A guide to pharmaceutical trends
Current trends in pharmaceutical manufacturing lean towards advancing the industry through automation and data exchange, with the help of new and emerging technologies.
This movement is known as Pharma 4.0, since it incorporates key concepts of Industry 4.0. However, the nature of the pharmaceutical industry means that rather than focusing purely on productivity and commercial benefits, Pharma 4.0 also has an emphasis on meeting regulation, enhancing data integrity, and supporting decision making.
Here are some ways in which technology is changing pharmaceutical manufacturing.
Digitalisation of data
As an industry, we utilise copious amounts of information and data. As regulatory pressures increase, so does the number of records we must keep to demonstrate compliance.
Many of these records have historically been made on paper, to then be re-transcribed to a system such as Excel for storage and analysis. Duplication of data not only harms your productivity, but introduces significant data integrity challenges, since paper records can easily be lost, damaged or illegible.
More facilities are therefore turning to digital solutions, to gain confidence in data whilst taking advantage of the tools on offer that can help them gain insight.
Let’s look at environmental monitoring teams as an example, since they often use significant volumes of paper, from recording procedures and results, to logging actions and generating batch records.
Dedicated digital solutions such as SmartControl EM allow analysts to enter data directly into the system. This reduces the amount of paper necessary in the lab, whilst ensuring compliance with ALCOA+ principles. No transcription is required from paper to databases, meaning that records can be made contemporaneously and accurately, in a legible, original and attributable way with full audit trails, ensuring that it is stored in a consistent, accessible, enduring format.
Digitalising your data will also transform the way you trend and analyse data. Using spreadsheets makes these tasks time consuming and involves the movement of data from one database to another. Picking out trends is another challenge, due to the sheer volume of data collected. Adverse or emerging trends in your EM data can indicate a loss of control, and if detected early enough, could prevent further issues.
SmartControl EM overcomes this, as all data is stored in one place ready to be pulled into easy-to-understand graphs and reports at the click of a button. With no delays for re-transcription, plus instant notification of limit and trend breaches, you can investigate faster and more thoroughly.
Identification of organisms
When Microbiologists identify isolates, they use the results to form impact assessments and root cause analysis of environmental monitoring or product contamination issues.
Accurate species level identification is required to maintain regulation, but also because the organism type can give detail about the source of contamination. Therefore, speed is also important, as the results could be the difference between continuing manufacture or discarding the batch.
Legacy methods such as API identification can make it difficult to get a valid result – not to mention it’s expensive and time consuming. However, MALDI-TOF (matrix-assisted laser desorption/ionisation time-of-flight), a powerful mass spectrometry technique, is able to quickly turn around accurate results in an economic way.
Strain sequencing is another identification method that has further developed in recent years. It’s important, as it can be used to show similarities and differences between isolates of the same species. If there are differences, you may consider that there is more than one source of contamination.
Previously, strain sequencing was expensive and time consuming. However, next generation sequencing methods are able to give same day results at a lower cost. In turn, you can react faster.
One of the most time-consuming activities in a Microbiology lab is colony counting. Not only does manual counting impact your productivity, but a high level of variability between people – or even the same operator depending on factors such as the time of day – opens your facility to data integrity issues.
Particularly in facilities with a high throughput, colony counting technology may be used as a first or second check. By automating an otherwise error-prone process, accurate results are ensured each time.
Currently, there are a wide range of colony counters on the market. However, a challenge with current technology is that classical computer vision can struggle to accurately count complex plates – such as environmental monitoring samples.
To overcome this, Microgenetics have developed a next generation colony counter, that uses cutting-edge Machine Learning technology to process even the most complex plates. Able to integrate with any software you may use in your lab such as a LIMS or Microgenetics own EMS, SmartControl EM, SmartControl Colony Counter can help you by:
- Ensuring repeatable results
- Removing subjectivity
- Saving you time
- Helping you to meet regulation
A pillar of Industry 4.0, automation is of growing importance – particularly in labs with a high throughput. Automation can reduce workloads, minimise contamination risks, improve efficiency and boost your data integrity.
Automation of colony counting is also supported using automated loading of the counter, such as with the Microgenetics plate handler. These robots allow users to process numerous plates at the same time. All that’s required is to stack the plates in the robot and walk away, giving you time to perform other tasks whilst your plates are being counted.
Endotoxin testing has also been automated. The time to prepare standards and samples can be long, is prone to human error and can lead to a lack of confidence in your results. By automating these preparation steps, the process can be streamlined, and risk of endotoxin contamination reduced.
A final automation you may be familiar with is for the incubation, transferral, and removal of plates. It’s too easy for Analysts to miss plates when manually incubating and moving plates. Automation of this process allows Analysts to scan samples as they come in, to be tracked. This removes issues when moving samples, plus reduces paperwork where information can be stored on software. The incubator itself can also be programmed; for example, if temperature changes are required during incubation, this can be set in advance.
The Annex 1 draft highlights that the greatest source of contamination in a facility is the operators – especially when entering and leaving the production area. Additionally, personnel may fatigue easily and quickly – especially considering the lengthy gowning processes required to enter the facility.
As a result, facilities looking to upgrade should consider which processes can be carried out without human intervention. An example of where this has been done is using automated filling lines. However, as these automations get older, constant maintenance is required. The downtime to fix current technology could arguably be better used to install fully automated units.
This “lights out production” movement has been suggested by many experts. It would not just substantially reduce contamination but increase the output of facilities many times over. Hundreds of vials can be filled per minute with precision and sterility that cannot be replicated by humans.
Of course, operators would still be required to ensure machines are working as they should. However, the number of personnel needed to enter environments, as well as the volume of intervention events, would be reduced.
As well as automated filling lines, Manufacturers are implementing barrier systems and isolators into facilities. These systems prevent operators from entering aseptic filling areas and contacting the product, again, minimising contamination risk.
With more new products entering the market with shorter shelf lives, the ability to identify contamination quickly is essential. Most facilities use traditional tests that take around 14 days to show results. In products with a short shelf life, the medicine could be administered to patients without confirmation of its sterility, risking patient safety and cost.
Microbiologists now have access to many rapid microbiological methods (RMMs). Rapid identification methods are available with next generation sequencing, reducing the amount of time to produce a result in the lab. Technology is also being used in production facilities to identify contamination quickly. In turn, root causes can be identified faster, as well as corrective action.
Some facilities are now also using processes allowing for the continuous monitoring of bioburden. These methods use fluorescence to detect the level of bioburden in a sample, providing further confidence in contamination levels. This testing can be applied to fermenters and growth mediums, eliminating requirement of manual sampling. As a result, you can use less consumables, have less interventions, and minimise risk further.
If contamination is detected earlier in the process, facilities don’t have to wait until a whole batch has been processed before discarding a batch and can identify excursions in real time. Several companies are developing sterility tests to identify contamination quicker than the 14-day turnaround of traditional methods. These tests can provide results in just 5-7 days.
However, Microgenetics are developing their SwiftDetect rapid test that test down to just a single cell of contamination in any given sample volume, within 6 hours. Manufacturers will therefore be able to release products with much higher confidence that there is no contamination in samples.
When pharma facilities introduce new technology, significant amounts of validation are required. Guidance often requires proof of equivalence to current methods, adding to the challenge of introducing new tech. As a result, it’s usually a lengthy process leading to a reluctance of facilities to introduce new tech. This is yet another area in which Microgenetics are setting the benchmark.
By providing robust in-house validation before release, Microgenetics aim to minimise customer validation. Our environmental monitoring software, SmartControl EM, is hosted on the cloud to allow our own testing and documentation to be used upon introduction and upgrade of the software.
Being cloud based means more input from the supplier, so less resource is required from the customer. For the implementation of SmartControl EM, Microgenetics can provide functional specs and OQ documentation, leaving just URS, PQ, planning and reporting for the customer. This significantly speeds up the process, so SmartControl EM can be up and running in just 6 weeks.
With regulatory bodies now looking to facilitate and encourage the use of new technologies, implementation is likely to continue to get easier in future.
The landscape of pharmaceutical technology is ever evolving, so what can we expect in the future?
Virtual Reality headsets are already being used to train operators. However, some companies are considering the use of this technology for virtual interventions, where operators can interact with machines from outside of the facility. This could reduce contamination risk.
AI is also being implemented across industries, using automated algorithms to perform tasks that traditionally rely on human intelligence. We’ve already mentioned SmartControl Colony Counter by Microgenetics, that uses AI to accurately count colonies and learn the difference between colonies and background noise. However, the technology could also be used for simulations and modelling as part of the drug discovery process, or to streamline processes in manufacturing and QC.
Finally, we’ve already mentioned the concept of “lights out production”. In reality, Operators will always be needed in such a strictly regulated industry; however, as validation of technology simplifies and regulation further tightens, we anticipate that the industry will move further towards this fully automated approach.
- Pharma 4.0 incorporates key concepts of Industry 4.0, such as automation. However, rather than focusing purely on productivity and commercial benefits. Pharma 4.0 also has an emphasis on meeting regulation, enhancing data integrity, and supporting decision making
- A variety of solutions are out there to help facilities benefit from technological advances. For example, automated colony counters
- Regulatory bodies are likely to encourage new technologies in the future. As uptake increases, validation should become easier
- In the meantime, Microgenetics is leading the way in simple validation, through cloud-based technologies
Learn more about Microgenetics technology