SQA Regulatory Surveillance Summary 3 | Monthly Update 2021
By Laurel Hacche, Debra Cortner, & Dondi Pulse-Earle SQA Associates
SQA Regulatory Surveillance Summary #3, 2021
European Commission (EC) – Biologics
The EC has extended until the end of June 2021 the transparency and authorization mechanism for COVID-19 vaccine exports. This follows persistent delays in some of the deliveries of vaccines to the EU. The EU continues to be the leading provider of vaccines around the world. Six weeks into the existence of this mechanism, 249 export requests to 31 different countries have been granted for a total of 34,090,267 doses, as they did not threaten the contractual engagements between the EU and the vaccine producers. Only one export request was not granted. The main export destinations include the United Kingdom, Canada, Mexico, Japan, Saudi Arabia, Hong Kong, Singapore, United States, Chile, and Malaysia.
The export authorization mechanism only applies to exports from companies with which the EU has concluded Advance Purchase Agreements (APAs). These APAs commit the vaccine producers to deliver to EU Member States a pre-agreed number of vaccines. The mechanism provides for authorizations of exports of COVID-19 vaccines outside the EU. Initially put in place on 30 January 2021, and with a timeframe lasting until 12 March 2021, the new regulation extends the duration of this mechanism until the end of June 2021. The new regulation also simplifies the procedure by allowing the grouping of exports to different final recipients in the same country in one single request. It also provides clarity by identifying the customs codes for the active substances covered by the measure. This measure is targeted, proportionate, transparent, and temporary. It is fully consistent with the EU’s international commitments under the World Trade Organization (WTO) and the G20 and is in line with what the EU has proposed in the context of the WTO Trade and Health Initiative. Committed to international solidarity, the EU excluded from this mechanism vaccine supplies for humanitarian aid and those supplies destined to countries under the COVAX Facility, as well as shipments to the EU neighborhood.
Regulation (EU) 2021/522 establishes a new and reinforced program for the Union’s action in the field of health, called the EU4Health Programme, for the period of 2021-2027. The focus includes strengthening the exchange of best practices between Member States to achieve Union-wide high-quality solutions, thereby unlocking the potential of innovation in health, and improving efficiency by avoiding the duplication of activities and optimizing the use of financial resources.
The COVID-19 crisis has highlighted many challenges. Given the rise of healthcare demand, Member States’ healthcare systems are facing challenges regarding the availability and affordability of medicinal products. This includes the dependence of the Union on third countries to ensure the supply of raw materials, active pharmaceutical ingredients, medicinal products, medical devices, and personal protective equipment. The program intends to provide support to actions that foster the production, procurement, and management of crisis-relevant products. These actions are intended to mitigate the risk of shortages. The program also intends to provide support to the generation of clinical and real-world evidence to enable the development of, authorization of, evaluation of, and access to effective medicinal products including generics and biosimilars, to medical devices, and to treatment. The program is expected to promote research and development with respect to new medicinal products, with particular attention to be given to antimicrobials and vaccines to tackle antimicrobial resistance and vaccine-preventable diseases, respectively. The program is also expected to promote incentives to boost the production capacity for antimicrobials, personalized treatment, and vaccination.
European Commission (EC) – Drugs, Devices, Food, and Cosmetics
The European Commission (EC) has issued a notice on the handling of duplicate MAAs of pharmaceutical products under Article 82(1) of Regulation (EC) No. 726/2004, which essentially means duplicate MAAs for products authorized via the centralized procedure. Applications that fall under the scope of Article 82(1) include the following:
- Active substance that is a different salt, ester, ether, isomer, mixture of isomers, complex, or derivative that does not differ significantly in properties regarding safety or efficacy
- Medicinal product containing different excipients that do not result in significant differences in safety or efficacy
- Different manufacturer or manufacturing site, unless this leads to significant differences in safety or efficacy
- Differences in the data submitted in connection with the marketing authorization application for a medicinal product with the same composition in active substance(s) and pharmaceutical form (e.g., data to show bioequivalence), provided that the product does not significantly differ in terms of safety or efficacy
In addition, considering the fact that one marketing authorization application is submitted in accordance with Article 8(3) of Directive 2001/83/EC and the other marketing authorization application is submitted under an abridged procedure (e.g., generic, biosimilar, or hybrid application), informed consent is irrelevant provided that both applications relate to a medicinal product with the same qualitative and quantitative composition in active substances and the same pharmaceutical form. Under Article 82(1) of Regulation (EC) No. 726/2004, the Commission can grant a duplicate marketing authorization:
- If there are objective, verifiable reasons relating to public health that show an increased availability of medicinal products to healthcare professionals and/or patients
- For co-marketing reasons when the marketing authorization holder can prove that they will stipulate a co-marketing agreement with one or more companies for the product for which the duplicate is requested. A co-marketing arrangement is generally understood as an agreement between two parties to commercialize a specific medical product under different trademarks.
Greater detail is provided in Annex I of the notice.
The European Medical Device Coordination Group (MDCG) has issued a new document covering key questions and considerations regarding custom-made medical devices in the context of Medical Devices Regulation (MDR) compliance. The new MDCG Q&A document identifies 10 key questions pertaining to which devices qualify as Custom-Made Devices (CMDs), as well as MDR-related obligations and compliance considerations manufacturers will need to address. The MDCG cites MDR Article 2(3) for defining a CMD as any device that has been produced according to a specific prescription from a qualifying physician or other qualified person; the prescriber sets specific design characteristics for the device, which is intended solely for use by a specific patient to meet their individual conditions and treatment needs. Another key issue included in the MDCG Q&A is how written prescriptions for CMDs are defined by the MDR. At the very least, a qualifying prescription should include a specific patient’s name, as well as specific design characteristics from an authorized prescriber that correspond to the patient’s features and disease or condition. Additional items for CMD written prescriptions may include physical or 3D model data, dental or orthotic molds, or dental impressions.
On 27 March 2021, the Regulation on the Transparency and Sustainability of the EU Risk Assessment in the Food Chain became applicable. The new rules improve the transparency of the EU risk assessment regarding food and cover a wide range of products of great concern for citizens. The Regulation will strengthen the reliability, objectivity, and independence of studies submitted to the European Food Safety Authority (EFSA) and give a greater role to Member States in the EFSA’s governance. In the next four years, the EC will also conduct fact-finding missions at laboratories to assess whether the laboratories apply the relevant standards for tests and studies submitted to the EFSA in the context of an application process. These missions will allow the Commission to identify, and, if necessary, correct any non-compliance or weaknesses.
European Medicines Agency (EMA) – Biologics
The EMA’s Human Medicines Committee (CHMP) is reviewing available data on the use of the monoclonal antibodies casirivimab, imdevimab, bamlanivimab, and etesevimab to treat patients with COVID-19 who do not require oxygen supplementation and who are at high risk of progressing to severe COVID-19. The committee will carry out two separate reviews, one for the casirivimab/imdevimab combination and another for bamlanivimab/etesevimab. The EMA is reviewing the data to provide a harmonized scientific opinion at the EU level to support national decision making on the possible use of the antibodies before a formal authorization is issued. The EMA has already started a rolling review of the antibody combination casirivimab and imdevimab. The reviews have been started in view of recent studies that looked into the effects of the combinations casirivimab/imdevimab and bamlanivimab/etesevimab in outpatients with COVID-19 who do not need supplemental oxygen. Preliminary results for both studies indicate that the combinations reduced the viral load (amount of virus in the back of the nose and throat) more than placebo (a dummy treatment) and led to fewer COVID-19-related medical visits and hospitalizations. The Committee will also look at the use of bamlanivimab alone based on a study indicating that bamlanivimab monotherapy can reduce viral load and provide clinical benefit.
European Medicines Agency (EMA) – Drugs, Devices, Food, and Cosmetics
The Committee for Medicinal Products for Human Use (CHMP) has provided guidance for marketing authorization holders to review all chemical and biological human medicines for the possible presence of nitrosamines at risk. An implementation plan was agreed to in February 2021 that sets out how the European medicines regulatory network, together with the European Directorate for the Quality of Medicines & HealthCare (EDQM), will be implementing the outcome of the CHMP’s review. This includes specific measures that the network will take if nitrosamines are detected in a medicine. The EMA and national competent authorities will continue to monitor the presence of nitrosamine impurities in medicines, in cooperation with regulators from outside the EU, and will work with marketing authorization holders to find rapid solutions to address any adverse findings.
International Pharmaceutical Excipients Council (IPEC)
The International Pharmaceutical Excipients Council Federation (IPEC Federation) announces the availability of a new position paper, Pharmaceutical Lactose used in oral preparations is a low-risk excipient. This paper describes the IPEC Federation’s position on the risk classification of lactose in all oral preparations. Regulatory authorities worldwide increasingly seek to classify pharmaceutical excipients according to the risk they may present to patients when used in dosage forms. Although lactose is derived from an animal-derived material (whey), this position paper seeks to support pharmaceutical grade lactose as a low-risk excipient in oral dosage forms. The
IPEC Federation considers that pharmaceutical grade lactose has a low-risk profile with respect to chemical and biological risks when used in oral pharmaceutical preparations.
Therefore, this paper could help to advocate this classification status with regulatory authorities and consequently result in fewer dossier requirements for lactose when applying for marketing authorizations, thus facilitating the availability of medicines.
The IPEC Federation announces the availability of the revised and updated IPEC General Glossary of Terms and Acronyms for Pharmaceutical Excipients (Version 2, 2021). The glossary was originally published in 2014 and has been used to define excipient terms and acronyms commonly found in IPEC guides. While updating the IPEC General Glossary of Terms and Acronyms for Pharmaceutical Excipients, the team developed a strategy with the following rationale for determining when a term/definition should be included in the IPEC Glossary:
The following types of terms/definitions should be included in the IPEC Glossary:
- Specific to excipients
- Used/referenced in multiple IPEC guides
- Provide a better understanding of manufacture or application of an excipient
- Describe and/or differentiate regulatory requirements for an excipient
The following types of terms/definitions should not be included in the IPEC Glossary:
- Commonly used dictionary terms
- Terms generally used by other industries, such as Standard Operating Procedure (SOP), Statistical Process Control (SPC), and Active Pharmaceutical Ingredient (API)
- Terms specific to one IPEC guide (better to describe and/or include reference in guide vs. adding to glossary)
- Terms defined in other official publicly available guidances/resources (reference the guidance and/or resource for the term directly in the guide). This would not include terms only referenced in documents that must be purchased (e.g., ANSI Standard, USP).
Terms not meeting the above criteria, which are currently bolded in at least one IPEC guide (indicating definition found in the IPEC Glossary), were highlighted (along with [reference to the guide(s)]). As the current versions of these guides are updated, highlighted terms will be un-bolded and eventually removed from the IPEC General Glossary.
International Society for Pharmaceutical Engineering (ISPE)
ISPE announced the release of its latest Guide, ISPE Good Practice Guide: Maintenance, 2nd Edition. The Guide describes current established good practices and seeks to provide a practical and consistent interpretation of the required elements of a pharmaceutical Maintenance Program, while offering maximum flexibility to enable widespread adaptation and encourage innovation. This new edition reflects alignment with the ICH Q9 risk-based approach with respect to maintenance and the industry as a whole. Updates include consolidating basic and good practices categories, adding clarification on terminology for users, and updating examples.
Russia – Ministry of Health of the Russian Federation
The Russian Government continues to take measures to increase the quality and accessibility of health care for all patients. They are doing this with a focus on countering the coronavirus. The Healthcare Development national program was updated, its parameters brought in line with the federal budget for this year and the next two years, as well as in line with the common plan for achieving national development goals. Special priority was given to modernizing primary medical care, as instructed by the President. At least 500 billion rubles will be allocated for this modernization in the next five years, including 90 billion this year. The plan includes building or renovating more than 1,000 healthcare facilities as soon as this year. A similar number of facilities will undergo major renovation. More than 25,000 units of medical equipment and 4,000 ambulances will be purchased.
World Health Organization (WHO)
In February 2021, the WHO published the new guideline Good Manufacturing Practices for Medical Gases on the manufacture, testing, storage, and distribution of medical gases for comment. The WHO created the new guideline to address the increased demand for oxygen for ventilation due to the COVID-19 pandemic. In addition to an introduction and a glossary, the draft comprises the following chapters:
- Quality management
- Equipment and utilities
- Qualification and validation
- Quality control
- Product life cycle and continuous improvement
- Storage and distribution
This WHO Medical Product Alert refers to falsified COVID-19 vaccine identified as “BNT162b2” detected in Mexico in February 2021 and recently confirmed as falsified to the WHO. The falsified product was supplied and administered to patients outside authorized vaccination programs. This falsified COVID-19 vaccine may still be in circulation in the region and may continue to be offered to patients outside authorized vaccination programs. Laboratory analysis of the contents of the falsified products is pending and this Alert will be updated as soon as results are available.
Genuine COVID-19 vaccine BNT162b2 is indicated for active immunization to prevent COVID-19 caused by the SARS-CoV-2 virus, in individuals 16 years of age and older. The use of genuine COVID-19 vaccines should be in accordance with official guidance from national regulatory authorities. Falsified COVID-19 vaccines pose a serious risk to global public health and place an additional burden on vulnerable populations and health systems. It is important to identify and remove these from circulation. The product identified in this alert is confirmed as falsified on the basis that it deliberately/fraudulently misrepresents identity, composition, or source:
- The genuine manufacturer of COVID-19 vaccine BNT162b2 confirmed they did not manufacture the product.
- The batch number and expiry dates are falsified.
- The glass vials and label are different from genuine COVID-19 vaccine BNT162b2 vials.
The product subject of this Medical Product Alert is:
- Product Name: COVID-19 Vaccine BNT162b2
- Stated Manufacturer: Pfizer BIONTECH
- Lot Number: 783201
- Expiration Date: AUG 24
- Packaging Language: English
- Identified In: Mexico