Regulatory Surveillance Summary | March 2020
By Laurel Hacche and Debra Cortner, SQA Associates
Personal Care Products Council
In an effort to comply with health authorities’ recommendations for social distancing and in an abundance of caution, PCPC has closed their offices, and staff is working remotely to maintain business continuity and operational functions. PCPC also postponed all in-person meetings and events until the current situation changes. Each of PCPC’s member companies is keeping the safety and health of their employees as their main priority. Many have instituted teleworking procedures, travel restrictions, canceling in-person meetings, and other actions recommended by federal, state, and local health authorities to implement prevention best practices. While member companies are focused on their employees’ safety and their ability to bring to market the essential products that help fight the spread of COVID-19, PCPC is working on the industry’s behalf with U.S. and foreign governments to ensure the supply chain remains safe and active, and manufacturing operations are not negatively impacted by COVID-19 mitigation requirements and restrictions. For example, PCPC recently worked with the U.S. Food and Drug Administration (FDA) to provide temporary guidance giving manufacturers flexibility to meet the demand for alcohol-based hand sanitizer products to increase the supply available to Americans.
World Health Organization (WHO)
A pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The WHO is working 24/7 to analyze data, provide advice, coordinate with partners, help countries prepare, increase supplies, and manage expert networks. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. The international community has asked for US$675 million to help protect states with weaker health systems as part of the Strategic Preparedness and Response Plan. On 11 February 2020, the WHO announced a name for the new coronavirus disease: COVID-19. Daily situation reports are provided by the WHO.
This guidance reflects greater knowledge of A (H5N1) subtype viruses (and other subtypes in general) and experience gained in the development and manufacture of vaccines against A (H5N1) viruses. Moreover, much has been learned from experience with the A (HlNl) pdm09 virus, and from the production of vaccines against it. The guidance is also intended to apply to threats from any IVPP (for example, H2, H7, and H9 viruses) that may be virulent in humans. Manufacturers and laboratories handling highly pathogenic avian influenza (HPAI) viruses should consult their National Regulatory Authority to determine whether additional biosafety and biosecurity measures are required. There is significant diversity in the pathogenicity of viruses used to make candidate vaccine viruses (CVVs) for the production of human vaccines and vaccines for other mammals. The transmission and pathogenicity of influenza viruses are multifactorial traits that are not completely understood. The haemagglutinin (HA) protein is the major virulence determinant of avian influenza viruses. Consequently, A (H5N1) HPAI viruses that cause fatal disease in humans have been used to produce reassortant viruses containing an HA that has been genetically modified to generate viruses of low pathogenicity for poultry. For viruses that are inherently less pathogenic for humans, the wild-type virus might be used directly for inactivated vaccine production. Thus, both reassortants derived by conventional reassortment and by RG – including those using synthetic nucleic acid as starting material (which may or may not be genetically modified) – and wild-type viruses are included in the scope of these Guidelines.
The IPEC Federation Connect has published the first edition of a bulletin providing all IPEC sister associations with a periodic round-up of what the IPEC Federation and other IPECs have been up to. The first edition includes:
- Priority Objectives
- Summary of the Annual Meeting
- Global Events
Pharmaceutical Inspection Co-Operation Scheme (PIC/S)
The document covers all relevant steps in the change management process from change proposal, change assessment, change planning, and implementation, through to change review and effectiveness checks, and it indicates within each step the aspects that render the Product Quality System (PQS) effective in that area. The document addresses the following points:
- The key elements that could be included in risk-based change proposals
- The pharmaceutical manufacturer assessment of change proposals from a risk perspective, where the level of rigor, effort, and documentation is commensurate with the level of risk, where risk assessments adequately assess potential risks and benefits of changes to product quality, safety, and efficacy, and where those risk assessments assess the potential risks and benefits to other products, processes, and systems
- The pharmaceutical manufacturer categorization of changes based on the level of risk
- The role of change planning and implementation, where the outcomes of risk assessments and the assigned risk levels drive change planning, prioritization, implementation, and their timelines
- Change review and effectiveness assessments at the pharmaceutical manufacturer, in terms of whether changes meet their intended objectives and pre-defined effectiveness criteria, where residual risks are assessed and managed to acceptable levels, and where changes are monitored via ongoing monitoring systems to ensure maintenance of a state of control
The PIC/S Expert Circle considers that the application of the above by a pharmaceutical company will provide evidence of the effectiveness of the PQS at that company in relation to risk-based change management. This is important in the context of the aforementioned PIC/S GMP requirements, and it is also important in the context of ICH Q10. If such a risk-based change management system were in place within a company’s PQS, it should lead to the timely management of risks to product quality and patient safety, as well as better quality and manufacturing performance, continual improvement, and innovation.
China Guidances and Regulations
The U.S. FDA has announced that due to the risk of FDA inspectors encountering the COVID-19 virus, all foreign drug manufacturer inspections are being halted through at least the month of April. Inspections in China had been put on hold earlier. The agency said it will consider “mission critical” inspections on a case-by case basis. It will rely on help from regulators in other countries, testing products at the border for safety, and wielding authority to deny entry to drugs considered defective or unsafe. The agency said in a statement, “We stand ready to resume foreign inspections as soon as feasible.” They acknowledged that approval of drug applications, particularly generic pharmaceuticals, may be delayed.
NMPA Issued the Announcement on Issues Pertaining to the Implementation of the Drug Administration Law of the People’s Republic of China, National Medical Products Administration Newsletter Volume 1, 2020
On 29 November 2019, NMPA issued the announcement (2019 No. 103) stating that the newly revised Drug Administrative Law (DAL) shall be effective 01 December 2019. The following are highlights of the issues pertaining to the newly revised DAL:
- The Drug Marketing Authorization Holder System: All undertakings or drug Research and Development (R&D) institutions holding drug registration certificates (drug approval numbers, import drug registration certificates, or medical product registration certificates) shall be considered Marketing Authorization Holders (MAHs). The MAHs should strictly perform their obligations and take responsibility for drug safety, effectiveness, and quality controllability in the entire process of drug R&D, production, distribution, and use.
- Record-filing management of clinical trial institutions: As of 01 December 2019, such institutions shall be subject to record-filing management. Applications accepted before that time shall be subject to record filing per the current (November 2019) regulations.
- Requirements for drug GMP and GSP administration: As of 01 December 2019, drug GMP and GSP certifications will be canceled and the corresponding applications no longer accepted. Applications accepted before 01 December 2019 shall be processed in accordance with relevant provisions of the original GMP and GSP certification. On-site inspections shall be carried out even after 01 December 2019 and the corresponding results shall be notified to the enterprise; any non-compliance found in the inspections shall be dealt with in accordance with regulations pursuant to the law.
- Associated review and approval for chemical APIs: Starting from 01 December 2019, no drug registration certificate shall be issued for chemical APIs, whose manufacturers shall register on the AEP (APIs, pharmaceutical excipients, packaging materials, and containers in direct contact with pharmaceuticals) registration platform for associated review and approval.
- Investigation and prosecution of drug-related illegal activities: For illegal activities that occurred before 01 December 2019 in drug R&D, production, distribution, and use, the former DAL (unrevised) shall apply, barring those aspects deemed by the newly revised DAL as overestimated or underestimated activities, for which the revised DAL shall be used. For illegal activities occurring after 01 December 2019, the newly revised DAL shall apply.
Drug regulatory authorities at all levels must resolutely implement the Four Strictest Requirements (Strictest Standards, Regulations, Punishment, and Accountability).
On 03 January 2020, Premier Li Keqiang presided over an executive meeting of the State Council, which approved the draft document. The draft requires the implementation of risk-specific registration and filing management of cosmetic products and raw materials. The document is intended to simplify the process, improve regulatory measures, clarify the enterprises’ principal responsibility for quality and safety of cosmetics, beef up punishment for violations of the law, substantially increase the amount of fines, add penalty provisions covering fines and industry debarment for those responsible, and promote the development of cosmetics and beauty care with guaranteed quality and safety well received by consumers.
ANVISA has approved a new regulation, ROC 305/2019, which lays out requirements for custom-made adaptable and patient-specific devices. The regulation defines a custom-made device as any device intended for use by a specific patient or user that has been manufactured for that user or patient based on a healthcare provider’s prescription and that includes specific design features. Prior to manufacturing the device, the manufacturers and importer must first submit to ANVISA a Request for Consent to manufacture and/or import a custom device based on a specific manufacturing plan. The device must be made under Brazilian Good Manufacturing Practices quality requirements.
The TGA aligns its regulatory approach to therapeutic products with the approaches of comparable international regulatory counterparts whenever possible. Technical data requirements for applicants to register in Australia are closely aligned with European Union (EU) Guidelines, Guidelines issued by the International Conference on Harmonization (ICH), and U.S. Food and Drug Administration (FDA) guidelines. While guidelines adopted in Australia are not generally mandated by legislation, they provide guidance to sponsors to assist them in meeting legislative requirements, and any deviation from a Guideline must be justified. The TGA publishes a searchable list of International Guidelines adopted in Australia that can be found at the link above.
Listed medicine ingredients and requirements for their use have been updated in the Therapeutic Goods (Permissible Ingredients) Determination (No. 1) 2019, which commenced on 02 March 2020. A total of 108 changes were made, including two new ingredients, three new ingredients and one varied ingredient for use as flavor/fragrance ingredients, changes to 24 ingredients as part of the annual low-negligible risk framework, and others. A complete list of changed ingredients can be found at the link above.
Implementation of the Australian Government Response to the Expert Panel Review of Medicines and Medical Device Regulation (MMDR), in particular Recommendation 20, prescribes that the regulation of medical devices in Australia, wherever possible, should be aligned with the European Union medical device framework. Following review of submissions by manufacturers regarding classification of specific categories, the TGA has decided to align with the EU regulations for most devices. For specifics, consult the link above.