SQA Regulatory Surveillance Summary | July 2020
By Laurel Hacche and Debra Cortner, SQA Associates
European Medicines Agenda (EMA)
The Committee for Medicinal Products for Human Use (CHMP) of the EMA published a final assessment report on nitrosamine impurities on 25 June 2020. The report calls on pharmaceutical manufacturers to reduce the presence of nitrosamines in medicinal products as far as possible and to comply with the defined limits. The PDA article summarizes the recommendations of the comprehensive 90-page report of the EMA. Marketing authorization holders are obliged to conduct risk assessments for Active Pharmaceutical Ingredients (APIs) and finished products to ensure that the medicinal products are manufactured in accordance with the latest scientific and technical standards in accordance with Article 23 and Annex I of Directive 2001/83/EC and Article 16 of Directive (EC) 726/2004 and, where necessary, to adapt the manufacturing processes accordingly. It must also be ensured that all active substances and excipients are manufactured in accordance with the principles of good manufacturing practices as laid down in Article 46(f) of Directive 2001/83/EC. Further detailed information for pharmaceutical companies can be found on the Nitrosamine website of the EMA.
On 20 July 2020, the EMA published the final 10-page guideline on the quality of water for pharmaceutical use. The guideline will go into effect on 01 February 2021. On that date, the guideline replaces the Note for Guidance on Quality of Water for Pharmaceutical Use from 01 May 2002. The new EMA guideline takes into account the following interim changes to the European Pharmacopoeia: the revised monograph on Water for Injection (WFI, 0169), which offers the possibility of using processes other than distillation for WFI (e.g., reverse osmosis), the new monograph on Water for the Production of Extracts (2249), and the suppression of the monograph for Highly Purified Water (HPW, 1927). The EMA guideline reflects the expectations for the minimum acceptable water quality in the manufacture of active ingredients and medicinal products for human and veterinary use. This is a guideline for the pharmaceutical use of different water qualities in the manufacture of active substances and medicinal products for use in human and veterinary medicine. The document also applies to Advanced Therapy Medicinal Products (ATMPs) and can be applied to Investigational Medicinal Products (IMPs). The new guideline can be used together with the corresponding Question & Answer (Q&A) paper, Questions and Answers on Production of Water for Injections by Non-Distillation Methods – Reverse Osmosis and Biofilms and Control Strategies, 01 August 2017.
International Organization for Standardization (ISO)
Biobanks are literally transforming our world. Holding hundreds of millions of biological samples, including those from humans, animals, plants, and microbes, biobanks help the global scientific community further everything from crop production to personalized medicine. ISO has a widely used International Standard that outlines the requirements for biobanking, ISO 20387:2018. A technical report (ISO/TR22758:2020) has been published to help organizations get the most out of ISO 20387. ISO/TR22758:2020, Biotechnology – Biobanking – Implementation Guide for ISO 20387, provides detailed guidance on how to implement the requirements of ISO 20387, Biotechnology – Biobanking – General Requirements for Biobanking. The new technical report is intended to be a supplement to, rather than a substitute for, ISO 20387, which details the requirements for the competence, impartiality, and consistent operation of biobanks. Together, the two documents help improve the quality of biological material and data collections that are stored and shared, enhance the outcomes of collaboration, strengthen trust between partners, and advance research and development.
The technical report, ISO/TR 24971:2020, Medical Devices – Guidance on the Application of ISO 14971, is a companion document to the globally recognized risk management standard ISO 14971, Medical Devices – Application of Risk Management to Medical Devices. The ISO 14971 standard, which was updated in December 2019, specifies the terminology, principles, and process for managing the risks associated with medical devices, including Software as a Medical Device (SaMD) and In Vitro Diagnostic (IVD) medical products. ISO/TR 24971:2020 provides detailed guidance on how to use the ISO 14971 standard most effectively, clarifies the requirements of the standard, and contains recommendations and practical examples on how to achieve compliance with those requirements. ISO/TR 24971:2020 follows the same structure and the same clause numbering as ISO 14971:2019 to facilitate its use. Intended for use by manufacturers of medical devices, the standard and guidance are designed to be read and applied together, providing information on how to identify the hazards associated with medical devices, and measure and manage related risks.
Parenteral Drug Association (PDA)
Focusing on important regulatory and technical updates surrounding isolator design, validation, and operations for aseptic processing, this Points to Consider addresses two primary types of isolators, open and closed, and is intended to support the identification and use of modern technology. It does not represent a standard or regulatory guidance. The document is organized by topics to consider in designing and managing isolator systems, followed by relevant points to consider. Each point begins with a problem statement in the form of a question, representing issues or points needing clarification on the specific topic. Recommendations from subject matter experts are presented in response to each question, along with the rationale for the recommendations and references, where available. The document describes best practices and considerations and encourages further dialogue with industry, health authorities, and suppliers of technology and materials, while taking into account the changes and needs of the modern, global, sterile healthcare product manufacturing industry.
PDA’s Points to Consider for Risks Associated with Sterilizing Grade Filters and Sterilizing Filtration summarizes the processes and outcomes of the risk assessment and control mapping exercises performed as part of the PDA/BioPhorum Sterilizing Filtration Quality Risk Management Consortium. It describes the identification of the sterilizing filtration value stream throughout the process. The authors also address the use of the Fault Tree Analysis (FTA) and Failure Mode and Effects Analysis (FMEA) tools to identify, analyze, and evaluate risks, as well as identification of risk controls intended to prevent sterilizing-grade filter failure. The overall risk to patient safety is discussed, focusing on the level of control over each identified risk. This Points to Consider document is the first in a series of four produced by the multicompany consortium comprising more than 50 subject matter experts from 25 biopharmaceutical manufacturing companies and filter suppliers that was formed by the PDA and BioPhorum to consider the different aspects of sterile filtration risk management.
Personal Care Products Council (PCPC)
The PCPC launched the Hand Sanitizer Ingredient Connection program as part of its ongoing COVID-19 relief efforts. Hand sanitizer is a critical tool in the industry’s collective response to the global pandemic. At the onset of the pandemic, member companies worked to quickly address this public health crisis by building manufacturing capacity for retail and institutional customers and donating more than 20 million units of hand sanitizer products to hospitals, community clinics, medical and emergency professionals, first responders, and industry employees. Shortages of some materials still remain. The PCPC has worked closely with members to support their efforts over the past several months. The PCPC hopes that the Hand Sanitizer Ingredient Connection will help expedite production and increase supply of these essential products. The Connection program is intended to facilitate the ongoing manufacture and marketing of hand sanitizers in the United States by connecting buyers and sellers of materials with one another. Participants can use the Connection program to publish information about their business needs and view a list of other participants whose needs closely match their own, according to material type and quantity. The PCPC is offering this as a public service and will not charge any fees.
Pharmaceutical Inspection Co-Operation Scheme (PIC/S)
Adoption and Entry into Force of New PIC/S Guidance Documents (PI 052-1 and PI 053-1), 01 June 2020
The following new PIC/S guidance documents have been successfully adopted:
- PI 052-1, Aide-memoire, Inspection of Health Based Exposure Limit (HBEL) Assessments and Use in Quality Risk Management
- PI 053-1, Questions and Answers on Implementation of Risk-based Prevention of Cross-contamination in Production and “Guideline on Setting Health-Based Exposure Limits for Use in Risk Identification in the Manufacture of Different Medicinal Products in Shared Facilities”
The above documents, which have been successfully developed by the PIC/S Expert Circle on Controlling Cross-Contamination in Shared Facilities, led by the Medicines & Healthcare products Regulatory Agency (MHRA), went into effect on 01 June 2020.
Russia State Institute of Drugs and Good Practices (SID&GP)
SID&GP recently conducted its first remote GMP inspection of a manufacturing facility for an international pharmaceutical company. The “social distancing” restrictions in place due to COVID-19 limit the number of staff members on site, necessitating an alternative. This article presents both sides of the experience to provide guidance for both manufacturers and regulators around the globe, as they migrate to this new form of inspection. Many regulatory agencies have postponed or completely discontinued GMP inspections due to the COVID-19 pandemic. Alternative inspection practices have been proposed by both PIC/S and the US FDA, using remote audits as an interim measure during COVID-19 quarantines and travel restrictions. SID&GP quickly adapted to the current situation to avoid medicine shortages, proposing to temporarily conduct remote inspections of foreign pharmaceutical manufacturers. This approach involves a thorough review of submitted documentation and a risk assessment of the manufacturing site. The inspectorate’s internal procedures were revised to include a detailed description of the inspection process based on the documents provided by the pharmaceutical manufacturer.
United States Food and Drug Administration (US FDA)
To enable industry to focus on responding to COVID-19 public health needs, the US FDA has pushed back compliance dates for its universal device identification (UDI) system for Class I and unclassified devices – other than implantable, life-supporting, or life-sustaining devices. The updated UDI policy “presents a less burdensome policy that is consistent with public health,” according to the US FDA. The guidance document, Unique Device Identification: Policy Regarding Compliance Dates for Class I and Unclassified Devices and Certain Devices Requiring Direct Marketing, establishes that in addition to UDI labeling, standard date formatting and submission of device information to the FDA database for Class I and unclassified devices will not be enforced before 24 September 2022, as will compliance with the additional direct marking requirement for reprocessed and reusable devices. The new dates are in effect regardless of when a device was manufactured and labeled. The new date change, according to the FDA, is the result of the agency continuing to work on questions from higher risk device manufacturers on UDI implementation, but the FDA also noted new demands on device manufacturers as a result of the novel coronavirus. “For those labelers that have not already implemented UDI requirements for Class I and unclassified devices, preparing to implement UDI requirements while addressing the challenges related to [COVID-19] could be very difficult and could divert resources from COVID-19 response efforts,” the agency wrote. “To the extent this policy helps labelers remain focused on public health needs related to COVID-19, we believe the policy is further consistent with the public health.”
On 23 July 2020, the US FDA published the proposed rule, Annual Summary Reporting Requirements Under the Right to Try Act, which when finalized will implement a statutory requirement for sponsors and manufacturers to provide an annual summary to the FDA for any eligible investigational drug they provide to eligible patients under the Right to Try Act. “The FDA is dedicated to achieving the goals that Congress set forth in the Right to Try Act, so that patients facing terminal conditions have another avenue to access investigational medicines,” said Anand Shah, M.D., Deputy Commissioner for Medical and Scientific Affairs. “Today’s proposed rule builds on the FDA’s long-standing dedication to enhancing access for patients who are facing life-threatening diseases or conditions and our continued commitment to transparency.”
The Right to Try Act, or the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017, provides a pathway for patients who have been diagnosed with life-threatening diseases or conditions who have tried all approved treatment options and who are unable to participate in a clinical trial, to access certain unapproved treatments. Ultimately, the sponsor or manufacturer who is developing the drug or biologic, not the US FDA, is responsible for determining whether to make their product available to patients who qualify for access under the Right to Try Act.
World Health Organization (WHO)
The provision of safe water, sanitation and waste management, and hygienic conditions is essential for protecting human health and for preventing infectious disease outbreaks, such as the coronavirus disease 2019 (COVID-19). Ensuring evidence-based and consistently applied requirements for control of Water, Sanitation, and Hygiene (WASH) and waste management practices in communities, homes, schools, marketplaces, and healthcare facilities will help prevent human-to-human transmission of pathogens including SARS-CoV-2, the virus that causes COVID-19. This guidance was originally published in March 2020. This third edition provides additional details on risks associated with excreta and untreated sewage, hand hygiene, protecting WASH workers, and supporting the continuation and strengthening of WASH services, especially in underserved areas. This additional information has been prepared in response to questions that the WHO and the United Nations Children’s Fund (UNICEF) have received about the prevention and control of COVID-19 in settings where WASH services are limited.