this week released product-specific guidance documents for 81 active pharmaceutical ingredients to aid generic drug development, including 28 new draft guidances and 53 revised draft guidances. The guidances, when finalized, are intended to promote generic competition by clarifying the FDA's expectations for the studies required to demonstrate that a generic drug is equivalent to a reference listed drug. So far, the FDA has issued nearly 1,800 product-specific guidances. The FDA is committed to issuing product-specific guidances for 90% of non-complex new chemical entity new drug applications (NDAs). Learn More

The World Health Organization (WHO) recently drafted a new guideline on data integrity that explains the important elements to ensure the reliability of data and information in the production and control of biopharmaceuticals. The WHO echoed similar concerns expressed by the US FDA in noting an uptick in recent years of the number of observations regarding the integrity of data, documentation and record management practices during inspections of good manufacturing practice (GMP), good clinical practice (GCP) and good laboratory practice (GLP). While recommending companies use a written data integrity policy, the guideline outlines the principles of data integrity and good documentation practices before delving into quality risk management. Learn More

Earlier this month, the European Commission's (EC) Pharmaceutical Committee met to discuss how the use of duplicate marketing authorization applications (MAAs) - including the use of duplicate reference biologics, dubbed "autobiologicals" - can impact the availability and pricing of biological products and biosimilars. According to the EC, requests for duplicate MAAs have increased steadily, and this is a trend that is likely to continue. As such, some are calling for stricter scrutiny of autobiologicals especially as they can be considered generics and therefore cut biosimilars out of certain markets where pharmacy substitution for biosimilars is not allowed. Learn More

As the EMA announced that it's finally completing its move from London to Amsterdam, its Committee for Medicinal Products for Human Use (CHMP) has recommended five new medicines for approval, revealed the outcomes of its safety reviews of Pfizer's Xeljanz and Sanofi's Lemtrada and discussed the withdrawal of three applications. Following the initial move to a temporary building in Amsterdam last March, EMA has been waiting on a new building with new technical equipment that was under construction. Staff will likely move into their new offices and workspaces in January 2020, the agency said. Learn More

The FDA's Endocrinologic and Metabolic Drugs Advisory Committee this week voted 16-0 to recommend that the agency expand the label of Amarin's Vascepa, a derivative of fish oil, to add an indication on reducing the risk of cardiovascular events. The meeting was closely watched because the expanded label could push Vascepa, which six years ago received a negative opinion from this same committee on an expanded label, to blockbuster status. In 2018, Vascepa brought in about $229 million in net revenue. Learn More

The US FDA needs to reconsider its use of surrogate outcomes in some guidance documents on developing treatments for infectious diseases, researchers from Harvard and George Washington University School of Medicine wrote in a review published this week in JAMA Internal Medicine. The review evaluated 22 FDA guidance documents, which included recommendations for pivotal clinical trials in 27 disease indications. For six indications (22%), only direct clinical outcomes were specified as primary endpoints, while for the other 21 indications, guidance documents recommended surrogate outcomes as sole primary endpoints or as part of composite primary endpoints. Learn More

The US FDA this week released a warning letter sent last week to Mylan's active pharmaceutical ingredient (API) manufacturing site in Andhra Pradesh, India, highlighting "contamination at levels above the limit" for some API batches. The FDA's inspection of the site in May and June uncovered, "Multiple contract manufacturers supplied solvents that were contaminated with , but your firm lacked documentation of which tanks were used to store these solvents," the letter says. "Although you acknowledged that there was no record of usage for each of the recovered solvent tanks, your response did not provide sufficient information on attempts to retrospectively reconcile the number, identification, and usage of the tanks." Learn More

Regenexbio has filed a lawsuit against the US FDA for failing to provide an explanation for placing a hold on a clinical trial for an experimental gene therapy to treat wet age-related macular degeneration. The FDA's decision effectively halted the development of the potential one-time subretinal treatment without a clear basis, the complaint said. "By failing to provide advance notice of, or any reasoned basis for, the clinical hold, FDA violated the FDCA and its own regulations. FDA's clinical hold on RGX-314 is therefore contrary to law and arbitrary and capricious under the Administrative Procedure Act," the company said. Learn More

The US FDA last week heard from more than two dozen stakeholders on opportunities for the agency to promote more effective drug development programs at a public workshop at its headquarters in Silver Spring, Maryland. During the meeting, speakers representing drugmakers, patient groups, research institutions and consulting firms suggested policies and approaches the FDA could pursue to promote more effective drug development. Jennifer Hamilton, head of precision medicine at Regeneron Pharmaceuticals, suggested that FDA and industry could make drug development "smarter" by collaborating on regulatory standards and guidance for using genomic data to support submissions and labeling changes. Learn More

Following an inspection that uncovered GMP deficiencies, the Danish Medicines Agency said this week that it has revoked Danish pharmaceutical company Scanpharm A/S's authorization to manufacture medicinal products and intermediate products. A three-day inspection in September showed the company lacked the necessary knowledge regarding its responsibilities related to qualified persons, as well as other issues with reporting of out-of-specification (OOS) results, OOS and missing data for stability studies and inconsistencies between registration files and specifications. The Danish Medicines Agency also found the company used non-validated analytical methods and did not perform its self-inspection sufficiently. Learn More

As quality issues have led to drug shortages, Donald Ashley, director of the FDA's Office of Compliance, raised several major concerns this week with the active pharmaceutical ingredient (API) industry, noting three trends related to the obfuscation of supply chain information, an increasing number of data integrity question marks and impurity concerns that have led to recalls. On the obfuscation front, Ashley noted that API companies sometimes fail to obtain and retain documents with the identity of the original manufacturer and certificate of analysis. While on data integrity, Ashley noted that of the warning letters issued to API manufacturers over the past four years, 73% have included data integrity charges. Learn More

Aurobindo Pharma is under the scrutiny of the US FDA once again. According to published reports, 3-4 inspectors from the U.S. FDA recently completed their inspection of the company's Unit IV in Telangana, India and this week are at the biopharma's Units V and VIII sites in Hyderabad. Spread over 33 acres, Aurobindo's Unit-IV is a dedicated mid-size manufacturing facility for generic sterile injectables, opthalmics and low volume parenterals. By contrast the facilities under the FDA lens this week, Units V and VIII, are smaller facilities that manufacture antibiotics, ARVs, CVSs and CNSs. Learn More

While noting that full regulatory harmonization may be out of reach, Suzette Kox, secretary general of the IGBA this week called for further convergence among stringent regulators in the biosimilar space, particularly on the acceptance of foreign-sourced reference products. Kox, speaking at the Association for Accessible Medicines' GRx+Biosim conference in Bethesda, MD, explained how a global framework for "truly global biosimilar development" is necessary to avoid repetitive, and therefore unethical, clinical studies. She also called for more regulators to share unredacted biosimilar assessment reports, although not publicly, especially as FDA often shares such reports with the WHO. Learn More

President Donald Trump has nominated Stephen Hahn, chief medical executive of the MD Anderson Cancer Center in Houston, to be the next US FDA commissioner. If confirmed by the Senate, a process that could take several months, Hahn will take the reins of FDA from Acting Commissioner Ned Sharpless, who moved over to FDA following a stint as head of the National Cancer Institute (NCI). Sharpless will return to direct NCI, while Brett Giroir, assistant secretary for health at the US Department of Health and Human Services (HHS), will serve as acting FDA commissioner while Hahn's confirmation process occurs. Learn More

Novartis this week said that the US FDA had placed a partial hold on intrathecal clinical trials of its gene therapy Zolgensma based on findings in a small preclinical animal study. This comes after a draft report of the preclinical safety findings was presented to the AveXis safety management team last March and the company "determined at that time that the safety finding should be included in the annual update of the investigator brochure planned for September 2019. Unfortunately, a mistake was made, and this update was not implemented." The omission was later identified as part of a Novartis review related to the Form 483 response from August. Learn More

As drug and API manufacturing moves overseas to cut costs, quality and reliability concerns have been raised and the House Energy & Commerce Committee's Subcommittee on Health met this week to discuss the supply chain with one of the US FDA's top officials and other experts. Janet Woodcock, director of the FDA's CDER, explained how part of the problem is that FDA does not know the volume of APIs coming from China or other countries to the US, and only knows the number of manufacturing facilities approved. According to Woodcock's written testimony, China has 230 (13%) of the API manufacturing facilities serving the US, while the US has 510 (28%) and the rest of the world has 1048 (59%). Learn More

Mylan is voluntarily recalling one lot of the anti-anxiety prescription drug Alprazolam, a generic form of Xanax, nationwide because of "the potential presence of a foreign substance," according to a recall notice posted on the website of the U.S. FDA. "Clinical impact from the foreign material, if present, is expected to be rare, but the remote risk of infection to a patient cannot be ruled out," the notice states. "To date, Mylan has not received any adverse events related to this batch." The recall is for Alprazolam 0.5 mg tablets that were distributed in July and August 2019 in 500-count bottles. The affected drug's lot No. is 8082708 and it has a September 2020 expiration date. Learn More

The US FDA Task Force on Drug Shortages supports the idea of creating a new rating system to help drug purchasers, including consumers, better understand the quality management of drug manufacturing facilities. "This idea envisions that pharmaceutical companies could, at their discretion, disclose the rating of the facilities where their drugs are manufactured," according to Janet Woodcock, director of FDA's CDER. The idea of a drug manufacturing ratings program follows the revelation that many drug shortages occur in the US because of quality issues. A team of FDA economists examined a sample of 163 drugs that first went into shortage between 2013 and 2017 and found that 62% were associated with manufacturing or product quality problems. Learn More

As another delay may push back Brexit to the end of January, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) this week published new guidance on comparator products (CPs) used in bioequivalence (BE), pharmacokinetic (PK) and therapeutic equivalence (TE) studies to support generic drug and other abridged marketing authorization applications following a no-deal Brexit. The guidance explains how it may be possible for an applicant to compare a proposed medicinal product with a non-UK-sourced CP, although the application would still be required to refer to an eligible UK reference medicinal product (RMP).  Learn More