Pharmaceutical companies selling their products in the UK need to consider the impact Brexit will have on their operations. Some changes will need to be made before the UK leaves the European Union on March 30, 2019.

In a press release, the European Medicines Agency (EMA) said:

“The guidance document outlines the practical and simplified requirements that companies should follow when they apply for changes to their marketing authorisation to allow for the continued marketing of their medicine in the European Economic Area after the UK withdraws from the EU. The guidance has been prepared on the basis that the UK will become a third country as of 30 March 2019. It should be read in conjunction with the Questions and answers related to the United Kingdom’s withdrawal from the European Union with regard to the medicinal products for human and veterinary use within the framework of the centralised procedure published in May 2017.”

The following questions are answered in the document:

1. Can I group Brexit-related variations?

2. How to classify Brexit-related changes impacting on the manufacturing activities for my medicinal product?

3. Can I submit several changes relating to manufacturing of the active substance or finished product under a single Type II variation?

4. How can I submit an application for the transfer of a marketing authorisation for my products and what would the applicable fees be?

4a. How to handle planned or ongoing regulatory procedures during the transfer of marketing authorisation?

4b. Is it possible to submit a transfer of the orphan designation in parallel with a transfer of the marketing authorisation?

4c. Is there any possibility to simplify transfer applications when these are Brexit related?

4d. Can requirement for mock-ups be waived for Transfers?

5. How can I submit a transfer or change in the name/address of an orphan drug designation sponsor for my products? (for medicines for human use)

6. How do I submit changes to Qualified Person for Pharmacovigilance (QPPV) and/or changes in the Pharmacovigilance Master File (PSMF)location? (for medicines for human use)

7. How do I submit changes to QPPV? (for veterinary medicines)

8. How do I submit changes to the person responsible of scientific services and to the person responsible for batch recall and quality defects? (for medicines for human use)

9. How do I submit changes to the person responsible for batch recall and quality defects? (for veterinary medicines)

To read the guidance, click here.

If you are interested in learning how Perficient can help you prepare for Brexit or help you evaluate the impact of new and proposed regulatory rules on your organisation, please reach out.

The European Medicines Agency (EMA) is will be moving its offices from London to Amsterdam, due to the UK’s decision to withdraw from the European Union. According to a press release issued by the EMA, the relocation effort needs to be completed by the end of March 2019.

The EMA currently employs close to 900 people, a majority of who have said they would be willing to move to Amsterdam. Nonetheless, the regulatory agency acknowledged that “activities will be impacted and we need to plan for this now to avoid the creation of gaps in knowledge and expertise.” A business continuity plan (BCP), which was published on September 26, 2017, indicates that it is prepared to handle a situation in which staff losses are significant.

Click here to read the press release.

The FDA has decided that it will update the ciphers for their Electronic Submissions Gateway (ESG), but what does this mean for you?

Here is the message that was received:

FDA Electronic Submissions Gateway (ESG) will update ciphers and SSL protocols in Production on Saturday, January 20, 2018 at 9:00 PM EST. Please make sure your AS2 system can connect to ESG with compatible secure ciphers and SSL protocols listed below. To make sure your AS2 system can connect to ESG, you may test in the ESG Pre-Production environment. The ESG Pre-Production environment already has the following updated SSL protocols and Cipher suites:

*  SSL Protocols

*  TLS 1.2

*  Cipher Suites (suites in server-preferred order)

*  TLS 1.2

*  TLS_RSA_WITH_AES_128_CBC_SHA (0x2f)

*  TLS_RSA_WITH_AES_256_CBC_SHA (0x35)

*  TLS_RSA_WITH_AES_128_CBC_SHA256 (0x3c)

*  TLS_RSA_WITH_AES_256_CBC_SHA256 (0x3d)

***Warning: if your AS2 system CANNOT connect to ESG with compatible secure ciphers and SSL protocols, you will not be able to send submissions to the FDA.***

A couple of things come to mind, as far as what steps you should take, based on the information the FDA has provided.

The first thing to do is to check which version of Axway you are using to see if the above cipher changes impact you.

Some companies do not have a version of Axway that will be able to deal with the new security settings, so one option is to upgrade to the newest version of Axway (5.12).

Some considerations need to be taken with this approach, depending on the partnerships you may have in place. For example, you may wish to test with other agencies/partners when an upgrade is being evaluated.

Also, there is the potential for downtime when upgrading. So, do you keep your current Axway running while installing the new version?

Something else to consider. If you have a version of Oracle Argus in 7.x, you will need to install the patch 8.9.9.97. This patch contains an updated JAR file, which will allow you to upgrade from 5.10.1 to 5.12 SP8 in product v7.x line. Upgrading Axway to 5.12 SP8 will be possible, but it requires Argus patch 8.9.9.97. This patch is not applicable if you are in the Argus 8.x range.

If you are interested in learning more about how we can help you upgrade Argus and Axway, feel free to reach out.

Oracle Argus Safety 8.1.1 was officially released today, so I thought I would share a question that came up recently from a hosting customer. The customer asked us what the difference between Argus Safety 8.1 and 8.1.1 is. While there are your standard bug fixes and improvements, there are two significant changes that companies should understand.

E2B(R3)

All companies that currently report safety data to regulatory agencies or partners using E2B will be required to adopt the new E2B(R3) format beginning in 2019. If you will be receiving cases from the European Medicines Agency (EMA) via the new EudraVigilance website, you will only be able to download these reports in R3 format. If you don’t upgrade to 8.1.1, you will need to use a backwards and forwards conversion (BFC) tool, which can transform the R3 file into an R2 file that you will then be able to import into Argus.

WHODrug B3/C3

The Uppsala Monitoring Centre (UMC) will be releasing WHODrug B3/C3, the new version of the dictionary, which will increase the length of two fields: CMCLAS and CMDECOD. This will help future-proof the dictionary. According to the UMC, the new version will be available alongside the current B2/C2 version until September 2018, at which point the new version will be the only option. While you will be able to load the new dictionaries into 8.1.1, Oracle said it will not be creating a patch for older versions.

If you are interested in upgrading to Argus Safety 8.1.1 and/or exploring our cloud hosting capabilities, I’d be happy to speak to you about it. Feel free to send me an email at indy.ahluwalia@perficient.com.

This is the final post in our brief series on drug safety. If you missed any of the previous posts, here are the links:

• Why Monitoring Adverse Events And Drug Safety Signals Matters
• What Exactly Is An “Adverse Drug Reaction?”
• The Role Of Signal Detection In Drug Safety
• What Pharmacovigilance Means And Why It Matters

In this week’s post, we’re discussing the ongoing monitoring of drug safety once a drug is on the market.

Where do safety signals come from in the world of drug development? They come from two broad areas, the first being clinical trials. Clinical trials are the way in which companies prove the safety and efficacy of their drugs in order to get them approved by various regulatory agencies. Even in their largest state with the most patients enrolled, clinical trials tend to be relatively small when compared to the potential reach of a product in the general public.

Clinical trials are typically not very diverse, especially when it comes to demographics such as race, gender, and ethnicity. They also tend to lack patients who are being treated for multiple conditions and/or who are receiving multiple therapies for a single condition. These are aspects of the real world that are essentially excluded from the clinical trial bubble.

This leads us to the second source of safety signals: the post-marketing area, in which a product that has been approved for general use hits a much more diverse and widespread community.

Historically, spontaneous reporting systems (or systems that rely on physicians and patients to report potential adverse events to the appropriate authorities) have been the go-to repository for gathering information and signals for particular drugs. However, there are problems with using spontaneous reporting systems, such as MedWatch, the United States Food and Drug Administration’s (FDA) safety information and adverse event reporting program. This is primarily due to a significant under-reporting of events. In fact, some journal articles suggest that only 10-15% percent of adverse drug reactions are reported.

While the reporting of adverse drug reactions is low, new and promising initiatives and methods are changing the way post-marketing analysis is performed. One example comes from the FDA’s Sentinel Initiative, which is using electronic healthcare data for signal evaluation. This concept combines data from disparate sources, ultimately enabling drug safety surveillance to be performed both proactively and in a holistic manner.

Mining a variety of data sources for safety signals, even social media, is becoming more prevalent in the industry and more feasible for pharmaceutical companies to perform. As the technology available to mine and analyze data becomes more effective and intuitive, the industry’s ability to detect signals will greatly improve.

Pharmacovigilance, or the practice of monitoring the effects of medicines after they have been released for commercial use, was expanded in 2002 by the World Health Organization (WHO) to include signal detection as a way of improving patient care and improving the overall health and safety of the general public. Today, pharmacovigilance activities should also contribute to the risk-benefit profile of the drug of interest.

It is also interesting to note that the WHO sees pharmacovigilance as having a role in helping the general public better understand the safety monitoring of individual drugs. In essence, this implies that the safety profiles of drugs should not reside solely with marketing authorization holders and regulatory authorities, but should instead be shared with the broader community.

Check back for the next post in this series on drug safety: post-marketing surveillance. While you wait, enjoy this guide on drug safety.

Hi everyone, it’s Indy here. For those of you who may not recognize my name, I’ve been helping lead our Argus Safety installations for the past few years. I wanted to drop a quick note to personally invite you to the webinar I’ll be presenting next week. It’ll be relatively short, by design, but it should be just enough to answer some of the burning questions you have about Argus Safety 8.1, the most recent version of Oracle’s drug safety and pharmacovigilance system.

As far as who should register, I recommend anyone who’s considering upgrading to 8.1, regardless of the version you’re currently running. If you’re running a safety system from a vendor other than Oracle and may be interested in switching to Argus, the presentation will be valuable to you, too. And, if you don’t currently have any sort of adverse event reporting system, the webinar will give you insight into some of the key Argus features.

Because this will be a shorter webinar, I won’t be taking any questions during the presentation. But, I’ll be happy to answer your questions afterwards and discuss your organization’s specific situation, needs, and requirements. You can email me anytime, now or after the webinar.

I look forward to seeing you Thursday, July 20, 2017.

Register Here↴

Due to the seriousness of adverse drug reactions, life sciences organizations perform something called “signal detection,” which is the process of evaluating potential safety signals. This entails looking at previously known associations between a drug and an adverse event, and looking at previously known drug-related issues that may be either improving or worsening. Not only do companies routinely do this type of analysis, they are obligated to do so under current regulatory guidelines.

Signal detection leverages a variety of methodologies, some of which are more comprehensive than others. One evaluation method, proposed by a number of signal detection specialists, is called the SNIP methodology. With SNIP, researchers consider the signal’s Strength, whether the signal is New, the Importance of the signal, and whether the signal can be prevented.

• Strength: This refers to the mathematical or scientific strength. Normally, the statistic used in this market analysis is an offshoot of an odds ratio of Proportional Reporting Ratio (PRR) or Bayesian statistic.
• New: How new is the event-drug relationship? Is it part of a well-established risk-benefit for the drug of interest or is it brand new?
• Importance: Is the ailment causing severe issues within the patient population or is this something that is a little more manageable, from a clinical perspective?
• Prevention: How easy is it to prevent this problem, from a public health perspective?

Various types of evaluation tools, like SNIP, are used to identify signals, regardless of whether they come from spontaneous reports, clinical studies, or scientific literature.

Check back soon for the next post in this series on drug safety: pharmacovigilance. In the meantime, check out this guide on drug safety and register for our upcoming webinar titled “The 5 Most Significant Changes in Argus Safety 8.1.”

When I’m approached by clients to discuss safety projects, it is generally about implementing Oracle’s Argus Safety, upgrading the system, or discussing their ability to comply with regulatory requirements.

Recently, I was asked about migrating from a legacy drug safety database to Argus. We discussed the methods available, such as leveraging an Oracle dump, a CSV file, and E2B+, as well as the level of effort each approach would require.

However, we began to question whether a data migration was even necessary, as our conversation about the requirements (or lack thereof) the company put forth, progressed.

SAS was being used for aggregate reporting and there was no current need for any reporting on the cases themselves, as this was an old legacy trial. But, the CRO’s customer was adamant that the data should be housed in a safety system.

All in all, unless safety reporting is necessary or another valid reason surfaces, then consider keeping the data in a CSV file and continue to use SAS for the aggregate reporting. It’s safe, effective, and will save your organization money.

***

If you’re interested in implementing Argus Safety, please reach out to discuss your situation. For over 20 years, we’ve helped many pharma, biotech, med device, and CROs implement clinical and safety systems, not to mention migrate data from legacy solutions. As far as deployment options, we’re flexible. However, most of our clients choose to implement in our compliant life sciences cloud. It’s worth a look, if you’re not familiar with it.

While there are many ways to define “adverse drug reaction,” let’s use one that is fairly simply to digest: an unintended, harmful response that is suspected to be caused by a medicinal product being taken under normal circumstances.

According to some sources, adverse drug reactions are the sixth-leading cause of death in the United States, with an estimated 100,000 deaths annually. To put it another way, more people die from the medicine they are taking to treat an ailment than die from the ailment itself.

Stay tuned for the next post in this series on drug safety: signal detection. While you wait, here is our latest guide on drug safety.

E2B(R3)

So, there we have it, the European Medicines Agency (EMA) has finally issued a statement, which confirms the date of release for the bigger, better EudraVigilance: November 22, 2017. Time to go into panic mode? Absolutely not. But, here are some of the things you should be thinking about as the deadline approaches:

Training

There is a large amount of training on the new EudraVigilance system already available on the EMA website. If you are a current Oracle Argus Safety user using a gateway, some of this is useful information, while some of it will not be relevant to the submissions that you make.

Going through the training will give you a clear understanding of what is required to be submitted and the useful tools that are available within EudraVigilance.

You will have the opportunity to test using the new XCOMP system beginning June 26, 2017.

Current Safety Database

You will need to consider if the new rules that will be required for the submission of cases to the new EudraVigilance systems will be supported by your system. If you are an Argus user, then considerations could be made to upgrade or use a backwards/forwards compatibility tool. Whatever you do, regardless of what system you use, you must consider if you need to be able to send R3 files. It would be a waste of time, money, and effort if you did not need to send the files in the first place.

If you’re using a backwards/forwards compatibility tool, considerations need to be made about what you do with the data and how you deal with this data, if you do eventually migrate to a system that can store the data in the correct tables. It could be possible that this data would require, essentially, a “mini-migration.” If a migration tool is used, will that need to be validated? How much testing is required? Is this effort, time-wise, fruitless if an upgrade takes the same amount of time? What would the total cost of this effort be?

If it is decided to upgrade, there are many considerations, again. How much will it cost? How long will the upgrade take? What version do I need to upgrade too?

Also, if you are an Argus user, any automated business rules you may have with European Health Authorities would need to be simplified for the new EudraVigilance system.

Business Processes

Finally, what business processes will be affected with the new system coming online? Do SOPs need to be updated? How about your Safety Data Exchange Agreements (SDEAs)? Does your current workflow for cases adapt to the changes? How are the new data analysis capabilities of EudraVigilance incorporated with the current internal system?

***

If you have any questions about EudraVigilance or our consulting and technology services, please let us know.

It takes an average of 10 to 15 years and $2.6 billion for a drug to reach pharmacy shelves. While there are many steps in the process that contribute to this lengthy timeline and cost, no aspect of the process is more critical than proving the safety of a drug.

Since a patient’s health is at risk throughout the testing of a drug, as well as the life of a drug once it has been approved, companies must leverage the most advanced methodologies and industry tools to mitigate any risk to the public.

In an upcoming series of posts, I’ll discuss the importance of monitoring adverse events and safety signals to ensure patients are always kept safe, from research through post-approval. In the meantime, check out our latest guide on drug safety.