I. Introduction

Background

On October 26, 2002, the Medical Device User Fee and Modernization Act of 2002 (MDUFMA), P.L. 107-250, amended the Federal Food, Drug, and Cosmetic Act (the Act) by adding new section 510(o), which provided new regulatory requirements for reprocessed single-use devices (SUDs). According to this new provision, in order to ensure that reprocessed SUDs are substantially equivalent to predicate devices, 510(k)s for certain reprocessed SUDs identified by FDA must include validation data. These required validation data include cleaning and sterilization data, and functional performance data demonstrating that each SUD will remain substantially equivalent to its predicate device after the maximum number of times the device is reprocessed as intended by the person submitting the premarket notification.

Before enactment of the new law, a manufacturer of a reprocessed SUD was required to obtain premarket approval or premarket clearance for the device, unless the device was exempt from premarket notification submission (510(k)) requirements of the Act. Under MDUFMA, some previously 510(k)-exempt reprocessed SUDs will no longer be exempt from the 510(k) submission requirements. Manufacturers of these identified devices will need to submit 510(k)s that include validation data. Reprocessors of certain SUDs that are currently subject to cleared 510(k)s also will need to submit the types of validation data specified by the agency.

This guidance document describes the types of validation data that FDA recommends be submitted under section 510(o) of the Act. In addition, it provides guidance to industry and FDA staff on how the agency will implement this new section with respect to the submission of validation data in 510(k)s for reprocessed SUDs.

FDA is implementing this Level 1 guidance document upon issuance because it is essential for the agency to provide immediate guidance on the timeframes and review procedures for the validation data required by MDUFMA to manufacturers of reprocessed SUDs. On April 30, 2003, FDA issued the list of critical Class I and II reprocessed SUDs that are no longer be exempt from 510(k) requirements. [1] Also on that date, FDA issued a list of the non-exempt reprocessed SUDs subject to the validation data submission requirement under MDUFMA. In addition, on April 13, 2004, FDA issued a list of those semi-critical reprocessed SUDs that will no longer be exempt from 510(k) requirements. [2] Manufacturers of the listed devices will have a limited period of time during which to develop and submit these data. This guidance will assist manufacturers of reprocessed SUDs in understanding and complying with this requirement.

FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidance documents 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 we believe need to be addressed before certain reprocessed devices can be marketed. In developing the guidance, we carefully considered the relevant statutory criteria for Agency decision-making. We also considered the burden that may be incurred in your attempt to comply with the guidance and address the issues we have identified. We believe that we have considered the least burdensome approach to resolving the issues presented in the guidance document. If, however, you believe that there is a less burdensome way to address the issues, you should follow the procedures outlined in the “A Suggested Approach to Resolving Least Burdensome Issues” document. It is available on our Center web page at: http://www.fda.gov/cdrh/modact/leastburdensome.html.

Effect of this Guidance Document on Previous Guidance Documents

This guidance provides FDA recommendations on the content and format of cleaning, sterilization, and functional performance validation data in 510(k)s for reprocessed SUDs that are required by MDUFMA to include such data. MDUFMA and this guidance on validation data submissions supersede any other guidance document that recommends less complete data and information than we have described in this document.

For example, Blue Book document K90-1 describes information on sterilization processes that FDA recommends manufacturers submit in 510(k)s. Section 302(b) of MDUFMA and this guidance supersede K90-1 as it relates to the scope of the validation data to be submitted in 510(k)s on the cleaning, sterilization, and functional performance aspects of reprocessed SUDs that require the submission of such validation data.

Definitions in MDUFMA

Section 302(d) of MDUFMA includes the following relevant definitions:

Single-use device: “The term ‘single-use device’ means a device that is intended for one use, or on a single patient during a single procedure.”

Reprocessed:  “The term ‘reprocessed’, with respect to a single-use device, means an original device that has previously been used on a patient and has been subjected to additional processing and manufacturing for the purpose of an additional single use on a patient. The subsequent processing and manufacture of a reprocessed single-use device shall result in a device that is reprocessed within the meaning of this definition.”

Original device:  “The term ‘original device’ means a new, unused single-use device.”

Critical reprocessed single-use device:  “The term ‘critical reprocessed single-use device’ means a reprocessed single-use device that is intended to contact normally sterile tissue or body spaces during use.”

Semi-critical reprocessed single-use device:  “The term `semi-critical reprocessed single-use device' means a reprocessed single-use device that is intended to contact intact mucous membranes and not penetrate normally sterile areas of the body.”

Paperwork Reduction Act of 1995

According to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520), a collection of information should display a valid Office of Management and Budget (OMB) control number. The valid OMB control number for this information collection is 0910-0120 (expires 5/31/2007). The time required to complete this information collection is estimated to average 40 hours per response, including the time to review instructions, search existing data resources, gather the data needed, and complete and review the information collection.

II.    Questions and Answers on the MDUFMA 510(k) Requirements for Certain Reprocessed SUDs

MDUFMA 510(k) Requirements for Certain Reprocessed Single-Use Devices

1.      What are the new requirements under MDUFMA for critical and semi-critical reprocessed SUDs that are currently exempt from 510(k) submission requirements?

The new law requires FDA to review the critical and semi-critical reprocessed SUDs that are currently exempt from premarket notification requirements and determine which of these devices require premarket notification to ensure their substantial equivalence to predicate devices. On April 30, 2003, FDA identified in the Federal Register those critical reprocessed SUDs whose exemption from premarket notification would be terminated. [3]   On April 13, 2004, FDA identified those semi-critical reprocessed SUDs whose exemption will be terminated. [4] FDA will update both of these lists as necessary.

In accordance with the new statute, manufacturers of reprocessed SUDs whose exemption from 510(k) submission requirements is terminated must submit 510(k)s that include validation data regarding cleaning, sterilization, and functional performance, in addition to all the other required elements of 510(k)s identified in 21 CFR § 807.87, within fifteen months of publication of the relevant Federal Register notice or no longer market their devices. (See the table on page 7.)

2.      What are the new requirements under MDUFMA for reprocessed SUDs that are already subject to 510(k) submission requirements?

MDUFMA requires FDA to review the types of reprocessed SUDs already subject to premarket notification requirements and identify which of these devices require the submission of validation data to ensure their substantial equivalence to predicate devices. FDA published a list of these devices in the Federal Register on April 30, 2003, and will update the list as necessary.

3.     How does a manufacturer know if its device is on one of the MDUFMA lists?

As mentioned above, FDA published Federal Register notices listing the affected devices. On April 30, 2003, FDA published a Federal Register notice containing two lists. [5] List I identified those critical reprocessed SUDs that were previously exempt from the 510(k) requirements but now require the submission of 510(k)s with validation data. (On June 26, 2003, FDA published a correction to this notice to include an additional device type whose exemption from 510(k) requirements would be terminated. [6] ) List II identified those reprocessed SUDs already subject to premarket notification requirements that now require the submission of validation data. Finally, on April 13, 2004, the agency published the list of semi-critical reprocessed SUDs that were previously exempt from premarket notification requirements but will now require the submission of 510(k)s with validation data. [7]

4.     How does a manufacturer know what type of validation data to submit in order to comply with the new law?

As discussed above, MDUFMA requires that manufacturers of listed reprocessed SUDs submit cleaning, sterilization, and functional performance validation data in order to demonstrate that reprocessed devices will remain substantially equivalent to the relevant predicate devices. Section III of this guidance provides a detailed discussion of the agency’s recommendations on the types of data to be submitted to comply with this requirement.

5.     Will FDA be able to take enforcement action against a manufacturer who does not submit the validation data required by MDUFMA?

Yes, but for many reprocessed SUDs there is a grace period during which FDA may not take action. As stated above, MDUFMA requires that validation data be submitted to FDA for listed reprocessed SUDs within nine months (for devices already subject to 510(k) submission requirements that had 510(k)s submitted before publication of the initial list) or fifteen months (for critical and semi-critical reprocessed SUDs whose 510(k) exemption was terminated) after publication of the Federal Register lists. Therefore, until the grace period expires, FDA may not take action against reprocessed SUDs identified in the published lists solely on the basis that validation data have not yet been submitted to the agency. After the submission of validation data, a manufacturer may continue to market the reprocessed SUD until FDA determines whether the data are acceptable.

6.      What data are needed in a 510(k) for a reprocessed SUD if the device type is not included on one of the published lists?

A 510(k) must include all the information required by 21 CFR § 807.87. In addition, FDA recommends that the 510(k) include any additional information recommended in an applicable FDA product-specific 510(k) guidance and this guidance.

7.      Do any of the requirements under new section 510(o) of the Act discussed above apply to original equipment manufacturers (OEMs)?

The new statutory requirements discussed above only apply to certain reprocessed SUDs. Therefore, the termination of 510(k) exemption for the listed critical and semi-critical reprocessed SUDs does not apply to original devices (as defined by MDUFMA). In addition, the requirement for the submission of validation data in a 510(k) does not apply to premarket submissions for original devices.

Table of Requirements and Timetable

Overview of Validation Data

8.      In general, what validation data must be included in a 510(k) for a reprocessed single-use device under MDUFMA?

MDUFMA requires that 510(k)s for listed reprocessed SUDs include “validation data, [as] specified by the Secretary, regarding cleaning and sterilization, and functional performance demonstrating that the [SUD] will remain substantially equivalent to its predicate device after the maximum number of times the device is reprocessed as intended by the person submitting the premarket notification.”

9.      How does FDA define “validation”?

FDA has defined validation in the context of the Quality System Regulation, 21 CFR Part 820, as follows:

§ 820.3(z) “Validation means confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can be consistently fulfilled.

1. Process validation means establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.*
2. Design validation means establishing by objective evidence that device specifications* conform with user needs and intended use(s).”
   *§ 820.3(y) “Specification means any requirement with which a product, process, service, or other activity must conform.”

10.  Where can I obtain more information on design and process validation?

Design and process validation requirements are further detailed in 21 CFR Part 820, Quality System Regulation. An educational guidance document is available for design controls, which include design validation, on FDA’s web site at http://www.fda.gov/cdrh/comp/designgd.html.  Also, the Global Harmonization Task Force has an educational guidance document on process validation found at http://www.ghtf.org/sg3/inventorysg3/sg3-n99-10.doc .  (Note: FDA’s Quality System regulation does not permit the use of option E in Figure 1 of the Global Harmonization Task Force's Process Validation Guidance.)

11.  How does FDA interpret the scope of validation data required under MDUFMA?

FDA interprets validation data as broad in scope, including information about processing at the point of use to the completion of packaging and sterilization, and other post-process considerations. This guidance provides more discussion on validation data in Section III.

Cleaning, sterilization, and functional performance validation of reprocessed SUDs include aspects of both design validation and process validation. Design validation, in this case, incorporates both the design of the product and the design of the processes to be used in reprocessing the device.

FDA interprets the cleaning process to include all steps to remove, inactivate, or contain contamination, beginning immediately after clinical use of the device, and all subsequent steps to decontaminate, clean, and package a device up to the first step of the sterilization process. This includes all quality control tests.

A clean device, as specified by the reprocessor, is the input for the sterilization process. The sterilization process begins with packaging and any preconditioning other than cleaning (e.g., prehumidification for ethylene oxide (EO)) to the end of any post-process conditioning.

Manufacturers assess functional performance during the cleaning and sterilization process validations. Successful process validations then support the overall design validation. The results of the cleaning and sterilization validations provide objective evidence that the particular requirements for a specific intended use can be consistently fulfilled and are equivalent to those of the predicate device.

12.  What are some general considerations regarding validation of reprocessed SUDs?

Proper design validation helps ensure equivalent functional performance of the device for established user needs and intended uses. The design of the product, in part, is dictated by the design of the original device because the manufacturer is starting with an existing device, albeit used at least once. Therefore, it is vital that the manufacturer understand and document the incoming device specifications important to safe and effective use (i.e., those of the original device), in order to understand the effects of any reprocessing, to develop the acceptance criteria for both the processes and the finished product that will be distributed, and to help establish equivalent performance. The design validation must be performed according to established procedures that define device specifications, processing specifications, operating conditions, and acceptance criteria for both product and processes. See 21 CFR § 820.30.

The design validation must also include a risk analysis when appropriate. See 21 CFR § 820.30(g). At a minimum, the risk analysis should document: the identification of hazards originating from the product, the processes utilized by the manufacturer and the users of the device both before reprocessing and after; the tools utilized to analyze the source(s) of the hazard(s); and the risk estimation. Additionally, the design validation will then address how these risks are managed and shown to be acceptable and equivalent to those of the original device. (For further information and guidance on Risk Management and Risk Analysis see ISO 14971.)

Design validation also encompasses a procedure for keeping track of and assessing any OEM changes in specifications, components, or materials in the original devices. The analysis of changes ensures that the design validation performed originally continues to be valid for the devices being reprocessed. Further, there should be a method that analyzes and demonstrates that any repairs or part replacements are equivalent to the original specifications used as the basis for the reprocessor’s design validation.

In addition, the design validation should also specify how many times the particular device being validated can undergo reprocessing. This helps decrease the risk of long-term adverse effects and helps ensure that the manufacturer can demonstrate after each reprocessing that the device is substantially equivalent to the originally marketed device and meets its intended use and user needs. The maximum number of times the reprocessor recommends that the device be reprocessed will also play an important role in the cleaning and sterilization process validations.

While cleaning and sterilization procedures, materials, and product performance/verification testing are developed and assessed during design, these processes must also undergo process validations, as required by 21 CFR § 820.75. Traditionally, process validation encompasses a series of installation qualifications, operational qualifications, and performance qualifications.

13.  How does MDUFMA affect documentation of validation reports by a reprocessor?

There is no change to the requirements under the quality system regulation for documentation of validation for a device. Reprocessors must continue to maintain records of their validation activities. See 21 CFR Part 820, Subpart M. Prior to MDUFMA, validation data could be requested by FDA on a device-specific basis if FDA believed it was pertinent to a finding of substantial equivalence. MDUFMA adds the requirement that validation report(s) pertaining to cleaning and sterilization, and functional performance must now be submitted with the premarket notification for certain devices identified by FDA.

FDA Recognized Standards and Validation Data

14.  Can a manufacturer use FDA-recognized standards to reduce the amount of specific validation documentation in a 510(k) submission? 

Yes. Declarations or statements of conformity to FDA-recognized standards are legitimate means to reduce premarket notification submission documentation. See http://www.fda.gov/cdrh/ode/guidance/1131.pdf.  However, FDA will not accept a declaration or statement of conformity pertaining to functional performance validation for a reprocessed SUD.  There are currently no FDA-recognized standards related to specific cleaning methodology.

15.  How can reprocessors use FDA-recognized standards to reduce the documentation needed to support 510(k)s?

A person submitting information to meet the premarket notification submission validation data requirements of MDUFMA should identify any consensus standards that the reprocessed SUD meets. FDA accepts declarations or statements of conformity to recognized standards that address sterilization aspects in lieu of the submission of the underlying information (except for the functional performance portion of sterilization validation for a reprocessed SUD). For example, if a reprocessor uses a steam sterilization process according to an FDA-recognized standard, then the reprocessor may submit a declaration or statement of conformity to the recognized standard in lieu of information that details the underlying raw data of the application or the standard. For devices that are already on the market, manufacturers should submit declarations of conformity rather than statements of conformity because only declarations attest that design and process validations are completed for the marketed devices.

Note:  There currently are no FDA-recognized standards related to cleaning. 

16.  Where can reprocessors find FDA-recognized standards that may be helpful in reducing the documentation burden?

FDA maintains a list of recognized standards at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.  For additional information on the use of standards in 510(k) submissions, see "Guidance on the Use of Standards in Substantial Equivalence Determinations,” http://www.fda.gov/cdrh/ode/guidance/1131.html.  These standards include, for example, recognized sterilization and packaging standards that may be used by reprocessors.

Submission of Validation Data to FDA

17.  What is the recommended format and content for 510(k)s subject to the MDUFMA validation data requirements?

A 510(k) for a listed reprocessed SUD should be identified as such and:

• must include the information described in 21 CFR § 807.87, Information Required in a Premarket Notification Submission; (The general format and content for a 510(k) is described in the regulation. Additional general format and content guidance is available on the CDRH website at Device Advice.)
• should address information discussed in any relevant FDA product-specific guidance and guidance generally applicable to premarket submissions for medical devices; and
• must contain validation data (MDUFMA § 302(b)). This should be included in the test report section of the 510(k).

FDA will accept electronic submissions from any manufacturer that wishes to submit in this format. (See CDRH's website at http://www.fda.gov/cdrh/elecsub.html.)

18.  If a 510(k) was submitted prior to publication of the MDUFMA lists and the substantial equivalence (SE) decision is still pending, must the reprocessor submit the validation data before FDA renders its decision?

No. FDA may still clear 510(k)s for reprocessed SUDs requiring validation data, even if the validation data are lacking, that were under review when the MDUFMA lists published, if the clearance occurs no later than nine months after publication of the MDUFMA lists. If nine months have passed, the manufacturer must submit the cleaning, sterilization, and functional performance validation data required by MDUFMA for the cleared device. While FDA reviews this data, the device may stay on the market. If the manufacturer does not submit the data by the nine-month deadline, the device may no longer be marketed. Alternatively, the manufacturer may supplement the pending 510(k) with the validation data, thus obviating the need for a post-clearance submission to the agency of the validation data.

19.  How should a reprocessor submit validation data for previously cleared 510(k)s subject to the new MDUFMA requirements?

MDUFMA does not refer to the submission of validation data to FDA for an already cleared reprocessed SUD as “a report.” Therefore, the agency does not believe a new 510(k) is needed in order to submit validation data for these devices. When submitting the validation data required under MDUFMA for an already cleared 510(k), a reprocessor should clearly label the submission as a “Supplemental Validation Submission” and reference the cleared 510(k) number. In addition, to facilitate the review process, reprocessors should either: (1) incorporate by reference or (2) again provide the required elements of a 510(k), as identified in 21 CFR 807.87, in the Supplemental Validation Submission. Reprocessors should send these submissions to the CDRH Document Mail Center (DMC). FDA will accept electronic submissions from any manufacturer that wishes to submit in this format. (See CDRH's website at http://www.fda.gov/cdrh/elecsub.html.) There will be no user fee for Supplemental Validation Submissions.

20. What is the status of 510(k)s containing the validation data described in MDUFMA that were cleared before April 26, 2003?

As discussed earlier, after April 26, 2003, certain reprocessed SUDs will be subject to MDUFMA's requirements regarding the premarket submission of cleaning, sterilization, and functional performance validation data. FDA recognizes that some manufacturers were submitting such data in their 510(k)s before it was required by MDUFMA. Therefore, the agency may already have cleared premarket submissions for listed devices that include these validation data. To ensure compliance with MDUFMA’s requirements, however, manufacturers should resubmit this data as a Supplemental Validation Submission, as discussed above. There will be no user fee for a submission containing validation data that was previously submitted to FDA as part of a cleared 510(k).

21.   How will FDA staff process and evaluate the validation data?

As previously discussed, the validation data may be submitted to FDA either as: (1) part of a new 510(k); (2) a supplement to a pending 510(k); or (3) a Supplemental Validation Submission, if a previously cleared 510(k) already exists for the specific device(s).

FDA will process these submissions as follows:

• The manufacturer should submit the new 510(k), 510(k) supplement, or the Supplemental Validation Submission to the DMC. The DMC will log the submission into the 510(k) database and forward the document to the appropriate review division.
   
• Upon receipt of the submission, the branch chief should determine as soon as possible if the branch has the resources to evaluate the validation data or if it requires expertise from other CDRH staff. In all cases, the review division should inform the branch chief of the Infection Control Devices Branch of the receipt of reuse validation data.
   
• If consultation from Center staff with expertise in the evaluation of reuse validation data is needed, the Infection Control Devices Branch, Office of Science and Technology, or the Office of Compliance should be consulted. The branch chief of the Infection Control Devices Branch can assist in identifying appropriate staff to provide the consultation.

FDA will train staff to help ensure consistent evaluation of the validation data. There will be active communication between all validation data review staff, including regular meetings coordinated by the branch chief of the Infection Control Devices Branch.

22.  How long will FDA take to review Supplemental Validation Submissions?

There is no statutory timeframe for the review of this information. However, FDA intends to review Supplemental Validation Submissions as described below. After the review of the validation data, FDA intends to issue either a new letter of substantial equivalence or a letter requesting additional information. If the data support an SE determination, we plan to issue a new SE letter and to replace the SE letter currently on the FDA website with the new letter. If, however, we need additional information (AI) to determine whether the reprocessed SUD remains SE to a predicate device, we intend to issue an AI letter and allow the manufacturer 30 days to respond. FDA does not plan to grant extensions of time to respond to the AI requests. We believe that manufacturers should have this validation information readily available since the reprocessed device(s) are currently being marketed and such data should have been developed and maintained as part of the Quality System requirements (21 CFR Part 820). After receipt of the additional information, FDA will review the data, and we intend to make a final decision (i.e., SE or not substantially equivalent) within 60 days. [9]

23.  What action will FDA take if, after reviewing the data, the agency determines that the device is not substantially equivalent (NSE)?

If FDA reviews the validation data for a previously cleared reprocessed SUD and determines that the data have rendered the device NSE to a predicate device, the agency will issue an NSE letter. Upon issuance of the NSE letter, the device may no longer be marketed and we plan to remove the previously issued SE letter from our website. Manufacturers may submit new 510(k)s with validation data at a later date when they believe they have the data to support a substantial equivalence determination.

24.  Will manufacturers have to pay user fees when they submit the validation data?

According to MDUFMA, any 510(k) submitted on or after October 1, 2002 is subject to a user fee. Manufacturers submitting new 510(k)s with validation data for listed devices will need to include user fees for this type of submission. If, however, the listed device was already cleared for marketing and the manufacturer is only submitting a Supplemental Validation Submission, no user fee is due.

25.  What will happen if FDA decides that validation data is needed for a device under review but not yet listed?

Section 510(o)(1)(C) of the Act enables FDA to require the submission of validation data for a reprocessed SUD before it is cleared for marketing, even if it is not yet listed by the agency. This allows FDA to identify new types of reprocessed SUDs for which validation data should be reviewed prior to marketing clearance. When FDA determines that validation data should be submitted for a type of reprocessed SUD that has not yet been listed, it will promptly post a notice on the web to inform reprocessors of the need to submit such data for that device type.

In order to ensure consistency in the requests for validation data, FDA will designate each ODE Division Director as the person responsible for determining whether validation data are necessary for an unlisted device. The Division Director will notify the 510(k) Staff of these determinations so that the list of devices subject to validation data submission requirements can be updated. When a reprocessed SUD is listed, all subsequent submissions for the same type of reprocessed SUD must contain validation data.

26.  Can master files be used to document validation data?

Yes. Master files are a means to reduce the potential documentation burden relating to the submission of validation data.

FDA enables manufacturers to submit master files with information that may apply to more than one submission. A master file is not cleared but rather is a depository of information that may be referenced by the manufacturer or by those with a right of reference given by the submitter of the master file.

If there are common aspects of the design and process validation data for multiple devices, then the common validation data may be provided in a master file. FDA will review the file when referenced in a 510(k), 510(k) Supplemental Validation Submission, PMA, or premarket report.

27.  Can the validation data for multiple devices be bundled in a single application?

Bundling is the combination of more than one device or multiple indications for use for one device in a single premarket submission. Validation data should be applicable to all the specific finished product(s) covered by each submission. Although there may be common aspects of validation (see previous discussion of Master Files) for reprocessed SUDs, there may also be unique aspects of designs (e.g., different OEMs) and unique process validations for each device type. Therefore, the manufacturer should justify how the data submitted apply to all the devices in the submission and only bundle those devices or indications that can be reviewed together. For more information on bundling, see the guidance entitled, “Assessing User Fees: PMA Supplement Definitions, Modular PMA Fees, BLA and Efficacy Supplement Definitions, Bundling Multiple Devices in a Single Application, and Fees for Combination Products,” www.fda.gov/cdrh/mdufma/guidance/1201.pdf.

III.  Specific Validation Data Recommendations

The following section provides recommendations on the specific types of validation data and information a person submitting a 510(k) for a listed device should provide to the agency.

Overview Information on Reprocessing Procedure

FDA recommends that the submission:

Cleaning

The manufacturer should provide a thorough summary of data and information on the cleaning portion of the design and process validation. A number of formats for this information may be suitable. One format, using the following headings, is based on a process design and validation scheme adapted from ISO 14937, “Sterilization of medical devices – General requirements for characterization of a sterilizing agent and the development, validation and routine control of a sterilization process for medical devices:”

Cleaning Agent Characterization

The submission should:

Note:  Tests demonstrating a reduction in contamination levels alone are insufficient as an endpoint. The common definition of a clean device is one that is visually free of contamination. This condition should be translated by the reprocessor into an objective and measurable endpoint specification. The endpoint should have a visual component but should be supplemented with chemical, microbiological, and/or other physical parameters with tolerances. Devices that have lumens, mated surfaces, and other blind areas should not have an endpoint based on visual examination alone.

Tests should demonstrate that the cleaning endpoint is achieved independently of subsequent process steps. Test methods may utilize simulations of contamination under controlled lab conditions; however, actual contamination should be used to complete validation testing.

Process and Equipment Characterization

The submission should:

Product Definition

The submission should:

Process Definition

The submission should:

• Provide a thorough summary of the specifications of the process and summarize the process definition activities. This includes information to demonstrate that the cleaning process attains the process parameters by objective endpoints. The biological safety of the product following exposure to the cleaning agents and after removal of residuals can be deferred to the sterilization validation step, if needed, since the end product of the entire process should be assessed.

• Identify and document, in the risk assessment, the limits for process residuals. The means to reduce the residuals should be documented.

• Demonstrate that the cleaned device meets the acceptance criteria.

• Specify the process used to determine the number of times each device has been reprocessed.

Note:  The functional performance assessment should be deferred until after the sterilization validation step, if sterilization is required. However, the effectiveness and safety of cleaning as a separate process should be individually documented. In other words, the manufacturer should show that the cleaning step results in a device that meets the cleaning endpoint and then show that the sterilization process achieves sterilization given worst case preprocess bioburden specifications (e.g., process achieves a sterility assurance level (SAL) of 10E-6 with overkill).

Process Validation

The purpose of process validation is explained above. There are three steps used in process validation that can be adapted to a cleaning process, including both equipment and manual procedures. These steps are installation qualification, operational qualification, and performance qualification. The submission should provide a summary of each of the process validation steps as they apply to the reprocessing of the specific device:

Routine Monitoring and Control

The submission should describe how the cleaning process is monitored and controlled on a routine basis.

Product Release

The submission should provide the procedures for product release for return to the user or for further reprocessing, (e.g., packaging and terminal sterilization). This includes the criteria for designating the cleaning process as conforming to its endpoint specifications.

Assessment of Change

The submission should describe how changes to the incoming device will be assessed to identify significant changes that may impact the effectiveness of cleaning. (See the discussion under the Scope of Validation section.)

Sterilization

The submission should include a summary of the sterilization process design and validation activities. As above, the ISO 14937 scheme may serve as a template for this documentation. FDA does not believe that reiteration of the provisions of these standards is necessary for purposes of this guidance. They can be accessed at various websites for the standards development organizations.

Packaging

Note under Product Definition that part of sterilization validation includes characterization and evaluation of the packaging to be used with the device. The summary of the sterilization validation should include the specifications for the packaging, a summary of the packaging material and closure integrity tests, and any expiration tests.

Pyrogen Tests

Devices that come into direct or indirect contact with blood should be assessed for residual pyrogens after the process. FDA-recognized standards may be referenced. A summary of the tests conducted during process definition should be described as well as routine monitoring.

Functional Performance

A reprocessor must evaluate functional performance of its reprocessed device(s) according to MDUFMA section 302 (the Act § 510(o)(1)(A), (2)(A)). Functional performance is a component of sterilization process characterization and validation, and also of cleaning process validation.

The reprocessor should assess functional performance on a worst case basis, i.e., after the maximum number of times the device is intended to be reprocessed as specified by the reprocessor. The reprocessor should simulate use of each sample of device between each reprocessing cycle and this step should be specified in the summary of the process design and validation. The specific types of engineering and other tests to be conducted will vary depending on the specific device.

The device should continue to meet performance specifications after the reprocessor has tested the maximum number of intended cycles. Current FDA product-specific guidance may include performance tests that the reprocessor may use in validating functional performance. The performance tests should be summarized in the process design and validation documentation submitted for review.