Embracing the Good and Avoiding the Bad and the Ugly in Pharma Manufacturing


Good manufacturing has always been about paying attention to the details. But now, thanks to competition, global sourcing, a higher compliance bar and increased regulatory scrutiny, there are more details to worry about than ever.
 
Some projects require thousands of steps towards completion. Under this new complexity, in which analyzing is as important as the manufacturing, the main manufacturing goal is to reduce the number of issues that can disrupt completion, which can range from major to minor. It’s important to realize that minor details, which once might not have represented issues before, can turn into a problem.

For example, producing a higher yield (27 kilos instead of 25) on a recent project is usually a good thing but this time, it actually caused a delay, jeopardizing more than seven months of work and an investment of more than $750,000. The minor detail was that the client’s ERP system rejected delivery of the 27-kilo yield because it did not match the purchase order (PO) that specified a 25-kilo yield. It was only after a minor delay when the client issued a second PO for the additional two kilos, that the project was able to move forward.

Over the past 15 years, PCI has developed best processes to minimize glitches that can slow down and raise the costs of drug manufacturing. These steps include:

1. Evaluate the project. The project may change in slight but important ways from the time the client has received proposals to when the project is assigned. Once it is assigned, the contract manufacturing organization (CMO) should identify the necessary skill sets, resources, outcomes.

  • Clients should make sure the CMO is aware of any changes, and understands the implications of those changes.

2. Assemble the project team. Internally, the CMO needs to assign the project team based on skills, experience, current workload and compatibility. Next, the team needs to hold an internal meeting with the business development team. The project manager takes over from biz dev, serving as a central point of contract for both the client and the internal team; the project manager is responsible from beginning to end. The scope of the project should be documented and discussed so everyone understands the dates, approach, achievable, and that there are no red flags.

  • Some firms assign teams based on availability, and just as you don’t want someone who is already overloaded on your team, clients don’t want a team whose main attribute is they’re not working on any other project. Clients should understand how the team was assembled.

3. Conduct a kickoff meeting. After the internal team has met and identified milestones and possible key issues, it should meet with the client’s team, whether face-to-face or by phone. In our experience, these meeting tend to be very long because there’s a lot to navigate, especially in order to make sure the client’s team and the project team understand the approach, the needs, the timing, compliance issues, reference standards, packaging specifications, etc. Discussion topics include the technology that is available as well as what needs to be developed to handle cutting-edge requirements.

  • Make sure it’s clear from the project plan what the deliverables are and when the milestones are scheduled. Also, client teams should make sure they understand staffing requirements, which change over the project lifecycle. For example, the number of staffers fluctuates as the project progresses into the plant or clinical suites. At a certain point, the analytical people gear up while the chemistry team slows down. Then manufacturing gears up, along with the regulatory experts. At that point, analytical and chemistry scale back.
  • This is an important time to make sure the client team and project team are on the same page in terms of addressing regulatory requirements. With the rise of virtual biotechs, CMOs are increasingly serving a consultative role on topics like compliance, preventing significant delays and reducing the likelihood of problems with FDA approval.

4. Develop a to-do list. The project manager should develop and distribute a to-do list along with the timeline for the entire project. The to-do list should be updated on an agreed-upon basis, such as monthly. At the beginning of a project, the client is likely to have the bulk of the to-dos but the number of to-dos shifts to the project team. The project manager puts together the Gantt chart to track progress and action steps.

  • Make sure the client understands all the steps, assumptions, responsibilities and deadlines.

5. Conduct regular check-in meetings. These meetings are important for both the client and project teams. At the kickoff meeting, the teams need to decide whether to meet weekly or bimonthly to ensure everyone is in synch. These meetings are an opportunity manage the budget and monitor against the Gantt chart for deliverables. Our Gantt charts are color-coded to enable both teams to determine whether the budget and project are on track. If the color is yellow or red, be prepared to dive into the project detail. This is a big area for concern for clients because a minor problem can grow into a bigger one.

  • Expect the project team to pose a solution for any problems or issues it is encountering. Ideally the issues and the proposed solutions should be listed at the top of the agenda for the next meeting.

6. Be true partners. While the CMO should come up with solutions to problems, the client team should be a full partner in the decisions. This is particularly true with projects that push boundaries – which increasingly happens as the necessary work to develop new molecules becomes increasingly complex – and require new tech and new processes. Sometimes there’s a yield problem because the underlying work conducted elsewhere was imprecise.

  • Be prepared to compromise. For example, if the yield was supposed to be 60 percent but turned out to be closer to 10 percent, the client and project teams need to consider: Which is more important – the timeline or the budget. The CMO should consider adding another FTE on the project to solve the yield problem, which might delay the project or whether it would be better to buy more raw materials to keep the project on time but add to the cost of the project. The CMO can make the recommendations but the client team needs to make the decision.

7. Benchmark the project. When the project is done, the CMO should conduct a survey of what it did right, what it did wrong and where it can improve. We incorporate as much as we can to continue to improve our future processes.

  • Client teams should make sure they understand the lessons learned from the project. The project manager should be willing to discuss what worked well, what could be improved, especially in terms of new technologies and processes.

These best practices can help clients and their CMOs embrace the good processes while avoiding the bad and the ugly. This is important for CMOs as much as for their clients; SNAFUs and delays can increase their costs/margins and stress. Improving the project processes can improve the situation for everyone involved.