FDA Compliance Help

Are you sure your distributors quality systems are adequate?

2012-02-04T10:05:00.000-08:00

Most medical device manufacturers and importers focus the lion’s share of quality assurance resources on their own facilities and those of their suppliers, rightfully so. However, at least a portion of the Quality/Regulatory Department resources should be devoted to assuring the distribution channel does not compromise product safety and effectiveness.

Some firms we have audited have no quality department involvement with the distribution channel at all, they leave it totally up to sales and marketing to assure the distributor quality management system and facility is appropriate. Consider this quote taken from the FDA Medical Device Quality Systems Manual: A Small Entity Compliance Guide:
“For manufacturers and importers, distribution is one of the most important steps in their quality system. After a product is distributed, a manufacturer rarely has direct control over the product or how it is used. Thus, it is important that controls be in place to assure that only correctly labeled, packaged and approved finished devices are distributed and, if necessary, installed…The QS regulation (820.60), Identification, requires manufacturers to set up and maintain identity control of their products from component receipt, production, distribution and through installation to prevent mixups. The regulation also requires that written procedures be provided for control and distribution of finished devices (820.160).” At this point the FDA has not issued a guidance document titled Good Distribution Practices for Medical Devices (GDP). However, a number of other countries have published GDP guidance. The European industry association for medical device manufacturers published a revision of the guide in May 2010 which includes an appendix for Consignment Stock. The 17 page guide is available for download at no cost. Here is the index:

1. Introduction

2. Principles

3. Glossary

4. Organization and Management

5. Personnel

6. Documentation

7. Procedures

8. Records

9. Premises and equipment

10. Receipt

11. Storage

12. Vehicles

13. Deliveries to Customers

14. Transportation and products in transit

15. Returns of non-defective medical device products

16. Emergency plans and recalls

17. Counterfeit

18. Internal audits

Appendix: Consignment Stock

It is recommended that Quality Management Systems (QMS) be established and maintained throughout the supply chain to ensure the quality of medical devices is not adversely affected during their distribution and to ensure that appropriate records are kept.

The procedures and record keeping need not be overly burdensome, but they should be in writing and appropriate for the operations carried out by the distributor including vigilance, receipt and checking of deliveries, storage, cleaning and maintenance of the premises, recording of the storage conditions, handling in transit, quarantine, returned products, trends of recalls, pest control, complaint handling, processing compliant samples for return to the manufacturer, etc.

Are you getting the most value from your Quality/Regulatory Projects?

2012-01-30T08:33:00.000-08:00

Scott Adams has captured the essence of what all seasoned project managers know and all too often what senior management fails to grasp; all but the simplest project requires data collection and planning.

Management with an eye toward cost savings will often look to cut data collection and planning. Few projects need to follow a full blown formal Six Sigma DMAIC process, but one key principle of Six Sigma applies to all projects—“All outcomes are determined by inputs with some degree of uncertainty”. When a project is commissioned without management’s approval of time allocated to data collection, planning, and project review the project more often than not ends costing the project sponsor much more than necessary.

Over the last 35 years we have completed numerous 510(k) submissions, Quality System Installations, Compliance Audits with CAPA follow-on, Process Improvement, Warning Letter remediation, and more. A retrospective analysis indicates our most cost effective projects follow these steps:

Defining the top level objectives and deliverables (I. Initiation Phase).
Taking inventory of materials and information on hand, identifying what is missing (gaps) plus available, and evaluating suitability (II. Planning Phase A).
Deciding what needs to be done and the best way to achieve the objectives (II. Planning Phase B).
Detailing time and cost of progress reports, meetings with upper management as well as factoring in allowances for course corrections within the project (II. Planning Phase C).
Determining the level of competency required to do the work, recruiting competent team members, estimating the time and materials required and total project cost (II. Planning Phase D).
Securing management’s sign off of the plan including provisions for the unknown that may result in plan changes and changes in deliverables (II. Planning Phase E).
Implementation─ complete work, track performance, make corrections, report and meet with management (III. Execution and Control Phase).
Acceptance of Project deliverables (IV. Closeout Phase).

In order to receive the most value from your projects (lowest cost and highest quality):

Commission your projects in two stages.

Stage One = steps 1-6. The deliverables for Stage One: (a) Inventory of materials, information, and resources to be applied and don’t need to be duplicated by the project team. (b) Project plan. (c) Project budget.

Stage Two – steps 7 and 8. The deliverables for Stage Two: Achievement of the top level project goals.

Agree in writing on decision making authority. What level of authority does the project manager have? The more decisions that are made outside the project team, the less effective the project team. If top managers, board members, and other non project team members must have a say in project decisions; then assure the scope, nature and level of the involvement is set forth in Stage One documents.
Don’t hold back information in Stage One, such as previous project failures or skeletons that pertain to the project. The flow of accurate information is critical to project effectiveness.
Provide uninterrupted resources (money, people, and access to information), start/stop delays increase the cost of a project and often result in waste and/or reduce effectiveness.
Avoid project changes once Stage Two has been commissioned, changes often create a domino effect on project elements that then must be reworked.
Changing the project manager is particularly detrimental and should be avoided if at all possible.
Be a reliable Project Sponsor: Enthusiastically support the project and Keep the project dissuaders in check

To quote Oliver Goldsmith:

“To aim at excellence, our reputation, and friends, and all must be ventured; to aim at the average we run no risk and provide little service.”

Importers Alert – Good Importer Practices Part 3, the last word…

2012-01-28T14:20:00.000-08:00

Importers Alert – Good Importer Practices Part 3, the last word…

In the first two articles we discussed the first three of the four guiding principles:

1. establishing a product safety management program

2. knowing the product and applicable U.S. requirements

3. verifying product and firm compliance with U.S. requirements throughout the supply chain and product life cycle

In this article we will address “Guiding Principle 4” – Taking corrective and preventive action when the imported product or firm is not compliant with U.S. Requirements and sum up.

The FDA recommends importers undertake the following four actions:

Establish procedures for developing corrective action plans, and for taking corrective and preventive actions if non-compliance with a U.S. requirement or a safety concern should arise. Address the potential need for disposal/destruction or export of non-compliant products, consistent with applicable U.S. statutes and regulations.
Identify and investigate the root cause of non-compliance with U.S. requirements for products they import, or by foreign firms with which they do business.
Take steps to remediate and prevent harm from present and future shipments, and to ensure non-compliance and safety problems do not recur. These corrective action plans must, of course, be consistent with the appropriate U.S. agency's regulations. They could, for instance, include product re-labeling, product re-working or further processing, product export or destruction (if the violative product is already at a U.S. port-of-entry or in U.S. commerce), or a decision not to offer the product for entry into the United States. Proper corrective action plans are based on practices that either ensure the product is in compliance when offered for entry into the United States, or that will correct any problems prior to marketing in the United States.
Work with the non-compliant firm to meet U.S. requirements, or stop conducting business with that firm.

If your firm imports medical devices that are sold under your own brand and your firm is not a specification developer, and you don’t hold any 510(k)s for the products imported, and not repackaging or relabeling; then following Good Importer Practices as recommended will add operating cost. On the other hand, if you are a specification developer or are importing under your own 510(k)s there would be little additional operating cost. That is assuming you already have a compliant Quality Management System in place.

With over 3,000 medical device manufacturers in China, many with thousands of employees it is tempting to start importing with a handshake and reliance on an ISO 13485 certificate alone. To do so would be taking an unreasonable level of risk. Just this week we reviewed an FDA warning letter issued January 13, 2012 concerning a sterile device manufacturer with over 5,000 employees. The letter noted serious violations and the subject products are subject to refusal of admission into the U.S.

IF THE MARKET FOR THE DEVICE(S) IS SIGNIFICANT ENOUGH TO JUSTIFY PRIVATE BRANDING AND MARKETING LAUNCH EXPENSES, THE COST ASSOCIATED WITH FOLLOWING GOOD IMPORTER PRACTICES WOULD SEEM JUSTIFIED AS WELL.

Comments welcome.

Will FDA’s New 510(k) Guidance be Helpful or reach the stated Goals?

2012-01-26T13:46:00.000-08:00

Is the FDA’s New 510(k) Guidance Helpful? Quick Answer: Yes. Will it meet all four goals? That remains to be seen.
The new 51(k) draft guidance was released in December 2011, it is titled: "The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications or 510(k)s."
There is also a CDRH Learn video training module delivered by Elias Mallis, the Director of the Division of Sm. Mfg., International and Consumer Assistance at CDRH.
As we all know, in recent years the 510(k) premarket notification clearance process has come under fire from a wide range of stakeholders. This new guidance is intended to replace the two pervious guidance documents, the Blue Book Memo K86-3 issued in 1986 and the New 510(k) paradigm guidance published in 1998.
The goal of the new guidance
1.      Provide clarity
2.      Transparency
3.      Consistency
4.      Predictability
New terminology and expanded definitions
·        Predicate Device. A predicate device is a legally marketed device that is used for comparison to a new device, for the purpose of determining substantial equivalence.
·        Substantial Equivalence. This is a determination that a new device, as compared to a predicate device, has the same intended use, the same technological characteristics, or differences that don't raise different questions.
·        “NEW” Reference device. A reference device is a legally marketed device. It is not a predicate device as defined previously, but is otherwise used to address certain performance characteristics of a new device. I'd like to point out that "reference device" is a new term that is defined in this draft guidance.
·        Intended Use. The intended use is the general purpose of a device and describes what the devices does.
·        Indications for Use. The indications for use describes the disease or condition that the device will diagnose, treat, prevent, cure, or mitigate. This term may also define the target patient population.
Key Points
1.      Selection of a predicate
2.      Principles of determining a new intended use
3.      Safety related to technological differences
4.      When clinical data is needed
5.      New standardized format for the summary, and that it will be verified by FDA
New flowchart for traditional and special
·        Combines Intended use with indications for use
·        Consistency of the indications for use statement
Summary
The extensive listing of information required in the summary, if enforced will be very helpful, down the road in selection of the primary predicate device. The clarification concerning intended use verses indications for use provide significant clarification.

When does FDA expect label changes for Off-Label use?

2012-01-25T12:20:00.000-08:00

When does FDA expect label changes for Off-Label use? Quick answer – when you have knowledge of it! Yet, following the “letter of the law” has implications.

The last sentence of “21 CFR 801.4 Meaning of intended uses.” establishes a requirement to add adequate labeling for UNINTENDED USES:

The words intended uses or words of similar import in 801.5, 801.119, and 801.122 refer to the objective intent of the persons legally responsible for the labeling of devices. The intent is determined by such persons' expressions or may be shown by the circumstances surrounding the distribution of the article. This objective intent may, for example, be shown by labeling claims, advertising matter, or oral or written statements by such persons or their representatives. It may be shown by the circumstances that the article is, with the knowledge of such persons or their representatives, offered and used for a purpose for which it is neither labeled nor advertised. The intended uses of an article may change after it has been introduced into interstate commerce by its manufacturer. If, for example, a packer, distributor, or seller intends an article for different uses than those intended by the person from whom he received the devices, such packer, distributor, or seller is required to supply adequate labeling in accordance with the new intended uses. But if a manufacturer knows, or has knowledge of facts that would give him notice that a device introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than the ones for which he offers it, he is required to provide adequate labeling for such a device which accords with such other uses to which the article is to be put.

Before introducing the implications of this regulatory requirement, be advised - I am not aware of any FDA enforcement action issued for failure to revise labeling because the manufacturer became aware of off label use but failed to change the labeling. That being said, it is regulation and therefore must be taken seriously.

What is covered by “Adequate Labeling”? Adequate labeling most often refers to a requirement for adequate directions for use. In the case of intended use it would include omissions, lack of warnings, and false statements.

Implications

Example 1: What if a number of physicians are using the device to treat a disease that was investigated during design and development and the safety and effectiveness of the device in treating that disease could not be demonstrated?

Implication 1: FDA has no control over how physicians use devices. Per FD&C Act, Section 906 [21 U.S.C. 396]:

Nothing in this act shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship. This section shall not limit any existing authority of the Secretary to establish and enforce restrictions on the sale or distribution, or in the labeling, of a device that are part of a determination of substantial equivalence, established as a condition of approval or promulgated through regulations. Further, this section shall not change any existing prohibition on the promotion of unapproved uses of legally marketing devices.

Implication 2: So to be in compliance with 801.4 you decide to add a warning, “Do not use for XYZ”. But that triggers the requirement for a new 510(k) per current guidance (A3):

Does the change add a contraindication? While all changes in the labeled contraindications for device use should be reviewed by the agency, CDRH recognizes that, in general, the addition of a contraindication based on new information is important to public health and should be implemented immediately. Because of this, manufacturers are encouraged to add new contraindications to their labeling and to notify existing users of their device as expeditiously as possible whenever a pressing public health need arises. The new labeling should be submitted to FDA as part of a new 510(k) (that is prominently labeled "change being effected") Manufacturers may continue to market their device with the modified labeling, unless otherwise notified by FDA. Manufacturers should be thoroughly familiar with what constitutes a true contraindication to do this.

Implication 3: You read a clinical paper indicating the use to treat the XYZ disease is safe and effective so you decide to add it to the indication for use. But that triggers the requirement for a new 510(k) per current guidance (A1):

…Changes in the indications for use section of labeling raise more agency concern than any other aspect of labeling. In fact, most changes in this part of the labeling will require the submission of a 510(k)...

Other opinions and comments welcome.

How to respond to Unsolicited Requests for Off-Label Use Information for Your Devices?

2012-01-13T13:25:00.000-08:00

By Walt Brittle

On December 29, 2011 FDA issue the document Guidance for Industry Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices (GD) in order to clarify how to respond to Off-Label questions without being subject to an FDA enforcement action of promoting a device for Off-Label use. Off-Label Use has long been a sticky issue for medical device manufacturers and it is a bigger concern today due to the use of electronic media. Obviously, medical device firms have no “control” over how their devices are used. Many device firms have no database related to Off-Label use Q and A. Some firms disavow having specific knowledge that their devices are being used Off-Label. Some firms have taken the conservative position only to answer questions concerning Off-Label use by limiting the response to providing regulatory department approved intended use and instructions for use information and stating it is company policy not to discuss Off-Label use of its products. The background section of the GD lists:

…The FD&C Act and FDA’s implementing regulations also prohibit device firms subject to premarket notification requirements under section 510(k), which includes most class II and some class I devices, from introducing such devices into interstate commerce for any intended use that is outside FDA’s substantial equivalence determination (clearance) for such devices. Statements that promote a drug or medical device for uses other than those approved or cleared by FDA may be used as evidence of a new intended use. Introducing a product into commerce for such a new intended use without FDA approval or clearance would, under these requirements, generally violate the law. However, once a drug or medical device has been approved or cleared by FDA, generally, health care professionals can lawfully use or prescribe that product for uses or treatment indications that are not included in the product's approved labeling (or, in the case of a medical device cleared under the 510(k) process, in the product's statement of intended uses). FDA recognizes that these off-label uses or treatment regimens may be important therapeutic options and may even constitute a medically recognized standard of care… FDA recognizes that it can be in the best interest of public health for a firm to respond to unsolicited requests for information about off-label uses of the firm’s products that are addressed to a public forum, as other participants in the forum who offer responses may not provide or have access to the most accurate and up-to-date information about the firm’s products. If a firm responds to unsolicited requests for off-label information in the manner described in this draft guidance, FDA does not intend to use such responses as evidence of the firm’s intent that the product be used for an unapproved or uncleared use. Such responses would also not be expected to comply with the disclosure requirements related to promotional labeling and advertising. Firms may choose to respond to unsolicited requests for information about off-label uses of their approved or cleared products in a manner other than that recommended in this draft guidance. Such activity would not constitute a per se violation of the law, but could potentially be introduced as evidence of a new intended use.

For anyone but the large multinational medical device firm we believe following this guidance document as well as the Good Reprint Practices Guidance document available via the this link - http://www.fda.gov/regulatoryinformation/guidances/ucm125126.htm would be difficultd to follow. It is far better to prepare additional 510(k) submissions and then properly promote your device for the new uses. Other points of view welcome.

IS YOUR RISK MANAGEMENT DOCUMENTATION UP TO DATE?

2012-01-07T15:20:00.000-08:00

By Walt Brittle

ISO 14971:2007 or EN ISO 14971:2009 is recognized for risk management of medical devices.

It is recognized by the U.S. FDA, European authorities, and Health Canada. The primary

requirement is that product risk should be reviewed and when possible mitigated over the

product’s lifetime. Every medical device manufacturer is to do risk assessment during design

and development and then again when changes are made and when customer feedback

(complaints or post market surveillance) received. Your Risk Management procedure should

include the frequency of review and the results of the reviews should be included in quality

system management review meetings. Your internal audit check list should also include

questions on risk management.

The risk management plan needs to include at least the following:

a) the scope of the planned risk management activities, identifying and describing the

medical device and the life-cycle phases for which each element of the plan is

applicable;

b) assignment of responsibilities and authorities;

c) requirements for review of risk management activities;

d) criteria for risk acceptability, based on the manufacturer’s policy for determining

acceptable risk, including criteria for accepting risks when the probability of occurrence

of harm cannot be estimated;

e) verification activities;

f) activities related to collection and review of relevant production and post-production

information.

Each medical device should have a risk management file and include documents or links to

documents that address the risk analysis, the risk evaluation, the implementation and

verification of the risk control measures, and the assessment of the acceptability of any residual

risk(s).

If your procedure, plan, or documentation falls short please gives us a call – we can help.

Did you ever wonder why foreign contract manufacturers have to register?

2012-01-05T17:41:00.000-08:00

HERE IS THE ANSWER.
All foreign contract manufacturers must register list and pay fees. Domestic contract manufacturers that simply make the device(s) for a Specification Developer and don't put the products into commercial distribution are exempt from registration. Even though a foreign contract manufacturer may only ship the product back to the Specification Developer the act of exportation constitutes commercial distribution in the eyes of the FDA.

When should you request a copy of the FDA Establishment Inspection Report (EIR)?

2011-12-31T09:17:00.000-08:00

By Walt Brittle

You should request a copy of the EIR if you have not received one within 60 days following an FDA inspection of your facility. In accordance with the agency’s directive, effective April 1, 1997 the narrative portion of the EIR should be released to the establishment inspected. It is issuable following closure. The Investigators Operations Manual proscribes the EIR should be closed within 30 days.

Under the Freedom of Information Act (FOIA) and FDA's regulations governing disclosures as set out at 21 C.F.R. Part 20, any inspection information including the list of inspectional observations (FDA-483), EIR, and the Agency's communication with the regulated establishment must be disclosed upon request by any member of the public.

Domestic EIRs
The district office that makes the initial inspection endorsement for domestic inspections will monitor and release the EIR. The endorsing office will ensure that the EIR for the closed inspection is appropriately redacted under FOIA and 21 C.F.R. Part 20 before releasing a copy to the establishment inspected. No information may be released to the establishment if it could not be released to that establishment in response to an FOIA request.
International EIRs
International EIRs will be monitored and released by the ORA headquarters or Center office responsible for maintaining the original establishment files. The releasing office will ensure that the EIR for the closed inspection is appropriately redacted under FOIA and 21 C.F.R. Part 20 before releasing a copy to the establishment inspected. No information may be released to the establishment if it could not be released to that establishment in response to an FOIA request.
All EIRs
The copy of the redacted EIR should be accompanied by a standard letter (See attached "model" letter ). The issuing office should send the package by an appropriate means, but should consider using certified mail if it may contain confidential commercial or trade secret information. The issuing office should endeavor to provide a copy of the EIR and the letter to the inspected establishment at the earliest time possible once the inspection is deemed closed by the Agency.
Establishment Inspection Report, Depuy Orthopaedics, Inc. FEI: 1818910
EI Start: 12/03/2007 EI End: 01/22/2008
Here are snippets from the report. They illustrate the benefits to reviewing the EIR. To the review the full redacted narrative of the report use reference #3 link.
SUMMARY
This was an ad hoc inspection to follow up eight product recalls reported to FDA by Depuy Orthopaedics since May 2005. Depuy Orthopaedics, Inc. is a large manufacturer that designs, manufactures, and distributes orthopedic implants listed as Class II and III medical devices. Products affected by Depuy's eight product recalls are all Class II medical devices for orthopedic use. Depuy is a Johnson & Johnson Company, New Brunswick, NJ. The previous FDA inspection of Depuy was completed on October 18, 2007 and classified as no action indicated (NAI).

The scope of this current inspection focused on Depuy's post market surveillance and recall activities for eight product recalls listed in FDA's Recall Enterprise System database under event numbers 45478, 44893, 38464, 36849, 36348, 34018, 32282, and 32192. Documents reviewed during this inspection included the firm's electronic complaint files and procedures, medical device reporting (MDR) files and procedures, root-cause investigation reports, health hazard evaluation reports, risk assessments reports, corrective and preventive action (CAPA) files and procedures.

My review of post market surveillance and recall activities required by Depuy's Warsaw facility was found to be sufficient and complete for each product recall. All customers were promptly notified and product inventories returned. Each of the eight product recalls has been terminated.

One of the eight product recalls (event number 34018) was under the direct responsibility of Depuy's Warsaw, IN facility. An FDA-483 "'Inspectional Observations" form was issued to Depuy management in Warsaw, IN for a design flaw that involved their Acclaim™ Total Elbow System. Depuy's design validation did not ensure that the devices conform to defined user/patient needs and intended uses. Specifically, Depuy's design validation test method H3KH did not did notfiSET (b) (4) (b) (4) As a corrective action the firm redesigned the Acclaim™ Total Elbow System and filed a special 510(k) for humanitarian use in March 2006. No design-related complaints or adverse events have been reported against the redesigned version of the device since being commercially available in April 2006.

Seven of the eight product recalls covered during this inspection were caused by manufacturing and quality system deficiencies that occurred under the direct responsibility of Depuy's manufacturing plants in Raynham, MA; Cork, Ireland; Blackpool, England, and Le Locle, Switzerland. I discussed with Depuy management about the following manufacturing and quality system deficiencies noted during this inspection.

In 2007 Depuy's Lc Locle, Switzerland plant manufactured two lots of TK2 Compression Hip Screw trauma plates that were not according to design specifications.

In 2007 Depuy's CMV plant in Blackpool, Lanshire, UK manufactured multiple lots of SmartSeal Wedge Femoral Pressurisers with outer pouch seals that were creased which may introduce the potential for sterility to be compromised during use of the device in surgical suites.

In 2006 Depuy's Cork Ireland plant manufactured Preservation Uni-Compartmental Knee Fixed Tibial Trays that were difficult to assemble. Process validation did not include verification that the chamfer detail was fiat.

In 2006 Depuy's Cork, Ireland plant had clean and pack operations that were insufficient to prevent packaging and labeling mix-ups. PFC Sigma Oval Dome Patella units containing size 32 mm patellas were mislabeled as 38 mm patellas.

In 2005 Depuy's Cork, Ireland plant manufactured multiple lots of Depuy brand LCS Complete Metal Backed Patellas with oversized inside diameters by 0.005 to 0.006 thousands of an inch, resulting in reduced fit between the base plate and the polyethylene articular bearing.

In 2005 Depuy's Raynham, MA plant packaged various polyethylene tibial insert components with incomplete seals on inner pouches which may result in oxidation and would affect long-term performance of the implant. In addition, the scope of Depuy's root-cause investigation was insufficient that resulted in an extended recall of the same products in 2007.

Corrective and Preventive Actions (CAPA)
I reviewed Depuy's complaint handling procedures and files, MDR procedures and files, CAPA procedures and files, and recall procedures. I used the procedures as guides to determine how they

completed post market surveillance activities and recall activities. Steven K. Dowell, Director of Regulatory Compliance and Bernard Newton, Quality Systems Manager, explained how the firm handles MDRs, CARs, medical device tracking, and customer complaints.

My review of the firm's MDR files found 62 MDRs been filed against the original design of the Acclaim™ Total Elbow System device. The last MDR was reported on February 9, 2007. None of the MDRs were filed late. Depuy's post market surveillance and recall activities were effective. All customers were promptly contacted and recalled devices returned. The recall has been officially closed since June 2006.

I had a discussion with Depuy management about the insufficient scope of their root-cause investigation of a 2005 recall involving polyethylene tibial insert components that resulted in an extended recall of the same products in 2007. The device was manufactured by Depuy's Raynham, MA plant. Details are presented in the "General Discussion With Management" section of this report.

OBJECTIONABLE CONDITIONS AND MANAGEMENT'S RESPONSE
A FDA-483 "Tnspectional Observations" form was issued to Depuy management in Warsaw, IN for a design flaw that involved their Acclaim™ Total Elbow System, Depuy's design validation did not ensure that the devices conform to defined user/patient needs and intended uses. Specifically, Depuy's design validation test method BgBHP Hid ™t Hid nnt dmi,ktP the full range of clinical performance while articulating through the Q^Q^^^^^|which may cause the device to fail. As a corrective action the firm redesigned the Acclaim™ Total Elbow System and filed a special 510(k) for humanitarian use in March 2006.

The inspect!onal observation was corrected by the firm and verified by me.

I also noted several inspectional observations for Depuy's manufacturing plants in Raynham, Cork, Blackpool, and Le Locle that have direct responsibility for manufacturing and quality system deficiencies that caused seven product recalls. Manufacturing and quality system deficiencies are presented in the "General Discussion With Management" section of this report.

Reference:
1. http://www.fda.gov/iceci/inspections/fieldmanagementdirectives/ucm061430.htm
2. http://www.fda.gov/ICECI/Inspections/FieldManagementDirectives/ucm103299.htm
3http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicReadingRoom/UCM248533.pdf

Are you prepared for a device recall?

2011-12-17T09:32:00.000-08:00

By Walt Brittle

2011 has been a year of increasing outcry for more regulatory powers over the device industry. Both the GAO’s report to congress on “MEDICAL DEVICES FDA Should Enhance Its Oversight of Recalls released June 2011 and the Institute of Medicine’s report “Medical Devices and the Public’s Health: The FDA 510(k) Clearance Process at 35 Years” call for MORE! On December 16, 2011 MassDevice staff commenting on the recent introduction of the "Medical Device Patient Safety Act" by Sens. Grassley (R-Iowa), Kohl (D-Wis.) and Blumenthal (D-Conn.) wrote:

“Regarding the bill’s provisions to implement recent Government Accountability Office’s (GAO) recommendations to improve the FDA’s handling of medical device recalls, we believe, consistent with GAO recommendations, the FDA could do more to enhance the clarity and consistency of its recall process, and we are pleased that the agency has a number of initiatives underway in this area.”

The GAO report concluded:

“FDA has a key role in identifying and minimizing the public health risks

presented by defective or unsafe devices. In this regard, FDA has

opportunities to close some of the gaps that currently exist in the medical

device recall process, and enhance its oversight of device recalls. As

currently structured, FDA’s approach to oversight of medical device

recalls is reactive—responding to individual recalls as they occur. Rather

than pursuing a strictly case-by-case approach to overseeing recalls, FDA

could take a more proactive approach to its oversight. The agency has a

plethora of data available on thousands of recalls, but at present, is not

effectively reviewing and analyzing these data in a systematic manner.

More routine analyses of these data could help FDA identify trends in the

numbers and types of devices being recalled, as well as the underlying

causes of device recalls. Such information would provide FDA with a

better understanding of the risks presented by defective or unsafe devices,

which could lead the agency to proactively identify strategies and

measures needed to address systemic problems with the design or

manufacture of individual devices or entire categories of devices. Armed

with the results of these types of analyses, FDA could then be in a position

to help mitigate safety risks before they occur, and thus minimize the need

for recalls. This is particularly important for the devices involved in the

highest-risk recalls, which place the public at risk of serious health

consequences, including death.”

The GAO reports firms initiated 3,510 device recalls between January 1, 2005 and December 31, 2009, an average of just over 700 per year. 87% of the recalls were from devices which were cleared via 510(k) the average recall process took just over 420 days from initiation to termination. Conclusion quote: “While the recall process may not eliminate 100% of heath risks associated with recalled devices, careful implementation and evaluation are critical to minimizing heath risk.”

Since it is not possible to eliminate recall, it is advisable to:

1. Be prepared for recall at any time.

2. Train your quality and regulatory staff and prepare for an FDA inspection so they know the scope and depth of the inspection, including what questions will be asked.

3. Confirm all stakeholders understand the consequences associated with a recall, 420 days of over-site can be costly.

4. Periodically conduct a mock FDA Recall inspection to confirm your Quality Management System is up to the challenge.

When we proactively prepare a client’s management team to be ready at any time for a recall we use the following.

From the FDA Investigations Operations Manual(FDA IOM) - UCM123513.pdf:

7.2.1 - INSPECTION PROCEDURES

An important part of your job is to identify the root cause for the recall and assure the firm has implemented procedures to prevent it from recurring. In some cases, management will have conducted its own analysis and reached conclusions about the problem and its cause. The initial judgments about the problem are not always correct nor discriminating enough to identify the underlying causes. You need to verify the steps taken were sufficient in depth and scope and reflect the correct conclusions about both the problem and correction.

Determine if the firm conducted a failure analysis using techniques such as fault tree analysis or failure mode analyses. Did it consider things such as the length of time the product has been manufactured and sold, complaints or returns for the same or similar problems, any reworking of product prior to release or distribution which may have been due to the same or similar problems and, process or personnel changes which occurred about the time the problem appeared?

For all recall inspections, in addition to verifying the identification of the root cause:

1. Issue a Notice of Inspection (FDA 482);

2. Discuss the suspected problem with management and review the firm's complaint file;

3. Investigate all areas, control points and/or circumstances which may have a bearing on the product's deficiency;

4. Fully develop individual responsibility for the problem;

5. Review batch records, processing logs and/or other types of records for violative lots and associated lots;

6. Review and obtain copies of the firm's quality control/analytical data;

7. Determine any actions the firm has taken, is taking, or has planned to take to prevent similar occurrences. If corrective action is not underway, determine the firm's timetable for achieving correction; and

8. Determine what action the firm has taken or plans to take, and the time frames involved, regarding questionable product(s) remaining in commerce

7.2.3 - MEDICAL DEVICE RECALLS

Medical device recalls may result from manufacturing defects, labeling deficiencies, failure to meet premarketing requirements [PMA, 510(k)], packaging defects or other nonconformance problems. How firms identify the causes of medical device recalls and corrective action activities is essential to the analysis of medical device failures and the determination of the effectiveness of the medical device GMP program. It is also useful in evaluating the medical device program, and for directing attention to problem areas during inspections. 21 CFR Part 806.1 requires device manufacturers and importers to report certain actions concerning device corrections and removals. They must also maintain records of all corrections and removals regardless of whether such corrections and removals are required to be reported to FDA. (See 21 CFR Part 806.20). Failure to report as required by 21 CFR 806.10 is a violation and should be listed on the FDA-483, "Inspectional Observations." This may be included in a direct reference Warning Letter.

Each device manufacturer or importer must submit a written report to FDA of any correction or removal of a device initiated by such manufacturer or importer, if one was initiated:

1. To reduce a risk to health posed by the device; or

2. To remedy a violation of the Act caused by the device which may present a risk to health, unless the information has been provided according to 21 CFR 806.10 (f), or the correction or removal action is exempt from the reporting requirements under 21 CFR 806.1(b).

Collection of complaint, PMA and 510(k) related information is necessary to determine compliance with the GMP requirements. During recall follow-up inspections, answers should be obtained to the questions below, in addition to routine recall information. For firms where it has been established a manufacturing defect led to the recall, conduct a complete GMP evaluation of the manufacturing operations. Report such inspections into FACTS as "qualifying" GMP inspections.

7.2.3.1 - Problem Identification

1. How did the firm identify the nonconformance which led to the recall, e.g., complaint, in-house data, etc.?

2. If the recall was due to a device defect, did the firm conduct a documented failure analysis of the device, using such techniques as fault tree or failure mode analyses? If so, report whether these results were provided for review.

a. Did the firm determine the failure mechanism, e.g., shorted component, incomplete weld, etc.?

b. If not, how did firm determine the cause of the nonconformance?

c. If not, what rationale does the firm have for not conducting a failure analysis?

3. Did the firm determine at what phase of the device life cycle the nonconformance occurred, i.e., design, manufacturing, storage, use, etc., and the actual cause of the nonconformance, for example, software design error, process out of specifications, employee error, user misuse, etc.? What evidence does the firm have to support the determination?

4. Did the firm determine if the nonconformance resulted in an injury or death?

5. If a component was responsible for the defect, determine if the same component was used in other devices manufactured by the firm. If so, has the firm conducted an analysis to assure the defect in the component will not have a deleterious effect on the operation of the other device(s)?

6. If a component was responsible for the device defect, what other device manufacturers use the same component (and especially the same lot number of the component)? Has the manufacturer of the recalled device notified the component manufacturer? Has the component manufacturer contacted its other customers about the problem?

7. Why was the component defective? Did the manufacturer of the component change the specifications with-out notifying the finished device manufacturer? Did the component fail to meet its release specifications?

NOTE: A visit to the component manufacturer may be needed to adequately answer questions 5, 6 and 7. Before doing so, confirm with CDRH and your supervisor that the matter is egregious enough to warrant this "next step."

8. Did the finished device manufacturer have an incoming component/raw material sampling and testing procedure? If not, why not?

9. If the manufacturer recalled the device because the labeling was inaccurate, or the wrong labeling was applied to the device (label mix-up) determine the following:

a. What quality system procedures should have been established to prevent the problem?

b. If the label or instructions for use were inaccurate, was the inaccuracy introduced in the design stage, or was it due to a printing problem?

10. If the device has been on the market for a year or more, and the manufacturer claims the problem is the result of design:

a. Why is the problem just now showing up? How many reports concerning the problem did the firm receive before deciding a recall was necessary? Does the firm have a procedure established for determining if a recall is necessary, and if so, did it follow the procedure? Obtain a copy of the procedure.

b. If the firm doesn't provide rational answers to the above questions, determine if they explored other possible causes for the problem.

c. Was the design feature which caused the problem included in the design of the device that was the subject of a premarket submission?

d. If the design feature which caused the problem is part of the original design, did the manufacturer re-call all products manufactured since the device was introduced to the market? If not, why not?

e. If the problem was introduced via a design change, did the manufacturer follow established design change or change control procedures? If yes, are the procedures adequate? Was the nature of the problem such that it should have been anticipated, and the design verification/ validation study fash-ioned to detect the problem?

f. Has the manufacturer recalled all products distrib-uted since the design change was introduced? If not, why not?

7.2.3.2 - Corrective Action

1. Describe the corrective action taken to correct the immediate problem, e.g., redesign, modify SOP, process validation, etc.

2. Did the firm qualify/validate the corrective action?

3. Did the firm establish responsibility to assure that the corrective action would be implemented and satisfactorily completed?

4. What action did the firm take to prevent recurrence of the nonconformance, e.g., training, increased process monitoring, etc.?

5. Was the nonconformance information provided to those responsible for the areas in which the nonconformance occurred?

6. Did the firm determine if the nonconformance extended to other devices?

7. Did the firm determine if changes were needed in procedures and, if so, did it validate and implement the changes?

8. Has the manufacturer taken appropriate corrective action?

Importers Alert - Good Importer Practices Part 2

2011-11-24T19:29:00.000-08:00

In part one, we started this three part series discussed the U.S. FDA's GIP Guidence Doucment. Part one introduced the four guiding principles, and reviewed one and two:
1.       establishing a product safety management program
2.       knowing the product and applicable U.S. requirements
3.       verifying product and firm compliance with U.S. requirements throughout the supply chain and product life cycle
4.       taking corrective and preventive action when the imported product or firm is not compliant with U.S. requirements

In this article we will address “Guiding Principle 3” - verifying product and firm compliance with U.S. requirements throughout the supply chain and product life cycle.

“Importers should ensure that the appropriate preventive controls have been implemented throughout the supply chain and life cycle of the product…”
For medical devices this means understanding and evaluating the controls in place not only at the foreign manufacturer’s facilities, but also at the raw material and sub-manufacturers. It also means evaluating the distribution channel in the U.S. to assure they have preventive control in place such as appropriate environmental conditions, product handling, and an effective complaint handling system.
“The importer should take responsibility for evaluating problems that develop with its imported products prior to importation, while under its control, or while under the control of domestic parties with whom it conducts business, and for determining the appropriate course of action.”
Practically speaking it is hard to envision the importer taking more than a collaborative of evaluating problems that occur early in the supply chain. The primary responsibility for preventing and evaluating problems in any segment of the supply change must rest primarily with operating management responsible for the process.
This section of the guide sets forth a number of recommendations. The following are the ones we believe are the most practical for the medical device importer:
A. Control, Monitor, and Verify Product and Producer Compliance Prior to the Arrival of the Product in the United States.

• “Know what preventive controls, if any, firms must institute at each critical point in the product's life cycle, and the steps firms need to take to ensure that those controls are being appropriately applied so that the product is safe for end users, such as consumers or healthcare professionals. The presence of inadequate preventive controls can alert you to potential safety risks.” Practically speaking we believe the importer should reference and rely primarily on FDA cGMP plus guidance documents as well as published industry standards to identify the controls and incorporate them into their supplier audit check list.

• Prior to doing business with a supplier, perform an assessment of the supplier to determine whether it has implemented an effective product safety program to help ensure you receive a product that meets applicable U.S. requirements. The assessment may include a review of documents, an on-site audit, or both. Even after doing business with a supplier for several years an assessment should be done. In our experience desk-top closed end audit questionnaires should not be relied on as the sole means of assessment of anything but the very low risk device supplier.

• Resolve any potentially significant or questionable information gaps about the firms involved in the product life cycle prior to importing their products, because the lack of information can raise concerns about the safety and security of the product.

• Obtain a written guarantee of product compliance from company representatives, if appropriate, based on a consideration of the risks associated with non-compliance and other conformity-assessment procedures employed. Insist on compliance with U.S. requirements in the purchasing contract, and impose remedies if the firm sells you non-compliant products for export to the U.S. Be as specific as possible about safety requirements. This can help ensure you receive a product that complies with applicable U.S. requirements. Firms can establish additional measures to ensure product safety through contracts or agreements with other participants in the supply chain, such as shippers.

• When appropriate, require foreign firms to train their employees on U.S. requirements applicable to their products when imported into the United States.

• Establish mechanisms to verify compliance with U.S. requirements. Possible mechanisms include the following acts by the importer:

• Periodically inspect the foreign firm where appropriate and feasible. The importer could conduct inspections either through periodic visits or by placing personnel in critical, foreign production facilities. Alternatively, the importer could hire qualified third parties to perform inspections. The inspections should verify that preventive controls (e.g., Hazard Analysis and Critical Control Point) are in place, review records, review sampling results of both finished products and raw materials and ingredients of those finished products, and perform independent analysis of representative product samples. Third party auditors should be independent of the foreign firm, with no conflict of interest. They should have adequate training and expertise, and be accredited by a nationally or internationally recognized accrediting body.

• Consider purchasing from certified firms. If the U.S. Government agency(ies) with jurisdiction over the product has established or recognized a certification program for foreign producers of the imported product, the importer should consider purchasing solely from those firms. In such instances, the frequency of inspections by the importer or an independent third party on behalf of the importer might be reduced. In our experience, ISO 13485 certification is not a very reliable indication that products are being manufactured or handled in accordance with U.S. FDA regulations. We have knowledge of overseas medical device facilities that have been awarded ISO 13485 certification based on audits by persons that did not speak or read the language in which the quality system documents, DHF, DMR, and DHR were written and either had no translator on site or used a translator the did not understand the terminology used.

• Determine if the source country has laws that regulate the product, if the foreign regulatory scheme applies to exports and covers U.S. requirements, if there is a competent regulatory authority that regularly inspects the facility for compliance with the source country's requirements, and whether the source country's oversight includes any sampling and analysis. The importer should assess whether the foreign firm has complied with, or is complying with the source country's regulations, if applicable and not inconsistent with U.S. requirements, by monitoring the foreign government's oversight results. These results can assist an importer to assess the source, quality, and compliance status of products they plan to purchase and import into the United States. If the foreign government issues any type of "export" certificate for the product, or requires that the product's manufacturer be certified or licensed, be aware of the meaning of the certificate or license, including whether it covers the appropriate safety, effectiveness, labeling or other factors relative to applicable U.S. requirements.

• Conduct paper audits. The importer should consider performing or consider having an appropriate third party perform periodic reviews of production/processing records. These records should document compliance, including procedures for all processes and operations relating to compliance with U.S. requirements, control of measuring and monitoring devices, sampling and testing, corrective action plans, and steps the foreign firm takes to verify compliance with U.S. requirements.

B. Control, Monitor, and Verify Product Compliance during Entry.

• Conduct a risk-based monitoring program of incoming products to target your resources where they will likely have the greatest positive impact on product safety. Such a program could include the following:

i. Examination of shipping records;

                                                             ii.      Examination of certifications, certificates of analysis, letters of guarantee, etc.;
                                                            iii.      Physical examination of the product, packaging, and labeling; and
                                                           iv.      Risk-based product sampling and testing by the importer or an independent third party, to ensure the product is authentic, and meets company specifications and U.S. requirements. Importers should use appropriately accredited laboratories.

• We believe one of the most effective forms entry verification for devices above class I is the use of the Certificate of Analysis with the final acceptance inspection and test results attached. If a single use sterile class II or III device, then the sterilization summary batch sheet should be included.

C. Control, Monitor, and Verify Product Compliance in U.S. Distribution.

• Establish procedures for the routine review and handling of safety complaints from consumers and customers to help ensure that safety problems are identified and addressed quickly. These procedures should include an analysis to determine if any patterns of problems are developing.

• Establish procedures for identifying non-compliant products, and for communicating information and problems regarding non-compliant products within the organization, and, where appropriate, to third parties, including Federal, State, and local authorities.

• In order to identify the source and destination of a potentially violative product, the importer should consider whether it should be able to trace the product from its origin to its destination. This would facilitate the removal of the violative product from the marketplace, as well as identify other implicated products. Importers should consider using contract provisions that require the use of "track and trace" technologies to accomplish these objectives.

• Establish procedures to isolate and hold the product to prevent its distribution in the United States until all applicable agencies have issued the relevant releases. If the U.S. Government denies entry, establish procedures to export or destroy the product, or take other action consistent with applicable U.S. laws and regulations. These actions can help ensure an unsafe product does not reach consumers.

• Establish, in advance, procedures for the recall of imported products from distribution channels in the United States to limit consumer exposure to unsafe products should they come into the United States. Firms should periodically evaluate and modify these procedures, as appropriate. Develop a plan to notify appropriate Federal agencies of the product recall, which may be required by U.S. statute or regulations.

• Establish procedures to notify distributors, retailers, consumers and other end users of unsafe imported products to minimize the exposure of consumers to unsafe products, and to facilitate their timely recall.

In summary, many of the elements of this section of the Good Importer Practices draft guidance would already be in place in most of the large initial importer operations. For the small importer a qualified medical device quality and regulatory consultant would be the most cost effective way to implement GIPs.

In Importers Alert - Good Importer Practices Part 3 we will address Guiding Principle IV - Taking Corrective and Preventive Action When the Imported Product or Firm Is Not Compliant with U.S. Requirements.

Source document: FDA GUIDANCE - GIP

Importers Alert - Good Importer Practices Part 1

2011-10-31T10:34:00.001-07:00

In the last few months we have seen a significant increase the number of medical devices being held at ports of entry. This, coming on the heels of announcements earlier in the year from FDA officials that protecting the public from adulterated product entering the country is one of their top priorities. FDA’s increasing enforcement efforts are becoming effective. This is only the tip of the enforcement iceberg. As we previously reported, now is the time for medical device importers to take steps to develop or improve their Product Safety Management Program.

Backdrop

In the July 2009 Report to Committee on Appropriations on FDA’s Approach to Medical Product Supply Chain Safety, In Response to The Joint Explanatory Statement to Accompany H.R. 1105 The Omnibus Appropriations Act, 2009 reported:

“Globalization presents serious challenges to the ability of the U.S. medical product¹safety system to protect American families. Among these challenges are the growth in the number of medical products produced abroad, the increasingly complex path that medical products travel from source materials to consumers, and the greater chance for the intentional substitution of ingredients for profit (economic adulteration).”

“FDA is implementing a comprehensive approach to medical product safety along the supply chain, similar to its approach to food safety.”

The comprehensive approach:

Four main strategies constitute the foundation of FDA’s comprehensive approach to medical product supply chain safety. Together, these four strategies—focusing on prevention, enhancing regulatory information, improving FDA’s scientific and analytic capabilities, and expanding risk based inspection and enforcement—provide a framework for the integrated approach that FDA is using to improve medical product safety. FDA is implementing this approach in collaboration and coordination with key public health partners, such as foreign governments.

FDA is focusing on prevention in several ways, including the implementation of quality management systems across the supply chain, harmonizing FDA standards with the international community, launching the Beyond our Borders initiative; developing Good Importer Practices (GIPs); and setting out a foundation for a track and trace system.

To reduce risks, manufacturers should build quality into the manufacturing of their products and implement effective preventive measures at their facility, as well as ensure the implementation of such measures at their suppliers’ facilities. Manufacturers should be accountable for assessing the hazards introduced by their operations and those of their suppliers and consignees, implementing QMS, monitoring for problems before they result in harm to consumers, taking swift corrective actions to prevent recurrence of any hazards that are not effectively managed and assuring that medical products that leave their facilities are safe and effective.

Develop good importer practices (GIPs)
Importers are uniquely positioned in the supply chain to make sure foreign-made products, ingredients, and components are safe, because they are responsible for bringing those items into the United States. In January 2009, FDA and other federal agencies issued a draft guidance for industry on GIPs to encourage importers to take proactive steps to prevent harm to consumers from the products they import. The guidance sets out recommendations to importers of products, including FDA-regulated products, on practices and procedures to follow to increase the likelihood the products they import are in compliance with applicable U.S. safety and security requirements. The recommendations are intended to promote and facilitate sound decision making by importers about how best to address the product's potential to cause harm and to facilitate compliance with U.S. requirements. GIPs are broadly organized under four guiding principles:

• establishing a product safety management program

• knowing the product and applicable U.S. requirements

• verifying product and firm compliance with U.S. requirements throughout the supply chain and product life cycle

• taking corrective and preventive action when the imported product or firm is not compliant with U.S. requirements.

The draft guidance recommends, generally, that importers should know the producer of the foreign products they purchase and any other manufacturers with which they do business; that they understand the products that they import and the vulnerabilities associated with these products; that they understand the hazards that may arise during the product life cycle, including all stages of production; and that they ensure proper control and monitoring of these hazards.

Establish systems to identify medical products

With respect to medical devices, under Section 519(f) of the FDCA, as amended by FDAAA, Congress granted FDA authority to issue regulations establishing a unique device identification (UDI) system for medical devices. The statute states that the unique identifier must adequately identify the device through distribution and use and may include information on the lot or serial number.

Now is the time for the medical device importer to step up its Supply Chain Quality and Regulatory Assurance practice and align them with the practical features set forth in the FDA’s draft guidance for a product safety management program that includes the following features:

Establish a clear management structure for product safety. Such a management structure would define and document functions, responsibilities, and reporting relationships for those individuals involved in product safety to demonstrate that management places a high degree of importance on the safety of imported products.
Assign responsibility for product control and compliance to specific individuals, and ensure they understand their role in the organization.
Ensure that the assigned individuals have the necessary training, knowledge, experience, skills, and competence to perform product compliance and control responsibilities, whether for finished products, raw materials, or other in-process components.
Maintain appropriate control activities by having clearly documented policies, specifications, and procedures to ensure product safety, and maintain records to demonstrate how compliance with requirements was achieved.
Establish a process to analyze and evaluate risks in the product life cycle, and develop an approach to control those risks appropriately. This process may include conducting risk assessments.
Develop and maintain a system for communication and information that allows the sharing of relevant information on safety and compliance within the organization, and, where appropriate, with third parties, including federal, state, and local authorities.
Establish a formal, documented quality-assurance program designed to control, monitor, and improve operations continually to ensure the safety of products and compliance with all applicable U.S. requirements.

Knowing the Product and Applicable U.S. Requirements [Not all of these elements are practical or necessary for all].

Know what you are importing.
Know the details of the product you import, such as its use, the packaging, size, quantity, quality, product composition, specifications, safety concerns, etc. These details can make a difference as to which U.S. requirements apply, and whether the product is in compliance with all applicable U.S. statutes and regulations.
Know whether the product is intended for commercial sale or use in the United States or for foreign markets, as this can help you to determine whether the product has been manufactured to comply with U.S. requirements, and is properly labeled. Some imported products are not intended for commercial use/distribution, or are intended solely for foreign markets and, therefore, might not need to meet U.S. requirements for commercial use/distribution in the United States. For example, some products are made in the United States for sale in other countries, and, therefore, may not meet U.S. requirements. However, if they are subsequently offered for import into the United States (commonly referred to as "American Goods Returned"), they must meet U.S. requirements to be lawfully imported.
Know which regulatory requirements apply.
Know which U.S. requirements apply to the imported product, and to its manufacturer. General information about these requirements typically appear on the website of the federal agency(ies) with jurisdiction over the product.⁶
Become familiar with the U.S. regulatory agency's policy statements, guidance, and other available information that it publishes to assist industry and end users. These generally appear on the website(s) of the agency(ies), may answer questions about the importation process, and may provide helpful recommendations on how to comply with U.S. requirements.
Seek assistance so you know the applicable U.S. requirements and help ensure compliance. Importers can develop internal expertise or seek outside consultants for assistance in understanding, regulatory requirements. As resources permit, agency personnel may respond to general questions, and may issue additional guidance or provide training concerning the statutes and regulations they administer.
Know the risks and compliance history of the products you import, and of the firms that manufacture, distribute, or transport those products.
Know the potential hazards or other compliance problems associated with the product.
Know if any of the firms or individuals involved in the product's life cycle have previously experienced product-safety problems. For example, know if agencies with jurisdiction over the foreign manufacturer or other entities in the supply chain have previously identified violations relating to product safety by searching the agencies' websites.
Know where to find enforcement information on the agency with jurisdiction's website, if available to the public, that can aid in understanding an agency with jurisdiction's concerns related to specific products and their foreign sources, as well as problems previously found. Determine whether the firm has corrected those problems.
Know if the manufacturer(s) and the product are compliant with applicable U.S. requirements. Ask to see official documentation of compliance.
Know if the manufacturer and the product are compliant with, applicable requirements imposed by the country of production. Ask to see official documentation of compliance. Violations of other country's requirements can alert you to potential problems with your goods.
Investigate a firm's reputation, and verify its legitimacy by using available public-source information (such as the Internet) or, if possible, by interviewing other customers of the firm. If the product is sold through a trading company, distributor, or other third party, consider investigating that firm's reputation and legitimacy as well.
Determine whether a firm is a subsidiary of a larger company, and whether the importer has recourse against the parent company if the subsidiary defaults on its obligations. Manufacturers may be more likely to comply with U.S. requirements and make a safe product if the importer has recourse against them or their parent company, if they are a subsidiary.
Be familiar with the relevant U.S., foreign, and international organizations, such as trade associations, that can alert you to emerging problems with the imported products. Communicate with sources known to provide reliable information about compliance or quality issues relative to the products imported.
Be alert to information that suggests the product is subject to counterfeiting or other fraudulent activities, such as an offer to sell the product at a price significantly below market value, or a history of prior counterfeiting.
Know, if possible, whether the product was or could have been exposed to pesticides, other chemicals, or contaminants or improper storage conditions during its growth, harvesting, manufacture, processing, packing, receipt, transportation, storage, importation, or distribution and, if so, whether those circumstances could affect compliance and/or product safety. The existence of these conditions can alert you to potential safety problems.

We will cover the remaining sections of the GIP in our next article. Here is the link to the guidance document posted for comments: http://www.fda.gov/RegulatoryInformation/Guidances/ucm125805.htm

Initial Importers Alert, ISO 13485 certification does not assure FDA QSR compliance!

2011-10-26T09:22:00.000-07:00

An instructive case in point— Rocket Medical plc (Rocket). The company website states:

” Rocket Medical products have attained the CE mark and are designed to ISO9001. All of our products are manufactured to the stringent requirements of the US Food & Drug Administration (FDA) and the dedicated European medical standard ISO13485.”

Rocket Medical’s ISO 13485: 2003 certificate number GB96/8561 indicates the certification has been in force since 28 October 1996.

Rocket received a warning letter from the FDA October 13, 2011 as a result of an inadequate response to a Form FDA 483 issued July 14, 2011 related to an inspection conducted July 11 – July 14, 2011. The warning letter included five warnings. For the purpose of this alert we will only address the first three of the five issues covered in the letter.

1. Failure to establish and maintain adequate procedures to control the design of the device in order to ensure that specified requirements are met, as required by 21 CFR 820.30(a).

For example, design procedure SOP 2200/Manufacture and sale of all Product Codes did not include requirements or the location of records for design planning, design inputs, design outputs, design verification, design validation, design transfer, and risk assessment.

Your firm’s response received July 29, 2011, is not adequate. Your response only states that your firm will review and update SOP 2200. Information on the systemic corrective action was not provided. Additionally, this observation was observed during the previous inspection conducted in 2006, and an adequate corrective action has still not been implemented.

2. Failure to establish and maintain adequate procedures for implementing corrective and preventive actions, as required by 21 CFR 820.100(a).

For example:

a. Your firm’s Standard Operating Procedure/Corrective & Preventative Action Report (SOP 3104) does not include the following requirements:

i. Analysis of potential causes of nonconforming products or quality problems does not take into consideration a review of work processes, service records, and returned products

ii. Investigating the cause of nonconformities

iii. Verification or validation of the corrective or preventive actions

iv. Ensuring that information related to quality problems on nonconforming product is disseminated to those directly responsible for assuring quality of products or prevention of problems.

b. CAPA/(b)(4) was opened in September, 2010, for (b)(4) Assay testing failures for IVF product. The CAPA does not include a documented investigation but identifies some process steps as potential corrective actions. These corrective actions were not implemented. The CAPA had a target completion date of December, 2010. At the time of FDA inspection, the investigation by the testing laboratory (b)(4) was not complete.

c. CAPA/(b)(4) was opened due to a complaint of (b)(4) of Bulb Tip Catheter/57635-00-18. The corrective action was to (b)(4) There is no documented investigation of the (b)(4) problem. There is no documentation that the corrective action was verified.

Your firm’s response received July 29, 2011, is not adequate. Your firm has indicated that it will review and update SOP 3104. The systemic corrective action was not provided nor was any corrective action mentioned for the missing information in the corrective actions CAPA/(b)(4) and CAPA/(b)(4).

3. Failure to adequately establish and maintain adequate procedures to control environmental conditions that could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 820.70(c).

For example, the (b)(4)/SOP 4102 does not describe the (b)(4) acceptance criteria, the alert and action levels, or where this information can be obtained. Also, the SOP 4100 for the (b)(4) does not describe the acceptance criteria or the alert and action levels used to determine when a corrective or preventive action needs to be opened. Your firm has experienced (b)(4) over the last year without prompt action.

Your firm’s response received July 29, 2011, is not adequate. Your firm has indicated that it will review and update SOPs 4100 and 4102. The response did not discuss the systemic corrective action.

Recommendations:

1. Review your supplier audit check list: Does it include questions that would result in identifying the nonconformance’s show above? If not, revise your questionnaire accordingly.

2. Evaluate your 2012 schedule for on-site supplier audits: Is it sufficient given FDA’s current enforcement initiative?

3. Review the Rocket warning letter for the two NC not addressed here.

Rocket Warning Letter: http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm276748.htm

Buying and Transferring 510(k) Clearance

2011-10-21T16:36:00.000-07:00

FDA permits 510(k) ownership transfer, but keep in mind only one company may use any one 510(k) clearance number.

Purchase Agreement
When you purchase a 510(k) it is important to have the seller agree in writing that he is transferring the exclusive right to use the 510(k) number, the device is describe exactly as it is included in the 510(k) approval letter, list any and all changes that have been made to the device since the 510(k) was first released to market attached as an exhibit, and the seller provides a warranty and representation that the existing 510(k) clearance is legally adequate for the device as currently manufactured and distributed, taking into account all modifications to the device after clearance. As a condition of purchase have the seller request a complete copy of the subject 510(k) via FOI and provide it along with the internal documentation.
FDA does not record 510(k) transfers per se, so it is not necessary to notify FDA about the transfer of a 510(k) clearance. However the 510(k) buyer’s listing will need to be updated by adding the device and all models of the device under the FDA registration of the buyer’s facility that will be responsible for the device. One of the recommendations of CDRH PRELIMINARY INTERNAL EVALUATIONS – VOLUME 1, 510(K) Working Group, Preliminary Report and Recommendations of August 2010 was:

The 510(k) Working Group recommends that CDRH develop guidance and regulations

regarding appropriate documentation of transfers of 510(k) ownership. The Center

should update its 510(k) database in a timely manner when a transfer of ownership

occurs.

A few more tips for the buyer:
You will also want to transfer the complete copy of all correspondence between the submitter of the 510(k) and the FDA related to the specific 510(k) being purchased including the original submission and subsequent correspondence, all letters to file concerning changes in labeling, components, or design, and the design history file including all changes documentation. The information will be needed when you make any changes to the product, labeling or printed marketing materials. GMP regulations require the assessment of safety and effectiveness of all changes and a copy of the 510(k) owner’s decision tree is to be added to the regulatory and design history file for the device. The buying firm will also need to conduct at least one formal post transfer design review to include in the Design History File.
In the event the device described in the 510(k) submission does not exactly match the device being transferred, we recommend having an FDA regulatory specialist review the list of all modifications and assess whether the seller’s decisions “not to file a supplemental 510(k)" was reasonable and appropriate.

Primary Check List

Copy of 510(k) as originally submitted to the FDA
A complete FOI copy of the 510(k) requested by the seller, copies requested by 510(k) owners are not redacted.
Copies of all correspondence to and from the FDA concerning the 510(k) during the FDA review process
Copies of all change orders for changes made to the device since FDA cleared the device
Copies of all letters to file and completed safety and effectiveness assessments including FDA decision tree assessment forms for each change
A copy of the Design History File
A copy of the Device Master Record (see DMR document check list – Exhibit A)

As an Initial Importer, your regulatory risk is about to go up!

2011-09-28T10:50:00.000-07:00

All of us that deal with FDA issues on a daily basis and don’t live under a rock see it coming—US FDA is focusing more on preventing “adulterated” devices from coming into the country. Earlier this year Alan Schwartz, former supervisor of field operations at the FDA published an article SUPPLY CHAIN OVERSIGHT IS THE FDA’S NEXT AREA OF CONCERN: WHAT DOES THAT MEAN FOR YOUR?

In the article Alan writes…

The FDA recently stated its intent to stretch its enforcement reach over foreign device suppliers through consent decrees. The FDA also asked manufacturers and importers to take bigger steps toward managing suppliers and tightening up the supply chain. Carmelo Rosa, an FDA compliance officer, explains that “Currently, the agency only has authority to establish import alerts for foreign companies with good manufacturing practice violations but it is looking for other options.”

The UPS 2011 PAIN IN THE (SUPPLY) CHAIN SURVEY report asked questions of nearly 250 pharmaceutical, biotech and medical device companies senior-level decision makers. Among U.S. companies, concern about heathcare reform have risen, with 60% reporting concern verses 55% in 2010 in answer to the question: what do think will be the greatest barrier to provide quality and affordable heathcare?

Regulatory compliance toped the list of supply chain concerns cited by 73% of respondents in the survey. No wonder, we hear the powers that be beating the drums forr “MORE REGULATORY OVERSIGHT” .

On September 17, 2011 the FDA’s Deborah Autor was reported to want Congress to grant the FDA more power to regulate the medical device supply chain. With the House Energy and Commerce Health Subcommitee on the regulatory environment for biomedical product and the impact on innovation and job creation currently holding hearings the proponents of stronger regulations are listening to the parade of industry CEOs, but not being dissuaded. Although, I stand with industry senior executives in calling for a less stifling regulatory environment, I must admit that FDA needs more effective ways of assuring the safety of medical devices imported into the US from overseas manufacturers.

FOLKS, YOU DON’T HAVE TO BE A PSYCHIC TO SEE THIS COMING:

The 510(k) owner is already responsible for contract supplier compliance.
The US FDA will start cracking down and imposing penalties on initial importers
Importers that own 510(k)s with the devices made by overseas may soon start receiving warning letters. Until the warning letter is lifted the FDA may not allow the volatile devices to come into the US.

WHAT SHOULD YOU DO TODAY?

Review and update your supplier audit program to assure your overseas contract manufacturers are in full compliance with 21 CFR 803, 807, and 820. Don’t rely on ISO 13485 certifications, or desk-top audits. Do or have a deep audit done to assure your overseas manufacturer’s are compliant with US FDA regulations.

Warning Letters in 2010 - Be ready for your next FDA Inspection

2011-09-24T16:30:00.000-07:00

In 2010 the U.S. FDA’s Center for Devices & Radiological Health issued 89 warning letters containing 577 citations to medical device and diagnostics makers. Based on our experience in dealing with FDA inspectors, results of recent inspections can be an indicator of what they will want to inspect at your facility. It would be appropriate to take the following into consideration when preparing your internal audit schedule.*

Corrective and preventative actions (CAPA) accounted for 186, 32% of all citations.

83 (14%) were related to 21 CFR 820.100 Corrective and preventive action

78 (13.5%) were related to 21 CFR 820.198 Compliant files, requirements

Production and process controls (P&PC) and Acceptance activities accounted for 168 citations, 29% of all citations.

35 (6%) related to 21 CFR 820.70 Production and process controls

34 (5.9%) related to 21 CFR 820.75 Process validation

34 (5.9%) were related to 21 CFR 820.80 Receiving, in-process, and finished device acceptance

If you are interested in having a fresh set of eyes doing your next internal audit please give FDA Compliance Help a call.

* Source: Data only - MassDevices May 25, 2011 article by Stewart Eisenhart, Emergo Group

FDA Complaint Handling

2011-01-26T08:46:00.000-08:00

Ask the CEO of any small medical device firm about Complaint Handling and if they trust you they will admit they can’t afford to fully comply with FDA regulations when it comes to Complaint Handling. In many cases they will be not be aware of the requirements, especially the dreaded Medical Device Reporting requirements and record keeping. Small to mid-sized are at greater risk now, due to the increasing level of FDA enforcement as the FDA puts user fees to work.

The problem: MANAGING A PROPER COMPLAINT HANDLING PROCESS REQUIRES SPECIAL SKILLS.

For example, here is the case of the “Distributor Importer serving as U.S. Registered Agent”. In order to get exclusive distribution rights of the products made by the overseas manufacturer the distributor smartly offers to register and list the manufacturer with the FDA, pay the annual fee for the manufacturer, serve as U.S. Registered Agent to the FDA for the manufacturer, and handle regulatory issues that come up. The manufacturer is ISO 13485 certified so the distributor assumes the manufacturer is in total compliance with FDA regulations, an assumption the is proven wrong more often than not. The distributor lives up to his side of the deal and as formal complaints are filed with the distributor they are sent on to be addressed by the manufacturer. However, the distributor didn’t know:

1. The complaint recordkeeping access requirement set forth in 21 CFR 820.198(g) "If a manufacturer's formally designated complaint unit is located outside of the United States, records required by this section shall be reasonably accessible in the United States at either: (1) A location in the United States where the manufacturer's records are regularly kept; or (2) The location of the initial distributor.

2. Although it is satisfactory to keep copies of the original complaint records that are maintained overseas the files kept in the U.S. must included the complaint records for complaints that originated outside the U.S. on any device that is cleared for distribution in the U.S.

3. Initial distributors and manufacturers are required to comply with medical device reporting requirements per 21 CFR 803 Part D. Sec. 803.42 If I am an importer, what information must I submit in my individual adverse event reports?

You must include the following information in your report, if the information is known or should be known to you, as described in 803.40.

These types of information correspond generally to the format of FDA Form 3500A:

(a) Patient information (Form 3500A, Block A). You must submit the following:

(1) Patient name or other identifier;

(2) Patient age at the time of event, or date of birth;

(3) Patient gender; and

(4) Patient weight.

(b) Adverse event or product problem (Form 3500A, Block B). You must submit the following:

(1) Identification of adverse event or product problem;

(2) Outcomes attributed to the adverse event (e.g., death or serious injury). An outcome is considered a serious injury if it is:

(i) Life-threatening injury or illness;

(ii) Disability resulting in permanent impairment of a body function or permanent damage to a body structure; or

(iii) Injury or illness that requires intervention to prevent permanent impairment of a body structure or function;

(3) Date of event;

(4) Date of report by the initial reporter;

(5) Description of the event or problem, including a discussion of how the device was involved, nature of the problem, patient followup or required treatment, and any environmental conditions that may have influenced the event;

(6) Description of relevant tests, including dates and laboratory data; and

(7) Description of other relevant patient history, including preexisting medical conditions.

(1) Brand name;

(2) Type of device;

(3) Manufacturer name and address;

(4) Operator of the device (health professional, patient, lay user, other);

(5) Expiration date;

(6) Model number, catalog number, serial number, lot number, or other identifying number;

(7) Date of device implantation (month, day, year);

(8) Date of device explanation (month, day, year);

(9) Whether the device was available for evaluation, and whether the device was returned to the manufacturer, and if so, the date it was returned to the manufacturer; and

(10) Concomitant medical products and therapy dates. (Do not report products that were used to treat the event.)

(d) Initial reporter information (Form 3500A, Block E). You must submit the following:

(1) Name, address, and telephone number of the reporter who initially provided information to the manufacturer, user facility, or distributor;

(2) Whether the initial reporter is a health professional;

(3) Occupation; and

(4) Whether the initial reporter also sent a copy of the report to us, if known.

(e) Importer information (Form 3500A, Block F). You must submit the following:

(1) An indication that this is an importer report (by marking the importer box on the form);

(2) Your importer report number;

(3) Your address;

(4) Your contact person;

(5) Your contact person's telephone number;

(6) Date that you became aware of the event (month, day, year);

(7) Type of report (initial or follow-up). If it is a follow-up report, you must include the report number of your initial report;

(8) Date of your report (month, day, year);

(9) Approximate age of device;

(10) Event problem codes--patient code and device code (refer to FDA MEDWATCH Medical Device Reporting Code Instructions);

(11) Whether a report was sent to us [FDA] and the date it was sent (month, day, year);

(12) Location where event occurred;

(13) Whether a report was sent to the manufacturer and the date it was sent (month, day, year); and

(14) Manufacturer name and address, if available.

Once the distributor learned what data collection and expertise was required to comply with FDA regulations and we addressed it by adding work instructions the the QMS and training staff, the distributor was brought into full compliance.