Review of Developments in GMP and the Regulation of Medicines January 2022


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INTRODUCTION


During the last 4 weeks there have been a number of developments in the regulation of the pharmaceutical industry. This month reported issues have come from the UK, EU, USA, PIC/S and Australian regulatory authorities.


The topics covered in this edition of the “Update” include:


UK

  • ATMP Roadmap Tool

  • Global pharmaceutical industry leaders meet with UK Prime Minister to discuss leadership in global health and innovation

MHRA

  • See product section


EU

  • EudraGMDP database update

  • Overview of comments on the draft guideline on quality requirements for drug-device combinations

  • Human Medicines Highlights Issue 153

  • SME newsletter issue 54

  • Q&A on labelling flexibilities for COVID-19 vaccines

  • Overview of comments received on ICH guideline M7

  • Report of EMA-Nuclear Medicine Europe (NMEU) bilateral meeting

  • Note on EMA’s involvement in HORIZON-HLTH-2022-TOOL-11-02: New methods for the effective use of real-world data and/or synthetic data in regulatory decision-making and/or in health technology assessment

  • Report of the EU Big Data Stakeholder Forum - 7 December 2021

  • Highlights from the second meeting of the Nitrosamine Implementation Oversight Group (NIOG) and pharmaceutical Industry

  • Journal of Pharmaceutical and Biomedical Analysis publishes results of the OMCL fingerprint study on omeprazole API samples

  • Replacement batches for European Pharmacopoeia (Ph. Eur.) reference standards

  • Outcome of the 171st session of the European Pharmacopoeia Commission

  • EP Supplement 10.8

  • Veterinary batch release network welcomes VMD, UK, as an observer

  • Ph. Eur. procedure 4


USA

  • Inspection of injectable products for visible particulates

  • Unannounced FDA inspections in India, China to begin soon

  • CMC Postapproval manufacturing changes for specified biological products to be documented in annual reports

  • Considerations for the use of Real-World Data (RWD)and Real-World Evidence (RWE) to support regulatory decision-making for drug and biological products

  • Development of anti-infective drug products for the pediatric population

  • Antisense Oligonucleotide Drug Products for Severely Debilitating or Life-Threatening Diseases (CMC guidance)

  • Cover Letter Attachments for Controlled Correspondences and ANDA Submissions

  • Q3C(R8) Impurities: Guidance for Residual Solvents


International


Australia TGA

  • Australian manufacturing licences and overseas GMP certification

  • Consultation: Compounded medicines and GMP

  • Consultation on Extemporaneous Compounding of Emergency Medicines

  • Guidance on the regulation of listed disinfectants in Australia

  • Regulator Performance Framework: Self-assessment Report July 2020 - June 2021


International Coalition of medicines regulatory Authorities (ICMRA) & World Health Organisation (WHO)

  • High-level meeting on global health emergencies and regulatory approaches

  • ICMRA and WHO map out flexibilities used by regulators to respond to the COVID-19 pandemic

  • Statement on Need for Continued Focus on COVID-19 Therapeutics


International Council for Harmonisation of technical requirements for pharmaceuticals for human use (ICH)


Quality Risk Management ICH Q9(R1)


Products

  • UK regulator (MHRA) approves use of Pfizer/BioNTech vaccine in 5 – 11 year olds

  • Oral COVID-19 antiviral, Paxlovid, approved by UK regulator

  • MHRA approves Xevudy (sotrovimab)

  • Increase in manufacturing capacity for COVID-19 vaccine from AstraZeneca

  • Nuvaxovid authorised in the EU

  • EMA recommends approval for use of Kineret in adults with COVID-19

  • EMA starts rolling review of Valneva’s COVID-19 vaccine (VLA2001)

  • EMA starts rolling review of Valneva’s COVID-19 vaccine (VLA2001)

  • COVID-19 Vaccine Janssen: EMA recommendation on booster dose

  • EMA recommends approval for use of RoActemra in adults with severe COVID-19

  • TGA Provisional Approval of Celltrion Healthcare Australia Pty Ltd COVID-19 treatment, regdanvimab (REGKIRONA)

  • Pfizer's COVID-19 vaccine (COMIRNATY) provisionally approved for use in individuals 5 years and over in Australia


RECENT DEVELOPMENTS IN GMP AND REGULATORY REQUIREMENTS


UK


The Association of the British Pharmaceutical Industry (ABPI)

ATMP Roadmap Tool

Advanced therapy medicinal products (ATMPs) have the potential to save and transform the lives of some of the sickest patients and potentially help to cure them.

But the process of getting these products to patients can often be complex, difficult to navigate, and hard for companies to understand.

The UK Government has recognised the potential of ATMPs and put in place initiatives to help develop Great Britain as a world leader in the sector, but more can still be done to help attract innovators to research, develop, manufacture, and launch their products in the UK.

The new roadmap aims to clarify the processes companies have to go through and how to engage with the system. It sets out four things that companies have to consider when launching a product:

The Roadmap Tool sets out the key steps and activities in the end-to-end pathway for ATMPs in England from non-clinical research through to patient treatment. The pathway signposts where differences exist between devolved nation (Scotland, Wales and Northern Ireland) and ATMP archetype:

  • Gene therapies (modification of the genetic material of living cells within or outside the body – in vivo and ex vivo)

  • Somatic cell therapies (the administration of human living cells which have been manipulated or processed outside the body – ex vivo)

  • Tissue-engineered products (which contains cells or tissues administered with a view to regenerating, repairing or replacing a human tissue)

England has a nationalised healthcare system with a single payer, NHS England, a singleregulator, MHRA, and a single Health Technology Assessment body, NICE, which makes market access reimbursement decisions. In order for a medicine to be commissioned as decided by the NHS in each devolved nation of the UK, the medicine must be licensed by the MHRA and undergo a Health Technology Assessment by NICE (or the applicable devolved nation body).

The content of the ATMP Roadmap was provided by multiple contributors including members of The Accelerated Access Collaborative (AAC) ATMP Workstream: The Association of the British Pharmaceutical Industry (ABPI), Cell and Gene Therapy Catapult, The MHRA, The Midlands and Wales Advanced Therapy Treatment Centre (MW-ATTC), NHS England (NHSE), The NICE, The NHS Specialist Pharmacy Service (SPS)

Global pharmaceutical industry leaders meet with UK Prime Minister to discuss leadership in global health and innovation

On 3rd December global leaders from the pharmaceutical industry met with the UK Prime Minister, senior Cabinet Ministers and the NHS Chief Executive, to discuss global health and innovation, on how to make the UK a life sciences superpower, and today’s The meeting with global underlined the progress so far. There is now a real opportunity to partner with the NHS and Government to deliver on the ambition set out in the Life Sciences Vision and ensure NHS patients can benefit from the latest medicines and vaccines.

MHRA

See product section


Europe


EMA

EudraGMDP database update

From 28 January 2022, manufacturers, importers and distributors need to ensure their organisation-related details such as name and address are correctly recorded in EMA’s Organisation Management Service (OMS) before applying to national competent authorities for any of the following (whether new or updated):

  • Manufacturing and importation authorisation

  • GMP compliance certificate

  • Wholesale distribution authorisation

  • Registration of an active substance manufacturer, importer or distributor

This applies to all EU and non-EU manufacturers, importers and distributors of human and veterinary medicines or active substances, which are mentioned in documentation uploaded in the EudraGMDP database.

Applicants whose details are not correctly recorded in OMS should submit a change request in OMS. National competent authorities (NCA) will no longer manually enter organisation-related details into EudraGDMP, but will rely on the master data held in OMS from January 2022.

Until further notice, these requirements do not apply to GDP compliance certificates.

Overview of comments on the draft guideline on quality requirements for drug-device combinations

EMA has updated its web page on Quality Documentation for medicinal products when used with a medical device. The effective legal date for the guideline itself is 1 Jan 2022.

Human Medicines Highlights Issue 153

This newsletter is addressed primarily to organisations representing patients, consumers and healthcare professionals. It provides a summary of key information relating to medicines for human use published during the previous month by the EMA.

SME newsletter issue 54

This newsletter is published 4 times a year by EMA and provides information for small and medium size enterprises on the EU regulatory environment for medicines.

Q&A on labelling flexibilities for COVID-19 vaccines

EMA’s Quality Review of Documents (QRD) group has issued revision 3 of this document

Overview of comments received on ICH guideline M7

EMA has published this overview of comments received on ICH guideline M7 on assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk. It will be sent to the ICH M7 EWG for consideration in the context of Step 2b of the ICH process. pharmaceuticals to limit potential carcinogenic risk

Report of EMA-Nuclear Medicine Europe (NMEU) bilateral meeting

This meeting was intended to provide an opportunity to engage in dialogue on key areas of mutual interest, share information, exchange views and enhance the respective mutual understanding of the needs and expectations of the respective organisations. NMEU organisation, radiopharmaceuticals’ stakeholders, specificities and current regulatory environment were identified topics of common interest.

It was recognized that radiopharmaceuticals are showing promise in oncology with many novel products entering clinical development EMA thanked NMEU for this timely sharing of information and positions in view of the on-going discussions of the pharmaceutical legislation review; recommendations were made to share these, where relevant, with the European Commission as part of the pharmaceutical strategy stakeholder’s consultation once available.

EMA emphasised and advised industry to consider applying for scientific advice, when considering the development of a new radiopharmaceutical product and when guidance are non-existent as this helps the regulatory network to reflect on new products requirements and guidance needs.

Note on EMA’s involvement in HORIZON-HLTH-2022-TOOL-11-02: New methods for the effective use of real-world data and/or synthetic data in regulatory decision-making and/or in health technology assessment

The principal aim of this topic is to address the data needs of health regulatory bodies and HTA bodies across the EU, as outlined in the recently published HMA-EMA Joint Big Data Taskforce (BDTF) Phase II report: ‘Evolving Data-Driven Regulation” and its associated Data Analysis and Real World Interrogation Network (DARWIN EU) project. In addition to national competent authorities, proposals could consider the involvement of the European Medicines Agency (EMA) for an added value in order to provide an effective interface between the research activities and regulatory aspects and/or to translate the research results into validated test methods and strategies that would be fit for regulatory purpose.

This document provides organisations planning to submit an offer to the HORIZON-HLTH-2022-TOOL- 11-02 call with information to be considered for proposing EMA’s involvement in their proposal.

Report of the EU Big Data Stakeholder Forum - 7 December 2021

165 registered participants attended the Forum by webinar and additionally the Forum was streamed live on the web. This report offers a high-level summary of the Forum discussions.

Highlights from the second meeting of the Nitrosamine Implementation Oversight Group (NIOG) and pharmaceutical Industry

Step 1 of the call for review requiring the evaluation of a potential risk of presence of nitrosamines in human chemical and biological medicinal products has now concluded.

More industry scientific data is needed in order to progress on critical topics such as the approach for mutagenicity assays, structure-activity relationship studies, root cause investigations and extrapolation of acceptable Intake limits from other substances.

These topics, along with other quality, safety and multidisciplinary topics will prioritised as part of the 2022 workplan.

More agile topic related scientific discussions between industry and regulators could be considered provided that there is sufficient relevant new information and scientific data to justify such interactions.

Nitrosamines International discussions (including at ICH level) amongst Regulators and Industry stakeholders is supported from EU perspective and being explored.


EDQM

Journal of Pharmaceutical and Biomedical Analysis publishes results of the OMCL fingerprint study on omeprazole API samples

In the study, official medicines control laboratories (OMCLs) tested the pharmaceutical quality of samples, checked compliance with the monographs of the European Pharmacopoeia and used chemometric methods to process analytical fingerprints. These fingerprints could then be used to differentiate between manufacturing sources in future authenticity investigations.

Replacement batches for European Pharmacopoeia (Ph. Eur.) reference standards

EDQM announces the availability of 13 replacement batches for European Pharmacopoeia (Ph. Eur.) reference standards

Outcome of the 171st session of the European Pharmacopoeia Commission

At this session, the Commission adopted 75 texts for publication in the 11th Edition of the European Pharmacopoeia: 66 revised texts and 9 new texts, including:

  • the revised and harmonised (through the Pharmacopoeial Discussion Group) chapter on Chromatographic separation techniques (2.2.46) ;

  • the new general chapter Implementation of pharmacopoeial procedures (5.26) ;

  • the revised and now harmonised monographs Paraffin, white soft (1799) and Paraffin, yellow soft (1554) ;

  • two new general chapters, Assay of Bet v1 allergen (2.7.36) and Microbiological examination of human tissues (2.6.39) ;

  • the revised monograph Vaccines for veterinary use (00062), including specific requirements for the microbiological quality of non-liquid vaccines for non-parenteral use.

The Ph. Eur. Commission also decided to add a further 9 new texts to its work programme

EP Supplement 10.8

The European Pharmacopoeia (Ph. Eur.) Supplement 10.8 is now available and will be applicable in 39 European countries as of 1 July 2022.

Veterinary batch release network welcomes VMD, UK, as an observer

The Veterinary Batch Release Network (VBRN) for immunological veterinary medicinal products (IVMPs) and the Veterinary Medicines Directorate (VMD), UK, have signed a memorandum of understanding (MOU) to renew the exchange and collaboration on common activities related to batch release of IVMPs post-Brexit.

The MOU is in force from 22/12/2021. It makes the VMD an observer to the VBRN and reinstates the sharing of information related to batch release in this field.

Note however that mutual recognition of certificates is outside the scope of this MOU.

Ph. Eur. procedure 4

This document is intended to help stakeholders understand the advantages of applying for a monograph elaboration via European Pharmacopoeia procedure 4. It describes how Group P4 has elaborated P4 monographs over the last 10 years. It also applies to monographs on biotherapeutics as elaborated by the P4 bio Working Party.



United States of America


The US Food and Drug Administration (USFDA)

Inspection of injectable products for visible particulates

Visible particulates in injectable products can jeopardize patient safety.

This draft guidance addresses the development and implementation of a holistic, risk-based approach to visible particulate control that incorporates product development, manufacturing controls, visual inspection techniques, particulate identification, investigation, and corrective actions designed to assess, correct, and prevent the risk of visible particulate contamination. The guidance also clarifies that meeting an applicable United States Pharmacopeia (USP) compendial standard alone is not generally sufficient for meeting the current good manufacturing practice (CGMP) requirements for the manufacture of injectable products. The guidance does not cover subvisible particulates or physical defects that products are typically inspected for along with inspection for visible particulates (e.g., container integrity flaws, fill volume, appearance of lyophilized cake/suspension solids).

Unannounced FDA inspections in India, China to begin soon

It is reported in a recent edition of Regulatory FocusTM,, Elizabeth Miller, assistant commissioner for medical products and tobacco operations in FDA’s Office of Regulatory Affairs (ORA), provided this update on the agency’s inspection activities at a 9 December virtual conference on enforcement sponsored by the Food and Drug Law Institute (FDLI). Miller also told industry to expect upcoming inspections to be a hybrid model combining records requests with on-site inspections. Miller told the webinar that an appropriations bill directs FDA to start a pilot in India and expand it to China for “short unannounced and short-term inspections.” Added Miller, “We are working to build a robust set of evaluations to assess the costs and the benefits and challenges of conducting these inspections. There is more to come on this as we plan to get this started.”

The House Appropriations Committee is concerned that FDA’s drug inspection program continues to fall behind the levels needed to match the growth in foreign drug manufacturing facilities. [I suspect that this will remain subject to COVID restrictions whilst the current concerns re new variants remains relevant MBH]

CMC Postapproval manufacturing changes for specified biological products to be documented in annual reports

This guidance provides recommendations to holders of biologics license applications (BLAs) for specified biological products regarding the types of changes to an approved BLA to be documented in an annual report under 21 CFR 601.12. Specifically, the guidance describes chemistry, manufacturing, and controls (CMC) postapproval manufacturing changes that FDA generally considers to have a minimal potential to have an adverse effect on product quality.

Under FDA regulations, postapproval changes in the product, production process, quality controls, equipment, facilities, or responsible personnel that have a minimal potential to have an adverse effect on product quality must be documented by applicants in an annual report.

This guidance focuses on reporting mechanisms.

Considerations for the use of Real-World Data (RWD)and Real-World Evidence(RWE) to support regulatory decision-making for drug and biological products

FDA is issuing this guidance as part of its RWE Program to satisfy, in part, the mandate under section 505F of the FD&C Act to issue guidance about the use of RWE to help support approval of a new indication for a drug already approved under section 505(c) of the FD&C Act or to help support postapproval study requirements.

For the purposes of this guidance, FDA defines real-world data (RWD) and RWE as follows:-

  • RWD are data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources.

  • RWE is the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD.

Development of anti-infective drug products for the pediatric population

The purpose of this guidance is to provide general recommendations on the development of anti-infective drug products, including antibacterial, antifungal, and antiparasitic products, for the pediatric population.

FDA encourages sponsors to discuss their initial pediatric study plans (iPSPs) for anti-infective drug products with the Agency early. In most instances, iPSPs must be submitted no later than 60 calendar days after the end-of-phase 2 meeting.

This guidance does not address the full scope of considerations for pediatric anti-infective drug product development. More detailed information on clinical pharmacology considerations for neonatal and pediatric studies (e.g., sample size, pharmacokinetic sampling, data analysis) is available in several guidances for industry.

This guidance also does not apply to preventative vaccines. The general principles set forth in this guidance apply to drug and biological products. However, because of the complexity and limited experience with some biological products regulated by the Center for Biologics Evaluation and Research (CBER) (e.g., cellular and gene therapies, phage therapies), there may be additional development considerations. In such cases, CBER encourages sponsors to reach out to the applicable review division, as appropriate.

Antisense Oligonucleotide Drug Products for Severely Debilitating or Life-Threatening Diseases (CMC guidance)

This guidance provides recommendations regarding the CMC information that should be provided in an investigational new drug application (IND) submitted by a sponsor-investigator developing an individualized antisense oligonucleotide (ASO) drug product for a severely debilitating or life-threatening (SDLT) disease caused by a unique genetic variant where only a small number of individuals are prospectively identified (typically one or two). These individualized ASO drug products should be from a well-characterized chemical class for which there is substantial clinical and nonclinical experience that is either publicly available or to which the sponsor has a right to reference.

Cover Letter Attachments for Controlled Correspondences and ANDA Submissions

This draft guidance is intended to assist prospective applicants, applicants, and holders of abbreviated new drug applications (ANDAs) with optional attachments that can be used when preparing cover letters that accompany controlled correspondence to the Office of Generic Drugs (OGD), as well as original ANDAs, amendments to ANDAs, and supplements to approved ANDAs submitted to FDA. These attachments do not replace the recommendations for the content of cover letters provided in other FDA guidances.

Q3C(R8) Impurities: Guidance for Residual Solvents

FDA has published this final guidance, which provides recommendations for permitted daily exposures (PDEs) for three additional residual solvents: (1) 2-methyltetrahydrofuran, (2) cyclopentyl methyl ether, and (3) tert-butyl alcohol.

As part of the maintenance process for the ICH guidance for industry Q3C Impurities: Residual Solvents (December 1997), the Q3C PDE levels are added and revised as new toxicological data for solvents become available.


International


Australia TGA


Australia Therapeutic Goods Administration (TGA)

Australian manufacturing licences and overseas GMP certification

This step-by-step guide is for:

  • Australian manufacturers of therapeutic goods (medicines, active pharmaceutical ingredients (APIs) and biologicals, human blood and blood components and haematopoietic progenitor cells) applying for a manufacturing licence for an Australian manufacturing site

  • Australian sponsors of therapeutic goods manufactured overseas applying for GMP certification of the overseas manufacturer

  • overseas manufacturers inspected by the TGA

Only Australian manufacturing sites can obtain a manufacturing licence. Overseas manufacturers can instead obtain GMP certification following a successful on-site inspection by the TGA.

GMP certification applications are required to be submitted by the Australian sponsor or an agent acting on the Australian sponsor's behalf.

GMP certification is usually only requested if it is not possible to obtain GMP clearance via the Mutual Recognition Agreement (MRA) or Compliance Verification (CV) pathways, for example due to lack of evidence.

The TGA reserves the right to undertake an inspection of an overseas manufacturing site, irrespective of any other evidence supplied.

Consultation: Compounded medicines and GMP

This consultation closed on 18 December 2020.

The draft guidance paper included proposed enhancements to the interpretation of current GMP requirements specified in the PIC/S Guide to GMP, PE009, specifically in relation to:-

  • The allocation of expiry dates for compounded goods.

  • Expiry dating of compounded goods manufactured from biological medicines, e.g. monoclonal antibodies.

  • The manufacture of non-sterile goods and re-packaged goods in dose administration aids (DAA)

Feedback on the proposed draft was received from a range of stakeholder groups.

TGA’s review of the submissions, and of further information subsequently sent directly to it, shows there are disparate views on some of the complexities associated with medicine compounding. It is investigating these concerns and further consultation will be required to confirm appropriate approaches.

A revised version of the guidance document is being prepared and will be sent to all respondents for comment. This targeted consultation is anticipated to commence early 2022.

Consultation on Extemporaneous Compounding of Emergency Medicines

TGA is seeking feedback on proposed regulatory reforms to support hospital pharmacists to extemporaneously compound certain medicines in advance of a patient being identified, so they can be available for immediate use in an emergency.

The consultation is to include a new exemption that would permit hospital pharmacists to extemporaneously compound certain medicines, prior to identification of a patient and without the requirement for the medicine to be included on the ARTG.

The public consultation opened on 7 December 2021 and closes on 7 February 2022.

Guidance on the regulation of listed disinfectants in Australia

Amendments were made to the Therapeutic Goods standard for disinfectants and sanitary products on 1 December 2021, and come into effect on 1 January 2022.

This instrument amends the Therapeutic Goods (Standard for Disinfectants and Sanitary Products) (TGO 104) Order 2019, to incorporate the definition and performance requirements for claims of residual activity. Updates were included in the TGA Instructions for Disinfectant Testing on 3 December 2021 to outline the testing requirements for claims of residual activity.

Regulator Performance Framework: Self-assessment Report July 2020 - June 2021

The health landscape has changed significantly since 2020, following the declaration of COVID-19 as a health pandemic. Balancing the impacts of COVID-19, and the demands of implementing regulatory reforms with our core business of providing high quality regulation of therapeutic goods in Australia, continues to be both a challenge and a priority.

The Government is committed to reducing the impact of inefficient regulation imposed on business, community organisations and individuals. The Regulator Performance Framework establishes a common set of performance measures for the assessment of regulator performance and their engagement with stakeholders. The Framework aims to encourage regulators to undertake their functions with the minimum impact necessary to achieve regulatory objectives.

The Framework comprises six outcomes-based Key Performance Indicators (KPIs) and associated measures. The KPIs articulate the Government’s expectations of regulator performance,

This is the final year regulators, including the TGA, are required to report under the Framework. From the 2021-22 financial year, regulators will measure and report performance under the Government’s new Regulator Performance Guide. The Guide sets out the Government’s expectations for regulator performance and reporting, including three new principles under which our performance must be measured:

  1. Continuous improvement and building trust

  2. Risk based and data driven

  3. Collaboration and engagement.


International Coalition of medicines regulatory Authorities (ICMRA) & World Health Organisation (WHO)


ICMRA high-level meeting on global health emergencies and regulatory approaches

On 1 and 2 December, ICMRA held a high-level meeting to discuss regulatory challenges, including those faced during the ongoing COVID-19 pandemic. Participants from the 24 members and 13 associated members and experts from the WHO and the European Commission also discussed the path towards regulatory alignment on the global response to the Omicron variant. One of the goals of the meeting was to exchange information on regulatory approaches to the COVID-19 response, draw lessons learned and identify future priorities and opportunities to strengthen regulatory preparedness for future public health emergencies. Meeting participants also reflected on other important issues that are on the agenda of medicines regulators and public health bodies, including the fight against antimicrobial resistance, medicines for use in pregnancy and supply chain integrity. A meeting report summarising the outcomes of the discussions will be published on the ICMRA website in due course.

ICMRA and WHO map out flexibilities used by regulators to respond to the COVID-19 pandemic

ICMRA & WHO have reviewed some of the practices applied by regulatory authorities worldwide to respond to the challenges faced during the COVID-19 pandemic.

The report now published by the two organisations features concrete examples of regulatory flexibilities and extraordinary measures that have been put in place in different areas of medicines regulation, including:

  • clinical trial oversight;

  • registration and Marketing Authorisation;

  • GMP, GCP, GDP /import & export, & GLP inspections;

  • post-authorisation activities and pharmacovigilance;

  • facilitating access and managing shortages of medicines;

  • medical devices (including personal protective equipment (PPE)) and sanitisers.

As a next step, global regulators are encouraged to share their experiences and exchange information concerning the effectiveness of the regulatory flexibilities they have applied during the pandemic.

Statement on need for continued focus on COVID-19 therapeutics

ICMRA presents this statement to highlight the significance of the continued need for development of additional therapeutics to treat and prevent COVID-19.

Building on the actions taken to-date, ICMRA, through international collaboration, pledges to continue the efforts towards developing new therapeutics for COVID-19. This is especially important in order to have treatment options for people who are unable to be vaccinated or who have lower immune response to vaccines (e.g., people who are immunocompromised), and to address issues such as break-through infections, the emergence of SARS-CoV-2 variants with some level of vaccine resistance, and waning immunity. For these reasons, there is an ongoing need for safe, effective and accessible treatments to complement vaccination.

Some advancements have been made with small molecules, including antivirals and glucocorticoids, to treat severe disease and monoclonal antibodies for prophylaxis or to treat mild-to-moderate COVID-19 in non-hospitalized patients. Many of these treatments have become available in several countries. While these treatments are helpful, all may require parenteral (intravenous or subcutaneous) administration and/or specialized healthcare settings to monitor for adverse events. This necessitates additional treatments with ease of administration and accessibility. Recent advancements in oral antivirals for mild-to-moderate infection are encouraging, and may help fulfil the unmet need for easily accessible options. Furthermore, the entire spectrum of COVID-19 illness could benefit from new treatments (including prevention, early mild-to-moderate disease in non-hospitalized patients, severe disease in hospitalized and ICU patients, and for patients with long-COVID symptoms).

ICMRA encourages collaboration to ensure the design of robust clinical trials that can deliver actionable results, with prioritisation of therapeutics with a high probability of success. Additionally, ICMRA will continue to support ongoing and sustained international collaboration on pharmacovigilance and post-approval systems to equip regulators with data and information that supports well-informed and timely action.


International Council for Harmonisation of technical requirements for pharmaceuticals for human use (ICH)


Quality Risk Management ICH Q9(R1)

This Step 2 document of the ICH Process, is a consensus draft text or guideline, agreed by the appropriate ICH Expert Working Group, is transmitted by the ICH Assembly to the regulatory authorities of the ICH regions for internal and external consultation, according to national or regional procedures.

Some key factors for the revision were:-

  • High levels of subjectivity in risk assessments and in QRM outputs

  • Product availability risks

  • Lack of understanding as to what constitutes formality in QRM work

  • Lack of clarity on risk-based decision-making

[Readers should acquaint themselves with the ICH background paper as well as the R1 paper for an indication of the required changes and the rationale behind them. MBH]


Products


UK regulator approves use of Pfizer/BioNTech vaccine in 5 to 11-year olds

A new paediatric formulation of the Pfizer BioNTech COVID-19 vaccine has been approved for children aged 5 to 11 after meeting the required safety, quality and effectiveness standards.

Oral COVID-19 antiviral, Paxlovid, approved by UK regulator

This new combination treatment is for people with mild to moderate COVID-19 who are at high risk of developing severe COVID-19

MHRA approves Xevudy (sotrovimab)

Another COVID-19 treatment, Xevudy (sotrovimab), has been approved by the UK MHRA after it was found to be safe and effective at reducing the risk of hospitalisation and death in people with mild to moderate COVID-19 infection who are at an increased risk of developing severe disease.

Developed by GSK and Vir Biotechnology, sotrovimab is a single monoclonal antibody. The drug works by binding to the spike protein on the outside of the COVID-19 virus. This in turn prevents the virus from attaching to and entering human cells, so that it cannot replicate in the body.

In a clinical trial, a single dose of the monoclonal antibody was found to reduce the risk of hospitalisation and death by 79% in high-risk adults with symptomatic COVID-19 infection.

Unlike molnupiravir, sotrovimab is administered by intravenous infusion over 30 minutes. It is approved for individuals aged 12 and above who weigh more than 40kg.

It is too early to know whether the omicron variant has any impact on sotrovimab’s effectiveness but the MHRA will work with the company to establish this.

Increase in manufacturing capacity for COVID-19 vaccine from AstraZeneca

EMA’s CHMP has approved a new site to manufacture Vaxzevria (previously COVID-19 Vaccine AstraZeneca) finished product. The site, operated by WuXi Biologics, is located in Leverkusen, Germany.

In addition to this new manufacturing facility, the CHMP has also given a positive opinion to scale up manufacturing to triple the batch size of finished product at a site operated by Amylin Ohio in West Chester Township, Ohio,USA.

Nuvaxovid authorised in the EU

Nuvaxovid is now authorised across the EU. This follows the granting of a conditional marketing authorisation by the European Commission on 20 December 2021.

Nuvaxovid (also known as NVX-CoV2373) is the fifth vaccine recommended in the EU to prevent COVID-19 in people from 18 years of age.

EMA recommends approval for use of Kineret in adults with COVID-19

Kineret (marketed by Swedish Orphan Biovitrum AB) is now authorised across the EU to treat COVID-19. This follows the granting of an extension of indication by the European Commission on 17 December 2021.

EMA starts rolling review of Valneva’s COVID-19 vaccine (VLA2001)

The CHMP’s decision to start the rolling review is based on preliminary results from laboratory studies (non-clinical data) and early clinical studies in adults. These studies suggest that the vaccine triggers the production of antibodies that target SARS-CoV-2, the virus that causes COVID-19, and may help protect against the disease. EMA will communicate further when the marketing authorisation application for the vaccine has been submitted.

The vaccine contains inactivated (killed) SARS-CoV-2 that cannot cause the disease. VLA2001 also contains two adjuvants, substances to help strengthen the immune response to the vaccine.

COVID-19 Vaccine Janssen: EMA recommendation on booster dose

EMA’s CHMP has concluded that a booster dose of COVID-19 Vaccine Janssen may be considered at least two months after the first dose in people aged 18 years and above. CHMP also concluded that a booster dose with COVID-19 Vaccine Janssen may be given after two doses of one of the mRNA vaccines authorised in the EU.

EMA recommends approval for use of RoActemra in adults with severe COVID-19

EMA’s CHMP has recommended extending the indication of RoActemra (tocilizumab) to include the treatment of adults with COVID-19 who are receiving systemic treatment with corticosteroids and require supplemental oxygen or mechanical ventilation.

The medicine, marketed by Roche Registration GmbH, is already approved in the EU for treating the inflammatory conditions rheumatoid arthritis, systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis and cytokine release syndrome (CRS).

The study also indicated that an increase in mortality cannot be excluded when using RoActemra in patients who are not receiving systemic corticosteroids. However, the safety profile of the medicine was favourable in those who are already receiving treatment with corticosteroids and the CHMP concluded that the medicine’s benefits are greater than the risks for these patients.

TGA Provisional Approval of Celltrion Healthcare Australia Pty Ltd COVID-19 treatment, regdanvimab (REGKIRONA)

The TGA granted provisional approval to Celltrion Healthcare Australia Pty Ltd for the use of regdanvimab (REGKIRONA) for the treatment of COVID-19. This is the fifth COVID-19 treatment to receive regulatory approval in Australia.

This monoclonal antibody treatment is now provisionally approved for the intravenous treatment of mild-to-moderate COVID-19 in adult patients who are confirmed to be infected with the SARS-CoV-2 virus.

The TGA's decision has been made on the basis of short-term efficacy and safety data.

Pfizer's COVID-19 vaccine (COMIRNATY) provisionally approved for use in individuals 5 years and over in Australia

The TGA has provisionally approved the Pfizer Australia Pty Ltd COVID-19 vaccine, COMIRNATY, for use in individuals 5 years and older. This decision follows the provisional approvals granted by the TGA to Pfizer for the use of COMIRNATY in individuals 12 years and older on 22 July 2021 and the booster dose for use in adults 18 years and older on 26 October 2021.


And finally…

Further information on these and other topics can be found in recent versions of the “Regulatory Update” on the PHSS website (members area) by utilising the hyperlink within that particular Update.

We hope that our readers find our reviews to be both informative and helpful in keeping up to date with pharmaceutical legislation and regulatory guidance.