Refusal to File (RTF) and how modern rendering can reduce non-compliance risk

Bringing a new medicine or a product to the market is a complex process that typically takes from 8 to 14 years. Although this process may vary from one Health Authority (HA) to another, there are some general stages that the medicine must go through before it can be safely distributed to patients. It starts with research and development (R&D), then slowly moves into the next steps, including assessment and evaluation through non-clinical and clinical trials, filing for marketing authorization to the HA and getting regulatory approval. The final stage is the post-market safety monitoring after the product is launched to the market.

Patient safety is crucial in the Life Sciences industry

There are high risks of taking any shortcuts in this long process. In fact, a study conducted by the Tulane University back in 2003 showed that each 10-month reduction in the US Food and Drugs Administration (FDA) review time period for a new drug can lead to an 18% increase in serious adverse reactions, an 11% increase in drug-related hospitalizations, and a 7.2% increase in drug-related deaths.

Patient safety is the reason why the process of bringing a new drug to the market takes so much time. And since it is the main focus of the entire Life Sciences industry, the new drug can be rejected even before filing for marketing authorization to the HAs if it isn’t considered safe for public use. For example, during the clinical trials, the first phase sees approximately 70% of drugs move to the next step. Phase III trials see only 25-30% of those remaining drugs enter the final stage leading to HA review.

Filing for marketing authorization – is success guaranteed?

Once the drug passes the testing phase, pharmaceutical companies finally reach the stage of submitting a request for authorization to the HA where the drug is going to be marketed. However, there is always a risk of getting a rejection from the HAs.

In fact, research shows that 25% of the marketing applications for drug authorization submitted in the past to the European Medicines Agency (EMA) were rejected. Additionally, looking at the statistics published by the FDA, a total number of 73 refusal-to-file (RTF) letters were issued to non-compliant pharmaceutical companies over a period of 7 years.

One of the main reasons of RTF is the inability to comply with the technical HA requirements.

As explained in one of our previous articles, it takes many years for a new drug to be approved. When the pharmaceutical company is finally able to file for marketing authorization, it must ensure that each document from the millions collected over so many years of research respects all the specific technical requirements from each national HA. This is where an automated document conversion solution like DocShifter can help companies: automatically convert all those documents into submission ready PDFs for any HA in the world and reduce the risk of receiving an RTF.

What are the consequences of receiving an RTF from the FDA?

When a Life Sciences organization’s marketing authorization for a new drug is rejected by the HA for non-compliance, the negative impact can be translated into significant financial losses and damages to the company’s image and reputation. To give you a better understanding of the importance of compliance in the Life Sciences industry, let’s focus on the consequences of receiving an RTF from the FDA.

  1. Fines imposed by the FDA. Under the Prescription Drug User Fee Act (PDUFA), when applying for the approval of a new drug, the pharmaceutical company must pay an application fee (for 2020, the current rates are: $1,471,483 – if no clinical data is required, and $2,942,965 – if clinical data is required). If a drug application is refused for filing, the pharma organization can receive back only 75% of the application fee, incurring financial penalties of $367,871 up to $735,741.
  2. Loss of R&D financial investments. Statistics in the industry show that pharmaceutical companies spend, on average, 17% of their revenue on developing a new drug. This amount translates into an average of $4 billion, and an RTF letter delays (months) in getting the product to market and causing loss of revenue. Even when the company takes actions to become fully compliant with the FDA’s requirements, it will still lose significant amounts of money every day that it doesn’t bring the new drug to the market.
  3. Stock price drops. This is another negative impact that contributes to the significant financial losses incurred after receiving an RTF from the FDA. For example, there was the case with a pharmaceutical company that filed for marketing authorization of its new drug with the FDA in December 2015. Two months later, in February 2016, the company announced that it received an RTF letter from the FDA. Soon after this announcement, the stock prices plummeted by 37.3% in a single day.what can an RTF letter lead to in life sciences? What are the consequences of technical non-compliance? DocShifter
  4. Negative press. Ensuring patient safety is vital in the Life Sciences industry. This means that patients also should be confident in the pharmaceutical company’s ability to bring a new drug to the market that may help improve their lives. If the press discovers that the pharma company’s drug application was refused by the FDA, all that negative buzz can end into losing the customers’ confidence. And when that happens, the consequences can be truly catastrophic and it can really be the end of the new drug, long before being launched to the market.

How can DocShifter help pharmaceutical companies achieve technical compliance?

Pharmaceutical companies can get an RTF for two main reasons: the inability to comply with content requirements (missing information or summaries, appendixes not submitted, etc.) or with technical PDF requirements of that HA. 

Even though there are some tools that can create compliant submission ready PDF documents, they are costly, time-consuming, and have to be manually configured. The DocShifter document conversion software makes sure that your electronic submission documents are fully technically compliant with any HA. Simple, automated, and fast. 

To ease compliance and reduce risk of RTF, DocShifter software provides technical PDF configurations, that are predefined to the technical requirements of each national HA like the FDA (in the US), EMA (in the EU), PMDA (in Japan), HC (in Canada) and many more. With this, every PDF you generate with DocShifter will exactly match what the HAs demand. 

DocShifter's compliant PDF configurations reduce risk of technical non compliance, and allow multiple PDF renditions for multiple health authorities.

Discover compliant PDF configurations

How to take PDF Rendering to warp speed in 2020

Introduction

Compliance is never far away in the Life Sciences industry. The different health authorities across the globe have set out very specific guidelines when it comes to providing documentation and data. For the right reasons. Life Sciences (pharma, biotech and medical devices) companies spend time and effort to ensure that the information supplied meets these requirements. Not an easy task, as documents live in different systems, versions, digital file formats etc. And that is where standardization comes in. The transformation to a neutral, generally recognized file format such as PDF plays a big role here.

During the entire product life cycle in Life Sciences, PDF files (amongst other formats) are created. PDF ensures consistency, helps to standardize across different departments and platforms. Thus, it helps increase efficiency in document centric processes.

The conversion of different file formats to PDF is often also referred to as ‘document rendering’. Converting documents is generally handled by very specific applications & systems, the so called ‘rendition engines’. This ensures the transformation of one digital file format into another, f.e. PDF.

Document rendering can be done in different ways. The most common approaches are:

  1. By making use of the ‘authoring’ application that was used to author the original document (Microsoft Word, OpenOffice, Microsoft Excel, etc.)
  2. Standalone document rendering, without using the authoring application(s).

Both approaches are very different, and vary greatly in terms of speed, quality, configurability. This article further explains the inherent differences of both.

About the author – Paul Ireland 

Paul Ireland - VP Life Sciences - DocShifter

20+ years in helping to provide regulatory software and service solutions to Life Sciences organisations globally. Industry and commercial experience in delivering Content Rendering, Regulatory Information Management, Submission and Report-level Publishing, and Electronic Document Management solutions. 

Can I help you with anything? Let’s jump on a brief call discuss more.

About DocShifter

Speed, quality and scalability and configurability are reasons why Life Sciences organizations choose DocShifter for the generation of technically compliant, submission ready PDF. High volume, high quality document conversion, on premises or in the cloud. Super easy to set up. Automate. Centralize. Eliminate manual intervention. Reduce Risk. Reduce IT infrastructure costs.

DocShifter 6.3 is rocking rendering again with new and improved functionality

DocShifter 6.3 was born as a result of our development team’s hard work. This release is very special to us, not only because it adds up to industry leading rendering capabilities but also because of how it was built. 6.3 was built completely remotely, as entire team was working from home. Impressive work.

DocShifter 6.3 focuses on improving ease of use, end user communications, administration, and performance. We are happy to share the highlights with you.

Improved end user satisfaction

  • Allow for direct communication between the authors of the content and the status of their transformations. Email notifications can now be sent to the individuals that requested the rendition and/or the user that last checked the document in.
  • Improved handling of Excel, text and PDF/A based files. Defining page sizes and punctuation characters plus more automated encoding detection as well as ensuring complete accuracy to the desired PDF/A compliance level.
  • Enhanced handling of grouped bookmarks reduces the time needed in manual formatting of the results.
  • Better workflow handling of Virtual Documents where concatenated renditions are required. Integrate Virtual Document processing- which was first introduced in DocShifter 6.2.5- into your more complex workflows.

Improved administration

  • Quickly and easily view the status of all your workflows and allow for instant enabling/disabling from the workflow list. This improves the general usability in a production environment.
  • Export all your workflows at once, saving time with upgrades & migrations.
  • Easily identify which configuration parameters are mandatory, saving time when setting up new workflows.
  • Easily identify which DocShifter server (where multiple servers are in use) an email notification was sent from. Speed up your error investigation processes.

Additional improvements have been made to increase performance and handling of the huge quantities of diverse content DocShifter is expected to process on a daily basis. Please refer to the release notes available on the customer portal for full details of this exciting new release.

Stay tuned for the release of our new Table of Contents module in the coming weeks.

PeopleScout significantly improves efficiency and speed in document and PDF conversion with DocShifter

PeopleScout Technology, a world leader in recruitment process outsourcing (RPO) has recently chosen DocShifter to convert all incoming digital formats to high quality PDF files. System administrator Chris Bellgard explains the impact of this decision at PeopleScout with numbers.

PeopleScout Infographic

How did automated document and PDF conversion impact Chris’ daily activities at PeopleScout?

See the video below from Chris to find out more.

 

Experience The Impact

 

DocShifter powers the document conversion solution in Generis new CARA cloud offering

We are happy to announce our DocShifter software will be the default enterprise document conversion solution in Generis’ new CARA cloud offering. The integration will further strengthen the bond between organizations and allows the new CARA to serve a larger range of clients with expanded document conversion functionalities.

New CARA cloud offering provides an enterprise content and information platform, able to store and manage data both in CARA as well as that stored in a range of other repositories.  While the integration has been available for classic CARA for some time, it will now be the default option for the New CARA Cloud platform for customers requiring rendering meeting a range of complex requirements of regulated industries. 

DocShifter solution automates any-to-any conversions with support for 300 input and output formats. The speed, scalability and connectivity with all DMS & RIM systems make DocShifter technology an essential for Life Sciences organizations that deal with complex content and document conversion requirements. 

 “With the integration of DocShifter as the default document conversion solution into the new CARA, we are able deliver our promise even better: drastically speeding up and simplifying the complex process of content and document conversion. DocShifter’s document conversion capabilities, combined with new CARA, are able to answer the complex requirements of highly regulated industries,” states Geert van Peteghem, CEO of DocShifter. 

“We already support many joint customers who have advanced document conversion requirements met by the integration of DocShifter with CARA,” said James Kelleher CEO of Generis. “We are now happy to be able to offer this on a pre-built package with New CARA on our cloud for such customers.”

About DocShifter

DocShifter

DocShifter was created in 2007 to respond to the need for easy and fast content conversion in highly regulated environments. Customers can be found worldwide in Life Sciences, Public Sector, Engineering, Banking & Insurance. The company is headquartered in Ghent, Belgium.

At DocShifter, we believe that relevant digital content should never become obsolete. Unstructured information needs to be kept in a readable and searchable format, for generations to come. In our fast-paced digital world, standards appear and disappear. Transforming all this digital content, in whatever shape or form is our goal. To ensure your information continues to provide value.

About Generis 

Generis is a global leader in content and information management systems, specialising in proven solutions for regulated industries. Established in 1997 as a consultancy group, Generis has since grown and developed alongside its flagship product CARA. Our mission is to provide a platform which is highly configurable and user friendly; a dedicated team works hard to guarantee customer satisfaction. Currently counting over 450,000 users across numerous industries worldwide, including 8 of the 10 largest Life Science companies, CARA continues to progress to become the answer for end-to-end data management. 

To find out more visit: www.generiscorp.com

How Document Conversion Can Impact Regulatory Operations [Whitepaper]

In highly regulated industries, like Life Sciences, where a lot is dictated by regulatory authorities, compliance comes first. Organizations must get to market fast, as business needs are growing.  At the same time, regulatory pressure can slow down innovation.

Organizing processes in the most efficient way is key. Document conversion plays a big role here.

This whitepaper broadens the spectrum of document and PDF conversion in Life Sciences, and demonstrates that document conversion goes beyond excellent technology.

 

Successful eCTD Implementation in China: 3 Lessons Learned

China is the most populous country on the planet accounting for more than 18% of the world’s population. Following the focus placed on biopharmaceutical development by the Chinese government in the last decade, the country’s global industry ranking rose from 9th largest in 2007 to 2nd in 2017. 

To help expedite the review and approval of new medicines, China will soon join other Asia Pacific countries in accepting submissions in a fully electronic eCTD format. The implementation of eCTD in Japan and Thailand highlighted many hurdles for both domestic and international biopharmaceutical companies, some of which can be avoided.

CFDA eCTD Adoption

After joining the ICH (International Conference on Harmonization) in June 2017, China’s draft eCTD guidance has now been provided by the CFDA (China Food & Drug Administration). It is time for any organisation looking to gain approval for their products in the Chinese market to prepare to take advantage of this regulatory change.

About the author – Paul Ireland 

Paul Ireland - VP Life Sciences - DocShifter

20+ years in helping to provide regulatory software and service solutions to Life Sciences organisations globally. Industry and commercial experience in delivering Content Rendering, Regulatory Information Management, Submission and Report-level Publishing, and Electronic Document Management solutions. 

Can I help you with anything? Let’s jump on a brief call discuss more.

About DocShifter

Speed, quality and scalability and configurability are reasons why Life Sciences organizations choose DocShifter for the generation of technically compliant, submission ready PDF. High volume, high quality document conversion, on premises or in the cloud. Super easy to set up. Automate. Centralize. Eliminate manual intervention. Reduce Risk. Reduce IT infrastructure costs.

6 Valuable Tips: Why should you convert to PDF?

Most companies are not demanding when it comes to the file formats they use. They just use the most common file formats as the logical extension of their software tools. The best example is the Microsoft Office package. Although Word is a good program for word processing, text editing and file formatting, a Word-file (.docx) is not the best suited file format for storage, archiving, sending sensitive and private data, and internet sharing purposes. Read more

How Docker puts your rendering farm on steroids

Infinite scalability in document conversion through container technology

Container technology* has been around for a while now. The benefits are clear: scalability, rapid deployment, cost savings, simplicity. In 2019, 78% of all companies have moved workloads to containers, according to a study by DivvyCloud.

Containerization has now come to the advanced rendering space. In this blog post, we focus on the use cases and advantages of running advanced rendering on Docker. 

*Container technology is a method to package an application so it can be run, with its dependencies, isolated from other processes. A container is a package that includes everything to run an application. Containers rely less on external hardware and software and can run on any environment (Microsoft, Linux, Mac etc.)DocShifter and Container (Docker) technology for infinite scalability and easier deployment

Why should you investigate running your rendering farm on Docker?

Document conversion is a resource intensive process. Moreover, the workload is highly unpredictable in most cases. And there is typically considerable time pressure. 

What to do with Legacy Data?

Many companies sit on a big pile of old data (information or old file formats, such as Excel 2.0 from 1987 or Excel 5.0 from 1993 for example) or use outdated systems to manage valuable company information. These legacy data and applications are still valuable to the organization, but their inefficiency, poor usability and high maintenance cost do not weigh up against the benefits. To get the most out of your legacy data you should convert these files to new file formats to keep them accessible, readable and searchable in the long term. Read more