Streamlining the Pharmaceutical Manufacturing Cycle: How Contract Manufacturers Can Benefit from Rapid Microbial Methods (RMMs)

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Streamlining the Pharmaceutical Manufacturing Cycle: How Contract Manufacturers Can Benefit from Rapid Microbial Methods (RMMs)

May 2012

PMPS magazine

View a PDF version of this article or view the article on the PMPS site.

Pharmaceutical contract manufacturers can benefit from streamlining their manufacturing cycle with rapid microbial methods (RMMs), which can reduce turnaround time and boost their competitive edge.

Any advantage that is easy for competition to match is not going to remain an advantage for long. That is why price-cutting rarely works as a competitive strategy. Prices can be matched or undercut by pennies and bidding wars commence. The key to non-price competition is to differentiate the business with something that is difficult for others to follow. 
 
In some industries it is possible, even desirable, to differentiate on quality. Consider a bespoke garment with its straight seams, fine stitching and hand-sewn finishes. Yet quality is not as useful a differentiator for contract manufacturers, since clients have an expectation of quality in the pharmaceutical industry. If a manufacturer does not follow regulatory guidelines, a product will not make it to market. So quality becomes something a Contract Manufacturer must have in order to compete.
 
Faster turnaround time can be a strong competitive advantage to a Contract Manufacturer. It is measurable in hours, days or weeks, and its benefits are clear. When products can be produced and delivered faster, customers can be more responsive to market needs. In addition to this there are other advantages, including; shorter production cycles, days' worth of inventory freed up, less warehousing space and a shortened cash cycle. 
 
As well as securing a competitive advantage that is not within the reach of the competition.
 
Faster Turnaround Options
 
Adding capacity and increasing efficiency are two basic ways to shorten overall turnaround time. 
 
Adding capacity to decrease turnaround time can be accomplished in several ways. If orders typically sit around waiting for their turn in formulation, filling or packaging, then it may be time to expand. Investment in high-speed production lines or a second or third shift is another way to add capacity, as more products can be produced in 24 hours with the same equipment. 
 
However, take a closer look at the manufacturing process. Just because manufacturing is faster, it does not mean products can be released faster. This may just simply create the need for additional warehousing space.
 
In many Contract Manufacturing facilities, the limiting step for faster turnaround time comes from the time it takes to get the results from microbial testing.
 
RMMs vs Traditional Methods of Testing
 
Pharmaceutical companies using traditional methods of testing usually wait 3-7 days for microbial limits results and 14 days or more for the results of sterile product testing. With the traditional method, a product sample is added to a growth medium or agar and incubated for multiple days to encourage the growth of any microorganisms that might be present. During this time, incubated samples are individually monitored for visual - and often very subjective - indicators of microbial growth. For most pharmaceutical companies, 98-99% of the time, samples will be free of microbial contamination. A rapid test that provides a positive or negative result quickly is therefore ideal for the vast majority of products. However, with traditional methods it is not until the end of the incubation period, after a significant amount of time and materials have been used, that the absence of contamination be confirmed. 
 
 
Fig. 1. For products that are expected to be clean, an absence/presence test provides actionable information to get products to distribution faster
 
It is not difficult to detect organisms in grossly contaminated products. What can be difficult and time consuming, however, is detecting very small numbers of microorganisms in materials and products that are expected to be free of contaminants. With traditional methods, a lot of time is spent waiting to confirm that nothing is growing.
 
In contrast, rapid methods are as effective as traditional microbiological methods, but they are faster. While it is often easy to detect gross contamination in a few short hours, the key to supply chain efficiency is confirming the absence of microbial contaminants. Today’s rapid detection systems can provide definitive results, both positive and negative, within 24 hours. RMM test results can be recorded objectively and presented in clear, colour-coded tables and graphics. This helps with interpretation of the results, so no “judgment calls” are needed. Also laboratory technicians are freed up to work on other, more valuable projects.
 
The Benefits for Contract Manufacturers
 
Almost any Contract Manufacturer can use rapid methods, but the system choice will impact the economic benefit of implementing one. A contract manufacturer should identify a system that has the testing capacity to keep up with full-scale operations. Also, if the RMM only works on one type of material, such as water, it will be less useful than a more flexible system that can test viscous or heavily pigmented samples as well. As important, the system should provide fast, definitive information about the product status so that they can be shipped to market safely.
 
RMMs allow contract manufacturers to:
 
- React faster to clients’ changing needs
- Recover from contamination events faster
- Use less energy & water; reduce waste 
- Reduce inventory & safety stock requirements
 
As well as creating a competitive advantage for business, a new RMM service may also help Contract Manufacturers attract new customers. An emerging factor is that the largest consumer health product companies in the world already use RMMs and they are starting to ask their Contract Manufacturers to test their products using this method. This helps the brand owners ensure consistency and be more responsive to market changes with a shorter production cycle. It is part of a larger effort by leading consumer product companies to harmonise their manufacturing and testing worldwide.
 
Tools are also available to help Contract Manufacturers explain the benefits of rapid screening to their clients who do not already use RMMs. 
 
Validation and Regulatory Support
 
Many thousands of products have been successfully validated around the world with RMM systems, and likely include products already being produced by many Contract Manufacturers. Use a RMM supplier who offers validation support to help get the system up and running quickly. 
 
Transitioning pharmaceutical release testing to a rapid method is supported by many regulatory bodies around the world. It is important to find a RMM provider who also has regulatory compliance expertise and can provide assistance and additional resources such as white papers and validation guides.
 
The Financial Rewards 
 
RMM systems not only offer faster results, which get clients’ products to market faster, they can also provide financial rewards, while meeting global quality and regulatory standards.
 
Contract Manufacturers can benefit from the following financial rewards after implementing a RMM:
 
- Shortened cash cycle. Finish client products faster, invoice faster and get paid faster. Produce more of the customers’ products in the same time, or take on additional work: all by freeing up capacity in the system. 
 
- Reduced warehouse requirements. Traditional testing methods require sufficient warehouse space to quarantine 3-7 days’ worth of production. RMMs provide results in 18-24 hours, freeing up several days’ worth of valuable space.
 
- Contamination cost containment. The sooner a contamination event is identified, the less it costs in terms of scrap, cleanup, rework, customer relations and lost time. 
Fig. 2. The benefits of a RMM are made clear in this simplified contamination event timeline
 
Quantifying the Economic Value
 
Some of the largest and most successful companies in the pharmaceutical industry benefit from the efficiencies offered by a RMM system. However, because RMMs are considered a competitive advantage this has not been widely publicised. For example, the company discussed below implemented a RMM system in 1996 and now uses the technology worldwide.
 
The company, a manufacturer of pharmaceutical products, was experiencing issues with inventory and periodic in-house contamination events. They were using traditional microbiological methods for screening raw materials and finished goods with a 5-day hold at each step. The value of their daily finished goods production at the time was roughly €75,000.00.
 
They completed a Financial Impact Assessment to demonstrate to corporate management the value to the company of implementing a RMM.  
 
Easily available information including the value of daily finished goods, the reduction in micro-hold days, the frequency of contamination events, instrumentation and reagent investments, was keyed into the Impact Assessment. The model calculated a five-year net present value (NPV) of over €677,000.00, payback of less than 9 months and savings relating to more rapid containment of contamination annualised at €64,000.00 per year.
 
Projecting these savings over the company’s five facilities with an 18-month roll-out programme, increased the 5 year NPV to almost €2.5 million with a payback of just 15 months. The later rollouts were financed through the working capital efficiencies generated from the earlier placements. Annualised contamination savings alone rose to almost half a million Euros.
 
The Impact Report (Fig. 3, below) provides a graph that identifies the typical economic impact by six-month periods along with cumulative discounted cash flow for a single plant.
 
Fig. 3. The Financial Impact Assessment Identifies the Economic Results of Implementing a RMM
 
The cost of the rapid system is shown in red. The initial outflow represents the initial investment in the instrument, followed by the implementation period and the ongoing cost of reagents.  
 
Above the line, in blue, is the positive impact of the reduction in working capital requirements driven by the reduction in inventory held in quarantine and safety stock. This includes the initial release of inventory during the implementation period and the ongoing value of redeploying that money into productive investments.  
 
At the top of each bar, in green, are the savings from the reduced impact of contamination events. In many cases, these savings pay for the programme on their own - the green bars are larger than the red bars in each period. 
 
In addition, the company was able to introduce some in-process testing at a critical point in production to detect contamination even earlier and to further reduce the potential impact of a contamination event. Their total micro-hold was reduced from 10 days to only 3 days, and was redistributed to better manage risk as it occurs in their operation.
 
Contract Manufacturers can accurately predict the value of adopting a RMM by completing a Financial and Environmental Impact Assessment. A “green” component is also available with calculated savings in energy and water consumption as well as measurable reductions in solid, liquid and/or hazardous waste disposal. The Environmental Impact Report is yet another way to differentiate Contract Manufacturers from their competition.
 
Summary
 
RMMs create a sustainable, competitive advantage for Contract Manufacturers by screening raw materials, work in process, and finished goods for contamination in less than half the time of traditional testing methods.
 
 
Fig 4. The Celsis AdvanceTM Rapid Detection System for the Pharmaceutical Industry

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