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Aegis’ Discoverant software system enables process understanding that allows customers to reduce process variability, and increase the predictability of yield and quality. Discoverant’s significant business benefits are available to pharmaceutical, biotechnology and medical device manufacturers as well as their related Contract Manufacturing Organizations (CMOs). Discoverant is configurable to individual processes and can be implemented progressively so that the areas of greatest need can be focused on first, regardless of the size of the business or the scale and distribution of operations.
Manufacturing:
In recent years, large investments have been made in IT infrastructure to improve pharmaceutical manufacturing performance. As an added benefit, these systems also accumulate large quantities of raw data about their respective portions of the manufacturing process. Continuous data is found in the data historians of DCS, SCADA and other control systems, and discrete data is found in the operational data stores of other systems. Data with a high-value as an information source for process improvement has also been accumulating on paper records. The result is a mountain of data of several different types scattered across several disparate data sources that can reveal a great deal about the sources of variability in the process and how to make significant improvements to process performance.
Until recently, once the FDA approved a product and the process to go with it, there was an over-reliance on QC to audit production and weed out defects. Stock outs, shortages, a rise in drug recalls deteriorating GMP inspection results have driven the FDA push for less dependence on QC and more reliance on Quality by Design. The need to build quality into the process is clear in the FDA’s recent Process Analytical Technology (PAT), Design Space and other risk reduction initiatives. The goal is “real-time quality assurance” wherever practical. This also makes good business sense – less variability in process outcomes means reduced costs and risks, improved supply chain predictability, and fewer, less intensive (and less costly) FDA inspections.
Some pharmaceutical manufacturers have rushed into the “real-time” aspect of PAT by acquiring new in-line, on-line and at-line measurements without first working with their existing data to understand what it tells them about the in-process parameters that drive process outcomes, i.e. the Critical Process Parameters or CPPs. Working with existing data first can drive significant improvements in the control of process variability without the costs and risks of jumping into new complex measurement technologies. It can also provide better guidance about where and what additional measurements may be needed so that the expense is justified and comparisons can readily be made to baseline performance.
A critical success factor for all process improvement initiatives including PAT, is easy, on-demand access by end users to all the data and data types in the operational data stores of manufacturing IT infrastructure systems so that multi-disciplinary teams can extract the information in context to understand cause-and-effect relationships. Thus, the software technology needed for PAT and other process improvement initiatives must allow immediate user-centric access to all the process development and manufacturing data sources and types so that their value can be leveraged in combination with data from newer (PAT) instruments. The data must be available immediately in the same working environment with investigational analytics, visualization and reporting capabilities that allow iterative exploration of correlations for collaborative multi-disciplinary teams of process development, manufacturing and quality users. This also applies to the data currently on paper records, which is often one of the single most valuable sources of data about how to reduce process variability.
Process Development:
To bring a new therapeutic to market, manufacturers must::
- Identify a molecule with a desirable therapeutic and safety profile
- Develop means of delivering the molecule to the site of action
- Develop a commercially viable process to make the molecule and its means of delivery,
- Demonstrate that the product is safe and efficacious for its intended use, and
- Demonstrate that each batch has, and will continue to have, the intended identity, potency, strength, quality and purity as required by the GMP regulations.
These five major requirements show the close relationship between the process, the product and the data. Process development, along with the data that supports process and product characterization, determines the exact chemical nature of the active ingredient and the spectrum of contaminants in the final product.
Process development plays a critical role in the success and timing of initial product launch by:
- Providing supplies of product for clinical trials
- Determining the feasibility of making commercial quantities of a stable, FDA-approvable product
- Successfully transferring the production technology to manufacturing operations ahead of competing products
- Provide the scientific basis for the CMC portion of the regulatory approval filing
With the release of the ICHQ8 guidance, regulatory bodies have signaled their willingness to accept post-approval changes to the manufacturing process without additional regulatory review provided that those changes are within the approved design space. This has given additional emphasis to the challenge and the opportunity of process development. The challenge is to develop a commercially viable and approvable process as quickly as possible so that time to value is not delayed. The opportunity is to establish at the same time a design space that allows for future changes to the process as may be needed for improvements to the quality, performance, scale or economics of the commercial process.
Given the reduced flow of new candidate molecules from discovery to commercial launch in recent years, competitive advantage is moving to those companies who are the best at process innovation and process development because these can bring their drugs to market faster and reduce the cost of later manufacturing operations. This helps mitigate some of the recent shrinkage in the effective period of patent-protected exclusivity in the marketplace (which now averages 11 to 12 years). Sustainable competitive advantage is now increasingly driven by how well the process development and manufacturing functions collaborate to supply clinical trials, comply with FDA regulations and meet aggressive deadlines for product launch.
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Manufacturing:
The new drug pipeline is increasingly comprised of biotech drugs for which the manufacturing processes are more complex than those of traditional pharmaceuticals. Furthermore, the patents are beginning to expire on biotech drugs, encouraging the rise of lower cost alternative “biogenerics” or “biosimilars.” Despite the apparent maturity of the biotech industry, understanding of the production processes of these complex products often lags significantly behind the understanding of their benefits to patients.
Biotech and bioprocess manufacturing depend on the use of living organisms or biological materials as the source of the active molecule. This is a significant source of inherent variability and requires sophisticated real-time control systems that collect very large volumes of continuous on-line or time-series data. The control systems and data historians that collect this data can provide profiles of these data while the batch is running as well as retrospectively. However, the traditional analysis methods they sometimes provide are not well suited for quantitative analysis of continuous data and the result is that its valuable information content often goes untapped.
To bring a new biotech drug to market, the team of scientists, process engineers, operations staff and quality professionals must overcome significant obstacles to achieve their goals. Although these same challenges also occur during the development of traditional chemical-based drugs, they are more severe for biotherapeutics because of their greater novelty, complexity and instability compared to traditional chemical entities. The production technologies for biotherapeutics are generally more complex than those for chemically based drug substances.
Process Development:
To bring a new therapeutic to market, manufacturers must::
- Identify a molecule with a desirable therapeutic and safety profile
- Develop means of delivering the molecule to the site of action
- Develop a commercially viable process to make the molecule and its means of delivery,
- Demonstrate that the product is safe and efficacious for its intended use, and
- Demonstrate that each batch has, and will continue to have, the intended identity, potency, strength, quality and purity as required by the GMP regulations.
These five major requirements show the close relationship between the process, the product and the data. Process development, along with the data that supports process and product characterization, determines the exact chemical nature of the active ingredient and the spectrum of contaminants in the final product.
Process development plays a critical role in the success and timing of initial product launch by:
- Providing supplies of product for clinical trials
- Determining the feasibility of making commercial quantities of a stable, FDA-approvable product
- Successfully transferring the production technology to manufacturing operations ahead of competing products
- Provide the scientific basis for the CMC portion of the regulatory approval filing
With the release of the ICHQ8 guidance, regulatory bodies have signaled their willingness to accept post-approval changes to the manufacturing process without additional regulatory review provided that those changes are within the approved design space. This has given additional emphasis to the challenge and the opportunity of process development. The challenge is to develop a commercially viable and approvable process as quickly as possible so that time to value is not delayed. The opportunity is to establish at the same time a design space that allows for future changes to the process as may be needed for improvements to the quality, performance, scale or economics of the commercial process.
Given the reduced flow of new candidate molecules from discovery to commercial launch in recent years, competitive advantage is moving to those companies who are the best at process innovation and process development because these can bring their drugs to market faster and reduce the cost of later manufacturing operations. This helps mitigate some of the recent shrinkage in the effective period of patent-protected exclusivity in the marketplace (which now averages 11 to 12 years). Sustainable competitive advantage is now increasingly driven by how well the process development and manufacturing functions collaborate to supply clinical trials, comply with FDA regulations and meet aggressive deadlines for product launch.
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Manufacturing:
Although medical device manufacturing was traditionally more like “discrete” manufacturing similar to the automotive industry, it is becoming more complex with the convergence of electronics, chemical and pharmaceutical technologies. This is exemplified by the increasing prevalence of various new coatings which may also contain active pharmaceutical ingredients and excipients. Medical device manufacturers must now:
- Become more adept at process manufacturing in parallel with discrete manufacturing,
- Account for more complex batch genealogies
- Implement new design, documentation, testing and control systems focused on finding and controlling the sources of variability in the process portion of manufacturing operations.
This has highlighted the increasing need for medical device manufacturers take steps to improve their understanding of the physics, chemistry and biology of their new processes so that these sources of process variability can be better controlled.
Process Development:
To bring a new device to market, manufacturers must::
- Identify a device with a desirable therapeutic and safety profile
- Develop a commercially viable process to make the device
- Demonstrate that the product is safe and efficacious for its intended use, and
- Demonstrate that each device has, and will continue to have, the intended propertiesrequired by the GMP regulations.
These five major requirements show the close relationship between the process, the product and the data. Process development, along with the data that supports process and product characterization, determines the safety and efficaciousness of the device.
Process development plays a critical role in the success and timing of initial product launch by:
- Providing supplies of product for clinical trials
- Determining the feasibility of making commercial quantities of a stable, FDA-approvable product
- Successfully transferring the production technology to manufacturing operations ahead of competing products
- Provide the scientific basis for the manufacturing portion the regulatory approval filing
With the release of the ICHQ8 guidance, regulatory bodies have signaled their willingness to accept post-approval changes to the manufacturing process without additional regulatory review provided that those changes are within the approved design space. This has given additional emphasis to the challenge and the opportunity of process development. The challenge is to develop a commercially viable and approvable process as quickly as possible so that time to value is not delayed. The opportunity is to establish at the same time a design space that allows for future changes to the process as may be needed for improvements to the quality, performance, scale or economics of the commercial process.
Given the reduced flow of new candidate devices from discovery to commercial launch in recent years, competitive advantage is moving to those companies who are the best at process innovation and process development because these can bring their devices to market faster and reduce the cost of later manufacturing operations. This helps mitigate some of the recent shrinkage in the effective period of patent-protected exclusivity in the marketplace (which now averages 11 to 12 years). Sustainable competitive advantage is now increasingly driven by how well the process development and manufacturing functions collaborate to supply clinical trials, comply with FDA regulations and meet aggressive deadlines for product launch.
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