SQA Regulatory Surveillance Summary 4 | Monthly Update 2021

By Laurel Hacche, Debra Cortner, & Dondi Pulse-Earle SQA Associates

SQA Regulatory Surveillance Summary #4, 2021

Agência Nacional de Vigilância Sanitária (ANVISA)

Brazilian Regulators Update Economic Monitoring Requirements for Some Medical Devices, 26 March 2021

ANVISA has issued new regulations regarding economic monitoring of certain device types in order to boost transparency and establish reference pricing for these products. The new regulation, RDC 478/2021, repeals economic monitoring and reporting processes previously established under RDC 185/2006, and initially reduces the number of medical device types for which economic monitoring will be required. The new regulation takes effect on 01 April 2021. In a new Normative Instruction, ANVISA identifies 13 device types falling under RDC 478/2021, including implantable defibrillators, cardiac valve prostheses, arterial stents, and pacemakers. Data pertaining to price and technical specifications of these devices must be provided to ANVISA according to the following timeframes:

  • For new registrations, submissions are required within 60 days of registration publication by ANVISA.
  • For existing registrations, submissions are required either upon renewal of those registrations or 60 days following ANVISA approval of a device modification, whichever comes first.

ANVISA: The Advances of 2020 in Regulatory Quality Improvement, 31 March 2021

ANVISA released on 05 March the report Regulation in Numbers, presenting the 2020 actions aiming to improve the regulatory quality of the Agency. The report summarizes the main activities of the year, such as general and normative publications, regulatory projects, community participation events, and innovations implemented. The Report shows that 161 regulatory instruments were published in 2020, covering Collegiate Board Resolutions (RDC), Normative Instructions (IN), Joint Normative Instructions (INC), and Guides. Regulations on drugs and medical devices were prevalent among those related to products subject to health regulation. Due to the COVID-19 pandemic, there was an increase of 39.2% on regulations published by ANVISA. A total of 53 normative acts and two Guides were issued regarding the access to essential products and services in the fight against the new coronavirus.

ANVISA has also released a set of 106 proposals for Regulatory Projects that will compose the 2021-2023 Regulatory Agenda. There are 11 regulatory projects for the medical devices’ field:

  • Implementation of the National Implant Registry (RNI) in Brazil’s public and private health services
  • Unique Device Identification (UDI) for medical devices
  • Revision of the medical device clinical trials normative (Resolution RDC No. 10/2015)
  • Creation of a normative to increase access to medical devices
  • Updates on the Normative of Blood Bags Good Manufacturing Practices
  • Reprocessing of Reusable Medical Devices
  • Regulation of importation, commercialization, and donation of used and refurbished medical devices
  • Regulation for Software as a Medical Device
  • Regularization of orthopedic implants
  • Parametric release of medical devices
  • Review of the Resolution RDC No. 183/2017, which provides the procedures to obtain the Brazilian Good Manufacturing Practices (BGMP) Certification for medical devices

In addition, 140 Regulatory Processes have been initiated, formalizing the start of the regulatory assessment that ends with the publication of normative by the Agency.

China: National Medical Products Administration (NMPA)

NMPA Announcement on Issuing the Provisions for the Change Management of Post-approval Drugs (Interim), 13 January 2021

In accordance with the relevant provisions of the Drug Administration Law, to reinforce the management of changes of post-approval drugs, the NMPA organized to formulate the Provisions for Change Management of Post-approval Drugs (Interim), which went into effect as of 12 January 2021. The provisions of this Announcement prevail over those previously announced. Each provincial drug regulatory department must implement the responsibility for supervision over change management of post-approval drugs at its administrative area, by specifying requirements, formulating working documents, and clarifying time limits. The cooperation between drug registration administration and production supervision should be consolidated for mutual support, to ensure the smooth and orderly implementation of change management of post-approval drugs.

NMPA Publishes Guidelines for Device Master File (DMF) Submissions, 06 April 2021

China’s NMPA has published Announcement No. 36 of 2021, which outlines the requirements for the voluntary record filing of a DMF for domestic Class III and imported Class II and III medical devices (including IVD reagents). The contents of this announcement became effective immediately upon publication. The NMPA initially released a draft guidance document concerning DMF record filing in early 2019. The DMF record filing procedure mainly concerns raw material supplier documentation and is intended to avoid the repeated submission and review of the technical data. The announcement describes the basic procedure and requirements for a DMF submission. Attachments to the announcement include the application forms, a record filing receipt template, and other information pertaining to the DMF record filing procedure. The Center for Medical Device Evaluation (CMDE) will issue a DMF registration number following the submission process.

European Pharmacopoeia (Ph. Eur.)

Update on the Ph. Eur. Policy on Elemental Impurities – Monographs on Substances for Veterinary use Only, 22 April 2021

The European Pharmacopoeia (Ph. Eur.) has launched a public consultation on its proposal to delete the test for “heavy metals” (HMs, general chapter 2.4.8) in monographs on substances “for veterinary use only.” The 16 monographs concerned have been published in Pharmaeuropa 33.2 together with other new texts and technical revisions of the Ph. Eur. The deadline for comments is 30 June 2021. This public enquiry is the most recent stage in the implementation strategy endorsed by the Ph. Eur. Commission in March 2015 after the publication, in December 2014, of the Q3D Guideline on Elemental Impurities (EI) by the International Council for Harmonization (ICH). Marking a true paradigm shift for the control of EI, implementing the guideline immediately became a top priority for the Ph. Eur. Commission.

Essential Oils: Revised Monograph and New General Chapter in the Ph. Eur., 16 April 2021

The 169th Session of the European Pharmacopoeia (Ph. Eur.) Commission, held in March, saw the adoption of the revised general monograph on essential oils (2098) and of the new chapter on monographs on essential oils (information chapter) (5.30). The essential oils general monograph has been completely overhauled to expand, among others, the definition, production, test, and labelling sections, providing additional detail and clarification. The text now offers more information concerning the herbal drugs and the quality of water to be used for the preparation of essential oils and gives requirements for heavy metals (2.4.27), pesticide residues (2.8.13), Aflatoxin B1 (2.8.18), and microbiological quality (5.1.4 or 5.1.8). The new chapter provides underlying principles for the elaboration of monographs on essential oils, with details of production methods, chromatographic profiles, and potential contaminants. The chapter also describes the conditions under which skip testing is justified and the various uses of rectification. Both texts will be published in Supplement 10.7 of the Ph. Eur.

General Chapter 2.5.42. N-Nitrosamines in Active Substances and Revised Sartan Monographs 17 March 2021

In February 2021, the Ph. Eur. Commission revised the five monographs on sartans with a tetrazole ring, namely Valsartan (2423), Losartan Potassium (2232), Irbesartan (2465), Candesartan Cilexetil (2573), and Olmesartan medoxomil (2600), using the rapid revision process. The Production section was reworded, and the N-nitrosamines test section was deleted. A reference to general chapter 2.5.42, N-Nitrosamines in active substances, was introduced in the Production section to assist manufacturers. The five revised monographs became legally binding on 01 April 2021.

Health Canada – Biologics

Backgrounder – Government of Canada Investments in Biomanufacturing, Development of COVID-19 Vaccines and Therapeutics, and Research, 18 May 2021

The Government of Canada’s number one priority is to protect the health of Canadians. That’s why the government is implementing a multi-faceted procurement strategy to provide a COVID-19 vaccine to every Canadian who wants one by September. The government established the Vaccine and Therapeutics task forces and Biomanufacturing Subcommittee, made up of leading industry experts and scientists, to advise the government on how to address this challenge as a national priority. Since the outset of the pandemic, the government has made a series of investments in biomanufacturing, the development of domestic vaccine and therapeutic candidates, and targeted research that will help advance medical counter measures to protect Canadians, and also improve Canada’s global competitiveness. The government continues to take action based on the best available science, both in pursuing vaccine and therapeutic candidates and investing in biomanufacturing opportunities to fight the current pandemic and to build resilience for future pandemics. Funding for investments in biomanufacturing, development of COVID-19 vaccines and therapeutics, and research is committed through the following areas:

  • Strategic Innovation Fund
  • Next Generation Manufacturing Canada Supercluster
  • National Research Council
  • Regional Development Agencies
  • Canada Foundation for Innovation
  • Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council (NSERC), and Social Sciences and Humanities Research Council (SSHRC)
  • Variants of Concern (VOC) Research
  • Additional Investments and Projects Underway

Health Canada – Drugs, Devices, Food, and Cosmetics

Face Masks that Contain Graphene May Pose Health Risks, 02 April 2021

Health Canada is advising Canadians not to use face masks that contain graphene because there is a potential that they could inhale graphene particles, which may pose health risks. Graphene is a novel nanomaterial (i.e., materials made of tiny particles) reported to have antiviral and antibacterial properties. Health Canada conducted a preliminary scientific assessment after being made aware that masks containing graphene have been sold with COVID-19 claims and used by adults and children in schools and daycares. Health Canada believes they may also have been distributed for use in health care settings.

Health Canada’s preliminary assessment of available research identified that inhaled graphene particles had some potential to cause early lung toxicity in animals. However, the potential for people to inhale graphene particles from face masks and the related health risks are not yet known and may vary based on mask design. The health risk to people of any age is not clear. Variables, such as the amount and duration of exposure, and the type and characteristics of the graphene material used, all affect the potential to inhale particles and the associated health risks. Health Canada has requested data from mask manufacturers to assess the potential health risks related to their masks that contain graphene.

Until the Department completes a thorough scientific assessment and has established the safety and effectiveness of graphene-containing face masks, it is taking the precautionary approach of removing them from the market while continuing to gather and assess information. Health Canada has directed all known distributors, importers, and manufacturers to stop selling and to recall the affected products. Additionally, Health Canada has written to provinces and territories advising them to stop distribution and use of masks containing graphene. The Department will continue to take appropriate action to stop the import and sale of graphene face masks.

Lots of Irbesartan, Losartan, and Valsartan Drugs Recalled Due to Azido Impurity, 30 May 2021

Health Canada is informing Canadians that the following companies are recalling multiple lots of irbesartan, losartan, and valsartan drug products after tests found an azido impurity above the acceptable limit:

  • Auro Pharma Inc.
  • Mint Pharmaceuticals Inc.
  • Pharmascience Inc.
  • Pro Doc Ltd.
  • Sandoz Canada Inc.
  • Sanis Health Inc.
  • Sivem Pharmaceuticals ULC
  • Sun Pharma Canada Inc.
  • Teva Canada Ltd.

 Irbesartan, losartan, and valsartan are all prescription Angiotensin Receptor Blocker (ARB) drugs, which are also known as “sartans.” Sartans are a class of drugs used to treat patients with high blood pressure to help prevent heart attacks and stroke. They are also used in patients with heart failure or those who have had a recent heart attack. The azido impurity, (5-(4′-(azidomethyl)-[1,1′-biphenyl]-2yl)-1H-tetrazole, is considered a mutagen. A mutagen is a chemical substance that can cause a change in the DNA of a cell. These mutations may increase the risk of cancer, but the specific risk for this azido impurity to cause cancer in humans is unknown. There are established international guidelines that recommend that mutagenic impurities be kept at or below a specific level because exposure to a mutagen over the long term at a level above what is considered to be safe has the potential to increase the risk of cancer. A person taking daily for 70 years a drug that contains this azido impurity at or below the acceptable level is not expected to have an increased risk of cancer.

Not all lots of irbesartan, losartan, and valsartan from these companies are affected by this issue; however, it is possible that the recalls may affect the supply of some products. Patients should speak with their doctor or pharmacist to discuss alternatives should their regular prescribed drug not be available. Health Canada expects manufacturers to take any necessary actions to reduce or eliminate the azido impurity. Impacted companies have been directed to implement control measures to ensure that the level of the impurity in their products is at or below the acceptable level. Health Canada is monitoring the effectiveness of the recalls. Should additional recalls be deemed necessary, Health Canada will inform Canadians.

India – Central Drugs Standard Control Organization (CDSCO)

India CDSCO Delays Regulation Deadline for Implantable Medical Devices, 27 April 2021

The CDSCO has postponed deadlines for regulating implantable devices and other medical products for which manufacturers or importers have already applied for licenses under the Medical Device Rules 2017. According to a recent CDCSO order, Notification S.O. 775(E) establishing regulation of the following medical devices will be delayed by six months:

  • Implantable medical devices
  • CT scan equipment
  • MRI equipment
  • Defibrillators
  • PET equipment
  • Dialysis machines
  • X-Ray machines
  • Bone marrow cell separator devices

Implementation of regulatory requirements for the above device types had been set for 01 April 2021, but CDSCO cites the need for additional time to prepare for compliance in order to complete procedural work such as audits of facilities, query resolutions, and related issues. As such, manufacturers and importers that have already submitted their applications to CDSCO may continue marketing their devices in India as they prepare for compliance.

India – United States Department of Justice

India  Cancer Drug Manufacturer Agrees to Plead Guilty and Pay $50 Million for Concealing and Destroying Records in Advance of United States Food and Drug Administration (FDA) Inspection, 09 February 2021

Indian drug manufacturer Fresenius Kabi Oncology Limited (FKOL) has agreed to plead guilty to concealing and destroying records prior to a 2013 U.S. FDA plant inspection and pay $50 million in fines and forfeiture. In a criminal information filed in federal court in the District of Nevada and unsealed on 09 February 2021, the United States charged FKOL with violating the Federal Food, Drug, and Cosmetic Act by failing to provide certain records to FDA investigators. As part of a criminal resolution, FKOL agreed to plead guilty to the misdemeanor offense, pay a criminal fine of $30 million, and forfeit an additional $20 million. FKOL also agreed to implement a compliance and ethics program designed to prevent, detect, and correct violations of U.S. law relating to FKOL’s manufacture of cancer drugs intended for terminally ill patients.

According to court documents, FKOL owned and operated a manufacturing plant in Kalyani, West Bengal, India, that manufactured active pharmaceutical ingredients (APIs) used in various cancer drug products distributed to the United States. The government alleges that prior to a January 2013 FDA inspection of the Kalyani facility, the FKOL plant management directed employees to remove certain records from the premises and delete other records from computers that would have revealed FKOL was manufacturing drug ingredients in contravention of FDA requirements. Kalyani plant employees removed computers, hardcopy documents, and other materials from the premises and deleted spreadsheets that contained evidence of the plant’s violative practices.

International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guidances – Efficacy, Multidisciplinary, and Safety

The ICH S1B(R1) Draft Guideline Reaches Step 2 of the ICH Process, 10 May 2021

The ICH S1B(R1) Addendum to the Guideline on Testing for Carcinogenicity of Pharmaceuticals reached Step 2 of the ICH process on 10 May 2021 and now enters the public consultation period. This addendum is complementary to the S1 Guidelines (S1A, S1B. and S1C(R2)). At Step 4 of the ICH process, the addendum will be integrated with the S1B Guideline. This addendum expands the testing scheme for assessing human carcinogenic risk of small molecule pharmaceuticals by introducing an additional approach that is not described in the original S1B Guideline. Application of this integrative approach would reduce the use of animals in accordance with the 3Rs (reduce/refine/replace) principles, and shift resources to focus on generating more scientific mechanism-based carcinogenicity assessments, while promoting safe and ethical development of new small molecule pharmaceuticals.

ICH E6 Guideline for Good Clinical Practice (GCP) – Update on Progress, 18 to 19 May 2021

On behalf of ICH, the ICH E6 GCP Expert Working Group (EWG) held a free public web conference to provide an update on the progress to revise this important and impactful guideline. This web conference was convened by the Clinical Trials Transformation Initiative (CTTI). The EWG held two similar meetings on 18 May 2021 (8:00 to 11:00 am EDT) and 19 May 2021 (6:00 to 9:00 pm JST) to reach a broad global audience across time zones. As described on the agenda, the same topics were presented each day with speakers from different regions to represent the global effort. 

In this web conference, members of the ICH E6 EWG discussed the work-in-progress to develop principles and annexes for ICH E6 GCP (third version or E6(R3)) that are intended to be responsive across clinical trial types and settings and to remain relevant as technology and methodologies advance. The draft, work-in-progress principles that were made public by the ICH on 19 April 2021 are designed to be flexible and applicable to a broad range of clinical trials. The principles are provided on the ICH website. The EWG is not taking public comments on the principles at this stage. However, once the ICH E6 guideline achieves Step 3 of the ICH guideline development process, the EWG will invite and consider public input.

The EWG also discussed its plans and approaches to update the guideline in general and its engagement efforts with a variety of stakeholders that greatly enriched the discussions of the EWG. As part of these continued efforts to engage with stakeholders, the web conference included presentations from stakeholders on their vision and aspiration for clinical trial design and conduct that are responsive to the needs of the community.

Medicines and Healthcare Products Regulatory Agency (MHRA) – Biologics

Guidance on the Licensing of Biosimilar Products, 06 May 2021

The purpose of the MHRA Guidance on the Licensing of Biosimilar Products is to provide developers of similar biological medicinal products (also known as biosimilars) with a clear outline of the requirements for biosimilar products in Northern Ireland / Great Britain / the UK. Applicants should also take into account principles contained within the Committee for Medicinal Products for Human Use (CHMP) guidelines:

This MHRA guidance contains further clarifications and some revisions to these CHMP guidance documents, which take into account the scientific and regulatory experience gained since the first biosimilar product was licensed in 2006, including biosimilar monoclonal antibodies and fusion proteins licensed from 2013.

MHRA – Drugs, Devices, Food, and Cosmetics

Targeted Communication: CE Mark Suspended for All MAGEC Systems Manufactured by NuVasive Specialized Orthopedics, Inc., 10 May 2021

This was a targeted MHRA communication that was sent to specific professional associations with respect to CE Mark suspension for all MAGEC systems manufactured by NuVasive Specialized Orthopedics, Inc. It was sent on 06 May 2021. It was also published on the MHRA website on 10 May 2021 for informational purposes.

In March 2020, NuVasive Specialized Orthopedics, Inc. (NSO) voluntarily suspended the supply of MAGEC systems to the UK. This was on the request of the MHRA, pending the outcome of an MHRA investigation. This was communicated by a MHRA’s Medical Device Alert and a Field Safety Notice (FSN) issued by NSO on 01 April 2020. The MHRA’s investigation has identified several deficiencies with the technical documentation relating to MAGEC systems and NSO’s quality management system. The MHRA sent its initial findings to NSO and their EU Notified Body in September 2020. Following this report, the Notified Body undertook its own review, which resulted in the CE certificate being suspended on 25 March 2021. Additional details on the MHRA’s investigation will be communicated in due course.

The MHRA, in consultation with its independent Spinal Expert Advisory Group, has continued to monitor the safety and performance of the MAGEC system. The MHRA recognizes that there are additional uncertainties stemming from the suspension of the CE certificate and, following feedback from the clinical community, has updated their recommendations for clinicians.

Recall of BD Venflon Pro Safety and Venflon Pro IV Cannula, 04 May 2021

Becton Dickinson (BD) is recalling all ethylene oxide (EtO) sterilized BD Venflon Pro Safety (VPS) and Venflon Pro IV Cannula after identifying an increase in reports of leakage from the injection port. BD has updated its FSN information and is now also recalling Venflon Pro products sterilized by EtO. It does not affect products sterilized by electron beam. The recall is being conducted due to a risk of blood or fluid loss from the injection port, which can result in serious harm if undetected. Reported issues to date include:

  • Minor to severe blood loss
  • Delay to treatment
  • Failure of cannula leading to replacement
  • Non-delivery of critical medications

Information from the manufacturer indicates an increased risk if there are larger cannulae and if the devices are used in combination with rapid pressurized fluid infusers.

Therapeutic Goods Administration (TGA)

Guidance on the Management of Good Manufacturing Practice (GMP) Compliance Signals for Domestic and Overseas Manufacturers of Medicines and Biologicals, 18 May 2021

The Guidance on the Management of GMP Compliance Signals for Domestic and Overseas Manufacturers of Medicines and Biologics outlines the GMP compliance requirements, according to the manufacturing principles for production of biologicals and medicines intended for supply in Australia and the framework for managing GMP compliance signals. GMP is used internationally to describe a set of principles and procedures that, when followed by manufacturers of therapeutic goods, helps ensure that each batch of a therapeutic good is safe, reliable, and of consistent high quality. This guidance applies to:

  • Licensed manufacturers in Australia
  • Sponsors responsible for any overseas site in the manufacture of a medicine or API supplied to Australia

This guidance is not intended for manufacturers and sponsors of medical devices.

Communication to Stakeholders: Remaking of Standards and Legislative Instruments for Human Cell and Tissue (HCT) Products, Blood, and Blood Components, 26 May 2021

The TGA is seeking feedback on a proposal to remake some of the legislative instruments relating to HCT products (including blood and blood components), which expire in October 2021. Although all these legislative instruments continue to operate largely effectively and efficiently, it would be beneficial to improve clarity on some requirements as well as create efficiency through increased international harmonization, thus ensuring they continue to be fit for their purpose. Accordingly, the TGA is proposing to remake these Therapeutic Goods Orders (TGOs) and the other legislative instruments under section 10 and section 32A of the Therapeutic Goods Act 1989 (the Act), respectively. The TGOs relevant to this consultation can be broadly categorized into three groups:

  • Product-specific standards for human musculoskeletal tissue, cardiovascular tissue, ocular tissue, and skin
  • Labeling requirements
  • General donor selection and testing requirements

TGA is seeking feedback on the suitability and potential regulatory impact that any proposed amendments may have on affected stakeholders. 

United States Department of Health and Human Services (HHS) – Laws, Regulations, and Guidances

Clinical Laboratory Pays $25,000 to Settle Potential Health Insurance Portability and Accountability Act (HIPAA) Security Rule Violations, 25 May 2021

Peachstate Health Management, LLC, doing business as AEON Clinical Laboratories (Peachstate), has agreed to pay $25,000 to the Office for Civil Rights (OCR) at the HHS and to implement a corrective action plan to settle potential violations of the HIPAA Security Rule. Peachstate is based in Georgia and is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Peachstate provides diagnostic and laboratory-developed tests, including clinical and genetic testing services. In December 2017, the OCR initiated a compliance review of Peachstate to determine its compliance with the HIPAA Privacy and Security Rules. The OCR’s investigation found systemic noncompliance with the HIPAA Security Rule, including failures to conduct an enterprise-wide risk analysis, implement risk management and audit controls, and maintain documentation of HIPAA Security Rule policies and procedures.

In addition to the monetary settlement, Peachstate has agreed to a robust corrective action plan that includes three years of monitoring. The resolution agreement and corrective action plan may be found at: https://www.hhs.gov/sites/default/files/peachstate-ra-cap.pdf – PDF.

United States FDA – Regulations and Guidances for Biologics and the Bioresearch Monitoring Program (BIMO)

Bispecific Antibody Development Programs Guidance for Industry, May 2021

The FDA has issued a final guidance, Bispecific Antibody Development Programs, which provides recommendations for industry and other parties involved in developing bispecific antibodies, which are antibody-based products that target more than one antigen. These recommendations include specific regulatory and scientific considerations for bispecific antibodies. Industry and other stakeholders can engage the FDA to discuss their individual bispecific antibody under development. With regard to changes from the draft version of this guidance, this final guidance clarifies quality, nonclinical, and clinical considerations when developing bispecific antibodies. Bispecific antibodies have potential advantages over other therapies, as they can target multiple disease-modifying molecules with one drug. Additional guidance is warranted regarding the regulatory pathway to evaluate bispecific antibodies.

FDA Provides Guidance on Master Protocols for Evaluating Prevention, Treatment Options for COVID-19, May 2021

The FDA has issued a final guidance, COVID-19: Master Protocols Evaluating Drugs and Biological Products for Treatment or Prevention. This guidance describes the FDA’s current recommendations to sponsors of master protocols evaluating drugs for the treatment or prevention of COVID-19. A master protocol is defined as a protocol designed with multiple substudies, which involve coordinated efforts to evaluate one or more investigational drugs, in one or more disease subtypes, with one or more objectives, all within the same overall trial structure. This guidance focuses on the design, conduct, and statistical considerations of master protocols intended to generate or contribute to substantial evidence of effectiveness and adequate characterization of the safety of drugs for the treatment or prevention of COVID-19. Additionally, this guidance provides administrative and procedural recommendations to sponsors of master protocols for COVID-19 drugs.

United States FDA – Regulations and Guidances for Drugs, Devices, Food, and Cosmetics

FDA Issues Final Guidance on Implanted Brain-Computer Interface Devices for Patients with Paralysis or Amputation – Non-clinical Testing and Clinical Considerations, 20 May 2021

Implanted brain-computer interface (BCI) devices have the potential to bring benefit to people with severe disabilities by restoring lost motor and sensory capabilities in patients with paralysis or amputation. Non-clinical device testing can be used to demonstrate that potential risks have been mitigated prior to initiating a clinical study. Proper design of clinical trials is essential to provide a reasonable assurance of safety and effectiveness necessary to support a regulatory submission, and translation of BCI devices from concept to assisting device users. The FDA has issued the final guidance, Implanted Brain-Computer Interface (BCI) Devices for Patients with Paralysis or Amputation – Non-clinical Testing and Clinical Considerations, which is intended to facilitate the development of safe and effective products employing this emerging technology.

United States Food and Drug Administration (FDA) – Warning Letters

FDA and Federal Trade Commission (FTC) Warn Five Companies Illegally Selling Dietary Supplements Claiming to Treat Infertility, 26 May 2021

The FDA and the FTC have issued warning letters to five companies for illegally selling dietary supplements that claim to cure, treat, mitigate, or prevent infertility and other reproductive health disorders in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The warning letters were issued to LeRoche Benicoeur/ConceiveEasyEU Natural Inc.Fertility Nutraceuticals LLCSAL NATURE LLC/FertilHerb, and NS Products, Inc.

Under the FD&C Act, products intended to cure, treat, mitigate, or prevent disease are drugs and are subject to the requirements that apply to drugs, even if they are labeled as dietary supplements. Unlike drugs approved by the FDA, the agency has not evaluated whether the unapproved products subject to the warning letters announced today are effective for their intended use, what the proper dosage might be, how they could interact with FDA-approved drugs or other substances, or whether they have dangerous side effects or other safety concerns. In general, consumers should be cautious of products marketed and sold online with unproven claims to prevent, treat, mitigate, or cure diseases. The FDA advises consumers to talk to their doctor, pharmacist, or other health care provider before deciding to purchase or use any dietary supplement or drug. Some supplements might interact with medicines or other supplements. Also, if claims sound too good to be true, they probably are.

The FDA has requested responses from the companies within 15 working days stating how they will address these issues or providing their reasoning and supporting information as to why they think the products are not in violation of the law. Failure to correct violations promptly may result in legal action, including product seizure and/or injunction.

United States Pharmacopeia (USP)

General Chapter <1xxx> Supplier Qualification, 26 March 2021

This informational general chapter will provide a quality risk-based approach for organizations and individuals involved in identifying, selecting, assessing, approving, and monitoring suppliers of materials (e.g., active pharmaceutical ingredient, excipients, components, and other raw materials), packaging material (e.g., primary, secondary, ancillary, and shipping packaging), and service providers (e.g., contract manufacturing/packaging/repackaging, logistic providers for warehousing and transportation, software providers, calibration/qualification services, and analytical services).

The chapter will discuss supplier qualification within the context of its lifecycle, where the five-step lifecycle process will be elaborated: Preparation, Identification and Selection, Evaluation and Acceptance, Performance Monitoring, and Disqualification. In the development of this chapter, USP will leverage Xavier Health’s document titled Good Supply Practices for the 21st Century.

General Chapter Prospectus: <1002> Filters and Membranes, 26 March 2021

USP intends to develop a new informational chapter that contains recommendations for the selection, characterization, integrity evaluation, use, and qualification of filters and membranes used in procedures such as, but not limited to, dissolution, chromatography, general sample preparation procedures, and in-vitro release testing. The following represents the sections for the proposed General Chapter: Introduction, Pore size and Pore Morphology, Types of Membranes and their Characteristics, Leachables and Extractables, Analyte Binding, Integrity Evaluation, and Uses and Applications.