May 4, 2023

​

The ETC is seeking a collaborator to generate a platform co-processing technology where API and excipients are crystallized and/or precipitated in a solvent-based process and combined via various mechanisms such as agglomeration, heteronucleation and surface coating with the goal of improving flow and bulk density of poorly flowing APIs to improve the robustness of continuous drug product manufacturing processes. The starting material choice is limited to crystalline APIs. Co-processing technologies including amorphous solid dispersions, dry coating, additive-mediated crystallization and adsorption into carrier approaches will be out of scope.

​

Download the Request for Information and submit your response.

​

RFI ISSUED:  May 4, 2023

QUESTIONS on RFI DUE to ETC:  May 19, 2023

RFI RESPONSES DUE to ETC:  June 16, 2023

​

Q&A - Note see FAQ document for answers to common questions​

​​

1. The Deliverables section asks for “Develop a solvent-based process to generate...”. However, we envision that the solvent-based crystallization process will be a conventional crystallization setup (such as stirred tank (batch or continuous)). Is it expected to provide a laboratory setup and skid and equipment at the end of the project?

   • ANSWER: We do not expect the vendor to provide a lab set-up. We request a thorough documentation of how each equipment is deployed, any specific equipment details that influence the control strategy (such as mixing), and how to scale up and down so the participating companies can reproduce the process.

2. The Deliverables section asks for “drug loading no less than 60 wt%”. Does this mean that ETC is not interested in HPAPI and low dose drug products?

   • ANSWER: We are asking for minimum drug loading of 60 wt% in the co-processed API. It is up to the participating companies to utilize the co-processed API for high drug load or low drug load formulations, which is out of scope for this project.

3. For demonstration of the 60 wt% loading via a hetero-nucleation approach, does this mean that all the 60 wt% API particles should be attached to the excipient particles, or it can be a physical mixture? For example, 40 wt% individual API particles and 20 wt% API particles attached to the excipient surface.

   • ANSWER:  We would like the API and excipients to be combined, such as via various mechanisms listed on the RFP. Physical mixtures are out of scope. The homogeneity needs to be demonstrated.

4. The Deliverables section asks for demonstration of yield “at appropriate scale”. Would you please elaborate more on the interested scale? What kind of “demonstration platform process” is expected? What is the 100 g referring to batch or continuous (100g per hour, per day?)

   • ANSWER: 100 g scale refers to per batch process. The scale will be determined in collaboration with the vendor if the process is continuous.

5. Should applicants use conventional model API (e.g. Acetaminophen), or any sample and proprietary API will be provided by ETC?

   • ANSWER: The list of APIs will be selected in collaboration with the vendor and the participating companies. The vendor is expected to make a proposal for non-proprietary compounds to study with justification. The final list will need to be agreed upon after award of the proposal and may include proprietary compounds.  If the APIs are commercially available, the vendor will purchase them. The participating companies will supply any proprietary APIs.  The vendor should submit the hazard class of compounds they can work with to determine if proprietary compounds can be handled.

6. To “demonstrate polymorphic form and crystallinity” is offline testing expected or in situ or both?

   • ANSWER: Off-line testing (such as PXRD) would be sufficient

7. What is ETC’s plan on managing protected intellectual property (the existing active patents) on this topic? Is ETC going to acquire the required legal rights, license, or loyalty from the patent owners?

   • ANSWER: This topic is covered in section 1.7 of the RFP announcement.  In brief, it is the responsibility of the respondent to acquire the required legal rights, license, or loyalty from the patent owners.

8. Specifically, in this RFP, section 2.2 at the end, it states "The starting material choice is limited to crystalline APIs. Co-processing technologies including amorphous solid dispersions, dry coating, additive-mediated crystallization and adsorption into carrier approaches will be out of scope".  I believe Acryspharm's "Hybrid Dispersion Composite" technology would meet these criteria.  However, I like to seek your feedback for confirmation.   

   • For your information, I am attaching a presentation of Acryspharm in ACS.  Please note that API crystallinity (up to 100%), particle size (nano-mircron size), drug loading (> 50%) and excipients are all tunable parameters in this platform technology.  Additionally, this technology can be successfully executed in current API and formulation equipment.

   • ANSWER: The technology would meet the criteria. However, as mentioned in the RFP, it is preferred that the process uses standard equipment and technology available in drug substance manufacturing plants and not require specialized equipment. If the vendor can offer equipment options other than a spray dryer, it would be preferable.

9. Will the following items be provided by collaborator?

   • API starting material (five different types)

   • Stability indicating assay methods for all 5 APIs.

   • Dissolution methods

   • ANSWER: The list of APIs will be selected in collaboration with the vendor and the participating companies. The vendor is expected to make a proposal for non-proprietary compounds to study with justification. The final list will need to be agreed upon after award of the proposal and may include proprietary compounds.  If the APIs are commercially available, the vendor will purchase them. The participating companies will supply any proprietary APIs.  The vendor should submit the hazard class of compounds they can work with to determine if proprietary compounds can be handled.  The stability indicating assay methods and dissolution methods for proprietary compounds will be provided by the companies, if those tests are included in the SOW.  For non-proprietary compounds, the methods should be found from the literature or developed by the vendor in consultation with the partner companies.

10.  Number of excipients required to screen for generating excipient database (5 or more?)

    • ANSWER: Number of excipients to screen is up to the vendor as long as the vendor demonstrates  that process can be executed with success with minimum of 5 excipients.  We acknowledge that specific APIs may require specific excipients to get good performance however the platform should be flexible enough with multiple excipients to accommodate a wider range of API properties. 

11.  Adsorption is excluded from the proposal. However, there are several approaches to
    adsorption which addresses different processing and formulation concerns. Is the ETC
    willing to review these possibilities?

    • ANSWER: We are willing to review the possibilities if the polymorphic form and crystallinity of starting API do not change upon the adsorption process.

12. What are ETC's expectations towards any IP developed as part of this project?

    • ANSWER: As a policy, ETC does not retain the rights to any IP developed as part of a collaborative project with a 3rd party.  However, given that this is a research project to develop a process/protocol using existing technology and provide this information back to ETC, it is the expectation of ETC to receive a license to the IP developed as part of this project which will allow for unrestricted use of the newly-developed IP including publication. 

Next Post

Protein-Product Seperation