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


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Vol27.4A Oct 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, Canadian, the Access Consortium of regulators and Australian and regulatory authorities.


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



Medicines and Healthcare Regulatory Authority (MHRA)

  • UK-Canada - UK Trade Continuity Agreement Protocol for Recognition of GMP


  • Biosimilar medicines can be interchanged

  • EMA pilot offers enhanced support to academic and non-profit developers of ATMPs

  • Big Data Update

  • Steps to support self-sufficiency in tissues and cells for human application and facilitate sharing of knowledge in this field

  • Newsletter-Transplant-2022-shows-a-global-increase-in-donation-and-transplantation-figures-lessons-learnt-from-covid-19-pandemic

  • European Pharmacopoeia Supplement 11.1

  • PDG welcomes Indian Pharmacopoeia Commission to pilot for global expansion.

  • New FAQ on EDQM HelpDesk: Ph. Eur. revised general chapter 2.2.46. Chromatographic separation techniques

  • Ph.Eur reference standards


  • Submitting Documents using Real-World Data (RWD) and Real-World Evidence (RWE) to FDA for Drug and Biological Products

  • Quantitative labeling of sodium, potassium, and phosphorus for human over-the-counter and prescription drug products

  • Statement of identity and strength — content and format of labeling for human nonprescription drug products

  • How To Obtain a Covered Product Authorization



Access Consortium

  • International work-sharing - First medicines approved by all five Access Consortium regulators

Australia

Therapeutic Goods Administration (TGA)

  • Sports supplements declared to be medicines

  • Review of paracetamol overdose

  • First combination COVID-19 and influenza self-tests approved for Australia


  • Adapted vaccine targeting BA.4 and BA.5 Omicron variants and original SARS-CoV-2

  • New medicine to protect babies and infants from respiratory syncytial virus (RSV) infection


RECENT DEVELOPMENTS IN GMP AND REGULATORY REQUIREMENTS


UK


MHRA

UK-Canada - UK Trade Continuity Agreement Protocol for Recognition of GMP

As of September 1, 2022, Health Canada, the (MHRA) and the UK Veterinary Medicines Directorate (VMD) agreed to expand the existing approach of recognizing GMP inspection results to include inspections that are conducted in countries outside of the respective Parties’ jurisdictions (i.e. extra-jurisdictional inspections) for human and veterinary finished products included in the operational scope of the Annex 1 of the Protocol for pharmaceuticals.

Stakeholders will benefit from the exchange of Certificates of GMP Compliance between Canada and the United Kingdom for inspections conducted outside of their respective jurisdictions. This will contribute to reducing the regulatory burden for the importers to obtain information to demonstrate compliance to GMP for their foreign buildings.

MHRA’s & Health Canada’s GMP requirements continue to be applicable. Therefore, there are no GMP exemptions for imported finished dosage form products from these foreign buildings.


Europe


European Medicines Agency (EMA)

Biosimilar medicines can be interchanged

EMA and the heads of Medicines Agencies (HMA) have issued a joint statement confirming that biosimilar medicines approved in the European Union (EU) are interchangeable with their reference medicine or with an equivalent biosimilar.

While interchangeable use of biosimilars is already practiced in many Member States, this joint position harmonises the EU approach. It brings more clarity for healthcare professionals and thus helps more patients to have access to biological medicines across the EU.

A biosimilar is a biological medicine highly similar to another already approved biological medicine (the 'reference medicine'). Interchangeability in this context means that the reference medicine can be substituted by a biosimilar without a patient experiencing any changes in the clinical effect.

“EMA has approved 86 biosimilar medicines since 2006. These medicines have been thoroughly reviewed and monitored over the past 15 years and the experience from clinical practice has shown that in terms of efficacy, safety and immunogenicity they are comparable to their reference products and are therefore interchangeable”, says Emer Cooke, EMA’s Executive Director. “This is good news for patients and healthcare professionals, who have wider access to important therapeutic options to treat serious diseases such as cancer, diabetes and rheumatoid arthritis.”

EMA pilot offers enhanced support to academic and non-profit developers of ATMPs

EMA is launching a pilot to support the translation of basic research developments into medicines that could make a difference in patients’ lives in the European Economic Area (EEA). The pilot is open to academic sponsors and non-profit organisations who are developing advanced therapy medicinal products (ATMPs). These medicines for human use are based on genes, tissues or cells and might offer ground-breaking treatment options to patients.

The pilot will focus on the needs of non-profit academic developers. They are a major contributor to the development of ATMPs and diagnostic and delivery devices, but experience has shown that navigating regulatory requirements can be challenging.

During the pilot, EMA will provide enhanced regulatory support for up to five selected ATMPs that address unmet clinical needs and are solely developed by academic and non-profit developers in Europe. EMA will guide the participants through the regulatory process with the aim to optimise the development of the ATMPs, starting from best practice principles for manufacturing to planning clinical development that meets regulatory standards.

The pilot’s first participant has already been selected. This ATMP is ARI-0001, a chimeric antigen receptor (CAR) product based on patients’ own T-cells, that is developed by the Hospital Clínic Barcelona.

Big Data Update

A good practice guide for the use of real-world metadata is available for public consultation until 16 November 2022.

This draft guide aims to help regulators, data holders, researchers, pharmaceutical companies and other interested stakeholders to use the catalogue of data sources that will replace the currently available ENCePP [a publicly available register of non-interventional post-authorisation studies (PAS)]catalogue.

For instance, it provides recommendations on how to identify suitable real-world data sources for studies, and describes the required metadata elements.


EDQM

Steps to support self-sufficiency in tissues and cells for human application and facilitate sharing of knowledge in this field

The Committee of Ministers of the Council of Europe has adopted a recommendation encouraging member states to harmonise the collection of data on the availability and use of tissues and cells according to a predefined set of parameters and definitions. This text aims to support self-sufficiency in tissues and cells for human application and to facilitate data sharing across borders, with the ultimate goal of ensuring rational, fair, timely and equitable access to safe tissues and cells for human application. The fact that human tissues and cells can restore essential functions or even save lives underlines the extreme importance of gaining proper knowledge in this field.

At present, only a fragmented and incomplete picture of tissue and cell activity is available, at both national and European levels. Current efforts to collect relevant activity data are undermined by the lack of consensus and clarity on the data needed for different purposes, harmonisation of the terminology used and a legal mandate to collect this type of data. The result is that data collection fails to achieve the desired goals, but is a huge burden for the establishments entrusted with the task.

Newsletter-Transplant-2022-shows-a-global-increase-in-donation-and-transplantation-figures-lessons-learnt-from-covid-19-pandemic

This report is produced thanks to the Spanish Organización Nacional de Trasplantes (ONT), which co-ordinates the collection, compilation and analysis of international data annually through a vast network of health authorities and officially designated individuals involved in donation and transplantation activities. This is done under the aegis of the European Committee on Organ Transplantation (CD-P-TO) of the European Directorate for the Quality of Medicines & Healthcare (EDQM)/Council of Europe. Although donation and transplantation activities continued to be affected by the COVID-19 pandemic in 2021, the return to pre-pandemic figures is well underway. Over time, an increased understanding of the SARS-CoV-2 virus in the transplant setting – of the testing and selection of donors and recipients or the impact of the disease on patients, for example – has prompted changes not only in the way we protect and treat patients, but also in how transplant programmes are managed. Close international co-operation has played a major role in these successes, enabling transplant programmes and professionals worldwide to adjust to adverse – and persistent – pandemic conditions.

European Pharmacopoeia Supplement 11.1

The European Pharmacopoeia (Ph. Eur.) Supplement 11.1 is now available and will be applicable in 39 European countries as of 1 April 2023

PDG welcomes Indian Pharmacopoeia Commission to pilot for global expansion.

The Pharmacopoeial Discussion Group (PDG), which brings together the European Pharmacopoeia (Ph. Eur.), the Japanese Pharmacopoeia (JP) and the United States Pharmacopeia (USP), with the World Health Organization (WHO) as an observer, is delighted to welcome the Indian Pharmacopoeia Commission (IPC) as a participant in the PDG pilot for global expansion. This announcement follows the decision to launch a pilot for expansion of membership taken at the 2021 PDG Annual Meeting and that represented a critical first step in the PDG’s commitment to expanding the recognition of harmonised pharmacopoeial standards with a view to achieving global convergence. The one-year pilot for expansion is scheduled to start as of the PDG Annual Meeting to be held virtually in October 2022.

New FAQ on EDQM HelpDesk: Ph. Eur. revised general chapter 2.2.46. Chromatographic separation techniques

Following queries received from users New FAQs on the application of revised general chapter 2.2.46. Chromatographic separation techniques (11.0) has been added to the existing series of FAQs dealing with the Ph.Eur & international Harmonisation.

Ph.Eur reference standards

2 new Ph. Eur. reference standards and 5 replacement batches released in August 2022.


United States of America


The US Food and Drug Administration (USFDA)

Submitting Documents using Real-World Data (RWD) and Real-World Evidence (RWE) to FDA for Drug and Biological Products

To facilitate FDA’s internal tracking of submissions to the Agency that include RWD and RWE, this guidance encourages sponsors and applicants to identify in their submission cover letters certain uses of RWD/RWE. This guidance does not address FDA’s substantive review of the RWD/RWE submitted as part of the Agency’s standard review process. This guidance applies to submissions for investigational new drug applications (INDs), new drug applications (NDAs), and biologics license applications (BLAs) that contain RWD/RWE intended to support a regulatory decision regarding product safety and/or effectiveness.

Quantitative Labeling of sodium, potassium, and phosphorus for human over-the-counter and prescription drug products

This guidance provides recommendations for quantitative labeling of sodium, potassium, and phosphorus present in human prescription and nonprescription (commonly referred to as over-the-counter (OTC)) drugs.

Products within the scope of this guidance’s recommendations are orally ingested products and injectable medications containing an amount of 5 mg or more of sodium, potassium, or elemental phosphorus per maximum single dose. Individuals or entities responsible for drug product labeling are encouraged to engage with FDA for advice on specific cases.

Statement of identity and strength — content and format of labeling for human non-prescription drug products

This draft guidance provides recommendations for the content and format of the required statement of identity on the labeling of human nonprescription drug products. This draft guidance also provides recommendations on the inclusion of the drug product’s strength on the labeling. The recommendations in this draft guidance are intended to help manufacturers, packers, distributors, applicants, relabelers, and sponsors ensure consistent content and format of the statement of identity and strength for all human non-prescription drug products. Consistent content and format of the statement of identity and strength may aid consumers in comparing nonprescription drug products and assist consumers in appropriate self-selection.

How To Obtain a Covered Product Authorization

This guidance describes how eligible product developers can obtain a Covered Product Authorization (CPA) from FDA under the law widely known as the CREATES Act (referred to herein as CREATES or the CREATES Act). The CREATES Act provides a pathway for eligible product developers to obtain access to the product samples they need to fulfill testing and other regulatory requirements to support their applications. As described in further detail below, to make use of this pathway, an eligible product developer seeking to develop a product subject to a Risk Evaluation and Mitigation Strategies (REMS) with elements to assure safe use (ETASU) must obtain from the Agency a Covered Product Authorization (see 21 U.S.C. 355-2(b)(2)). This guidance replaces the December 2014 draft guidance for industry How to Obtain a Letter from FDA Stating that Bioequivalence Study Protocols Contain Safety Protections Comparable to Applicable REMS for RLD.

The December 2014 guidance has now been withdrawn.


International


Access Consortium

International work-sharing - First medicines approved by all five Access Consortium regulators

Asciminib (Scemblix®) & Faricimab (Vabysmo®) were the first applications jointly evaluated by all five Access Consortium members - the TGA, Health Canada, Health Sciences Authority (HSA) Singapore, Swissmedic and the Medicines and Healthcare products Regulatory Authority (MHRA) of the United Kingdom, and are the twenty-second and twenty-third medicines approved through the NASWSI since it commenced in 2018.

The Access Consortium is an alliance of like-minded regulatory authorities, whose goal is to maximise international cooperation, reduce duplication, and increase each agency's capacity to ensure consumers have timely access to high quality, safe and effective therapeutic products.

The Access work-sharing initiatives streamline the medicine registration process and reduce duplication of evaluation effort, with each participating agency leading the evaluation of a different part of the submission dossier. However, each agency makes an independent decision regarding approval (market authorisation) of the new medicine.

[It’s good to see such international systems ‘growing in use. MBH]


Australia


Therapeutic Goods Administration (TGA)

Sports supplements declared to be medicines

In Australia, a sports supplement can be classified as either a food or a medicine in law. How it is classified depends on factors including the product's ingredients, marketing claims and how it is presented (including the dosage form - pill, food bar, powder etc.).

Many sports supplements are appropriately marketed as foods in Australia. However, some contain ingredients that have stimulant or other drug-like effects, such as changes to hormone levels, or are in a medicinal dosage form (e.g. tablets, pills and capsules). These products can present a higher risk to the consumer and it is therefore inappropriate to have them available for purchase as foods.

Because of safety concerns related to the use of certain sports supplements, a declaration has been made providing legal clarification on which sports supplements are considered therapeutic goods in Australia. Determining whether a product is a food or a medicine is important because there are different requirements for medicines and foods that depend on factors including product ingredients, and how they are manufactured, labelled and advertised.

The legal clarification provided by the declaration means that sports supplements will be regulated by the TGA as therapeutic goods if:-

  • they are presented in the medicinal dosage form of a pill, tablet or capsule, or

  • their ingredients are higher-risk to consumers

Review of paracetamol overdose

TGA has published an independent expert report examining the incidence of serious injury and death from intentional paracetamol overdose, and will now consult widely on the recommendations including possible options to amend the Poisons Standard.

The report was commissioned to examine the rate of serious injury and death from intentional paracetamol overdose, and to understand whether the current access controls for purchasing paracetamol products are appropriate, particularly in younger more vulnerable groups in the community. In addition, the report assessed whether if stricter controls on access to paracetamol were implemented, individuals would likely seek other means for self-harm, however assessment of the international literature and experience of the authors suggested that this was not likely.

The panel made seven recommendations to help reduce the harms from intentional paracetamol overdose.

First combination COVID-19 and influenza self-tests approved for Australia

TGA has approved the first two nasal combination self-tests (for use at home) that detect both COVID-19 and influenza viral infections in humans. Combination self-tests are like other COVID-19 rapid antigen tests (RATs) but feature an additional line on the test cassette that indicates the presence of influenza A and B. For many consumers, distinguishing between COVID-19 and influenza is important in managing their infections.


Products


Adapted vaccine targeting BA.4 and BA.5 Omicron variants and original SARS-CoV-2

This adapted bivalent vaccine targeting the Omicron subvariants BA.4 and BA.5 in addition to the original strain of SARS-CoV-2 is now authorised for use across the EU.

Comirnaty Original/Omicron BA.4-5 is for use in people aged 12 years and above who have received at least a primary course of vaccination against COVID-19. This vaccine is an adapted version of the mRNA COVID-19 vaccine Comirnaty (Pfizer/BioNTech).

New medicine to protect babies and infants from respiratory syncytial virus (RSV) infection

EMA has recommended a marketing authorisation in the European Union (EU) for Beyfortus (nirsevimab) for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease in newborn babies and infants during their first RSV season (when there is a risk of RSV infection in the community).Nirsevimab, the active substance in Beyfortus, is an antiviral monoclonal antibody (a type of protein), which has been designed to attach to the F (fusion) protein that RSV needs to infect the body. When nirsevimab is attached to this protein, the virus becomes unable to enter the body’s cells. This helps to prevent RSV infection. Because the medicine is removed slowly from the body, over a period of several months, a single dose of Beyfortus protects infants against RSV disease during the entire RSV season.

Beyfortus was supported through EMA's Priority Medicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to promising new medicines that address unmet medical needs. Beyfortus was also evaluated under EMA's accelerated assessment mechanism because prevention of RSV infection in all infants is considered to be of major public health interest.

The opinion adopted by the EMAs CHMP is an intermediary step on Beyfortus’ path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation.


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.


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