No, only non-GLP and GLP Tox Pkg animal studies (#1 and #2) are planned to be done in the existing facility. The human clinicals (#3) will be done in the new facility, which must be cGMP for US trials or cGMP-like (same practices but without FDA designation) for OUS trials, as in Australia which the company seems to have chosen for their FIM (First in Man) trial (old industry term holdover though not politically correct).
While it might be theoretically possible for them to manufacture cGMP-like materials for clinicals in the smaller lab, they have consistently stated in PRs that they plan to make these in the new facility. There may be constraints in the existing labs that prevent or make costly achieving cGMP.
NOTE: I have made an assumption that #1 (non-GLP) are different lots on different scale than #2 (GLP) based on the Annual Report that stated they were still waiting on equipment for the 3-5 batches needed for a large enough composite to complete their Tox Package. It is possible, though I think unlikely, that the statement in the September-30-released Annual Report applied to the June fiscal year end and that in the few months after June 30 they got the equipment, made the batches, completed batch release and characterization testing, blended and batch released the composite batch, and started the studies using one master batch intended for both #1 non-GLP and #2 GLP. As I said possible ... but not as likely.
As for why it took 18 months from pre-IND to initial Tox testing, there are/could be several reasons.
1. My speculation is that it wasn't until the pre-IND meeting that they really knew everything the FDA wanted to see for CMC and characterization. As they said after the pre-IND in March 2012, FDA gave them specific recommendations for FluCide not included in the standard FDA Guidance documents. FDA likely asked for specific assays and tests and testing plans that needed to be developed, validated and executed. And then multiple lots would have had to be made and tested to set representative specs and tolerances.
2. Annual Report (excerpt below) states they intended to build all Tox study materials at the larger-scale new facility, but schedule and resource constraints there forced them to scale up and make in the smaller-scale laboratory facility. And then they didn't have all the equipment. My opinion - by not realizing sooner the new facility wouldn't be done in time, they cost themselves some time to do the lab scale up in existing facilities. But to their credit, they did recover and find a way to get an important portion of the Tox studies started (barely) by end of the wide range of their self-imposed deadline.
3. Multiple process optimizations followed by builds to establish reproducibility, capability to specs and consistency in characterizations all take time as well to make sure batches made now for non-GLP are consistent with batches to be made for GLP animal and Human Clinical studies.
Excerpts:
Press Release Oct 7, 2013
The non-GLP safety and toxicology study was begun in late September at KARD Scientific in Massachusetts. The results of this study will provide the basis and focus for the IND-enabling GLP safety and toxicology studies of FluCide that are required for the IND submission to the U.S. FDA.
Annual Report June/Sept 2013
After declaring the injectable FluCide drug candidate in February 2012, we have been focused on taking our technology from the small scale syntheses needed for small animal studies to the large scale syntheses for making large batches of our nanoviricides as would be needed for Safety and Toxicology (“Tox Package” studies) and later for human clinical trials. Because of the significant safety observed during the several animal studies designed to test the effectiveness of FluCide drug candidates in small animals, the scale required for the tox package studies was estimated at kilograms. Originally we had intended to perform kg-scale syntheses only after the new lab and facilities designed for such scale up was available. However, the facility program was significantly behind due to challenges related to resources availability as well as significant challenges posed by the need for designing complex functionality in a limited space while performing renovation of an existing space. We therefore decided to perform the synthesis of FluCide for tox package in our existing small-scale laboratory. We have been optimizing the processes and translating laboratory operations to appropriate chemical process unit operations in the subsequent time frame. This is a very significant undertaking, given the constraints of our current small-scale facility. After we have completed these process optimizations, we will still need to produce at least three to five batches of the injectable FluCide, analyze the product for comparability, and combine these batches to produce a master batch sufficient to perform the tox package studies with. These activities are currently in progress.
While we have made significant progress in this scale up program at our current facility, certain key equipment pieces that we need are still on back order at present with certain vendors. After these equipment pieces arrive, we will need to set them up, validate them and then use them for the operations they are intended for. This continues to be an item causing delays in our goal of making sufficient quantities of FluCide for the tox package study and it is outside of the Company’s control.
