News from Emerging Technology Program (ETP)
Emerging Technology Program Graduates its First Technology
The Emerging Technology Program (ETP) is proud to announce it graduated its first technology, Continuous Direct Compression (CDC) on October 21, 2021. Graduation is the process through which ETP transfers review responsibility of future application submissions from ETP to the standard quality assessment process. This is a major milestone for the program, OPQ, and FDA and demonstrates ETPs understanding and capability of reviewing CDC regulatory submissions. With graduation, future CDC regulatory submissions will be submitted and reviewed through the appropriate OPQ review offices.
CDC is a pharmaceutical manufacturing process that consists of dispensing materials, mixing them together, and compressing the blend to form tablets using equipment that is integrated together, resulting in no breaks in the process. CDC offers flexible scale up approaches by operating the process for longer periods of time that can better meet changes in product demand. CDC also minimizes the need for human interventions with the process and takes advantage of process analytical technology (PAT) both of which can improve the assurance of product quality.
CDC was first accepted to ETP in 2015 and since then, the program has engaged with CDC sponsors across multiple applications to provide scientific input on the technology’s development. To facilitate graduation, ETT members apply their knowledge and experience working with CDC to train and provide guidance to FDA reviewers on the technology.
Graduation is an important step in the lifecycle of an ETP technology. Through graduation, FDA indicates confidence that industry’s quality (CMC) submissions related to CDC require little input or guidance from ETT members. By graduating CDC and training additional reviewers on the technology, ETP improves OPQ’s ability to assess applications at a faster rate and increases the program’s capacity to evaluate other novel technologies to keep pace with industry innovations. Future CDC regulatory submissions can be submitted through the standard quality assessment process.
The following table presents CDC experience bands. Experience bands are defined as the criteria used to identify what portion of CDC applications have graduated out of the Emerging Technology Program. Applications meeting the experience bands should be submitted through the standard quality assessment process. Applications not meeting all the experience bands should continue to work with ETP.
CDC Experience Bands
| Category | Criteria *acronyms provided below |
|---|---|
| Drug Product | Immediate release only Either single API or fixed dose combination products Either high (>25%) and medium (5-25%) drug load BCS Class 1, 2, 3, 4 |
| Formulation Changes (legacy products) | Only SUPAC Level 1 Quantitative differences in components if products are to be marketed congruently2 |
| Manufacturing Process (drug product only) | Integrated Process Steps Limited to loss-weight-feeding, continuous blending, compression, and continuous non-functional coating step (processes with fewer integrated steps such as batch coating are included in experience bands) |
| Advanced In-process controls | IPCs include ratio control for LIW feeders Quantitative spectroscopic based measurement for blend uniformity for routine commercial production (Process models such as RTD models for blend uniformity are currently excluded from experience bands) |
| Material diversion | Includes RTD based diversion strategies |
Real time release (RTRT is not required) | Assay and CU only: Spectroscopic measurement & tablet weight; Dissolution: Compendial test for batch release or RTR based on PLS models |
| Batch definition/Batch size | Must conform to definition in draft guidance |
*Acronyms
API: Active Pharmaceutical Ingredient
BCS: Biopharmaceutics Classification System
SUPAC: Scaleup and Post Approval Changes
IPC: In Process Control
LIW: Loss in Weight
RTD: Residence Time Distribution
CU: Content Uniformity
RTR: Real Time Release
RTRT: Real Time Release Testing
PLS: Partial Least Square
2 For more information on Scale-up and Post Approval Changes (SUPAC) please review Guidance for Industry: Immediate Release Solid Oral Dosage Forms
Emerging Technology Program 2.0
The Emerging Technology Program was established in 2014 to promote and facilitate the adoption of innovative approaches to pharmaceutical project design and manufacturing. The program’s initial processes and stakeholders were instrumental in the program’s success. Some of these early successes included:
- An increasing rate of program proposal submission
- An 8.9/10 industry satisfaction rating
- Approval of 12 regulatory applications
- Publishing of Advancement of Emerging Technology Applications for Pharmaceutical Innovation and Modernization Guidance for Industry
As ETP became more established, it experienced an increase in participation requests. Industry also began to request more dedicated support from ETP on the technologies accepted into the program. To better meet the changing needs of industry, ETP recognized the need to review and enhance its existing processes and structures. This review resulted in the development of ETP 2.0.
ETP 2.0 standardizes and streamlines its scalable processes, aligns organizational and existing quality assessment components, and identifies opportunities to strengthen the program’s performance. ETP 2.0 updates include:
| ETP 2.0 Focus Areas | Description |
|---|---|
| Graduation | Transfer review responsibility of regulatory submissions to appropriate OPQ review offices after ETP determines FDA has sufficient experience with a technology |
| Knowledge Management and Transfer | Improve existing ETP knowledge management systems to support the continued growth of the program |
| Governance | Update existing ETP governance structure to support program operations |
| Technology Intake Process | Develop standardized technology intake process to triage requests from industry to participate in the program |
| Industry Engagement | Improve interactions with ETP stakeholders and identify new opportunities for engagement with pharmaceutical industry |
| Program Communications | Create a standardized ETP communications plan to effectively interact with industry and share information about the program |
| Technology and Tools | Configure ETP tools and technology to support current projects and to anticipate future program needs |
| Skills and Training | Catalog and connect team member technical competencies and skills to specific projects and technologies and provide training opportunities to support continued learning |
| Workload Management | Track and assess distribution of project assignments among team members to promote sustainability and meet operational requirements |
| Program Strategy | Review and update policies, standards, and decision-making processes to enhance program functions and interactions with industry |
| Awareness | Create a standardized communications toolkit to build a consistent understanding and awareness of the program |
By implementing ETP 2.0, the program is better prepared to work with industry to support the development and adoption of innovative approaches to manufacturing.