The Poultry Products Inspection Act (PPIA) requires post-mortem inspection of all carcasses of slaughtered poultry subject to the Act (21 U.S.C. 455(b)). Under the New Turkey Inspection (NTI) System regulation (9 CFR 381.68), one or two inspectors on each eviscerating line examine the whole carcass and viscera of each bird. The NTI System regulation provides maximum line speeds for: (1) One inspector and two inspector lines; (2) light (under 16 pounds) and heavy (16 pounds and over) turkeys; and (3) turkeys with J-type cut openings and turkeys with Bar-type cut openings.

Some turkey slaughter establishments cut a J-type opening in the turkey carcass, which is a large abdominal opening in the turkey that facilitates the removal of the viscera. These establishments use a metal or plastic device that is inserted into the cavity of the carcass to hold the hocks. Other establishments leave a section of skin intact between the vent and body opening to secure the hocks. This type of opening is called a Bar-type cut opening.

When the final NTI System regulation was published in 1985 (50 FR 37508), because of the shackles that were in use, Bar-type cut turkeys presented for inspection on a three-point suspension required an extra inspection hand motion to raise the bar-cut skin flap to observe the under side of the bar-cut skin flap and the kidney area. This extra hand motion is not necessary to inspect J-type cut turkeys. Therefore, the regulation requires a slower line speed for Bar-type cut operations than for J-type cut operations. In addition, the regulation states that the inspector in charge may reduce inspection line rates when, in his or her judgment, the prescribed inspection procedure cannot be adequately performed within the time available because the health conditions of a particular flock dictate a need for a more extended inspection (9 CFR 381.68(c)).

In 1988, a turkey slaughter establishment developed a turkey shackle that positioned the three-point hung turkey carcasses on a shackle with a 4-inch by 4-inch selector (or kickout), a 45 degree bend of the lower 2 inches, an extended central loop portion of the shackle that lowered the abdominal cavity opening of the carcasses to an angle of 30 degrees from the vertical in direct alignment with the inspector's view, and a width of 10.5 inches. This shackle allows light to illuminate the total inside surfaces of the carcass and allows FSIS inspectors to view and properly inspect the inside surfaces of the carcass with minimal manipulation. Thus, with the modified shackles, the Bar-type cut inspection hand motions are similar to the J-type cut inspection hand motions.

After this turkey slaughter establishment installed the modified shackles, FSIS conducted a study on the effectiveness of these shackles. FSIS concluded that, in a Bar-type cut operation using the modified shackle and regulatory maximum J-type cut line speeds, establishment employees and FSIS inspectors are able to perform as well as they did when using the slower, regulatory maximum Bar-type cut line speeds. FSIS also concluded that, because the modified shackle allows for modification of the inspection hand motions, use of the modified shackle decreases the inspector's work load under the Bar-type cut inspection procedure.

Under 9 CFR 381.3(b), for limited periods, the Administrator of FSIS may waive provisions of the regulations to permit experimentation so that new procedures, equipment, and processing techniques may be tested to facilitate definite improvements. Under this regulation, on July 21, 1989, the Administrator waived the NTI System regulation for the first establishment that installed the modified shackles, so that the Bar-type cut establishment could run at the maximum line speeds for J-type cut turkeys. That establishment is no longer using the modified shackle.

FSIS has, however, allowed two other establishments that installed the modified turkey shackles described above to run at the maximum line speeds for J-type cut turkeys. Under 9 CFR 381.3(b), FSIS authorized one to begin operating at the faster line speeds on June 15, 2001, and the other on March 17, 2004. FSIS reviewed in-plant trial data from these establishments, including disposition accuracy, contamination rate, microbiological characteristics, and other product characteristics. The data show no statistical difference between turkeys processed using the modified Bar-type cut shackle running at the faster J-type cut line speeds and turkeys processed at the same establishment using the original Bar-type cut shackle (non-modified) running at the slower Bar-type cut line speeds.

On February 19, 2004, ConAgra Foods, the parent company of the two establishments that process Bar-type cut turkey carcasses with modified shackles, using the faster line speeds for J-type cuts, submitted a petition to FSIS requesting that the Agency revise its regulations to allow turkey establishments that use Bar-type cuts and modified shackles to operate under the inspection rates (line speeds) established for J-type cuts. On September 9, 2005, FSIS proposed to amend the regulations consistent with the petitioner's request (70 FR 53582).

This final rule amends the NTI System regulation, consistent with the petitioner's request, to provide that turkey slaughter establishments that open turkey carcasses with Bar-type cuts may operate at the maximum line speeds established for J-type cuts if the establishment uses a shackle with a 4-inch by 4-inch selector (or kickout), a 45 degree bend of the lower 2 inches, an extended central loop portion of the shackle that lowers the abdominal cavity opening of the carcasses to an angle of 30 degrees from the vertical in direct alignment with the inspector's view, and a width of 10.5 inches. The final rule provisions are the same as those that FSIS proposed. FSIS did not make any changes in the final rule based on comments received in response to the proposed rule.

Based on the in-plant trial data discussed above, FSIS has determined that product quality and safety will not be affected by allowing establishments producing Bar-cut turkeys to operate at the maximum regulatory line speeds for J-type cuts, provided these establishments use the type of shackle described in this final rule. FSIS has concluded that this rule will facilitate post-mortem inspection of turkey carcasses. For the two Bar-type cut turkey establishments that use the modified shackle to be able to run at these line speeds on a permanent basis, it is necessary that FSIS amend 9 CFR 381.68. In addition, it is necessary that FSIS amend the regulation to allow all turkey slaughter establishments that may use Bar-type cut openings to run at the maximum J-type cut line speeds, provided that such establishments use the correct shackles, and provided that the health conditions of the flock or other factors do not cause the inspector-in-charge to reduce the line speed.

Under this final rule, as under current regulations, the inspector in charge can reduce line speeds when, in his or her judgment, the prescribed inspection procedure cannot be adequately performed within the time available because of the health conditions of a particular flock. In addition, this final rule makes clear that the inspector-in-charge could reduce line speeds when the prescribed inspection procedure cannot be adequately performed within the time available because of factors other than the health conditions of the flock. This rule specifies that such factors could include the manner in which birds are being presented to the inspector for inspection and the level of contamination among the birds on the line.

FSIS received three comments in response to the proposed rule on allowing Bar-type cut turkey operations to use J-type cut maximum line speeds, one from an FSIS employee and two from animal rights organizations.

Comment: The FSIS employee asked whether studies have been completed to determine what effect the increase in line speed will have on the upper extremities of FSIS inspectors and establishment employees.

The commenter also questioned whether concrete guidelines would be given to inspection program personnel to assist them in making an objective decision regarding reducing line speeds.

In addition, the employee questioned whether FSIS performed baseline studies concerning the safety of those who work on the evisceration line when the initial NTI System regulation was proposed. This commenter stated that FSIS employees are ignorant as to the debilitating and potentially disabling effects that increasing line speeds have on the muscles, nerves, tendons, joints, and ligaments of their upper extremities.

Response: In 1989, based on the study of the effectiveness of the modified shackle discussed above, FSIS determined that, by eliminating the tilting motion at establishments operating with the J-type cut maximum line speeds, the inspection procedure was improved. Tilting the turkey normally required an ulner deviation of the hands, which is one of the motions thought to lead to Carpal Tunnel Syndrome. Therefore, FSIS determined that the modified shackle is ergonomically better than the traditional turkey shackle.

FSIS did not conduct baseline studies concerning the safety of those who work on the evisceration line when the initial NTI System regulation was proposed in 1984 (49 FR 44640) or finalized in 1985 (50 FR 37508). FSIS determined it was unnecessary to conduct such baseline studies because the NTI System regulation eliminated certain inspector motions. By eliminating motions, the regulation increased the safety for inspection program personnel who work on turkey evisceration lines.

FSIS does not intend to issue new guidance to inspection program personnel to assist them in making an objective decision regarding reducing line speeds. Under this rule, as under current regulations, inspection program personnel are to use their professional judgment when making a decision to reduce line speeds.

Comment: The two animal rights organizations stated that faster line speeds will result in a great deal of additional suffering to birds during shackling. One of the commenters stated that when line speeds are increased, workers grab the birds more roughly and snap their legs into shackles more violently. The other commenter stated that meat and poultry slaughter establishment workers involved in incidents of inhumane handling often explain that they were forced to mistreat animals because of the pressure of keeping up with the slaughter line. The commenter further stated that FSIS should consider the potential impact on animal treatment when proposing changes to slaughter practices, such as line speeds.

Response : FSIS believes that faster line speeds will not result in additional suffering to birds. With the increased line speed, the company may hire additional handlers with the result that the time to hang the birds remains the same. As FSIS explained in the Federal Register notice on the treatment of live poultry before slaughter (70 FR 56624, September 28, 2005), under the PPIA and Agency regulations, all poultry establishments must handle live poultry in a manner that is consistent with good commercial practices, which means they should be treated humanely. In this notice, FSIS also explained that the Agency considers humane methods of handling birds and humane slaughter operations a high priority and takes seriously any violations of applicable laws and regulations. Under 9 CFR 381.71, FSIS condemns poultry showing, on ante mortem inspection, certain diseases or conditions. Bruising is one condition that may result in condemnation (9 CFR 381.89). Bruises are likely to result when birds are not treated humanely.

This action has been reviewed for compliance with Executive Order (EO) 12866. This rule has been designated “non-significant” and therefore has not been reviewed by the Office of Management and Budget.

This rule is necessary to provide more production options for turkey slaughter establishments. For the two Bar-type cut turkey establishments that use the modified shackles to be able to run at the faster line speeds on a permanent basis, it is necessary that FSIS amend the regulations. In addition, it is necessary that FSIS amend the regulations to allow all turkey establishments that may use Bar-type cut openings to run at the maximum J-type cut line speeds, provided that such establishments use the correct shackles, and provided that the health conditions of the flock or other factors do not cause the inspector in charge to reduce the line speed.

According to FSIS' Animal Disposition Reporting System (ADRS), the U.S. turkey industry consists of approximately 80 slaughter and processing establishments, of which 25 are considered very small, 30 are considered small, and 25 are considered large. 1 The total industry employs between 20,000 and 25,000 people in the United States, with thousands more employed in related industries, such as contract growing, product distribution, equipment manufacturing, and other affiliated services. 2

Turkey companies are vertically integrated, meaning that they control or contract for all phases of production and processing—from breeding through delivery to retail. In a vertically integrated framework of turkey contracting, establishments (integrators) accept much of the risk of turkey growing in exchange for greater control over both the quality and quantity of birds. Usually, the contract calls for establishments to provide growers with chicks or poult hatchlings and feed from their own hatcheries and feed mills, veterinary services, medication, and field supervisors to monitor operations. The contract growers provide housing, equipment, labor, water, and all or most of the fuel and litter. Growers raise the birds until ready for shipment to the establishments. In their contractual arrangements with growers, establishments usually agree to pay a pre-established fee per pound for live turkeys plus a bonus or penalty for performance relative to other growers. 3

In 2006, the number of turkeys raised in the United States was 262 million head, weighing an average of 24.8 pounds. In 2006, the number of pounds of turkey produced was 6.5 billion pounds. At a rate of 45 cents per pound, the value of production equaled $2.9 billion.

U.S. consumption of turkey and turkey products is estimated to be nearly 17.1 pounds per person for 2007. The most popular turkey product continues to be the whole turkey, comprising 25 percent of all turkey sales in 2006. The product distribution for turkey products is as follows: 41.1 percent to grocery stores and other retail outlets; 23.1 percent sold in commodity outlets; 21.6 percent sold to foodservice outlets; and 10 percent exported.

U.S. exports of turkey products in 2006 were 545 million pounds, comprising 9.6 percent of total turkey production. In 2006, the top four export markets for U.S. turkey were Mexico (310.0 million pounds), China (35.4 million pounds), Russia (25.2 million pounds), and Canada (21.9 million pounds).

Traditionally, turkey plants face highly seasonal demand, with most production occurring in the last quarter of the year to accommodate the increased consumption of turkeys around Christmas and Thanksgiving. Because of a shift in consumers' taste for turkey and turkey products, consumers are consuming more turkey products, such as turkey sausages, ground turkey, luncheon meat, and tray packs; pre-cooked turkey products such as deli breasts, turkey ham, and turkey bacon; and other further processed turkey products, on a year-round basis. More consumers are consuming turkey on a year-round basis because of health concerns and turkey's nutritional value, which addresses those concerns. 4 This trend in consumption reduces the excess capacity that plants were experiencing during much of the year to a more balanced production cycle year round. By supplying turkey and turkey products year round, turkey plants have been able to stabilize production rates. Stabilized production rates lower production costs because plants are able to avoid hiring, training, laying off employees, and starting up and shutting down of facilities on a seasonal basis.

Establishments that process Bar-type cut turkeys and install the modified shackles will likely realize benefits because these establishments will be able to process more turkeys by using the J-type cut line speeds. According to ConAgra (who has petitioned FSIS to amend the regulations, consistent with this rule), by using the J-type cut line speeds, a turkey plant processing Bar-type cut turkeys can increase its production capacity by 13 percent. Also according to ConAgra, under typical pricing and operation parameters, this increase will result in $600,000 to $3,000,000 more in revenue annually per establishment. In addition, this increase in capacity for processing turkeys will allow establishments to receive a greater return on their fixed assets.

In addition to the two establishments that use Bar-type cuts that FSIS has authorized to run at the maximum line speeds for J-type cuts, any other Bar-type cut establishment also can begin using the modified shackle and faster line speeds under this final rule. If other turkey slaughter establishments produce a large volume of whole turkeys, some of these turkey establishments may decide to install the shackles to process Bar-type cut turkeys and may obtain benefits similar to those ConAgra projected in its petition.

The use of the modified shackles for Bar-type cut turkeys, compared to the traditional shackles for these turkeys, changes the presentation of the turkey so that the inspector need not manipulate the bar skin strip to observe the underside of that flap and the kidney area. Therefore, the Agency may also realize benefits because the inspectors would not be required to perform an extra hand motion. The elimination of this extra hand motion may reduce undue fatigue among turkey inspectors.

Based on data from an FSIS study at a Bar-type cut turkey plant that ran at the J-type cut maximum line speeds and used the modified shackle that met the criteria to be included in this rule, this rule will not affect product quality or safety.

The costs of the final rule will be the costs establishments incur in purchasing and installing the modified shackles. Establishments are not likely to incur these costs unless they will realize benefits. Industry sources estimate that it would cost a typical plant $55,000 (in 2006 dollars) to install the modified shackles on two assembly lines.

FSIS has examined the economic implications of the final rule as required by the RFA (5 U.S.C. 601-612). If a rule has a significant economic impact on a substantial number of small entities, the RFA requires that regulatory options that would lessen the economic effect of the rule on small entities be analyzed. FSIS has determined that the final rule will not have a significant impact on a substantial number of small entities for the reasons discussed below.

One of the establishments using the modified shackle is small, and one is large. Under the final rule, turkey slaughter establishments are not required to install modified shackles and are only likely to do so should they incur profits through the faster line speed for the production of whole turkeys. Based on the ADRS data discussed above, there are about 30 small turkey slaughter establishments that could potentially install modified shackles. Very small establishments are not likely to install modified shackles because they are seasonal turkey processors.

This final rule has been reviewed under Executive Order 12988, Civil Justice Reform. This rule: (1) Preempts all State and local laws and regulations that are inconsistent with this rule; (2) has no retroactive effect; and (3) does not require administrative proceedings before parties may file suit in court challenging this rule.

There are no paperwork or recordkeeping requirements associated with this final rule under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

Public awareness of all segments of rulemaking and policy development is important. Consequently, in an effort to ensure that the minorities, women, and persons with disabilities, are aware of this final rule, FSIS will announce it on-line through the FSIS Web page located at http://www.fsis.usda.gov/Regulations_&_Policies/2008_Interim_&_Final_Rules_Index/index.asp . FSIS also will make copies of this Federal Register publication available through the FSIS Constituent Update, which is used to provide information regarding FSIS policies, procedures, regulations, Federal Register notices, FSIS public meetings, and other types of information that could affect or would be of interest to our constituents and stakeholders. The Update is communicated via Listserv, a free e-mail subscription service consisting of industry, trade groups, consumer interest groups, health professionals, and other individuals who have requested to be included. The Update is also available on the FSIS Web page. Through the Listserv and Web page, FSIS is able to provide information to a much broader and more diverse audience. In addition, FSIS offers an e-mail subscription service that provides automatic and customized access to selected food safety news and information. This service is available at http://www.fsis.usda.gov/news_and_events/email_subscription/ . Options range from recalls to export information to regulations, directives, and notices. Customers can add or delete subscriptions themselves, and have the option to password protect their accounts.

The FAA issued a supplemental notice of proposed rulemaking (NPRM) to amend 14 CFR part 39 to include an AD that supersedes AD 2008-04-02, amendment 39-15374 (73 FR 8187, February 13, 2008). The existing AD applies to certain Bombardier Model DHC-8-400 series airplanes. That supplemental NPRM was published in the Federal Register on June 26, 2008 (73 FR 36285). That supplemental NPRM proposed to continue to require inspecting all barrel nuts to determine if the barrel nuts have a certain marking, inspecting affected bolts to determine if the bolts are pre-loaded correctly, and replacing all hardware if the pre-load is incorrect. For airplanes on which the pre-load is correct, that supplemental NPRM also proposed to continue to require doing repetitive visual inspections for cracking of the barrel nuts and cradles and replacing all hardware for all cracked barrel nuts. That supplemental NPRM also proposed to continue to require replacing all hardware for certain affected barrel nuts that do not have cracking, which would end the repetitive inspections for those airplanes. In addition, that supplemental NPRM also proposed to continue to provide an optional replacement for all affected barrel nuts. Finally, that supplemental NPRM also proposed to require replacing all affected barrel nuts and applying a certain compound to the affected barrel nuts and bolts.

We provided the public the opportunity to participate in the development of this AD. No comments have been received on the NPRM or on the determination of the cost to the public.

We have carefully reviewed the available data and determined that air safety and the public interest require adopting the AD as proposed.

This AD affects about 48 airplanes of U.S. registry.

The actions that are required by AD 2008-04-02 and retained in this AD take about 3 work hours per airplane, at an average labor rate of $80 per work hour. Based on these figures, the estimated cost of the currently required actions is $11,520, or $240 per airplane, per inspection cycle.

Replacement of the hardware of a barrel nut, if required, takes about 12 work hours per airplane, at an average labor rate of $80 per work hour. Required parts cost about $800 per barrel nut. Based on these figures, we estimate the cost of a replacement to be $1,760 per barrel nut.

Application of the compound, if required, takes about 4 work hours per airplane, at an average labor rate of $80 per work hour. Based on these figures, we estimate the cost of a replacement to be $320 per application.

Title 49 of the United States Code specifies the FAA's authority to issue rules on aviation safety. Subtitle I, Section 106, describes the authority of the FAA Administrator. Subtitle VII, Aviation Programs, describes in more detail the scope of the Agency's authority.

We are issuing this rulemaking under the authority described in Subtitle VII, Part A, Subpart III, Section 44701, “General requirements.” Under that section, Congress charges the FAA with promoting safe flight of civil aircraft in air commerce by prescribing regulations for practices, methods, and procedures the Administrator finds necessary for safety in air commerce. This regulation is within the scope of that authority because it addresses an unsafe condition that is likely to exist or develop on products identified in this rulemaking action.

We have determined that this AD will not have federalism implications under Executive Order 13132. This AD will not have a substantial direct effect on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government.

For the reasons discussed above, I certify that this AD:

(1) Is not a “significant regulatory action” under Executive Order 12866;

(2) Is not a “significant rule” under DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and

(3) Will not have a significant economic impact, positive or negative, on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

We prepared a regulatory evaluation of the estimated costs to comply with this AD and placed it in the AD docket. See the ADDRESSES section for a location to examine the regulatory evaluation.

We issued a notice of proposed rulemaking (NPRM) to amend 14 CFR part 39 to include an AD that would apply to the specified products. That NPRM was published in the Federal Register on June 24, 2008 (73 FR 35595). That NPRM proposed to correct an unsafe condition for the specified products. The MCAI states:

We gave the public the opportunity to participate in developing this AD. We received no comments on the NPRM or on the determination of the cost to the public.

We reviewed the available data and determined that air safety and the public interest require adopting the AD as proposed.

We have reviewed the MCAI and related service information and, in general, agree with their substance. But we might have found it necessary to use different words from those in the MCAI to ensure the AD is clear for U.S. operators and is enforceable. In making these changes, we do not intend to differ substantively from the information provided in the MCAI and related service information.

We might also have required different actions in this AD from those in the MCAI in order to follow our FAA policies. Any such differences are highlighted in a NOTE within the AD.

We estimate that this AD will affect about 20 products of U.S. registry. We also estimate that it will take about 3 work-hours per product to comply with the basic requirements of this AD. The average labor rate is $80 per work-hour. Required parts will cost about $0 per product. Where the service information lists required parts costs that are covered under warranty, we have assumed that there will be no charge for these parts. As we do not control warranty coverage for affected parties, some parties may incur costs higher than estimated here. Based on these figures, we estimate the cost of this AD to the U.S. operators to be $4,800, or $240 per product.

Title 49 of the United States Code specifies the FAA's authority to issue rules on aviation safety. Subtitle I, section 106, describes the authority of the FAA Administrator. “Subtitle VII: Aviation Programs,” describes in more detail the scope of the Agency's authority.

We are issuing this rulemaking under the authority described in “Subtitle VII, Part A, Subpart III, Section 44701: General requirements.” Under that section, Congress charges the FAA with promoting safe flight of civil aircraft in air commerce by prescribing regulations for practices, methods, and procedures the Administrator finds necessary for safety in air commerce. This regulation is within the scope of that authority because it addresses an unsafe condition that is likely to exist or develop on products identified in this rulemaking action.

We determined that this AD will not have federalism implications under Executive Order 13132. This AD will not have a substantial direct effect on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government.

For the reasons discussed above, I certify this AD:

1. Is not a “significant regulatory action” under Executive Order 12866;

2. Is not a “significant rule” under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and

3. Will not have a significant economic impact, positive or negative, on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

We prepared a regulatory evaluation of the estimated costs to comply with this AD and placed it in the AD docket.

You may examine the AD docket on the Internet at http://www.regulations.gov ; or in person at the Docket Operations office between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. The AD docket contains the NPRM, the regulatory evaluation, any comments received, and other information. The street address for the Docket Operations office (telephone (800) 647-5527) is in the ADDRESSES section. Comments will be available in the AD docket shortly after receipt.

Discussion

We issued a notice of proposed rulemaking (NPRM) to amend 14 CFR part 39 to include an airworthiness directive (AD) that would apply to certain McDonnell Douglas Model 717-200 airplanes. That NPRM was published in the Federal Register on April 7, 2008 (73 FR 18725). That NPRM proposed to require inspecting the drive assembly of the aft elevator standby loop for interference between the clevis and bolt of the bellcrank assembly, correct orientation of the pull-pull cable clevis bolt, and excessive freeplay of the bellcrank assembly bearing, and corrective actions if necessary. That NPRM also proposed to require modifying the pull-pull cable clevis in the drive assembly of the aft elevator standby loop for certain airplanes.

We gave the public the opportunity to participate in developing this AD. We considered the comments received.

Boeing asks that the second sentence of the Summary section in the NPRM, which describes what is to be inspected, be changed as follows: “This proposed AD would require inspecting the aft elevator standby loop drive assembly of the elevator standby cable system for interference between the clevis and bolt of this bellcrank assembly, correct orientation of the pull-pull cable clevis bolt, and excessive freeplay of the bellcrank assembly bearing, and corrective actions if necessary.” Boeing states that this would more accurately describe the drive assembly being inspected since there are two drive assemblies in the elevator standby cable system.

We agree that the description in the Summary section of the AD should be clarified. Therefore, we have changed the Summary section and all other relevant sections in the AD to meet the commenter's intent.

Midwest Airlines asks that the compliance time in the NPRM be changed to one of the following: “Complete the inspection and modification within 27 months of the effective date of the AD,” or “Complete the inspection and modification within 3,000 flight hours or 27 months, whichever occurs later from the effective date of the AD.” Midwest Airlines states that it currently has a utilization of 3,450 flight hours per year, and if the compliance time is not changed, it would require compliance for all its airplanes in less than one year. Midwest Airlines also states that it checked some of its airplanes for the interference and none was found.

Air Tran proposes that the inspection and clevis replacement specified in the NPRM be done concurrently at 27 months after the effective date of the AD, rather than the inspection being limited to 3,000 flight hours. Air Tran states that since similar access is required for both the inspection and clevis replacement, it is more practical to accomplish the clevis replacement at the same time as the inspection. Twenty-seven months aligns with the Model 717 maintenance program heavy maintenance visits, but 3,000 flight hours does not.

We agree to extend the compliance time for performing the inspection for the reasons provided by the commenters. We have determined that a compliance time of within 3,000 flight hours or 27 months after the effective date of the AD, whichever occurs later, is appropriate and will ensure an acceptable level of safety. We have changed paragraph (f)(1) of this AD accordingly. The compliance time for doing the clevis modification specified in paragraph (f)(2) of this AD remains the same. Changing the compliance time for the inspection provides the opportunity to do the inspection and modification at the same time.

Midwest Airlines states that the work-hour estimate specified in the Costs of Compliance section of the NPRM is underestimated. Midwest Airlines notes that the NPRM specifies 1 work-hour for the inspection and the referenced service bulletin specifies 2.4 to 11.9 work hours. Midwest Airlines adds that the NPRM specifies 4 work-hours for the modification and the referenced service bulletin specifies 5.4 work-hours. Midwest Airlines believes the service bulletin is more accurate than the NPRM.

From this comment, we infer that Midwest Airlines would like us to increase the work-hour estimate given in the NPRM. We do not agree. The cost information below describes only the direct costs of the specific actions required by this AD. Based on the best data available, the manufacturer provided the number of work hours (1 for the inspection, 4 for the modification) necessary to do the required actions, as specified in the service bulletin. We recognize that, in doing the actions required by an AD, operators might incur incidental costs in addition to the direct costs. The cost analysis in AD rulemaking actions, however, typically does not include incidental costs such as the time required to gain access and close up, time necessary for planning, or time necessitated by other administrative actions. Those incidental costs, which might vary significantly among operators, are almost impossible to calculate. We have made no change to the AD in this regard.

We reviewed the relevant data, considered the comments received, and determined that air safety and the public interest require adopting the AD with the changes described previously. We also determined that these changes will not increase the economic burden on any operator or increase the scope of the AD.

We estimate that this AD will affect 123 airplanes of U.S. registry.

It will take about 1 work-hour per product to do the inspection. The average labor rate is $80 per work-hour. Based on these figures, we estimate the cost of the inspection required by this AD to the U.S. operators to be $9,840, or $80 per product.

It will take about 4 work-hours per product to do the modification. Required parts will cost about $163 per product. Based on these figures, we estimate the cost of the modification required by this AD to the U.S. operators to be $59,409, or $483 per product.

Title 49 of the United States Code specifies the FAA's authority to issue rules on aviation safety. Subtitle I, section 106, describes the authority of the FAA Administrator. “Subtitle VII: Aviation Programs,” describes in more detail the scope of the Agency's authority.

We are issuing this rulemaking under the authority described in “Subtitle VII, Part A, Subpart III, Section 44701: General requirements.” Under that section, Congress charges the FAA with promoting safe flight of civil aircraft in air commerce by prescribing regulations for practices, methods, and procedures the Administrator finds necessary for safety in air commerce. This regulation is within the scope of that authority because it addresses an unsafe condition that is likely to exist or develop on products identified in this rulemaking action.

This AD will not have federalism implications under Executive Order 13132. This AD will not have a substantial direct effect on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government.

For the reasons discussed above, I certify that this AD:

(1) Is not a “significant regulatory action” under Executive Order 12866,

(2) Is not a “significant rule” under DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979), and

(3) Will not have a significant economic impact, positive or negative, on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

You can find our regulatory evaluation and the estimated costs of compliance in the AD Docket.

Discussion

We issued a notice of proposed rulemaking (NPRM) to amend 14 CFR part 39 to include an AD that would apply to the specified products. That NPRM was published in the Federal Register on May 20, 2008 (73 FR 29085). That NPRM proposed to correct an unsafe condition for the specified products. The MCAI states:

We gave the public the opportunity to participate in developing this AD. We received no comments on the NPRM or on the determination of the cost to the public.

We reviewed the available data and determined that air safety and the public interest require adopting the AD as proposed.

We have reviewed the MCAI and related service information and, in general, agree with their substance. But we might have found it necessary to use different words from those in the MCAI to ensure the AD is clear for U.S. operators and is enforceable. In making these changes, we do not intend to differ substantively from the information provided in the MCAI and related service information.

We might also have required different actions in this AD from those in the MCAI in order to follow our FAA policies. Any such differences are highlighted in a NOTE within the AD.

We estimate that this AD will affect about 101 products of U.S. registry. We also estimate that it will take about 1 work-hour per product to comply with the basic requirements of this AD. The average labor rate is $80 per work-hour. Based on these figures, we estimate the cost of this AD to the U.S. operators to be $8,080, or $80 per product.

Title 49 of the United States Code specifies the FAA's authority to issue rules on aviation safety. Subtitle I, section 106, describes the authority of the FAA Administrator. “Subtitle VII: Aviation Programs,” describes in more detail the scope of the Agency's authority.

We are issuing this rulemaking under the authority described in “Subtitle VII, Part A, Subpart III, Section 44701: General requirements.” Under that section, Congress charges the FAA with promoting safe flight of civil aircraft in air commerce by prescribing regulations for practices, methods, and procedures the Administrator finds necessary for safety in air commerce. This regulation is within the scope of that authority because it addresses an unsafe condition that is likely to exist or develop on products identified in this rulemaking action.

We determined that this AD will not have federalism implications under Executive Order 13132. This AD will not have a substantial direct effect on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government.

For the reasons discussed above, I certify this AD:

1. Is not a “significant regulatory action” under Executive Order 12866;

2. Is not a “significant rule” under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and

3. Will not have a significant economic impact, positive or negative, on a substantial number of small entities under the criteria of the Regulatory Flexibility Act.

We prepared a regulatory evaluation of the estimated costs to comply with this AD and placed it in the AD docket.

You may examine the AD docket on the Internet at http://www.regulations.gov ; or in person at the Docket Operations office between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. The AD docket contains the NPRM, the regulatory evaluation, any comments received, and other information. The street address for the Docket Operations office (telephone (800) 647-5527) is in the ADDRESSES section. Comments will be available in the AD docket shortly after receipt.

On August 11, 2008 (73 FR 46550), we published a final rule AD, FR Doc. E8-18102, in the Federal Register . That AD applies to RR RB211-524 series turbofan engines. We need to make the following correction:

Monkeypox is a sporadic, zoonotic, viral disease that occurs primarily in the rain forest countries in central and west Africa. (A zoonotic disease is a disease of animals that can be transmitted to humans under natural conditions.) The illness was first noted in a monkey in 1958 (which explains its name), but, in Africa, serologic evidence of monkeypox infection has been found in many other species, including some species of primates, rodents, and lagomorphs. Lagomorphs include animals such as rabbits. African rodents are considered to be the most likely natural host of the monkeypox virus (Ref. 1). In Africa, however, direct viral evidence of monkeypox has been found in only one native African rodent species (a rope squirrel), but this may be due to the limited scope of the ecologic studies that have been done in Africa (Ref. 1).

In humans, monkeypox is marked by rashes that are similar to those seen in smallpox; other signs and symptoms include a temperature at or above 99.3 degrees, chills and/or sweats, headache, backache, lymphadenopathy (a disease of the lymph nodes), sore throat, cough, and shortness of breath (Ref. 2). The disease's incubation period in humans is approximately 12 days (Ref. 3). In Africa, monkeypox has a mortality (death) rate in humans ranging from 1 to 10 percent of the people who become infected, although higher mortality rates have been seen.

In May and June of 2003, public health officials identified an outbreak of human monkeypox in the United States. Epidemiological and traceback investigations by State and Federal agencies revealed that the patients became infected primarily as a result of contact with prairie dogs that had contracted monkeypox from diseased African rodents. The investigations indicated that a Texas animal distributor imported a shipment of approximately 800 small mammals from Ghana on April 9, 2003. This shipment contained 762 African rodents, including rope squirrels ( Funiscuirus sp.), tree squirrels ( Heliosciurus sp.), Gambian giant pouched rats ( Cricetomys sp.), brushtail porcupines ( Atherurus sp.), dormice ( Graphiurus sp.), and striped mice ( Hybomys sp.). Some of these African animals were infected with monkeypox, and laboratory testing confirmed the presence of monkeypox in several rodent species, including two Gambian giant pouched rats, nine dormice, and three rope squirrels (Ref. 23). Of the 762 rodents from the original shipment, 584 were traced to distributors in 6 states. A total of 178 African rodents could not be traced beyond the point of entry in Texas because records were not available (Ref. 4).

Some African rodents made their way to an animal distributor in Illinois who also sold prairie dogs (Ref. 5). The Illinois animal distributor had approximately 200 prairie dogs. Thirty-nine of these prairie dogs, along with one Gambian giant pouched rat, went to another animal distributor in Wisconsin in early May, 2003; it was at this time that several prairie dogs appeared to be ill, and several of the animals died (Ref. 5). By late May, the first human cases began to appear in Wisconsin (including the Wisconsin animal distributor), with other human cases appearing later in Kansas, Missouri, Illinois, Indiana, and Ohio (Refs. 5 and 6).

Of the 200 prairie dogs that were at the Illinois animal distributor, only 93 were able to be traced during the traceback investigation (Ref. 4).

The 2003 monkeypox outbreak in the United States eventually resulted in 72 human cases, with 37 of those cases being laboratory-confirmed (Ref. 7). Most patients had direct or close contact with prairie dogs. For example, 28 children at an Indiana day care center were exposed to 2 prairie dogs that later became ill and died. Twelve of these exposed children reported handling or petting the prairie dogs, and seven of these children later became ill with symptoms that were consistent with monkeypox infection (Ref. 7). In Wisconsin, more than half of the human monkeypox cases occurred through occupational exposure to infected prairie dogs, with veterinary staff being at greater risk of acquiring monkeypox than pet store employees (Ref. 21). The human cases in the United States included children as young as 3 years old, and 19 people were hospitalized, although some were hospitalized primarily for isolation purposes (Ref. 6). The initial signs or symptoms seen in some patients included skin lesions or fever with drenching sweats and severe chills (Ref. 5). Other signs and symptoms seen most often included:

• Headache;

• Persistent cough;

• Lymphadenopathy; and

• Sore throat (Ref. 5).

Less frequent signs and symptoms included:

• Pharyngitis;

• Tonsillar hypertrophy;

• Tonsillar erosions;

• Malaise;

• Mild chest tightness;

• Diarrhea;

• Myalgias;

• Back pain;

• Nasal congestion;

• Blephartis; and

• Nausea (Ref. 5).

In general, the human cases in the United States were milder than those seen in Africa (Ref. 6), and patients who had been vaccinated against smallpox appeared to have milder cases compared to those who had not been vaccinated against smallpox. However, two children suffered serious clinical illnesses. One child had severe encephalitis that improved during a 14-day hospital stay, and another child had pox lesions on many parts of her body, including lesions inside her mouth and throat which created difficulty in breathing and swallowing (Refs. 6, 9, and 19). At least 5 patients (3 adults and 2 children) had temperatures greater than or equal to 38.3 °C (100.94 °F) and rashes comprised of 100 or more lesions (Ref. 9). One adult patient remained symptomatic for approximately 5 months; the patient became asymptomatic only after having a corneal transplant (Ref. 9).

On June 11, 2003, the Director of the Centers for Disease Control and Prevention (CDC) and the Commissioner of Food and Drugs, under 42 CFR 70.2 and 21 CFR 1240.30 respectively, issued a joint order (Refs. 10 and 11) prohibiting, until further notice, the transportation or offering for transportation in interstate commerce, or the sale, offering for sale, or offering for any other type of commercial or public distribution, including release into the environment, of:

• Prairie dogs ( Cynomys sp.);

• Tree squirrels ( Heliosciurus sp.);

• Rope squirrels ( Funisciurus sp.);

• Dormice ( Graphiurus sp.);

• Gambian giant pouched rats ( Cricetomys sp.);

• Brush-tailed porcupines ( Atherurus sp.), and

• Striped mice ( Hybomys sp.).

The June 11, 2003, order did not apply to the transport of listed animals to veterinarians or animal control officials or other entities pursuant to guidance or instructions issued by Federal, State, or local government authorities. In addition, under 42 CFR 71.32(b), CDC implemented an immediate embargo on the importation of all rodents (order Rodentia ) from Africa.

FDA and CDC issued the June 11, 2003, order to address quickly what was then a new and rapidly developing monkeypox outbreak (Ref. 11). As the two agencies became more experienced with the order and more knowledgeable about the monkeypox outbreak, it became apparent that we and CDC needed a regulatory approach to prevent the monkeypox virus from becoming established and spreading in the United States and to modify the June 11, 2003, order, such as creating exemption procedures to accommodate special circumstances. Consequently, on November 4, 2003 (68 FR 62353), FDA and CDC issued an interim final rule that superseded the June 11, 2003, order. The interim final rule created two complementary regulations. First, with respect to certain animals that are in the United States, the interim final rule added 21 CFR 1240.63 entitled “African rodents and other animals that may carry the monkeypox virus.” Second, for African rodents that are being imported or offered for import to the United States, the interim final rule added 42 CFR 71.56 that is also entitled “African rodents and other animals that may carry the monkeypox virus.” We are responsible for 21 CFR 1240.63, and CDC is responsible for 42 CFR 71.56; both sets of regulations are intended to prevent the further introduction, establishment, and spread of the monkeypox virus in the United States.

We also indicated that we would revoke or amend, as warranted, all or parts of 21 CFR 1240.63 if we concluded that monkeypox is eradicated or adequately controlled so that the virus does not become established in the United States (see 68 FR at 62359).

We issued the interim final rule under section 361 of the Public Health Service Act (PHS Act) (42 U.S.C. 264). Section 361 of the PHS Act gives the Secretary of Health and Human Services (the Secretary) the authority to make and enforce regulations to prevent the introduction, transmission, or spread of communicable diseases from foreign countries into the States or from one State to another State.

The preamble to the interim final rule stated that:

(Id. at page 62359.) However, the preamble to the interim final rule also cautioned that:

After the interim final rule's publication in the Federal Register on November 4, 2003, CDC notified us that it had test information that warranted our continued application and enforcement of 21 CFR 1240.63. This information confirmed monkeypox virus infection in several prairie dogs and in a few animals from other species, including a Gambian giant pouched rat, dormice, rope squirrels, a ground hog, a South American opossum, and a chinchilla. Some of these infections were subclinical (the animal was infected with the virus, but did not appear to be ill). Some of this preliminary information subsequently appeared in peer-reviewed scientific journal articles, and, in a Federal Register notice dated February 21, 2007 (72 FR 7825), we announced the addition of those articles and other recent journal articles to the docket. However, follow-up investigations confirmed that the human monkeypox cases in the United States were not associated with exposure to any animals except prairie dogs.

CDC also was monitoring the progress of a human case where a patient had developed monkeypox in late June 2003, but still had symptoms 5 months later. Conjunctival swabs from this patient were positive (following polymerase chain reaction (PCR) analysis) at 139 days after onset and culture positive at 126 days after onset. This patient eventually required a corneal transplant (see Ref. 9 which discusses this case briefly).

We also note that, when we wrote the interim final rule, efforts were continuing to track down animals from the original African shipment as well as prairie dogs from the Illinois distributor. Ultimately, over 170 African rodents from that shipment and 103 prairie dogs from the Illinois distributor were never recovered or located.

In the Federal Register of April 14, 2004, the Department of Health and Human Services published a notice announcing that the Secretary's Council on Public Health Preparedness (Secretary's Council) would hold a public meeting where one topic would be “Transport of Possibly Infected Exotic Animals” (see 69 FR 19854 (April 14, 2004)). The Secretary's Council invited FDA and CDC to make presentations regarding the interim final rule. FDA made a presentation to the Secretary's Council seeking its advice on assessing the risk of monkeypox in the United States so that we could determine the appropriate way to manage that risk. CDC presented information concerning the new data, thus making the data publicly available. The Secretary's Council did not assess the risk of monkeypox; it recommended instead that the interim final rule's restrictions on prairie dogs and certain African rodents remain in place, although it also recommended that we make minor clarifications or changes to the rule so that prairie dog owners could take their animals to receive veterinary care and to transport their animals in certain situations. The Secretary's Council did not issue its recommendations in writing.

From mid-2004 through 2007, more information regarding the 2003 monkeypox outbreak appeared in the scientific and medical literature. For example, two scientific articles demonstrated that the monkeypox virus easily infected prairie dogs and that infection in prairie dogs could occur through contact or through inhalation (Refs. 13 and 17). Another article described the laboratory evaluation of animals associated with the monkeypox outbreak; the authors examined tissue samples from 249 animals of 26 different species and found the monkeypox virus in 33 animals (Ref. 23). These animals included three rope squirrels, two Gambian giant pouched rats, and nine dormice from the shipment of African rodents (Ref. 23). Additionally, 14 of 20 prairie dogs tested were PCR positive for the monkeypox virus deoxyribonucleic acid (DNA), and infectious virus was recovered from 9 of 11 prairie dogs (Ref. 23). In general, prairie dogs also had higher levels of monkeypox virus or monkeypox virus DNA than other animal species (Ref. 23). The authors also found monkeypox virus DNA in tissues of other animal species housed at the Illinois establishment; this suggested that monkeypox could infect several animal species (Ref. 23). The article also described the limited, live-trapping of wild animals that the United States Department of Agriculture's Wildlife Service and the United States Geologic Survey's National Wildlife Health Center completed after the United States monkeypox outbreak. Trapping of 201 animals occurred at sites located near where six human monkeypox cases (and associated captive prairie dogs) in Wisconsin occurred. No evidence of orthopox virus infection in any of these animals was detected. (The term “orthopox virus” refers to a genus (a term used in biology to denote a type or group that is above that of a species) of poxviruses. Examples of orthopox viruses include monkeypox virus, cowpox virus, and the variola virus; the variola virus causes smallpox.) The Illinois Wildlife Services program conducted further trapping studies in Illinois at three locations linked by trash disposal routes to the Illinois animal distributor. Forty-three animals were trapped, and all were negative for evidence of orthopox virus infection (Ref. 23).

Other articles (Refs. 14, 15, and 9) shed more light as to why the 2003 outbreak in the United States was not as deadly as those seen in Africa; for example, there are two different strains (or “clades”) of the monkeypox virus, and the virus that appeared in the United States was representative of the less virulent (and less transmissible between humans) strain insofar as humans are concerned (Refs. 14 and 20). The risk of infection in humans correlated with the type of exposure to infected prairie dogs, and most human cases in the United States were associated with direct contact to (specifically the handling of) infected prairie dogs (Refs. 16 and 22). Children (persons under 18 years old) who were infected were more likely to be hospitalized in intensive care compared to infected adults (Ref. 9). Additionally, while some adults had received smallpox vaccinations before 1972, it is unclear as to whether childhood smallpox vaccinations offer durable protection against monkeypox. Some articles indicated that there did not appear to be significant differences in serious clinical observations or complications between vaccinated and unvaccinated adults (Ref. 9 and 20), yet another suggested that an individual's history of smallpox vaccination might protect against monkeypox illness (Ref. 21). In brief, the recent publications validate and reinforce the facts that:

• Prairie dogs are easily infected with the monkeypox virus, and infected prairie dogs have higher levels of monkeypox virus than other infected animals;

• Human cases in the United States were linked to contact with infected prairie dogs; and

• Monkeypox is a serious disease, particularly in children, but the virus implicated in the United States was representative of the less virulent and less transmissible between humans strain.

More significantly, one recent article assessed the risk for monkeypox associated with domestic trade in certain animal species in the United States (Ref. 18). The authors evaluated the data and uncertainties concerning monkeypox and its potential spread to animal and human populations in the United States and characterized in a qualitative analysis the probability of harm based on that data. They concluded that the risk for further domestically acquired human infections is low with the restrictions that FDA and CDC had established. The authors noted that there have been no new cases in humans or animals in the United States since the outbreak, despite the likelihood that some surviving infected animals may have been kept alive by pet owners or dealers. However, there have been no prospective surveillance activities that would fully address this question.

As we explained in the preamble to the interim final rule, we issued the interim final rule under section 361 of the Public Health Service Act (PHS Act) (42 U.S.C. 264) (see 68 FR at 62360) to prevent the spread of communicable disease. Section 361 of the PHS Act authorizes the Secretary to make and enforce such regulations as judged necessary to prevent the introduction, transmission, or spread of communicable diseases from foreign countries into the States or from one State to another State. We may regulate intrastate transactions under this authority as appropriate (see State of Louisiana v. Mathews , 427 F. Supp. 174 (E.D. La. 1977)).

We have invoked section 361 of the PHS Act to regulate various activities and articles. For example, we have invoked this authority to prevent the transmission of communicable disease through certain shellfish, turtles, certain birds, and human tissue intended for transplantation (see 21 CFR 1240.60 (molluscan shellfish), 1240.62 (turtles), 1240.65 (psittacine birds), and 1270.1 through 1270.43 (human tissue)).

Our regulations, at 21 CFR 1240.30, provide further insight as to when we will use our communicable disease authority. The regulation, in relevant part, states that:

Thus, when we issued the June 11, 2003, order and later issued the interim final rule, we acted because we determined that measures taken by State health authorities, in 2003, were insufficient to prevent the spread of monkeypox. We took those actions because infected and potentially infected animals were crossing State lines, and human cases were appearing in several States; the multi-state impact, as well as the then-rapidly developing outbreak, indicated that measures taken by individual States would be insufficient to prevent the spread of monkeypox.

The risk assessment published in 2006, however, suggests that the risk of further monkeypox transmission from the original events of 2003, particularly to humans, in the United States is low. Consequently, based on that low risk, we believe that the import controls of CDC's interim final rule in 42 CFR 71.56 and routine State surveillance and disease prevention measures should be sufficient to prevent further human and animal monkeypox cases. Therefore, we have concluded that the domestic controls in 21 CFR 1240.63 are no longer necessary, and we are removing our regulation.

Please note that this revocation pertains solely to FDA's provisions at 21 CFR 1240.63; the requirements imposed by the CDC at 42 CFR 71.56 remain in effect.

The interim final rule provided an opportunity for public comment; this comment period expired on January 20, 2004. We received over 570 comments on the interim final rule. We received comments from State government agencies or departments, zoos, zoological associations, animal interest groups, animal breeders, animal vendors, and individuals, including foreign citizens. The comments reflected a wide array of differing and sometimes conflicting opinions. For example, most, but not all, State agencies supported the rule. Most State agencies appreciated Federal efforts in responding to the monkeypox outbreak, but one State agency criticized the rule as interfering with the State's wildlife management obligations, and another State agency commented that it, rather than FDA, should operate a permit system that would enable certain animals to move within a State. As another example, many individuals commenting on the rule either captured, sold, owned, or wanted to own prairie dogs and objected strongly to the rule's impact on the prairie dog trade and to continuing the rule. In contrast, a few individuals supported the rule and advocated more stringent measures regarding the pet trade, including animals that the interim final rule did not address.

The comments also varied in their complexity and familiarity with the rule. For example, the American Zoo and Aquarium Association (AZA) recommended a specific change in the rule for AZA-accredited zoological parks because of the quarantine protocols used by AZA-accredited zoos; the AZA included its detailed accreditation standards as part of its comment. In contrast, many comments simply expressed their strong objections to the rule, particularly as it applied to prairie dogs, without explaining the reasons for their objections, discussing any specific regulatory provision, or suggesting any alternative approaches. Some comments advocated defiance or violations of the rule. Several comments denied that monkeypox is a serious disease, although they offered no evidence to contradict the scientific or medical reference we had cited. Other comments criticized the rule or FDA harshly, yet some criticisms pertained to issues that were not in the interim final rule or to actions, statements, or positions that were mistakenly attributed to us. For example, some comments accused us of killing or conspiring to kill prairie dogs. Virtually none of these comments mentioned any other animal covered by the interim final rule, and none offered any evidence to support their accusations.

Additionally, we received over 120 more comments on a notice that appeared in the Federal Register on February 19, 2004 (69 FR 7752). The notice was a routine opportunity for public comment on the information collection provisions in a rule pursuant to the Paperwork Reduction Act of 1995. In this particular case, the notice pertained to the information we were requiring from persons who wanted our permission to capture, offer to capture, transport, offer to transport, sell, barter, or exchange, or offer to sell, barter, or exchange, distribute, offer to distribute, and/or release into the environment any animals covered by the rule. Specifically, the notice sought comment on the numerical estimates pertaining to the permit information, such as the estimated number of persons who would request a permit, the number of hours they would spend in preparing a permit request, the frequency at which permit requests would be submitted, etc. Most comments either interpreted or treated the notice as either a new opportunity to comment on the interim final rule or as finalizing the interim final rule. As a result, almost all comments submitted in response to the Paperwork Reduction Act notice focused on whether the interim final rule should remain in effect and did not address the collection of information under the Paperwork Reduction Act or any of our Paperwork Reduction Act estimates. Even though most comments submitted in response to the February 19, 2004, notice were not relevant to the Paperwork Reduction Act and were submitted months after the interim final rule's comment period had expired, we considered those comments in addition to the comments that were submitted in response to the interim final rule.

Finally, we received seven comments in response to a Federal Register notice which we published on February 21, 2007 (72 FR 7825). The notice added new information, primarily in the form of peer-reviewed scientific literature, to the administrative record, and we invited comment on the information being added. Of the seven comments, only one addressed a specific new reference. (The comment challenged the risk assessment article discussed earlier in section III.C of this document. The comment opined that the article “may underestimate the potential disease transmission risk associated with wild-caught prairie dogs,” but did not challenge the authors' methodology or the authors' conclusion that the risk of monkeypox associated with the 2003 introduction of the virus into the United States was low. Rather, the comment noted a risk of transfer or importation of infectious pathogens risk remains due to illegal importation of animals, as well as the risk that domestic wild animals, particularly prairie dogs, may be a source for diseases other than monkeypox, such as plague and tularemia. The comment argued that there is no way to estimate the degree of illegal importation of African rodents or the legal importation of other potentially infected species. We note that the article does address each of these points.) Most comments discussed issues that were outside the scope of the Federal Register notice of February 21, 2007, such as urging FDA to retain its regulation, discussing the invasive species potential of a Gambian Giant Pouched Rat population located in Florida, discussing plague and tularemia in prairie dogs, or discussing the pet trade, zoonotic diseases generally, or gaps in Federal authority.

Given our decision to remove the regulation based on the current evidence and circumstances, we will not respond in detail to all of the comments that opposed the rule. However, we would like to clarify a few points as follows:

• Many individuals believed that the rule was unfair because the Federal Government did not act against other animals that are capable of transmitting disease to humans. These individuals often argued that the Federal Government did not “ban” cows despite bovine spongiform encephalopathy (BSE, or “mad cow disease”) disease; dogs despite rabies; birds due to West Nile virus; or other animals associated with zoonotic diseases. Some claimed that we were discriminating against prairie dogs because they believed a rabbit had been infected with monkeypox, yet we did not include rabbits in the rule.

As a preliminary matter, the existence of other zoonotic diseases does not, and cannot, mean that we must treat all diseases in the same manner and at the same time. We agree that BSE and several other diseases cited by the comments raise public health concerns, but that fact does not mean that we are compelled to promulgate regulations for other or all zoonotic diseases before we can issue regulations to deal with monkeypox. In addition, it is important to note that monkeypox, as we stated in the preamble to the interim final rule (see 68 FR at 62353), is a zoonotic disease that, until mid-2003, occurred in central and west Africa. The monkeypox virus' appearance in the United States demanded our immediate attention because monkeypox is a potentially fatal disease in humans, so it was important to prevent the virus from becoming established in the United States. West Nile virus is an example of how a virus can become established in the United States and result in sickness and death. Before 1999, West Nile virus had not been recorded in the United States; in 2002 alone, more than 4,000 Americans had become ill, and 284 had died (see 68 FR at 62361). Many animal species also suffered as the West Nile virus became established in the United States (id.).

To put it another way, unlike most of the pathogens or factors responsible for the diseases cited by the comments, the monkeypox virus was new to the United States in 2003, and (unlike West Nile virus) could be controlled through regulation of human activity; as a result, a regulatory approach was taken that we anticipated would prevent the virus from becoming established in the listed animal populations or in other domestic animal populations. To the best of our knowledge, the efforts undertaken in 2003 were fully successful.

We also wish to point out that, contrary to the comments' assumptions, we have taken regulatory action regarding other animals and other diseases. Those regulatory actions varied depending on the risk presented. For example, we have issued regulations restricting the sale and commercial distribution of turtles (21 CFR 1240.62) and restricting the transportation of psittacine birds (21 CFR 1240.65) because of their potential to transmit certain diseases to humans. We prohibited the use of mammalian protein in ruminant feed (21 CFR 589.2000) and have taken a number of additional actions to reduce the potential risk of BSE in cattle (see, e.g., 72 FR 1582 (January 12, 2007) (proposed rule to prohibit the use of certain cattle material in or in the manufacture of drugs intended for use in ruminant animals); 70 FR 58570 (October 6, 2005) (proposed rule to prohibit the use of certain cattle origin materials in the food or feed of all animals); 69 FR 58448 (September 30, 2004) (notice of availability of a guidance titled “Use of Material from Bovine Spongiform Encephalopathy-Positive Cattle in Animal Feed”); 69 FR 42288 (July 14, 2004) (advance notice of proposed rulemaking inviting comment on Federal measures to mitigate BSE risks)). We also have taken action to prohibit the use of certain cattle material (such as brain, skull, eyes, spinal cord, and other material) in human food to minimize human exposure to materials that are highly likely to contain the BSE agent (see 69 FR 42256 (July 14, 2004); see also 69 FR 42275 (July 14, 2004) (proposed rule to require manufacturers and processors of human food and cosmetics that are manufactured from, processed with, or otherwise contain material from cattle to establish and maintain records sufficient to demonstrate that the food or cosmetic is not manufactured from, processed with, or does not otherwise contain prohibited cattle materials)). Thus, we have taken regulatory actions when necessary to protect the public health, and the nature of the risk presented shaped our regulatory response to that risk.

Finally, insofar as rabbits and monkeypox are concerned, we acknowledge that a report issued as the 2003 outbreak was unfolding (Ref. 24) suggested that a rabbit might have transmitted the monkeypox virus to a human. However, subsequent tests on the rabbit in question and the human patient proved negative. Consequently, there are no documented cases of monkeypox transmission from rabbits to humans in the United States (Ref. 22).

• The 2003 monkeypox outbreak was significant because it involved a potentially fatal disease that had never been seen within the United States. It was important to stop monkeypox from becoming established in the United States because, once established, the disease could become a greater public health problem. If the virus became established in the United States, the potential impact on humans and other animal species could have been significant. In brief, final analysis of the 2003 monkeypox outbreak showed the following: (1) Besides rope squirrels, additional native species of African rodents (Gambian giant pouched rats and dormice) are susceptible to monkeypox; (2) prairie dogs are susceptible to monkeypox; (3) infected prairie dogs can transmit the disease to humans; and (4) children may be affected more severely than adults. Additionally, laboratory experiments demonstrated that additional North American animal species are susceptible to monkeypox (Ref. 23). We did not know, in 2003, and, in many cases, still do not know, whether the virus had spread or could spread to other domestic animal species (such as rodents) which, in turn, could expose more humans to monkeypox. In short, when dealing with a novel communicable disease, trying to prevent the disease from spreading has both present effects (i.e., fewer individuals become sick or die) and future effects (i.e., the potential for more animals and humans to become infected decreases if prevention efforts are successful).

• With respect to the comments that supported the interim final rule, we agree that the risks of communicable disease spread justified the measures taken in the interim final rule. Because we have decided to remove the regulation, we will not address the details of the comments that suggested variations on the permit system or other modifications to the rule. Nor will we address the issues related to other diseases of prairie dogs or to zoonotic diseases in general, which are outside the scope of this rule.

• The circumstances being addressed by most of the comments supporting the interim final rule have changed significantly, in large part because of the success of the interim final rule. As discussed in section III.C above, the current evidence supports the conclusion that the risk of further infections from the monkeypox virus in the United States is low. Only one comment challenged the risk assessment that concluded that the current risk is low, but that comment did not challenge the authors' methodology. Instead, the comment expressed concern about future illegal importation of African rodents or legal importation of other animals that could be infected with monkeypox. Although we agree that the risk of future importations of animals infected with the monkeypox virus is not zero, we believe that the restrictions in 42 CFR 71.56 have been successful, and will continue to be successful, in keeping this risk low. Together, the measures taken by FDA and CDC under 21 CFR 1240.63 and 42 CFR 71.56 have successfully brought the risk of further human or animal monkeypox infection in the United States associated with the 2003 outbreak to its current low level. Based on the evidence, we believe that the risk will remain low in the absence of the measures in FDA's interim final rule. Under these circumstances, including the fact that CDC's interim final rule at 42 CFR 71.56 remains in effect, we have decided to remove 21 CFR 1240.63 in its entirety.

We have determined under 21 CFR 25.32(g) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required.

We have examined the impacts of this regulatory action under Executive Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive Order 12866 directs agencies to assess all costs and benefits of available regulatory alternatives and, when regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health and safety, and other advantages; distributive impacts; and equity). We believe that the removal of the regulation is not a significant regulatory action under the Executive order.

The Regulatory Flexibility Act requires agencies to analyze regulatory options that would minimize any significant impact of a rule on small entities. Because the removal of FDA's regulation would eliminate most of the small administrative costs imposed by the interim final rule, we certify that it will not have a significant economic impact on a substantial number of small entities.

Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires that agencies prepare a written statement, which includes an assessment of anticipated costs and benefits, before publishing “any rule that includes any Federal mandate that may result in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted annually for inflation) in any one year.” The current threshold after adjustment for inflation is $127 million, using the most current (2006) Implicit Price Deflator for the Gross Domestic Product. We do not expect the removal of FDA's regulation to result in any 1-year expenditure that would meet or exceed this amount.

We issued a regulation on November 4, 2003, that modified existing restrictions on the import, capture, transport, sale, barter, exchange, distribution and release of African rodents, prairie dogs and certain other animals in order to prevent the spread of monkeypox. The decision to remove the regulation pertaining to domestic trade in prairie dogs and certain African rodents will eliminate most of the costs of the regulation to the extent that they have been realized.

In the interim final rule, we stated that incomplete data precluded us from developing quantitative estimates of the economic costs and benefits of the rule. The analysis of the rule, however, did contain a discussion about the sale of prairie dogs prior to and immediately after the June 11, 2003, administrative order banning the sale of these animals in order to reduce the spread of monkeypox. In effect, the analysis described the loss of the market for these pets that resulted from the earlier administrative order restricting their further distribution. The removal of the regulation would reopen the domestic market for pet prairie dogs, which prior to 2003 was estimated at about 30,000 animals per year with a retail value of about $4.5 million. The domestic markets for certain African rodents would also be reopened, but the CDC restrictions on the importation of African rodents would remain in effect. Although we do not have data to estimate the size of these markets in 2003, the analysis in the interim final rule concluded that they would be fairly small.

The interim final rule also allowed for exemptions from the rule's restrictions on trade in these animals by requesting written permission from FDA. The analysis estimated that individuals requesting these exemptions would incur annual administrative costs ranging from about $3,500 to $6,500. FDA's administrative costs to process these requests each year were estimated at $13,300. These administrative costs will be eliminated with the removal of FDA's regulation.

The analysis of the interim final rule also concluded that the regulation may have a significant impact on a substantial number of small entities, including trappers and distributors of prairie dogs, other small animal distributors, and retail pet stores. Most of these impacts will be negated with the removal of FDA's regulation.

The following references have been placed on display in the Division of Dockets Management (see ADDRESSES ) and may be seen by interested persons between 9 a.m. and 4 p.m., Monday through Friday.

FDA has analyzed this rule in accordance with the principles set forth in Executive Order 13132. We have determined that the rule does not contain policies that have substantial direct effects on States, on the relationship between the National Government and the States, or on the distribution of power and responsibilities among the various levels of government. Accordingly, we have concluded that the rule does not contain policies that have federalism implications as defined in the Executive Order, and, consequently, a federalism summary impact statement is not required.

Since the development of the CGMP regulations for drug products in 1962, FDA has balanced the need for easily understood minimum standards with the need to encourage innovation and the development of improved manufacturing technologies. We strive to give manufacturers latitude to determine how to achieve the level of control necessary for CGMP compliance, recognizing that, in some instances, more direction from FDA is necessary to provide a uniform standard to the entire industry, minimize the potential for harm, or achieve some other CGMP objective. We periodically reassess and revise the CGMP regulations to accommodate advances in technology and other scientific knowledge that further safeguard the drug manufacturing process and the public health.

In 1996, as part of this reassessment process, we proposed to: (1) Amend certain requirements of the CGMP regulations for finished pharmaceuticals to clarify certain manufacturing, quality control, and documentation requirements and (2) ensure that the regulations more accurately encompassed current industry practice (61 FR 20104, May 3, 1996) (1996 proposed rule). Subsequently, as a part of the risk-based Pharmaceutical CGMPs for the 21st Century initiative, we created a CGMP Harmonization Analysis Working Group (CGMP Working Group) to analyze related CGMP requirements in effect in the United States and internationally, including those related to quality systems. The CGMP Working Group compared parts 210 and 211 (21 CFR parts 210 and 211) with the CGMPs of the European Union (EU), as well as other FDA regulations (e.g., the Quality Systems Regulation, 21 CFR part 820) to identify the differences and consider the value of supplementing or changing the current regulations. Based on the CGMP Working Group's analysis, we decided to take an incremental approach to modifying parts 210 and 211.

Because of this change in approach, we decided not to finalize the 1996 proposed rule. On December 4, 2007, we published a document withdrawing the 1996 proposed rule (72 FR 68111) (the December 2007 proposed rule). On the same date, we published a direct final rule (72 FR 68064) and companion proposed rule (72 FR 68113) to clarify and modernize certain provisions of the CGMP regulations. The comment period for the direct final rule closed on February 19, 2008. On April 4, 2008, we published a document withdrawing the direct final rule because we received significant adverse comments (73 FR 18440). In the document withdrawing the direct final rule, we explained that the comments received would be considered under our usual procedures for notice and comment in connection with the notice of proposed rulemaking that was published as a companion to the direct final rule.

After careful consideration of all comments received, we are now publishing this final rule. The final rule represents the culmination of the first increment of modifications to parts 210 and 211.

The final rule revises the drug CGMP regulations primarily in three areas: Aseptic processing, use of asbestos filters, and verification of operations by a second individual.

The final rule revises § 211.113(b) to clarify that required written procedures designed to prevent microbiological contamination of sterile drug products must include procedures on the validation of all aseptic processes in addition to sterilization processes. Other changes related to aseptic processing include the following:

• Revised § 211.67(a) requires that equipment and utensils be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized “and/or sterilized” at appropriate intervals to prevent malfunction or contamination. This change recognizes that for sterile drug products, sterilization (sometimes in addition to sanitization) is appropriate.

• Revised § 211.84(d)(6) requires microbiological tests before use of each lot of a component, drug product container, or closure “with potential for microbiological contamination” that is objectionable in view of its intended use, consistent with longstanding agency interpretation of this regulation.

• Revised § 211.94(c) requires validation of depyrogenation processes for drug product containers and closures, consistent with longstanding industry practice and agency interpretation of this regulation.

• Revised § 211.110(a) adds bioburden testing to the list (which is not all-inclusive) of in-process control procedures relating to the sampling and testing of in-process materials, which again is consistent with industry practice.

We revised §§ 210.3(b)(6) and 211.72 to eliminate provisions permitting limited use of asbestos-containing filters used in processing injectable drug products. We had proposed to simply delete references to asbestos filters in these provisions. However, in response to comments, we also added to § 211.72 the statement “The use of an asbestos-containing filter is prohibited.” Also in response to comments, we revised § 211.72 to reflect appropriate technical standards for nonfiber-releasing filters.

The final rule makes several changes to the regulations to acknowledge, consistent with our longstanding interpretation, that certain operations may be performed by automated equipment and verified by a person, rather than one person performing an operation and another person verifying that the operation was correctly performed. In particular, we added new paragraph (c) to § 211.68 stating that automated equipment used to perform operations addressed in §§ 211.101(c) or (d), 211.103, 211.182, or 211.188(b)(11) can satisfy the requirements in those sections for the performance of an operation by one person and checking by another person if the equipment is used in conformity with § 211.68 and one person checks that the operations are properly performed. In response to comments, we revised the paragraph to minimize the possibility that the provision might be misinterpreted as requiring a person to repeat by hand all calculations performed by automated equipment.

In accordance with the addition of § 211.68(c), we are adopting corresponding changes to the following provisions:

• Section 211.101(c) and (d) (concerning charge-in of components and containers),

• Section 211.103 (calculation of yields),

• Section 211.182 (equipment cleaning and maintenance), and

• Section 211.188(b)(11) (batch production and control records).

In addition to the revisions to the regulations previously noted, we have made minor revisions to the following provisions to provide greater clarity without changing meaning or intent:

• Section 211.82(b) (storage of components, containers, and closures),

• Section 211.84(c)(1) and (d)(3) (collection and testing of samples of components, containers, and closures), and

• Section 211.160(b)(1) (laboratory controls for determining conformity to specifications).

We received comments on the proposed rule from drug and biologic manufacturers, industry associations, consultants, and other interested persons. A summary of the comments received and our responses follow. We first respond to comments of a general nature and then to comments on the five topics set forth in the preamble of the direct final rule.

To make it easier to identify comments and our responses, the word “Comment,” in parentheses, appears before the comment's description, and the word “Response,” in parentheses, appears before our response. We have numbered each comment to help distinguish between different comments. Similar comments are grouped together under the same number if the same response would be given for each. The number assigned to each comment is purely for organizational purposes and does not signify the comment's value or importance or the order in which it was received.

(Comment 1) One comment stated that it will be very important for FDA to ensure clarity and consistency in the understanding of the final rule among agency staff, including both product reviewers and CGMP inspectors, to minimize different interpretations and applications of these regulations.

(Response) We agree that it is important that FDA employees who perform application reviews, as well as conduct CGMP inspections and other compliance activities, understand these regulations and apply them in a consistent manner in the performance of their duties. Therefore, we will take appropriate steps to ensure that agency staff receive adequate training regarding the new regulations.

(Comment 2) One comment stated that we should not withdraw the 1996 proposed rule because it contained many good features with respect to test method validation and the out-of-specification test result problem. The comment maintained that the guidance for industry entitled “Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production” (71 FR 60158, October 12, 2006) is not helpful to people working with biological drugs and other products. Another comment stated that the December 2007 proposed rule should have incorporated many of the changes in the 1996 proposed rule regarding such matters as validation, quality control unit responsibilities, batch failure investigations, and stability samples because they involve some of the most common CGMP deficiencies.

(Response) As we stated in the December 4, 2007, document, we withdrew the 1996 proposed rule because we concluded that, given our new approach to CGMP under the 21st century initiative, it would be preferable to revise the CGMP regulations incrementally rather than in a one-time, comprehensive fashion. Furthermore, we believe that it is appropriate to reevaluate some of the matters considered in the 1996 proposed rule in light of recent scientific and technological advances. We appreciate the comments' interest in the specified CGMP issues, and we will consider these issues in future phases of our CGMP modernization efforts.

(Comment 3) One comment encouraged FDA to consider other CGMP regulations that need modernization or clarification, or are no longer necessary due to technological advances, such as aspects of 21 CFR 610.12 concerning the requirements for bulk sterility testing and allowance for sterility retesting for biological products.

(Response) We appreciate the comment's interest in modernizing CGMP regulations. As previously stated, this final rule represents only our first step in updating the drug CGMP regulations to reflect current industry practice and harmonize the regulations with international CGMP requirements. We will consider other aspects of CGMP in future rulemaking proceedings.

Section 211.48(a) requires that potable water be supplied under continuous positive pressure in a plumbing system free of defects that could contribute contamination to any drug product. It further requires that potable water meet the standards established by the U.S. Environmental Protection Agency (EPA) for primary drinking water in 40 CFR part 141. Proposed § 211.48(a) would have deleted the requirement that the potable water used in a plumbing system meet EPA's standards for primary drinking water, and instead required that the water be “safe for human consumption.” This proposed revision was intended to improve harmonization with foreign regulations (particularly those of the EU and Japan) and to make the U.S. regulation more consistent with the United States Pharmacopeia standard. In the preamble of the direct final rule, we stated that the revised requirement could be met by compliance with the standards in the EPA regulations or in the current regulations of the EU or Japan for potable water used to prepare water for pharmaceutical purposes.

(Comment 4) Four comments objected to the proposed change. Among other things, the comments stated that the standard of “safe for human consumption” is not sufficiently prescriptive.

(Response) Because of the comments received and other considerations, we have decided not to revise § 211.48(a) at this time. We will address the issue of standards for water used in a facility's plumbing system when we consider proposing regulations for water used as a drug product component in the next phase of our CGMP initiative.

In the proposed rule, we sought to amend several regulations on aseptic processing to reflect current industry standards and practices. Some of the proposed revisions would also affect other types of processes and operations. We noted that the proposed changes would not affect the applicability of the guidance for industry entitled “Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice” (Aseptic Processing Guidance), issued on October 4, 2004 (69 FR 59258).

The version of § 211.67(a) amended by this final rule stated: “Equipment and utensils shall be cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.” We proposed to add the phrase “and/or sterilized” after the word “sanitized” in § 211.67(a) to reflect the fact that sterilization is appropriate for sterile drug products.

On our own initiative, we have revised § 211.67(a) to state that equipment and utensils shall be cleaned, maintained, “and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals * * *.” This revision does not alter the meaning of the proposed rule change, but clarifies that for some equipment and utensils used in the production of certain drug products, sanitization is appropriate; for other equipment and utensils, sterilization is appropriate; and for still others, both sanitization and sterilization are appropriate.

(Comment 5) One comment stated that it is not appropriate to address sterilization in § 211.67(a). Instead, the comment recommended that a reference to sterilization of equipment and utensils be added to § 211.113(b), which requires the adoption of written procedures designed to prevent microbiological contamination of drug products purporting to be sterile.

(Response) We do not agree with the comment because, as previously noted, equipment and utensils used in the production of sterile drug products must be sterilized, not merely sanitized. In addition, we have revised § 211.113(b) as discussed in section III.C.5 of this final rule.

(Comment 6) One comment suggested that we could simplify the language in this regulation by changing the phrase “beyond the official or other established requirements” to “beyond the established (or other official) requirements.”

(Response) We do not believe that the suggested change simplifies the current phrase, which we believe is clear. Therefore, we do not believe that the suggested change is necessary.

(Comment 7) One comment stated that § 211.67(a) should not apply to the production of medical gases because most medical gas manufacturing lines are product-specific, closed systems that are not subject to cleaning or sanitation as part of an established periodic cycle, but instead are specially cleaned to be “oxygen ready” and carefully handled in accordance with established procedures. The comment maintained that additional cleaning efforts beyond the initial cleaning regimen substantially increase the risk of introducing contaminants into the system. Therefore, the comment stated, it is not necessary to require cleaning of equipment at “appropriate intervals” for medical gas manufacturing. The comment suggested that, alternatively, it might be appropriate for the agency to state that medical gases may represent unique circumstances that will be reflected in a separate guidance.

(Response) We decline to exempt medical gases from the requirements of § 211.67(a) as recommended because this would exceed the scope of our proposed change to clarify that sterilization is appropriate for sterile drug products and would instead focus on whether there is any need for periodic cleaning of medical gas systems. We might consider in a future CGMP rulemaking whether it is appropriate to revise § 211.67(a) to address its application to medical gases.

The version of § 211.84(d)(6) amended by this final rule stated: “Each lot of a component, drug product container, or closure that is liable to microbiological contamination that is objectionable in view of its intended use shall be subjected to microbiological tests before use.” We proposed to change the phrase “that is liable to microbiological contamination” to “with potential for microbiological contamination.”

(Comment 8) One comment stated that the proposed change was unnecessarily restrictive and might lead to testing every lot when the risk of microbial contamination is low and the impact on the intended use is insignificant. This comment suggested replacing “that is liable to microbial contamination” with “prone to microbial contamination.” One comment stated that the proposed change could make it more difficult for drug manufacturers to replace a less effective, quality control-based inspection and test method with a more modern and effective quality audit method. The comment stated that because the bioburden of dry items such as vials and stoppers is often heterogeneous, improved assurance of this quality attribute is better achieved through the audit, selection, and control by the manufacturers of these items. This comment maintained that knowledge of and control over the manufacturing processes for containers and closures might fall short of justifying that those products do not have a “potential for contamination.”

(Response) We decline to adopt the recommended change to § 211.84(d)(6) from “that is liable to microbial contamination” to “prone to microbiological contamination.” We believe that our proposed change to “with potential for microbiological contamination” clarifies our longstanding interpretation of the regulation that each lot of component, drug product container, or closure that is susceptible to contamination must undergo microbiological testing before use. Therefore, we have revised § 211.84(d)(6) to refer to components, containers, or closures “with potential for microbiological contamination” as proposed.

The version of § 211.94(c) amended by this final rule stated: “Drug product containers and closures shall be clean and, where indicated by the nature of the drug, sterilized and processed to remove pyrogenic properties to assure that they are suitable for their intended use.” In the preamble to the direct final rule, we stated that it has been longstanding industry practice to validate the sterilization and depyrogenation processes used for drug product containers and closures to ensure consistent removal of microbial contamination and pyrogens or endotoxins. Therefore, we proposed to add a provision to § 211.94(c) requiring the validation of these depyrogenation processes.

(Comment 9) One comment suggested that we require validation of “sterilization” as well as depyrogenation processes.

(Response) We do not believe that the suggested change is needed because § 211.113(b) already requires validation of sterilization processes for the prevention of microbiological contamination of drug products purporting to be sterile.

(Comment 10) Four comments objected to the requirement in existing § 211.94(c) because it requires depyrogenation of components based on the nature of the drug and does not take into account the fact that some containers and closures are inherently nonpyrogenic, have been qualified not to require active depyrogenation, or do not require depyrogenation because of handling procedures. Three of the comments proposed that in addition to the nature of the drug, the drug's manufacturing process be included as a factor in determining when containers and closures must be sterilized and processed to remove pyrogenic properties. Two of the comments recommended that the requirement to validate depyrogenation processes be limited to containers and closures that are made nonpyrogenic by a designated depyrogenation process (thus excluding inherently nonpyrogenic containers and closures from the regulation).

(Response) We decline to adopt the suggested revisions because they go beyond the scope of our proposed change to require validation of depyrogenation processes and instead focus on the need for depyrogenation itself.

Section 211.110(a) requires that written procedures be established and followed that describe in-process controls and tests or examinations to be conducted on samples of in-process materials of each batch of a drug product. The regulation specifies five control procedures that must be established, where appropriate, to monitor the output and to validate the performance of manufacturing processes that may be responsible for causing variation in the characteristics of in-process material and the drug product. We proposed to add bioburden testing to this list (which is not all-inclusive) because testing for bioburden is standard industry practice for in-process materials and drug products that are produced by aseptic processing.

(Comment 11) Three comments objected to the addition of bioburden testing to § 211.110(a). One comment objected to the inclusion of any specific test and suggested that specific tests be addressed in agency guidance. One comment stated that bioburden testing is not conducted at the same time as other tests specified in § 211.110(a) and is not an in-process test or control because it does not yield immediate results that allow for process adjustment. The comment stated that it would be more appropriate to address bioburden testing in § 211.84. One comment suggested that because § 211.110 covers the sampling and testing of all in-process materials and drug products, adding bioburden testing as a mandatory control procedure could expand current industry validation procedure and produce diversity among the industry and regulators on the circumstances in which validation of bioburden testing is appropriate.

(Response) We do not agree with the comments. As stated in the direct final rule, testing for bioburden is an important in-process control, particularly for drug products that are produced through aseptic processing. Section 211.110(a) provides flexibility to manufacturers so that they need only conduct bioburden testing where the testing is appropriate to assure batch uniformity and drug product integrity. We believe that manufacturers understand for which types of drug products, and at what point in the manufacturing process for these drugs, bioburden testing is appropriate. Accordingly, we have added bioburden testing to § 211.110(a).

Section 211.113(b) states that appropriate written procedures, designed to prevent microbiological contamination of drug products purporting to be sterile, must be established and followed. The version of § 211.113(b) amended by this final rule further stated: “Such procedures shall include validation of any sterilization process.” We proposed to substitute “all aseptic and sterilization processes” for “any sterilization process.” As noted in the preamble of the direct final rule, even before we issued the now-replaced guidance on “Sterile Drug Products Produced by Aseptic Processing” in 1987, industry routinely conducted validation studies (often referred to as media fills) that substituted microbiological media for the actual product to demonstrate that its aseptic processes were validated (72 FR 68064 at 68066). The proposed change was intended to clarify existing practice and to harmonize § 211.113 with Annex 1 of the EU CGMPs.

(Comment 12) Several comments objected to the proposed change to § 211.113(b) on the basis that aseptic processing cannot be validated. One comment stated that validation of aseptic processing technically cannot be done, although the manufacturer can ensure tight control over the process. One comment stated that aseptic processing simulations demonstrate the capability of a facility, equipment, and operational controls to provide a minimal microbial contamination rate in a single event, but they cannot predict the outcome of a similar process performed at a different time. The comment maintained that to consider aseptic processing to be validated overstates the ability to measure and control the process and could be interpreted as approval to relax the controls necessary for its success. The comment recommended that § 211.113(b) be revised to require validation of “all sterilization/depyrogenation processes” and to direct that aseptic processes “be subjected to periodic assessment to demonstrate the capability of the control strategy to adequately support end product sterility.”

One comment stated that there is currently no means to comply with the proposed requirement to validate aseptic processes. The comment maintained that the microbiological and decontamination methods used in aseptic processing lack the sensitivity, recoverability, and accuracy of the physical and chemical measurement systems normally associated with process validation. The comment further claimed that media fills do not validate aseptic processing because they measure only detectable micro-organisms and do not verify that no micro-organisms exist. The comment stated that although aseptic processing cannot be validated, a state of control can be established, ensuring that the aseptically produced drug consistently meets its specifications and quality attributes. The comment recommended that rather than validation of aseptic processes, § 211.113(b) require “a formalized quality risk management and control strategy for aseptic processes to provide assurance of requisite and continued process capability and product quality.”

One comment stated that although media fills can evaluate an aseptic process, they cannot be considered to validate the process. The comment recommended that we either not adopt the proposed requirement to validate aseptic processes or provide more clarity on what is expected for validation of aseptic processes. Similarly, another comment recommended that we not revise § 211.113(b) as proposed unless we clarify that more than media fills are required to validate an aseptic process. The comment stated that a well-controlled, robust process is required for aseptic processes and that once a state of control has been established for the process, media fills can be useful in confirming the state of control.

(Response) Although we acknowledge that aseptic process validation does not provide absolute assurance of product sterility, we do not agree that aseptic processes cannot be validated. Validation of aseptic processes, which is a common practice throughout the pharmaceutical industry, means establishing documented evidence that provides a high degree of assurance that a particular process will consistently produce a product meeting its predetermined specifications and quality attributes. Media fills, together with operational controls, environmental controls, and product sterility testing, provide a sufficient level of assurance that drugs purported to be sterile are in fact sterile.

(Comment 13) One comment suggested adding a definition of aseptic processing to part 210.

(Response) We do not believe that it is necessary to define aseptic processing in the regulation. The Aseptic Processing Guidance makes it clear to manufacturers what aseptic processing entails.

(Comment 14) One comment requested confirmation that it is acceptable to follow the current FDA guidance and use media fills to meet the requirement to validate aseptic processes.

(Response) As stated in the preamble to the direct final rule and reiterated previously in this document, manufacturers can follow the recommendations in the Aseptic Processing Guidance to comply with CGMP requirements for aseptic processing, including validation. However, as with any guidance, the Aseptic Processing Guidance is not binding on industry or the agency, and manufacturers may use an alternative approach to achieve compliance if the approach meets the requirements of the act and FDA regulations.

(Comment 15) One comment sought clarification that the requirement to validate aseptic processing would not inhibit implementation of novel technologies recommended by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) in the ICH Q8, Q9, and Q10 guidances, or other innovative approaches in these areas.

(Response) We do not believe that the requirement to validate aseptic processing will interfere with the implementation of new technologies either as part of following ICH recommendations or as part of other efforts to meet CGMP requirements. As stated in section I of this document, we have always attempted to balance the need for easily understood minimum CGMP standards with the desire to encourage innovation and the development of improved manufacturing technologies. We are confident that industry can meet the requirement to validate aseptic processing with no adverse impact on technological innovation in drug product manufacturing.

As stated in the preamble to the direct final rule, we need to update our regulations on filters used in processing liquid injectable products. The version of § 211.72 amended by this final rule required manufacturers, before using an asbestos-containing filter, to submit proof to FDA that an alternative nonfiber-releasing filter will, or is likely to, compromise the safety or effectiveness of the product. However, we are not aware that asbestos filters are currently commercially manufactured for pharmaceutical use or are used in drug production, and their use is not considered a good manufacturing practice. Therefore, we proposed to delete the reference to the use of asbestos-containing filters from § 211.72 and to delete the reference to asbestos filters from the definition of “nonfiber-releasing filter” in § 210.3(b)(6).

(Comment 16) Two comments stated that the regulations should state that the use of asbestos filters is prohibited. One comment stated that if asbestos-containing filters are in fact available and the proposed changes were interpreted as permitting their use, this might pose a risk to patients.

(Response) We agree with the comments. Therefore, in addition to deleting the reference to asbestos-containing filters in § 210.3(b)(6), we have revised the last sentence of § 211.72 to state that the use of an asbestos-containing filter is prohibited.

(Comment 17) One comment recommended that we clarify the second sentence in proposed § 211.72, which stated: “Fiber-releasing filters may not be used in the manufacture, processing, or packing of these injectable drug products unless it is not possible to manufacture such drug products without the use of such filters.” The comment recommended that this sentence be revised to state as follows: “Fiber-releasing filters may be used when/where it is not possible to manufacture such drug products without the use of such filters.”

(Response) We agree with this proposed change and have revised § 211.72 accordingly.

(Comment 18) Four comments recommended revising the following provision in proposed § 211.72: “If use of a fiber-releasing filter is necessary, an additional nonfiber-releasing filter of 0.22 micron maximum mean porosity (0.45 micron if the manufacturing conditions so dictate) shall subsequently be used to reduce the content of particles in the injectable drug product.” Each of these comments stated that it is technically more accurate to describe a filter in terms of its nominal pore size rating than its mean porosity. One comment stated that the filter pore size standard of 0.22 micron is outdated and should be changed to 0.2 micron.

(Response) These suggested technical changes are consistent with statements in our guidances for industry (e.g., the Aseptic Processing Guidance) concerning filters. Therefore, we have revised § 211.72 to require that if use of a fiber-releasing filter is necessary, an additional nonfiber-releasing filter having a maximum nominal pore size rating of 0.2 micron be used.

The current CGMP regulations include several provisions requiring that certain activities be performed by one person and checked as specified by a second person.

• Section 211.101(c) requires that: (1) Each container of component dispensed for use in manufacturing be examined by a second person to assure that it was released by the quality control unit, (2) the weight or measure is correct as stated in the batch production records, and (3) the containers are properly identified.

• Section 211.101(d) requires that each component be added to the batch by one person and verified by a second person.

• Section 211.103 requires that specified yield calculations be performed by one person and independently verified by a second person.

• Section 211.182 requires the persons performing and double-checking the cleaning and maintenance of major equipment to date and sign or initial equipment logs indicating that the work was performed.

• Section 211.188(b)(11) requires that batch production and control records include identification of the persons performing and directly supervising or checking each significant step in the operation.

When we amended the CGMP regulations in 1978, we established § 211.68, which provides that automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product, subject to the following requirements:

• Equipment is routinely checked according to a program designed to assure proper performance,

• Changes to records are made only by authorized personnel,

• Input and output are checked for accuracy, and

• Appropriate backup of data is maintained.

In the preamble to the 1978 final rule, we stated that the verification requirements in § 211.101 for charge-in of components when automated systems are used would be met if a person verified that the automated system was working properly (43 FR 45014 at 45051, September 29, 1978). Thus, in this situation, the first individual is replaced by a machine or other automated process, and only one person is necessary to verify that the automated system is functioning as intended.

Because we have received questions about the performance and checking requirements in §§ 211.101(c) or (d), 211.103, 211.182, or 211.188(b)(11) when the operations are performed by automated equipment, such as the widespread and increasing use of computer-controlled operations, we proposed to revise these sections. We proposed to amend these regulations to indicate that when automated equipment is used to perform certain operations, only one person is needed to verify that the automated equipment is functioning adequately. Correspondingly, proposed § 211.68(c) stated that automated equipment used for performance of operations addressed by §§ 211.101(c) or (d), 211.103, 211.182, or 211.188(b)(11) can satisfy the requirements included in those sections for the performance of an operation by one person and checking by another person if such equipment is used in conformity with § 211.68 and one person verifies that the operations addressed in those sections are performed accurately by such equipment. We stated in the preamble of the direct final rule that these revisions would clarify our longstanding policy that verification by a second individual may not be necessary when automatic equipment is used under § 211.68.

(Comment 19) One comment stated that validated, automated systems equipped with real time alarms that do not require any human intervention should not require human verification. Another comment stated that such systems should not require human verification with each use and, when human verification is needed, the level of verification required should be consistent with the level of automation used. Both of these comments maintained that requiring operator verification of automated, validated equipment under §§ 211.68(c), 211.101(c)(3) and (d), 211.103, and 211.188(b)(11) might hinder the implementation of process analytical technology (PAT) in the drug industry.

(Response) In the Federal Register of February 12, 1991 (56 FR 5671) (the 1991 proposal), we issued a proposed rule in part to amend § 211.68 to add what is now the third sentence of § 211.68(b): “The degree and frequency of input/output verification shall be based on the complexity and reliability of the computer or related system.” This revision was adopted as part of the final rule issued on January 20, 1995 (60 FR 4087) (the 1995 final rule).

In the 1995 final rule, we responded to several comments on the proposed revision. Two comments suggested that the revised regulation did not accommodate the accepted use of validated computerized drug production and control systems. We declined to change the revision as proposed, stating our belief that the wording in the revised rule adequately encompasses the use of these systems (60 FR 4087 at 4089).

Two comments on the 1991 proposal questioned the need for human verification of operations that are performed by validated computer systems. The comments listed other regulations that were not the subject of the proposed rule that required more than one person to verify certain manufacturing operations, apparently to show that additional personnel would be needed to comply with proposed § 211.68. We noted in the 1995 final rule that the revisions to § 211.68 do not impose any specific personnel requirements. We also noted that the agency is aware that computers are subject to malfunctions, some of which could possibly result in the loss of critical information regarding the manufacturing process or a serious production error and the possible distribution of an adulterated product. Therefore, we stated that while increasingly sophisticated system safeguards and computerized monitoring of essential equipment and programs help protect data, no automated system exists that can completely substitute for human oversight and supervision. We further indicated that while the degree of verification is left to the manufacturer's discretion, the exercise of such discretion under § 211.68 requires the use of routine accuracy checks to provide a high degree of assurance that input to and output from a computer or related system are reliable and accurate. We stated our intent that each manufacturer exercise reasonable judgment based on a variety of factors, including, but not limited to, the complexity of the computer or related system, in developing a method to prevent inaccurate data input and output (60 FR 4087 at 4089).

The December 4, 2007, direct final rule and companion proposed rule were intended to amend the regulations involving second-person checks only to clarify our longstanding policy that verification by a second individual may not be necessary when automatic equipment is used under § 211.68, and that in such situations only one person is needed to verify that the automated equipment is functioning adequately. The amendments were not intended to either add to or detract from any existing requirements in this regard, but only to clarify our longstanding interpretation and policy for these requirements. We note that the same basic considerations apply in this regard today as we expressed in the 1995 final rule. Although increasingly sophisticated controls and safeguards have been implemented for some automated systems, our policy has been that some degree of human oversight, supervision, verification, monitoring, or checking is still necessary to verify proper performance as part of assuring the identity, strength, quality, and purity of drug products. For suitably validated automated systems, even with real time alarms, it is still necessary for a human to verify that the systems are operating as planned and to monitor for abnormalities. We agree that the level, nature, and frequency of such human verification will vary depending on the level of automation used as well as the nature of the system and controls, and the manufacturer has the flexibility and responsibility to determine what is suitable and necessary. Contrary to the comments, we believe that manufacturers can conduct human verification of automated operations in conjunction with the use of PAT in drug production.

For these reasons, we continue to believe that human verification is necessary to ensure that automated systems are functioning properly.

(Comment 20) One comment stated that many current biotech processes include component additions and deletions in a continuous or periodic manner over long periods of time. The comment stated that there would be no added value in requiring a manual verification of this component management scheme in a fully automated scenario.

(Response) For the reasons stated in our response to comment 19, we believe that some degree of human oversight, supervision, verification, monitoring, or checking is a necessary part of CGMP for such processes and that there is added value in having greater assurance that the automated systems are operating properly as intended. We do not expect that each individual component change must be witnessed in person, but rather that a suitable system of human oversight be established and followed to effectively verify that the automated processes are indeed operating correctly in the performance of these operations.

(Comment 21) One comment maintained that our statement in the preamble of the direct final rule that the verifying individual may be, but is not required to be, the operator is a contradiction of the CGMP regulations, which require (in § 211.25(a)) that all individuals have the education, training, and experience to enable them to perform their assigned functions. The comment asked why the agency would allow an untrained operator to perform a sole verification of a critical step if an automated system is used and recommended that we retract the noted preamble statement.

(Response) The comment incorrectly concluded that allowing the verifying individual to be a person other than the operator would thereby allow an untrained individual to perform the function of verifying a critical step. Section 211.25(a) requires each person performing an assigned function to have the education, training, and experience, or any combination thereof, to enable that person to perform the function. Thus, any person, whether the operator or not, who performs such a verification step would necessarily be required to have the knowledge, training, and experience needed to perform that function. Therefore, our preamble statement does not conflict with the regulations.

(Comment 22) One comment stated that the proposed changes regarding second person verification should be extended to include § 211.188(a), which requires the preparation of batch production and control records that include an accurate reproduction of the appropriate master production or control record, checked for accuracy, dated, and signed. The comment stated that when there is only one signature needed, but the system is automated, it would also follow that no human signature or signature equivalent would be necessary, such as in issuance of a batch record under § 211.188(a), when the record is electronic. The comment also stated that in this case, it is impossible to check the pages for a true and accurate copy. The comment recommended revising § 211.68(c) to include § 211.188(a) in the listing of sections affected and to state that there could be single performance verification under § 211.188(a).

(Response) We do not agree with the recommended changes to § 211.188(a), which would eliminate any human verification of the records. As previously stated, we are clarifying in this rule that the checking of automated equipment by one person can satisfy the requirements of those regulations that address the performance of a step by one person and the verification of the step by a second person. Our proposal regarding verification of operations was intended to make clear that only one person is needed to verify that automated equipment for a processing step is functioning properly; we did not propose deleting all human verification of the step. In addition, we disagree with the comment's apparent contention that no human signature would be needed for issuance of electronic batch production and control records. If such records are generated and issued electronically as part of an automated system, a person must verify that the correct records were issued and that they are still accurate and complete. We believe it is clear that § 211.188(a) requires only one check for accuracy, with date and signature (which could be electronic), and that it does not require a separate second check of this step. Therefore, no changes to § 211.188(a) are necessary or appropriate.

(Comment 23) Three comments addressed second-person verification in § 211.194. Section 211.194(a) requires that laboratory records include complete data derived from all tests necessary to assure compliance with established specifications and standards as specified in that subsection. Section 211.194(a)(7) requires that laboratory records include the initials or signature of the person who performs each test and the date(s) the tests were performed. Section 211.194(a)(8) requires the initials or signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards. Two of the comments stated that the principle behind the proposed second-person verification revisions should be extended to § 211.194 to include checking laboratory records involving automated laboratory equipment. The first comment recommended revising § 211.194 generally. The second comment specifically recommended that § 211.194(a)(8) be revised to add that if laboratory tests have been performed by automated equipment under § 211.68, the laboratory record need only include the identification of one person conducting the review of the tests performed by the automated system. The comment also asked that § 211.194(a)(8) be added to the list of sections affected in § 211.68(c). The third comment stated that the failure to include § 211.194(a)(7) and (a)(8) in the proposed revisions implies that the use of automated systems to perform or check testing is not allowed.

(Response) We decline to include § 211.194 among the sections enumerated in § 211.68(c) concerning second-person verification of operations performed by automated equipment. We acknowledge that automated equipment may be used to conduct certain laboratory testing operations. However, when automated equipment is used to perform a laboratory test, typically a person initiates the test and ensures that the correct equipment is used and that it operates properly. In this situation, one person assists in or oversees the performance of the laboratory test and a second person reviews the records for accuracy, completeness, and compliance with established standards. Thus, the use of equipment to perform laboratory tests, though permissible, is not a situation in which automated equipment (rather than a person) performs an operation and a person verifies that performance, which is the situation addressed in revised § 211.68(c). Therefore, it would not be appropriate to include a reference to § 211.194 (or to § 211.194(a)(8) specifically) in revised § 211.68(c).

(Comment 24) One comment stated that § 211.68 is no longer in line with the technological improvements of the past 30 years and with the increasing knowledge of computer validation by industry and regulators. The comment recommended that § 211.68 be aligned with 21 CFR 820.70(i), section 5.4 of the ICH Q7A guidance entitled “Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients,” and the Pharmaceutical Inspection Cooperation Scheme's Annex 11 on computerized systems.

(Response) We decline to adopt the suggested revisions because they exceed the scope of our proposed revision of § 211.68, which only addressed second-person verification of operations performed by automated equipment. We might consider revising other provisions of § 211.68 as part of a future rulemaking to update the CGMP regulations and make them consistent with international CGMP provisions.

(Comment 25) One comment recommended that instead of our proposed changes to § 211.68(c) and other regulations concerning second-person verification, we revise § 211.68(a), which permits the use of automatic, mechanical, or electronic equipment in the manufacture, processing, packing, and holding of drug products. The comment stated that the wording of our proposed changes only allows for actions to be performed by automated equipment and checked by a person, which would prevent the introduction of automated systems to check operations performed by a person. The comment also stated that our proposed changes would still require the involvement of at least one person in each of these circumstances and prevent the use of a controlled system or systems that both perform and independently verify the relevant operations. One comment suggested that rather than our proposed revisions, the desired clarification concerning automated equipment and second-person checks would be better achieved by adding to § 211.68(a) the following sentence: “Automated equipment can satisfy the requirements for the performance of an operation by one person and/or checking by another person.”

(Response) We do not agree with the recommended change. The proposed rule simply clarified our longstanding position that only one human check is necessary to verify a processing step performed by automated equipment. The suggested revision of § 211.68(a), however, would allow manufacturers to rely solely on automated equipment to verify the human performance of certain processing steps and allow automated equipment to both perform and check operational steps, which would constitute a significant change from the current regulations. As stated in our response to comment 19, we believe that human verification of certain processing steps, even when those steps are performed by automated equipment, is still necessary.

(Comment 26) One comment stated that although proposed § 211.68(c) implies that the automated equipment is doing the work and a person can verify that the work is done, there are cases in which a person does the work and automated equipment might be able to verify the person's work. The comment cited as an example the case in which an automated system scans the bar codes of ingredients and equipment to ensure that the ingredient is correct for use with the equipment for that step in the process, but the physical addition of the ingredient is by the human operator (followed by the automated system scanning). The comment recommended, therefore, that § 211.68(c) be modified to allow both the automated system and the person to do either the performance or the verification tasks for the operations addressed by §§ 211.101(c) or (d), 211.103, 211.182, 211.188(b)(11), or 211.194(a)(8), or a single performance verification in the case of § 211.188(a).

(Response) We acknowledge that it might be possible to design an automated system to verify operations performed by humans, but as stated in our response to comment 19, we continue to believe that some human verification of the processing steps performed by an automated system is necessary.

(Comment 27) One comment suggested revising § 211.68(c) to state that automated equipment can satisfy the requirements for verification of operations addressed by the listed sections as follows: (1) If such unit operation is fully automated, no manual verification is necessary and (2) if there is an operator for the automated equipment, the verifying individual may be, but is not required to be, the operator. The comment gave several reasons for this change:

• Automated, validated systems equipped with real-time alarms that do not require any human intervention should not require human verification because § 211.68(a) adequately addresses the maintenance and verification of performance of these systems.

• The need and type of verification required should be consistent with the level of automation used. For example, operations that are not fully automated and require operator participation may serve as verification of the operator's activities, while fully manual operations would require a second human verification.

• As proposed, § 211.68(c) might hinder the adoption of PAT (e.g., there would be no value added by manual verification when components are charged in a fully automated manner according to a validated algorithm).

(Response) As stated in our response to comment 19, we do not agree with the contention that no human verification is necessary when fully automated systems are used, and we therefore decline to make these requested changes to § 211.68(c). We also do not believe that § 211.68(c) will hinder the adoption of PAT. As stated in the preamble to the direct final rule, we agree that if there is an operator for the automated equipment, the verifying individual may be, but is not required to be, the operator. However, § 211.68(c) does not require that the verifying individual be the operator, and we do not believe that it is necessary that the provision explicitly state that the verifying individual need not be the operator.

(Comment 28) One comment stated that the proposed revision of § 211.68(c), when applied to § 211.188(b), might be more restrictive than FDA's position in Compliance Policy Guide (CPG) Sec. 425.500, Computerized Drug Processing; Identification of “Persons” on Batch Production and Control Records (formerly CPG 7132a.08). CPG 425.500 states that when significant steps in the manufacturing, processing, packing, or holding of a batch are performed, supervised, or checked by a computerized system, an acceptable means of complying with the identification requirements in § 211.188(b)(11) would consist of conformance to certain requirements. The comment maintained that CPG 425.500 gives companies the flexibility to automate not only the performance of critical actions but also the supervision and checking of these actions if it is shown that the efficacy of these controls would be at least equivalent to the level of efficacy if the verification were done by a second person. The comment stated that this flexibility should be extended to all CGMP sections in which a verification is requested. The comment therefore asked that § 211.68(c) be revised to state that automated equipment used for performance of operations addressed by §§ 211.101(c) or (d), 211.103, 211.182, or 211.188(b)(11) can satisfy the requirements included in those sections for the performance of an operation by one person and checking by another person if such equipment is used in conformity with § 211.68 and one person either performs the operations addressed in those sections under the control of the automated equipment or verifies that these operations are performed accurately by such equipment.

(Response) We do not agree with the comment's apparent interpretation of CPG 425.500 that the CPG allows for elimination of human oversight. The purpose of the CPG is to explain what constitutes “identification” of persons in batch records under § 211.188(b)(11) when automated systems are used for various functions. The CPG states that when an automated system is used to perform, directly supervise, or check significant steps in the production of a drug, the identification requirements in § 211.188(b)(11) are met if there is documentation that the system contains adequate checks (and documentation of the performance of the system itself), validation of the system's performance, and recording of specific checks in batch records (including initial, branching, and final steps). These conditions for applying the identification requirements to steps using automated equipment involve the responsibilities of persons. For example, a person, rather than automated equipment, is needed to record these checks of production steps in batch records. Therefore, contrary to the comment's implication, the CPG does not state that human oversight is unnecessary when an automated system is involved in the performance, supervision, or checking of production steps. All automated systems require some level (commensurate with the complexity and risk inherent in the system) of human oversight or checking for expected performance at appropriate intervals. Therefore, we decline to revise § 211.68(c) as recommended.

(Comment 29) One comment, although supportive of the proposal to allow initial activities to be performed by automated equipment, objected to requiring that the output of an automated and adequately validated activity be checked for accuracy by a person. The comment maintained that the act of having validated software and its related processes itself constitutes an independent check that operations are being performed accurately and argued that this is more reliable than any contemporaneous check by a person. The comment therefore asked that § 211.68(c) be changed to state that independent checks may consist of contemporaneous analysis and verification by a second person following completion of the activity; or, where the automated process has been validated to a high degree of confidence, the prior validation can satisfy this requirement and a second person's check may then consist of verifying the validated status of the equipment and processes.

(Response) We do not agree with the suggested change. Although we agree that it is an important part of process controls to ensure the validated status of equipment and processes even before they are used, we do not believe that verifying this validated status can satisfy the requirement for checking the actual performance of automated equipment. However, we believe that the requirement in proposed § 211.68(c) that one person “verifies that the operations * * * are performed accurately” by automated equipment may have led some comments to believe that we were requiring a more specific and detailed repetitive type of check than we intended. When automated equipment is used for operations addressed by revised § 211.68(c) in conformance with § 211.68, the person doing the checking must verify that the automated equipment is functioning properly and that the operations are reliably performed in the intended manner. As discussed in the response to comment 19, the nature and frequency necessary for such verification will vary depending on the level of automation used as well as the nature of the system and controls. We do not expect that it will normally be necessary, under § 211.68(c), for a person to repeat all of the automatic calculations by hand to ensure their accuracy. Therefore, we have revised § 211.68(c) to clarify that automated equipment can be used to perform an operation when the performance is checked by a person provided that “such equipment is used in conformity with this section [§ 211.68] and one person checks that the equipment properly performed the operation.”

Section 211.101 concerns charge-in of components. Proposed § 211.101(c) stated, in part, that if the weighing, measuring, or subdividing operations for components are performed by automated equipment under § 211.68, only one person is needed to ensure that the requirements in § 211.101(c)(1), (c)(2), and (c)(3) are met.

(Comment 30) One comment proposed broadening § 211.101(c) to clarify that the weighing, measuring, and subdividing operations could be either performed by automated equipment or checked by automated equipment after being performed manually.

(Response) We decline to make this suggested change for the reasons provided in response to comments 19 and 25. Revised § 211.101(c) only permits human checking of weighing, measuring, and subdividing operations performed by automated equipment; we did not propose to allow automated checking of these operations. We continue to believe that human verification of these processing steps is necessary.

(Comment 31) One comment stated that with respect to medical gases, there is no measurement of components to be dispensed for manufacturing that needs to be double-checked to ensure that the right quantity of the right component was added, because transfers of pure gases are within product-specific systems. However, the comment stated, with respect to gas mixtures, it is appropriate to have a verification of hook-ups as different components are added unless there is subsequent purity testing for each component.

(Response) We decline to exempt single gas filling operations from certain requirements of § 211.101(c) as recommended because such a change would exceed the scope of our proposed change to § 211.101(c), which only addressed human checking of weighing, measuring, and subdividing operations performed by automated equipment. We might consider in a future rulemaking whether it is appropriate to exempt medical gases from certain requirements of § 211.101(c).

Proposed § 211.101(d) would have required that each component be either added to the batch by one person and verified by a second person or, if the components are added by automated equipment under § 211.68, only verified by one person.

(Comment 32) One comment stated that eliminating a double check for adding materials to a batch is problematic because an error in those operations would be difficult to detect and might not be discovered before the product is distributed, which could result in patient injury and product recall. The comment recommended deleting or modifying the ability to use a sole verifier for operations involving addition of materials.

(Response) The comment appears to suggest that we proposed to eliminate the requirements concerning verification that appropriate components were added to a batch. The revisions we are adopting do not eliminate the requirement to verify performance in § 211.101(d); they simply codify our longstanding policy that components may be added either by a person or by suitable automated equipment. The addition of components still must be checked by a person.

(Comment 33) One comment stated that under the proposed change to § 211.101(d), if a validated system performs a function, it is acceptable for one person to verify that action, but if an automated system prompts an operator to perform a function, a second person would be required to confirm the proper execution of the action. The comment recommended changing § 211.101(d) to state that each component must be added to the batch by one person and verified by a second person, “unless the components are added by automated equipment under § 211.68, in which case verification can be performed by one person.”

(Response) We decline to accept the suggested change because we do not believe that it constitutes a substantive difference from the language of proposed § 211.101(d). It is irrelevant whether use of a particular automated system for component charge-in requires an operator to perform a related function; in either case, verification of the charge-in operation(s) must be performed by a person.

(Comment 34) One comment recommended changing § 211.101(d) to specify that the weighing, measuring, or subdividing operations might be performed by automated equipment or checked by automated equipment after being performed manually. The comment also stated that in many instances, the verification by a person of actions performed by automated equipment can only be done on the basis of outputs from the equipment. As an example, the comment stated, when the introduction of components in a liquid production line is fully automated, there is no possibility for the operator to check that the correct amount of materials was incorporated into the batch other than by relying on information given by the same automated equipment. The comment stated that in that case, the verification would consist of confirming that the component's incorporation process was completed without errors or alarms.

(Response) We decline to make this suggested change for the reasons stated in response to comments 19 and 25. Revised § 211.101(d) only permits human checking of component additions performed by automated equipment; we did not propose to allow automated checking of component additions performed by humans. In the example given in the comment, human verification that components were properly added to the liquid production line by the automated equipment would be needed to ensure that the equipment performed properly. We continue to believe that human verification of this processing step is necessary.

We proposed, in § 211.103, to require that calculations of actual yields and percentages of theoretical yields be performed by one person and independently verified by a second person or, if the yield is calculated by automated equipment under § 211.68, be independently verified by one person.

(Comment 35) One comment stated that it is not necessary to have a person recalculate a yield manually after a validated system does it automatically. The comment asked that § 211.103 be revised to limit the human interaction to data entry and data verification, but not recalculation of yields if yields are calculated by a validated, automated system. A similar comment stated that § 211.103 should be changed to state that if the yield is calculated by automated equipment, a person must verify the data entries, rather than regenerate the calculations.

(Response) We do not believe that the recommended changes are needed or appropriate. Revised § 211.103 does not require that all yield calculations be repeated manually. Manual recalculation might be a suitable approach to verifying yield calculations, but § 211.103 also permits the use of other approaches, including verification that automated equipment functioned properly while performing yield calculations.

(Comment 36) One comment reiterated the views expressed in its comments on the CGMP for medical gases draft guidance. Thus, the comment requested that the requirements for yield calculation in § 211.103 not be applied to medical gases because of the atmospheric-gas-separation and cylinder-filling processes associated with medical gases. In further support of its position, the comment referred to an FDA publication (Human Drug CGMP Notes, vol. 5, no. 2, June 1997) in which the agency stated that it would propose to revise the CGMP regulations to exempt medical gases from the requirements for yield reconciliation.

(Response) We decline to exempt medical gases from the requirements for yield calculation in § 211.103 as recommended because this would exceed the scope of our proposed change to § 211.103, which addressed only human checking of yield calculations performed by automated equipment. We might consider in a future CGMP rulemaking whether it is appropriate to exempt medical gases from certain requirements of § 211.103. In addition, we might consider providing specific recommendations to medical gas manufacturers to help them comply with the requirements for calculating yields in the course of finalizing the draft guidance on CGMP for medical gases.

We proposed, in § 211.182, to require the persons performing and double-checking equipment cleaning and maintenance (or, if the cleaning and maintenance is performed using automated equipment under § 211.68, only the person verifying the cleaning and maintenance done by the automated equipment) to date and sign or initial the log indicating that the work was performed.

(Comment 37) One comment stated that eliminating a double check for cleaning equipment is problematic because an error in those operations would be difficult to detect and might not be discovered before the product is distributed, which could result in patient injury and product recall. The comment recommended deleting or modifying the ability to use a sole verifier for operations involving equipment cleaning.

(Response) The comment appears to suggest that we proposed to eliminate the requirements concerning verification that equipment was appropriately cleaned and maintained. The revisions we are adopting do not eliminate the requirement to verify performance in § 211.182; they simply codify our longstanding policy that equipment may be cleaned and maintained either by a person or by suitable automated equipment. Cleaning and maintenance of equipment must still be checked by a person.

(Comment 38) One comment stated that operations addressed by §§ 211.182 and 211.188(b)(11) are often performed using semi-automated equipment that requires an operator to select the correct menu. The comment stated that major pieces of equipment such as “Clean in Place” (CIP) skids and vial washers often require the operator to select the appropriate process menu before the execution of the actual automated cycle by the equipment's controller. The comment asked whether, when operator input is necessary to select but not perform an operation, the signature of the operator selecting the menu is required in cases when there is a second signature that verifies the performance of the cycle. One comment requested that we verify in § 211.182 or the preamble of the final rule that a single verification remains sufficient when automated but portable cleaning skids are used.

(Response) We do not believe that initiation of the automated cleaning cycle by a human operator constitutes performance of the cleaning process for purposes of revised § 211.182. The revised regulation requires that after an automated cleaning process (such as CIP) is completed, the human operator must date and sign or initial the log verifying that the equipment performed the automated cleaning process properly. The regulation does not require the operator to date and sign or initial the log simply for the initiation of the automated cleaning cycle. This approach applies to both portable equipment skids and fixed equipment.

(Comment 39) One comment stated that in many instances, the human verification of an action performed by automated equipment can only be done on the basis of outputs from the equipment. As an example, the comment stated, when equipment is cleaned through CIP, the verification should consist of confirming that the system reports the cleaning as successfully completed without alarms.

(Response) What constitutes adequate verification that equipment has been properly cleaned or maintained using automated equipment in accordance with revised § 211.182 depends on the particular circumstances. The outputs from the automated equipment will normally be key factors, but not necessarily the only ones. The manufacturer should determine the reliability of the outputs and periodically check them. For example, it might be appropriate to verify that an alarm is working properly and is successfully monitoring the equipment's critical functions. There might be other ways of verifying the adequate performance of cleaning and maintenance by automated equipment, such as by monitoring the usage of cleaning supplies in a cleaning cycle or conducting an independent check of the rinse.

(Comment 40) One comment stated that for most medical gas systems, routine or periodic cleaning is not performed because the industry is characterized by product-specific closed systems that undergo an appropriate cleaning process before initial use. The comment stated that because of the high number of batches produced on a weekly/monthly basis in the medical gas industry, it is more appropriate to keep cleaning and maintenance records separate from batch records. The comment maintained that although requiring documentation of equipment cleaning, maintenance, and use in individual equipment logs may be appropriate for traditional pharmaceuticals (where key processing equipment may be used for multiple products and lot numbers), applying this requirement to medical gases would make retrieval and management of cleaning and maintenance records much more difficult. The comment added that use logs are not appropriate for medical gases because batch record documentation provides a consecutive listing of products manufactured on each system.

(Response) We decline to exempt medical gases from certain requirements of § 211.182 as recommended because this would exceed the scope of our proposed change to § 211.182, which addressed human verification of cleaning steps performed by automated equipment. We might consider in a future CGMP rulemaking whether it is appropriate to exempt medical gases from certain requirements of § 211.182.

Section 211.188 concerns batch production and control records. Proposed 211.188(b)(11) specified that when a significant step in the operation is performed by automated equipment under § 211.68, the record would need to identify the person checking the significant step performed by the automated equipment.

(Comment 41) One comment stated that § 211.188(b)(11) should be changed to state that a significant manufacturing step could be either performed or checked by automated equipment. The comment stated that this approach is permitted by CPG 425.500.

(Response) We decline to make this suggested change. As stated in our response to comment 28, CPG 425.500 does not, as the comment implies, state that human oversight is unnecessary when an automated system is involved in the performance, supervision, or checking of production steps. To revise § 211.188(b)(11) as recommended by the comment might be interpreted as permitting manufacturers to rely solely on automated equipment to verify the human performance of certain production steps. As stated in our response to comments 19 and 25, we believe that human verification of processing steps is still necessary.

We proposed to make miscellaneous minor changes to CGMP regulations to clarify certain manufacturing, quality control, and documentation requirements and to align the regulations with industry practice.

The version of § 211.82(b) amended by this final rule stated: “Components, drug product containers, and closures shall be stored under quarantine until they have been tested or examined, as appropriate, and released.” We proposed to replace the phrase “as appropriate” with the phrase “whichever is appropriate” to eliminate any ambiguity in § 211.82(b) and to emphasize that it is accepted industry practice to conduct some testing or examination before components, drug product containers, or closures are released from quarantine.

(Comment 42) One comment requested that medical gas container-closure assemblies returned from customers and reused be exempted from § 211.82(b). The comment stated that assembled cylinder/valve medical gas combinations are reused and handled differently than they would be at the time of initial receipt. The comment stated that returned assemblies are individually inspected for all critical quality issues immediately before filling; those assemblies that do not meet the inspection criteria are moved to a quarantine area. The comment stated that this practice satisfies the intention that components, containers, and closures be inspected to ensure that unacceptable assemblies are not used in the manufacturing process.

(Response) Under revised § 211.82(b), manufacturers of medical gases would retain the ability to sequester and inspect returned valve/cylinder assemblies before refilling in accordance with the industry practice described by the comment. The practice described by the comment is to have the assembled valve/cylinders placed in a segregated area (apparently not identified using the word “quarantine”), examined for conformance to quality standards, and, if the criteria are met, immediately made available for refilling. This practice would meet the requirement for a quarantine status if goods in such areas or under such a status are not acceptable for use as-is unless and until they are qualified to be suitable for use. Therefore, we do not believe that the practice as described violates revised § 211.82(b), and there is no need to exempt medical gas manufacturers from this requirement.

The version of § 211.84(c)(1) amended by this final rule stated: “The containers of components selected [for sampling] shall be cleaned where necessary, by appropriate means.” We proposed to replace the phrase “where necessary, by appropriate means” with the phrase “when necessary in a manner to prevent introduction of contaminants into the component.” This change was intended to clarify that the act of cleaning is done for a particular purpose—to prevent the introduction of contaminants—and must be done unless cleaning is not necessary to prevent contamination.

(Comment 43) One comment expressed concern that the proposed change might be interpreted to require validation of this prevention of contamination during sampling. The comment requested that we confirm that our intent is to place the contamination concern into the controls and procedures for sampling and into the training of staff who perform these activities, rather than to require validation of the absence of contamination.

(Response) Revised § 211.84(c)(1) does not require manufacturers to conduct validation studies to prove that the method of sampling prevents contamination. When properly designed and followed, the cleaning procedures, training, and facility and equipment controls, along with supervisory and quality unit oversight, should ensure compliance with § 211.84(c)(1).

We proposed minor editorial changes to two regulations, §§ 211.84(d)(3) and 211.160(b)(1). The version of § 211.84(d)(3) amended by this final rule stated: “Containers and closures shall be tested for conformance with all appropriate written procedures.” We proposed to replace the word “conformance” with “conformity” and the word “procedures” with “specifications.” The first sentence of the version of § 211.160(b)(1) amended by this final rule stated: “Determination of conformance to appropriate written specifications for the acceptance of each lot within each shipment of components, drug product containers, closures, and labeling used in the manufacture, processing, packing, or holding of drug products.” We proposed to replace the word “conformance” with “conformity” and the word “appropriate” with “applicable.” We stated in the preamble to the direct final rule that these revisions would provide clarity without changing the meaning or intent of these regulations. We received no comments on these proposed changes, and we have revised these provisions as proposed.

FDA has examined the impacts of this final rule under Executive Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive Order 12866 directs agencies to assess all costs and benefits of available regulatory alternatives and, when regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health and safety, and other advantages; distributive impacts; and equity). The agency believes that this final rule is not a significant regulatory action as defined by the Executive order, because the rule either clarifies the agency's longstanding interpretation of, or increases latitude for manufacturers in complying with, existing CGMP requirements.

The Regulatory Flexibility Act requires agencies to analyze regulatory options that would minimize any significant impact of a rule on small entities. Because this final rule does not impose any new regulatory obligations, the agency believes that the rule will not have a significant economic impact on a substantial number of small entities.

Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires that agencies prepare a written statement, which includes an assessment of anticipated costs and benefits, before proposing “any rule that includes any Federal mandate that may result in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted annually for inflation) in any one year.” The current threshold after adjustment for inflation is $127 million, using the most current (2006) Implicit Price Deflator for the Gross Domestic Product. This rule does not result in any 1-year expenditure that would meet or exceed this amount.

The purpose of this final rule is to update the codified language to reflect current practice and to harmonize requirements in the CGMP regulations with requirements in other regulations and with international CGMP standards. It does not impose any additional requirements; therefore, industry will not incur incremental compliance costs for these proposed changes.

FDA concludes that issuing these clarifying amendments to the CGMP regulations will not have a significant impact on the human environment. Therefore, an environmental impact statement is not required.

FDA has analyzed this final rule in accordance with the principles set forth in Executive Order 13132. We have determined that the rule does not contain policies that have substantial direct effects on the States, on the relationship between the National Government and the States, or on the distribution of power and responsibilities among the various levels of government. Accordingly, we have concluded that the rule does not contain policies that have federalism implications as defined in the Executive order and, consequently, a federalism summary impact statement is not required.

This final rule contains collections of information that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520) (the PRA). The collections of information (recordkeeping requirements) in part 211 have already been approved by OMB under control number 0910-0139. The final rule amends certain sections of part 211 as well as § 210.3 (§ 210.3 does not contain information collection requirements). As concluded in section IV of this document, “Analysis of Impacts,” the purpose of the final rule is to update the regulations to reflect current practice and to harmonize requirements in the CGMP regulations with requirements in other regulations and with international CGMP standards. The final rule does not impose any additional requirements. Thus, because the final rule does not substantively revise the information collection requirements in part 211 or add new information collection requirements, there is no need to conduct an analysis under the PRA.

Electronic Availability

This document and additional information concerning OFAC are available from OFAC's Web site ( http://www.treas.gov/ofac ) or via facsimile through a 24-hour fax-on-demand service, tel.: (202) 622-0077.

Because this interim final rule imposes no obligations on any person, but only explains OFAC's enforcement policy and procedures based on existing substantive rules, prior notice and public comment are not required pursuant to 5 U.S.C. 553(b)(A). Because no notice of proposed rulemaking is required, the provisions of the Regulatory Flexibility Act (5 U.S.C. chapter 6) do not apply. This interim final rule is not a significant regulatory action for purposes of Executive Order 12866.

Although a prior notice of proposed rulemaking is not required, as discussed in more detail below, OFAC is soliciting comments on this interim final rule in order to consider how it might make improvements to these Guidelines. Comments must be submitted in writing. The addresses and deadline for submitting comments appear near the beginning of this notice. OFAC will not accept comments accompanied by a request that all or part of the submission be treated confidentially because of its business proprietary nature or for any other reason. All comments received by the deadline will be a matter of public record and will be made available to the public via regulations.gov.

The collections of information related to the Reporting, Procedures and Penalties Regulations have been previously approved by the Office of Management and Budget (OMB) under control number 1505-0164. A small adjustment to that collection has been submitted to OMB in order to take into account the voluntary self-disclosure process set forth in these Guidelines. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a valid control number assigned by OMB. This collection of information is described in subpart F of Part I, subpart G of part III and subpart B of part V of these Guidelines, which will constitute the new Appendix to part 501. The referenced subparts explain that the voluntary self-disclosure of an apparent violation to OFAC will be considered in determining the appropriate agency response to the apparent violation and, in cases where a civil monetary penalty is deemed appropriate, the base penalty amount and the proposed penalty amount. As set forth in subpart B of part V of the Guidelines, an apparent violation involving a voluntary self-disclosure will result in a base penalty amount at least 50 percent less than the base penalty amount in similar cases that do not involve a voluntary self-disclosure. This provides an incentive for persons who have or may have violated economic sanctions laws to come forward and provide OFAC information that it can use to better enforce its economic sanctions programs. The submitters who will likely seek to avail themselves of the benefits of voluntary self-disclosure are financial institutions, businesses, other entities, and individuals who find that they have or may have violated a sanctions prohibition and wish to disclose their actual or potential violation.

The estimated total annual reporting and/or recordkeeping burden: 1,250 hours. The estimated annual burden per respondent/record keeper: 10 hours. Estimated number of respondents and/or record keepers: 125. Estimated annual frequency of responses: Once or less, given that OFAC expects that persons who voluntarily self disclose their violations will take better care to avoid future violations. Comments are invited on: (a) Whether this collection of information is necessary for the proper performance of the functions of the agency, including whether the information has practical utility; (b) the accuracy of the agency's estimate of the burden of the collection of information; (c) ways to enhance the quality, utility, and clarity of the information to be collected; (d) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques or other forms of information technology; and (e) estimates of capital or start-up costs and costs of operation, maintenance, and purchase of services to provide information. Comments concerning the above information, the accuracy of the estimated average annual burden, and suggestions for reducing this burden should be directed to OMB, Paperwork Reduction Project, control number 1505-0164, Washington, DC 20503, with a copy to the Office of Foreign Assets Control, Department of the Treasury, 1500 Pennsylvania Ave., NW., Washington, DC 20220. Any such comments should be submitted no later than November 7, 2008. Comments on aspects of this rule other than those involving collections of information subject to the Paperwork Reduction Act should not be sent to OMB.

The primary mission of OFAC is to administer and enforce economic sanctions against targeted foreign countries and regimes, terrorists and terrorist organizations, weapons of mass destruction proliferators, narcotic traffickers, and others in furtherance of U.S. national security, foreign policy, and economic objectives. OFAC acts under Presidential national emergency powers, as well as specific legislation, to prohibit transactions and block (or “freeze”) assets subject to U.S. jurisdiction. Economic sanctions are designed to deprive the target of the use of its assets and deny the target access to the U.S. financial system and the benefits of trade, transactions, and services involving U.S. markets, businesses, and individuals. These same authorities have also been used to protect assets subject to U.S. jurisdiction of countries subject to foreign occupation and to further important U.S. nonproliferation goals.

OFAC administers and enforces economic sanctions programs pursuant to Presidential and statutory authorities. OFAC is responsible for civil investigation and enforcement of economic sanctions violations committed by Subject Persons, as defined in the Guidelines. Where appropriate, OFAC may coordinate its investigative and enforcement activities with federal, state, local and/or foreign regulators and/or law enforcement agencies. Active enforcement of these programs is a crucial element in preserving and advancing the national security, foreign policy and economic objectives that underlie these initiatives. Penalties, both civil and criminal, serve as a deterrent to conduct that undermines or prevents these sanctions programs from achieving their various goals.

On January 29, 2003, OFAC published, as a proposed rule, generally applicable Economic Sanctions Enforcement Guidelines, as well as a proposed Appendix to the Cuban Assets Control Regulations (CACR) providing a schedule of proposed civil monetary penalties for certain violations of the CACR (Cuba Penalty Schedule). Though this proposed rule was not finalized, OFAC has used the generally applicable guidelines set forth therein as a general framework for its enforcement actions and the Cuban Penalty Schedule as a framework for the imposition of civil monetary penalties for the violations of the CACR described therein. On January 12, 2006, OFAC published, as an interim final rule, Economic Sanctions Enforcement Procedures for Banking Institutions which withdrew the January 29, 2003 proposed rule to the extent that it applied to banking institutions, as defined in the interim final rule.

On October 16, 2007, the President signed into law the International Emergency Economic Powers Enhancement Act (Enhancement Act), 3 substantially increasing the maximum penalties for violations of the International Emergency Economic Powers Act (IEEPA), 4 a principal statutory authority for most OFAC sanctions programs. The increased maximum penalty amounts set forth in the Enhancement Act, as well as its application to pending or commenced cases involving apparent violations of IEEPA, prompted the development of these new Guidelines for determining an appropriate enforcement response to apparent violations of sanctions programs enforced by OFAC (as defined in the Guidelines), and, in cases involving civil monetary penalties, for determining the amount of any civil monetary penalty. The Guidelines set forth in this interim final rule supersede the enforcement procedures for banking institutions set forth in the interim final rule of January 12, 2006, which is hereby withdrawn, as well as the proposed guidelines set forth in the proposed rule of January 29, 2003, which is also hereby withdrawn, with the exception of the Cuba Penalty Schedule. (Those withdrawn enforcement procedures and guidelines continue to apply to the categories of cases set forth in OFAC's November 27, 2007 Civil Penalties—Interim Policy.) The Guidelines set forth herein are applicable to all persons subject to any of the sanctions programs administered by OFAC. As discussed in greater detail below, OFAC requests comments on this interim final rule. The Guidelines set forth in this interim final rule are not applicable to penalty or enforcement actions by other agencies based on the same underlying course of conduct, the disposition of goods seized by Customs and Border Protection, or the release of blocked property by OFAC.

The Guidelines set forth in this interim final rule are applicable to all enforcement matters currently pending before OFAC or that will come before OFAC in the future, whether such matters fall under IEEPA or any of the other statutes pursuant to which OFAC is authorized to enforce sanctions (including, but not limited to, the Trading With the Enemy Act), with the exception of (i) those categories of cases set forth in OFAC's November 27, 2007 Civil Penalties—Interim Policy and (ii) those matters addressed in the Cuba Penalty Schedule or the Service Provider Program Circular periodically issued by OFAC pursuant to the CACR. The Guidelines reflect the factors that OFAC will consider in determining the appropriate enforcement response to an apparent violation of an OFAC sanctions program, and those factors are consistent across programs. The civil penalty provisions of the Guidelines take into account the maximum penalties available under the various statutes pursuant to which OFAC is authorized to enforce its sanctions programs.

The Guidelines reflect several changes from the 2003 proposed rule and the 2006 interim final rule. First, rather than identifying “aggravating” and “mitigating” factors, the Guidelines set forth General Factors that OFAC will consider in determining an appropriate enforcement response to an apparent violation and, if a civil monetary penalty is warranted, in establishing the amount of that penalty. The General Factors reflect the considerations that OFAC believes are most critical to a determination of appropriate agency action. The move away from “aggravating” and “mitigating” factors was motivated in part by the realization that in many cases, a particular factor could be considered either aggravating or mitigating (e.g., remedial action was considered a mitigating factor in the 2003 proposed rule, while the absence of remedial action was considered an aggravating factor). Rather than list such factors as both aggravating and mitigating factors, OFAC believes it is better practice to identify the General Factors it will consider as part of a holistic consideration of the facts and circumstances of a particular case.

Second, the Guidelines provide for the issuance of either cautionary letters or findings of violation under certain circumstances, rather than the cautionary letters and warning letters provided for in the 2003 proposed rule and the evaluative letters provided for in the 2006 interim final rule. Cautionary letters reflect OFAC's enforcement response to an apparent violation when OFAC determines either that there is insufficient evidence to conclude that a violation has occurred or that a finding of violation is not warranted under the circumstances. A cautionary letter does not constitute a final agency determination that a violation has or has not occurred, but serves to place the Subject Person on notice that any such similar conduct in the future may result in a finding of violation or the imposition of a civil monetary penalty. Findings of violation are reserved for cases in which OFAC determines that a violation has occurred and considers it important to document the occurrence of a violation, but nevertheless concludes that the imposition of a civil monetary penalty is not the most appropriate enforcement response. Because a finding of violation constitutes a final agency determination that a violation has occurred, OFAC will afford the Subject Person an opportunity to respond to OFAC's determination. OFAC will give careful consideration to the appropriateness of issuing a cautionary letter or finding of violation in lieu of the imposition of a civil monetary penalty.

Third, in recognition of OFAC's position that the enhanced maximum civil penalties authorized by the Enhancement Act should be reserved for the most serious cases, the Guidelines distinguish between egregious and non-egregious civil monetary penalty cases. Egregious cases are defined as those representing the most serious sanctions violations, based on an analysis of all applicable General Factors, with substantial weight given to considerations of willfulness or recklessness, awareness of the conduct giving rise to an apparent violation, harm to sanctions program objectives, and the individual characteristics of the Subject Person. As described below, the Guidelines generally provide for significantly higher civil penalties for egregious cases. OFAC anticipates that the majority of enforcement cases will fall in the non-egregious category.

Fourth, in those cases in which the imposition of a civil monetary penalty is deemed appropriate, the Guidelines provide a new process for determining the penalty amount. This process involves first determining a base penalty amount. This base penalty amount is based on two primary considerations: (i) Whether the conduct, activity, or transaction giving rise to a violation is egregious or non-egregious and (ii) whether the case involves a voluntary self-disclosure by the Subject Person. As discussed above, egregious cases are generally subject to significantly higher penalties, a result reflected in the base penalty amount for such cases. In keeping with the previous enforcement guidelines and in recognition of the importance of voluntary self-disclosures to OFAC, the existence (or lack) of a voluntary self-disclosure is a major factor in establishing the penalty amount. The base penalty amount for a case involving a voluntary self-disclosure reflects a 50 percent or more reduction from the base penalty amount that would otherwise be applicable. As set forth in greater detail in the Guidelines themselves, once a base penalty amount is calculated based on the transaction value and egregiousness/voluntary self-disclosure factors, the amount may be adjusted upward or downward based on the other General Factors set forth in the Guidelines. The resulting amount reflects OFAC's proposed civil monetary penalty.

Pre-penalty notices issued pursuant to these Guidelines will set forth the actual civil monetary penalty that OFAC proposes to impose. Thus, the pre-penalty notice will provide a Subject Person with notice of the actual penalty that the agency deems appropriate under the circumstances, rather than merely identifying the maximum possible penalty. Subject Persons will be afforded an opportunity to respond to a pre-penalty notice with arguments and/or evidence respecting the amount of the proposed penalty, which OFAC will consider prior to issuing a final penalty notice. By adopting this approach, OFAC intends to bring greater transparency to the civil penalty process and to provide more useful notice to Subject Persons that may be subject to a civil monetary penalty.

The Guidelines also address the process for settling allegations of violations.

Although this interim final rule is effective immediately, OFAC is soliciting comments for a 60-day period with a view to improving the Guidelines. Comments are requested on all aspects of the Guidelines, but are particularly sought with respect to the following:

• Are the General Factors Affecting Administrative Action the appropriate factors the agency should consider in determining the type of enforcement response to an apparent violation, and, if a civil monetary penalty is warranted, the amount of that penalty? Are there other factors that should be identified in the Guidelines? Are there factors that should be eliminated? Are there factors that should be defined with greater specificity?

• Is the definition of an egregious case appropriate?

• Are the proposed base penalty amounts appropriate for the types of cases to which they are applicable?

• Does the new penalty process, whereby the pre-penalty notice sets forth the penalty that OFAC proposes to impose, constitute an improvement on current practice? Can the process be improved in other ways?

On May 29, 2008 we published a notice of proposed rulemaking (NPRM) entitled Safety Zone; Gulf of Mexico—Johns Pass, FL in the Federal Register , 73 FR 30868. We did not receive any letters commenting on the proposed rule. No public meeting was requested, and none was held.

Flatiron Construction will be performing construction work on the new Johns Pass Bridge. This work will involve setting girders, installing a new fendering system, setting the deck, setting overhangs, placing resteel, pouring the bridge deck, and wrecking the old bridge's deck. These operations will require the closure of the navigable channel. The closures will only be for limited times, during nighttime hours, and scheduled to accommodate the local marine traffic. The nature of the operation and environment surrounding the Johns Pass Bridge presents a danger to the workers and mariners transiting the area. This proposed safety zone is being established to ensure the safety of life on the navigable waters of the United States.

No comments were received for this rule and no changes were made to the proposed rule text.

We developed this rule after considering numerous statutes and executive orders related to rulemaking. Below we summarize our analyses based on 13 of these statutes or executive orders.

This rule is not a significant regulatory action under section 3(f) of Executive Order 12866, Regulatory Planning and Review, and does not require an assessment of potential costs and benefits under section 6(a)(3) of that Order. The Office of Management and Budget has not reviewed it under that Order. We expect the economic impact of this rule to be so minimal that a full Regulatory Evaluation is unnecessary.

The rule will only be enforced during a time when vessel traffic is expected to be minimal. Moreover, vessels may still enter the safety zone with the express permission of the Captain of the Port St. Petersburg or a designated representative.

Under the Regulatory Flexibility Act (5 U.S.C. 601-612), we have considered whether this rule would have a significant economic impact on a substantial number of small entities. The term “small entities” comprises small businesses, not-for-profit organizations that are independently owned and operated and are not dominant in their fields, and governmental jurisdictions with populations of less than 50,000.

The Coast Guard certifies under 5 U.S.C. 605(b) that this rule would not have a significant economic impact on a substantial number of small entities. This rule may affect the following entities, some of which may be small entities: The owners or operators of vessels intending to transit Johns Pass, FL. This safety zone will not have a significant economic impact on a substantial number of small entities for the following reasons: This rule will be enforced for a limited time when marine traffic is expected to be minimal; additionally traffic will be allowed to enter the zone with the permission of the Captain of the Port Sector St. Petersburg or a designated representative.

Under section 213(a) of the Small Business Regulatory Enforcement Fairness Act of 1996 (Pub. L. 104-121), in the NPRM, we offered to assist small entities in understanding the rule so that they could better evaluate its effects on them and participate in the rulemaking process.

Small businesses may send comments on the actions of Federal employees who enforce, or otherwise determine compliance with, Federal regulations to the Small Business and Agriculture Regulatory Enforcement Ombudsman and the Regional Small Business Regulatory Fairness Boards. The Ombudsman evaluates these actions annually and rates each agency's responsiveness to small business. If you wish to comment on actions by employees of the Coast Guard, call 1-888-REG-FAIR (1-888-734-3247). The Coast Guard will not retaliate against small entities that question or complain about this rule or any policy or action of the Coast Guard.

This rule calls for no new collection of information under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

A rule has implications for federalism under Executive Order 13132, Federalism, if it has a substantial direct effect on State or local governments and would either preempt State law or impose a substantial direct cost of compliance on them. We have analyzed this rule under that Order and have determined that it does not have implications for federalism.

The Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-1538) requires Federal agencies to assess the effects of their discretionary regulatory actions. In particular, the Act addresses actions that may result in the expenditure by a State, local, or tribal government, in the aggregate, or by the private sector of $100,000,000 or more in any one year. Though this rule will not result in such an expenditure, we do discuss the effects of this rule elsewhere in this preamble.

This rule will not effect a taking of private property or otherwise have taking implications under Executive Order 12630, Governmental Actions and Interference with Constitutionally Protected Property Rights.

This rule meets applicable standards in sections 3(a) and 3(b)(2) of Executive Order 12988, Civil Justice Reform, to minimize litigation, eliminate ambiguity, and reduce burden.

We have analyzed this rule under Executive Order 13045, Protection of Children from Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and does not create an environmental risk to health or risk to safety that may disproportionately affect children.

This rule does not have tribal implications under Executive Order 13175, Consultation and Coordination with Indian Tribal Governments, because it does not have a substantial direct effect on one or more Indian tribes, on the relationship between the Federal Government and Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes.

We have analyzed this rule under Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use. We have determined that it is not a “significant energy action” under that order because it is not a “significant regulatory action” under Executive Order 12866 and is not likely to have a significant adverse effect on the supply, distribution, or use of energy. The Administrator of the Office of Information and Regulatory Affairs has not designated it as a significant energy action. Therefore, it does not require a Statement of Energy Effects under Executive Order 13211.

The National Technology Transfer and Advancement Act (NTTAA) (15 U.S.C. 272 note) directs agencies to use voluntary consensus standards in their regulatory activities unless the agency provides Congress, through the Office of Management and Budget, with an explanation of why using these standards would be inconsistent with applicable law or otherwise impractical. Voluntary consensus standards are technical standards (e.g., specifications of materials, performance, design, or operation; test methods; sampling procedures; and related management systems practices) that are developed or adopted by voluntary consensus standards bodies.

This rule does not use technical standards. Therefore, we did not consider the use of voluntary consensus standards.

We have analyzed this rule under Commandant Instruction M16475.lD and Department of Homeland Security Management Directive 5100.1, which guide the Coast Guard in complying with the National Environmental Policy Act of 1969 (NEPA) (42 U.S.C. 4321-4370f), and have concluded under the Instruction that there are no factors in this case that would limit the use of a categorical exclusion under section 2.B.2 of the Instruction. Therefore, this rule is categorically excluded, under figure 2-1, paragraph (34)(g), of the Instruction, from further environmental documentation. A final “Environmental Analysis Check List” and a final “Categorical Exclusion Determination” are available in the docket where indicated under ADDRESSES.