Cloud-based information technology makes it easier for pharma companies and outsourcing partners to collaborate on quality, if risk-management steps are followed.
Ten years ago, installing quality management system (QMS) software was an intense process that could take years. Increased outsourcing of strategic manufacturing and development operations have only added to the potential complexity.
More recently, a number of pharmaceutical companies, including Teva Pharmaceuticals and AP Pharma, have moved from traditional to Internet-based QMS programs. Even FDA, which began installing QMS in its Office of Pharmaceutical Science in 2009, added a Web-based QMS for additional divisions in 2014 (1).
QMS vendors, including EtQ, Sparta Systems, and MasterControl, have adapted to changes in the pharma market by improving the user interface and making it less difficult for strategic contract partners to access documents. The newer approach does not require that companies buy additional licenses.
These changes have made everything from corrective actions and preventive actions (CAPA) to root-cause analysis easier to do. However, sponsor companies must still have the correct approach to documentation and data and risk management if they don’t want to export the wrong processes to their business partners.
Two of the biggest potential pitfalls that pharma companies face are “tribal data” approaches and “death by CAPA.” Matt Lowe, executive vice-president, and Patricia Santos-Serrao, director of clinical and regulatory solutions for the pharmaceutical industry, both with MasterControl, discussed issues and accomplishments with Pharmaceutical Technology.
PharmTech: Before a company invests in QMS software, especially if they are outsourcing to contract partners, what should they do to ensure the best results?
Santos-Serrao: One of the most important things to remember is that, if you plan on using a certain method or approach and it is part of the way that you manufacture products, you will need to document all of the procedures and all of the actions and activities that are required for this approach. Optimizing standard operating procedures (SOPs) becomes a cornerstone for this process.
SOPs document how procedures are executed, what methods are used to execute them, what the related procedures are and how are they connected, for example, when one procedure refers to another. Regulators expect clarity and full documentation, but this is an area where some pharma company sponsors may still fall short. A surprising number of companies today still rely on tribal knowledge, or the ‘we just know that that’s what we’re supposed to do. It’s not really written down anywhere’ approach. That kind of approach cannot be audited or validated and it’s not repeatable. It’s word of mouth, and it’s not good enough.
The industry is well aware that all of its processes must be documented, but questions often arise as to who should be responsible for it, and when and how often it should be done. SOPs provide the foundation for best practices.
Once everything has been documented, the next question becomes one of training. Who will carry out which procedures, what training will they need, and what will their roles be?
Our solutions focus on document management. We have solutions around good manufacturing, laboratory, and clinical practices (GMPs, GLPs, and GCPs), but SOPs form the foundation for each of them. Once you know which procedures are strategically important, you can develop training programs to align with them.
PharmTech: What mistakes do pharma companies make with documentation and training?
Santos-Serrao: Some companies assume that a procedure is so basic that it needn’t be documented. When an auditor comes in, watches processes, and asks, ‘After this procedure, what does the operator do next?’, all too often, the SOP detailing that information just isn’t there.
PharmTech: How about when you are outsourcing your R&D or manufacturing operations?
Santos-Serrao: Sponsors bear the responsibility for what their business partners do. Contract partners are just an extension of their organizations. One can outsource anything, down to the nittiest grittiest detail, but responsibility canot be outsourced.
PharmTech: How are QMS systems being designed to allow better communication about quality with suppliers and contract partners?
Santos-Serrao: Over the past few years, we have broadened the ability to allow our customers to bring more collaboration to how they manage procedures, and push out more collaboration to partners. For instance, we have a GuestConnect feature that allows external users to access sponsors’ systems in a controlled way, to upload sponsor documents and to share theirs.
Our license model is targeted to concurrent users. Partners can use a guest account. This approach encourages collaboration, without requiring additional licenses and cost. We’re creating supplier portals to allow companies that are working with contract partners to create work spaces for partners where they can collaborate.
This approach allows for open-door communication and sharing tasks, and, eventually, the collaboration sustains and maintains itself. Sponsors and contract manufacturing organizations (CMOs) alike can share areas of risk and concern and suggestions on how to address them. Such portals will be critical to making partners an extension of the company. Partners can be treated like a department within an organization.
PharmTech: CAPAs are an area where individual companies often fall short, as evidenced by 483s and warning letters. When collaborating with contract partners, there is even more potential for problems to fall between the cracks. Why is handling CAPA such a problem for companies, and what steps should they take before buying a QMS platform to ensure a successful approach?
Lowe: One of the biggest problems that we see is ‘death by CAPA.’ Some companies don’t reserve CAPAs for the significant issues that deserve that approach. Instead, they put anything and everything that goes wrong through their CAPA systems. As a result, they cannot identify the real problems that require a CAPA and can’t solve them all. Then they get written up in an audit as having 400 open CAPAs.
Best practices require the use of an internal risk filter or risk gateway. The filter sifts through all the quality channels that feed into a CAPA system (e.g., nonconforming materials, deviation, variance).
The filters are relatively simple. Typically, they are two-variable matrices using frequency and impact to ask ‘how often does this happen, and, when it does, what kind of impact does it have?’ That will set a risk profile so that, when a situation falls into a higher priority area, it triggers a CAPA.
Another area where we see problems is around recurring CAPAs. A company opens a CAPA, does something about it, then closes it out, yet the problem comes back. This usually happens when root-cause investigation was inadequate and failed to get to the root cause of the problem the first time. We suggest asking who, what, where, when, why, and how to dive deeper and identify trends. For instance, are you always seeing these types of problems with specific healthcare customers?
PharmTech: How do web-based programs help ensure more thorough investigations?
Lowe: Web-based enterprise QMS systems allow supply-chain partners to participate directly in the root cause analysis process and to add data in the CAPA. Trying to do this via email or passing paper back and forth can be extremely difficult, and, if a sponsor and a partner have very different IT systems, things can get very messy, very fast.
PharmTech: How can sponsors ensure that they use QMS for CAPAs properly?
Lowe: It helps to have a system in place that will allow external collaborators to input data easily and to access documents from the sponsor efficiently. For any questions, they need to be able to reach the initiator. But the sponsor also needs to engage its partners in communications such as: ‘Here is a corrective action. Participate with us in the verification and validation process to ensure that we’ve addressed the problem and have put preventive actions in place to keep this from recurring in the future.’ Often, when you are dealing with the CAPA process, the outcome may be changes to documentation or recipe specifications. A system that allows those changes to be made seamlessly is crucial.
Training is another issue. If a change occurs, how do you train partner companies on the change and record that they were changed? Having a system that has a mechanism to launch automatically when those changes occur is important.
PharmTech: What changes have you made to help sponsors manage change?
Lowe: We recently completed a major overhaul of our user experience to make it much more friendly to the casual user, a term that will define most partners in the typical pharma sponsor’s supply chain. These users will be in a sponsor’s system once or twice a month. If it will take a major process to relearn what’s required every time, compliance will become an issue. You need to give them something simple that allows them to provide the information needed, but get out quickly.
In addition to GuestConnect, we have added a quality event analyzer for CAPA that allows users to set up ‘analyzer agents,’ which look through the entire quality system to find trends and identify problems that might not yet be visible but are happening across a number of different channels. It is like having predictive analytics in place, and allows sponsors to take proactive measures to prevent things from getting worse.
1. “MasterControl Continues Role as QMS Provider for FDA Office of Regulatory Affairs,” press release, mastercontrol.com, November 12, 2014.