Watch the Webinar On-Demand

About the Webinar

The recent successes of approved gene therapies have resulted in a surge of interest by biopharmaceutical developers. In fact, the gene therapy industry is expected to grow 30% year over year in research and development spending to help treat diverse therapeutic indications.

With this growing market comes a variety of challenges that sponsors, CROs, institutions and their sites must consider when running these trials: How do teams handle and interpret the changing regulatory landscape as a result of COVID-19? How do teams know when a study is subject to the NIH Guidelines and therefore need to engage an IBC? What are the ways organizations can make study reviews more efficient when working with an IBC?

If your organization is planning or participating in a gene therapy trial, it’s critical that you join us in our upcoming webinar, as we’ll tackle these considerations head-on.

In this webinar you will learn:

  • What the key regulatory guidelines are governing the approval of gene therapies, and provide strategies for adhering to them
  • The sponsor perspective on engaging stakeholders involved in gene therapy research to ensure best practices and communications are in place throughout the trial
  • When Institutional Biosafety Committee (IBC) review is required and how to engage with IBC providers
  • How a coordinated IRB and IBC review of the protocol enables a more efficient trial start-up

Meet the Speakers

Photo of Daniel Kavanagh

Daniel Kavanagh, PhD

Senior Scientific Advisor, Gene Therapy, WCG

Riki Cullingford, MS

Clinical Project Manager, REGENXBIO Inc.

Photo of Dawn Flitcraft

Dawn Flitcraft

President, WCG IRB

Questions & Answers from the Audience

Q: How does a pharmacy manual and an IB differ?

A: Cullingford: I think we’re all accustomed to the IB, which outlines for the investigator, the risk benefit to the potential subject. So, it’s more about the preclinical and clinical aspects of your product that the investigator needs to evaluate. It’s not specific to the handling instructions as we spoke about. The pharmacy manual doesn’t necessarily touch on risks. It touches on how you handle the product in the clinic, from storage to transportation and even disposal, and none of that is usually outlined in the IB itself.

Q: How has COVID-19 affected IBC reviews and approvals?

A: Kavanagh: It depends on how the sites are handling their staffing and attendance during the time, and it also depends on how the sites are ready to interact with their committees. Some things we’ve seen is that minimal staff may be present at sites while they’re there preparing for IBC reviews. A lot of the components of review can be handled remotely, but some of them really are facilities assessments. In most cases, if the site wants to have somebody present on site with an iPhone to do a walkthrough, show all the facilities, that is in many cases just as good as an in-person inspection. Sometimes it’s even better, when you have a permanent record. So, even during COVID, we can manage a lot of reviews remotely and provide good site assessments that way.

Another interesting aspect is that the Operation Warp Speed vaccine roll-outs were a wakeup call for everybody who wanted to participate in the trials and move very quickly. So, I think it helped us on the IBC side really think about how to speed up approvals, and I think it motivated a lot of investigators and sites to get all their paperwork in on time. It was a very interesting experience for us to see turnaround times rapidly decreased, specifically for those clinical trials. Because everybody was pulling together, the NIH was very cooperative and getting expedited authorization of new IBCs, and staff and sponsors really wanted to roll out correctly. I think we’ll be able to take some lessons forward from that.

Q: Daniel, what is the role of a pharmacist from your perspective, sitting in and managing an IBC? Then Riki, maybe you can speak to that in terms of managing your sites, involving a pharmacist in your assessments.

A: Kavanagh: When we set up an external, remote IBC committee, we ask each site to appoint a committee member who will serve as a representative on the committee of the site. That is sometimes a clinical coordinator or other member of the administrative staff. Often it’s a pharmacist, and pharmacists have a great perspective on product handling. A research pharmacist may be the key person who’s looking over the pharmacy manual when it comes in, and planning out product storage, and product preparation, if not the administration and disposal, but those are key aspects of site preparation.

If sponsor and site decide that the site is going to be falling under USP 797 requirements for product preparation, that introduces a lot of special considerations regarding a biological safety cabinet. A typical cabinet that you’re going to prepare is a class 282 cabinet that recirculates air into the room. If you are going to also be having hazardous chemicals in the cabinet, you’re going to want a ceiling vent to go to a class 2B cabinet or a class 3 cabinet.

Pharmacists are the people who handle all those questions, so the IBC often has a very useful conversation with the pharmacist while we’re planning site assessments, depending on how complex the site needs are. In many clinical trials, those considerations are not really necessary because it’s a simple preparation step. A product can be received, stored, and administered without all of that input. But certainly, when a pharmacist is involved in the trial, their input is very valuable to accelerate site preparation.

A: Cullingford: I agree with Daniel completely, because my current lens is a vial that goes from the freezer to the Principal Investigator (PI) for administration. So, the pharmacist’s job in those trials isn’t very elaborate. But I have participated in trials where there is a substantial dilution step, or you must merge several vials into one administration syringe, and all of that’s done in a biosafety hood. I would certainly involve the pharmacist in the development of the pharmacy manual. Maybe that’s why it’s called a pharmacy manual, of course. But I think that their evaluation of the process and making sure that it’s protecting and keeping the product safe would be massively helpful in the review process.

Q: With your lessons learned over the years in working with CROs, when you look at a new trial, how do you think about dividing up the responsibility between your team and a CRO? And you mentioned a video, but what are some of the other methods tried and true that you’ve used for training?

A: Cullingford: I think the industry is just exploding, and so a lot of people are entering it for the first time and they’re just not familiar yet. I have early on considered doing IBC submissions in house, because like I said, I think the sponsor knows all the questions and all the answers. But I found that spending the time educating our CRO partners to be the most valuable, because they do ultimately become accountable for the trial and working with the sites, and so they need to be just as much involved and experts in the process.

I think the planning must happen early on, like at study kickoff meetings, where you’re sitting down and saying, “Who has experienced with this? How can we cover the gaps? Who’s new?” I have even had Daniel spend some time with partners before, just to make sure that they know as much as we do about the process. It pays off in the end, because especially for larger trials, they do really need to take on most of the burden of the work with the sites.

Q: Do IRBs and IBCs communicate? What are the advantages of using the same IRB and IBC?

A: Kavanagh: Certainly, the IRB and IBC should communicate as necessary. Sometimes the reviews are simple enough, and the administration of the different committees may be under different entities, and they just do their job on their own. But as soon as any complications pop up, any special considerations, they should not be shy about communicating, whatever the administrative arrangement is, to provide the best safety and review at the sites. So, it could be a formal arrangement, as I mentioned, such as the IRB members attending an IBC meeting, or it could be a phone call between the chairs. But they should certainly be available to each other, and in many cases, it’s a vital part of the review.

Even though review of the informed consent document, for example, is no longer required by the NIH, many sites will still want the IBC to do those reviews. Our WCG IBC team will frequently be consulted on those issues, just because we have experience and expertise. I’ve experienced composing those documents and our teams have experience in reviewing them. Together, we can provide valuable input to the IRB.