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Pharmaceutical Manufacturing and Packing Sourcer

Total Recall


The acceleration of quality control in pharmaceutical manufacturing can be achieved through prominent innovations in testing that have recently come to light. Pharmaceutical manufacturing has a problem: high profile shortages and record recalls are making headline news. Lack of regulatory oversight for overseas production and the extended supply chain for raw materials have resulted in less than trustworthy ingredients that can vary dramatically in their critical quality attributes. Combining variable raw material quality with rigid validated production procedures results in unpredictable finished product quality.

Shifting manufacturing economic dynamics has increased outsourcing and caused a reduction in the number of technical support staff that are available to address root technology and quality issues. What worked well 10 years ago is not working well today and the media, politicians and consumers are becoming increasingly aware of the issues. The single largest FDA identified cause of shortages and recalls is the inadequacy of testing methods to detect the problem.

Case in Point

In 2008 Baxter International had a high profile recall involving a raw material contaminated deliberately with a common health food supplement. This contamination was possibly designed to increase the profit of the material being sold to Baxter while being undetected by Baxter’s quality control tests employed at the time. Baxter thus passed on to the consumer the contaminated material and the result was that several hundred people were injured or died.

The situation serves to portend things to come and unfortunately much has already come to pass. In the last three years recalls have been at record highs as plants are coming under consent decrees and shortages now hit the news with increasing frequency. Whether a product is unavailable or of bad quality, both can have disastrous effects on human health.

The Root of the Problem

The problem’s source is manifold, including:

  • An extended unsecure supply chain
  • A lack of regulatory scrutiny of foreign production
  • Outdated quality testing programmes
  • A reduction in technical headcount at manufacturing sites to troubleshoot problem issues
  • Counterfeit economics
  • Internet purchasing trends
  • Rigid regulatory paradigms

Can we reverse the trend of outsourcing and overseas production? Not likely. Some amount of manufacturing will always move toward lower wage areas, and this trend can only be reversed if the costs outweigh the benefits. The extended supply chain has given rise to increased opportunities for deliberate and accidental contamination of raw materials, as well as introduction of materials not suitable for pharmaceutical use. Unless the source problem is addressed, the only solution becomes a means of identifying the problem before it becomes a liability to the pharmaceutical manufacturer. Some rethinking about accelerating quality testing can have a big impact on this problem.

Today’s pharmaceutical manufacturing site relies heavily on laboratory testing methods. Many of these methods are codified in pharmacopoeia testing chapters. Most require controlled laboratory conditions, sample preparation skill, and analysts with the technical training to interpret the results properly. The vast majority of pharmaceutical quality testing is performed in a location other than where the manufacturing is performed and therefore typically after the production has been finished. This is known as ‘producing at risk’; if a quality problem exists, it is too late to affect a bad lot. One alternative is to delay the different stages of production until testing is complete, extending manufacturing lead times. The real goal should be moving the testing from the lab to the manufacturing line to facilitate instantaneous feedback of quality.

PAT Headache

The FDA has been keenly aware of reducing manufacturing risk for more than a decade, and issued its guidelines for pharmaceutical manufacturing for the 21st century some 12 years ago. Yet the process analytical technology (PAT) initiative has fallen on hard times. Testing systems that require an elaborate setup of intricate models and lack robustness for manufacturing suites have in fact led to a perception that PAT is too costly and time consuming to implement. As Big Pharma has consolidated and its manufacturing arms have begun to compete with generic alternatives, one of the first casualties of lean initiatives has been internal PAT groups. The big-win applications have been implemented, but the vast majority of the small-win applications lay fallow due to a lack of time and a failure to understand what the financial return could be. PAT is now a label that is more likely to kill a project than produce funding.

Part of the PAT problem has been the lack of easy-to-apply tools. Instrumentation is a mature and consolidating industry where innovation is an acquisition target, not a development activity. The vast majority of instruments used in pharmaceutical testing are lab-based. For instruments to be truly usable in a manufacturing suite, they must be:

  • Hardened to the environment, such as being waterproof for suite wash down. However it is difficult and expensive to make laboratory tools waterproof
  • Easy to use, providing the right interface to the right person at the right time. Not all users should have access to administrative rights or be able to calibrate the instrument
  • Customisable for GUI to fit into the proper workflow and in the native language. The fewest number of user actions needed to get an answer is also a goal
  • Provide information, versus data, in fast paced manufacturing environments that lack chemists and spectroscopists. Allowing manufacturing suite workers to get ‘thumbs up’ or ‘thumbs down’ indicators without having to look at a chromatogram or spectrum is critical. Instruments that can make decisions have huge benefits over traditional data generation boxes
  • Flexible, so that at the same time a technically proficient analyst can review detailed raw data and decision rules
  • Easily tuneable for selectivity and sensitivity of the information given. When it comes to analytical goals, not all problems are equally risky. For instance, variance in raw material quality of an excipient may pose a lower risk than that of an active ingredient
  • Quick to install and begin using. In today’s tough business climate, setup and validation must be a simple process and accomplished in a business quarter

Conclusion

If the extended supply chain risks are not addressed at their source, pharmaceutical companies should seek to reduce the risks of manufacturing by employing better at line and inline testing devices. Rapid screening tools appropriate for use in pharmaceutical manufacturing are needed to reduce the number of recalls and shortages. The best time to consider the problem is before it happens. New instruments that are designed by the manufacturing technician for use in the manufacturing environment, are desperately needed to address the high profile business problem that exists today.




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Todd Blonshine is CEO of Mustard Tree Instruments. He holds a BSc in Chemistry from Mercer University and spent several years performing biochemical and environmental research before entering the commercial instrumentation industry. Over the next two decades he accrued experience with laboratory, process and field-deployed scientific instrumentation, holding positions as a field based applications chemist, before moving on to global management within both start-ups and NYSE-listed conglomerates.
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