Strategic Partnerships: A Regulatory Operations Perspective

Strategic partnerships play a big role in today's biopharmaceutical industry. Most of these partnerships involve a relatively small company with an interesting molecule partnering with a larger company with cash to invest. The partners come together with a shared goal to develop and market a product, but often differences in company cultures, processes, and technology get in the way. Regulatory Operations usually has a few key roles to play in partnerships, including due diligence activities, setting up collaboration platforms, and managing document reviews.

Due Diligence

The path to a partnership agreement starts with due diligence activities where prospective buyers sign a confidentiality agreement and check out the seller's goods. Those goods include key clinical and preclinical study reports, an overview of manufacturing and process development, and records of correspondence with regulatory agencies. For products that are already in the clinic, the easiest way to present this information to prospective partners is to give them access to the contents of the regulatory archive.

The message to Regulatory Operations groups: manage your archive well and you're always ready for due diligence. In addition to providing the complete archive of all submissions and correspondence, you also need a chronological list of all submissions and correspondence. If your company doesn't have a document management system, you can create this chronological list in a spreadsheet or simple database. Whatever system you use should track the application and sequence (or serial) numbers, date, submission or correspondence type, and a brief description of each item. If you want to get fancy you can create a link from the list to each submission. This list serves as a nice table of contents to your archive that will allow people performing due diligence to quickly find what they are looking for.

Virtual Data Rooms

To facilitate due diligence and reduce travel costs, many companies now use a virtual data room (VDR). A VDR is a secure web site that provides authorized individuals access to documents, but prevents the reader from saving or printing documents. It's a simple process to provide someone access to the VDR for a defined period of time, and then review log files to see who looked at which documents. VDRs can be created on an isolated part of a company's existing systems such as SharePoint, or Box, but it's often simpler to use a separate hosted system. VDRs are used widely in the financial industry for mergers and acquisitions, so most commercial offerings have well-established security models. Using a VDR can dramatically simplify the due diligence process, allowing the selling company to work with several potential buyers at the same time. Without a VDR, the company with the information has to host several day-long sessions in a secure conference room as each potential buyer comes through. A VDR enables companies to get through that process more quickly and move on to serious negotiations.

For Regulatory Operations, it should be a simple matter to load the archive of information, including the table of contents, into the VDR. Often there are other documents loaded into a VDR, but the submission archive is usually the bulk of the material. If possible, highlight clinical protocols and study reports, key toxicology reports, and major manufacturing changes in the table of contents, since those are the documents most people will look for.

Collaboration Platforms

Once a deal is signed, the partners need to establish a common set of working practices. One of the first things set up is a way to share the large number of documents that will need to go back and forth between the two companies.  This usually starts with the information provided during due diligence, but expands rapidly from there. Often one of the companies (usually the larger, more established partner) will have an existing system that they want to use to share documents. Sometimes the use of this system is written into the contract.

It's important to remember that a platform for collaboration is not the same as an archive. One of the partners typically owns the system, and neither partner puts all their documents on the system. It's most useful for everyone involved to make contact with their counterparts at the other company to work out the details of sharing information. RegOps is often left out of this process, but talking early can head off misunderstandings down the road.

Here are a few suggestions for how to manage the collaboration platform:

  • Identify the process owners for the system at both companies, who are usually from project management or alliance management
  • Agree on a high level folder structure to manage the breadth of information the project requires
  • Identify which documents need to be shared, who is responsible for uploading them, and timeliness requirements for uploading new information
  • Periodically clean up the organic growth of folders and documents
  • Determine which documents from your partner should be downloaded into your company's systems
    • Set up processes to maintain these documents as if they were your own company's confidential information
    • Determine who is responsible for downloading new documents and create a schedule for that
    • Set up notification procedures on the system so that the project team gets an email informing them of recent changes, such as new documents
    • Treat the collaboration platform as a temporary site for sharing information, not an archive

Document Development and Review

Partnerships usually start with the best intentions on both sides. There is broad agreement on common goals, and a sense of shared excitement as people join the project. When it comes time to conduct joint reviews of documents, people are often surprised to realize that the companies have very different goals for the project. Often, partners divide projects geographically, so that one partner has marketing rights in the US, and the other in the EU or rest of world (ROW). This can lead to challenges, if, for example, FDA guidance from an end of phase 2 meeting differs from European scientific advice. Resentment can easily build if authors under deadline face the prospect of optimizing their submission at their partner's expense or slowing down to try to accommodate the needs of both partners.

One of the challenges of the review process is that the smaller company usually has the technical experts who know the molecule, while the larger company has more drug development experience.  Big company processes can appear ponderous and labor-intensive to small companies, while large companies may not be comfortable having to rely on the expertise of people who may not have as much drug development experience. Unfortunately, these kinds of issues tend to come out during the document review process.

To try to head off this kind of friction, it's useful to have a well-defined document development and review process that includes both partners.  One of the key steps is to try to get agreement on strategic issues before writing begins.  Circulating well-developed templates or model documents that include key messages is a great way to identify potential issues at a time in the process when they can be more easily addressed.  Too often, companies wait until they have a near final draft before sharing it with their partner.  If the partner then raises substantial issues during the review process it can lead to an escalating tide of resentment and frustration.

There are some nice online tools that can help facilitate large review processes.  These types of tools bring transparency to the process and help eliminate multiple iterations of the same comment.  Allowing reviewers to see each other's comments also tends to encourage people to take a more positive approach in their comments.

Organizational Structure

People at the smaller company may get frustrated as they try to navigate the larger organization. Often, the organizational structures do not line up exactly.  For example, in smaller companies, Regulatory and QA often report to the same person, while in larger companies they usually don't. Larger companies also have geographic diversity, so a clinical development team in the US might be working with a manufacturing group in Europe, or vice versa. This situation can be especially challenging for Regulatory Operations, since publishing groups at larger companies are often viewed as service providers, and are not included in collaboration activities with partners.

Transferring a Product

Sometimes, based on reaching a development milestone, a product or an application gets transferred from one partner to the other. This is another reason RegOps should have a well-organized archive. To ease the transfer, establish contact with the partner's RegOps group, if possible. Also, talk to someone in your company who can explain the legal requirements of the transfer and get a copy of the agreement, if possible. Most of these agreements allow the partner that is letting the product go to maintain an archive copy, for example, but it may need to be segregated from other product information. The receiving partner should do an inventory of the material they receive and work with the other RegOps group to understand how they have organized the files. Both parties need to understand and follow any agreements about future documentation.

If the transfer involves legacy eCTD submissions, the receiving partner will have to import those submissions into their publishing system so they can maintain the application lifecycle. There are subtle differences in the way publishing vendors implement agency guidance into their systems, as well as changes in guidance and DTDs over the years. These differences can make the import process a challenge, and may be another source of friction between the companies.

Conclusion

There are many challenges to strategic partnerships, but they are a fact of life in the biopharmaceutical industry. Even for companies that are not involved in partnerships now, it's prudent to plan for them in the future. For Regulatory Operations, setting up and managing a comprehensive archive is essential. That archive is like the crown jewels during the due diligence process.  RegOps also has an important role to play in helping set up and maintain collaboration platforms and managing or assisting with the document development and review process. A little forward thinking and good communication with your company's partner can make this process go more smoothly.