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Changes in Warning Letter Policy Likely Permanent, Ulatowski Says
Devicemakers hoping to return to having 30 days to respond to Form 483 observations and prior attorney review of all warning let-ters are likely to be disappointed, a CDRH official says.
The FDA has been reviewing both policy changes. A determina-tion was expected on the attorney review policy at the end of Sep-tember, and continuation of the 15-day response policy should be decided in February, according to the agency.
Once the review process is complete, the policy changes will likely become permanent, Tim Ulatowski, director of CDRH’s Office of Compliance, told GMP.
FDA: Proposed Rule for UDI Database Expected to Be Released This Year
Three years after Congress mandated that the FDA create a unique device identifier (UDI) regulation and database, the agency is getting close to releasing a proposed rule.
The rule is expected to be released in two months, Jay Crowley, the FDA’s senior adviser for patient safety, said during a September webinar to update devicemakers on the status of the database.
Recently, Crowley said the agency plans to publish, within the next few months, a request for proposals to begin the development and building of the UDI database, which it hopes to have completed within a year. Implementation of the database is predicated on the publication of the final UDI rule (GMP, September).
The database would serve as a valuable postmarket tool that would enable the FDA to track adverse device events or locate recip-ients of faulty, recalled products.
Issue No. 369October 2010
Canadian inspections to be ranked by risk .........Page 3
‘Late’ 483 response triggers warning to Teco Diagnos-tics ...........................Page 3
Form 483 Insider ...Page 5
FDA warns Frontier Medi-cal for not following proce-dures .......................Page 7
Procedural, documentation issues lead to warning for CeraSys ...................Page 8
First inspection in years leads to warning letter for InTec .......................Page 9
Storz gets warning for fail-ures in handling of defective devices ....................Page 9
Maquet forms response team after getting warning letter ......................Page 10
CDRH touts suggested changes to 510(k) pro- cess amid inspection con-cerns ....................Page 11
INsIde thIs Issue
(See UDI, Page 2)
(See Warning, Page 4)
the gmp letter October 2010Page 2
The proposed rule will require devicemak-ers to provide information for 12 attributes, down from the 47 the agency required last year as part of a prototype database, Terrie Reed, associate director for informatics at the FDA, said during the webinar.
Devicemakers that participated in the trial run of the prototype asked for a more modest set of clearly defined attributes that would relate to all products and that would be globally harmonized where possible. While many of the prototype attri-butes asked for standard safety information, others — such as whether a device is MRI-compatible — were considered unnecessary.
Dataset to Evolve
Neither Crowley nor Reed disclosed what the 12 attributes would be, but Crowley said they were ones devicemakers have seen before. As feedback about the regulation and the database comes in, the number of required attributes could rise, he added.
“I want to caution people that this initial set of data elements is what we’re starting with,” Crowley said. “We intend that the dataset will grow and evolve as new issues arise.”
The agency had hoped to have a final UDI rule in place by next April, but that was based on releasing the proposed rule for comment this past summer (GMP, April). The agency has proposed phasing the rule in with all Class III devices required to be in compliance 12 months after the final rule is posted. Class II devices would have to comply within three years and Class I devices would have to be in compliance in five years.
For the UDI database to be successful, health-care providers, as well as devicemakers, must use it, Reed said. However, the FDA does not have the regulatory power to require hospitals to adopt the database.
To get providers on board, the agency is kick-ing off outreach initiatives to express the benefits
of the system and correct inaccurate perceptions that may have sprung up. One misconception is that the database will replace CDRH’s adverse event and recall databases. “All this database does is collect information,” Reed said.
The FDA also may turn to sister agencies, such as the Centers for Medicare & Medicaid Services, for help in getting hospitals to embrace the system, Crowley said.
The agency already has buy-in from some provider groups. The Advancing Patient Safety Coalition, which includes the American Health Association and the American Nurses Associa-tion, has been aggressively pushing for the FDA to release a proposed regulation, going as far as writing to Commissioner Margaret Hamburg (GMP, August).
No Exemptions
However, the UDI rule may go further than some providers wanted. Jean Sargent, director of supply chain management at the University of Southern California Health Sciences Center, said last year she hoped the most innocuous devices would be exempt. “Nursing time at bedsides is shrinking,” Sargent said. “We don’t need to be scanning bedpans.”
But during the webinar, held by the Associa-tion for the Advancement of Medical Instrumen-tation, Crowley said the rule would apply to all devices, at least initially.
The FDA is not alone in developing a UDI system. Crowley acknowledged the work being done in other countries, but he expects the FDA’s rule will be out before anyone else’s.
All along, devicemakers have expected the agency to lead the way globally. “The world will look to the FDA because it oversees the biggest device market,” Jeffrey Secunda, associate vice president of technology and regulatory affairs at AdvaMed, recently told GMP. “What the FDA says in the rule will influence how other jurisdic-tions implement UDI.” — Virgil Dickson
UDI, from Page 1
the gmp letterOctober 2010 Page 3
Health Canada Begins Ranking Inspections According to Risk
Observations made during device facility inspections in Canada are now being ranked according to risk, a final Health Canada guid-ance says.
The new approach, which went into effect this month, applies to regular, follow-up and tar-geted inspections. It is intended to ensure unifor-mity among Health Canada inspectors and advise devicemakers on deviations the agency considers unacceptable.
Inspectors will classify violations as Risk 1, 2 or 3, with Risk 1 posing an immediate or latent health risk. If procedures are in place to mitigate a serious health risk, the violations will be con-sidered Risk 2. Failure to meet manufacturing, import or distribution requirements also will be
considered a Risk 2. Other noncompliances will be a Risk 3.
Observations made during an earlier inspec-tion that have not been corrected at the follow-up inspection may be upgraded to a higher risk cat-egory, the guidance says.
Following an inspection, devicemakers will be given an overall compliance rating based on the number of observations and risks involved, the guidance says.
If a devicemaker corrects all the problems immediately, it may receive a compliant rating, but the risks assigned to the observations will remain.
“Guidance on Risk Classification of Medical Device Observations” is available at www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/compli-conform/info-prod/md-im/gui-0079-eng.pdf. — Meg Bryant
‘Late’ 483 Response Triggers Warning to Teco Diagnostics
When Teco Diagnostics was handed a Form 483 with 13 observations in April, it corrected two issues immediately and committed to cor-recting everything else by June 3.
The Anaheim, Calif., company sent the FDA a response letter June 2, notifying the agency that it had kept its commitment and explaining how it had corrected the remaining 11 observations, which mostly dealt with documentation and pro-cedural deficiencies.
However, the response was sent 25 business days after the close of the inspection, so the FDA refused to consider it before sending the company a warning letter Aug. 20.
In the past, the company has had 30 days to respond to the agency, a spokesman told GMP, noting that neither the Form 483 nor the investi-gators indicated that the response must be sub-mitted within 15 business days. Since no regula-tion or guidance had been issued, the company was unaware that the FDA changed its response policy last September.
In addition to the observations made during the inspection, the warning letter, which was posted last month, claims Teco has no clearance or approval for its TC-101 urine analyzer, an alcohol saliva dipstick and a rapid plasma reagent (RPR) kit.
However, the company received a 510(k) exemption for the urine analyzer in 2000, and the device has a waiver from the Clinical Laboratory Improvement Amendments program, the spokes-man says. Since Teco has begun making the ana-lyzer for private labels, it is seeking a 510(k) for the device.
The company does not consider the dipstick a diagnostic device because it does not diagnose, prevent or treat a disease, nor is it intended to affect the structure or function of the body.
As for the RPR kit, Teco purchases it, under a private label, from a supplier that has a 510(k) for the product, the company said.
Company officials plan to have a face-to-face meeting with the FDA and will take whatever steps are necessary to clear up the warning letter.
The warning letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm225059.htm. — Mari Serebrov
the gmp letter October 2010Page 4
The changes, which eliminated attorney review for most warning letters and cut the 483 response time to 15 business days, were imple-mented on a trial basis last year to tighten and speed up enforcement efforts (GMP, August 2009).
Having FDA attorneys review warning letters added more burden to getting warning letters out in a timely fashion.
“More thumbs in the pie is not helpful,” Ula-towski said. “If there is added value to steps in the process, then certainly that’s warranted. But checkers checking checkers is not helpful.”
Letter Quality
Ever since the policy was implemented in September 2009, device attorneys have noted what appears to be a decrease in the quality of warning letters — from the legal basis of cita-tions to typographical errors (GMP, August).
These are not new issues, Ulatowski said. “These are things that [investigators] are always struggling with as you develop responses to very complex issues,” he explained.
“You want to make sure you are trying to respond as quickly as possible without forfeiting quality you want to sustain. I’m not going to take them to task for a typo here or there,” he added.
As for the 15-day response time, it has become a “necessary process,” Ulatowski said. “People peppering us with submissions over the course of three to four weeks is not helpful to them or to us,” he noted.
Several devicemakers have complained that they were not aware of the shortened response time — until they got a warning letter indicat-ing their response was late. Some have wondered why they weren’t told of the change during an inspection or why it’s not noted on the Form 483.
They expected such a change to be addressed in a rule or guidance. But Ulatowski said that’s unlikely due to the straightforward nature of the change.
Ulatowski, who will be retiring from CDRH Jan. 1, hopes his successor, Steven Silverman, will continue taking a broad view of inspection and compliance issues by looking for company-wide deficiencies and issuing corporate warning letters.
Silverman, the former senior adviser at CDRH’s Office of Compliance, has begun transi-tioning into his new position.
Other major enforcement issues facing Silver-man are global supply chain security and the need to crack down on counterfeiting, Ulatowski said.
As for Ulatowski’s future plans, he said sev-eral private companies have contacted him about employment opportunities.
But he has not had serious discussions with any of them, he added. Ulatowski has been with the FDA since 1974 and has been in his current position nearly eight years. — Virgil Dickson
Warning, from Page 1
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the gmp letterOctober 2010 Page 5
Inability to Trend for Defects Results in 483 for Medtronic
Medtronic Puerto Rico Operations’ pro-cess of evaluating adverse product tendencies is unable to establish adverse tendencies for indi-vidual products, so the company does not always conduct the appropriate investigations, according to a March 10 Form 483.
The company only investigates when all the devices that are part of the same family together exceed the pre-calculated threshold for a specific defect or hazard, the form says. If only one prod-uct within a family is having an adverse trend and it is not enough to exceed the established group threshold, Medtronic will not be able to detect the problem and will not investigate.
The Dec. 10, 2009, to March 10 inspection revealed that complaints generated from litera-ture, as well as those related to old events, are excluded from threshold signal investigations. No retrospective analysis is performed to evaluate the excluded old events within their correspond-ing time frames.
Several additional observations involved the company’s complaint-handling procedures.
Medtronic is working with the FDA to address the concerns and has an action plan in place, company spokesman Christopher Garland told GMP.
The Form 483 is available at www.fdanews.com/ext/files/Medtronic100110.pdf.
Abbott 483 Notes Problem With Cleaning Procedure
Abbott Vascular was handed a Form 483 after an FDA investigator observed an assembler tak-ing steps that could lead to the transfer of foreign particles from a waste container to a device.
The assembler wiped a StarClose SE device with an alcohol wipe, then opened the lid of a waste container with her gloved hand to dispose of the wipe, despite the fact that the container
had a foot pedal, and then continued work on the device without changing the glove, the Aug. 30 form says. The investigator observed the same event at least twice.
The July 9 to Aug. 30 inspection also found Abbot failed to implement its corrective and pre-ventive action (CAPA) investigation procedure when investigating the root cause and identifying actions needed to correct and prevent recurrence of nonconformities and other quality problems related to a complaint for its StarClose SE vascu-lar closure system.
A CAPA investigation was incomplete be-cause the record did not include the list of poten-tial root causes and the justification for rejecting them.
Additional observations were related to medi-cal device reporting.
Abbott has taken corrective action and has communicated its actions to the FDA, company spokesman Jonathon Hamilton told GMP.
The Form 483 is available at www.fdanews.com/ext/files/Abbott100110.pdf.
Philips 483 Details MDR Failures
Philips Medical Systems has received a Form 483 with several observations related to medical device reporting (MDR) violations.
For example, the San Jose, Calif., facility did not submit an MDR within 30 days after learn-ing a patient ripped off a fingernail and broke a finger while pulling it out from between the table and table cover of a CardioMD table, the June 14 form says.
A June 1 to 14 inspection also found Philips failed to submit MDRs for complaints describing malfunctions similar to ones already submitted as MDRs.
form 483 INsIder
(See Form 483 Insider, Page 12)
the gmp letterOctober 2010 Page 7
FDA Warns Frontier Medical For Not Following Procedures
Nonexistent forms and procedure failures resulted in a warning letter to Frontier Medical Products, which makes blood pressure cuffs.
The company also has not submitted its annual establishment registration or device list-ings since 2007, according to the Sept. 1 letter that stems from a June inspection of Frontier’s Port Washington, Wis., facility.
An FDA investigator noted that Frontier implemented a change to its manufacturing pro-cess in April, but the company had no evidence that the change was reviewed, approved, or veri-fied or validated. The company’s quality manual references a procedure for design change, but the procedure does not exist, the letter says.
Frontier has not implemented its corrective and preventive action (CAPA) procedure, which requires the use of a nonexistent form. In addi-tion, issues not remedied through other systems were not logged into the company’s CAPA sys-tem as required.
Other procedural problems Frontier is cited for include failure to:
● Enter a customer complaint as required by the company’s complaint-handling proce-dure. The investigator noted that a form described in this procedure does not exist;
● Implement its purchasing process proce-dure and a supplier questionnaire. The investigator found that the supplier of one of the cuff components had not been evaluated to determine if it could meet specifications. The company also had no approved supplier list;
● Conduct annual quality system audits as required by its audit procedure. No quality audit had been conducted since 2006; and
● Conduct management reviews of the qual-ity system. The company’s quality manual requires at least four management re-views a year, but the investigator found no management reviews had been conducted since 2006.
In its response to the Form 483, Frontier promised to correct all the issues cited. The response is inadequate, the FDA says, because it does not include documentation showing how the violations will be corrected.
Frontier did not respond to a request for com-ment by press time. The warning letter is avail-able at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm224904.htm. — Mari Serebrov
Beckman Coulter CEO Resigns Amid Compliance Concerns
The unexpected resignation of Beckman Coulter’s CEO Scott Garrett last month is being blamed on the company’s ongoing regulatory issues.
“The abruptness of this resignation surprises us, and suggests that the issues facing [Beckman] are not improving, forcing the board to consider alternative approaches,” Bruce Cranna, a Jeffer-ies & Co. analyst, writes in a research note.
Beckman provided no reason for the resigna-tion in an announcement last month. However, it did say initiatives to address “previously dis-closed quality issues are proceeding.”
Problems with Beckman’s cardiac troponin assays have led to a recall, a warning letter and a mandate to conduct a clinical trial.
Garrett will continue as a full-time, non- executive employee through Jan. 15 to help with the transition. He has been with the company for eight years, the last five as CEO, the company says.
Beckman’s board named J. Robert Hur-ley to serve as interim CEO, effective immedi-ately. Hurley, who joined the company in 2005, has served as senior vice president of human resources and chairman of Beckman Coulter Japan. He most recently led the integration of the Olympus acquisition.
(See CEO, Page 8)
the gmp letter October 2010Page 8
Procedural, Documentation Issues Lead to Warning for CeraSys
CeraSys received a warning letter citing it for not listing a product and for a number of proce-dural and documentation failures in the manufac-ture of its zirconia dental blocks.
The letter stems from an April 28 through May 4 inspection of the company’s Buena Park, Calif., facility. CeraSys responded to the Form 483 June 14, but the FDA refused to consider the response because it was submitted late.
CeraSys is still dealing with the FDA to address the issues, a company spokeswoman told GMP last month.
While the company is registered, it did not have a device listing for the porcelain powder used to manufacture the dental blocks, according to the Sept. 8 letter posted last month.
The company also did not have a device master record for the CeraSys-ZR blocks and had not validated the manufacturing process for the blocks.
As for procedural issues, CeraSys was cited for having:
● No design control procedures; ● Inadequate procedures for corrective
and preventive action. For instance, the company’s procedure does not state how to conduct an investigation or prevent a problem from recurring;
● Inadequate complaint-handling proce-dures, as they do not address how to receive, review and evaluate complaints in a timely manner;
● No procedures to calibrate specific equipment. The investigators also noted that regular maintenance for particular equipment had not been performed and documented;
● No procedures to evaluate suppliers of raw materials or contractors used to repair equipment;
● No written training procedures and no documentation that training has taken place; and
● No written medical device reporting procedures.
The warning letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm225786.htm. — Mari Serebrov
Morgan Stanley analyst David Lewis says he hopes Hurley doesn’t stay in the position perma-nently. “After lapses in quality control and regu-latory functions, we think that the market would respond best to an outsider as the new CEO,” he says.
During an earnings call in July, Garrett him-self openly pondered if the company needed more quality and regulatory experience in its leadership. “There is an obvious approach to remediating the situation by getting more exper-tise and stronger leadership into our quality and regulatory function,” he said.
The company’s regulatory problems began in February when Beckman contacted customers about discrepancies between AccuTnI results for troponin on its UniCel DxI platform versus the Access or Access 2 platforms, Cranna says.
Beckman recalled a portion of the tropo-nin assays in March after making unapproved changes to the diagnostics. It also said it would submit new 510(k)s for the AccuTn1 tests used with both the DxI and Access systems.
An FDA warning letter citing the company for the unapproved changes was sent in June. In response to the letter, the company announced plans to conduct a clinical trial (GMP, August).
The financial impact of the ordeal has been substantial, Beckman’s Chief Financial Officer Charlie Slacik said during the July earnings call. — Virgil Dickson
CEO, from Page 7
the gmp letterOctober 2010 Page 9
First Inspection in Years Leads To Warning Letter for InTec
InTec Industries received a warning letter fol-lowing the first FDA inspection it’s had in 16 years.
The Birmingham, Ala., company, which makes face shields and extended eye shields, was inspected in August. Its last inspection was in 1994, InTec President Frank Lee told GMP, not-ing that all the forms and required paperwork have changed since then.
The FDA considered InTec’s response to the Form 483 inadequate because it did not provide any information or documents to reflect that cor-rections were made, according to the Sept. 3 warn-ing letter, recently posted to the agency’s website.
In addition to that documentation, the FDA requests a time frame indicating when each correc-tion will be implemented. InTec is submitting the necessary documentation to the agency, Lee said.
Most of the compliance issues noted by the FDA inspector involve procedures. For instance, the letter says the company has no:
● Medical device reporting procedures; ● Measures in place to investigate a device
nonconformance and determine a way to prevent a recurrence;
● Complaint-handling procedure; ● Specifications for purchasing controls; ● Procedures to assess the suitability and
effectiveness of the quality system at de-fined intervals;
● Procedures for quality audits; ● Written procedures for employee train-
ing. Employees had not been trained to recognize device defects, and records are deficient to cover all training received;
● Procedures for handling and controlling nonconforming products; and
● Written procedures to cover device his-tory records. The record was not docu-mented during the actual manufacturing process, no labeling was included in the record and there is no assurance the de-vice is manufactured in accordance with the device master record.
InTec also was cited for failure to maintain its device master records with all the required information and failure to document in-process inspections, tests or other verification activi-ties and approvals in accordance with its quality assurance programs.
The letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm2250 96.htm. — Mari Serebrov
Storz Gets Warning for Failures In Handling of Defective Devices
Storz Medical has received an FDA warning letter for GMP failures in its handling of defec-tive devices.
Storz’ Tagerwilen, Switzerland, facility had no protocol, including acceptance criteria, for a change implemented to fix cracked cooling pumps in its Modulith SLX-F2, a urological stone therapy device, according to the Aug. 24 letter posted online recently. Additionally, there was no documentation to show the change was validated.
A March inspection also found Storz did not follow its procedure for control of nonconform-ing products. It had no documentation of the evaluation and disposition of certain pumps with cracked intakes. The defect was spotted during production.
Further, the company did not extend a com-plaint investigation for a crack at the inlet hose attachment of the cooling pump in the SLX-F2 to other units with the same defect.
During the complaint investigation, three pumps with the same defect were detected in pro-duction, but Storz has no documentation that the units were evaluated and that results or conclu-sions were included or referred to in the com-plaint, the letter says.
A follow-up inspection is required to assure the company’s corrections are adequate, the letter says.
Storz did not return a request for comment by press time. The warning letter is available at www.fda.gov/ICECI/EnforcementActions/Warn ingLetters/ucm224014.htm. — April Hollis
the gmp letter October 2010Page 10
Maquet Forms Response Team After Getting Warning Letter
When Maquet Cardiovascular got a warning let-ter in August citing it for the way Boston Scientific handled a recall four years ago, it formed a special team, including external consultants, that met daily so it could resolve the issues as quickly as possible.
Each team member was assigned specific duties with deadlines attached, Christian Keller, president and CEO, told GMP. As an added measure, the vice president for quality moved into the office next to Keller’s, and the two met every morning.
The letter, posted last month, stems from an inspection in April and May of Maquet’s Wayne, N.J., facility, which it acquired when it purchased Boston Scientific’s cardiac and vascular surgery business in 2008.
Product Correction
At the crux of the letter is a correction Boston Scientific made in 2006 without notifying the FDA. After receiving reports of condensation forming inside the blister packaging of its Hemashield vas-cular grafts when they were stored in extreme heat and humidity, Boston Scientific sent its customers a letter asking them to check their inventory of the grafts. If they spotted this problem, they were told to return the device for a free replacement.
Boston Scientific did the right thing in informing customers of the problem, which did not affect the safety of the collagen-coated implants, Keller said. However, the FDA is citing Maquet for Boston Scientific’s failure to notify the agency.
Boston Scientific began redesigning the pack-aging in 2007 so it could withstand higher temper-atures. The new package design was rolled out in December 2008 after Maquet, which is part of the Getinge Group, acquired the division, Keller said.
During this year’s inspection, the FDA inves-tigator advised Maquet to consider a second vol-untary recall action covering all Hemashield prod-ucts in the old packaging. That Class II recall was initiated in July. The FDA acknowledges the recall in the Aug. 11 warning letter, but it notes that no
corrective or preventive actions were implemented to prevent a recurrence of the problem.
The company also is cited for not validating its cleaning and sanitizing procedures and for not revalidating the five-year shelf life of its pouch and blister tray packages after a validation study failed to meet the acceptance criteria for the mechanical peel test.
Maquet responded to the observations noted in the Form 483, but the FDA wanted more docu-mentation. Keller said the company has submit-ted the documentation.
The warning letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm225051.htm. — Mari Serebrov
FDA Defines ‘Manufacturer’ In Final Lenses Guidance
Addressing devicemaker concerns, the FDA has clarified the definition of a manufacturer of impact-resistant lenses in a final guidance released last month.
A manufacturer is a person or company that puts the lens in the form ready for its intended use or that alters the physical or chemical char-acteristics of the lens by grinding, heat treat-ing, beveling, applying scratch resistant coating, applying anti-reflection coating, cutting or per-forming other pertinent actions, the agency says in the question-and-answer guidance.
The agency was asked to clarify this definition in comments to the October 2007 draft guidance. Public input also resulted in other revisions. For instance, the FDA removed a question regarding the salability of plastic prescription lenses tested as part of a statistical sample. And it modified sev-eral questions on testing requirements. The final guidance says all plastic prescription lenses and OTC glass lenses can be tested in either “un-cut finished” or “finished” form.
“Impact-Resistant Lenses: Questions and Answers,” which supersedes a 1987 guidance, is available at www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocu ments/ucm070579.htm. — Virgil Dickson
the gmp letterOctober 2010 Page 11
CDRH Touts 510(k) Changes Amid Inspection Concerns
CDRH is trying to sell devicemakers on sug-gested changes to the 510(k) process, saying the changes would increase regulatory predictability.
“It is not our intent to turn the world upside down for device manufacturers,” Christy Foreman, acting director of CDRH’s Office of Device Evalua-tion, said during an agency webinar last month.
One proposal that raised concerns was pre-clearance inspections. When the suggestion appeared in a working group report, Mark Lea-hey, president of the Medical Device Manufac-turers Association, argued that the agency lacked evidence that this suggestion would improve the clearance process.
During the webinar, held to discuss the recom-mendations included in a report released last month by a CDRH working group, some devicemakers said requiring the inspections would slow the pro-cess as it would stretch CDRH’s already limited inspection resources.
CDRH Director Jeffrey Shuren responded that the impact of such inspections on devicemakers would likely be small.
Third-Party Review
CDRH also reaffirmed plans to enhance its third-party reviewer program, created to help ease the application review burden on staff reviewers. This would include providing third-party reviewers with information that is now available only to FDA reviewers, Shuren said.
Currently, external reviewers cannot access the predicate database used by the FDA when evaluating submissions. Because of such obsta-cles, only 8 percent of 510(k) applicants opt for a third-party review.
Although not addressed in the report, the cor-rective fix program came up during the webinar. Under the program, some manufacturers have had to recall older devices when CDRH clears improvements (GMP, May). Shuren denied that
the program required recalls of devices that pre-sented no safety concerns.
“We’ve seen situations where a manufacturer had safety problems with a device and, rather than go through a recall, may have submitted a 510(k) instead,” he said.
“A lot of questions have been raised about the circumstances under which a 510(k) should be submitted versus when a recall should be con-ducted,” Shuren said. “We plan to issue a guid-ance to clarify these circumstances, which some folks have identified as a corrective fix.”
(See 510(k), Page 12)
FDA Gives Warning to CTI For Notification Problems
Circulatory Technologies Inc. (CTI) was hit with a warning letter for failure to notify the FDA within 10 days of initiating a removal of one lot of its Bigger Better Bladder because of leakage problems.
However, CTI did notify the FDA, but appar-ently not the right office, company President Yehuda Tamari told GMP. When the company became aware of three units that had leakage between the bladder and the end cap, it notified all the customers and the main FDA office.
During a March inspection of its Oyster Bay, N.Y., facility, CTI was told that it should have informed the district office of the removal, Tamari said.
The company also was cited for not estab-lishing procedures for corrective and preventive actions, engineering changes, complaint han-dling, medical device reporting, and supplier evaluation and selection.
Tamari said all the issues were resolved before CTI received the July 12 warning letter, which was posted last month. This time, CTI submitted the information to the branch office, he added.
The warning letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm225454.htm. — Mari Serebrov
the gmp letter October 2010Page 12
Throughout the webinar, many of the ques-tions centered on a proposed Class IIb device certification. The subclass would be used for 510(k) devices that are more likely to require additional clinical information.
The data requested for these devices would generally be less extensive than the requirements for PMA devices, which must be supported by randomized, double-blind studies, Foreman said.
Instead, device sponsors might be asked for human factors data or data from studies con-ducted outside the U.S., Shuren added.
CDRH officials promoted the upsides of a Class IIb process, touting it as a step toward global har-monization. By adding the subclass, the U.S. device regulatory system would more closely resemble the four-class systems used in Canada and the EU.
Having such harmonization could lead to devices being simultaneously cleared domesti-cally and abroad, Shuren said.
CDRH is still developing the criteria that would be used to determine which devices should be Class IIb, and it’s not sure how many devices would fall into that category.
CDRH’s de novo process also may be re-vamped. Currently, devices must go all the way through the 510(k) process and receive a not- substantial-equivalency notice before they are eli-gible for the de novo program, which is typically used for Class II devices that have no predicates. One possibility is to inform devicemakers much
earlier that their device could be considered de novo, Shuren said.
He prefers creating overarching regulation and then introducing special controls for each de novo device, rather than going through a new rulemaking process for each device.
CDRH hopes to release the suggestions included in the 510(k) report that it wants to pur-sue by the end of the year, Shuren said. — Virgil Dickson
510(k), from Page 11
Reporters: David Belian, Virgil Dickson, LaCrisha Butler, Wilson Peden
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Copyright © 2010 by Washington Business Information Inc. All rights reserved. The GMP Letter (ISSN 0196-626X), an executive brief-ing on FDA enforcement and quality systems requirements for medical devices and diagnostics, is published monthly, 12 issues, for $945. Photocopying or reproducing in any form, including electronic or facsimile transmission, scanning or electronic storage is a violation of federal copyright law and is strictly prohibited without the publisher’s express written permission. Subscribers registered with the Copyright Clearance Center (CCC) may reproduce articles for internal use only. For more information, contact CCC at www.copyright.com or call (978) 750-8400. For site licenses for multiple users or to purchase multiple copies, contact Alka Desai at (703) 538-7669.
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One of these involved an MDR submitted after a Transcam detector fell off the camera and hit the floor, missing the technician’s foot. The investigation found that the camera was serviced by a third-party vendor and the screws holding the detector onto the camera had fallen to the floor or were not completely screwed in.
A subsequent complaint that reported screws holding a detector onto the support arm of a Transcam were stripped and voiced a concern that the detector could fall off was not reported as an MDR. The decision tree for the complaint states that the device malfunctioned but that a recurrence would not be likely to lead to a death or serious injury, the form says.
Philips has responded to the observations and has not heard anything further from the FDA, company spokesman Ian Race told GMP.
The Form 483 is available at www.fdanews.com/ext/files/Philips.pdf.
Form 483 Insider, from Page 5
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