Failure Mode and Effects Analysis (FMEA) is a core aspect of risk management and risk analysis in medical devices. FMEA is essentially about analyzing the reasons for which a problem arises and the effects it has on the system. In the field of medical devices, it is absolutely critical to understand the failure mode and effects because the consequences of not doing this can be disastrous and many times, even fatal.
Required, but not clear about the steps
The FDA only broadly states that risk management has to be built into the manufacturing process. This leaves medical device manufacturers in a kind of quandary, because although the FDA is clear about the requirement for risk management; there is no clear-cut guideline on how this needs to be carried out. This leaves the implementation of FMEA in medical devices something that is at the discretion of the medical device company.
The FDA’s Final Rule on cGMP Quality System Regulation (QSR) is, to quote its own words, “less prescriptive and gives the manufacturer the flexibility to determine the controls that are necessary to be commensurate with risk” (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/QualitySystemsRegulations/ucm230127.htm). In other words, there is no specific guideline on risk management, using which medical device manufacturers can decide the ways and processes of implementing risk management. The guideline is all the more vague about risk analysis approaches and procedures like FMEA.
Complementarity with ISO 14971Since the guidelines on medical devices FMEA are rather general medical device companies that implement FMEA have to go by a buzzword: implementing FMEA at every level. In this regard, they can work complementarily with ISO 14971, whose guidelines relate to risk management.
Organizations in any industry involving process control have to implement advanced process control mechanisms for maximizing return on investment (ROI). Maximization of ROI being a very important objective of any industry involving plant management; the key to realizing this is putting the right regulatory process control in place. No external activity, such as buying the most sophisticated control equipment or loading systems with the most advanced software is going to be of any use unless the organization gets its regulatory process control right.
An understanding of regulatory process control
Regulatory process control is the means of monitoring and controlling the process of metamorphosing raw materials and other inputs into final products. Since there is no clearly laid out, authoritative regulation concerning process control in the generalized sense; organizations have to rely on established best practices and principles to arrive at optimal regulatory process control. There is the existence of the proportional-integral-derivative controller (PID controller), but this is more a mechanism than a standard.
So, meeting stringent quality standards involves the application of many highly scientific and precise steps and processes. It involves the use of tightly controlled techniques, into which a hierarchy of well-defined functions and responsibilities consisting of people, facilities and systems has to be instilled from management.
The basis to all this, as we have seen, has to be a regulatory process control system in which people and systems harmonize their functions.
General principles for regulatory process controlAn organization needs to put in a user-ready systems infrastructure which personnel having the requisite qualifications and experience should be able to start using straightway. A faulty or inaccurate regulatory process control mechanism or strategy will impede this, leading to suboptimal control.
The same principles of regulatory process control apply to control system testing as well. This is a process in which the organization uses established documentation techniques to record data relating to problems that could occur at any stage of the regulatory process control.
Types of regulatory process controls
Two kinds of controls are often cited in regulatory process control: feedback and feedforward. These are usually implemented in tandem. In short, feedback control is the regulatory process control that is configured for control schemes such as the ratio, selective, cascade, and certain other kinds of control schemes, all of which are related to a common reference point called the setpoint. Any deviation from the setpoint should lead to remedial action by the person in charge of system control.
On the other hand, feedforward regulatory process control is a preventive step in which a load disturbance is measured and a corrective measure of dynamically compensating the disturbance is implemented beforehand.
Purpose of regulatory process controlThe essential role of regulatory process control is to bring down any unacceptable variability in the control system that is subject to changing and often, volatile conditions. In the absence of an effective regulatory control system; each succeeding operation unit has the potential to cause an amount of variation, however small or big, which can pile up throughout the process to eventually impact the quality and cost of the product. Regulatory process control aims to address this by introducing analytical and corrective measures at every stage of the control process.
Lyophilization is the clinical term for freeze-drying. In the simplest terms, it can be described as a technical process in which the moisture level of many materials is reduced, most times frozen, for the purpose of creating a new product or an ingredient.
When an injectable drug is freeze-dried -this is the process of lyophilization -its compounds are stabilized. This reconstitution process is helpful and necessary because substances in the drug get affected by outside or natural factors such as sunlight, oxygen, and pH values. These influences can bring down the effectiveness of these materials and molecules. It is to help them weather these countering factors that lyophilization is used. The aim of lyophilization is to make the best use of these compounds by preserving and protecting them in the form that can be used on patients.
Lyophilization not only shields the product from unwanted biological activity; it also extends shelf life, and can bring about greater precision in the dosage. This reconstitution is done just before administration.
Where is lyophilization technology applied?
Lyophilization technology is used in a number of applications. The most prominent ones that use lyophilization include biotech drugs, as well as a few complex or very sensitive molecules.
Many industries are in a state of flux, in that new technological keep coming up every now and then. Lyophilization should keep abreast of these technologies and help businesses in these industries to innovate their products to meet the market needs.
Is lyophilization a new process?
No. It may surprise many that its roots can be located to more than a millennium, to ninth-century Asia! However, it has regained some prominence of late, with the rise in the use of compounds, chemicals, molecules and other related substances in our daily lives. Today, nearly a third of products in the parenteral segment that come to the FDA for approvals are for lyophilized drugs. Market watchers speculate that in the very near future; this proportion to set to go up to 50 percent.
Characteristics of lyophilization
- Products that are lyophilized can be expected to maintain their stability for 2 to 3 years in ideal conditions
- Lyophilization calls for a high degree of expertise on the part of the manufacturer, since these drugs are derived out of formulations that are very complex
- Labs form lyophilization cycles that help in optimizing its efficacy. They seek a reduction in the residual moisture, which is something that has to be done for every product. This process usually begins at a product’s clinical development stage and gets finessed at the time of commercial manufacture.