Documents transfer information; people transfer knowledge.
A bit prosaic for your tastes? Perhaps. But there’s little debate regarding the applicability of this axiom to drug development and manufacturing. You’ll hear it espoused by industry veterans with decades-long experience in transferring projects from one organization to another, and even by our younger professionals who’ve grown up communicating virtually.
Rather, any discussion on this concept centers on how to access and activate both sides of the equation –document (data) and knowledge (knowhow) transferal. We heard some of this firsthand among audience and panelists at Outsourced Pharma San Diego.
That conversation started with tools: DropBox, Box, Sharepoint, data rooms, and others were mentioned. Email was labeled the black sheep, with Paul Maffuid, EVP Research & Development, MabVax Therapeutics, commenting, “I think email is the universal dislike, because of the burden it puts on the organization in terms of file management.”
Here’s a further taste of some of the discussion on tech transfer.
What’s In A Document?
“Look at the different data formats used globally as part of any tech transfer,” continues Maffuid, whose company is focused on novel human antibodies. “It could include raw data reports, protocols, batch records, meeting minutes, and yes, those emails.” He suggests establishing a data room or other document structure well ahead of a project, “so you know where information belongs in a hierarchical manner, and to help automate the data transfer.”
“We think of this in terms of the future filing of an IND or an NDA. There’s a certain structure for how all that documentation has to reside to allow us to write up the appropriate sections for CMC, regulatory, toxicology groups, and others.”
“That’s a great start,” agrees Brian James, SVP Operations, Rondaxe, a CMC consulting company. “Having the documents, though, is really the first ten percent of the equation. We’ve just received about 500 documents, probably between 50,000 and 75,000 pages for three, phase-three tech transfers for a customer. But that’s all they are right now: documents sitting on a server. We have to go in and find the relevant data, extract the important information, and use that for the tech transfer. That’s the other 90 percent. That can be slow.”
These comments prompt more along this line from a member of the audience:
“Its not simply transferring and mining documents. You’re also transferring nuance, and knowhow about a process, often not captured in these reports. It’s important sponsors engage in verbal communication to ensure CMOs actually understand everything. I’m focused on chemistry. Reports, for example, document the step-by-step manufacture of an API: add this to this in this amount. But it’s as valuable to have your scientist present at the CMO to relay, ‘If you add that too quickly, there’s an exotherm. You’d better watch out for that.’”
She continued: “We have an in-licensed project that just came in, but frankly we don’t have the resources to review all those documents. So we have to try to establish a relationship where the out-licensing company can talk to our current CMO. You just hope that all this communication with your CMO will help bridge some of the gaps.”
Custom Cars And Bug-Out Bags?
Kevin Haehl, General Manager North America, Unither Pharmaceuticals, a CMO that started with the purchase of a Sanofi manufacturing plant in France, agrees on the concern for missing information, and offers this analogy:
“Important as the data that is transferred, is the information that isn’t transferred. Where were the problems that occurred in early development? So tools, automation, templates and defined procedures to transfer knowledge is helpful. But I would describe this in practice as less like a car assembly line with all the parts, and more like a custom shop. What we need are craftsmen and women experienced enough to start with what is known, and then make a custom car each time. In drug development, every project is a little different.”
Remarkably, Olivier Laurent, Vice President Development, Dauntless Pharmaceuticals, a biotech with an all-outsourcing model, morphs the discussion from customized VW Bugs to survivalist bug-out bags. **
“You have to do things ahead of time,” he says. “Yes, it’s obvious, but then you fall behind. I joke that it’s like being a ‘prepper’ with those bug-out bags, and you can run away if zombies attack or there’s some other catastrophe.”
Laurent clarifies: “The point is that in biotech, you have to be ready at any time. You can’t assume – despite your best plans – that in a year from now you won’t have to do yet another tech transfer. By that time the project may look different. You should always document as if you are bringing your project back in house some day. Start by getting the right documents into the contract with your CMO. But you also need to attempt ‘human curation.’ We get an operator at the CMO to summarize in two pages what’s important if we had to run, for example, a certain type of press ourselves. What do we need to know practically? You have to distill that to the essential activity allowing somebody knowledgeable in the field to start at another facility. That’s human curation.
Doug Jolly, EVP Research & Pharmaceutical Development, Tocagen, a biotech with the branding of “No One Should Die Of Cancer,” perhaps best sums up the need for sponsor and CMO interaction. While like others, his company utilizes a form of document automation and structure, “one thing we do with all contractors is go and camp out there, so we understand how they perform their jobs. We find out how to communicate in a way that will work for them, as well as for us.” (He didn’t mention if his camping out included Laurent’s bug-out bags.)
Final Thought (On Longevity)
Axiomatic or not, tech transfer – even as the industry progresses towards more advanced document and project automation tools and repositories – remains reliant upon the people as much as the paper, and diligence as much as data.
But there’s a final caveat, vocalized by Haehl:
“Turnover in this industry is high. Thinking you can depend on a person to bring a certain knowledge along with a project or product is risky. These days, as much as possible we have to instill the discipline to document in detail, make sure that everything we need to know or pass on is actually written down, so that years later that information is still available.”
Olivier Laurent, Vice President Development, Dauntless Pharmaceuticals; Paul Maffuid, EVP Research & Development, MabVax Therapeutics; Doug Jolly, EVP Research & Pharmaceutical Development, Tocagen, Kevin Haehl, General Manager North America, Unither Pharmaceuticals; and Brian James, SVP Operations, Rondaxe.
** Bug-out bag: a portable kit containing the items one would require to survive immediately after or when evacuating a disaster.
Survivalism: a movement of individuals or groups (called survivalists or “preppers”) actively preparing for emergencies, including in social or political order, and on scales from local to international.