SQA Regulatory Surveillance Summary | December 2020 –
By Laurel Hacche and Debra Cortner, SQA Associates
SQA Regulatory Surveillance Summary for December 2020
European Commission
The European Commission has issued a new technical document agreed by national authorities and stakeholders that further clarifies which claims producers of cosmetic products cannot make regarding their products. It adds to the Coronavirus crisis guidance, which informs economic operators on applicable regulations (e.g., the Cosmetic Products Regulation or the Biocidal Products Regulation) and claims that can be made to the consumer. Enhanced personal hygiene is one of the keyways to prevent the spread of the COVID-19. Leave-on hand gels can be effective in this regard, but they are also subject to different European Union (EU) regulatory frameworks depending on their properties and purpose. This is one of the reasons whythe Commission adopted the Coronavirus crisis guidance.
The new technical guidance provides full clarity on the claims that must not be used on cosmetic leave-on hand gels. These include claims such as “kills bacteria” or “sanitizing,” pictures or graphics related to coronavirus, and symbols with medical connotation such as a hospital red cross. EU economic operators and national competent authorities can now refer to this technical guidance and implement the applicable legal framework in a more harmonized and coherent way.
Based on the outcome of the evaluation of the medicines for rare diseases and children legislation, the European Commission will examine the impacts of future policy options to update the legal framework on medicines for rare diseases and pediatric medicines. The first step is an inception impact assessment (roadmap). The proposed revision to regulations will address shortcomings that were identified in a recent evaluation, aiming to ensure that:
- Products addressing the specific needs of children and patients with rare diseases are developed.
- These groups have timely access to medicines.
- There are efficient assessment and authorization procedures.
European Medicines Agency (EMA)
Zerbaxa (ceftolozane/tazobactam) is indicated for the treatment of the following infections in adults: complicated intra-abdominal infections, acute pyelonephritis, complicated urinary tract infections, and hospital-acquired pneumonia (HAP), including Ventilator-Associated Pneumonia (VAP). According to the analysis performed by Merck Sharp & Dohme Corp. (MSD), seven batches of Zerbaxa failed sterility tests, and manufacturing of the product has been temporarily stopped. A total of five of these batches tested positive for Ralstonia pickettii, and two batches produced turbid results that could not be further identified. The investigation into the source of the contamination is ongoing, and the seven batches have not been released to the market. While all product batches distributed to the market have met the registered specifications for release, including the test for sterility, as a precautionary measure, MSD is conducting a voluntary Class II (healthcare professional level) global recall of all Zerbaxa within expiry. Accordingly, MSD is informing healthcare professionals (HCPs) to immediately discontinue use of Zerbaxa in their patients. HCPs should consider alternative treatment.
Submission of batch safety test data from target or laboratory animals is a requirement for
batch release of veterinary vaccines in several regions participating in the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) and may also be required in other regions. The VICH Steering Committee has proposed to harmonize the batch safety tests across the regions to minimize the need to perform separate studies for regulatory authorities of different countries. The initial steps were focused on the Target Animal Batch Safety Test (TABST) and adoption of two guidelines harmonizing criteria for waiving the TABST for inactivated (VICH GL50(R)) and live vaccines (VICH GL55). This guideline addresses Laboratory Animal Batch Safety Tests (LABST) and harmonization of criteria for waiving it in regions where it is required.
Cyberattack on EMA – Update 3, 22 December 2020
The ongoing investigation of the cyberattack on the EMA, carried out by the Agency in close collaboration with law enforcement and other relevant entities, has revealed that the data breach was limited to one Information Technology (IT) application. The perpetrators primarily targeted data related to COVID-19 medicines and vaccines and unlawfully accessed documents belonging to third parties. The companies concerned at this stage have been contacted and duly informed. As the investigation proceeds and all potentially suspicious activity is analyzed, the Agency will ensure that any additional third party whose documents may have been subject to unauthorized access is notified. The EMA and the European medicines regulatory network remain fully functional, and timelines related to the evaluation and approval of COVID-19 medicines and vaccines are not affected. The EMA will continue to provide information in due course, to the extent possible, given its duty toward the ongoing investigation.
United States Food and Drug Administration (USFDA) – Guidances and Discussion Papers
Communicating Cybersecurity Vulnerabilities to Patients: Considerations for a Framework outlines considerations for the USFDA, federal partners, and industry stakeholders to help thoughtfully inform patients and the public about cybersecurity vulnerabilities. This discussion paper includes proposed considerations received during the Patient Engagement Advisory Committee (PEAC) meeting held on 10 September 2019 on cybersecurity in medical devices.
The final guidance, Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs, Guidance for Industry, which was first issued as a draft in 2019, provides the USFDA’s current thinking on steps to broaden eligibility criteria in clinical trials through inclusive trial practices, trial designs, and methodological approaches. The guidance aims to provide recommendations for how sponsors can increase enrollment of underrepresented populations in their clinical trials. This guidance offers recommendations on how product sponsors can improve clinical trial diversity by accounting for logistical and other participant-related factors that could limit participation. For example, clinical trials requiring frequent visits to specific sites may place an added burden on participants. Sponsors are encouraged to think about reducing visit frequency, when appropriate, in addition to considering whether flexibility in visit windows is possible and whether electronic communications, such as phone, email, social media platforms, or other digital health technology tools can replace site visits and provide investigators with real-time data.
This guidance is being issued to assist the industry in understanding when a microneedling product is a device as defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. § 321(h), and is, therefore, subject to the device requirements under the FD&C Act and its implementing regulations. This document also provides information on the regulatory pathway to market for microneedling devices for aesthetic use. This guidance addresses certain “microneedling products,” which is a generic term that encompasses instruments with common technological features that include an array of needles, “micro-protrusion” tips, or pins, which can be blunt or sharp and of varying lengths. The needles are incorporated into the body of an instrument that facilitates rolling or stamping of these needles across or into the skin. For example, the needles may be attached to a cylinder that is rolled across the skin, attached perpendicular to a flat surface that is applied to the skin in a “stamping” fashion, or arranged in an array on the tip of a pen-shaped instrument. The application of needles to skin may be performed manually or motorized, where the depth and speed of penetration of needles into the skin can be controlled. Other generic terms used to describe microneedling products include microneedling or needling instruments, needlers, dermal rollers, microneedle rollers, microneedle stamps, dermal stamps, and variations thereof.
Insanitary Conditions at Compounding Facilities, Guidance for Industry, November 2020
This guidance describes examples of insanitary conditions that the USFDA has observed at compounding facilities. This guidance specifically addresses drugs (including biological products) produced by pharmacies, federal facilities, and outsourcing facilities that compound or repackage drugs, or that mix, dilute, or repackage biological products. The USFDA is issuing this guidance to help compounding facilities and state regulatory agencies understand some examples of what the USFDA considers to be insanitary conditions that could cause a drug product to become contaminated or rendered injurious to health. These examples are intended to help compounding facilities prevent the occurrence of these and other insanitary conditions. This guidance is also intended to help compounding facilities identify and remediate such insanitary conditions when they already exist.
United States Food and Drug Administration (USFDA) – Recalls
Nostrum Laboratories, Inc. is voluntarily recalling two lots of Metformin HCl Extended-Release Tablets, USP 500 mg to the consumer level. The Metformin HCl Extended-Release Tablets, USP 500 mg have been found to contain levels of nitrosamine impurities above the ADI limit of 96 ng/day as published in the FDA Guidance Document issued in September 2020. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables. Nostrum Laboratories, Inc. has not received any reports of adverse events related to this recall. The product is indicated as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes mellitus and is packaged in high-density polyethylene (HDPE) bottles of 100 tablets, under NDC 29033-055-01. The product can be identified as an off-white oblong tablet debossed with “NM5.” Metformin HCl Extended-Release Tablets, USP 500 mg was distributed nationwide to wholesalers.
MPM Medical is voluntarily recalling one lot of Regenecare HA Hydrogel to the consumer level. Following two customer complaints of visible contamination, the product was found to be contaminated with the bacteria Burkholderia cepacia (B. cepacia). Topical application of Regenecare HA Hydrogel contaminated with B. cepacia may result in local skin infections. For immunocompromised patients, including patients receiving chemotherapy and patients with cystic fibrosis, the skin infection is more likely to spread into the blood stream, leading to life-threatening sepsis, which includes symptoms such as fever, difficulty breathing, low blood pressure, fast heart rate, mental confusion, and possibly death. To date, MPM Medical has not received any reports of adverse events related to this recall. Regenecare HA Hydrogel is an over-the-counter (OTC) product that contains 2% lidocaine and is used topically for temporary relief of pain and itching associated with minor burns, sunburn, minor cuts, scrapes, insect bites, or minor skin irritations, and it is packaged in 3 oz. plastic tubes and distributed in boxes of 12.
Penumbra has issued an urgent recall of all configurations of the Penumbra JET 7 Reperfusion Catheter with Xtra Flex Technology (JET 7 Xtra Flex) based on the risk of unexpected death or serious injury while used for removing clots in stroke patients. All users should stop using this device, and facilities should remove these devices from inventory as directed in Penumbra’s Urgent Voluntary Medical Device Recall Notification.
The affected devices include:
- JET 7 Xtra Flex catheter, originally cleared under K190010 on 16 June 2019
- JET 7MAX configuration (which includes the JET 7 Xtra Flex catheter and MAX Delivery Device), cleared under K191946 on 27 February 2020
This recall does not apply to the Penumbra JET 7 Reperfusion Catheter with Standard Tip. The USFDA has received more than 200 medical device reports (MDRs) associated with the JET 7 Xtra Flex catheter, including deaths, serious injuries, and malfunctions. Twenty of these MDRs describe 14 unique patient deaths, which include reports from different reporting sources for a single adverse event. Other MDRs describe serious patient injury such as vessel damage, hemorrhage, and cerebral infarction. Device failure modes reported in the MDRs include ballooning, expansion, rupture, breakage or complete separation, and exposure of internal support coils near the distal tip region of the JET 7 Xtra Flex catheter.
United States Food and Drug Administration (USFDA) – Warning Letters
USFDA Warns Companies Illegally Selling CBD Products, 22 December 2020
The USFDA issued five warning letters to companies for selling products containing cannabidiol (CBD) in ways that violate the FD&C Act. All five warning letters address the illegal marketing of unapproved CBD products claiming to treat medical conditions. The warning letters include CBD products that are especially concerning from a public health perspective due to the route of administration, including nasal, ophthalmic, and inhalation. In addition, they address violations relating to the addition of CBD to food, as well as the impermissible marketing of CBD products as dietary supplements. Two of the letters also address CBD products illegally marketed for pets, including a product for use in the eye.
The warning letters were issued to:
- Bee Delightful
- G&L Wellness (C Better Daily)
- New Leaf Pharmaceuticals
- NextL3vel Services Group, LLC doing business as This Stuff Is Good For You
- Wellness BioSciences
The USFDA has posted a warning letter that was issued to Whole Foods Market for a pattern of receiving and offering for sale misbranded food products necessitating a series of food recalls for allergens. In the last year, Whole Foods Market has recalled more than 30 food products because the presence of major food allergens was not listed on the finished product labels. The USFDA noticed similar patterns of numerous recalls by Whole Foods Market for undeclared allergens in previous years as well. These products included a variety of foods sold under the Whole Foods brand, primarily in the deli and bakery sections of the store. This is the first time the USFDA has warned a retailer for engaging in a pattern of receiving and offering for sale misbranded food products containing undeclared allergens.
Food allergies and other types of food hypersensitivities affect millions of Americans and their families. To protect consumers, US law requires that food or ingredients that contain major food allergens be specifically labeled with the name(s) of the allergen source. The eight foods identified as major food allergens are:
- Milk
- Eggs
- Fish (e.g., bass, flounder, cod)
- Crustacean shellfish (e.g., crab, lobster, shrimp)
- Tree nuts such as almonds, walnuts, and pecans (complete list of tree nuts)
- Peanuts
- Wheat
- Soybeans
Undeclared food allergens have been the number one leading cause of Class I food recalls for at least the last three years. As part of the USFDA’s ongoing efforts to address undeclared allergens as the leading cause of food recalls, the Agency has analyzed patterns of recalls and has begun several initiatives to improve industry’s compliance with allergen labeling requirements and reduce undeclared allergen-related food recalls.
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