Abstract
Executive Summary
Development of a single application portal for renewable chemicals and production strains and the establishment of an interagency cooperation office to manage the review of these submissions is necessary because many renewable chemicals have multiple applications, some of which are discovered only well after initially developing the bio-manufacturing pathway. Also, the applications are so diverse that they may well be subjected to oversight by multiple regulatory agencies, sometimes under more than one regulatory framework even within the US EPA (e.g., Toxic Substances and Control Act [TSCA] and/or Federal Insecticide, Fungicide, and Rodenticide Act [FIFRA]) or within the US FDA (e.g., food and/or cosmetic applications)—each of which comes with its own historical set of partially overlapping requirements:
Complexity in Navigating Regulatory Route
Finding out which agency handles which application can be a daunting task, especially for start-up companies without extensive regulatory expertise. An interagency office could serve as the clearinghouse for questions regarding the appropriate regulatory route for approval.
Redundancy in Data
In addition, if the requirements for two different applications managed by 2 different agencies (or 2 centers within an agency) were highly specific, there would be little to no redundancy; however, each agency has the safety of the manufacturing process (including the generically engineered production organism) in scope, but requires different but overlapping (and hence, redundant) data packages to support the manufacturing chemistry/safety.
Redundant Processes and Extended Timelines
Dual oversight with review of redundant data packages also slows down the regulatory processes by each agency/center. If one agency (or an interagency office) took the lead in the review process, most parts of the overall data package would need to be reviewed only once instead of multiple times by the various agencies partaking in the Biotechnology Coordinated Framework.
Critical industries where this would be impactful are the following and not limited to: Fermentation-based substances with multiple applications across the regulatory landscape, including chemicals and pesticides (EPA), food ingredients, processing aids, and cosmetics (FDA) Biofuels industry (EPA) with co-generation of distillers products for animal feed or human food (FDA) Alternative proteins/meats and seafood subject to oversight either by FDA or by both FDA and USDA Improved micro-organisms for crop biological application (EPA, USDA/Aphis, State agencies), environmental applications, or probiotics/direct-fed microbials (FDA)
Objective
The efficiency of having one inter-agency would enable responding to one entity in the federal government and would mitigate data requirements promulgating from several agencies for the same manufacturing chemical or strain. Therefore, an interagency coordinator position and office, with a dedicated review group, and uniform timeframes for reviews to foster cooperation and avoid not only duplication of effort but cost requirements and delays.
Purpose, Intent and Outcomes
The interagency coordinating office would:
respond to enquiries by companies seeking clarity on regulatory requirements,
review a basic brief that describes the product, how it is manufactured, and how it is used, to determine which agencies’(s) have regulatory oversight,
direct the inquiring company to the correct agency, if indeed a single agency has regulatory oversight or recommend dossier submission into a central portal,
address pre-submission questions,
manage the submission portal, identify parts of the submission (specially manufacturing chemistry including molecular biology) that can be reviewed centrally (by the interagency office) and other parts that need specialist review (based on application exposure considerations) by a specific agency/center. The various parts can be reviewed in parallel.
For an interagency office to be effective in directing applicants and eliminating redundant reviews, the following prerequisites would need to be developed:
coordinated information requirements for applications currently separately reviewed by different groups in EPA, FDA, and APHIS,
identifying duplicative information requirements in these agency programs and convert these into a single format with uniform information needs,
establishing a pool of experts to review dossier sections of common interest to multiple agencies.
This would require upfront close collaboration across agencies to harmonize requirements and accept a single format. Alternatively, agencies may also determine that mutual recognition of certain data reviews/approvals may be sufficient to satisfy their requirements, and this may be easier to accomplish than complete harmonization into a single dossier format.
No change in the existing product processes in these agencies is required and no changes that would adversely affect product programs that are running well independently, and no requirement that companies have to use the single portal application process—this is a voluntary requirement. The final approvals for each specific application area would still be by each individual agency, hence no change is needed in regulatory structure. The single portal process is optional but highly recommended given the option to build in pre-submission consultation.
Moreover, federal statutes and/or regulations to facilitate a single application entry point will not be required if final approvals will still be in the hands of each regulatory agency/center. Coordination may be mandated (e.g., by executive order) and implemented via Memorandum of Understandings (MOU) without affecting regulatory authority.
Science-based and risk-based principles for sameness, so that renewable chemicals and production strains are not subject to duplicative applications and reviews, such as the case of minor manufacturing changes (e.g., deletions in strains that do not change strain phenotype or chemical identity of end-product chemical). Risk-based principles to establish mutual recognition of approvals not requiring identical data review.
Advancing renewable chemicals and production strain innovation under the principles established by the National Defense Authorization Act (NDDA) Sustainable Chemistry Act, the new allocation of resources by Congress, and the formal establishment of a coordination office within Office of Science and Technology Policy (OSTP) or within one of the participating agencies in the Coordinated Framework.
Current and Future Actions
Any proposal will need to be tested for relevant criteria such as:
Will a new construct speed up overall data collection?
Will a new construct reduce (redundant) data burden, including animal data?
Will a new construct streamline (speed up) the approval process?
The new proposal should address the critical key questions:
Is this construct for biobased chemical / materials / strains only?
How does the proposed construct advance innovation?
Future actions include:
Discussing the idea with White House OSTP to get high-level support. This may be needed to get the agencies around the table for constructive dialogue.
Discuss the construct with agencies for a detailed portal with adequate representation and expertise from agencies.
Determine initial priority chemicals/strains and product markets since Biotechnology Coordinated Framework operates on the basis of end use or application and not the process—optionality for use and examples.
Provide suggestions to agencies for the design of an adequate and easy service oriented federal agency portal.
Further discussion with White House OSTP and federal agencies—the stakeholder's goals and implementation. Request for information from White House OSTP for the development of a single use portal.
Discuss with other interested stakeholders (consumer groups, federal agencies, advocacy groups) for the implementation of a single application portal for renewable chemicals and production strains and the establishment of an interagency cooperation office to manage the review of these submissions.