Pilot Study Finds Unresolved Issues As FDA Works to Release UDI Rule

A second FDA unique device identifier (UDI) pilot study reveals several issues that are unlikely to be resolved before the FDA pub-lishes a proposed rule in 2011, a new report says.

Devicemaker feedback from the second pilot raised a number of questions the agency doesn’t expect to answer for at least a year after the rule has been released, according to the FDA report.

The questions include how many brand or design changes can occur within a single UDI, whether the UDI changes with each 510(k) or PMA submission and how many indications can be included in one UDI.

Devicemakers Say Increase in MDRs For AEDs Not Due to Manufacturing

An increase in serious adverse events tied to automatic external defibrillators (AEDs) may have less to do with faulty manufacturing issues than with industry confusion over the FDA’s medical device reporting (MDR) policy.

To address the issue, the agency plans to revamp its 1994 MDR guidance, Megan Moynahan, leader of CDRH’s Cardiac Electro-physiology and Monitoring Devices Network, said last month at a public workshop on AEDs.

CDRH received more than 28,000 adverse event reports involv-ing AEDs from January 2005 through May; the incidents include deaths, patient injuries and device malfunctions.

Many of the reports can be attributed to a conservative reading of the agency’s MDR policy, Derek Smith, a senior vice president at Philips Healthcare, said at the workshop.

Issue No. 372January 2011

Devicemakers told to fol-low GHTF in lieu of delayed FDA UDI rule ..........Page 3

Form 483 Insider ....Page 5

OsteoSymbionics works to resolve warning letter is-sues ..........................Page 6

Inadequate procedures lead to first warning letter for Gunnell ....................Page 7

FDA warning cites Eagle Health for lack of manufac-turing procedures .....Page 8

Anchor warned after FDA finds complaint, MDR de-viations.....................Page 9

Steris facility warned for is-sues with sterilizing proce-dures ........................Page 9

GHTF asks devicemakers to have a plan before QMS in-vestigations ............Page 10

Align Technologies warned for MDR failures ....Page 11

WalkMed warned for han-dling of device failures, complaints ..............Page 11

INsIde thIs Issue

(See AEDs, Page 12)

(See UDI, Page 2)

the gmp letter January 2011Page 2

The FDA expects to release the proposed rule in June.

The pilot looked at the business processes — submission, receipt, and analysis and use of data — that will involve the UDI database.

The subsequent feedback helped identify issues and, where possible, answer questions related to populating and using the database to improve the identification of device information, the FDA says.

As part of the pilot study, devicemakers sub-mitted 23 data elements, down from the 47 used in the prototype UDI database in 2009.

Companies that participated in the prototype study had balked at some of the elements, say-ing the database should ask for a set of clearly defined attributes that relate to all products and are globally harmonized where possible.

Data Accessibility

Another problem with the prototype was the accessibility of required data.

To easily provide the majority of the attri-butes required in the prototype, companies would have to maintain them in a central loca-tion, an unidentified devicemaker told the agency.

The company also would have to develop procedures and assign resources to collect and maintain the required data.

In some instances, that was still a prob-lem with the second pilot. For example, data on allergens, as well as storage conditions, sterility and restricted number of uses, “are not stored in an easy-to-obtain, discrete form,” participants said.

Most devicemakers already have latex infor-mation on their labels and in a centralized data-base, but “information about other allergens is more problematic,” the report says.

Other devicemaker concerns about the UDI system include the cost of complying with the regulation.

“To maintain margins, industry must either gain efficiencies or pass along the added costs,” one devicemaker said.

Costs could get excessive if bar codes must be placed on small units of use such as cap-sules, syringes, vials, tubes or cartridges, another devicemaker noted, adding that some product packages are too small for bar codes.

Implementing UDI also could prove costly and time-consuming for the FDA itself.

The report identifies several challenges facing the agency, including:

● Ensuring that UDI is included as an at-tribute in all databases containing product information;

● Revising forms and instructions to ac-commodate a place for the UDI and developing shorter-term solutions until forms have been changed or updated;

● Devising a linking method for the UDI da-tabase application so there is a connection among a device’s packaging levels; and

● Training FDA staff to use the UDI data-base information.

The agency’s UDI group also needs to under-stand and identify whether there will be any dif-ficulties incorporating specific attributes, the report says.

For instance, issues with electronic submis-sion should be discussed to ensure that the expe-riences in the test environment mirror what the actual submission process will be, the report adds.

“Results of FDA Pilot Activities to Explore Opportunities and Challenges with the Imple-mentation of a Unique Device Identifier System” is available at www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentifi ers/ucm235962.htm. — Virgil Dickson

UDI, from Page 1

the gmp letterJanuary 2011 Page 3

Devicemakers Told to Follow GHTF In Lieu of Delayed FDA UDI Rule

As CDRH has once again pushed back the release of its long-anticipated proposed unique device identifier (UDI) rule, devicemakers should look at the Global Harmonization Task Force’s (GHTF) new draft guidance on UDI so they can begin planning their internal systems.

Jay Crowley, senior adviser for patient safety at CDRH, said GHTF’s Nov. 4 draft reflects sug-gestions laid out in CDRH’s upcoming proposed rule (see story, page 1).

The GHTF guidance is intended to establish a single UDI system to facilitate the traceability of devices worldwide.

But the safety benefits will only be achieved if all stakeholders use the globally harmonized system without regional adaptations, GHTF says.

The guidance proposes a risk-based approach to implementing the global system and determin-ing what level of packaging requires a UDI.

It also includes several recommendations about the formatting and placement of the UDI:

● The UDI should be “human readable” and accessible;

● Durable devices, devices that are not packaged, or ones that require reprocess-ing, cleaning, sterilizing or adjusting between uses should be directly marked with a permanent UDI carrier, in addition to the marking on the primary packaging;

● The UDI is required on only one part of a device that consists of multiple components;

● Direct part marking may not be possible or warranted on some devices because of size, design, materials, processing or per-formance issues;

● The UDI carrier for low-risk devices packaged and labeled individually can be on a higher level of packaging, such as a shelf pack, unless the user does not have access to the higher-level packaging; and

● A kit should have a UDI, but individual devices in the kit do not need a UDI car-rier as long as the manufacturer has a way to identify them.

The draft guidance also recommends a new UDI whenever a significant change is made to a device. Therefore, reprocessors of single-use devices and remanufacturers would need to create a new UDI.

The UDI serves as an access key to a global device database that contains basic information. GHTF suggests each entry include more than 22 data elements, down from the 47 CDRH required last year as part of a prototype database, but up from the 12 CDRH’s proposed rule is expected to have.

Beyond basic information, such as the name and address of a devicemaker, the GHTF pro-poses data elements such as whether a device should be sterilized before use, it has a restricted number of reuses or it contains latex.

Originally, GHTF had planned to follow the FDA’s lead on UDI, as it wanted its guidance to be compatible with the U.S. mechanism.

FDA’s Efforts

The FDA began taking comments on a UDI system in 2006 (GMP, September 2006). The system was mandated a year later by the FDA Amendments Act.

The agency has consistently missed numerous target dates for issuing the proposed rule.

CDRH also has delayed issuing a request for proposals (RFP) to develop its UDI database (GMP, September 2010). It had expected to publish the RFP before the end of 2010, but it is still working through technical issues and security concerns.

Comments on GHTF’s draft guidance are due by April 30, but the task force hopes to get input in the next few months so it has time to refine the guidance for a GHTF steering committee in May, Crowley said.

The draft guidance is available at www.ghtf.org/documents/AHWG-PD2-N2R2.doc.— Virgil Dickson

the gmp letter January 2011Page 4

Regulatory Compliance Software

Regulatory Compliance

GMP

Medical Device

Biotechnology

MedWatch

Medical Device Reports

Complaint Handling

FMEA

Quality Assurance

MedWatch Plus

FDA Compliance

ISO 13485

ISO 14791

Blood Services

cGxP

FDAGxP

FDA Submissions

Electronic Signatures

eValidationFDA Regulations

Risk Management

Risk Assessment

Quality

Risk

FDA

Pharmaceuticals

21 CFR Part 1270

FDA

FDA

cGxPCFR 11

ISO

Medical Device

ISO 13485Quality CFR

21 CFR Part 11

21 CFR Part 11cGxP

FDA Submissions

MedWatch PlusFMEA

Quality

Electronic Submissions

ISO 14791

ISO 14791

FMEA21 CFR Part 1270

Biotechnology

Biotechnology

Electronic SubmissionsFDA

CFR 11Life Sciences

Life Sciences

cGMP

cGMP

cGMPQuality Assurance Software

Quality Assurance Software

Quality Assurance Software

ISO

FDA Submissions

Quality

Complaint HandlingMedical Device

Medical Device

21 CFR Part 1271

21 CFR Part 1271

FDA

Failure Mode E�ects Analysis

Failure Mode E�ects Analysis

ISO

Failure Mode E�ects Analysis

MedicalDevice

Regulatory Compliance

Regulatory ComplianceeValidation

Life Sciences

Biotechnology

BiotechnologyQuality Assurance Software

Complaint Handling

Quality

FDA RegulationsMedical Device

FMEA

eValidation

eValidation

eValidation

eValidation

cGMP

Regulatory Compliance SoftwarePharmaceuticals Risk Management Quality

Pharmaceuticals

Pharmaceuticals

CFR 11

Compliance

Quality Assurance

Quality Assurance

21 CFR 11

21 CFR 11

Life Sciences

Risk Assessment

Risk Assessment

Risk Management FDA Submissions21 CFR Part 1271Pharmaceuticals

Blood Services FMEA

ISO 13485Compliance

Compliance

ISO 14791

ISO 14791

21 CFR 11

GMP

eMDR

eMDR

Good Manufacturing Practices

Good Manufacturing Practices

Good Manufacturing Practice21 CFR 11

21 CFR Part 1271

Blood & Tissue

Blood & Tissue

FDA Regulations

Med Watch

MedWatch Plus

FDA Compliance

GMP

ISO

eMDR

FDAGMP

Risk

ISO

eVal

CFR

GxP

FMEA

eMDRGMP

21 CFRGxP

Blood

eMDR

RiskFMEA

GxP

cGMP

ISO

FDA

21 CFR

FMEAGxP

Biotech

21 CFReVal

GxP

FMEA

cGMP

Pharma

Quality

ISO

FDA

Blood

ISOFDA

GMP

CFR

Quality

Change Management

Change Management

Change Management

Change Management

Change

www.etq.com/value 800-354-4476 • info@etq.com

Best Practices: Integrated modules for Quality and FDA Compliance Management:Document Control • Reporting • Audits • Training • Nonconformance CAPA • Change Management • Risk Assessment ...and more!

Risk Management: Identifies, mitigates, and prevents high-risk events

Flexible: Leading edge flexible workflow adapts to all business processes, without programming

Integration: Integrates with 3rd party business systems

Scalable: Readily adapts to enterprise and multi-site deployments

FDA Compliance: Configurable solution for regulated companies, 21 CFR Part 11 compliant

Business Intelligence: Enterprise reporting tracks KPIs, aids in decision-making with hundreds of configurable charts and reports

...with the most VALUE

Select the Enterprise Quality & Compliance Management Solution...

the gmp letterJanuary 2011 Page 5

FDA Gives Invacare a 483, Citing Corrective Actions

Invacare failed to take adequate corrective action in response to reports of patients being trapped in its medical beds, sometimes resulting in death, a recent Form 483 says.

In one instance, a patient was found with her head in the left side of the rail, face down in the mattress, the form says. Invacare’s investigation of the March 2009 complaint was inadequate because it did not document its attempt to get information on the mattress involved, make a good faith effort to get information about the complaint and deter-mine the most likely root cause.

An August 2 to 18 inspection of the Sanford, Fla., company found it also did not determine the most likely root cause for a May 2009 com-plaint involving a patient who was found dead with her legs on the floor and her head trapped in a bed rail.

After receiving an April complaint about a fire that started at the foot of an Invacare bed, resulting in a consumer’s death, the company failed to document a review for similar incidents, identify potential root causes and ensure no cor-rective action was needed, the form says.

Invacare will follow through with all FDA requests, company spokeswoman Lara Mahoney told GMP.

The Form 483 is available at www.fdanews.com/ext/files/Invacare.pdf.

Abbott Gets 483 for GMP Issues And Unreported Field Actions

Abbott Point of Care received a Form 483 related to unreported field actions, environmental controls and process validation protocols.

The Princeton, N.J., company failed to report two field actions, implemented in 2006 and 2008, involving its i-STAT cartridges. It also failed to submit four medical device reports (MDRs) within

30 days. In one instance, it filed the MDR 140 days after it learned of the incident, the form says.

The FDA investigator notes that Abbott’s environmental specification for deionized water does not identify the quality control methods required for monitoring the total organic car-bon in the deionized water, including remedial actions for out-of-specification results.

During a July 19 to August 11 inspection, the investigator found protocols for several process validations did not include or document accep-tance criteria.

The company has implemented corrective actions to ensure all requirements are being met, spokesman Don Braakman told GMP. The Form 483 is available at www.fdanews.com/ext/files/Abbott122710.pdf.

Defibtech Gets 483 Noting Issues With AED Batteries

Defibtech has received a Form 483 after an FDA inspection uncovered issues with its auto-mated external defibrillator (AED) batteries.

A July 29 to August 18 inspection of the Guilford, Conn., company found a corrective measure was implemented to address high volt-age during the charging of new battery packs.

The corrective action report notes the device failed to shock due to an overshoot charge on the bat-tery pack and an error code. But the company did not specify the error code in its data trend analysis.

In a review of nonconforming material reports, the FDA investigators found 15 reports, dated from April 9 to June 1, 2007, that lacked final disposition, according to the form.

Additionally, Defibtech’s procedure for inspection, measuring and test equipment does not identify the process to identify, remove and evaluate equipment due for calibration.

The company did not respond to a request for comment by press time. The Form 483 is available at www.fdanews.com/ext/files/Defibtech.pdf.

form 483 INsIder

the gmp letter January 2011Page 6

OsteoSymbionics Works to Resolve Warning Letter Issues

OsteoSymbionics, a maker of cranial plate implants, is hoping to resolve a recent warning letter that cited problems with several manufac-turing procedures early this year.

The Cleveland company is well on its way to addressing most of the issues, CEO Cynthia Bro-gan told GMP. The warning letter stems from an Oct. 13 inspection, the first the 3-year-old device-maker has had.

During the inspection, an FDA investiga-tor noted that several design controls for the development of the implant were inadequate. For instance, OsteoSymbionics failed to estab-lish design inputs, as well as a design and devel-opment plan. It also did not fully implement its design verification procedure or validate the implant design, the letter says.

In other validation problems, the company failed to validate the mixing, curing, casting and cleaning processes for the implants. Although the instructions for use provide directions for

re-sterilization, the company did not validate ster-ilizing the device more than one cycle, according to the Nov. 30 letter posted in December.

The instructions for use also give a steriliza-tion parameter of 30 percent to 80 percent relative humidity. But the company had validated steriliza-tion at 55 percent, rather than at the entire range.

Other problems noted include:

● A corrective and preventive action proce-dure doesn’t list manufacturing processes and noncomformances as sources that should be analyzed to identify existing and potential causes of quality problems;

● None of the engineering change notices reviewed by the investigator documented why no verification or validation was conducted, as required by the company’s procedure; and

● The company failed to maintain a device master record for the implants.

The warning letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm235310.htm. — Mari Serebrov

While there are more than 20 references to training within the FDA’s GMP regulations, the vagueness of the requirements is a constantsource of confusion for companies, their training officers and their employees. Unfortunately, GMP trainers are often expected to create atraining course, get everyone’s signature on the “happy sheet,” and go away. As a result, these reportedly trained professionals can’t pos-sibly have learned the material.

This critical workshop thoroughly covers the best way to convey your GMP knowledge to your staff efficiently, accurately and effectively.Through a series of hands-on exercises, you'll develop and deliver a clear and concise GMP training program that will fully prepare youremployees to handle GMP with confidence. At this workshop, you will:

• Examine training systems and programs• Identify current expectations that regulatory agencies and quality auditors have of training systems and programs• Examine models that are used to efficiently design and produce training solutions• And much more

An Interactive Workshop Presented by LearningPlus and FDAnews

From Training to Learning:Improving GMP Performance

An ConferenceMarch 28–29, 2011 • Doubletree Hotel Bethesda • Bethesda, MD

Register online at: www.fdanews.com/2992AOr call toll free: (888) 838-5578 (inside the U.S.) or +1 (703) 538-7600

the gmp letterJanuary 2011 Page 7

Inadequate Procedures Lead To First Warning for Gunnell

Wheelchair manufacturer Gunnell is working with the FDA to clear up its first warning letter.

The Millington, Mich., company, which has been in business since the 1950s, failed to get approval or clearance for some of its products, and several of its manufacturing procedures are inadequate, according to a Nov. 9 warning letter posted last month.

As a result of the June inspection, the com-pany is working on documentation issues and implementation of revised procedures, a Gunnell spokesman told GMP.

The company has responded to the warning letter, which notes that, prior to June 2, several of Gunnell’s procedures had not been approved by management.

Complaint Handling

The FDA investigator also found that Gun-nell had no documented procedure for receiving, reviewing and evaluating complaints. Since com-plaints had not been documented, the company could not produce complaint files.

At least eight of the return authorization forms the company received from July 4, 2008, to May 11 met the definition of a complaint, the letter says.

But the company did not investigate to deter-mine why the wheelchairs involved did not meet specifications.

In addition, Gunnell’s corrective and preven-tive action procedure “does not describe how quality data sources such as complaints, non-conformities and service logs are to be analyzed at regular intervals using statistical methods to identify existing or potential problems,” the let-ter says.

The company also did not have a documented procedure to ensure a device history record is maintained for each serial number to demonstrate

that the product is manufactured in accordance with the device master record.

Of the 47 serial numbers selected for review, the investigator found that 37 were missing inspection sheets and 25 did not have order sheets.

Of the 22 order sheets available for review, 19 lacked the date the order was received for ship-ping and the name of the person who shipped the finished chair. None of the order sheets had the date the order was received for assembly and the name of the person completing the assembly.

Other citations include failure to:

● Document the evaluation of a supplier or an approved supplier list;

● Properly store nonconforming parts. For instance, nonconforming parts were stored in an unlabeled box in the assem-bly area, along with unlabeled wheels that had been returned, refurbished or were new;

● Calibrate the digital calipers used for measuring incoming parts. The company had no documentation showing that they had been calibrated previously;

● Set up an internal audit schedule or record of having conducted an audit within the past five years;

● Specify or define, in the qualification training procedure, the fundamental qual-ity improvement concepts that are to be included in employee training; and

● Establish a documented procedure for evaluating and investigating complaints to determine when medical device reports should be submitted to the FDA and how they are to be reported.

The FDA informed Gunnell a follow-up inspection would be required to ensure correc-tions are adequate.

The warning letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm234820.htm. — Mari Serebrov

the gmp letter January 2011Page 8

FDA Cites Eagle Health for Lack Of Manufacturing Procedures

Failure to establish several basic manufactur-ing procedures for its disposable CPR mouth bar-riers resulted in a warning letter to Eagle Health Supplies.

The letter stems from a July inspection of the Orange, Calif., company, which is a specification developer, initial importer and distributor of the mouth barriers.

During the inspection, an FDA investiga-tor noted that the company did not have proce-dures for handling complaints, submitting medi-cal device reports or implementing corrective and preventive actions (CAPAs). In fact, management told the investigator that it was not aware of the CAPA requirements, according to the Nov. 24 letter posted last month.

Although the company imports the devices from contract manufacturers overseas, it has no procedures to ensure the suppliers meet quality

requirements. It also does not require suppliers to provide finished device acceptance records or certifications of compliance, the letter says.

Eagle Health also lacked:

● Finished device acceptance procedures; ● A procedure to control design changes; ● Device master records. The company

indicated it gives drawing specifications to contract manufacturers, but it did not present them to the investigator;

● Device history records; ● Document control procedures; ● Management review procedures. The

company has not conducted management reviews;

● Quality system procedures and instruc-tions; and

● A quality policy.

The company declined to comment. The let-ter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm236591.htm.— Mari Serebrov

We know your time is precious. That's why, for just 5 minutes of yours, FDAnews will provide you with our best-selling Taming the Change Control Beast management report as a way of saying thank you for your participation.And rest assured — all participant responses will be kept confidential.

A $377 value, this management report is indispensible for anyone involved in producing or maintaining changecontrol forms that work. The report includes step-by-step analysis of what elements must be included in a changecontrol form, as well as guidance on what to leave out, plus text of the FDA rules that mandate change controlforms. And it’s yours for participating in the survey.

We appreciate your time and input. Please feel free to share this survey invitation with any of your colleagues.

Visit www.BrandAwarenessSurvey.com to begin.

Hurry — response intake ends on Jan. 14, 2011.

Take the FDAnews Brand Awareness Surveyand receive a complimentary report!

the gmp letterJanuary 2011 Page 9

Anchor Warned After FDA Finds Complaint, MDR Deviations

Anchor Products has received a warning letter citing it for a number of issues, including handling of complaints and medical device reports (MDRs).

During a May 26 through June 4 inspection of the Addison, Ill., company, FDA investigators noted that Anchor’s complaint procedure doesn’t address the types of adverse events that should be submitted as MDRs, the time frame required for reporting them or the manner in which they should be reported.

The investigators identified several complaints involving malfunctions of Anchor’s tissue retrieval system that should have prompted MDRs, accord-ing to the Nov. 8 warning letter posted last month.

No MDRs

For example, the company received a com-plaint in October 2009 that one patient needed surgery to remove metal parts of the device that had broken inside the patient’s abdomen during a prior procedure. But no MDR was filed.

Following that incident, the company received five similar complaints, and again, no MDRs were submitted, the letter says.

The company also lacks adequate procedures involving:

● The maintenance of records of complaint investigations. A company official told the investigators that Anchor didn’t document visual inspections of returned product. The company doesn’t keep photographs or include visual results in the record of the investigation;

● Corrective and preventive actions (CAPAs) to identify existing and potential causes of nonconforming product and other quality problems. The company’s complaints and CAPA procedure only addresses actions taken in response to product complaints. It does not consider other sources of qual-ity problems, such as service records and returned product;

● Design changes. Anchor made design changes to the tissue retrieval system. When it released the new models, it only had an unsigned, undated document not-ing the changes; and

● Document control. The company’s pro-cedure permits department managers and area supervisors to create new forms for use in their areas. The plant manager documented 14 CAPAs on an unapproved form. And complaints were documented on an unapproved form.

Anchor also is cited for its organizational structure. During the inspection, two employ-ees claimed to be the management representative. Another employee told the investigators the man-agement representative wasn’t documented.

A company spokeswoman declined to comment.

The letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm234624.htm. — Mari Serebrov

Steris Facility Gets Warning For Sterilizing Procedures

Steris Isomedix Services has received a warning letter citing it for not establishing ade-quate procedures involving its relative humidity (Rh) monitors.

During a June inspection of the company’s Grand Prairie, Texas, facility, FDA investigators found Steris had no procedures to address how many monitors are placed in a sterilization load and how it accepts or rejects Rh data recorded during routine sterilization cycles subject to parametric release.

The company, which performs contract ster-ilization of devices, also has struggled to keep up with corrective and preventive actions (CAPA), according to the Sept. 27 letter posted last month.

The investigators found some sterilization loads had Rh levels at the end of the humidity

(See Steris, Page 10)

the gmp letter January 2011Page 10

GHTF Asks Devicemakers to Have A Plan Before QMS Investigations

Before investigating an existing or potential nonconformity, a devicemaker should have a doc-umented plan in place, a final guidance from the Global Harmonization Task Force (GHTF) advises.

The plan should include resources, time frame, a description of activities to be performed, methods and tools, the investigation team and their respon-sibilities, and the scope of the investigation, which should be in line with the determined risk of the nonconformity. The plan also should describe the nonconformity in a problem statement.

Released by GHTF last month, the quality management system (QMS) guidance finalizes a draft that was released in 2009. The final docu-ment makes a few changes to the draft, including the recommendations for the investigation plan.

It also encourages companies to review infor-mation from external data sources, including the media, as part of the investigation. “The aggre-gation of information from more than the origi-nal data source may lead to more comprehensive knowledge,” the guidance says, adding that the increased knowledge will help the manufacturer better determine appropriate action.

Another change in the final guidance is the addition of a list of questions to help manufactur-ers determine the effectiveness of corrective or improvement action. These questions should be con-sidered throughout the process and in a final review:

● Has the problem been comprehensively identified?

● Has the extent of the problem been iden-tified? This includes such things as the range of affected devices, patient out-comes, the process, production lines and operators.

● Have the root cause and contributing fac-tors been identified and addressed?

● Has the improvement action been de-fined, planned, documented, verified and implemented?

The final guidance includes an additional appendix, which provides examples for docu-menting various requirements of improvement processes.

The “Guidance on Corrective Action and Pre-ventive Action and Related QMS Processes” is available at www.ghtf.org/documents/sg3/sg3_n18.pdf. — Mari Serebrov

dwell that were outside the customers’ specifica-tions, but only the readings within the specifica-tions were reported to the customers, the letter says. No CAPA was initiated to investigate and evaluate the out-of-specification Rh levels.

On a related note, the investigators saw that Steris had opened a CAPA in March because some Rh monitors had not been calibrated in accordance with the manufacturer’s instructions. While the monitors were calibrated a month later, the company’s assessment didn’t address the risk the calibration failure posed to the sterilization process.

A fourth citation involves failure to follow internal procedures for calibrating environmental monitors.

Steris also was cited for not maintaining ade-quate device history records.

Steris is currently under a consent decree to transition its customers from its System 1 ster-ilizer to other alternatives (GMP, May 2010). In February, CDRH informed healthcare providers that they had until Nov. 2, 2011, to transition to a new device sterilizer.

The warning letter will have no impact on the consent decree, Steris spokesman Stephen Norton told GMP. The issues raised in the let-ter are specific to the Texas facility and are being addressed, he added.

The letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm235752.htm. — Virgil Dickson

Steris, from Page 9

the gmp letterJanuary 2011 Page 11

Align Technologies Warned For Failure to File MDRs

Align Technology, the maker of Invisalign orthodontic devices and appliances, has received a warning letter for failure to report adverse events within 30 days.

Although the San Jose, Calif., company received a complaint indicating that a patient had to be treated with a steroid due to adverse events that occurred after using the Invisalign system, it did not submit a medical device report (MDR), according to the Nov. 17 warning letter posted last month.

Align also didn’t file MDRs after receiving complaints of a patient experiencing swollen, irri-tated lips and a swollen gingival and another patient who had a burning tongue sensation, sore throat, mouth ulcerations and swollen lymph nodes.

Devicemakers are required to submit MDRs within 30 days of learning that one of their prod-ucts may have contributed to or caused a seri-ous injury or illness. An MDR also is required if

a device malfunctions and the malfunction could contribute to or cause a death or serious injury if it were to recur.

The complaints were reviewed during an FDA inspection of Align’s San Jose facility this past sum-mer. The agency says it can’t determine if Align’s Aug. 26 response to the Form 483 is adequate because the company didn’t submit documentation of revised forms and standard operating procedures.

The company had sent a second response Nov. 8 with a complete update on the actions it was taking. That response may have crossed in the mail with the warning letter, Roger George, Align’s vice president and general counsel, says.

The company responded to the warning letter Nov. 22 and included the documentation the FDA requested. It has asked to meet with the agency to ensure that the issues in the warning letter have been fully addressed, George says.

The warning letter is available at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm234578.htm. — Mari Serebrov

WalkMed Warned for Handling Of Device Failures, Complaints

WalkMed Infusion has received an FDA warning letter related to its complaint handling and device risk analysis procedures.

The Englewood, Colo., company, which man-ufactures electronic infusion pump systems, did not investigate certain complaints of severe under-delivery of infusion fluid to determine patient outcome and whether medical interven-tion was required, according to the Nov. 22 letter posted online last month.

WalkMed’s risk management procedure requires it to revise the device risk analysis to incorporate newly identified hazards, but the company failed to revise its infusion pump sys-tem risk analysis after receiving complaints of severe under-infusion when patients were using the pumps at home, the letter says.

A risk analysis/failure modes and critical-ity document for the company’s Triton infusion pump is inadequate because it determined that over-infusions would always be detected.

But the failure of the door-open alarm resulted in over-infusions and led to a product recall, according to the letter.

In its Form 483 response, WalkMed said it had revised the Triton pump design and risk assessment documents and would conduct user testing.

The FDA deemed the response inadequate because it did not include the revised documents and the company did not plan to complete user testing soon enough.

WalkMed did not return a request for com-ment by press time. The warning letter is avail-able at www.fdanews.com/ext/files/UCM237261.pdf. — April Hollis

the gmp letter January 2011Page 12

For instance, devicemakers or AED users may submit an MDR when a defibrillator — sit-ting on a crash cart, in a wall cabinet or in a closet — signals it may need service.

“Should a report be made in cases where the manufacturer has data showing the issue can be detected prior to emergency use?” Smith asked.

Not knowing exactly what to report in such situations has led Philips to adopt an aggressive approach to MDRs over the past five years, he added.

Others devicemakers at the meeting said they have similar policies.

Another quandary involves patient deaths. When a company investigates such an incident, it may not be able to get all the information nec-essary to assess whether the patient could have benefited from defibrillation therapy, Smith said.

The volume of MDRs also could be tied to the increase of AEDs on the market over the past five years. Currently, about 1.5 million AEDs are in place around the world, workshop panelists said.

As financial pressures mount, the use of out-dated AEDs could become a bigger problem.

A new challenge stems from environmen-tal legislation that forced suppliers of commer-cial off-the-shelf components used in AEDs to change the materials they use.

The changes make the components less reli-able in the long run, Webster said.

Despite the problems raised by devicemakers, Alford Taylor, director of CDRH’s Division of Electrical & Software Engineering, wouldn’t let them completely off the hook.

“There are a lot of the situations where defi-cient product design or poor engineering was a cause,” he said.

Putting more funds into engineering systems up front “will pay off in the long run,” he added.

The workshop was part of a new industry-wide initiative the FDA launched in November.

The agency plans to convene an advisory panel early this year to determine the appropriate AED approval pathway that promotes the best prac-tices for design and testing. The pre-amendment devices are considered Class III, but some have been cleared through the 510(k) process.

CDRH hopes to make a final decision on the classification this year. — Virgil Dickson

AEDs, from Page 1

Reporters: David Belian, Virgil Dickson, Wilson Peden, Molly Cohen

President: Cynthia Carter; Editorial Director: Pamela Taulbee; Executive Editor: Mari Serebrov

Copyright © 2011 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.

300 N. Washington St., Suite 200 • Falls Church, VA 22046-3431 • Phone: (888) 838-5578 • +1 (703) 538-7600 • Fax: +1 (703) 538-7676www.fdanews.com

Customer Service: Kim Williams Editor: April Hollis Ad Sales: Matt Salt Content Sales: Alka Desai(888) 838-5578 • +1 (703) 538-7600 (703) 538-7650 (703) 538-7642 (703) 538-7669customerservice@fdanews.com ahollis@fdanews.com msalt@fdanews.com adesai@fdanews.com

Correction: An article in the December GMP Letter states that the FDA requires device facility inspections every two years for Class II devices, whereas Canada requires them every five to six years (GMP, December 2010). How-ever, a Health Canada official said manufactur-ers of Class II, III and IV devices marketed in Canada are subject to quality management sys-tems audits on an annual basis.