One of the cool things about being part of technology industry is living through certain hype cycles. I have experienced, in past 20 years of my professional life, ups and downs that tend to get everybody riled up about ‘this is going to end the world’ dooms day scenarios like Y2K to ‘this can do everything’ conversations about things like Artificial Intelligence, Virtual Reality etc. I still remember back in the day when my friends in the Computer Science branch in college had subjects like Virtual Reality, Neural Networks and Artificial Intelligence. I am talking about 1994 – 1998, which is almost 2 decades+ to the day. Not many of them pursued their careers in those areas, but it is amazing to think that it took as long as it did to get to current developments in this space that is revolutionizing the consumer and enterprise software industry.
There have been many developments along the way that got us here from Internet to client / server technologies to cloud to big data to NLP, to name a few. Today we can genuinely claim there are things that machines can do, faster and cheaper and more than anything else, SMARTER than humans with very little to no intervention from us. As BigData hype reaches a plateau, Deep Learning is picking up steam and more and more companies are investing in this area to genuinely unleash the power of data through smarter analysis with help from neural networks, NLP, Deep Learning and the likes.
Having spent considerable amount of time dealing with Life Sciences industry for the past 14 years, I can speak to the utmost conservative approach these companies take when it comes to technology adoption. It is a heavily regulated industry and rightfully so since it deals with human lives. Life Sciences companies can release life saving ‘Elixirs’ but can also unleash ‘Drug from the Devil’. In my experience Life Sciences companies typically are 2 to 3 years behind in terms of technology adoption. This may change depending on the department within the value chain but this tends to be the average duration before they use the latest version of Windows or IE or Office.
I hope to highlight some of the use cases where newer technology developments can be leveraged in Drug/Device/Vaccine development, specifically in the areas of Regulatory and Safety in a series of posts starting with this one. I will try to prioritize areas where there is a lot of manual intervention (Compliance) as well as areas that could leverage technology to deliver faster ROI (increase Revenue) and improve Operational Excellence (Reduce Cost).
One of the first areas that I thought could benefit from these technological advances is Regulatory Intelligence. The EU Regulatory Intelligence Network Group (RING Europe) defines it as “Regulatory intelligence is the act of processing targeted information and data from multiple sources, analysing the data in its relevant context and generating a meaningful output – e.g. outlining risks and opportunities – to the regulatory strategy. The process is driven by business needs and linked to decisions and actions.” RI is a key part of Life Sciences industry primarily for three reasons:
- It is a heavily regulated industry
- If companies operate globally they ought to comply with ever changing regulations and
- Influence policy and advocacy of future development
Please refer to this presentation from Carol Hynes of GSK for more details on “Regulatory Intelligence: Implications for product development“.
Many organizations have built Regulatory Intelligence Repositories by collating information from various sources. The diagram below represents various sources of RI data (courtesy : Regulatory Intelligence 101 By Meredith Brown-Tuttle).
These repositories cannot be built overnight. They have to be collated piece-by-piece over a period of time. The sources could go beyond the ones identified in the above diagram. Also, the repository may contain structured as well as unstructured content and data. Extracting information from such repositories is typically not a straight forward process. It definitely will not be as easy as asking a colleague who would then manually conduct the research needed and collate the information that can then be circulated to one or more individuals in the Reg Affairs organization for consumption and decision making . Therefore leveraging Automation, Machine Learning and Natural Language Processing in order to glean into the information in such repositories will make the life of Regulatory Intelligence colleagues lot easier. They can easily query the repository in their language of preference (for regular users with NLP capabilities) or write No-SQL and Semantic queries (experienced/super users) to extract the relevant information.
Information thus obtained can be leveraged to put together documents, newsletters and other communication vehicles which in turn could be stored back in the repository thus continually enriching and expanding the wealth of information available. This idea can be extended to create a federation of such repositories (internal, external, partners, vendors etc.) that can be scoured for the necessary information. Also leveraging even more advanced technology advances like Deep Learning might enhance the effectiveness and Return on Investment even more.
As always, your feedback and comments are most welcome. Thank you.
I was looking at the FDA report from Sep 2014 titled “Standardizing and Evaluating Risk Evaluation and Mitigation Strategies (REMS)” to better understand the need for the new DRAFT guidance to submitting REMS using SPL, as outlined in the guidance document issued in Sep 2017 titled “Providing Regulatory Submissions in Electronic Format — Content of the Risk Evaluation and Mitigation Strategies Document Using Structured Product Labeling”. I felt it would be easier for people to understand the need for the guidance if they understand the backstory leading up to the new guidance. Please refer to the original report and subsequent guidance for more details.
Feedback to FDA, through various stakeholder engagement sessions participated by vendors, healthcare community and other impacted groups:
- Stakeholders are not uniformly impacted by REMS requirements
- Communication about REMS requirements should be improved
- There should be flexibility to implement a REMS program based on the nature and variety of health care settings.
- REMS are vital tools that will be increasingly necessary, and content delivery must be streamlined without compromising the content itself
- FDA should standardize REMS across platforms, media, and delivery technologies and work to fully integrate them into health care systems—which will increase access by both health care providers and patients, and enable improved assessments to further advance standardization.
- FDA should use human factor evaluation approaches like Failure Mode and Effects Analysis (FMEA) to support and standardize REMS program design.
- FDA can improve REMS assessments with a variety of tools and techniques
- FDA should structure and standardize REMS information.
Based on engagement with industry stakeholders and the feedback received, FDA prioritized 4 projects in four different areas:
- Patient Benefit/Risk Information under REMS
- Providing Patient Benefit/Risk Information by Improving Tools for Prescriber-to-Patient Counseling
- Prescriber Education under REMS:
- Prescriber Education—REMS and Continuing Education (CE) for Health Care Providers
- Pharmacy Systems under REMS:
- Standardizing REMS Information for Inclusion into Pharmacy Systems Using Structured Product Labeling (SPL)
- Practice Settings under REMS:
- Providing a Central Source of REMS Information for Practice Settings
Of these projects, the project titles “Pharmacy Systems under REMS” led to issuing the guidance that is issued in September 2017 and distributed for public comments. The objectives of this project were:
- Make structured REMS information available to health care providers, patients, and FDA.
- Provide a single conduit of comprehensive information about REMS programs.
- Facilitate the integration of REMS into pharmacy systems and health information technology, including systems for electronic prescribing.
- Improve the efficiency of FDA’s review of proposed REMS by allowing the Agency to receive REMS submissions in a consistent format.
- Support FDA’s ongoing REMS standardization efforts by enabling the cataloging of similarities and differences between REMS programs.
The project’s final deliverable was set to be a revised SPL Implementation Guide that describes how sponsors, health care information system developers, and other stakeholders can share REMS information leveraging the existing SPL standard.
To help address the concerns expressed by various stakeholders, FDA wants to take steps to streamline the access to REMS information
- FDA intends to require applicants of NDAs, ANDAs, and BLAs to submit the content of their REMS documents in Structured Product Labeling (SPL) format
- SPL can be used to capture and present REMS information in a format that is:
- Easily shared with stakeholders and
- Readily incorporated into health information technology
- Twenty-four months after the final version of the guidance is published in the Federal Register, applicants must submit REMS documents in electronic format consistent with the requirements set forth below:
- Types of submissions : NDAs, ANDAs and certain BLAs
- Also applies to all subsequent submissions including amendments, supplements, and reports, to the submission types identified above
Apple has sold millions of iPads in the past 18 months. The adoption of the device in the market is phenomenal. This trend is reflected in Life Sciences & Healthcare industry as well. A mobile Health News article (2012: About 62 percent of physicians use tablets) puts the adoption of tablets by the physicians at 62%. Another report by IDC puts the Smart Devices sales exceeding the combined sales of laptops and desktops. All these trends are indicative of the rate of adoption of mobile and smart devices by the population in general. The healthcare and life sciences industries are no exception to this.
While the adoption is growing in general, the challenges and bottlenecks are numerous for adoption of the devices in an Enterprise/Business setting. To make this even more complex, consider using the tablets and smart phones in a validated environment to capture and manage personal health information of patients.
Some key questions to be asked while considering adoption of Mobile devices in a validated environment are:
- Will the device and application be considered a Mobile Medical Device?
- If so, what should we do to validate the application?
- What are the regulatory requirements and guidance from the agencies?
- Should we consider a native application vs. a web based application?
- If so, how does the validation activities and artifacts differ?
- Would the data be stored on the device or would it be transferred to the server as soon as it is captured?
- Should we make it available offline to enable usage without internet connectivity?
- What are the synchronization challenges?
- How do we handle identity management?
- How do we ensure data security?
While some of these questions are applicable to any enterprise mobile application, they are even more important to consider if the Mobile device is slated to be used in a regulated environment. For customers in the US, one key document to be considered as input, to answer some of the questions, is FDA’s DRAFT Guidance for Mobile Medical Applications.
mHIMSS Policy & Regulatory Implications Workgroup has provided a very good summary of how the guidance should be interpreted with respect to Mobile Medical Applications. You can read the summary here (needs registration).
FDA also provides more useful information on Mobile Medical Applications here.
I look forward to comments and insights into any specific experiences that you might have had with respect to developing Enterprise Mobile Applications in a regulated environment. These applications may or may not be companion applications to devices, but may fall under the MMA purview as defined in the guidance.
Implementing FDA REMS Elements to Assure Safe Use (ETASU) Requirements using a Business Process Management Suite(BPMS)
It is essential that all new products developed and marketed by bio-pharma and device companies are safe to use and fulfill their efficacy requirements. However, it has been our practical experience over many decades that in most cases there are certain unwanted side effects. Hence, to ensure that the benefits outweigh the risks, regulators have been approving certain drugs under strict risk management assurances from the license holders.
In the US, the Federal Drug Administration (FDA) has been trying to address this through various regulations for over five years through Risk Management Action Plans (RiskMAP) and Risk Evaluation and Mitigation Strategies (REMS). The most recent guidance on this subject was issued in September 2009 through “Guidance for Industry Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications”. In this guidance one of the important REMS elements that may be required is “Elements to Assure Safe Use”.
As part of this requirement the NDA/BLA applicants have to take measures to provide safe access for patients to drugs with known serious risks that would otherwise be unavailable. If a product is assessed to fulfill ETASU requirements then the sponsors are required to train and certify health care providers, pharmacies, patients and drugs. The drugs may be released to patients in a controlled manner only upon receiving evidence of their lab results. The sponsors may also have to register the patients and might subject them to certain monitoring as well. In a few cases the sponsor may be asked to extend the certification process to wholesalers, distributers etc. as well.
In order to fulfill the above mentioned requirements sponsors typically set out to build new IT systems. This is a challenging task as there is a possibility that these requirements could change over time and also there aren’t any commercial off the shelf products available in the market to address the specific REMS ETASU requirements.
To overcome this challenge, sponsors can look up to a Business Process Management System (BPMS) that is precisely built to handle such scenarios. Many other industries have successfully used BPMS to meet their ever changing requirements and priorities by integrating their business processes based on rules. Many commercially available BPMS systems typically include a process engine, Business Analytics, Content Management and Collaboration tools. These BPMS system building blocks can be effectively leveraged to fulfill the ETASU requirements by effectively providing features like Rules management, Content Management, Training Management, Patient/Provider/Pharmacy Registries, Collaboration Portal/Website, IVR/IWR, 21 CFR Part 11 compliance, Audits and integration with other enterprise applications.
My Article on the same topic is published on “Drug Safety Directions” Website. You can access the article here: “Implementing FDA REMS Elements to Assure Safe Use (ETASU) Requirements using a Business Process Management Suite“.