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.

New EMA’s Union Product Database production release

The EMA released version 01.02 of the Union Product Database on 16th March 2021.

As part of the New Veterinary Regulations (NVR) implementation, the EMA is developing a Union Product Database (UPD) to allow the management of veterinary medicinal products in the EU. The UPD has been welcomed by many and will certainly improve the safety, availability and maintenance of veterinary medicinal products. In a previous blog we looked at the UPD, how it impacts Marketing Authorisation Holders (MAHs) and to better understand purpose and advantages.

Today though, I shall look at the latest UPD product release version 01.02 that contains additional functionality compared to its previous releases. But there are also some alarming uncertainties that require urgent attention.

The important updates

The new UPD version 01.02 provides the following additions:

  • Additional functionality compared to release 01.00 (core UPD Repository and Application Programming Interface (API), including document management and validation).
  • The first version of the National Competent Authority (NCA) User Interface (UI), providing search, view and create functionality.

It should be noted though, that this release is limited to centrally and nationally authorised products with functionality for DCP and MRP to be provided in the release scheduled for July 2021.

The important notes

Besides not supporting DCP and MRP, it is important to understand that this new UPD version is compliant with the EU implementation guide dated back to 2020. It is not compliant with the more recent guidance published in January 2021 for which the consultation period just closed. This however highlights at least one major challenge for all stakeholders: any new implementation guide might require changes to the underlying data structure of the UPD. This by itself brings another challenge as the data already entered into the UPD might not be retainable. The notification from the EMA is clear: “… we do not recommend to use this release of the UPD for production purposes yet.” Considering the tight timetable for implementation, this will be a further blow to outside stakeholders such as the Marketing Authorisation Holders (MAHs) and solution providers who eagerly await a stable data structure and API. According to the EMA, more functionality will be made available gradually between now and January 2022 but for a successful interaction with the UPD, stable APIs and data structure are a must.

The changes

The new UPD version 01.02 provides mainly four areas of improvements via the User Interface (UI) for National Competent Authorities (NCAs):

  • Create product via UI (for centralised and national procedures)
  • Search product via UI
  • View product via UI
  • Manage notifications via UI (for centralised and national procedures)

This should allow NCAs to test their interaction with the UPD using the UI.

The API has been enhanced too with the following:

  • Get a specific Product version
  • Get everything of Product version
  • Get all Product versions
  • Update Product
  • Validate Product
  • Create document
  • Retrieve document (by ID)
  • Search document (by ID)
  • Update document (by ID)

There are further updates on existing APIs such as changes to the “create Product key” and “update Product” in line with the changes in the UI. Some examples will help defining and understanding the FHIR (Fast Healthcare Interoperability Resources) messages. However, there is also a long list of issues with the UI and API.

In summary

Release 01.02 of the UPD brings some additional functionality, allowing NCAs to test their data exchange method with the UPD. However, as this release is based on the guidance document from 2020, the data structure as well as API and UI might still change which will make life difficult for MAHs and solution providers alike. With the implementation timeline for the NVR in January 2022 looming, not much time is left for stakeholders to comply. A stable data structure and API will be a must to move forward successfully.

EMA’s Union Product Database user research

Union Product Database: EMA’s Veterinary Medicines Division released user research.

In January 2021, the EMA released some interesting findings about how stakeholders might want to make use of the Union Product Database (UPD).

What is the UPD?

According to the New Veterinary Regulations (NVR) EU 2019/6, the European Medicines Agency (EMA) shall establish and maintain a Union Product Database. In an earlier blog we provided other details about the UPD itself [link] as well as the latest updates [link].

To get access to data maintained in the UPD, the future public portal should provide access for everybody with an interest in veterinary medicines including veterinary professionals, agencies (full access), marketing authorisation holders (access to their own Marketing Application data) and the public (limited read access) to

  • search and view information on all authorised veterinary medicines in the EU;
  • check on availability of veterinary medicine in specific member states;
  • ability to consider alternative treatments.

The public will be able to search the UPD for product information nationally and in the wider EU. Data fields of interest include but are not limited to the product name, active substance, country of authorisation, target species, and Marketing Authorisation Holder (MAH).

EMA’s UPD user research

In 2020 the EMA conducted user research with regards to the public portal of the UPD, providing some interesting insights from nearly 400 responses. (ref. EMA/33780/2021, Union Product Database user research). In this blog we will focus only on a few areas that will be of interest.

  1. How often do you look up information on veterinary medicines?
Source: EMA

From the data analysed, it seems users are looking for information regularly on a weekly or daily basis.

2. What drives you to look up information on veterinary medicines?

Source: EMA

The main reason for stakeholders to access data seems based around product and safety information for the veterinary medicinal product.

3. How would you typically search for information on veterinary medicines?

The ability to search the UPD was one of the most important factors for all user groups. In particular, users were interested in searching the following:

  • Active substance name;
  • Medicine name;
  • Species;
  • Indication;
  • Medicine’s availability in member states
Source: EMA

4. Other areas of the user research

EMA’s user research included some further details on

Safety data
– Finding comprehensive safety data on veterinary medicines, including possible side effects.
Tracking changes
– The ability to monitor changes on a specific medicine.
Downloading data
– The ability to download data for offline use.
Language
– Which language users mostly use for searching.

In summary

From the user research undertaken by the EMA it is clear that users would prefer a single database where they can find data about the veterinary medicine as well as further information about availability and safety. One of the main functionalities desired is the ability to search and filter the data to each individual need. To make the UPD successful, the EMA will need to ensure that the end user’s needs are met.

FDA’s eCTD end of life?

Action required: The FDA withdraws support for eCTD Module 1 US Regional DTD 2.01.

FDA’s eCTD end of life? Not quite, but it looks like we are getting there. In October last year, the FDA announced the end of support for eCTD Module 1 US Regional DTD 2.01 for marketing applications. By 1st March 2022, the FDA requires all submissions to be compliant with eCTD Module 1 US regional DTD 3.3. Although the new format has been around for some time, the deadline is in less than a year from now!

But that seems just to be the beginning of the move to more structured automated data driven assessment. The FDA is doing more and has launched new initiatives such as KASA (Knowledge-aided Assessment and Structured Application) for a more data driven approach to Marketing Application (MA) assessment. In particular, the KASA system has been designed to

  1. Capture and manage knowledge during product life cycle.
  2. Establish rules and algorithms for risk assessment, control and communication.
  3. Perform computer aided analysis of applications to compare regulatory standards and quality risks across applications and facilities.
  4. Provide a structured assessment that minimises text-based narratives and summarises provided information.

KASA will modernise the process of MA assessment via the use of structured data. We will come back to KASA in more detail in a future blog.

So what about eCTD 4.0?

But what about some kind of middle ground between eCTD 3.2.2 and KASA? What about eCTD 4.0? Any mileage in that? Although no firm dates have been set yet for eCTD 4.0 to become mandatory, checking on the ICH website the following timelines are revealed:

Source: ICH

With most agencies planning to go into pilot during 2022, not much time is left for Marketing Authorisation Holders (MAHs) to get ready. So what is eCTD 4.0 all about?

Advantages of eCTD 4.0

eCTD 3.2.2 has served the industry and regulators well over the years, but it is showing its limitations with the limited ability of changing meta data assigned to eCTD nodes being one of them. Another limiting factor is document granularity that, without major effort, is fixed for the entire life cycle of a document. Both of these have been addressed in eCTD 4.0.

There are other advantages of moving to eCTD 4.0:

  1. All content from Module 1 to 5 is contained in one exchange message, harmonising the submission units.
  2. Documents can be referenced via unique IDs from the same or different submission units.
  3. Allows reuse and life cycle of meta data.
  4. Ability to apply changes to keywords that further define the submission content.
  5. Introduction of controlled vocabularies, a method the IDMP SPOR project is already benefiting from.

The move from eCTD 3.2.2 to eCTD 4.0 comes at a price though, as without a Transition Mapping Message (TMM) sponsors will not be able to move to eCTD 4.0. The TMM requirement is for all submission content in ‘current view’, which is to be referenced in the new format. Just a few weeks back in January 2021 the FDA released the eCTD v4 Technical Conformance Guide version 1.1, containing updates mainly made following comments during the comment period. One major change is the removal of two-way communication. I will come back to the eCTD 4.0 itself in a future blog.

In summary

So is this indeed the end of life of eCTD? Probably not yet. At least for now, regulators in Europe, North America, Australia and elsewhere require MAHs to submit MA in eCTD 3.2.2 format with eCTD 4.0 approaching fast. Additional meta data together with further flexibility on document granularity and attribute life cycle will ease the assessment process somewhat, but a more structured data driven approach such as KASA is desirable.

EMA’s Union Product Database implementation guide updated (again!)

Action required: Union Product Database implementation guide is available for consultation until 21/March/2021.

Today, I shall look at three of the many changes proposed.

The first important update.

Under the New Veterinary Regulations (NVR) EU 2019/6, the European Medicines Agency (EMA) shall establish and maintain a Union Product Database (UPD). In previous blogs we looked at some of the new requirements such as UPD access policies and what it might mean for Marketing Authorisation Holders (MAHs) to deliver additional information on veterinary medicinal products. Now on 21/January/2021 the EMA released a draft implementation guide on the UPD for public consultation and one of the main areas for MAHs to consider is the implementation timelines.

Source: EMA Veterinary Regulation Highlights, Issue 3, January 2021

These timelines define when MAHs and competent authorities have to manage veterinary medicinal product information in the UPD. And these timelines are tight.

The Veterinary EU Implementation Guide for the Union Product Database

The second important update.

The EMA provided the UPD implementation guide (EMA/536780/2020, 21/January/2021) to support MAHs as well as competent authorities who are submitting veterinary medicinal product data into the UPD. The main emphasis of the implementation guide is to standardise the definition of the data elements and to assist competent authorities during the implementation. In particular, the implementation guide provides the following:

  • Chapter 1: Registration and data access requirements for the User Interface and Application Programming Interface (API)
  • Chapter 2: Format for the electronic submission of veterinary medicinal products information
  • Chapter 3: Process for the initial submission and maintenance of veterinary medicinal products information
  • Chapter 4: Processes for the submission of legacy data on veterinary medicinal products
  • Chapter 5: API Technical specifications
  • Chapter 6: Practical examples

One of the major aspects the implementation guide confirms is that “The UPD is building on the existing PMS database structure with connection to the three other services of SPOR”.

As a reminder, then, SPOR is based on the four pillars of

  • Substance Management Services (SMS)
  • Product Management Services (PMS)
  • Organisation Management Services (OMS)
  • Referentials Management Services (RMS)

With the SPOR portal providing the following data management services:

  • view, search, export SPOR data
  • request new and updated SPOR data
  • translate SPOR data
  • browse relevant SPOR documentation

The UPD message format

The third important update.

A further important aspect of the UPD implementation guide is the definition of the message format for the delivery of data and documents to the UPD , which will be based on the Fast Healthcare Interoperable Resource (FHIR) message format (“The information and documents related to a veterinary medicinal product shall be submitted to the UPD via a Health Level 7 (HL7) Fast Healthcare Interoperable Resource (FHIR) message based on the terminology and reference standards available in the SPOR system.”). Using the FHIR format, from 28/January/2022 MAHs shall submit the following:

(a) the dates when their authorised veterinary medicinal products are placed on the market, information on the availability of each veterinary medicinal product in each relevant Member State, and the dates of any suspension or revocation of the marketing authorisations concerned.
(b) the annual volume of sales for each of their veterinary medicinal products.

Products placed on the market before 28/January/2022 have a slightly longer deadline and should be recorded by 28/January/2023.

In summary

The EMA is inviting interested parties to comment on the UPD implementation guide until 21/March/2021. The UPD implementation guide provides timelines, details on data exchange message formats (FHIR) and further details about the use of SPOR. Stakeholders are advised to act in a timely fashion to address any issues that this implementation guide might present.

With the above, we only touched on three of the important aspects of the UPD implementation guide. More details will follow in future blogs.

Machine Learning for the benefit of Life Sciences

Machine Learning (ML) is a form of Artificial Intelligence (AI), allowing applications to learn from the data processed. This is in contrast to programming, which follows a defined route to write a specific computer program. During the absorption of data, the ML algorithms learn to produce better, more precise ‘models’. These ML ‘models’ are an output from training the ML algorithms. Training can be performed on smaller data sets, but best results are achieved when using large data sets.

After training a ‘model’, when you provide the model with an input, you will be producing an output. For example, a data extraction algorithm will create a data extraction model. Then, when you feed this model with data, you will receive a data extraction based on the data that trained the ‘model’. In most cases this will be an iterative process, allowing the ‘model’ to learn continuously.

ML differs from data mining as data mining is based on the principle of statistics. Traditionally data mining is used on structured data, intended to demonstrate data patterns. In contrast, ML automates the identification of patterns, mainly used to make predictions. To be fair, there are some similarities as both are analytical processes and are good for pattern recognition.

Although ML is already widely used in life sciences with analysing medicinal images, to give one example, it seems in Regulatory Affairs we are trailing behind. The recent implementation of IDMP highlighted several issues with regards to data and its granularity but also where it is maintained and how it can be accessed. Many found that accessing unstructured data, usually as part of documents, is a real challenge. This is where companies can benefit from ML.

The challenges with unstructured data.

Pharmaceutical companies are required to create SPCs (Summary of Product Characteristics) and PLs (Package Leaflets) for each and every medicinal product on the market. Both documents contain the required data to keep the public and health professionals informed about substances, excipients, Marketing Authorisation Holders (MAH), possible side effects and more. But here lies the challenge: structured data is contained in unstructured documents. The implication is that the data extraction project will be abandoned or time-consuming manual more error prone processes have to be used. But both options seem unsuitable if these documents are the only place where this type of data is managed. So, are there other more sophisticated methods available?

The benefit of Machine Learning.

ML seems an ideal approach here for many reasons. First of all, with SPCs available for nearly all medicinal products on the market, a large data set is available for training the ML ‘model’. Secondly, SPCs are semi structured documents with predefined sections, which partly supports the extraction process of product name, indication, substance, excipients and other data fields. Moreover, ‘models’ have to be trained to identify different SPCs for different products from different regions, independent of whether these products are for human or animal use.

Data granularity is another challenge, specifically with IDMP (Identification of Medicinal Products) in mind. The IDMP data model for example defines the “Authorised Medicinal Product” in detail with components including but certainly not limited to “Medicinal Product Name”, “Manufacturer/Establishment (Organisation)”, “Contra-Indication” and “Indications”. Now “Name of Medicinal Product” is also part of the SPC and so are “Therapeutic Indications” and “Contra-indications”. However, the granularity of SPC data compared to IDMP data is different. Here is where ML algorithms can be of benefit. ML algorithms will learn how to interpret the data structure and extract the data in IDMP compatible format. This process of “supervised learning” is based on certain understanding of the data to be analysed. The benefits are clear: an automated process via ML to establish structured data, which then can be used company wide for analysis and future processing, whether in Regulatory, Labelling or elsewhere.

Another underestimated benefit specifically for Generics would be the ability to easily compare SPCs with the originator’s SPC. Data from both documents, the originator SPC and the Generics SPC, can be extracted and compared on data level to identify any differences that might have occurred, especially after updates following an adverse event. ML algorithms will learn the layout of both versions of the SPC, train their ‘models’ accordingly and allow for precise data extraction, which then can be easily compared. Here we might get into Deep Learning utilising neural networks but more on that in a future post.

Join us at the upcoming DIA conference, 8th to 10th February 2021 to learn more about Machine Learning for the benefit of Life Sciences.

UK spearheading Pathway for faster Time to Market

The UK is spearheading a new initiative on how innovative medicinal products can be brought to market faster and therefore made accessible to patients more quickly. In December 2020, the MHRA released new guidance documents on ILAP or Innovative Licensing and Access Pathway to clarify new opportunities for stakeholders in medicinal product development. Already operational, this initiative encourages early pipeline discussions between stakeholders. The aim of ILAP is to accelerate the time it takes to get a medicinal product to market and does not replace the Early Access to Medicines Scheme in areas of unmet medical needs. The Pathway brings together innovative approaches to support the safe, timely and efficient development of innovative products.

What are the criteria for acceptance to the new Pathway?

To take part in ILAP, interested parties have to submit an Innovative Passport application for each medicinal product. This process is open from the pre-clinical trial phase through to mid-development and the Passport itself contains a broad and inclusive definition of ‘Innovation’. To fulfill the Passport requirements, the following criteria have to be met:

  • Criteria 1: details of the condition, patient or public health area.
    a) the condition is life threatening or seriously debilitating or
    b) there is a significant patient or public health need
  • Criteria 2: the medicinal product fulfils one or more of the following areas
    a) Innovative medicine such as an advanced therapy medicinal product or new chemical or biological entity or novel drug device combination
    b) The medicine is being developed in a clinically significant new indication
    c) Medicine for rare disease and/or special populations such as neonates, children, pregnant women and the elderly
    d) Development aligns with the objectives for UK public health priorities.
  • Criteria 3: the medicinal product has the potential to offer benefits to patients
    For this criterion the applicant is expected to provide a summary of how patients are likely to benefit from the product or indication coming to market, including:
  • proposed improved efficacy or safety
  • contribution to patient care or quality of life, as compared to alternative therapeutic options.

What Regulatory Tools are utilised?

ILAP utilises Regulatory Tools supporting the following:

• Adaptive inspections
• Certifications
• Continuous Benefit Risk Assessment integrating Real World Evidence
• Clinical Practice Research Datalink (CPRD) Assisted Patient Recruitment
• Enhanced patient engagement
• Innovative and Flexible Licensing Routes
• Novel Methodology and Innovative Clinical Trial Design
• Rapid Clinical Trial Dossier Pre-Assessment

More details about Regulatory Tools including description, benefits and expected use can be found on the MHRA website.

What might the impact be on Regulatory professionals?

There are many areas that might have an impact on Regulatory professionals. One specific area worth mentioning can be found under the section “Innovative and Flexible Licensing Routes”. This Regulatory Tool has the potential to expedite timelines for review and accelerate assessment so valid marketing applications will reach opinion on approvability within 150 days of submission. This option is available for good quality marketing applications for both new and existing active substances.

The other area worth mentioning is “Rolling Review”. It is a new route for marketing applications, offering ongoing regulatory input and feedback. The process is envisaged as a phased, modular, iterative approach of evaluation.

Summary

Overall, ILAP might be the next step that supports the safe, timely and efficient development of innovative products. It is a cutting-edge approach to allow early reviews supported by an increasing number of useful Regulatory Tools that assist stakeholders to make better decisions more quickly, thus bringing medicinal products to the market faster.

UPDated – EMA updated Union Product Database implementation guide

According to the New Veterinary Regulations (NVR) EU 2019/6, the European Medicines Agency (EMA) shall establish and maintain a Union Product Database (UPD). In July 2020 the EMA published the UPD access policy (EMA/198149/2020), which outlines who gets access to which data stored in the UPD. It outlines how all parties can meet their obligations as provided in the Veterinary Medicinal Product (VMP) regulations and at the same time protect personal as well as confidential data.

But who can access the UPD?

The UPD will be open to agencies, marketing authorisation holders as well as the public. Different access levels will be provided, allowing data entry and updates where required. Considering the needs and requirements from different UPD stakeholders, UPD access levels are as follows:

  1. Full access for authorities, EMA and Commission.
  2. MAH will have access to their own MA.
  3. Limited read only access for the public (including veterinary practitioners).

The public will be able to search the UPD for product information nationally and in the wider EU. Data fields of interest include but are not limited to the product name, active substance, country of authorisation, target species, and MAH.

How will it all work?

The status of the Union Product Database (UPD) has again been updated. The release notes from the EMA have been published (EMA/556635/2020) together with additional information on which data can already been accessed. This release of the UPD makes the first components such as the API available, thereby providing access initially for National Competent Authorities (NCA). However, the functionality is limited to reading information on centrally authorised products and automatically creating MRP/DCP/NAP product information. NCAs can link to the UPD via an API to extract Centralised Authorised Product (CAP) information. NCAs can also start testing product information upload. Further information on increased functionality is planned to be released gradually throughout the coming months.

What about other stakeholders?

The Federation of Veterinarians of Europe (FVE) has very specific expectations with regards to the UPD search capabilities (FVE/20/doc/055, August 2020). The following search criteria are especially seen as relevant for veterinary practitioners:

  • Product name,
  • qualitative and quantitative composition of the pharmacologically active substance(s),
  • the pharmaceutical form,
  • countries the veterinary medicinal product is authorised in,
  • indications for use,
  • target species and dosage for each species,
  • method and route of administration,
  • contra-indications and adverse events,
  • drug-drug interactions,
  • information essential for safety or health protection,
  • withdrawal time,
  • distribution category,
  • Marketing Authorisation Holder (MAH) and
  • therapeutic group.

Although only from one stakeholder’s point of view, the benefits of a single database seem obvious.

In summary

The expectations are high, the list of demands looks excessive. But it also highlights the benefits that can be achieved with the UPD if implemented correctly with all stakeholders in mind. If combined with keyword or wildcard searching and access to SPC and PIL documents, the UPD will truly be single source of information for many – as long as all product information is actually managed within it of course.

Please feel free to contact us if you require further information.