In the event of a pandemic or bioterrorism threat, manufacturing capacity must be reconfigured and deployed for the manufacture of drugs and vaccines to meet the threat. The challenge of how we respond rapidly to a new virulent disease is one that governments and industry continue to address. Investment in this area has been stimulated by two factors: biosecurity issues post-9/11 and the expectation that a major flu pandemic is possible. The recent outbreak of H1N1 is a timely reminder of the need to bring on capacity rapidly; in this case, up to 1 billion doses may be required in a six-month time frame.
In this two-part article, we look at the role disposable technologies play in rapid response manufacturing. In part 1, we examine exactly what we mean by rapid response and its implications on manufacturing today. Here in part 2, we will look toward the future and how disposables could lead to truly flexible manufacturing platforms. To support this review, we spoke with key stakeholders from both the manufacturing and supplier sides of the industry for their views on the response to H1N1 and the future of disposables in rapid response manufacturing. The people we interviewed included Tibor Nemes, head of the project office at Novartis Vaccines* in Marburg, Germany; Parrish Galliher, founder and chief technology officer at Xcellerex; Guenter Jagschies, director of strategic customer relations, BioTechnologies, GE Healthcare Life Sciences; and the head of worldwide vaccine manufacturing of a leading vaccine manufacturer, who asked that his name not be used.
KEY FEATURES OF RAPID RESPONSE
Rapid response to a new disease depends on many factors. Through Biopharm Services' role as process modelers in the US government's Accelerated Manufacture of Pharmaceuticals program (validating the targeted vaccine cost per dose through process modeling and assessing the technical feasibility of moving from gene to bulk drug substance in 12 weeks through dynamic facility simulations), we have defined the following key requirements to develop and manufacture new medicines quickly:
- Process development
- High yield expression system(s)
- Low cost, efficient platforms for downstream processing
- Rapid, high-throughput process development
- High speed, high accuracy analytics
- IT infrastructure and systems
- Effective program/data management
- Automated data management
- Data sharing among all parties (development, manufacturing, and quality)
- Efficient technology transfer
- Scalable plan in place
- Fast implementation (i.e., in less than three months)
- Flexible, high performance, single-use manufacturing
- Upstream processing
- Downstream processing
- Facility concept.
The Key Questions
Here, we will focus on the manufacturing requirements. The fundamental question is, How do we rapidly bring on development capacity for the manufacture of a novel drug or vaccine? In the past, governments have put drug stockpiles in place (only useful for known agents, such as anthrax vaccine) or run (or have contractors run) cold or warm facilities, or funded dedicated plants. As facilities become more complex, expensive, and difficult to reconfigure, however, we realize that all of these alternatives are costly and impractical. We wanted to find out if disposable technologies could be a good alternative, and therefore, we asked the following questions:
1. How can disposables help to reconfigure existing manufacturing lines to make a new product? This approach works very well in the response to a flu pandemic because existing flu manufacturing facilities can be quickly reconfigured.
2. How can we use next-generation disposable manufacturing platforms to rapidly re-purpose commercial facilities to meet a critical emergency manufacturing need?
3. What are the possible solutions for countries that don't have manufacturing capacity?
Broadly, we already know that the use of disposable technologies is transforming small-scale manufacturing (Figure 1). However, we wanted to gain insight into the practicalities of the approaches mentioned above. The interviewees provided useful insights into the role disposables play today.
Figure 1. Disposable technologies have transformed small-scale manufacturing.