SQA Regulatory Surveillance Summary 6 | Monthly Update 2021
By Laurel Hacche & Debra Cortner SQA Associates
SQA Regulatory Surveillance Summary #6, 2021
Agência Nacional de Vigilância Sanitária (ANVISA)
ANVISA has rolled out its proposed framework for Unique Device Identification (UDI) requirements. According to ANVISA Public Consultation 1051/2021, the regulator plans a six-year rollout of UDI requirements in order to boost traceability and monitoring of medical devices and equipment commercialized in Brazil. UDI compliance lead times for manufacturers will depend on the risk classification of their devices:
- Two years for Class IV (highest risk) devices
- Three years for Class III (high risk) devices
- Four years for Class II (moderate risk) devices
- Six years for Class I (low risk) devices
It is anticipated that ANVISA will review stakeholder feedback on the public consultation through November 2021, then issue a final regulation on UDI in December 2021. Based on these projections, Class IV device registrants would face a December 2023 deadline for UDI compliance. Registration holders of reusable medical devices with direct UDI marking will be granted two additional years following the deadlines listed above for compliance, noting that custom-made devices as well as investigational devices are exempt from UDI requirements, according to the consultation.
ANVISA plans to establish its own UDI database into which manufacturers or their Brazil Registration Holders (BRHs) will upload required UDI data. Once the database has gone live, BRHs will be responsible for ensuring that device UDI data are submitted to the database prior to commercialization in Brazil. Furthermore, submissions to the UDI database must also include Global Device Nomenclature (GMDN) codes, and device registration holders will be required to include UDI numbers on post-market vigilance notifications involving their products.
China: National Medical Products Administration (NMPA)
With the view to strengthening registration management of drug-device combination products, in accordance with relevant provisions for registration management of drugs and medical devices, matters concerning the registration of drug-device combination products were announced by NMPA on 23 July 2021 as follows:
- Drug-device combination products refer to medical products composed of drugs and medical devices and produced as a single entity.
- Drug-led drug-device combination products shall be registered in accordance with the relevant requirements for drugs, and device led drug-device combination products and shall be registered in accordance with the relevant requirements for medical devices, including the following guidances, as applicable:
- Medical Devices Exempted from Filing, issued 28 June 2021
- Guidance for Nomenclature for Generic Names of Medical Software, issued 12 July 2020
- Guidance for Nomenclature for Generic Names of Respiratory, issued 12 July 2021
- Anesthesia and First Aid Instruments and Guidance for Nomenclature for Generic Names of Obstetrics and Gynecology, issued 12 July 2021
- Assisted Reproduction and Contraceptive Devices, issued 12 July 2021
- The Applicant shall fully evaluate the attributes of the drug-device combination products for which to apply. For the drug-device combination products whose attributes cannot be determined, the applicants shall apply for attribute definition to Center for Medical Device Standards Management, NMPA (CMDSM) prior to registration application.
Further details with respect to the registration and NMPA approval process for drug-device combination products are provided in the NMPA Newsletter (27 July 2021).
The NMPA has revealed plans to set up a technical division focused on clinical evaluation of medical devices and has issued new guidelines for animal testing studies related to medical devices. The NMPA has announced the establishment of a national technical authority to address medical device as well as in vitro diagnostic (IVD) clinical evaluations. The new unit will oversee development and maintenance of general as well as special standards pertaining to clinical evaluations, including the following components:
- Clinical trial quality management
- Clinical data management and data exchange
- Real-world research requirements
- Clinical data processing
The NMPA announcement also identifies several expert groups that will help steer the new authority; these groups will consist of universities, hospitals, healthcare provider networks, life sciences and medical device company representatives, and regulatory agencies. Chinese regulators have published new guidelines pertaining to animal testing studies and investigations for medical device registrants. The NMPA has issued the guidelines in two parts. Part 1 covers decision-making principles to help determine whether animal testing for a device is warranted as well as how to reduce the number of such studies when possible. Part 2 covers test design and quality assurance considerations.
European Commission (EC)
The EC’s Medical Device Coordination Group (MDCG) has published a new guidance pertaining to MDR compliance for legacy devices already sold in the European Union. The MDCG has issued a report and guidance stemming from a task force’s examination of how to effectively apply transitional provisions for legacy medical devices that have been certified and commercialized in Europe prior to the MDR’s 26 May 2021 date of application. The MDCG task force focused on three key issues:
- Applying MDR Chapter VII requirements to legacy devices
- Applying other MDR requirements to legacy devices
- Applying MDR requirements to “old” devices—those placed on the EU market according to Medical Devices Directive (MDD) 93/42/EEC or Active Implantable Medical Devices Directive (AIMDD) 90/385/EEC, before the MDR took full effect
Task force recommendations regarding these issues have now been incorporated into the MDCG guidance for legacy devices.
Regulators in Europe have updated their implementation plan for sweeping new in-vitro diagnostic (IVD) medical device regulations taking effect in 2022. The updated joint implementation plan for the In-vitro Diagnostic Medical Devices Regulation (IVDR), developed by the European Commission as well as European Union member states, prioritizes essential as well as high-priority actions to be undertaken ahead of the IVDR’s 26 May 2022 date of application. Top-priority efforts targeted by European Commissioners within the next six to seven months are grouped together as “essential actions” under three key topics in the joint implementation plan:
- Contingency planning and monitoring
- Availability of Notified Bodies
- Designate EU reference laboratories
Action plans to address each of the three key topics have been established. European regulators have detailed high-priority actions as “not essential to allow manufacturers to place devices on the market, but which would greatly facilitate the work of the involved actors.” These actions pertain to:
- Common specifications
- Guidance for Notified Bodies such as batch testing and Article 110(3) of the IVDR
- Performance evaluation and expert panels
- Standards referred to by the IVDR
- Companion diagnostics and collaboration with appropriate stakeholders such as the European Medicines Agency (EMA)
- In-house devices
While some of the essential and high-priority actions may seem ambitious given the IVDR’s May 2022 date of application, many of these efforts have been assigned rolling or ongoing timeframes, and many items in the high-priority section have already been completed. Furthermore, a proposed postponement of deadlines for some IVDR components may provide European regulators and stakeholders more time to conduct some of these actions.
European Medicines Agency (EMA)
The EMA and the U.S. Food and Drug Administration (FDA) have established a pilot program to provide Parallel Scientific Advice (PSA) to applicants of Marketing Authorization Applications (MAAs) for hybrid products (EMA) and abbreviated new drug applications (ANDAs) for complex generic drug products, hereafter referred to as “complex products” (FDA). The goal of the PSA program is to provide a mechanism for the EMA and FDA to concurrently consider and jointly exchange with applicants the agencies’ views on scientific questions during the development phase of hybrid/complex generic products. Such interactions are expected to increase dialogue between the two agencies and applicants from the beginning of the lifecycle of a hybrid/complex generic drug product. Successful collaboration may provide applicants with a deeper understanding of the basis of regulatory decisions, optimize product development, and avoid unnecessary replication of studies or unnecessary testing methodologies. The agencies conduct PSA meetings under the auspices of the confidentiality arrangement between the European Commission, the EMA, and the FDA. The EMA and FDA have agreed to the following principles for the pilot program. Posting this “General Principles” statement on the websites of both agencies will make the PSA program’s process and goals more transparent and help answer questions about the program.
The pilot will begin on 15 September 2021 and meeting requests will be received until a sufficient number of PSA meetings are held to support the pilot program. There are three stages in this pilot PSA meeting process:
- Stage 1: Applicants request a meeting with EMA and FDA
- Stage 2: EMA and FDA assess the meeting package, conduct a preparatory bilateral meeting, and then conduct a trilateral meeting with the applicant
- Stage 3: EMA and FDA communicate written responses to the applicant
During and after conclusion of the pilot, each agency will evaluate the benefits and challenges of the program, including the resources required, and determine next steps.
The Clinical Trial Regulation will come into application and the Clinical Trial Information System (CTIS) will go live on 31 January 2022. This follows the publication of the Commission decision on 31 July 2021 in the Official Journal of the European Union. The Board noted the progress in the development and preparations for “go-live” of the CTIS and the CTIS global go-live plan. The Board endorsed the joint controllership arrangement for the processing of personal data when using the CTIS, which has been negotiated and agreed between representative groups of CTIS users. The CTIS functionalities, agreed for the go-live release, have been delivered and the focus is now on stabilizing the system. The developer together with EMA, Member States, sponsor, and Commission experts are testing the system in October to identify any potential remaining issues that would need to be resolved prior to go-live. EMA is providing tools and support to Member States and clinical trial sponsors, and their staff, to facilitate preparations for go-live, including registration of CTIS administrators, support in Member State and sponsor organization configuration planning, an extensive online training program, information events, and the publication of supportive documentation such as the CTIS sponsor handbook. The CTIS is the cornerstone for application of the Clinical Trial Regulation. Clinical research and patient health in the EU will benefit from the streamlined regulatory processes that the Regulation and CTIS will bring. It is important that clinical trial sponsors and authorities prepare their staff and processes to work with CTIS and deliver the benefits of the Clinical Trial Regulation.
The EMA has published a guidance to provide key methods and good regulatory practices to pharmaceutical organizations on the planning and conduct of registry-based studies. A patient registry is an organized system that collects uniform data over time on patients who are diagnosed with a particular disease or condition, or who receive particular medicines. A registry-based study is a clinical trial or a non-interventional study that investigates a research question using the data collection infrastructure or the patient population of one or several patient registries. Medicine regulators may sometimes suggest that pharmaceutical companies use the data collection infrastructure or population of a patient registry to exploit information from clinical use and to monitor the safety and effectiveness of authorized medicines when used in the real-world setting.
There can be significant differences in requirements for types, structures, and processing of data across existing registries. These often present challenges in the assessment of the suitability of existing registries to be used in clinical studies.
The Guideline on Registry-based Studies aims to help those involved in registry-based studies to better define study populations and design study protocols. It provides further guidance on data collection, data quality management, and data analysis to achieve higher quality evidence. This in turn will facilitate EU regulators’ assessment of the safety and effectiveness of medicines, for the benefit of public health. As patient registries are key to conducting registry-based studies, the guidance includes an annex with good practices in the establishment and management of patient registries and their use for other regulatory purposes.
Health Canada is warning consumers that Ayurvedic medicinal products sold by Kerela Ayurvedic & Natural Herbal Consultation located in Toronto, ON are unauthorized and may pose serious health risks. This includes products purchased at the clinic or ordered by the clinic from its supplier and shipped directly to customers. Health Canada seized products from the clinic after Public Health Ontario notified the Department of a case of lead poisoning following the use of products obtained from the clinic. Laboratory testing, facilitated by Public Health Ontario, identified high levels of lead and mercury in products the patient had been taking.
Lead and mercury are heavy metals that may pose serious health risks when consumed in excessive amounts, as they can accumulate in vital organs of the body. Children, pregnant women, and breastfeeding women are most susceptible to the toxic effects. Lead effects include abdominal pain, anemia, changes in blood pressure, reproductive disorders such as miscarriage, weakness, concentration problems, weight loss, insomnia, dizziness, and kidney and brain damage. Mercury effects include irritability, tremors, memory loss, insomnia, concentration problems, and kidney and brain damage. Ayurvedic medicinal products are used in traditional South Asian healing practice and are often imported. Improper manufacturing processes may result in dangerously high levels of heavy metals in the final products. Health Canada reminds consumers who choose to use Ayurvedic medicinal products to only select those authorized for sale in Canada. These products will have a Natural Product Number (NPN) on the label.
The products seized by Health Canada were packaged in clear plastic containers with handwritten labels and may have been distributed to patients in resealable plastic bags. These products are not authorized for sale by Health Canada, which means they have not been evaluated for safety, effectiveness, and quality. Selling unauthorized health products is illegal in Canada. Kerela Ayurvedic & Natural Herbal Consultation was also found to be operating without a Health Canada site license. At Health Canada’s direction, the clinic stopped importing and selling unauthorized Ayurvedic products, including products shipped directly to consumers from foreign suppliers. Health Canada is testing seized products and is continuing to work with Public Health Ontario and Toronto Public Health. The Department will inform Canadians as needed, should any new health risks be identified.
International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guidances
The ICH E8(R1) Guideline on General considerations for Clinical Studies reached Step 4 of the ICH Process on 06 October 2021. Clinical studies of medicinal products are conducted to provide information that can ultimately improve access to safe and effective products with meaningful impact on patients, while protecting those participating in the studies. ICH E8(R1) provides guidance on the clinical development lifecycle, including designing quality into clinical studies, considering the broad range of clinical study designs and data sources used. This modernization of ICH E8 is the first step towards the Renovation of Good Clinical Practice initiated in 2017. The revision incorporates the most current concepts achieving fit-for-purpose data quality as one of the essential considerations for all clinical trials.
The ICH M7(R2) draft Guideline and Addendum on Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk reached Step 2 of the ICH process on 06 October 2021 and now enters the public consultation period. The ICH M7 (R2) Addendum provides useful information regarding the acceptable limits of known mutagenic impurities or carcinogens and supporting monographs. Seven new compounds have been added in this revision: Acetaldehyde, Dibromoethane, Epichlorohydrin, Ethyl Bromide, Formaldehyde, Styrene, and Vinyl Acetate. Additionally, a Step 2 Informational Presentation has been developed by the Maintenance Expert Working Group.
International Pharmaceutical Excipients Council (IPEC)
The International Pharmaceutical Excipients Council Federation, (IPEC Federation) announced the availability of the revised IPEC GDP Audit Guide for Pharmaceutical Excipients (Version 3, 2021). The revised guidance has been developed by a team consisting of members from IPEC Europe and IPEC-Americas. This document is a consolidation and revision of IPEC Europe’s GDP Audit Guideline (2011) and IPEC-Americas GDP Audit Guide for North American Distribution of Pharmaceutical Excipients (2011). The IPEC Good Distribution Practices Audit Guide is an important element in the supply chain management and control of pharmaceutical starting materials. The revised Audit Guide provides a comprehensive tool for companies auditing the supply chain of pharmaceutical excipients. Several incidents in the past were caused by a lack of supply chain security and inappropriate handling of pharmaceutical excipients. This has moved regulators, users, manufacturers, and distributors to take action. The revised GDP Audit Guide should be used in conjunction with the IPEC Good Distribution Practices Guide. It serves as a valuable tool to help the auditor conduct a complete audit of all relevant GDP principles for pharmaceutical excipients.
The IPEC Federation announced the availability of a new International Pharmaceutical Excipient Council Guide, the IPEC Safety Guide for Pharmaceutical Excipients. This guide is applicable globally. Building off of articles published by both IPEC-Americas (A New Approach to the Safety Assessment of Pharmaceutical Excipients) and IPEC Europe (The Proposed Guidelines for the Safety Evaluation of New Excipients) in 1996 and 1997, respectively, the IPEC Safety Guide has been designed to give an overview on recommended toxicological studies for different therapeutic applications, routes of administration, and treatment periods. Toxicological safety studies described in this guide are intended for consideration by excipient manufacturers who market excipients for use in drug formulations and excipient users who conduct toxicology studies required for the initial approval of a novel excipient in a drug formulation. Excipient users formulating an excipient beyond its approved, prior use are responsible for conducting the appropriate safety studies.
Medicines and Healthcare Products Regulatory Agency (MHRA)
Company-led medicines recall: Glucose 10%w/v 10ml injection (unlicensed medicine) and Trometamol 7%w/v injection 5mL (unlicensed medicine) was issued on 04 October 2021. Batches of Glucose 10% w/v injection 10mL and Trometamol 7%w/v injection 5mL are being recalled due to limited assurance of product sterility. This is a precautionary recall. The affected stock should be quarantined when replacement is available.
Class 2 Medicines Recall: Tesco Flu-Max All In One Chesty Cough & Cold Powder for Oral Solution Wrafton Laboratories Limited (trading as Perrigo) EL (21)A/24 was issued on 12 October 2021. Batches of Tesco Flu-Max all in one chesty cough and cold powder for oral solution are being recalled due to an error on the product sachet. The affected sachets incorrectly state that the product can be used in children 12 years and over, while the product information and carton correctly state that this product should not be given to children under 16 years old. Stop supplying the batch immediately, quarantine all remaining stock, and return to supplier.
Class 2 Medicines Recall: Pfizer Ltd, Champix (all strengths) film-coated tablets, EL (21)A/25 was issued on 14 October 2021. Batches of Champix 0.5mg film-coated tablets, 0.5mg + 1mg film coated tablets, and 1mg film-coated tablets are being recalled. This is a precautionary measure due to the presence of levels of N-nitroso-varenicline above acceptable levels. Stop supplying the batch immediately, quarantine all remaining stock, and return to supplier. Healthcare professionals should advise patients undergoing treatment with Champix to discuss any questions or concerns with their prescriber.
Company-led medicines recall: Irinotecan 200mg/260mL in sodium chloride 0.9% w/v intravenous infusion and Infliximab (Remsima) intravenous infusion in sodium chloride 0.9% was issued on 21 October 2021. A single batch of Irinotecan 200mg/260mL in sodium chloride 0.9% w/v intravenous infusion and several batches of Infliximab (Remsima) intravenous infusion in sodium chloride are being recalled due to reduced product stability and reduced product sterility, respectively. Hospital pharmacies should stop supplying the batch immediately, quarantine all remaining stock, and return to supplier once replacement stock is available.
Class 3 Medicines Recall: Bimatoprost Aspire 0.3mg/ml eye drops, solution in single-dose container, Aspire Pharma Limited, EL (21)A/26, was issued on 26 October 2021. Batches of Bimatoprost Aspire 0.3mg/ml eye drops are being recalled due to variability in plastic thickness of the single dose containers. This is a precautionary recall, as some patients find the defective containers difficult to squeeze to access the product. Stop supplying the batch immediately, quarantine all remaining stock, and return to supplier.
There was also a recent Class 2 recall (issued 11 November) of Cold & Flu Relief Capsules available on general sale. Perrigo is recalling the listed batches available under various liveries due to an error on the leaflet and carton stating an incorrect maximum daily dose for patients aged 12 to 15 years. MHRA considered the assessment of risk to safety for 12 to 15-year-olds who may have taken the incorrect daily dose as very low and there is no evidence of any harm; therefore, this recall is not direct to patient level. Retailers and wholesalers have been asked to stop supplying the batches immediately, quarantine all remaining stock, and return to supplier.
Personal Care Product Council (PCPC)
The Personal Care Products Council (PCPC) is aware of the study reporting the presence of benzene in some antiperspirant and deodorant body spray products. According to the U.S. Centers for Disease Control and Prevention (CDC), benzene is formed from both natural processes and human activities and can be present at low levels in the environment. Benzene is not an intentionally added ingredient in body spray products; however, the U.S. FDA, as well as product manufacturers, are aware that it may be present in food and drug products at very low levels. The FDA offers guidance on the level of residual benzene in drug products in its companion document for the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), and PCPC strongly supports the FDA’s guidance and activities in monitoring for conformance to these recommendations.
PCPC and its member companies are firmly committed to ensuring consumers have access to cosmetics and personal care products with ingredients that have been thoroughly tested for safety and follow the requirements of the law. There is nothing more important than safety. If consumers can’t believe in a product and rely on it to do what it says, then nothing else matters.
Deodorant and antiperspirant products and their ingredients must be shown to be safe before they can be marketed to consumers, like all cosmetics and personal care products. In the U.S., cosmetics are regulated by the FDA under the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the Fair Packaging and Labeling Act (FPLA). All cosmetic products and ingredients are subject to the same safety requirement under the FD&C Act: They must be safe for consumers under labeled or customary conditions of use. In addition, antiperspirants are regulated by the FDA as Over-the-Counter (OTC) drugs and must comply with all other requirements listed in the OTC antiperspirant monograph. Companies and individuals have a legal responsibility to ensure their products and ingredients are safe for the intended use.
Therapeutic Goods Administration (TGA)
The TGA has issued new guidance on plans to reclassify medical devices involved in circulatory and nervous systems from Class IIa (moderate risk) to Class III (high risk). According to the TGA guidance, the following devices will be reclassified to Class III beginning 25 November 2021:
- Devices in direct contact with the heart and central circulatory system (CCS), and intended for short-term or transient use
- Devices in direct contact with the central nervous system (CNS), and intended for transient use
The TGA guidance identifies several examples of devices affected by the reclassification. Up-classified devices with CCS applications will include cardiac vent catheters, central venous catheterization kits, and cardiopulmonary cannulas. Affected devices targeting the CNS include flexible fiberoptic neuroscopes, rigid neuroscopes, and spinal needles. For affected Australian medical device market registrants, meeting TGA registration requirements as Class III device sponsors entails providing more detailed assessments of both manufacturers’ quality management systems and technical documentation for these devices. In addition, market applicants must provide conformity assessment documentation that demonstrates processes and procedures in line with Class III classification requirements. Affected applicants will also be subject to mandatory audit assessments by the TGA regarding device inclusion applications.
Guidance for Declaration of Conformity: For Class I Non-Sterile Non-Measuring, Class 1 In Vitro Diagnostic (IVD) Medical Devices, Class I Medical Device (Export Only), and Class 1 IVD Medical Device (Export Only), 26 November 2021
This guidance applies to the Declaration of Conformity procedures for Class I non-sterile, non-measuring medical devices, Class 1 in-vitro diagnostic (IVD) devices, Class I Medical Device (Export Only), Class 1 IVD Medical Device (Export Only), and Class I Systems and Procedure Packs. This document is designed to assist manufacturers in completing the relevant Declaration of Conformity and to assist sponsors confirming that documentation prepared by the manufacturer is complete. Sponsors must obtain a Declaration of Conformity from the manufacturer to upload as part of their application. This guidance is not legislative in nature and is subject to the requirements of therapeutic goods legislation.
United States Food and Drug Administration (FDA) – Guidances
This draft FDA Q13 Guidance on Continuous Manufacturing of Drug Substances and Drug Products (based on ICH draft Q13 guidance, published 27 July 2021) is proposed to:
- Capture key technical and regulatory considerations that promote harmonization, including certain Current Good Manufacturing Practices (CGMP) elements specific to Continuous Manufacturing (CM)
- Allow drug manufacturers to employ flexible approaches to develop, implement, or integrate CM for the manufacture of small molecules and therapeutic proteins for new and existing drug substances and drug products
- Provide guidance to industry and regulatory agencies regarding regulatory expectations on the development, implementation, and assessment of CM technologies used in the manufacture of drug substances and drug products.
The FDA has developed a draft guidance for labelers of class I devices to revise “Section III. Policy On Standard Date Formatting, UDI Labeling, and GUDID Submission Requirements for Class I and Unclassified Devices” of the guidance Unique Device Identification: Policy Regarding Compliance Dates for Class I and Unclassified Devices and Certain Devices Requiring Direct Marking, (“2020 UDI Compliance Policy Guidance”) which was issued on 01 July 2020. When this draft guidance is finalized, the updates in Section III of this draft guidance would supersede the recommendations in Section III of the 2020 UDI Compliance Policy Guidance. This draft guidance explains that there are certain Class I devices for which the FDA does not intend to enforce Global Unique Device Identification Database (GUDID) submission requirements under 21 CFR 830.300, and describes how a labeler of a Class I device can determine whether its device is within the scope of this compliance policy.
The FDA plans to incorporate the final version of this draft guidance into “Section III. Policy On Standard Date Formatting, UDI Labeling, and GUDID Submission Requirements for Class I and Unclassified Devices” of the 2020 UDI Compliance Policy Guidance. The remainder of the 2020 UDI Compliance Policy Guidance, with the exception of technical edits for consistency with the newly amended Section III, would not be substantively changed.
The FDA is providing blood establishments that collect or process blood and blood components with recommendations for implementing a pathogen reduction device for the manufacture of pathogen-reduced blood components. The FDA has received specific questions from blood establishments who have chosen to use the INTERCEPT® Blood System for Platelets and Plasma and who have questions on implementation of this pathogen reduction device. As a result, the FDA is providing guidance in a question and answer format, addressing the most frequently asked questions.
United States Food and Drug Administration (FDA) – Recalls
SterRx, LLC announced the voluntary nationwide recall of approximately 240 lots within their expiry period due to equipment and process issues that could lead to a lack of sterility assurance for products intended to be sterile. To date, SterRx, LLC has not received reports of any product complaints or adverse events associated with this issue. SterRx, LLC has initiated this voluntary recall to the hospital pharmacy level out of an abundance of caution.
Nutracap Holdings, LLC of Norcross, Georgia is voluntarily recalling various dietary supplements due to undeclared milk on the labels. People who have an allergy or severe sensitivity to milk run the risk of serious or life-threatening allergic reaction if they consume products containing milk.
During a recent FDA inspection, the firm was notified that their labels failed to disclose the presence of milk on some of their products. The recalled products were shipped between January 2020 and November 2021 to distributors and retailers in Arizona, California, Colorado, Florida, Georgia, Idaho, Illinois, Indiana, Kentucky, Louisiana, Minnesota, Nevada, New Jersey, New York, North Carolina, Ohio, and Texas. There have been no illnesses reported to date.
On 08 October 2021, Cook Medical issued a global, voluntary recall of the Transseptal Needle and the Transseptal Needle with Catheter. This recall includes all unexpired lots for both of these products. The needles were recalled due to complaints of rust on the products. Use of affected products could result in increased procedural time and inflammatory reactions, including systemic reactions that may lead to permanent impairment or death. The FDA has not yet classified the recall. A complete list of products affected by this recall is provided. Transseptal Needles, including Transseptal Needles with Catheters, were found to have rust internally, externally, or both. To date, Cook Medical has received no reports of injury or illness related to this recall. Cook has received four complaints where the presence of rust was identified prior to patient contact. However, please be advised that the presence of rust may go undetected by the user. The FDA and other regulatory agencies around the world have been notified of this action.
United States Food and Drug Administration (FDA) – Warning Letters
FDA issued a Warning Letter to Surgenex LLC (Surgenex) on 15 November 2021. This Warning Letter was based on the outcome of an FDA inspection that was conducted at the Surgenex facility in Scottsdale, AZ from 05 to 16 April 2021. The Warning Letter states that Surgenex products fail to meet the criterion in 21 CFR 1271.10(a)(2) that the Human Cells, Tissues, or Cellular or Tissue-Based Products (HCT/Ps) be “intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent.” Surgenex products are not intended to perform the same basic function or functions of umbilical cord or amniotic membrane in the recipient as in the donor, such as serving as a conduit (for umbilical cord) or serving as a selective barrier for the movement of nutrients between the external and in utero environment, protecting the fetus from the surrounding maternal environment, and serving as a covering to enclose the fetus and retain fluid in utero (for amniotic membrane). Rather, using Surgenex products to treat orthopedic conditions, for example, is not homologous use as defined in 21 CFR 1271.3(c). In addition, Surgenex products fail to meet other criteria set forth in 21 CFR 1271.10(a). The umbilical cord derived product, SurCord®, and amniotic membrane derived products, SurForce® and SurFactor®, fail to meet the minimum manipulation criterion set forth in 21 CFR 1271.10(a)(1) and defined for structural tissue in 21 CFR 1271.3(f)(1) because Surgenex processing alters the original relevant characteristics of the umbilical cord or amniotic membrane related to their utility for reconstruction, repair, or replacement.
Additionally, during the inspection, FDA investigators documented evidence of significant deviations from current good manufacturing practice (CGMP) requirements, including deviations from section 501(a)(2)(B) of the FD&C Act and 21 CFR Parts 210 and 211. The Form 483 issued to Surgenex included observations relating to:
- Failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes [21 CFR 211.113(b)]
- Failure to have an adequate system for monitoring environmental conditions in an aseptic processing area [21 CFR 211.42(c)(10)(iv)]
- Failure to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess [21 CFR 211.100(a)]
- Failure to thoroughly investigate any unexplained discrepancy, or the failure of a batch or any of its components to meet any of its specifications, whether or not the batch has been already distributed [21 CFR 211.192]
- Failure to establish and follow a written testing program designed to assess the stability characteristics of drug products and to use the results of such stability testing to determine appropriate storage conditions and expiration dates [21 CFR 211.166(a)]