FDA Guidance for Industry: Development of Abbreviated New Drug Applications during the COVID-19 Pandemic

In April 2021 the FDA released a new question & answer guidance document for the industry, specifically addressing Generics and their challenges during the COVID-19 pandemic. As the guidance is coming into effect immediately without prior public comments, it is worth having a closer look.

The FDA has issued this guidance to provide general recommendations to (prospective) applicants of abbreviated new drug applications (ANDAs) related to generic drug product development and regulatory submissions. The FDA has collated the questions and is presenting the responses in this guidance document for the benefit of all stakeholders. The FDA intends to revise/update this guidance as appropriate.

What does the guidance contain?

The guidance document has been structured into the following categories:

A) Generic drug product development;
B) Submission and assessment of ANDAs; and
C) Marketing and exclusivity.

Each category addresses different areas of concerns.

Category A: Generic drug product development

Questions in this category are mainly about bioequivalence studies and how any study interruption can be handled and whether multiple batches of reference products can be used in particular circumstances.

Category B: Submission and assessment of ANDAs

Questions in this category mainly address concerns about ANDA submissions for medicinal products that help with the COVID-19 public health emergency and possible site inspections that cannot take place because of restrictions invoked by the COVID-19 pandemic.

Category C: Marketing and exclusivity

Questions in this category address tentative drug approval and any impact of COVID-19 on timelines, specifically on exclusivity for Generics.

What other support is available for Generics?

Although not directly linked to the COVID-19 pandemic, the FDA has just launched the “Generic Drug Cluster” to improve global regulatory alignment among agencies, specifically in countries with focus on development of generic medicines. The “Generic Drug Cluster” aims to increase scientific alignment with the following objectives:

• Achieving a common understanding of each Agency’s regulatory requirements for approval and current thinking on topics related to generic drug development through information sharing on approval requirements and recommendations conveyed in guidance documents.
• Offering a confidential forum for exchange of discussion on policies in development, including draft guidances for industry, and the scientific basis for decisions on those policies.
• Provision of a forum for a discussion of general and product/class-related scientific review issues and fostering alignment in approaches to scientific evaluation whenever possible.
• Addressing long-term safety issues to ensure a global safety net for generic drugs through confidential sharing of reports.

Hopefully other agencies will also see a benefit in this forum to support global generic drug development.

In summary

With this Q&A guidance for industry, the FDA has addressed some of the questions faced by the Generics industry, in particular about the possible impact of the COVID-19 pandemic. The FDA provides some of the options available to the industry for handling studies and batches used to conduct bioequivalent studies as well as inspections. For Generics it will be a relief though that the FDA is not automatically rejecting applications that include sites that cannot be inspected because of COVID-19 restrictions. Approval decisions will be based on the entire information available. A key point is that marketing of a tentatively approved ANDA will not be possible.

With the recently launched “Generic Drug Cluster”, the FDA opened a communication forum for the world’s leading regulatory agencies to address generic drug development globally. Let’s hope that other agencies will also see a benefit in this forum and participate.

EMA’s new veterinary product information template

To be able to support the new veterinary regulations coming into effect in January 2022, the EMA updated the product information template that can be accessed here . The new template includes a new section on restrictions on the use of antimicrobials and antiparasitic veterinary products in an attempt to reduce resistance.

The other thing to notice is that the new template will address the need for Marketing Authorisation Holders (MAHs) to address any environmental issues. One notable example is the need to include information on special precautions for the protection of the environment – this information will help users of the medicinal product to better defend the environment.

What are the timelines?

One of the main aspects of the new template is that it supports the requirements under Regulation (EU) 2019/6, coming into effect 28/January/2022. Therefore, template version v9.0 should be used for all initial marketing applications after 28/January/2022. For product information of medicinal products placed on the market in accordance with Regulation (EC) 726/2004, template v8.2 may be used until 29/January/2027.

Please note that QRD template v.8.2 was revised in December 2021 to specify Northern Ireland as a local representative.

What does the new template v9.0 contain?

• a new structure of the SPC labelling and package leaflet with the order of sections aligned as far as possible;
• information only to be included in the package leaflet that was formerly in the labelling, simplifying the outer and immediate labelling;
• a consolidated section on ‘minimum particulars to appear on small immediate packaging units’ which now incorporates blisters and strips;
• a new section on any restrictions on the use of antimicrobial and antiparasitic veterinary products. This includes restrictions on conditions of use that are not in accordance with the terms of the marketing authorisation (MA);
• expanded guidance text in many sections to improve clarity for applicants and regulators;
• standard text for “marketing authorisation” granted for veterinary limited markets and under exceptional circumstances;
• reference to national collection systems for disposal of waste veterinary medicines.;
• guidance on specific content for novel therapies;
• increased flexibility in some sections;
• consolidated section for all contact details.

EMA also simplified the SPC and package leaflet sections on ‘frequency and seriousness of adverse events’.

In summary

It is clear that a big effort has been made to align the QRD template with the NVR coming into effect in January 2022. Although we can expect finalisation of the combined label-leaflet QRD in the fourth quarter of 2021, companies can already align their data and processes with the new template v9.0.

EMA electronic Product Information (ePI) Consultation

Expert and public comments sought on ePI, open until 31/July/2021.

The EMA has opened a public consultation on the draft EU common standard for electronic product information or ePI. The consultation period is open until end of July 2021 so there is little time left to give feedback. Comments should be provided via an online form accessible here.

Consultation is sought on the following documents:

• ePI API (Application Programming Interface) specification and the associated ePI API service list;
• A FHIR (Fast Healthcare Interoperability Resources) XML (eXtensible Markup Language) template based on the QRD (Quality Review of Documents) template for human medicines.
• An instance of an ePI sample message is provided in XML and HTML (Hypertext Markup Language), along with a sample XSL (eXtensible Stylesheet Language) transformation.

All documents are available on GitHub here.

What is ePI?

EU Common Standard for electronic product information (ePI) is authorised, statutory product information for EU medicines including the summary of product characteristics or SmPC, labelling for outer and inner packing and the package leaflet in a semi-structured format. ePI is adapted for electronic handling and allows dissemination via the web, e-platforms and print.

What is the ePI FHIR message template?

The objective of the ePI (FHIR) template is that it is to be used by template engines to transform PI information, in structured or semi-structured format to an ePI FHIR message.

Transformation of PI information (Source: EMA)

The resulting ePI XML message contains a FHIR resource, a Bundle of Bundles, each of which is a document having a composition, and supporting resources. The EMA will publish progress updates and details of stakeholder consultations and share these with patients, healthcare professionals, and the pharmaceutical industry.

Considerations on ePI

I believe it is important to state that the ePI initiative does not change the product information leaflet itself. It is merely a move away from a cumbersome paper-based system and an opportunity to streamline the processes of creating accurate product information leaflets on time in electronic format. The current mixture of structured and semi-structured data that we have seen in SPC documents for years does not support sophisticated data research and analysis. Maximum benefits of ePI would only be achieved via the use of electronic based package information leaflets. Updating or printing of the ever-changing leaflets would be a thing of the past, reducing the risk of having outdated package leaflets or even medicinal product recalls because of incorrect or outdated information. Professionals and the public would have instant access to the correct data online.

In summary

The ePI is well overdue, allowing the move away from outdated paper-based systems to modern electronic data management. With the envisaged use of FHIR for ePI, the path is set to modernise paper-based management of package leaflets. This more data driven approach is promising as long as it can be implemented European wide, not only at the EMA but also for national competent authorities. The benefits for professionals and the public include immediate access to the latest approved product information, availability of additional materials such as video and possible alerts informing about major leaflet updates.

The EMA has opened up a consultation period for professionals and the public alike to gather information on how best to support regulators, marketing authorisation holders, and the public using ePI, electronic product information. They need to know that the adopted Common Standard meets the needs of its future users, confirming they can access, view and disseminate product information in electronic format, ePI.

EU pilot project ‘Market Launch of Centrally Authorised Medicinal Products’

Action required: Pilot started 25/March/2021.

In March 2021 the European Commission, together with the EMA and Member States, committed to initiate a pilot to better understand the root causes of deferred market launches for centrally authorised products. The initiative has been launched with the engagement of future Marketing Authorisation Holders (MAHs).

The pilot’s overall objective is to “improve regulators’ knowledge of the planned marketing of centrally authorised medicinal products (CAPs) and on the reasons behind delayed market launch by engaging with prospective marketing authorisation holders through voluntary sharing of their marketing intentions for specific types of CAPs in the pre-authorisation phase.”

Why are Marketing Authorisation Holders not launching medicinal products European wide?

MAHs are not obliged to market a medicine in all EU countries even though they have achieved approval under the Centralised Procedure (CP). The reasons could be many, for example

  • National pricing and reimbursement policies
  • Market size and hence market potential
  • Organisation of health system including distribution of medicinal products
  • Administration burden
  • Operational limitations
  • Therapeutic area and availability of specialised staff and/or infrastructure

Which products are eligible for the pilot?

It is envisaged that only certain medicinal products will take part in this pilot. These products are orphan and oncology medicines in the context of newly submitted centralised applications, as well as centralised applications under assessment. Products are identified by their link to unmet needs and high public interest.

What method will be used?

Any MAH can take part in this pilot. MAHs will supply information about planned market launch and rollout of the medicinal product. Reasons for not bringing products to market or delayed launches will help to analyse and understand any possible impact, on both the MAH and member states.

MAHs should provide the following information:

  • Identification of the marketing authorisation applicant;
  • Identification of the medicinal product and its active substance;
  • Member States in which the company intends to market the product;
  • The envisioned timing of market launch per country;
  • Remarks on market launch intentions.

Templates for MAHs to notify any ‘Market Launch Intentions’ are provided by the EMA.

It is planned to run this pilot for a period of 18 months, beginning 25/March/2021. If you wish to take part, details can be found on the European Commission website here.

In summary

The aim of the pilot is to get a better understand of why MAHs that pursue the centralised procedure choose not to market their products in all European Union countries. Upon completion of the pilot, the data gathered will be analysed to see whether the reasons mentioned above (if any) are the contributing factors. Results and lessons learnt from this pilot will be published by the European Commission.

Can our four-legged friends help us get out of the COVID-19 pandemic?

Dogs are well known for their abilities to sniff out drugs even when hidden in the most concealed containers. K-9s assist humans worldwide by supporting the visually disadvantaged, hearing impaired and diabetic patients and they are well known to many of us undertaking security checks on airports. In more recent years though dogs are also assisting patients with other life-threatening health conditions.

How can K-9 be so effective?

Dogs are lucky to have about 300 million olfactory receptors in their noses, compared to a mere six million in humans. Hence dogs will be able to sniff out far more than humans will ever be able to. Furthermore, the part of a dog’s brain that is responsible for analysing smells is about 40 times larger than in humans. With that in mind, it is no wonder that dogs are able to retrace their steps for days as many of our dog walkers can relate to. There is another thing though. Dogs also have something called neophilia, which means they are attracted to new and interesting odours. Another factor many owners are far too familiar with.

Another more unknown factor is that when humans exhale through their nose, the spent air comes out in the same way it came in. In contrast, when dogs exhale, the spent air exits through the slits in the sides of the nose. This basically means, that dogs can more or less sniff continuously.

All these factors make dogs prime targets to assist in medicine by sniffing.

Any chance of K-9 assisting with fighting the COVID-19 pandemic?

In the UK, ‘Medical Detection Dogs’ has many years of experience in training dogs to detect different kinds of odours of diseases. These “bio detection dogs” are trained in a controlled environment to detect the odour of disease from samples, and then to apply that knowledge to detect certain medical conditions.

Previous work in this area has been published in the Lancet Infectious Diseases, funded by the Bill and Melinda Gates Foundation. During an earlier study, dogs were able to detect the presence of malaria with an effectiveness of over 90%.

Against COVID-19, ‘Medical Detection Dogs’ undertook a small study to assess whether four legs and a wet nose are the next weapon. The, until 01/June/2021, unpublished study found that people that were infected with the COVID-19 virus give off a distinct odour, detectable by our K-9 friends. The most accurate sniffer dog achieved 94.3% sensitivity. Comparing that with 97.2% for PCR (Polymerase chain reaction) tests, an astonishing result.

Another initiative led by the ‘National Veterinary School of Alfort’ is in line with the findings from ‘Medical Detection Dogs’, i.e. that dogs excel in the detection of COVID-19. With an efficiency of 97% based on over 300 people tested, our K-9 friends are very effective in sniffing out the true positives of the virus.

What type of dog might be suitable?

Sighthounds such as deerhounds or greyhounds are probably not a good idea as they are more interested in ‘chasing’, especially moving targets. What is needed are gundogs such as labradors, retrievers or spaniels that are best suitable as their main desire is ‘searching’, less ‘chasing’.

In summary

With K-9s being special to many individuals, by supporting people affected by diabetes or other life-threatening conditions, their support in medicines seems to be just starting. Sniffing out COVID-19 is the latest achievement our four-legged friends can assist with. And with an accuracy of over 90% in detecting COVID-19 during two independent studies that is comparable to more invasive COVID-19 tests, opportunities for support during this pandemic seem endless. Being able to sniff out the virus in airports, train stations or major events in seconds rather than waiting for a more traditional PCR test is an advantage not to be underestimated. The veterinary sector just became another important factor in beating COVID-19.

Samarind RMS is already supporting many clients in the veterinary sector, including the New Veterinary Regulations coming into effect next year.

SPC harmonisation: Call for Contribution to the Public Consultation of the Best Practice Guides of the CMDv

Action required: Consultation period for ‘SPC harmonisation’ ends 29/June/2021.

The CMDv (Co-Ordination Group for Mutual Recognition and Decentralised Procedure – Veterinary) is seeking feedback on its Best Practice Guides (NPGs) related to the New Veterinary Regulation (NVR), coming into effect on 28/January/2022. The Best Practice Guides have either been newly created or are updated accordingly. If you would like to get further information about the NVR itself, please refer to a previous blog here.

The CMDv published the table below, containing a list of documents and deadlines for consultation.

Please note that the CMDv will update the list of available documents as and when appropriate.

As a reminder, the initial objectives of the Regulation (EU) 2019/6 should be taken into account when commenting on the Best Practice Guides. And here more specifically the objectives of reducing administrative burden, enhancing the functioning of the internal market, increasing availability and safeguarding public health, animal health, animal welfare and the environment.

These Best Practice Guides have been prepared by the CMDv to be used during the SPC harmonisation procedures by Reference Member States (RMS), Concerned Member States (CMS) as well as the marketing authorisation holders (MAH), in order to facilitate the SPC harmonisation procedure.

What are the Harmonisation Procedure phases?

The SPC harmonisation procedure for veterinary medicinal products (VMP) can be divided into three phases:

1. Selection phase; MAH as well as Member States (MS) can suggest products to be considered.
2.A Examination phase for the reference veterinary medicinal product; determination whether the acceptance criteria to be eligible for the harmonisation procedure have been met.
2.B National phase for updating the SPC of the reference veterinary medicinal product.
3.A Harmonisation of the SPCs of generic and hybrid veterinary medicinal products.
3.B National phase for updating the SPCs of the generic and hybrid veterinary medicinal products.

According to these procedures National Competent Authorities (NCA) as well as MAHs may propose harmonisation of the SPCs of Reference Veterinary Medicinal Products (RVMPs) for which a marketing authorisation has already been granted.

A number of criteria for the prioritisation of the SPC harmonisation have been identified. However, it is probably disappointing that taking resource limitations within the agency network into account combined with untried and untested procedures, it is estimated that during the first year of implementation only 5-6 veterinary products can be short listed.

What is the impact of the SPC harmonisation on MAHs?

For products that are shortlisted by the CMDv, the CMDv working group on SPC harmonisation will first identify all MAHs with MA from the Union Product Database (UPD). VMPs should have the same active substance as those of the reference VMP. Targeted requests will be sent to MAHs concerned to provide information on the link between the MA of their product and the products identified on the CMDv shortlist.

For the reference VMPs listed in the CMDv shortlist for which the proposal for SPC harmonisation was not made by the MAH themselves, the MAH will be requested to provide the following information on their reference VMPs:

  • List of countries where the reference VMP is authorised;
  • Product name(s) and name and address of the MAH in all the countries where the reference VMP is authorised;
  • Type of marketing authorisation procedure in each of the MS where the reference VMP is authorised;
  • MRP number (if applicable);
  • MAH contact point for the SPC harmonisation (name, email and telephone number).

MSs might ask for additional information in case – for example – drug safety might be affected.

Comparative table to be submitted by the MAH

The CMDv provides further assistance (shown in the sample table below) to MAHs with regards to the information that should be provided in case the MAH (for each MS) makes a request to shortlist a reference VMP for the SPC harmonisation procedure.

Additional templates for requests are also provided. Users of the Samarind RMS solution have this information available at their fingertips, minimising time and effort spent to collect the right information from multiple sources accurately.

In summary

The Best Practice Guidance documents provide a good overview of the process to be adapted for the new SPC harmonisation procedure. Further details describe what MAH and NCA can expect and should provide. The provision of templates will simplify the process, but if you have a solution such as Samarind RMS, the information is already available at your fingertips.

Please keep in mind that the consultation deadline is 29/June/2021 if you wish to share your thoughts on the proposed SPC harmonisation guides.

EMA introduces additional measures to streamline assessments

Published by the EMA 11/May/2021.

In the process of streamlining assessment for medicinal products during the COVID-19 pandemic, the EMA is implementing additional temporary measures in the European medicines regulatory network . This should allow assessors to concentrate on the ever-increasing volume of COVID-19-related applications, whether vaccines or treatments. The focus will be on vaccines and therapeutics and – of course – safety monitoring of vaccines already given.

To ensure high standards of scientific evaluations during this pandemic, when the EMA has to dedicate resources specifically to COVID-19, the EMA has agreed a number of measures with the Management Board as outlined below. These measures complement the arrangements prioritising COVID-19 procedures that are already in place.

Temporary measures, starting from May 2021 for initial marketing authorisations, include:

For pre-authorisation procedures (text from the EMA website)

• All initial marketing authorisation applications (MAAs) for COVID-19 vaccines and therapeutics will continue to be given first priority. There will continue to be two independent, simultaneous scientific assessments with separate initial reports for these procedures, with no change to the current responsibilities of the rapporteur and co-rapporteur at EMA’s human medicines committee (CHMP).
• For initial MAAs for non-COVID-19 products, unless they are advanced therapy medicinal products (ATMPs) or other very complex medicines to be considered by the CHMP, the co-rapporteur will no longer provide a separate assessment report to the rapporteur in the first phase of the evaluation. Instead, he or she will review the submitted data and give a detailed critique of the rapporteur’s assessment report. These measures will free up some of the co-rapporteur resources to focus on COVID-19 activities.
• For all applications, there will temporarily no longer be a separate, formally appointed peer reviewer, but the assessment will rely on the intrinsic peer review that is part of the CHMP’s role in the evaluation process. In the case of COVID-19 products, there are additional reviews by the COVID-19 EMA pandemic Task Force (COVID-ETF).

It is anticipated, that the responsibilities for rapporteur and co-rapporteur will not change though.

For post-authorisation procedures (text from the EMA website)

Currently, the involvement of co-rapporteurs in the assessment of post-authorisation procedures to extend indications and extension applications (so-called line extensions) depends on the complexity of the file. The approach to these procedures is being temporarily amended as follows:

• For COVID-19 products, the co-rapporteur will be systematically involved in all such procedures; however, the need for two separate assessment reports, or for providing a detailed critique of the rapporteur’s assessment report, will depend on the complexity of the application.
• For non-COVID 19 products, when the co-rapporteur is involved, the co-rapporteur will produce comments on the rapporteur’s assessment report but will not draft a full separate report in the first phase of the evaluation.

These changes will also take effect from May 2021.

Additional activities will be implemented as needed, here specifically to facilitate the appointment of any rapporteur or co-rapporteur. The EMA will, in agreement with the CHMP and the Management Board, regularly review the measures if required and further support by the EMA might be available.

New EMA veterinary product information template

Action required: The EMA invites comments for the new product information template by 14/May/2021.

The EMA just released a new product information template for public consultation. Besides smaller adjustments, the template mainly addresses changes required in line with the New Veterinary Regulations (NVR) that is coming into effect January 2022. Although no firm date for implementation has been provided for the new template, the EMA will inform Marketing Authorisation Holders (MAHs) when to start using the new template after the NVR comes into force.

What does the new template contain?

The new template contains the following:

• a new structure of the SPC and package leaflet; MAHs have to adjust their own templates accordingly to stay compliant;
• Simplification of outer and immediate labelling by providing information only in the package leaflet;
• a consolidated section on ‘minimum particulars to appear on small immediate packaging units’;
• a new section on any restrictions on the use of antimicrobial and antiparasitic veterinary medicines;
• standard text for marketing authorisations granted for veterinary limited markets and under exceptional circumstances;
• reference to national collection systems for disposal of waste veterinary medicines;
• guidance on specific content for novel therapies.

The EMA also simplified the SPC and package leaflet sections on frequency and seriousness of adverse events.

Changes to be considered by Marketing Authorisation Holders (MAHs)

The main purpose of the new template is to be compliant with the NVR and hence it is now based on “Article 35 of Regulation (EU) 2019/6” instead of “Article 14 of Directive 2001/82/EC”.

Another update MAHs will notice is the link to EMA’s SPOR, or better to the Referentials of SPOR. Here MAHs can already benefit from solutions such as Samarind RMS, providing an interface to SPOR and therefore minimising list management and eliminate data entry mistakes. The EMA changed template references accordingly from “Target species: according to the target species CTL on the EUTCT website” to “Target species: according to the target species list under “Referentials” on the SPOR website.”

MAHs that are more focused on regional markets will also notice the addition of the national procedure.

More subtle changes are for specific field formats such as the expiry date, changing from “EXP {month/year}” now to “Expiry dates should be expressed with the month given as 2 digits and the year as 4 digits. e.g.02/2007”. Another example is the manufacturing batch number, which previously was given as “<Batch> <Lot> <BN> {number}”, now defined in a new format as “Lot {number}”.

In summary

Although some changes are more subtle with only minor impact on the actual content of the veterinary product information template, MAHs still need to address any alterations to stay compliant. This of course brings further demands on MAHs in the veterinary space. With the deadline of the NVR looming in January 2022, and a deadline for comments on the veterinary product information template coming up imminently, MAHs do not have much time to get involved. However, SPOR Referentials should help to simplify reference data management significantly.

EMA’s PRIME draft toolbox: Consultation ends July 2021

Action required: Consultation for the EMA PRIority MEdicine (PRIME) draft toolbox guidance closes 31st July 2021.

What is PRIME about?

The European Medicines Agency (EMA) launched the PRIority MEdicines (PRIME) scheme in March 2016. The scheme was launched to provide early and enhanced scientific and regulatory support for medicines that target an unmet medical need. PRIME focuses on medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without any treatment options.

PRIME benefits

PRIME aims to bring promising innovative medicines to patients faster by optimising and supporting medicine development. PRIME benefits patients, but also the industry.

Benefit for patients:

  • PRIME is driven by patients’ needs
  • PRIME focuses on medicines to address unmet needs and rare diseases
  • PRIME helps to translate research into development while meeting regulatory requirements
  • PRIME brings promising treatment to patients earlier

Benefit for industry

  • PRIME assists development of promising medicines
  • PRIME fosters early dialog with the EMA to facilitate robust data collection
  • PRIME supports creation of high-quality Marketing Authorisation Applications
  • PRIME aims to speed up the evaluation process
  • PRIME encourages developers to focus on medicines that are likely to make a real difference

Challenges:

Experience to date has shown that applicants face challenges to complete quality, manufacturing development and data requirements during development of medicines for early access. Initiatives such as the ‘rolling review’ are trying to address such challenges for promising or urgently required medicines.

How does the PRIME process work?

Data from the EMA shows that only just over 20% of PRIME requests are actually granted. However, once a candidate medicine has been selected, the Agency:

  • appoints a rapporteur from the Committee for Medicinal Products for Human Use (CHMP) or from the Committee for Advanced Therapies (CAT), to provide continuous support and help to build knowledge ahead of Marketing Authorisation Application (MAA);
  • organises a kick-off meeting with the CHMP/CAT rapporteur and a multidisciplinary group of experts from relevant EMA scientific committees and working parties;
  • issues guidance on a company’s overall development plan and regulatory strategy;
  • offers a dedicated EMA contact person;
  • provides scientific advice at key development milestones, involving additional stakeholders as needed.

It is important to note that medicinal products eligible for PRIME are potentially eligible for accelerated assessment during the Marketing Application process, a benefit not to be underestimated.

EMA’s PRIME toolbox

Until 31/July/2021 the EMA is now looking for feedback on their PRIME toolbox (reference EMA/CHMP/BWP/QWP/IWG/694114/2019, 02/February/2021). Consultation is sought on this ‘toolbox style’ document that provides guidance by summarising scientific elements and regulatory tools, available in the existing EU regulatory framework. It is seen as support for the development and completion specifically of Module 3 quality data packages in the preparation of MAAs. It is hoped, that a well-prepared Module 3 will support timely access to the medicine whilst providing assurance that product quality, efficacy and safety are not compromised.

The document includes two major sections:

Scientific tools

Referring to scientific concepts, principles or technologies used for development, manufacture and quality risk management of medicinal products. These might include modelling, analytical or platform technologies.

Regulatory tools

The EMA seeks to support the medicinal product development process early on and to offer regulatory mechanisms to help a ‘faster time to market’ approach without compromising quality, safety or efficacy. This process for example includes giving scientific advice during medicinal product development.

In summary

EMA’s ‘PRIME toolbox’ document outlines the available support from the Agency with scientific and regulatory tools, easing the way for the industry to be able to gain quicker market access for medicinal products addressing unmet medical needs. Action is required as comments are required by 31/July/2021.

FDA Adverse Event Reporting System (FAERS)

FDA launches FAERS public dashboard for COVID-19 emergency use authorization products.

Covid-19 is currently in the news worldwide and that on a daily basis. With vaccinations now becoming more widely available, not only healthcare professionals are interested in post vaccination information. The public too is getting hungrier not only for information on vaccination success, but also on possible side effects even though these are minimal.

With that in mind, the US Food and Drug Administration (FDA) has launched a new public dashboard, allowing tracking of adverse event reporting for drugs treating Covid-19. The FAERS public dashboard is a highly interactive web-based solution, allowing extensive querying functionality. The FDA acknowledges though that there are limitations. One being that a report in FAERS does not necessarily mean that the drug in question actually caused the side effect. Other limitations include

  • FAERS can include duplicates and incomplete reports
  • Reports reflect only the reporter’s opinion and are not necessarily linked to the cause of the drug event as the event could have been triggered by other reasons.
  • Reports and their content have not been (medically) verified.
  • Rates of occurrence cannot be established with reports.

Despite these limitations, the FDA emphasises that improving data access and transparency were core concepts that drove FAERS development. The FDA anticipates that increased transparency will lead to more detailed and complete report submissions by health care professionals and the public.

The dashboard itself provides the ability to display data according to regions, seriousness, age group and others. The below example shows a report by report type.

Another example shows a report by age group (data view as of March 11, 2021).

An easier representation of the same data is also available in graphic view (data as of March 11, 2021):

The user interface is very flexible and allows further drill down into the data, such as viewing of a specific age group or year.

In summary

FDA’s Adverse Event Reporting System (FAERS) is a good example of how agencies can increase transparency of adverse event reporting for medical professionals as well as the public. The FDA states that “Complete and detailed reports are immensely helpful to the agency when identifying safety signals”. Sharing additional information during difficult times such as the Covid-19 pandemic will be appreciated and can only lead to better safety monitoring and ultimately to better medicinal products, benefiting all patients.