Ranica Arrowsmith, Associate Editor09.10.13
Process validation conducted in the “proper” way, with painstaking documentation of each manufacturing step, detailed master control documents, statistical process control (SPC) documentation, and comprehensive historical data, easily starts to seem like overkill. However, if as a manufacturer you don’t validate your process, you inevitably will end up with an unreliable product. And as Andrew Thomas, director of operations at Upper Saddle River, N.J.-based contract manufacturing services provider Triangle Manufacturing Company Inc., said, “[The medical device industry] is a serious business—the things that we make go inside peoples’ bodies, and we take that very seriously.”
There certainly are mandatory requirements surrounding process validation for contract manufacturing organizations (CMOs) in the medtech space as laid out by the Global Harmonization Task Force’s guidance document on “the Controls of Products and Services Obtained from Suppliers,” published in December 2008. Not every manufacturing process requires validation, as some devices easily can be tested at the end stage of production to ensure quality. However, there are some processes that require process validation due to the product’s inherent nature. For instance, plastic injection molding requires process validation because a plastic component cannot simply be visually inspected for quality. Wall thickness and density cannot be tested non-destructively—that is, without destroying the product. Similarly, in sterilization procedures, absolute sterility cannot be proven without compromising the sterility of the product.
“For example, with laser welding, there’s no way to look at a weld and see that the weld is strong,” said Dana Schramm, vice president of engineering at Donatelle, a CMO based in New Brighton, Minn. “The reason they separate injection molding out and say it has to be process-validated is because we could mold two parts that look and measure identical, but one of them could be more dense than another and therefore have a different strength property. One could have voids that can’t be seen because the part isn’t transparent. So with the molding process, you can’t just inspect a part and say ‘yeah, this looks good.’ We would either go through process validation and supply our customer with parts, or we would test the parts —subject them to design verification testing. A lot of times that involves not only assembling the parts but doing some mechanical testing on them and verifying that even when manufactured at the validated process limits, the intended performance of the part is not adversely affected.”
Process validation ensures that a manufacturing process for any device or component will run reliably, continuously producing parts to the specifications required by the original equipment manufacturer customer that commissioned the product. The U.S. Food and Drug Administration (FDA) does have documents and guidances available to device manufacturers, to which many quality assurance and validation engineers refer for updates and new insights into validation processes. In the current version of the process validations section of the agency’s Medical Device Quality Systems Manual, the FDA outlines why a company would validate their processes:
“Through careful design of the device and packaging, careful design and validation of processes, and process controls, that there is a high probability that all manufactured units will meet specifications and have uniform quality,” the FDA document reads. “The dependence on intensive in-process and finished device testing can be reduced. However, in-process and finished product testing still play an important role in assuring that products meet specifications. A properly validated and controlled process will yield little scrap or rework, resulting in increased output. Consistent conformance to specifications is likely to result in fewer complaints and recalls. Also, when needed, the validation files contain data to support improvements in the process or the development of the next generation of the process.”
There are two main types of process validation: prospective and retrospective. Prospective validation is conducted before a product is released for distribution, and the process is begun right at the beginning of the conception of the product. Validation teams will have master plans, check lists, and a range of points they will test and prove before the product manufacturing process is underway—this is called the validation protocol. Concurrent validation is a subset of prospective validation, and is conducted after prospective validation has been completed and a full understanding of the machinations of the process has been gained.
Retrospective validation is a process no manufacturer wants to ever have to carry out. This type of validation typically is needed
after a device already is on the market, and a problem is discovered that causes the manufacturer to have to go back and evaluate its manufacturing process to see what went wrong. Of course, a manufacturer can go back and conduct a retrospective validation any time it wants to, but if prospective and concurrent validation has been conducted diligently, it is unlikely a retrospective validation will be needed. A retrospective validation will require the examination of accumulated historical production records, testing, control, and other information for a product already in production and distribution. This type of validation makes use of historical data and information which may be found in batch records, production log books, lot records, control charts, test and inspection results, customer complaints or lack of complaints, field failure reports, service reports, and audit reports.
Validation requires carefully detailed logging not only of manufacturing processes, but also of any and all communication between the CMO and the OEM. If a complaint or concern was brought to the attention of a CMO, for instance, and the CMO did not follow through or did not record its follow-through adequately, that can cause trouble down the line if a question is ever raised about the finished product. It even may cause the need for a retrospective validation, which is time-consuming and expensive.
These are the bare bones of process validation in medical device manufacturing, and yes, it may seem like it’s all about checklists and endless records. However, as most experts who talked to Medical Product Outsourcing agreed, validation ultimately boils down to a philosophy. Continuous, diligent validation needs to be in the company bloodstream in order to ensure a superior and reliable state of product quality.
“We have a development engineering staff, and although they author and execute validation protocols, validation is more of a philosophy [at our company],” said Donatelle’s Schramm. “Once you validate a process, it really doesn’t mean anything unless you’ve got controls in place downstream to make sure you’re running within that validated process. One thing we continually press upon our folks is once we go through the effort to validate a process, there’s still a lot of work in maintaining that validation throughout the life cycle of the product.”
PHL101: Validation as Philosophy
“A lot of people think of validation as something you execute up front, file away, and you’re done,” continued Schramm. “It’s really a philosophy for long-term manufacturing.”
By creating unique, company-specific procedures surrounding process validation, manufacturers can create an environment that works for their specific processes—be it injection molding or coating or packaging—and for their customers. Flambeau Inc., a plastics manufacturer based in Phoenix Ariz., has developed a colorful approach to validation that enables intuitive movement between stages and the space to check and re-check itself. Lee Hernandez, quality manager at Flambeau, explained that his company has three launch stages before the start of product manufacturing—the red launch, yellow launch, and green launch.
The red launch begins when Flambeau receives the manufacturing tool from where it’s made, whether in-house or even perhaps in China.
“We receive the tool in and see if it is operational,” Hernandez said. “The red launch is mainly: ‘Get the tool in the press, is it functional , will it make parts, and are the parts close to print?’ During the red launch we’ll have a launch checklist where the project manager, manufacturing engineer, quality engineer, and myself the quality manager will be there, and we’ll go through this whole checklist of what we expect from the red launch. This is also the time where we’ll introduce whether we need special equipment, robots, sonic loading fixtures, etc.”
In validation-speak, Flambeau’s red launch would be the installation qualification (IQ) stage of validation. IQ verifies that the equipment and its ancillary systems have been installed in accordance with installation drawings and or specifications.
Then comes Flambeau’s yellow launch.
“Here is where we collect samples from a stable process after performing a scientific or four corner study,” said Hernandez. “Quality begins breaking down the part dimensionally after the red launch, which would have taken care of any tooling issues we might have had.”
The yellow launch is equivalent to operational qualification (OQ). Together, the IQ and OQ phases of process validation may include examining equipment design and supplied documentation; determining installation requirements; establishing any needed environmental controls and procedures; assuring that the work area has sufficient space to perform the processing and associated activities; installing the equipment; verifying correct installation; establishing manufacturing procedures for the monitoring, operation, and control of the equipment including the minimum number of operators; determining calibration, cleaning, maintenance, adjustment, and expected repair requirements; identifying important elements of the equipment that could affect the output or finished device; verifying that the system or subsystem performs as intended throughout all anticipated operating ranges; and documenting the above information.
Finally, Flambeau moves into the green launch—but, as Hernandez explained, very rarely does the company move straight from the yellow launch to the green. OQ is the phase that affords Flambeau the opportunity to move back and forth between manufacturing steps, ensuring each one is as close to perfect as possible. The validation team is examining product cosmetics and dimensions and running multiple shots—one cycle of production—to determine there is little variation between lots, and so on.
Once the team is satisfied with the product output, they can move to the green launch, or the process qualification (PQ) stage
“We confirm that all the deficiencies from the previous launch were taken care of,” Hernandez said. “This is where we get approval from the customer, provide documentation to the customer, whether it’s first articles or samples we’ve put through the system. It’s during the green launch that we start to implement inspection plans, molding parameters, the master process, and just start tightening everything up, so when it does go to run, everyone has the information they need on the floor to run that part.”
Speaking of philosophy, how much more philosophical can one get than Socrates? The famed Socratic Method—the method of teaching practiced by the ancient Greek philosopher that involves asking questions until an answer is reached—is very present in process validation. If a problem is found in a process during the critical OQ phase, a root cause analysis often is conducted to find the root of the problem. Victor Gurany, manager of quality assurance and compliance at New Freedom, Pa.-based Crescent Industries Inc., employs an interrogative method to find out the root cause of a problem in a process: “The Five Whys.” It is what it sounds like. When a problem is found, the question “why?” is asked until the root cause is discovered.
Crescent, like Flambeau, is a plastics injection molder. A common problem in plastics manufacturing is flash, or excess plastic protruding from the product, often at the seams, a familiar sight on plastic dolls and other toys (not something you want on a medical device).
“Let’s say flash was found on different parts in every stage of the process,” Gurany said. “That shows you there’s a problem. When you’re talking about a medical device, flash is very risky. You don’t want that flash hanging off a ventilator, for instance, as it can go through the lungs of a patient. Flash for us is a very risky and critical thing. But it’s a very difficult problem in an injection molding environment, and can be caused by many different reasons. It could be process related; you could be injecting more plastic or exerting more pressure than necessary; or you are increasing the temperature and therefore you’re creating thinner more watery plastic; or your mold wears. Every mold has a fixed lifetime, and if it wears, a gap can be created between the parting lines—the interaction between the two parts of the mold—and that can create flash. It could be a combination of these causes or it could be just one of those. You ask ‘why?’ then you analyze which part is the problem. You have to ask why five times to make sure you get to the root of the cause.”
Gurany was quick to note that the problem is never blamed on the people working on the process. Working as a team is central to solving validation problems, and placing blame on people is never conducive to a collaborative, problem-solving environment.
Many factors that affect the product manufacturing process are examined, from material and environment to labor and work instructions, but if the ‘whys’ lead to a person, the company examines the training and instructions handed to that worker.
Philosophy also is key from an OEM’s perspective. When Iapyx Medical, for instance, a San Diego, Calif.-based maker of infection prevention technology, looks for a CMO, it looks for a manufacturer that understands its own philosophy around medical devices.
“What Iapyx looks for in a CMO, because of our smaller size, is for a full-service contract manufacturer who is on the same page as us philosophically first,” explained Tom Flannery, chief operating officer at Iapyx. “Trying to change someone’s mindset takes too much time, and once they’ve realized that there’s value in [our approach], it’s too late. Once you recognize that your CMO philosophically understands what it is you’re talking about when you say ‘process validation’—that it’s not just an activity they have to complete in order to be compliant—then it’s whether they have the tools to accomplish the mission, and that isn’t a difficult task to determine.”
Flannery is an advocate for moving away from a “checklist” attitude toward process validation. Though having been with Iapyx for a year, he spent the 12 years prior managing a major medical manufacturing services provider’s facility in Mexico. During those years, he managed the transfer and/or development of dozens of medical devices from start to finish, and worked on hundreds of re-validations to maintain a process’ validated state. This, of course, meant immeasurable interactions with OEM customers of all types and sizes.
“A lot of people look at validation as a check-the-box type of activity, and then they move forward,” Flannery said. “Really, validation paints a picture that must be maintained through the life of the device—and it can be adjusted to allow for continuous improvement as long as effective change controls are in place. Most companies lose the validated state shortly after they’ve completed the validation because there’s no statistical tie-in to what they do after while in production. Therefore, they’re not able to prove to themselves or to their end user that what they’re doing in production is maintaining that validated state. Every one of those critical to quality criteria that you establish in validation needs to be verified going forward.”
It’s All About the End
Process validation has two endpoints to consider. The first is obvious—the product that emerges from the end of the manufacturing process. The second is something, according to Triangle’s Thomas, that should be most central to any medical technology manufacturing validation philosophy—the patient.
“Validation is something we take really seriously here,” Thomas said. “Where you can’t measure a particular process or part by some means of measurement, we have to default to the validation route. We feel that validation, when done properly, has the potential of saving lives every day.”
Triangle manufactures surgical tools and instrumentation, as well as orthopedic implants including hip, knee and spine implants. Because orthopedic implants are placed inside a patient’s body sometimes permanently, the atmosphere at Triangle is
reportedly one of a heightened sense of responsibility.
“There’s a higher risk when you’re making something that’s implantable as opposed to an instrument that maybe cleans something or drills something or screws something in,” Thomas said. “So we put a heavy weight on our finished devices.”
Also, because Triangle has one validation team working on all devices and instruments, the extremely high level of validation control applied to orthopedic implants carries over to the lower-risk devices such as surgical drills and bone files.
“We keep one standard—we don’t bend the standard or lower the standard at all depending on what the process is,” Thomas said. “The amount of work that goes into our validation processes is risk-based… It’s the same team doing it, so they wouldn’t differ the validation process applied to an implantable for a powered instrument.”
On the other hand, Holt, Mich.-based manufacturer Orchid Orthopedics Inc., which also focuses on orthopedic devices and components, takes a very customer-centric approach. Validations and quality engineers at Orchid tweak their approach based on what their customer OEMs require.
“We do a lot of customer specific validation here,” said Laela Hampton, validations engineer at Orchid. “If there’s a new implant, and a medical device company wants to get it to market, we work with our customer—our first goal is to meet FDA requirements, but our overall goal is to meet out customer requirements. If they have a different type of material, for example, we’ll work with customers to make sure that it’s validatable and that we can package that material.”
And the whole point of process validation, as Iapyx’s Flannery illustrates, is to ensure end product quality by maintaining control from the very beginning of the manufacturing process. According to Flannery, a decade or so ago, quality teams ironically focused too much on the end product to verify quality rather than the beginning of the process. Despite the focus on the end product, this was an ineffective way to maintain quality.
“The best way to describe how things have changed is if you think of a water pipe,” Flannery said. “The quality was verified at the end of the pipe, as the water was flowing out, rather than back at the molecular level with the hydrogen oxygen combination. When you’re inspecting the quantity and quality of the water at the end of the pipe, you’re missing opportunity. Because really, the quality of the water happened at the other end. Manufacturers have now recognized that value in reducing the cost of quality and improving your product quality is found in developing your processes, understanding your process limits, and monitoring those limits. Being able to tell that we’ve got a problem—that’s too late. It’s being able to tell that you’re going to have a problem. Being predictive rather than reactive.”
An OEM’s Wrap-Up Perspective
“The world-class companies really understand that validation is not just check-the-box,” concluded Flannery. “You’re creating a state, and if you can prove that you’re maintaining that state, design controls and everything that flows out of design controls—change control, process development—all those things become crystal clear.”
Editor’s note: For extended expert opinions on process validation, visit the online exclusives section on the MPO website, www.mpo-mag.com.
There certainly are mandatory requirements surrounding process validation for contract manufacturing organizations (CMOs) in the medtech space as laid out by the Global Harmonization Task Force’s guidance document on “the Controls of Products and Services Obtained from Suppliers,” published in December 2008. Not every manufacturing process requires validation, as some devices easily can be tested at the end stage of production to ensure quality. However, there are some processes that require process validation due to the product’s inherent nature. For instance, plastic injection molding requires process validation because a plastic component cannot simply be visually inspected for quality. Wall thickness and density cannot be tested non-destructively—that is, without destroying the product. Similarly, in sterilization procedures, absolute sterility cannot be proven without compromising the sterility of the product.
“For example, with laser welding, there’s no way to look at a weld and see that the weld is strong,” said Dana Schramm, vice president of engineering at Donatelle, a CMO based in New Brighton, Minn. “The reason they separate injection molding out and say it has to be process-validated is because we could mold two parts that look and measure identical, but one of them could be more dense than another and therefore have a different strength property. One could have voids that can’t be seen because the part isn’t transparent. So with the molding process, you can’t just inspect a part and say ‘yeah, this looks good.’ We would either go through process validation and supply our customer with parts, or we would test the parts —subject them to design verification testing. A lot of times that involves not only assembling the parts but doing some mechanical testing on them and verifying that even when manufactured at the validated process limits, the intended performance of the part is not adversely affected.”
Process validation ensures that a manufacturing process for any device or component will run reliably, continuously producing parts to the specifications required by the original equipment manufacturer customer that commissioned the product. The U.S. Food and Drug Administration (FDA) does have documents and guidances available to device manufacturers, to which many quality assurance and validation engineers refer for updates and new insights into validation processes. In the current version of the process validations section of the agency’s Medical Device Quality Systems Manual, the FDA outlines why a company would validate their processes:
“Through careful design of the device and packaging, careful design and validation of processes, and process controls, that there is a high probability that all manufactured units will meet specifications and have uniform quality,” the FDA document reads. “The dependence on intensive in-process and finished device testing can be reduced. However, in-process and finished product testing still play an important role in assuring that products meet specifications. A properly validated and controlled process will yield little scrap or rework, resulting in increased output. Consistent conformance to specifications is likely to result in fewer complaints and recalls. Also, when needed, the validation files contain data to support improvements in the process or the development of the next generation of the process.”
There are two main types of process validation: prospective and retrospective. Prospective validation is conducted before a product is released for distribution, and the process is begun right at the beginning of the conception of the product. Validation teams will have master plans, check lists, and a range of points they will test and prove before the product manufacturing process is underway—this is called the validation protocol. Concurrent validation is a subset of prospective validation, and is conducted after prospective validation has been completed and a full understanding of the machinations of the process has been gained.
Retrospective validation is a process no manufacturer wants to ever have to carry out. This type of validation typically is needed
after a device already is on the market, and a problem is discovered that causes the manufacturer to have to go back and evaluate its manufacturing process to see what went wrong. Of course, a manufacturer can go back and conduct a retrospective validation any time it wants to, but if prospective and concurrent validation has been conducted diligently, it is unlikely a retrospective validation will be needed. A retrospective validation will require the examination of accumulated historical production records, testing, control, and other information for a product already in production and distribution. This type of validation makes use of historical data and information which may be found in batch records, production log books, lot records, control charts, test and inspection results, customer complaints or lack of complaints, field failure reports, service reports, and audit reports.
Validation requires carefully detailed logging not only of manufacturing processes, but also of any and all communication between the CMO and the OEM. If a complaint or concern was brought to the attention of a CMO, for instance, and the CMO did not follow through or did not record its follow-through adequately, that can cause trouble down the line if a question is ever raised about the finished product. It even may cause the need for a retrospective validation, which is time-consuming and expensive.
These are the bare bones of process validation in medical device manufacturing, and yes, it may seem like it’s all about checklists and endless records. However, as most experts who talked to Medical Product Outsourcing agreed, validation ultimately boils down to a philosophy. Continuous, diligent validation needs to be in the company bloodstream in order to ensure a superior and reliable state of product quality.
“We have a development engineering staff, and although they author and execute validation protocols, validation is more of a philosophy [at our company],” said Donatelle’s Schramm. “Once you validate a process, it really doesn’t mean anything unless you’ve got controls in place downstream to make sure you’re running within that validated process. One thing we continually press upon our folks is once we go through the effort to validate a process, there’s still a lot of work in maintaining that validation throughout the life cycle of the product.”
PHL101: Validation as Philosophy
“A lot of people think of validation as something you execute up front, file away, and you’re done,” continued Schramm. “It’s really a philosophy for long-term manufacturing.”
By creating unique, company-specific procedures surrounding process validation, manufacturers can create an environment that works for their specific processes—be it injection molding or coating or packaging—and for their customers. Flambeau Inc., a plastics manufacturer based in Phoenix Ariz., has developed a colorful approach to validation that enables intuitive movement between stages and the space to check and re-check itself. Lee Hernandez, quality manager at Flambeau, explained that his company has three launch stages before the start of product manufacturing—the red launch, yellow launch, and green launch.
The red launch begins when Flambeau receives the manufacturing tool from where it’s made, whether in-house or even perhaps in China.
“We receive the tool in and see if it is operational,” Hernandez said. “The red launch is mainly: ‘Get the tool in the press, is it functional , will it make parts, and are the parts close to print?’ During the red launch we’ll have a launch checklist where the project manager, manufacturing engineer, quality engineer, and myself the quality manager will be there, and we’ll go through this whole checklist of what we expect from the red launch. This is also the time where we’ll introduce whether we need special equipment, robots, sonic loading fixtures, etc.”
In validation-speak, Flambeau’s red launch would be the installation qualification (IQ) stage of validation. IQ verifies that the equipment and its ancillary systems have been installed in accordance with installation drawings and or specifications.
Then comes Flambeau’s yellow launch.
“Here is where we collect samples from a stable process after performing a scientific or four corner study,” said Hernandez. “Quality begins breaking down the part dimensionally after the red launch, which would have taken care of any tooling issues we might have had.”
The yellow launch is equivalent to operational qualification (OQ). Together, the IQ and OQ phases of process validation may include examining equipment design and supplied documentation; determining installation requirements; establishing any needed environmental controls and procedures; assuring that the work area has sufficient space to perform the processing and associated activities; installing the equipment; verifying correct installation; establishing manufacturing procedures for the monitoring, operation, and control of the equipment including the minimum number of operators; determining calibration, cleaning, maintenance, adjustment, and expected repair requirements; identifying important elements of the equipment that could affect the output or finished device; verifying that the system or subsystem performs as intended throughout all anticipated operating ranges; and documenting the above information.
Finally, Flambeau moves into the green launch—but, as Hernandez explained, very rarely does the company move straight from the yellow launch to the green. OQ is the phase that affords Flambeau the opportunity to move back and forth between manufacturing steps, ensuring each one is as close to perfect as possible. The validation team is examining product cosmetics and dimensions and running multiple shots—one cycle of production—to determine there is little variation between lots, and so on.
Once the team is satisfied with the product output, they can move to the green launch, or the process qualification (PQ) stage
“We confirm that all the deficiencies from the previous launch were taken care of,” Hernandez said. “This is where we get approval from the customer, provide documentation to the customer, whether it’s first articles or samples we’ve put through the system. It’s during the green launch that we start to implement inspection plans, molding parameters, the master process, and just start tightening everything up, so when it does go to run, everyone has the information they need on the floor to run that part.”
Speaking of philosophy, how much more philosophical can one get than Socrates? The famed Socratic Method—the method of teaching practiced by the ancient Greek philosopher that involves asking questions until an answer is reached—is very present in process validation. If a problem is found in a process during the critical OQ phase, a root cause analysis often is conducted to find the root of the problem. Victor Gurany, manager of quality assurance and compliance at New Freedom, Pa.-based Crescent Industries Inc., employs an interrogative method to find out the root cause of a problem in a process: “The Five Whys.” It is what it sounds like. When a problem is found, the question “why?” is asked until the root cause is discovered.
Crescent, like Flambeau, is a plastics injection molder. A common problem in plastics manufacturing is flash, or excess plastic protruding from the product, often at the seams, a familiar sight on plastic dolls and other toys (not something you want on a medical device).
“Let’s say flash was found on different parts in every stage of the process,” Gurany said. “That shows you there’s a problem. When you’re talking about a medical device, flash is very risky. You don’t want that flash hanging off a ventilator, for instance, as it can go through the lungs of a patient. Flash for us is a very risky and critical thing. But it’s a very difficult problem in an injection molding environment, and can be caused by many different reasons. It could be process related; you could be injecting more plastic or exerting more pressure than necessary; or you are increasing the temperature and therefore you’re creating thinner more watery plastic; or your mold wears. Every mold has a fixed lifetime, and if it wears, a gap can be created between the parting lines—the interaction between the two parts of the mold—and that can create flash. It could be a combination of these causes or it could be just one of those. You ask ‘why?’ then you analyze which part is the problem. You have to ask why five times to make sure you get to the root of the cause.”
Gurany was quick to note that the problem is never blamed on the people working on the process. Working as a team is central to solving validation problems, and placing blame on people is never conducive to a collaborative, problem-solving environment.
Many factors that affect the product manufacturing process are examined, from material and environment to labor and work instructions, but if the ‘whys’ lead to a person, the company examines the training and instructions handed to that worker.
Philosophy also is key from an OEM’s perspective. When Iapyx Medical, for instance, a San Diego, Calif.-based maker of infection prevention technology, looks for a CMO, it looks for a manufacturer that understands its own philosophy around medical devices.
“What Iapyx looks for in a CMO, because of our smaller size, is for a full-service contract manufacturer who is on the same page as us philosophically first,” explained Tom Flannery, chief operating officer at Iapyx. “Trying to change someone’s mindset takes too much time, and once they’ve realized that there’s value in [our approach], it’s too late. Once you recognize that your CMO philosophically understands what it is you’re talking about when you say ‘process validation’—that it’s not just an activity they have to complete in order to be compliant—then it’s whether they have the tools to accomplish the mission, and that isn’t a difficult task to determine.”
Flannery is an advocate for moving away from a “checklist” attitude toward process validation. Though having been with Iapyx for a year, he spent the 12 years prior managing a major medical manufacturing services provider’s facility in Mexico. During those years, he managed the transfer and/or development of dozens of medical devices from start to finish, and worked on hundreds of re-validations to maintain a process’ validated state. This, of course, meant immeasurable interactions with OEM customers of all types and sizes.
“A lot of people look at validation as a check-the-box type of activity, and then they move forward,” Flannery said. “Really, validation paints a picture that must be maintained through the life of the device—and it can be adjusted to allow for continuous improvement as long as effective change controls are in place. Most companies lose the validated state shortly after they’ve completed the validation because there’s no statistical tie-in to what they do after while in production. Therefore, they’re not able to prove to themselves or to their end user that what they’re doing in production is maintaining that validated state. Every one of those critical to quality criteria that you establish in validation needs to be verified going forward.”
It’s All About the End
Process validation has two endpoints to consider. The first is obvious—the product that emerges from the end of the manufacturing process. The second is something, according to Triangle’s Thomas, that should be most central to any medical technology manufacturing validation philosophy—the patient.
“Validation is something we take really seriously here,” Thomas said. “Where you can’t measure a particular process or part by some means of measurement, we have to default to the validation route. We feel that validation, when done properly, has the potential of saving lives every day.”
Triangle manufactures surgical tools and instrumentation, as well as orthopedic implants including hip, knee and spine implants. Because orthopedic implants are placed inside a patient’s body sometimes permanently, the atmosphere at Triangle is
reportedly one of a heightened sense of responsibility.
“There’s a higher risk when you’re making something that’s implantable as opposed to an instrument that maybe cleans something or drills something or screws something in,” Thomas said. “So we put a heavy weight on our finished devices.”
Also, because Triangle has one validation team working on all devices and instruments, the extremely high level of validation control applied to orthopedic implants carries over to the lower-risk devices such as surgical drills and bone files.
“We keep one standard—we don’t bend the standard or lower the standard at all depending on what the process is,” Thomas said. “The amount of work that goes into our validation processes is risk-based… It’s the same team doing it, so they wouldn’t differ the validation process applied to an implantable for a powered instrument.”
On the other hand, Holt, Mich.-based manufacturer Orchid Orthopedics Inc., which also focuses on orthopedic devices and components, takes a very customer-centric approach. Validations and quality engineers at Orchid tweak their approach based on what their customer OEMs require.
“We do a lot of customer specific validation here,” said Laela Hampton, validations engineer at Orchid. “If there’s a new implant, and a medical device company wants to get it to market, we work with our customer—our first goal is to meet FDA requirements, but our overall goal is to meet out customer requirements. If they have a different type of material, for example, we’ll work with customers to make sure that it’s validatable and that we can package that material.”
And the whole point of process validation, as Iapyx’s Flannery illustrates, is to ensure end product quality by maintaining control from the very beginning of the manufacturing process. According to Flannery, a decade or so ago, quality teams ironically focused too much on the end product to verify quality rather than the beginning of the process. Despite the focus on the end product, this was an ineffective way to maintain quality.
“The best way to describe how things have changed is if you think of a water pipe,” Flannery said. “The quality was verified at the end of the pipe, as the water was flowing out, rather than back at the molecular level with the hydrogen oxygen combination. When you’re inspecting the quantity and quality of the water at the end of the pipe, you’re missing opportunity. Because really, the quality of the water happened at the other end. Manufacturers have now recognized that value in reducing the cost of quality and improving your product quality is found in developing your processes, understanding your process limits, and monitoring those limits. Being able to tell that we’ve got a problem—that’s too late. It’s being able to tell that you’re going to have a problem. Being predictive rather than reactive.”
An OEM’s Wrap-Up Perspective
“The world-class companies really understand that validation is not just check-the-box,” concluded Flannery. “You’re creating a state, and if you can prove that you’re maintaining that state, design controls and everything that flows out of design controls—change control, process development—all those things become crystal clear.”
Editor’s note: For extended expert opinions on process validation, visit the online exclusives section on the MPO website, www.mpo-mag.com.