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Guidance for Industry, FDA Staff, and Third Parties
Implementation of the Inspection by Accredited Persons Program Under The Medical Device User Fee and Modernization Act of 2002; Accreditation Criteria
This document supersedes “Implementation of the Inspection by Accredited Persons Program Under The Medical Device User Fee and Modernization Act of 2002; Accreditation Criteria: Guidance for Industry, FDA Staff, and Third Parties” issued on April 28, 2003
The information collection provisions in this guidance have been approved under OMB control number 0910-0510. This approval expires 11/30/2006. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number.
For questions regarding this document contact John F. Stigi, Center for Devices and Radiological Health (CDRH) at 301-443-6597 ext. 124, or by e-mail at: email@example.com. For questions regarding the application of this guidance to devices regulated by the Center for Biologics Evaluation and Research (CBER) contact Carol Rehkopf at 301-827-6202 or by e-mail at: firstname.lastname@example.org.
|U.S. Department of Health and Human
Food and Drug Administration
Center for Devices and Radiological Health
Center for Biologics Evaluation and Research
Third Party Implementation Team
Contains Nonbinding Recommendations
Written comments and suggestions may be submitted at any time for Agency consideration to the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD, 20852. Alternatively, electronic comments may be submitted to http://www.fda.gov/dockets/ecomments. When submitting comments, please refer to Docket No. 03D-0117. Comments may not be acted upon by the Agency until the document is next revised or updated.
Additional copies are available from the Internet at: http://www.fda.gov/cdrh/mdufma/guidance/1200.html or http://www.fda.gov/cdrh/mdufma/guidance/1200.pdf, orto receive this document by fax, call the CDRH Facts-On-Demand system at 800-899-0381 or 301-827-0111 from a touch-tone telephone. Press 1 to enter the system. At the second voice prompt, press 1 to order a document. Enter the document number 1200 followed by the pound sign (#). Follow the remaining voice prompts to complete your request.
I. What is the Purpose of this Guidance?
III. What is the Inspection by Accredited Persons (AP) Program?
IV. What is the Format and Content of an AP’s Initial Application?
V. How Can I Obtain Additional Information?
These documents are available on the FDA and CDRH Home Pages in text or PDF versions. The URL's are included in Section V of this guidance.
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.
This guidance is intended to implement new section 704(g) of the Federal Food, Drug, and Cosmetic Act (FDCA or the act) by accrediting third parties (Accredited Persons) to conduct inspections of eligible manufacturers of Class II and Class III medical devices. Inspections by Accredited Persons will be conducted in essentially the same manner as those conducted by FDA. The Inspection by Accredited Persons Program will be conducted independent of third party inspections performed under the U.S./EC Mutual Recognition Agreement (MRA), http://www.fda.gov/cdrh/mra/introduction.html, currently in progress. However, some features of the two programs will be similar.
The Inspection by Accredited Persons Program will provide manufacturers an alternative to the traditional inspection by an FDA official. At the same time, it will allow FDA to utilize its inspectional resources in a more flexible manner.
This guidance provides information for those who are interested in the new program (Inspections by Accredited Persons), including:
For purposes of this guidance, an Accredited Person (AP) is a third party recognized by FDA to:
Note: Although this guidance provides a general outline of the elements of the program that apply to establishments who may wish to use a third party inspector, the focus of this document is on third parties who want to apply to become APs under this program. “Requests for Inspection by an Accredited Person under the Inspection by Accredited Persons Program Authorized by Section 201 of the Medical Device User Fee and Modernization Act of 2002,” available at http://www.fda.gov/cdrh/comp/guidance/1532.pdf, provides establishments with more information about procedures for participating in this program.
This guidance represents the Agency's current thinking on the implementation of the Inspection by Accredited Persons Program under MDUFMA. MDUFMA requires FDA to "publish in the Federal Register criteria to accredit or deny accreditation to persons who request to perform" inspections of eligible manufacturers of Class II and Class III medical devices in lieu of FDA inspection. (Section 704(g)(2)). These criteria were published in the Federal Register on April 28, 2003 at 68 FR 22400. On October 4, 2004 FDA published revised accreditation criteria in the Federal Register 69 FR 59250 to incorporate changes to MDUFMA made by the Medical Devices Technical Corrections Act (MDTCA)(Public Law 108-214) which was signed into law on April 1, 2004. The published criteria are binding on those persons who apply to become APs under this program.
The criteria for APs that FDA published in the Federal Register are repeated in this guidance, as well as additional information that will assist with the implementation of this program. Although guidances are generally non-binding and should be viewed only as the agency's recommendations, the portions of this document that repeat the criteria FDA will use to select APs (see sections III.G-H, and IV.A-B below) have binding effect; therefore, the standard language that generally appears in FDA guidances stating that such documents constitute mere recommendations does not apply to these portions. However, with respect to the remainder of this document, the following standard language still applies:
FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.
The Least Burdensome Approach
The issues identified in this guidance document represent those that FDA believes need to be addressed by participants in this program. In developing the guidance, FDA carefully considered the relevant statutory criteria. FDA also considered the burden that may be incurred in complying with the guidance and addressing the issues we have identified. FDA believes that we have considered the least burdensome approach to resolving the issues presented in this guidance document. If, however, you believe that there is a less burdensome way to address the issues, please contact us. You may send your comments to the contact person listed in the preface of this guidance. Also, comprehensive information on dispute resolution at Center for Devices and Radiological Health (CDRH) is listed on the CDRH Ombudsman's web page: http://www.fda.gov/cdrh/ombudsman/. Information on dispute resolution for Center for Biologics Evaluation and Research (CBER) regulated devices is listed on the CBER web site at: http://www.fda.gov/cber/inside/ombudsman.htm
A. Why Are Medical Device Establishments Subject to Mandatory Inspections?
The FDCA established a requirement that FDA inspect manufacturers of Class II and III devices at least once every two years because Congress believed regular oversight would help ensure that appropriate manufacturing conditions and controls were in place to produce safe and effective products [see Section 510(h) of the FDCA]. The agency’s ability to perform biennial inspections of all eligible establishments has diminished with decreasing resources and the significant growth of the medical device industry. Over the years, the agency has reengineered its inspection policy and work plans to embrace a risk based approach that targets limited resources to inspections that will best protect the public health. The AP inspection program established by MDUFMA will be another tool the agency and stakeholders can use to leverage resources by permitting qualified independent third parties to perform certain biennial inspections.
B. What is the Quality System / Good Manufacturing Practice (GMP) Regulation?
The GMP requirements for medical devices were first authorized by the Medical Device Amendments of 1976 in section 520(f) of the act. As a result of this new authority to inspect medical device facilities, FDA published final regulations in July 1978, prescribing GMP requirements for the methods used in, and the facilities and controls used for, the manufacture, packing, storage, and installation of medical devices. This regulation became effective in December 1978 and was codified in Title 21 of the Code of Federal Regulations, Part 820 (21 CFR Part 820).
In developing the 1978 GMP regulation, FDA recognized that the medical device industry consists of manufacturers whose devices and manufacturing processes differ significantly. Therefore, the GMP regulation was designed to specify general requirements in areas of concern applicable to all manufacturers. Under the GMP regulation, FDA expects each manufacturer to develop a set of appropriate procedures for the manufacture of each device. FDA conducts inspections and evaluates these procedures to determine whether the manufacturer is complying with the regulation.
In November 1990, the Safe Medical Devices Act (SMDA) amended section 520(f) of the act to give FDA the authority to add preproduction design controls to the GMP regulation. The SMDA also added a new section 803 to the act. This section encourages FDA to work with foreign countries toward mutual recognition of the GMP and other regulations. This section also encourages any revision of the GMP regulation to be consistent with the requirements contained in applicable international standards.
In October 1996, FDA published the Quality System regulation (QS regulation), which revised the 1978 GMP regulation, incorporating new requirements for preproduction design controls, supplier and service controls, and management controls. As part of this process, FDA attempted, to the extent possible, to harmonize the QS regulation with the international standard ISO 13485:1996, Quality Systems, Medical Devices, Supplementary Requirements to ISO 9001:1994.
C. What is FDA’s Experience with Third Party Quality System Inspections?
U.S./EC Mutual Recognition Agreement
On June 20, 1997, the United States (U.S.) and the European Community (EC) signed a Mutual Recognition Agreement (MRA) which covers a variety of product sectors, including medical devices. The aim of this agreement is to facilitate transatlantic trade while reducing costs for compliance with regulatory requirements. This agreement became effective December 1, 1998 and initiated a three-year transition period during which time both sides have engaged in confidence-building activities. The confidence-building period was extended to December 2003.
The medical device annex to the MRA covers the exchange of quality system evaluation/inspection reports for all medical devices and premarket notification (510(k)) reports for selected low-to-medium risk devices. An EU Conformity Assessment Body (CAB) can conduct inspections for all classes of devices and 510(k) evaluations based on FDA requirements for selected devices produced for the U.S. market. Similarly, a U.S. CAB can conduct a quality system evaluation based on EU requirements for all classes of devices or type-testing evaluation for selected devices produced for the EU market. See FDA’s Guidance for Staff, Industry, and Third Parties for more information about the third-party programs established under the MRA.
Under the MRA, both the U.S. and the EU may eventually be able to save resources by relying on evaluations conducted by the other party, thereby saving overseas travel time and expense. CABs are required to participate in rigorous joint activities in order to demonstrate proficiency in conducting either FDA or EU evaluations. Based on such demonstrated proficiency, both parties expect to "normally endorse" evaluations conducted by the other party, while reserving the final decision making to themselves and reserving the right to conduct their own evaluations should significant deficiencies be found in any reports. As of this date, FDA has verified four European Union Conformity Assessment Bodies (EU CABs) to conduct independent inspections for FDA under the MRA.
D. How does the Medical Device User Fee and Modernization Act of 2002 Affect FDA Inspections?
The Medical Device User Fee and Modernization Act of 2002 (MDUFMA) was signed into law by the President on October 26, 2002. Most provisions went into effect on that day, while other provisions have later effective dates and/or require implementing regulations.
Section 201 of MDUFMA establishes a new subsection “g” to section 704 (Factory Inspection) of the act, which requires FDA to accredit third parties (APs) to perform inspections of eligible manufacturers of Class II or III devices. This is a voluntary program. While all firms remain subject to inspection by FDA, eligible manufacturers have the option of being inspected by an AP. However, inspections by APs are limited by the act to manufacturers who meet the conditions described in section III B of this document.
MDUFMA requires that no more than 15 firms be accredited during first year of the AP Program. On October 26, 2003, FDA posted on its web page a list of 15 APs that were accredited. These APs will not be eligible to perform inspections for FDA until they have successfully completed the Tier 1 and Tier 2 requirements which includes FDA’s training program and the conduct of a satisfactory performance inspection under FDA’s observation. Applicants that applied in 2003 and were not accredited, as well as first time applicants, are invited to reapply this year. On April 28, 2004, FDA began accepting new applications. Newly accredited APs will be added to the current list of APs within 30 days after being accredited by the Third Party Recognition Board (TPRB). MDUFMA requires FDA to inform those requesting accreditation, within 60 days of receipt, whether their application is adequate for review. (See section III.G. for qualifications to become accredited.) The list of APs will be updated periodically but no later than one month after a new accreditation, the withdrawal of an accreditation, or a change in activities for which an AP was accredited.
A. What Are the Primary Features of the Program?
The primary purpose of the Program is to permit APs to perform the equivalent of an FDA Quality System inspection and to submit the findings to FDA for final determination. In accordance with the requirements of section 704(g) of the act and based on FDA’s experience with third parties under the MRA, the Inspection by APs Program includes features designed to maintain a high level of confidence in inspections by APs and to minimize risks to the public health. These include:
B. What Establishments are Eligible for Inspection by APs?
Not all device establishments are eligible for inspection by an AP. In order to be eligible to employ an AP in lieu of an inspection by FDA, establishments must meet the following basic criteria under section 704(g)(1) and 704(g)(6)(A) of the act:
1. You "manufacture, prepare, propagate, compound, or process" class II or class III medical devices. (Sec. 704(g)(1) of the act.) The shorthand term "manufacture" will be used for convenience throughout this document instead of listing each of these activities (i.e., "manufacture, prepare, propagate, compound, or process") repeatedly. ;
2. Your establishment markets at least one of these devices in the United States;
3. Your establishment markets or intends to market at least one of these devices in one or more foreign countries and one or both of the following two conditions are met:
(a) One of the foreign countries certifies, accredits, or otherwise recognizes the AP you have selected as a person authorized to conduct inspections of device establishments, or
(b) Your firm submits a statement that the law of a country where you market or intend to market your devices recognizes an inspection by the FDA or by the AP. (Sec. 704(g)(6)(A)(iii)(I), (II) of the act.);
4. Your most recent inspection performed by FDA, or by an AP under this program, was classified by FDA as either "No Action Indicated" (NAI) or “Voluntary Action Indicated" (VAI). (Sec. 704(g)(6)(A)(i) of the act.); and
5. You submit a notice to FDA requesting clearance (approval) to use an AP, identify the AP you selected, and FDA agrees to the use of the selected AP. (Sec. 704(g)(6)(A)(ii).).
The intent of these provisions is to focus the use of third party inspections
on manufacturers that operate in a global market and are likely to be subject
to multiple inspection requirements.
C. How Do I Request an Inspection by an AP?
The FDA guidance document entitled, “Requests for Inspection by an Accredited Person under the Inspection by Accredited Persons Program Authorized by Section 201 of the Medical Device User Fee and Modernization Act of 2002,”which is available on-line at http://www.fda.gov/cdrh/comp/guidance/1532.pdf, provides details about requesting a third party inspection. In general, however, the establishment will send a notice to the applicable Office of Compliance in CDRH or CBER requesting clearance (approval) to employ a specific third party to do a QS regulation inspection during a 2 year period in lieu of a required FDA inspection. Under section 704(g)(6)(B)(i), FDA must respond within 30 days of receiving an establishment’s notice requesting clearance to employ an AP to conduct an inspection. If FDA fails to respond to a notice within 30 days, the establishment is deemed to have clearance to use the AP it selected.
FDA’s response to a notice may include:
When FDA requests additional information, the statute requires FDA to either
provide or deny clearance to use the selected AP within 60 days of receiving
the additional information. If FDA denies the request, the reasons for denial
will be stated. If FDA does not respond, the selection is deemed to have been
accepted. (Sec. 704(g)(6)(B)(iv) and (v)).
D. What Can I Do if FDA Denies My Request to Use an AP?
If FDA determines that your establishment is not eligible to use an AP to do an inspection in lieu of an FDA inspection, you may:
If FDA rejects your establishment’s selection of an AP, you may:
If an establishment is inspected by an AP and receives an Official Action Indicated (OAI) determination from FDA following the inspection, the act provides at section 704(g)(6)(C) that the establishment becomes ineligible to use an AP again until:
Participation in the program is entirely voluntary. Eligible manufacturers may utilize an AP or continue to have FDA perform inspections.
E. Are There Limits to the Number of AP Inspections that can be Performed?
MDUFMA sets limits on the number of consecutive inspections that can be performed by APs in lieu of FDA inspections. Section 704(g)(6)(A)(iv)(I) does not permit an establishment to use an AP for more than four years (two complete third-party inspections, each completed within a two-year period) unless the establishment first petitions FDA for and receives a waiver.* This provision of MDUFMA is intended to ensure periodic inspections by FDA while avoiding penalizing companies who are prepared for an inspection before FDA can conduct it. As depicted on the chart below, there are two paths for approval of a waiver petition allowing continued use of APs to conduct inspections: one requires explicit FDA approval, the other is deemed granted.
*Note: The statute describes the applicable time limits using the words “during the previous four years.” (see section 704(g)(6)(A)(iv)(I)). FDA reads “during” to mean “throughout the course or duration of” as cited in Webster's II New Riverside University Dictionary, 1984 edition.
FDA may grant the petition if
The petition is “deemed to be granted” if
F. How Can I Become an AP?
FDA will use the TPRB to accredit persons to conduct inspections of medical device establishments under MDUFMA. In 1998, the FDA established the TPRB to accredit persons under section 523 of the act. The FDA also utilized the TPRB to verify the qualifications of EU CABs under the U.S./EC MRA. EU CABs perform a scope of work similar to the APs for inspection.
Applications to become an AP under MDUFMA's Inspection by Accredited Persons Program should be submitted to the TPRB. Information on how to submit an application is provided at section IV. B of this document. FDA accredited 15 firms in the first year of the program. Organizations may apply to be an AP for the inspection of all eligible establishments or limit their scope to specific types of devices. FDA will accredit only applicants with qualified personnel (technically competent) and who meet stringent conflict of interest standards. FDA will accept applications from both domestic and foreign persons. To facilitate timely review, applications and communications should be in English.
MDUFMA required FDA to post on its Internet site a list of persons that have been accredited by the agency. To meet this statutory timeframe, FDA posted the first list of 15 accredited persons on October 26, 2003.
FDA will maintain a list of APs eligible to conduct inspections on the CDRH Home Page. This list will include the name, contact person, address, telephone number, e-mail address, status (e.g., foreign certifications, eligibility to do independent inspections, etc.), and any limitations in the APs' scope of work.
G. What Qualifications Are Necessary to Become an AP?
Only those applicants that demonstrate that their organization has the relevant qualifications and competence to perform inspections and that they have instituted effective controls to prevent any conflict of interest or appearance of conflict of interest that might affect the inspection outcome may be accredited. In addition, before APs can conduct independent inspections, they will need to successfully complete classroom training and qualifying inspections performed under FDA’s observation.
As specified at section 704(g)(3) of the act, to be accredited, the applicant must, at a minimum, meet the following general requirements:
In addition to the minimum requirements described above, FDA will also consider the following criteria when selecting APs:
FDA expects APs to have sufficient personnel, with the necessary education, training, skills and experience to review records and perform inspections. We will consider several factors when evaluating personnel. These include:
a. whether personnel have knowledge of:
- the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321 et seq.);
- the Public Health Service Act (42 U.S.C. 201 et seq.);
- regulations implementing these statutes, particularly 21 CFR Parts 11 and 800-1271, with special emphasis on Parts 11, 801, 803, 806, 807, 809, 814, 820 and 821;
- FDA Compliance Program 7382.845, Inspection of Medical Device Manufacturers;
- Guide to Inspection of Quality Systems: Quality System Inspection Technique (QSIT); and
- FDA Investigations Operations Manual, Chapter 5-Establishment Inspection.
b. whether the applicant:
- has established, documented, and executed policies and procedures to ensure that inspections are performed by qualified personnel, and whether it will maintain records on the relevant education, training, skills, and experience of all personnel who contribute to the performance of inspections;
- has available to its personnel clear, written instructions for duties and responsibilities with respect to inspections;
- has identified personnel who, as a whole, are qualified in all of the quality system disciplines for the inspections under the AP’s scope of work; and
- has identified at least one individual who is responsible for providing supervision over inspections and who has sufficient authority and competence to assess the quality and acceptability of inspection reports.
APs need the capability to interface with FDA's electronic data systems, including the FDA Internet websites, and the CDRH Facts-On-Demand system. At a minimum, this would entail a computer system with a modem and an independent facsimile machine. FDA will rely extensively on the use of our electronic systems for timely dissemination of guidance documents to APs and other interested parties.
APs must have physical security and safeguards for protecting trade secret and confidential commercial or financial information, as well as personal identifier information in medical records, such as adverse event reports, that would reveal the identity of individuals if disclosed.
3. Prevention of Conflicts of Interest (COI)
MDUFMA requires that APs be impartial and free from any commercial, financial, and other pressures that might present a conflict of interest or an appearance of a conflict of interest (section 704(g)(3)). To that end, when deciding whether to accredit a person, we will consider whether they have established, documented, and executed policies and procedures to prevent any individual or organizational conflict of interest, including conflicts that contractors or individual contract employees may have.
Although it is not feasible to identify all of the circumstances that would raise concerns about conflicts of interest in this document, the most common conditions that indicate an actual or a potential conflict of interest are:
a. the AP is owned, operated, or controlled by a manufacturer, supplier or vendor of any article regulated under the act; See http://www.fda.gov/ohrms/dockets/yellow/yellotoc.htm for examples of firms that are regulated by FDA and, therefore, would create a conflict. This includes manufacturers of radiation-emitting electronic products such as televisions, microwave ovens, CD players, laser printers, industrial lasers, as well as foods, drugs, biologics, cosmetics, veterinary products, and medical devices.
b. the AP has any ownership or financial interest in any product, manufacturer, supplier or vendor regulated under the act;
c. any personnel of the AP involved in inspections or their spouse or minor children have an ownership or other financial interest regarding any product regulated under the act (see link at 3 a. above);
d. the AP or any of its personnel involved in inspections participates in the design, manufacture, promotion or sale of any product regulated under the act;
e. the AP or any of its personnel involved in inspections provides consultative services to any manufacturer, supplier, or vendor of products regulated under the act (see link at 3 a. above);
f. any personnel of the AP involved in the inspection process participates in an inspection of a firm they were employed by within the last 12 months;
g. the fees charged or accepted are contingent or based upon the report made by the AP.
When the AP uses the services of a contractor in connection with an inspection, it is responsible for the work of the contractor and its personnel. It will be the APs responsibility to assure that the contractor meets the same criteria for freedom from conflicts of interest as the AP and its personnel.
In addition to conducting inspections as an AP, you may also conduct other activities, such as objective laboratory testing of products regulated under the act or assessment of conformance to standards, if those other activities do not affect the impartiality of inspections. Examples of conflicted laboratory testing, activities an AP may not perform, are those tests linked to the manufacturing process and which are usually performed by manufacturers such as routine quality production tests, validation/verification studies, and quality assurance related testing.
Information on the conflict of interest standards FDA applies to its own personnel is included in Appendix 1, “Standards for Ethical Conduct for Employees of the Executive Branch.” An AP may adopt these standards, utilize the Model Conflict of Interest Policy FDA has provided (see Appendix 2), or explain alternative equivalent procedures that will safeguard operations against conflicts of interest.
H. If I Am Approved as an AP, What Additional Training Will Be Required Before I Can Do Inspections and Who Will Provide that Training?
If you are approved to be an AP, you will be asked to designate employees to participate in classroom training and joint qualifying inspections. FDA conducted the initial training program for AP auditors in January 2004. FDA will periodically provide either “face to face” or electronic training of AP auditors. Training for new AP auditors consists of a two-tiered program as follows:
1. Tier one will include formal classroom training. At a minimum this will include:
a. The Association for the Advancement of Medical Instrumentation (AAMI) GMP/ Quality System: Requirements and Industry Practice (or equivalent). AAMI conducts this training throughout the United States and in foreign countries; See AAMI web site at http://www.aami.org/meetings/courses/gmp.html for specific dates and locations. A copy of each trainee’s certificate of successful completion of the AAMI training should be submitted to FDA's Third Party Recognition Board.
b. Successful completion of FDA’s Quality System Inspection Technique (QSIT) training module.
c. FDA Investigator Training, which will include training by FDA on:
- Food and Drug law,
- Advanced QSIT,
- FDA inspectional procedures,
- FDA policies and device regulations, and
- Evidence development.
Those trainees who successfully pass the test given at the end of each Tier one training session will qualify for the second tier of training.
2. Tier two of the training will include successful completion of three joint inspections with FDA. Joint inspections will be carried out in accordance with the relevant parts of Compliance Program 7382.845-Inspection of Medical Device Manufacturers and the QSIT guidance-Guide to Inspection of Quality Systems. The three joint inspections include:
a. Collaborative Inspection- The FDA investigator will be the lead inspector and the AP trainee will act primarily as an observer. The FDA investigator will prepare a list of any non-conformities and an inspection report. The trainee will prepare a “practice” list of non-conformities and an inspection report.
b. Modified Performance Inspection- Using established criteria, the FDA investigator will observe and evaluate the trainee performance of an inspection and may provide assistance. The trainee will prepare a list of any non-conformities to be presented to the facility and an inspection report. The FDA investigator will review the list of non-conformities and provide feedback before it is presented. In addition, the FDA investigator will review the inspection report and, if necessary, write an addendum to supplement the inspection report.
c. Full Performance Inspection- The AP trainee will perform an independent inspection and will be observed and evaluated by the FDA investigator using established criteria. The FDA investigator may not provide assistance to the trainee. The trainee will prepare a list of any non-conformities to be presented to the facility and an inspection report. The FDA investigator will review the list of non-conformities and provide feedback before it is presented. In addition, the FDA investigator will review the inspection report and, if necessary, write an addendum to supplement the inspection report. The FDA investigator's evaluation of the trainee and recommendation will be presented to the FDA Office of Regulatory Affairs (ORA) certifier in the FDA Division of Human Resource Development who will determine if the trainee is qualified to perform independent inspections.
The criteria FDA will use to evaluate the joint inspections will be addressed at the FDA training sessions.
Training for APs will be “modeled” after the training program FDA put in place for EU CABs under the MRA Implementation Plan. (See http://www.fda.gov/cdrh/mra/guidance/mraprocedure.html for additional information about that program.)
EU CABs that have been accredited as APs, whose personnel have previously successfully completed the required classroom training and/or joint inspections under the MRA program, should state this in their application. If confirmed by FDA, the AP will not be required to have a representative repeat the classroom training or joint inspections. However, FDA does recommend that the AP send a representative to the FDA Investigator Training module (See III.H.1.c above) as an update. Personnel trained by FDA under the MRA program who do not attend the current training will need to review a videotaped FDA presentation on evidence development.
FDA will provide APs with information on its inspection procedures, criteria, general guidance, and any additional training programs. Also, APs may access the FDA’s Office of Regulatory Affairs (ORA) Home Page, http://www.fda.gov/ora/, the Center for Devices and Radiological Health (CDRH) Home Page, http://www.fda.gov/cdrh/, and the Center for Biologics Evaluation and Research (CBER) Home Page, http://www.fda.gov/cber for general information on regulatory guidance and on MDUFMA. APs may also access existing guidance documents specific to FDA inspections listed in Section V of this document.
I. How Will APs be Monitored?
The CDRH Office of Compliance (OC) will monitor APs for inspections relating to devices regulated by CDRH and the CBER Office of Compliance and Biologics Quality (OCBQ) will do so for inspections relating to devices regulated by CBER. These two offices, together with the ORA Office of Regional Operations (ORO), will perform an evaluation based on the first three independent inspections by the AP. Subsequently, FDA will audit APs on a periodic and “for cause” basis. The APs must continue to demonstrate technical competency in order to maintain accreditation.
FDA will inspect the APs’ facilities to assure they have maintained records and are operating in accordance with procedures as specified in their application and section 704(g)(7) of the act. In addition, FDA will monitor inspections conducted by APs and may periodically accompany them on an inspection or perform an audit of an AP-inspected facility.
J. How will FDA Address Concerns about the Independence of APs?
As discussed above, each AP will be expected to demonstrate that there are no actual or perceived conflicts of interest and that there are procedures in place to ensure that the AP will maintain its freedom from conflicts of interest. In addition, the statute requires each AP to publish actions it has taken to ensure that it has followed the prevention of conflict of interest requirements of the AP program at the end of each year.
Because the statute requires FDA to monitor each request from an establishment to use a particular AP, the agency will have the ability to stop inspections by APs who may have developed inappropriate business relationships with certain companies.
If FDA’s monitoring of the program reveals that manufacturers are developing business relationships with APs that call into question the independence or objectivity of the AP, FDA will consider implementing a process that limits the submitter's choice of APs for a specific inspection. Business relationships that may undermine the independence or objectivity of an AP include contracts between a manufacturer and an AP that represent a significant share of the AP's income such that continuation or termination of the contract may create undue financial influence or at least the appearance of such influence. Where there is evidence of a financial conflict of interest between the AP and the owner or operator of the inspected device establishment, FDA may take steps to withdraw the AP's accreditation in accordance with section 704(g)(5) of the act.
K. What Inspection Records Are to be Submitted to FDA?
APs will need to prepare an FDA prescribed report, using the format defined in the Investigations Operations Manual (IOM), http://www.fda.gov/ora/inspect_ref/iom/ subchapters 559 and 590. Also see List of Observations, http://www.fda.gov/ora/inspect_ref/iom/exhibits/x510b.html. FDA will provide instruction in the preparation of a list of observations and the report at the FDA training course. See Regulatory Procedures Manual: http://www.fda.gov/ora/compliance_ref/rpm_new2/ for timeframes for submitting reports.
At the conclusion of the inspection, when deficiencies have been observed, the AP Inspector lists all significant objectionable conditions observed and presents them in writing to notify the manufacturer’s top management of significant objectionable conditions. Each observation is discussed with the firm’s most responsible person at the facility. In addition, the AP inspector will prepare and send a report to FDA and the manufacturer’s designated representative at the same time, but no later than three weeks following the last day of the inspection. As required by section 704(g)(7)(B), the report, at a minimum shall:
FDA expects the APs' reports and any clarifying information requested by FDA to be provided in English. Any documents collected from the manufacturer may be in the operational or working language used in the manufacturer’s facility. However, the time necessary to translate the firm’s documents may delay FDA’s endorsement.
FDA may not be able to evaluate and classify an inspection report submitted by an AP if the information discussed above is not included. If information necessary for the agency's review is not included, we will begin our review only after we receive the necessary information.
If at any time during an inspection the AP discovers a condition that it believes could cause or contribute to an unreasonable risk to public health, the AP must report the problem to FDA immediately. This will be a topic of discussion at the FDA training.
L. How will APs and FDA Treat Confidential Information?
The AP must protect trade secret and confidential commercial or financial information, and must treat as private personal identifier information in records such as adverse event reports, except that such information may be made available to FDA. FDA recommends that any contract between an AP and an establishment include a provision that specifies protection of trade secret and confidential commercial or financial information.
FDA will determine the releasability of inspection records and information collected from the manufacturer and submitted to FDA by an AP in accordance with applicable disclosure laws, including the Freedom of Information Act (5 U.S.C. 552) , the Trade Secrets Act (18 U.S.C. 1905), section 301(j) of the Act (21 U.S.C. 331(j)) and FDA regulations implementing these statutes. For information on FDA treatment of confidential information and definitions of what constitutes trade secret or confidential commercial or financial information, see the FDA regulations implementing the Freedom of Information Act in 21 CFR Part 20. See also FDA’s FOI web page at http://www.fda.gov/foi/foia2.htm
In general, inspection records and information collected from the manufacturer and submitted to FDA by APs will be available for disclosure by FDA after the agency has issued a compliance decision, unless such information is exempt from disclosure by law.
Note also that information submitted by an AP to obtain approval for participation in the program will be available for disclosure by FDA except to the extent it constitutes trade secret, confidential commercial or financial information, or information that is otherwise exempt from public disclosure by law.
M. What Records Should an AP Maintain?
At a minimum, an AP should maintain records that support the initial and continuing qualifications to be an AP. These records include:
In accordance with section 704 of the act, an AP must make these records available upon request to an officer or employee of FDA at all reasonable times and FDA may view, copy, or verify these records.
In addition, an AP should retain the following records for at least three years following its submission of an inspection report to FDA and the inspected device establishment:
N. What Fees May an AP Assess?
An AP may assess a reasonable fee for services. The fee for an inspection is a matter to be determined by contract between an AP and the device establishment to be inspected. FDA will consider the fee to present a conflict of interest if it is contingent or based on the type of report made by the AP.
O. Can FDA Withdraw AP Accreditation?
In accordance with section 704(g)(5) of the act, FDA may withdraw accreditation when an AP is substantially not in compliance with the standards of accreditation, poses a threat to the public health, or fails to act in a manner consistent with the act or where FDA determines that there is a financial conflict of interest between the AP and the owner or operator of a device establishment that the AP has inspected. Before FDA withdraws an AP's accreditation, we will notify the AP and provide an opportunity for an informal hearing. FDA may at its discretion suspend the accreditation of the AP prior to the outcome of this process.
P. Did MDUFMA Change the Prohibited Acts Section of the act?
MDUFMA amended Section 301 of the act by adding the following prohibited acts as paragraph (gg):
Q. How Do Manufacturers Identify an AP?
Manufacturers should access the CDRH Home Page at: http://www.fda.gov/cdrh for a list of APs and the name and address of each AP's contact. The listed APs are not eligible to perform inspections under section 704 (g) of the act until FDA determines that all training has been successfully completed. The list will reflect the status of APs. Manufacturers should see section III B of this guidance for information about eligibility to participate in this program.
Persons wishing to become APs under section 704(g)(2) of the act should apply to the TPRB. Detailed information about the application process is set forth below. FDA will inform those requesting accreditation, within 60 days of receipt of the application, whether their application is adequate for review.
A. How Will FDA Evaluate the AP Application?
1. The TPRB Chairman will e-mail the applicant’s contact person, within 24 hours of receipt of the AP application, acknowledging receipt.
2. Members of the TPRB will perform an initial review to determine if the request for accreditation addresses the information in section IV B and is adequate for review by the full TPRB.
3. The TPRB Chairman will advise the contact individual, via e-mail, within 60 days after the receipt of such request for accreditation, whether the request is adequate for review by the TPRB or if additional information is needed.
4. If the application is deficient, FDA will identify its shortcomings and advise the applicant so it may submit additional information within the designated time period. FDA may deem the application incomplete and deny the request for accreditation if the applicant fails to respond to a request for additional information in a timely manner. All information submitted to FDA in response to any requests for additional information should be received by the date indicated in the FDA request.
5. If the application is adequate, FDA will file it for full review, rating and ranking by the TPRB. The rating criteria checklist (see Appendix 3) will be used to assess the relevant qualifications and competence of persons applying to become APs. The agency has assigned a weight (5, 15 or 20) to each of eight elements. The eight elements are addressed in the next section, IV. B., What are the Contents of an AP Application. The weight of the element is based on how essential the information is in determining if the applicant is suitable to perform Quality System / Good Manufacturing Practices (QS/GMP) inspections on behalf of FDA. Each member of the TPRB will assess each of the eight elements and will vote a “quality level” score from 0 to 4 (0 = Unsatisfactory, 2 = Satisfactory, 4 = Exceeds) for each element. The final Quality Level Score will be determined by a majority vote of the TPRB. Quality Level Score x Weight = Element Score. The eight element scores will be totaled to yield an “Application Rating” (maximum rating attainable is 400). An applicant with one or more elements assessed as “unsatisfactory” will be deemed to have failed to meet the criteria established for an AP.
6. FDA may deny the request for accreditation if we determine that the application does not meet the criteria established for APs.
7. FDA plans to update the List of Persons Accredited for Inspections published on its web site within 30 days of accrediting or withdrawing accreditation of an AP.
B. What Are the Contents of an AP Application?
Applicants should include the information described below to demonstrate that they meet the qualifications addressed in section III, G, What Qualifications are Necessary to Become an AP. In addition, the rating details for information submitted in the application are included in Appendix 3. The AP may want to include the rating criteria checklist as a coversheet to the application with all applicable documented sections of the application cross-referenced next to the criteria under the right hand column of the checklist, “Where document is found in AP application”. Using the checklist this way can help ensure timely and efficient review of the information you have submitted to establish your qualifications.
1. Administrative Information
FDA will assess this section of the application according to information in section 1, “Administrative Information” of the rating criteria checklist (Appendix 3).
2. Prevention of Conflict of Interest
The applicant should submit a copy of the written policies, procedures and sample certification/compliance statements established to prevent conflicts of interest. MDUFMA requires that the AP and its employees (including contract employees) involved in the performance of inspections and the preparation and approval of reports be free from conflicts of interest and the appearance of conflicts of interest that might affect the inspection process. No personnel of an AP involved in inspections, nor their spouses or minor children, may have ownership of or other financial interest in any product regulated under the act. In accordance with section 704(g)(3)(E), APs will annually make available to the public the extent to which the AP complies with conflict of interest requirements.
FDA will assess this section of the application according to information in section 2, “Conflict Of Interest”, in the rating criteria checklist (Appendix 3). An applicant’s documentation of conformity with the Model Conflict of Interest Policy (see Appendix 2), or similar procedures or standards, will carry significant weight in the rating process. See pages 15-17 of this guidance for a discussion of conflict of interest concerns.
3. Technical Competence
FDA will consider several factors with respect to personnel qualifications and the preparedness of the applicant to conduct technically competent inspections. The applicant should document these factors in its application and include:
FDA will assess this section of the application according to information in section 3, “Technical Competence” of the rating criteria checklist (Appendix 3). Technical competence and the thoroughness with which the requirements are addressed will carry significant weight in the rating process.
The applicant should identify what reference materials are available to inspectors and other personnel involved in inspections, (e.g., the act, regulations, manuals, standards). Also, the application should identify equipment and resources available that will enable the inspector to perform technical and administrative tasks. At a minimum, this should include a computer system with a modem and an independent facsimile machine. FDA will rely extensively on the use of our electronic systems for timely dissemination of guidance documents to APs and other interested parties.
APs should have physical security and safeguards in place for protecting trade secret and confidential commercial and financial information, as well as personal identifier information in medical records, such as adverse event reports, that would reveal the identity of individuals if disclosed.
FDA will assess this section of the application according to information in section 4, “Resources” in the rating criteria checklist (Appendix 3).
The applicant should include established procedures to ensure confidentiality of reports and all information obtained during an inspection. These should address aspects of authorized disclosure and the procedures by which the applicant maintains confidentiality between itself and the manufacturer. In addition, the applicant should describe the procedures through which the applicant's personnel and any contractors are made aware of confidentiality requirements.
FDA will assess this section of the application according to information in section 5, “Confidentiality” of the rating criteria checklist (Appendix 3).
FDA will consider several factors to determine whether the applicant ensures that contractors are properly qualified, utilized and monitored. Special emphasis will be placed on personnel qualifications and preparedness to conduct technically competent inspections, and on conflict of interest controls. The applicant should document these factors in the application and include:
FDA will assess this section of the application according to information in section 6, “Contractors” of the rating criteria checklist (Appendix 3).
7. AP Quality System
FDA will consider the following factors to determine whether the applicant has established an adequate quality system to ensure compliance with FDA policies and procedures relevant to inspections:
8. Certification Agreement Statement
The applicant should provide a copy of a documented statement, which will be signed by the most responsible individual, certifying that:
This information is included in section 8, “Certification/Agreement Statement” of the rating criteria checklist (Appendix 3).
C. Where Do I Send an Application to Become an AP?
Send applications to become an AP to the following address by a method such as registered mail that returns to you proof of delivery. Submit 3 complete copies, with all attachments, to the address below and keep a complete copy for your files. FDA will accept electronic submissions from any applicant that wishes to submit in this format.
Anthony Rodgers, Chairman
Third Party Recognition Board (HFZ-220)
Center for Devices and Radiological Health
Food and Drug Administration
1350 Piccard Drive
Rockville, Maryland 20850 USA
D. Can I Request Reconsideration of a TPRB Decision?
A written request for reconsideration of a decision by the TPRB should be addressed to:
Director, Division of Small Manufacturers, International and Consumer Assistance
Center for Devices and Radiological Health (HFZ-220)
Food and Drug Administration
1350 Piccard Drive
Rockville, Maryland 20850
Interested parties can obtain additional information on the Inspection by Accredited Persons Program under the MDUFMA through the FDA or CDRH Home Pages and/or on 3.5" IBM formatted disks. To request a copy of these documents on disk, FAX a request to the Division of Small Manufacturers, International, and Consumers Assistance, Attention: Publications, at 301-443-8818 or telephone 301-443-6597 ext. 114.
Also, persons interested in obtaining a copy of the documents listed below may do so using the Internet. CDRH maintains an entry on the Internet for easy access to information, including text, graphics, and files that may be downloaded to a PC with access to the Internet. The FDA Home Page may be accessed at http://www.fda.gov and the CDRH Home Page may be accessed at http://www.fda.gov/cdrh. The appendices of this guidance also list currently available documents for third-party programs under MDUFMA.
Appendices 1 - 10 are available on the FDA and CDRH Home Pages:
1. Standards of Ethical Conduct for Employees of the Executive Branch; http://www.fda.gov/cdrh/modact/soc917.pdf
2. Model Conflict of Interest Policy; http://www.fda.gov/cdrh/mdufma/mcipolicy.html
3. AP Inspection Program Rating Criteria Checklist; http://www.fda.gov/cdrh/mdufma/aprating.html
4. The Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321 et seq.); http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm
5. The Public Health Service Act (42 U.S.C. 201 et seq.); http://www.fda.gov/opacom/laws/phsvcact/phsvcact.htm
6. Title 21, Code of Federal Regulations, Parts 1-1271; http://www.fda.gov/cdrh/devadvice/365.html
7. FDA Compliance Program 7382.845, Inspection of Medical Device Manufacturers; http://www.fda.gov/cdrh/comp/7382_845.pdf
8. Investigations Operations Manual; http://www.fda.gov/ora/inspect_ref/iom/
9. Guide to Inspection of Quality Systems (Quality System Inspection Technique); http://www.fda.gov/ora/inspect_ref/igs/qsit/QSITGUIDE.HTM
10. Guidelines for the Regulatory Auditing of Quality Systems for Medical Device
Manufacturers – Global Harmonization Task Force (GHTF) SG-4 (99) 28 http://www.ghtf.org/sg4/inventorysg4/99-28genreq.pdf
Updated October 4, 2004
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