SubscribePAT means "Process Analytical Technology" and was launched as a FDA initiative in 2002. PAT is a system for better understanding and control of the pharmaceutical production processes.
The initiative
FDA’s vision is risk based monitoring of processes, e.g. by intelligent sensors in closed loops, and GMP compliant documented control routines including real time release.
The initiative is part of FDA activities for drug quality increase in this decade (“A Risk-Based Approach to Pharmaceutical Current Good Manufacturing Practices (cGMP) for the 21st Century”, September 2002).
The final FDA guidance “PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance” issued on September 2004 describes a new approach of pharmaceutical production and quality control.
Most important for PAT implementation is process understanding and efficient control of the pharmaceutical production process. The pharmaceutical industry has grown increasingly intrigued with the promise of Process Analytical Technology.
Industry is encouraged achieving higher levels of drug quality, regulatory assurance, and manufacturing efficiency.
PAT is defined as a system for designing, analyzing, and controlling manufacturing processes through timely measurements of critical quality and performance attributes of raw and in-process materials with the goal of ensuring final product quality.
FDA’s organisational basis for PAT promotion and support consists of PAT Subcommittee, Steering Committee, several PAT Inspection Teams as well as PAT Research Team and the Policy Development Office.
A classical PAT approach is firstly to analyse the processes in manufacturing. The identification of critical control points and critical to quality attributes is prerequisite. PAT tools such as innovative analysers or sensors have to explored.
The second step is to develop appropriate statistical methods for process capability calculation, calibration models or design of experiments (DoE). The impact of different parameters can be calculated on statistical basis and have to be shown in experimental studies.
Once the impact of input variables and control parameters has been determined, analytical instrumentation, data management and process specifications should be chosen. If possible, in- and on-line process controls shall be implemented. At-line testing is not the best way of checking quality attributes, but is better than sampling and off-line testing in a laboratory.
The last step is to develop robust manufacturing processes, which are monitored and controlled under routine conditions by intelligent sensors, assessed by (often) statistical calculations and released by trained personnel such as qualified persons dealing with production, quality and regulatory concerns.
Introducing a PAT philosophy into a companies corporate culture would mean a change of the management system with the need of measuring the capability of any process. The final benefit is the highest quality that reaches near perfection.
The integration of the new PAT guidance in the world of machine supplier and the pharmaceutical industries will be step by step. It’s a developing process of understanding, acceptance and realisation.
Quality today
"Documented"
- test 30 tablets of 1 batch
- final product quality
dissolution, content uniformity, impurities, hardness
detection of failures: depends - process information: none
- facilitating process understanding: no
PAT step 1
"Novel technology"
- test every tablet
- final product quality focused
- no root cause analysis
- detection of variability
- process information: none
- facilitating process understanding: no
PAT step 2
"Quality by design"
- Process attributes
- critical to quality
parameters by experimental design - analyse: appropriate
- control: feed-forward / feed backward with real-time control tools to adjust process
Process security and high efficiency in encapsulation are constant topics of conversation at capsule filler supplier. New Process Analytical Technology (PAT) solutions, which are an FDA initiative, are also helping in the development of new technology in these areas.
In the development of capsule filling and checkweigher machinery, machine designer constantly work on improvements concerning the quality of the encapsulation process and the analysis of process-critical parameters. Results are immediately realized on such machines. The most recent example is PAT.
The primary aim: understanding and controlling the process
Manufacturer`s strategy is to avoid quality-relevant influences wherever possible. If this is not possible, sources of faults must be identified and eliminated. To ensure the quality and release of the end product, relevant parameters are monitored and controlled.
Avoidance: preliminary sorting of empty capsules offers the opportunity to remove poor quality capsules before they reach the filling process.
Downtimes are therefore minimized and a high degree of efficiency achieved. Compressed air and vacuum-monitoring units constantly check the required operating pressure to stop the machine before any malfunctions can arise in the production process.
Identification and elimination: Some capsule fillers have functions of automatic fault elimination, faults are quickly identified and effectively eliminated.
E.g. blockages in the capsule-infeed system or repeated instances of defective capsules are detected. Deformed capsules are then targeted and removed by air. In the closing process, incomplete capsules are identified, removed separately and do not advance to the next process.
Closed Loop Control
The real thought of PAT is to detect faults of the process and to solve these in a closed loop. An example is weight feedback to the filling station. The weight of the capsule is accurately calculated using the capsule checkweigher. If the weight should drift, the amount of powder placed in the capsules is automatically reduced or increased by the capsule filler.
Monitor and control
In addition to the filling weight, the accurate strength is an important attribute for the product release. Spectroscopy is used for measurements on this machine. The recorded quality data allows the immediate batch release.
The new PAT solutions contribute to a better product and improve process quality and efficiency. The immediate product release shortens the cycle time and increases the efficiency.
All expenditures to realise the though of PAT has the target and the gain to have customer benefits and improvements of product quality!
Benefits by using PAT tools for encapsulation processes:
- Increased final drug and right first time quality
- Reduced risks by efficient risk management
- Reduced cycle times and minimized production cost
- Quality system built-in by decision
- Growing process knowledge & understanding
Summary:
PAT goals: Increasing quality of drugs by…
- understanding & controlling the manufacturing process
- managing risks
- getting rid of variability
Possible benefits for pharmaceutical industry:
- improving efficiency & reducing costs
- higher quality by real time quality assurance
- time-to-market by real time release
- better process understanding by monitoring of critical attributes
- facilitating innovation & optimisation