Getting in Step: How to Meet Compliance with Electronic ICSR Reporting

Patient safety and monitoring adverse events is mission critical and as such it’s top priority for every life sciences company. Sometimes, however, staying on top of new regulations and guidelines around the myriad of safety reporting requirements can be a challenge – not because companies aren’t committed to doing so, but simply because there just aren’t the resources.

This is certainly true of the regulations for Individual Case Safety Reports (ICSRs). In June last year, it became a requirement to submit ICSRs for marketed drug and biologic products to the Food and Drug Administration (FDA) in electronic format. What this means is instead of sending paper MedWatch forms to the FDA, ICSRs must be submitted in XML format to the FDA Adverse Event Reporting System (FAERS), a database containing all adverse event and medication error reports submitted to the FDA. The new XML format includes all of the same data elements as the MedWatch form – just in a more standardized and easier-to-process format.

The point of these changes is two-fold: 1) To facilitate a move toward global standards for reporting safety events to regulatory health authorities, and 2) to encourage the industry to be more proactive about doing safety reports and getting them out on time so the agency can have a broader and better database of adverse events in order to identify potential problems with medications.

Behind the drive for more timely safety reporting are some high-profile recalls, in particular Vioxx in 2006, further underscored by the FDA placing severe restrictions on Avandia in 2010 due to heart attack concerns. These events caused the FDA to expect more and timelier reporting from the industry, which led them to create standards to facilitate safety reporting and try to make it easier and more consistent for both the industry and FDA.

Overcoming Hurdles

So far, about 50% of companies I’ve discussed these changes with are still not complying with the new regulations. Why is that? As I mentioned, the first hurdle for companies is just being aware of the requirement. The problem is that while regulatory or pharmacovigilance departments should be aware of these regulations, FDA releases many guidelines and rulings and some might fall through the cracks.

The next issue is that the entire process, while not necessarily difficult, is extremely time sensitive and time consuming.

Starting with the test phase, you have to provide 10 XML test files that cover specific scenarios outlined by the FDA, create a dedicated test gateway account to submit test files, and communicate regularly throughout the entire test process with the agency’s electronic submissions gateway (ESG) and with FAERS. If there is an issue with any one of the test files, typically you are required to correct errors and re-submit all 10 until you get no error messages for any of the files.

It should be noted that there are two options for submitting ICSRs electronically: database-to-database transmission (“E2B”) and the Safety Reporting Portal (SRP). We have found a number of companies prefer the latter, as it leverages many facets of their current submissions’ infrastructure and creates visibility between regulatory and pharmacovigilance.

Another time-consuming issue is that unlike with other submissions to the gateway where you can batch documents in one folder, ICSRs must be sent individually. So if you have 50 ICSRs, for example, you have to send 50 individual submissions.

Seeing the Benefits

Nevertheless, the new ICSR regulation will benefit companies in the long run. Going forward, companies won’t have to fill out countless MedWatch forms and send them piecemeal and won’t have to include copies in periodic safety reports (PSR). Instead, you submit the ICSR only to FAERS within the reporting timeline, e.g., 7 days, 15 days, etc., and then simply include identifying details in the aggregate PSR to close the loop for reviewers.

Another benefit will be at a global level. Eventually, when the various regional agencies adopt a global reporting standard, the same report that is sent to the FDA can be sent to the European Medicines Agency, Health Canada, Japan’s Pharmaceuticals and Medical Devices Agency and so on.

On the flip side, non-compliance can not only result in a strongly worded letter from the FDA, but if safety issues arise for a particular medication, and it turns out that a company didn’t report related safety information, there could be serious ramifications for the responsible company.

Where to Get Help

Given the importance of regulatory compliance and the time-consuming nature of ICSR preparation and reporting, many companies are choosing to work with a business process service (BPS) provider to better manage the process.

However, you do want to take a number of factors into consideration when partnering. First, is the infrastructure to submit and track the ICSRs available on an as-needed basis to meet the timelines? These can be required in very tight timeframes.

Following an adverse event report, a third-party safety committee, such as a medical review board, reviews the full details and determines whether it’s reportable to the FDA. The decision to report starts the clock – for example, for a 7-day or 15-day report. A company or its pharmacovigilance partner then generates the XML ICSR report that is submitted to FAERS. Often, it can take 10+ days from the time the board makes the decision to the time the XML report is generated and validated as being complete, which allows little time to get the report submitted to the FDA. In fact, sometimes, by the time all the back and forth is completed, it has to be submitted the same day to meet the reporting deadline. So it’s important to make sure your partner has the resources to handle the time-sensitive nature of the reports.

It also helps to work with a partner who already has an existing relationship with groups within the FDA, such as ESG and FAERS, because the process does entail a lot of communication, and those with an established rapport tend to get a better response.

You want to make sure your partner has extensive experience with high-volume submissions so they are comfortable managing all the tracking details that are required. Because the XML ICSRs are only submitted to FAERS, and not to eCTD applications, key details from all ICSRs will need to go into the descriptive portion of your PSRs so reviewers can locate them in the FAERS database. So, it also makes sense to partner with a BPS vendor that is publishing other submissions on your behalf so the two groups can share information that goes into the aggregate quarterly or annual PSRs. The ability to share information back and forth and ensure the correct details are captured in aggregate PSRs is vastly simplified if you’re working with the same partner who is managing your eCTD product applications.

Taking Action

Companies with marketed drugs and biologics must act quickly to move to fully electronic post-approval safety reporting. Bear in mind if you have a product on the market and you aren’t yet submitting your ICSRs electronically, you are out of compliance. The last thing you want to do is give the FDA cause to scrutinize your safety protocols, so acting now is imperative.

For those with newly marketed products, you want to start right now because the requirement for ICSRs starts from day one of product approval through the entire life cycle of your product on the market. For those with pending approvals, you have a little time to prepare, but forewarned is forearmed, and so it makes sense to begin planning your test ICSR submission now. That way when those post-approval safety reports start to come in, you’re ready to respond.

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