The development path for bringing new drugs and therapeutics to market requires extensive planning to meet the short- and long-term needs of products intended for global registration. Because international regulatory agencies may have different requirements for Investigational New Drug (IND) submissions, it might seem more straightforward to file separately; however, planning a comprehensive global IND submission has the potential to save drug developers time and money.
A global IND program reduces the possibility of conducting repeat studies, and because it is a unified program, it enables faster expansion into foreign markets. Still, team members may not understand the different requirements of each approval pathway. To achieve optimal results, developers must make the decision to file a global IND submission early in the planning phase. With appropriate foresight, you can ensure all studies adhere to current standards, typically including the U.S. Food and Drug Administration (FDA), Organization for Economic Co-operation and Development (OECD), European Authority (EU), and the National Medical Products Administration (NMPA) of China.
Drug development teams pursuing global IND submissions can categorize these significant regulatory differences into three areas:
- Study conduct (including personnel roles, documentation and changes in the scope of work)
- Reporting expectations
- Archiving procedures
But if you know what to look for, you can help minimize development challenges and delays in your timeline.
Detailing the Study Protocols and Study Conduct Elements
Many study designs are essentially the same, but the fundamental terminology, documentation requirements and explicit participant roles and responsibilities can differ. Both the NMPA and OECD require unique identification for each study, and test systems need to be traceable to their origin. However, U.S. FDA regulations and Good Laboratory Practices (GLP) requirements state that they only need to be adequately labeled with specific information. These minor details may feel like a matter of semantics, but noting these nuances can help ensure your submission will meet all the requirements and not result in potentially significant deviations.
Identification of the testing facility, Testing Facility Management (TFM), study director, principal investigators and contributing scientists are critical to all regulatory bodies. Although, some differ in the level of authority, ability to allocate resources, and required signatures on final documents (like study protocols and protocol amendments). While the single point of control remains with the study is the study director, the overall authority of TFM is broader and defined in the OECD and EU regulations.
Study designs also vary between regulatory agencies, though the U.S. FDA and OECD are more similar due to the adoption of International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. One example of study design variation is that the NMPA requires a laboratory to conduct certain studies within a double barrier system versus, while the U.S. FDA follows conventional housing guidelines. Differences also arise where the NMPA requires acute studies to adhere to GLP, which is unnecessary when filing under the U.S. FDA.
The test system requirements for in vitro and in vivo studies are examples of expectations that differ between regulatory bodies. Some details like identifying test, control, and reference articles vary slightly, although all have the same essential meaning; some are more explicit depending on the agency. Lastly, the U.S. FDA also stipulates that clinical pathology and gross pathology findings be available to the pathologist during the histology exam, yet neither the NMPA nor the OECD specifically states this requirement. There are other instances where the study protocol’s cohesiveness and clarity are directly affected by the countr(ies) intended for IND submission, so it’s essential to understand what elements are shared and those that differ when designing studies.
Reviewing reporting expectations
Reporting standards vary among regulatory agencies, and the scope, content and context of IND submissions can differ even in the smallest of details. To stay attuned to these specifics, drug developers must diligently review the comprehensive guidelines each regulating agency follows and stay abreast of regulatory changes and ongoing initiatives that change from time to time.
Other notable differences for report finalization are that the NMPA and OECD require a signature by the testing facility management and a unique identification number for the NMPA. And even though the OECD does not require an amendment if reformatting for particular submission requirements, you might need to provide one to meet the U.S. FDA, and NMPA requirements as this is considered a change, although an editorial one rather than content in nature.
Archiving study data
Thinking globally at the onset of development can help meet each agency’s archival requirements in the long haul. The OECD does not reference a specific duration for archiving data, but rather leaves the decision to “appropriate authorities.” However, both the U.S. FDA and NMPA provide detailed guidelines. The NMPA requires data archival five years after the drug is in market and specifically calls out terminated studies, requiring documentation of the reason and the data to be archived. On the other hand, the U.S. FDA states that it is necessary to archive for two years post-approval, five years post-IND submission and two years post-study completion for non-submitted studies. The storage of study samples is always contingent on the viability of these items for possible future analysis.
It can be challenging to navigate and manage all the regulatory requirements, but working with a laboratory testing partner can ease the process. Many laboratory testing partners provide expertise in preparing studies to file globally. Some also provide the full spectrum of inspection support, including translation services, regulatory planning and strategy, dossier preparation and communications with regulatory agencies, and submissions on your behalf. Allowing a testing partner to focus on these details can free up your team to handle other pressing development responsibilities.
Drug developers approaching the application process must anticipate the agencies’ differences and modify their applications to fit each submission. Often, filing IND packages for multiple global agencies can save time and money if regulatory variances are accounted for during study design, testing, reporting and throughout the archival lifecycle.
A laboratory’s approach to designing preclinical studies can impact the test results, the scope of generated data and overall assessment of safety – which means drug developers must keep these factors in mind when selecting a laboratory testing partner and making decisions about budgeting and program elements. Learn more about how to efficiently file with multiple agencies in our blog post, ‘Dual Filing your IND Package: Planning Pays Off.’
About WuXi AppTec
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