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I dunno Doc. Are you certain they received treatment immediately after their vaccines were made? It seems extremely unlikely to me, and it’s far easier for me to believe that their stories got misinterpreted, than regulatory manufacturing protocols for safety were overridden. (even if they were knocking on heaven’s door) Those tests for contamination require lengthy incubation periods, and they seem particularly critical because the manufacturing process for the treatments use the manual “open” method, where the cells are exposed to the cleanroom environment (and potential contamination risk), and not in a closed system like Flaskworks. How would it look if a patient were to die, and it was later discovered that safety testing was disregarded?
Not a fan of ChatGPT. BeTheMatch has established relationships with the major cell therapy logistic companies and says this:
24 hours or less for continental U.S. delivery*
48 hours or less for international delivery*
https://bethematchbiotherapies.com/solutions/cell-therapy-supply-chain/
right flipper. Northwest Bio stipulates that the leukapheresis material should arrive the manufacturing facility within 20 hours if its fresh. I believe they would begin manufacturing the treatment that same day, or the next at the latest.
ATLnsider, I admire and respect those (like you) who share their research and theories and are willing to go out on a limb. Admittedly, I haven’t read all of your posts or the board lately, but I’ve read a few posts like this one, presenting a case for the approval of ICLC along with DCVax. From what I’ve read, you make a pretty good case. I don’t have time to get into a back and forth, so I’ll just state my thoughts, and you can have the last word if you wish.
Normally, when a company develops a drug, they establish its safety and efficacy in clinical trials, then apply for and potentially receive approval based on data from those trials, and then continue to make manufacturing improvements, and begin various trials to expand its use. I think the dilemma of whether to include poly ICLC in the marketing application arises because it has taken Northwest Bio so damn long to complete the phase III trial, present the results, and apply for approval. In the extraordinary time it has taken, an incredible amount of knowledge outside of the trial has been established about DCVax itself, and its efficacy with different combinations, by Dr. Bosch, the Neuro-Oncology teams at UCLA and Kings college, et al, that it almost makes the outstanding clinical trial results seem obsolete. I agree with your theory about current and future trials including poly ICLC in the treatment regimen with DCVax, and I understand the rationale for the approval of ICLC along with DCVax. However, I still don’t believe that Northwest Bio will include poly ICLC in its initial application for marketing approval because I believe the data is incomplete.
As Linda Powers said a few years ago, it’s important to establish DCVax-L as a safe and efficacious therapy to discover what it can achieve on its own, as a baseline. DCVax may be combined with many different agents that have different mechanisms of action that may be best for a particular or different types of cancers, and it wouldn’t be prudent to limit its formulation, or use, in any way initially.
I’m pretty sure that poly ICLC was not used in any part of the manufacturing process to make DCVax-L. Every (redacted) manufacturing protocol that I’ve read for DCVax-L, (including the supplement to the JAMA article) only lists granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) as the cytokines used in the cell culture media, which is the most common, reliable, and well established method for differentiation, maturation, and activation, when the clinical trials started.
Generally, during clinical trials, the use of other medicines or treatments that could have an effect on, or interfere with, the safety or efficacy of the drug or therapy being investigated, are excluded and prohibited. This is evidenced in the trial protocol in Supplement 1 of the JAMA journal article where it said this under the heading concomitant medications:
Okay flipper, that is exactly what I thought. You seem to be misinterpreting the part you highlighted “And it can take as much as 30 hours for a qualified person to release a product.” to mean how long it takes for final product testing, but that’s not what that means.
The final product is tested for identity, purity, potency, and stability against pre-established release criteria for the product. And then as I just said, there are a number of additional tests (sterility, endotoxin, mycoplasma) to ensure that the product contains no contaminants. All of this testing takes about a month or more.
And then after all that, but before the product can be released to a patient in the UK, a qualified person (QP) must review all the manufacturing, quality assurance, and quality control data. This is the part that Linda was discussing in your highlighted text. It could take up to a few days for a qualified person to review all of the hundreds of pages of manufacturing data to ensure the product is safe to be released to the patient.
flipper, differing opinions can act as a peer review of sorts, and can make this message board a better place. I’ve never claimed to be an expert, and I’m admittedly often wrong in my speculations about Northwest Bio. But in this case, I will maintain that having a leukapheresis date of 12 June, (in my opinion: a manufacturing start date of 13 June), and then availability of the vaccine by the middle to end of July, would still be consistent with using fresh, not frozen leukapheresis material.
As I said, the final release testing of a cell therapy product may not take the full 35 to 40 days as it did almost a decade ago, since some previously manual assays may have been automated over this period, and some of the work (sterility testing) is apparently no longer outsourced, but I’m pretty sure that all of the required tests can not possibly be completed in 30 hours.
Because cell therapy products can’t be sterilized, and the regulators still want to ensure a safe final product, manufacturers are required to conduct the various manufacturing processes in an environment where the conditions are controlled and monitored, and become a part of the manufacturing record. Further, extensive testing of the final product is required, to ensure that it’s not contaminated in any way. While there are more rapid sterility tests nowadays, they are not preferred by the regulators, and I believe they would only be acceptable in the instance that a cell therapy product cannot be frozen, and therefore unable to last until the typical 14-day incubation period has completed before final release. And in that instance, I believe the manufacturer must have further testing available for the patient after administration. I’m not certain, but I also believe that mycoplasma testing, (which takes 28 days) would also be required, since the dendritic cells have a fairly long culturing period.
If you want to post the particular part of the ASM that makes you believe that testing can be accomplished in 30 hours, then I will respond, but otherwise I’m not wasting my time. If I had to guess though, I’d say that it’s actually you who may be confusing Linda’s remarks about “product release testing” with how long it could take for the QP to review all the manufacturing and quality control data, (after all of the final-product testing has been completed) which I’ve also said that the QP review could take up to a few days for a cell therapy product.
Also, if the leukapheresis material is now frozen, are you able to explain:
1.) Why the label in the picture that was posted states that it must be “stored between 20-25C and used within 48 hours“?
2.) Why the patients are required to fly to London for the leukapheresis procedure?
senti, I’ve never heard of hypothermic storage supplemented with autologous plasma before this, but I think pausing cells at hypothermic temperatures seems to be a valid and safer method for short-term cell preservation. It wouldn’t completely remove time constraints though, it would only extend them. I only did a cursory review, but it appeared to be clinical studies using this method for stem cells. Has this been regulatory approved? Meaning, would it require more . . . I hate to say it . . . pioneering?
Cryopreserving cells is the gold standard, and I think you’re right that the additional cost of this wouldn’t be prohibitive. I personally doubt that Cognate/Advent would’ve tried cryopreservation and then discontinued it. I know that there can be viability issues (it works better for single cells, than for tissue), but the cryopreservation procedures are fairly well established now (used for thousands of patients), and cryopreserved cells have to be very close to the equivalent of fresh cells or it wouldn’t be regulatory approved for several cell therapy manufacturers.
I’m guessing that in early development, Cognate/Northwest Bio wanted to use the most viable cells, and also the least complicated manufacturing procedure, so they chose fresh cells. Scheduling the leukapheresis and coordinating the manufacturing time slots isn’t a problem in low volumes, so using fresh cells wasn’t an issue during the clinical trials, or even now for compassionate use. It only becomes an issue in higher volumes, after commercialization begins. With limited resources, Advent may have pushed cryopreservation development to the lower priority list in favor of the Sawston buildout, licensing preparations, Flaskworks’ development, and development of the manufacturing module of the MAA. That’s a full plate, and an impressive list of achievements for Advent. But, it’s also very possible that this cryopreservation development work has been ongoing in the background, like the automation and digitization of the manufacturing workflows, to overcome other commercial bottlenecks, so I never intended to make it as big of an issue as I’ve already made it.
Thanks Lykiri (and sharpie), that’s some good diligence. (and also a good reminder to - help Tracy)
I don’t think that this actually disproves that fresh monocytes are used. For one thing, that picture is of fresh leukapheresis material, and the labeling states that it is “non-mobilised” and must be “used within 48 hours, and stored between 20-25C” (68-77F), so definitely not cryopreserved. (and likely not intended to be with that label)
Where did you read that quality control testing only takes 2 days? The last manufacturing timeline I read (according to Carol Powers almost 10 years ago), it takes 8 days to manufacture the vaccine, and an additional 35-40 days for final product testing. Although this may be shortened somewhat by now (especially with in-process testing), I don’t think 2 days for final-product testing is correct, since sterility testing alone would likely take a couple weeks (samples must be incubated for that long to detect evidence of microbial contamination). So a leukapheresis date of 12 June, and an availability date of the vaccine by the middle to end of July, would still be consistent with that. (the final product will be frozen, which allows some flexibility for the exact patient-administration date)
Also not sure why else the patients would have to fly to London for the leukapheresis procedure if the blood draw was frozen. (unless maybe Northwest Bio’s exact cryopreservation procedure wasn’t yet established at other hospitals outside of London? But if cryopreservation was being developed with a London hospital, then the labeling would be different, so likely still fresh.)
Thanks for the confirmation senti. I don’t think that I actually corrected you, but merely stated my understanding which was different from yours.
Yes, it’s true that fresh cells begin losing viability between 24-48 hours. As the article states, and as the CAR-T manufacturers have proven; the better the starting material, the better the final product. So, the more viable the cells are, the better. Viable cells are a very real problem for patients who've undergone radiation therapy, chemo, and are on steroids. Many years ago, there was a conversation posted between Carol Powers, who was a Patient Liaison for Northwest Biotherapeutics, and a patient who was inquiring about compassionate use of DCVax, and Carol stated that the leukapheresis material had to arrive Northwest Bio’s manufacturing facility within 20 hours for processing. So this requires that the leukapheresis procedure be performed near, and coordinated with, the manufacturing facility so that a manufacturing time slot can be reserved within the 24-hour window. Scheduling and coordinating this will become increasingly difficult as volumes increase.
I think it was biosectinvestor who said that the specialized shipping companies that handle the logistics for cell therapy companies could ship from the US just the same as shipping from the UK, but it’s simply not true. Yes, it may be possible for some hospitals that are located near an airport to ship from the US to London within a 24-48 hour window, but it’s not only the flight that takes time, there are many other logistical aspects that I won’t get into. It certainly couldn’t be guaranteed for more rural hospitals that are a distance from the airport, or require connecting flights. It’s simply not possible to transport within the window on a near-100% consistent basis, which would be necessary for commercial manufacturing. Commercial manufacturing is all about minimizing risk, and shipping fresh cells from most parts of the US would present an unacceptable supply chain risk.
So yes, the solution is to cryopreserve (freeze) the leukapheresis material, which would alleviate any time constraints that fresh blood materials present. This way, the leukapheresis procedure could be performed anywhere in the world and the material could be frozen and shipped to any DCVax manufacturing facility in the world . . . even Minneapolis. Why do you mention Minneapolis by the way? Do you know something that the rest of us don’t? Or did you mean Memphis? (Charles River Labs)
Northwest Bio (Advent) will have to determine through studies, the optimal temperature range, maximum hold time for stability, optimize the cryopreservation process, and demonstrate through an equivalency study that the cryopreserved leukapheresis material is the same as fresh leukapheresis material, which in my estimation would take at least a year or two.
I’m quite certain that they know about all this. Other CAR-T companies conducted these studies early in the development process and used cryopreserved apheresis material during their clinical trials. The question I’ve been wondering for a couple years now is; why does Advent continue to use fresh cells?
The other bottleneck that I highlighted was enlightening. I didn’t realize that demand for leukapheresis in 2027 is anticipated to be around 350,000 but the supply is only anticipated to support roughly 50,000 patients. That’s a tremendous business opportunity, that I sure hope someone will fill.
Thanks for sharing Lykiri, that’s great news. It’s especially rewarding to hear this when you contribute to these patient’s gofundme campaigns for DCVax treatment. I feel like I’ve helped both Joel, and Northwest Bio.
Thanks Lykiri, yes interesting insights from someone who has considerable knowledge of the subject. Regional manufacturing is acceptable for now, but the matter of cryopreserving leukapheresis material will certainly be an issue (as I’ve repeatedly said) for Northwest Bio in the future, as the production numbers increase, or for global shipping to occur. (although the DCVax final product could still be shipped globally)
Despite what biosectinvestor says, your other post today is yet another confirmation that the current manufacturing process still uses fresh monocytes, since the patient (Tracy) was required to fly from Ireland to London to have the leukapheresis procedure performed.
And did you catch this part? Leukapheresis capacity is another bottleneck that many here probably didn’t realize, which could certainly limit the potential of any future large-scale tissue agnostic approval.
Thanks Lykiri, you’re right; I see they’re on the acknowledgment slide. (probably for some of the compassionate use info)
Where you been jed? Shashi Murthy updated his resume last year indicating that he’s moved onto his next business venture, and it’s unclear what his level of involvement is with Flaskworks. I noticed that Dr. Murthy’s name wasn’t mentioned on the slide attributed to Flaskworks (dated last year), although I don’t think much can be read into that.
btw - Dr. Bosch also didn’t mention Vlad Munteanu, the Product Development Engineer who Flaskworks hired in January, probably since he wasn’t there, and is likely working on other projects. (which was probably true for Shashi Murthy & my point)
ATLnsider, I agree that Northwest Bio seems to state at every opportunity that DCVax is potentially applicable to other solid tumors, and there seems to be a lot of discussion around an “all-solid-tumors approval” lately. But I don’t think that necessarily means that they intend to apply for tissue-agnostic approval at this time. I believe the primary focus right now, is on applying for, and receiving marketing approval for ndGBM and rGBM. Then, once that is achieved, they will attempt to expand the label for other indications.
Right Pharmboy, but it was kinda rhetorical.
You don’t have to assume flipper. Andrew, Lekhana, and Shashi actually proved years ago, that dendritic cells generated in the Flaskworks’ MicroDEN system, induced greater T cell proliferation than dendritic cells generated manually in well plates.
sorry georgebailey, I hadn’t read the board or posted for a while and missed this. The term “semi-automated” did not refer to Eden. It referred to the manufacturing process that I believe Advent used to apply for the commercial manufacturing license. That process employed the use of some automated cell processing and fill & finish equipment, along with a manual culturing process, making it partially (or semi) automated.
I don't think Eden is being utilized in the "Specials" Program. But to clarify: Eden is a fully automated system. I don't think there is any such thing as a semi-automated Flaskworks system. So when the comparability testing is/was conducted, it is/was fully automated.
Oh okay, then disregard my previous post.
Right flipper, great minds . . . :)
Regulators present? Nah, I think the odds are probably better that some spies were in attendance though.
I had the same thought ATLnsider. It seems Northwest Bio may be researching potential tissue-agnostic biomarkers and laying the groundwork for future trials/approvals.
By the way, while a few of the Immune Checkpoint Inhibitors have received tissue agnostic approvals using genetic sequencing to discover common molecular targets, there may be another way using proteomics. (I’m not saying they will - just that it’s impressive how far technology has come)
antihama, even the intro of that FDA guidance states that when companies are applying for marketing approval, they are not only required to include the clinical trial data that proves that their drug or treatment is safe and effective, but they must also include supporting, non-clinical data from animal or in vitro studies that prove that the treatment performs in the patient, or has the pharmacological effects or mechanism of action, the way that the company claims:
The FDA just released draft guidance on GASK in applications for drug and biological products. Northwest Bio has clearly been in discussions with the regulators, and I don’t think it’s a coincidence that this new MOA information was provided in their ASCO presentation this year. I think it’s likely that this non-clinical information was one of the prerequisites that Linda discussed. Yep, I think they're close.
Generally Accepted Scientific Knowledge in Applications for Drug and Biological Products: Nonclinical Information
https://www.fda.gov/media/168408/download
Very impressive ASCO presentation from a medical/scientific perspective. It certainly appears that Northwest Bio has (by far) the most advanced Dendritic Cell Therapeutic ever produced, as well as the knowledge and understanding of its mechanisms of action.
I sincerely hope Northwest Bio posts the full recording on their website.
No Doc, not Eden related. Fun fact though; blue horseshoe crab blood (which is blue/green) contains a unique clotting agent (it coagulates around and encases gram-negative bacteria, which produce harmful endotoxins) that is used to make an important test reagent, Limulus Amoebocyte Lysate (LAL). LAL has been used to detect endotoxins in vaccines, injectable medicines, and medical devices for decades.
Charles River Labs is one of the few companies that has a license to harvest blue horseshoe crabs from US public waters to produce LAL, which is a huge competitive advantage, so they have been reluctant to develop or change to a more eco-friendly test, despite greatly declining horseshoe crab populations, (most die from having their blood drained) and lawsuits from environmental groups.
Supply chain disruptions caused by the pandemic, along with vastly increased covid-vaccine testing, has forced Charles River to begin using alternative testing methods, [recombinant factor C (rFC)] which was developed a decade ago by a competitor, Lonza.
Thanks Lykiri, you saved me the time to look up the transcript.
Thanks ATLnsider, sounds reasonable.
Yes of course London was using the exact manual process that was used during the trial - it was the the legacy process established by Cognate that was used to manufacture for compassionate use in the UK. That manual process was then transferred to Sawston for the initial investigational license there.
I can’r recall if London has a commercial license. If it’s only an investigational license, then Advent could manufacture for the pediatric trial or another small trial there. That’s the only reason I can think of to keep the facility open using an obsolete, less efficient, manual process. I think it’s likely the new established semi-automated process will be transferred to London and used to apply for a commercial license if it doesn’t already have one, and then the facility could be used for extra commercial capacity, or for small clinical trials.
Well Doc, since I don’t believe that Eden is a prerequisite for marketing approval, or currently a part of the marketing application, I think that “comparability” could mean the semi-automated process that was used to apply for the commercial license at Sawston, and will be used in the marketing application. This would be the comparability protocol to establish “comparability” of the new process using the automated cell processing and fill & finish equipment, to the former manual processes, so I believe that one has already been completed.
Thanks senti. My understanding is that patients still need to fly to the UK for the leukapheresis procedure.
Sure biosectinvestor, you said the same thing a couple years ago, (without providing any evidence) that the comparability studies were previously done. And yet, the most recent confirmation (in January) that the PBMCs are not frozen, was by Dr. Toms, when he stated at the Lifespan WPRI news conference, that the tumor lysate could be shipped from the US, but the leukapheresis procedure would have to be performed in the UK. This would be consistent with using fresh, not frozen, leukapheresis material, as Northwest Bio has always done. If the comparability studies had already been done, and the monocytes were frozen, then it wouldn’t be necessary to perform the leukapheresis in the UK, they could be shipped from the US, just like the tumor tissue.
I’ve stated multiple times that the logistics for cell therapy products are considered a part of the manufacturing process, and will be a part of the marketing application, so of course this has been discussed with regulators. For marketing approval in the UK, performing the leukapheresis locally and using fresh monocytes is perfectly acceptable. However, to ship in commercial volumes globally, the leukapheresis material will absolutely need to be frozen. This is why I raised the issue years ago, not because I think it’s some insurmountable task; it’s not, the procedures are well established. Both Kite and Novartis conducted comparability studies on frozen leukapheresis material well before CAR-T's commercialization. There certainly has been sufficient time for Advent to conduct the comparability studies, but Northwest Bio has been rather elusive on the details about this for some reason, which is curious.
Yes, but my old question remains: Has Advent conducted comparability studies for the cryopreservation of the leukapheresis material? (which would allow shipping from the US) Or are patients still required to fly to the UK for the leukapheresis procedure?
For reference:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=170890424
Is this the first time the workstreams are listed from the Statement of Work #6? Seems to be a little more detail in this Q than I remember about this, and as of the end of March, nine of the ten milestones that were prerequisites for regulatory approval, were completed:
10 reasons why DCVax will be approved worldwide:
1. The DCVax phase III clinical trial met its primary and secondary endpoint with high statistical significance.
2. The positive phase III clinical trial results are confirmed by real world compassionate-use data.
3. The positive phase III clinical trial results are confirmed by early clinical trial data.
4. DCVax can be manufactured to commercial standards.
5. DCVax is extremely safe.
6. DCVax treats a rare and deadly disease for which there are no other or very limited treatment options.
7. The clinical trial results passed peer review in JAMA, one of the world’s top 3 medical journals.
8. Regulatory agencies are modernizing and creating new accelerated approval pathways for treatments exactly like DCVax.
9. The world’s top Neuro-Oncologists support DCVax approval.
10. Brain tumor patients and brain tumor charity groups are advocating for DCVax approval.
DCVax is going to be approved worldwide whether the handful of naysayers like it or not. They would be wise to start coming to terms with that.
Thanks Estevito. Yeah Dave is full of . . . useful information.
rkawong, the company has not announced whether Advent’s commercial license included Flaskworks or not, so we can only speculate about it. Flaskworks’ Eden is a pretty big deal, and if it was included in the commercial license, I would think that it would have been announced. Right? Since it wasn’t, my post was about the reasons why Eden might not have been included in the commercial license. If it wasn’t completely qualified and validated, then I don’t think it would have been included, which is why I don’t think it was.
The Flaskworks system was originally designed and commercially sold as a clinical device (to be used for clinical trials). The GMP regulations for this type of investigational product only requires that the final product be tested to meet the pre-defined final-release specifications. However, to produce a commercial product, the GMP regulations require in-process controls and the ability to test, monitor, and maintain the quality of the product throughout each manufacturing process, to ensure a consistent and high quality final product.
Therefore, in order to be used in the commercial manufacturing process, the Flaskworks system had to be modified and enhanced with a way to monitor and maintain, or adjust the conditions during the culture process. This is accomplished with the use of biosensors which measure and analyze the critical conditions in a culture vessel. They provide real-time, in-process quality control data on measures like cell count, cell viability, cell size, acidity, dissolved oxygen, temperature, and level of metabolites and nutrients. Based on this continual feedback information, adjustment can be made to the different culturing parameters to maintain the optimum culturing conditions to induce differentiation of the patient's monocytes into dendritic cells.
This is just one of the many tasks the Flaskworks' team/Advent has been working on for the past couple of years in order to get the Flaskworks system ready for the comparability studies (along with the qualification of the system and process validation) to prove that it can produce a similar product as the manual method. As far as I can tell, this wasn’t accomplished prior to the filing of the application for the commercial manufacturing license.
Thanks for your thoughts and comments dmb. I understand what you’re saying, and agree that the MAA could include Flaskworks, and if it was in fact included, then that could be a reason the MAA application has taken so long. However, my thinking is that Northwest Bio only needs the Flaskworks system for commercial scale up, but not necessarily to gain marketing approval, so they may not want to include the Flaskworks process, which could potentially complicate and/or delay receiving marking approval, which could also delay other (financial?) plans. I think a less risky and preferred approach, (even if it takes a bit longer) would be to add the Comparability Protocol (CP) for the Flaskworks’ process after the marketing application has been approved, as a Post Approval Supplement (PAS). I’ve always maintained that this was a possibility, and now I think it may be likely, given what we know.
I agree with your validation concerns. Shashi Murthy commented at the ASCO presentation in June, that more validation work needed to be done, and that language “integrating technology for monitoring cell culture to ensure reliability” sounds like validation work, so this is why I believe that Flaskworks’ Eden was left out of the initial commercial licensing process, and likely, the final MAA as well.
It makes sense (to me) that Advent would do it step by step; file a CP for the initial change to a semi-automated manufacturing process (which had all been validated) for the general commercial license, excluding the Flaskworks system; so basically automated cell selection, manual culturing, and automated fill & finish. The idea is to get the initial commercial manufacturing license approved, and then use that approved semi-automated commercial manufacturing method in the marketing application without further complication.
Meanwhile, in the intervening period since the ASCO presentation, the Flaskworks’ team has been working to get the Eden system fully validated including in-process controls. Then, once validation has been completed, Advent will plug the Flaskworks system into that established approved process, run the comparability study using the Flaskworks automated process to show equivalence to the established semi-automated process, and then submit the CP to regulators as a PAS . . . and hopefully within 60 days, it will be approved. Simple as that!
By the way, I’m not trying to convince anyone of this, or even saying that this is correct, but just saying that this is what makes the most sense to me at the moment.
Good to know, thanks Lykiri.
Actually dmb2, I wasn’t being pragmatic. As you may know, after the ASCO manufacturing presentation last year, I was convinced that the Flaskworks’ Eden system had been qualified and was completing validation, and I thought it had been included in the automated process that Advent used for the commercial license. However, last fall, I was told by an associate (who talks to management) that Flaskworks wasn’t included because its development wasn’t completed by July, when Advent applied for the commercial license for Sawston.
When I saw the biosensors on the prototype system on the slides of the ASCO presentation, (after nearly 2 years of development time) I assumed that it was completely functional, (and mostly validated) but maybe it wasn’t. Flaskworks and Advent both hired some key personnel in September which appeared (to me) to be related to Flaskworks’ development. (Flaskworks hired for product development engineers whose responsibilities included “Identifying design improvements and integrating technology for monitoring cell culture to ensure reliability” and Advent hired for multiple computer validation, and software/firmware script writing positions) So, as of last fall, Flaskworks/Advent may still have been working to control the biosensors for the culturing/feedback parameters of the automated culture process, and the software integration with the Autolomous Manufacturing Execution System software at Sawston to control the Flaskworks system, and/or validation work on the biosensor controls. Perhaps a sense of urgency finally occurred last fall for the proper resources to get the Flaskworks system ready for the comparability study, so that it could be approved in time for commercial production by the end of this year.
I think marketing approval in the UK can be much faster than the comparable timeframe in the US that you’re referencing. In the UK, DCVax has been designated as a Promising and Innovative Medicine (PIM) for a rare and deadly disease with limited treatment options, so it qualifies for an accelerated review process. Many of us believe that it could already be in a rolling review, which allows modules of the eCTD dossier to be submitted incrementally for pre-assessment by the MHRA, rather than as part of a consolidated full dossier, and it also allows enhanced regulatory interaction and advice to reduce the risk of failure, and “the final decision on approvability reached by Day 100.”
I anticipate that Northwest Bio will announce the MAA filing when the final submission has been accepted by the MHRA. Northwest Bio is likely interacting with a very busy, and back-logged regulatory agency, and potentially may be working out a schedule, so that once the completed final MAA has been submitted, it can be assessed and approved within the MHRA’s 100-day window.
.
If that is true, then I would anticipate regulatory approval within about 3 months of the filing announcement, but potentially up to 5 months, if there are issues that require follow up information. And by the way, that previously mentioned associate also thinks that approval in the UK will be very rapid.
Also Doc, “Approval of L changes everything” because it puts the naysayer’s primary false narrative (that the clinical trial failed, and DCVax won’t be approved) to death.
MHRA approval is important because it’s the first major step that allows a chain of events to occur. It lowers the risk of FDA approval, which also significantly lowers the risk of investment in Northwest Bio, which is necessary to: attract large risk adverse institutional investors, attract large industry partners, uplist to a major stock exchange, and attract large-scale media attention, which all should lead to a significantly increased stock price. (hopefully even a short squeeze somewhere in there)