CHAPTER 6

• The Division Difference Dmg To Target Out Of Cover Rangers
• The Division Difference Dmg To Target Out Of Cover Range Chart
• The Division Difference Dmg To Target Out Of Cover Ranges
• The Division Difference Dmg To Target Out Of Cover Ranger

COMBAT TECHNIQUES OF FIRE

When I say DTA/DTH is the final calculation, I mean its being applied on top of all other buffs the second that damage is dealt to your target. For example if you have a ChC build with 10% DTA, then your bullets are dealing your base damage( x 10% dmg against armor), and your crits ( x 10% dmg against armor) too. Somewhat situational. They're both their own multiplicative categories. However, DMG out of cover does nothing on enemies in cover while damage to armor does, but damage to armor stops working when the armor bars are gone. +5% DMG to target out of cover. Classified Set Bonus (6): Talent: Improved Banshee. While rogue, the time to clear manhunt status is decreased by 5% for every group member within 10 meters. All rogue status actions that result in a rank up are doubled. Rewards for clearing manhunt status are improved. The Division Difference Dmg To Target Out Of Cover Rangers Weapon Talents; Accurate: Accuracy is improved by 25% (instead of 20 to 50%) The Division Difference Dmg To Target Out Of Cover Range 2017; Adept: Using a skill increases your critical hit chance.

Technique of fire is the method of delivering and controlling fire. Each member of the machine gun crew must be trained in standard methods of applying fire, either as a crewmember or a gunner, and must perform his assigned task automatically and effectively. The simplest and most effective technique of delivering fire with the machine gun mounted on its ground or vehicular mount is to align the sights of the gun on the target and fire; this is called direct laying. At times, techniques of fire other than direct laying are more appropriate and effective. When delivering overhead fire or fire from position defilade, the gunner must use the appropriate technique.

Section I. FUNDAMENTALS

Before the machine gun can be employed to the best advantage using any firing technique, certain fundamentals must be understood and applied. These include:

• Characteristics of fire.
• Classes of fire.
• Fire control.
• Target types and methods of engagement.
• Overhead fire.
• Methods of laying the gun.
• Firing from position defilade.
• Final protective fires.

6-1. CHARACTERISTICS OF FIRE

The gunner's knowledge of his machine gun is not complete until he learns something of the action and effect of the projectiles when fired. This section discusses various characteristics of machine gun fire, including trajectory, cone of fire, and the beaten zone.

a. Trajectory. The trajectory is the curved path of the projectile in its flight from the muzzle of the weapon to its impact. The major factors that influence the trajectory are the velocity of the round, gravity, rotation of the round, and resistance of the air. The farther the round travels, the greater the curve of the trajectory. The highest point of the trajectory is called the maximum ordinate. This is a point approximately two-thirds of the distance from the gun to the target. The maximum ordinate increases as the range increases (Figure 6-1).

b. Cone of Fire. When the weapon is fired automatically in bursts, all the rounds do not follow the same path. This is due to the vibrations of the gun and mount, variations in ammunition, and atmospheric conditions, which cause the rounds to follow a slightly different trajectory. This group of trajectories formed by a single burst is called the cone of fire (Figure 6-2).

c. Beaten Zone. The beaten zone is an elliptical pattern formed by the cone of fire as it strikes the ground. The beaten zone is always about 2 meters in width.

(1) Effect of range. As the range to the target increases, the beaten zone becomes shorter and wider.

(2) Effect of terrain. The length of the beaten zone for any given range will vary according to the slope of the ground. On rising ground, the beaten zone becomes shorter but remains the same width. On ground that slopes away from the gun, the beaten zone becomes longer but remains the same width.

6-2. CLASSES OF FIRE

Machine gun fire is classified with respect to the ground (Figure 6-3), the target (Figure 6-4), and the gun (Figure 6-5).

a. Classes of Fire with Respect to the Ground.

(1) Plunging fire. Fire in which the angle of fall of the rounds (with reference to the slope of the ground) is such that the danger space is confined to the beaten zone, and the length of the beaten zone is materially shortened. Plunging fire is obtained when firing from high ground to low ground, when firing from low ground to high ground, and when firing at long ranges.

(2) Grazing fire. Grazing fire is fire in which the center of the cone of fire does not rise more than one meter above the ground. When firing over level or uniformly sloping terrain, the maximum extent of grazing fire obtainable is about 700 meters.

b. Classes of Fire with Respect to the Target.

(1) Frontal. The long axis of the beaten zone is at a right angle to the long axis of the target.

(2) Flanking. Fire is delivered against the flank of a target.

(3) Oblique. The long axis of the beaten zone is at an angle (but not a right angle) to the long axis of the target.

(4) Enfilade. The long axis of the beaten zone coincides or nearly coincides with the long axis of the target. This class of fire is either frontal or flanking. It is the most desirable class of fire with respect to the target because it makes maximum use of the beaten zone.

c. Classes of Fire with Respect to the Gun.

(1) Fixed fire. This is fire delivered on a point target with little or no manipulation needed. After the initial burst, the gunners will follow any change or movement of the target without command.

(2) Traversing fire. This is fire distributed against a wide target requiring successive changes in the direction of the gun. When engaging a wide target requiring traversing fire, the gunner should select successive aiming points throughout the target area. These aiming points should be close enough together to ensure adequate target coverage; however, they need not be so close as to be wasteful of ammunition by concentrating a heavy volume of fire in a small area. Two clicks on the traversing handwheel after each burst ensure coverage (2 clicks = 2 mils = constant width of beaten zone).

(3) Searching fire. This is fire delivered against a deep target or a target that has depth, requiring changes in elevation of the gun. The amount of elevation change depends upon the range and slope of the ground.

(4) Traversing and searching fire. This is fire delivered both in width and depth by changes in direction and elevation. It is employed against a target whose long axis is oblique to the direction of the fire.

(5) Swinging traverse. This is employed against targets that require major changes in direction but little or no change in elevation. Targets may be dense, wide, in close formations moving slowly toward or away from the gun, or vehicles or mounted troops moving across the front. The traversing slide lock lever is loosened enough to permit the gunner to swing the gun laterally.

(6) Free gun. This is when fire is delivered against moving targets that must be rapidly engaged with fast changes in both direction and elevation. Examples are aerial targets, vehicles, mounted troops, or infantry in relatively close formations moving rapidly toward or away from the gun position. To fire free gun on the M3 tripod mount, remove the T&E mechanism from the receiver and traversing bar and put it down. When firing swinging traverse and free gun, the weapon is normally fired at the cyclic rate of fire which is in excess of 450 rounds per minute. This consumes a lot of ammunition, and there is no beaten zone because each round seeks its own area of impact.

Section II. FIRE CONTROL

Fire control of machine guns includes all operations connected with the preparation and actual application of effective fire on a target. It implies the ability of the leader to open fire at the instant he desires, to adjust the fire of the gun(s) on the target, to regulate the rate of fire, to shift from one target to another, and to cease firing. This ability to exercise proper fire control depends primarily on the discipline and the proper training of the crew. Failure to exercise fire control results in danger to friendly troops, loss of surprise, premature disclosure of positions, application of fire on unimportant targets, loss of time in adjusting fire, and waste of ammunition.

6-3. METHODS OF FIRE CONTROL

Of the several methods of controlling machine gun fire, the noise of battle will limit the use of some. Therefore, the leader must select the method or combination of methods that will best accomplish his purpose. The chain of fire control begins with the leader. He is responsible for both the technical and tactical employment of the gun and the training of the crew. He is responsible for passing on to the crewmembers all instructions and orders from his next higher leader regarding the situation and mission. He assigns sectors of fire and firing positions, designates targets to be engaged, adjusts fire, and ensures effective coverage of the targets.

a. Oral. Oral control is effective unless the leader is too far away from the gun crew(s), or the noise of battle makes it impossible for the gun crew(s) to hear him.

b. Arm-and-Hand Signals. This is an effective method when the gun crew(s) can see the leader. All crewmembers must understand the standard arm-and-hand signals used to control machine gun fire.

c. Prearranged Signals. These are either visual or sound signals such as pyrotechnics or blasts on a whistle. These signals should be included in the units' SOPs and must be clearly understood by all crewmembers.

d. Personal Contact. In many situations, the leader must move to individual crewmembers to issue orders. This method is used more than any other by small-unit leaders. The leader must use maximum cover and concealment to keep from disclosing the gun crew's position.

e. Standing Operating Procedures. SOPs cover actions the gun crews perform without command because they were developed and practiced during the training of the gun crews. Their application eliminates many commands and simplifies the leader's job of fire control.

6-4. TARGETS AND THEIR ENGAGEMENT

Targets presented to the machine gunners during combat will in most cases consist of enemy soldiers in various formations, which require distribution and concentration of fire. These targets have width and depth, and the application of machine gun fire is designed to completely cover the area in which the enemy is known or suspected to be. These targets may be easy to see or may be indistinct and difficult to locate.

a. When machine gun fire is under direct control of a leader, he designates the midpoint and flanks or ends of a target unless they are obvious to the gun crew(s). When a target other than a point target is engaged by two gunners, it is always divided. Each gunner applies his fire to that portion of the target corresponding to his position with relation to the other gun. Normally, each gunner engages one-half of the target; however, gunners must be prepared to engage the entire target if necessary. Gunners continue to fire on the target until it is neutralized or until another signal is received from the leader.

b. The gunner's positions (including vehicular-mounted) should be numbered so each gunner will know which portion of a target he should engage. It should be emphasized that the positions are numbered--not the guns or gunners. To ensure that gunners react quickly and properly when they detect a target or when a target is designated by the leader, standard methods of applying fire to the various type targets are taught. These methods are the same for ground and vehicular-mounted guns. The following are the different types of targets and how they are engaged with the MG.

(1) Point targets are targets that require the use of a single aiming point. Enemy bunkers, weapon emplacements, vehicles, small groups of soldiers, and aerial targets such as helicopters or descending paratroopers are examples of point targets. A point target is engaged with fixed fire. If the target moves after the initial burst, the gun crew(s) keeps fire on the target by following its movement with the gun(s).

(2) Linear targets have sufficient width to require traversing fire and no more depth than can be effectively covered by the beaten zone. Linear targets are engaged with traversing fire.

(a) Two guns, normal division. The target is divided at the midpoint; the right gun engages the right half of the target, and the gun on the left engages the left half of the target. The point of initial lay and adjustment for both guns is at the midpoint of the target. After adjusting on the midpoint, the right gun traverses the right half of the target to include one aiming point beyond the last visible target flank and returns to the midpoint.

(b) Two guns, special division. If one portion of the target presents a greater threat than another, the target can be divided so fire is concentrated on that portion presenting the greatest threat. The special division of the target is accomplished by a subsequent fire command after firing begins. The gunners initially lay at the midpoint, regardless of the special division to be made, thus precluding confusion.

(c) One gun. A single gunner must engage the entire width of a linear target. The point of the initial lay and adjustment is on the midpoint, or that portion of the target presenting the greatest threat. The gunner traverses to either flank and then covers the remainder of the target (Figure 6-6).

(3) Linear targets with depth are targets that have sufficient width to require traversing fire and depth which cannot be covered by the beaten zone. A combined change in direction and elevation (traversing and searching fire) is required to maintain effective fire on these targets (Figure 6-7). Linear targets with depth are engaged with traversing and searching fire. When range is announced, the range to the midpoint is given.

(a) Two guns. The method of division, the point of initial lay and adjustment, and the extent of manipulation for both guns are the same as prescribed for linear targets. The gunners, however, apply enough search between each burst to ensure the center of the beaten zone is maintained at the center base of the target (Figure 6-8).

(b) One gun. A single gunner initially lays and adjusts on the midpoint of a linear target with depth unless some other portion of the target presents a greater threat. The gunner traverses and searches to the near flank, then he covers the entire target area (Figure 6-8).

(4) Deep targets have depth but very little width and can be effectively covered by searching fire (Figure 6-9). When the range is announced, it is given to the midpoint of the target.

(a) Two guns. The point of initial lay of both guns is on the midpoint, which is also the point of division. Since enfilade fire is delivered, it is not necessary to adjust on the midpoint of the target because the long axis of the beaten zone will compensate for missing the midpoint. However, should the gunner's beaten zone be out of the lateral confines of the target, it will be necessary to adjust fires into the target area. After the initial bursts, the right gun searches to the near end of the target, and the left gun searches to the far end of the target. Both gunners then reverse their direction of search and return to the midpoint (Figure 6-10).

(b) One gun. A single gunner initially lays and fires at the midpoint of a deep target, unless another portion of the target presents a greater threat. The gunner immediately searches to the near end, then covers the entire target (Figure 6-10).

(5) Area targets as discussed in this manual have considerable width and depth, and they require extensive traversing and searching fires. This type target exists when the enemy is known to be in a certain area, but his exact location is not known. A hilltop is a typical area target. The leader designates an area target by indicating to the gun crew(s) the width and depth of the target.

(a) Two guns. The target is divided at the center of mass; the right gun fires on the right half and the left gun fires on the left half. The point of initial lay and adjustment for both guns is on the center of mass. After adjusting on the center of mass, fire is distributed by determining the size of the beaten zones and applying direction and elevation changes that cause the most effective coverage of the target area. Both guns traverse and search their respective halves to the flanks, then return to the midpoint (Figure 6-11).

(b) One gun. A single gunner engages an area target by laying and adjusting on the center of mass, traversing and searching to either flank, then reversing the direction, traversing and searching to the other flank (Figure 6-11).

The Division Difference Dmg To Target Out Of Cover Rangers

NOTE: After the target is engaged in whatever formation it is in, the configuration of that target will change. The gunner must be trained to compensate for this change and still place effective fire on the target.

6-5. OVERHEAD FIRE

Overhead fire is fire delivered over the heads of friendly troops. A machine gun on a tripod is capable of delivering this type of fire because of the small and uniform dispersion of the cone of fire. In the attack, the use of overhead fire permits the machine gun to support the advance of rifle units. Sectors of fire allow the trainers to plan safe training while still incorporating the combat realities of overhead fires.

a. Minimum Clearance. The center of the cone of fire must clear the heads of the friendly troops by a prescribed distance (Figure 6-12). This distance, known as minimum clearance, is found by adding together the following elements:

• The height of a standing man, taken as 1.8 meters.
• Half the vertical dimension of the 100-percent cone of fire at the range to the troops.
• A margin of safety equal to the vertical distance which extends a 5-mil angle at the gun or 3 meters, whichever is greater.
• An additional allowance to compensate for a 15-percent error in range determination.

b. Safety Angles. To obtain this minimum clearance, the gun is elevated so that the center of the cone of fire is raised from the feet-of the friendly troops to maintain clearance above their head. The amount of this elevation change is known as the safety angle. When the gun is fired from the tripod with the required safety angle, the center of impact determines the shortest range at which fire can be delivered over the heads of friendly troops. The range from the gun to the point of strike is called the corresponding range. When the ground is level or uniformly sloping between the gun and the target, the corresponding range for the safety angle used is obtained by converting the angle of elevation expressed in mils into range.

c. Conditions. Overhead fire is used only when the following conditions have been met:

(1) The safety limit has been determined and has been identified on the ground.

(2) The gun mount is firmly seated.

(3) Friendly troops have been notified, if at all possible, that fire is to be delivered over them.

(4) The rate of fire does not exceed 40 rounds per minute.

(5) The gun barrel is not badly worn. This condition is indicated by excessive muzzle blast.

d. Uneven Terrain. Level or uniformly sloping ground is seldom found in the field. This limits the use of firing tables and corresponding ranges in determining the limit of troop safety. In lieu of firing tables, a rule of thumb has been devised to give the gunner a simple method of checking for troop safety.

(1) The gunner's rule can be applied when the friendly troops are at least 350 meters in front of the gun position, and the range to the target is 850 meters or less (Figure 6-13).

(a) Lay the gun on the target with the correct sight setting to hit the target.

(b) Without disturbing the lay of the gun, set the rear sight at a range of 1,600 meters.

(c) Look through the sights and notice where the new line of aim strikes the ground. This is the limit of troop safety. When the feet of the friendly troops reach this point, fire must be lifted or shifted.

(2) When the range to the target is greater than 850 meters, overhead fire should be delivered only in an emergency and then only out to a range in which either the tracers or the strike of the bullets can be seen by the gunner. In this situation the leader's rule applies (Figure 6-14).

The platoon or section leader uses the leader's rule only when the target is greater than 850 meters. The rule is as follows:

(a) Select a point on the ground where it is believed friendly troops can advance with safety.

(b) Determine the range to this point by the most accurate means available.

(c) Lay the gun on the target with the correct sight setting to hit the target.

(d) Without disturbing the lay of the gun, set the rear sight to 1,600 meters, or the range to the target plus 500 meters, whichever is greater. Under no conditions should the sight setting be less than 1,500 meters.

(e) Note the point where the new line of aim strikes the ground.

• If it strikes at the selected point, that point marks the limit of safety.
• If it strikes short of the selected point, it is safe for troops to advance to the point where the line of aim strikes the ground and to an unknown point beyond. If it is desired to fire after friendly troops advance farther than the point where the line of aim strikes the ground, this farther point is determined by testing new selected points until the line of aim and the selected point coincide.
• If it clears the selected point, it is safe for the troops to advance to the selected point and to an unknown point beyond. If it is desired to have troops advance beyond the selected point, this farther point must be determined by testing new selected points until the line of aim and the selected point coincide. This point marks the line of safety.

e. Precautions. The following safety precautions must be observed in delivering overhead fire.

(1) Firmly emplace the tripod mount.

(2) Use depression stops to prevent the muzzle of the gun from accidentally being lowered below the safety limit.

(3) Do not deliver overhead fire through trees.

(4) Inform commanders of friendly troops when fire is to be delivered over their heads.

(5) Ensure that all members of the gun crew(s) are aware of the safety limit.

(6) Do not deliver overhead fire if the range from the gun to the target is less than 350 meters or more than 850 meters.

(7) Do not use a barrel that has excessive muzzle blast or is otherwise determined to be badly worn.

(8) Do not lay machine guns so their fire will cross at any point over the heads of friendly troops.

6-6. DEFILADE POSITIONS

To achieve maximum effectiveness, the machine gun must be employed using the technique of direct lay; however, at times it may be desirable to employ guns from defilade positions.

a. Full Defilade. A machine gun is in defilade when the gun and its crew are hidden from enemy ground observation by a land mass such as the crest of a hill. The position may be on the reverse side of the crest or the forward slope of the next higher ground (Figure 6-15). The gun must fire up and over the hill. Fire must be observed and adjusted by a crewmember who can observe the target from a position on a flank or to the rear of the gun (on higher ground). A defilade position allows little opportunity to engage new targets.

b. Partial Defilade. A machine gun is in partial defilade when a mask (usually the crest of a hill) provides the gun and gunner with some protection from enemy direct fire, but the gunner is able to engage the target using direct laying techniques. The gun is far enough up the slope so that the gunner can see the target through the sights but the lower portion of his body and lower portion of the gun are protected by the mask. Partial defilade positions are desirable when a fire mission cannot be accomplished from a defilade position.

c. Advantages. The gun and crew have cover and concealment from direct fire weapons. The crew has some freedom of movement in the vicinity of the gun position, and control and supply are facilitated. The characteristic smoke and flash of the gun are partially concealed from observation.

d. Disadvantages. Rapidly moving ground targets are not easily engaged because adjustment of fire must be made through an observer. Targets close to the mask usually cannot be engaged, and it is difficult to secure grazing fire for a final protective line.e.

e. Position Selection. The fire unit leader selects the location of the gun position. To select a position in partial defilade, he moves up the reverse side of the slope until he has the target in view above the mask when sighting at the height of the gunner's eye. To select a position in maximum defilade, he estimates the lowest point below the mask at which the gun can still engage the target without danger of hitting the mask.

6-7. METHODS OF LAYING THE GUN FOR DEFILADE FIRING

The essential elements in engagement of a target from defilade position are direction, elevation, mask clearance, and adjustment of fire.

a. Direction. An observer places himself on the gun-target line in a position from which he can see the gun and the target. He aligns the gun approximately by having the gunner shift the mount. The gunner then loosens the traversing slide lock lever and, as directed by the observer, moves the gun right or left until it is aligned on the target; he then clamps it in that position. A prominent landmark, visible to the gunner through his sights, is selected as an aiming point. An aiming point on the gun-target line and at an equal or greater range than the target is desirable. However, an aiming point on the mask may be used. If the aiming point is on the gun-target line, the gun is laid on the aiming point and is thereby aligned for direction. If the aiming point is not on the gun-target line, the deflection is measured by binoculars or compass. This measured deflection is laid off with the gun.

b. Elevation. An aiming point visible from the gun position is selected (preferably a point at a greater range and at a higher elevation than the target) and the range to the target is determined. The leader, using binoculars, measures the vertical angle in mils from the aiming point to the base of the target. He then lays the gun on the aiming point with the sight set to hit the target. He directs the gunner to manipulate the gun through the number of mils measured. For example, in Figure 6-16, the range to the target is 1,300 meters. The angle read with the binoculars from the aiming point down to the base of the target is 12 mils. The sight is set at 1,300 meters, the gun laid on the aiming point, and the muzzle depressed 12 mils. If the aiming point is off the gun-target line, deflection in mils may be taken with the rear sight windage screw knob if it is not over 5 mils; otherwise, the deflection must be taken up on the traversing handwheel.

c. Mask Clearance. After the gun has been laid, determine if the entire cone of fire will clear the mask.

(1) Visual method. When the range to the mask is not more than 450 meters, mask clearance exists when the axis of the bore is elevated 7 mils or more above the gun-mask line. Mask clearance can be checked after the gun has been laid on the target by depressing the muzzle of the gun 2 mils and sighting along the bottom of the receiver and the barrel support. If this line of sight clears the mask, the clearance exists. Elevate 2 mils before firing.

(2) Firing tables method. Determine the range to the mask and obtain the corresponding angle of elevation for mask clearance from the firing tables. The range corresponding to the angle of elevation is set on the gun sight. If the line of aim through the sight clears the mask, the clearance exists.

d. Adjustment of Fire. Under field conditions, even the most practical methods of laying the gun on the target quickly do not always result in the initial burst being on the target. For this reason, adjustment of fire on the target is essential. Creeping fire should be avoided. (See paragraph 6-10 for details on adjustment of fire.)

6-8. FINAL PROTECTIVE FIRES

These are types of fire that are placed on a predetermined line along which grazing fire is placed to stop an enemy assault. This fire is fixed in direction and elevation; however, a few mils of search are employed during firing to compensate for irregularities in the terrain. FPLs are always laid in using the extreme left or right of the tripod, causing the T&E to move to the extreme left or right on the traversing bar. The FPFs can be delivered in any visibility conditions. When terrain permits, final protective lines are assigned to machine guns along the forward line of troops as a part of the FPFs of the defending unit. The signal used to call for FPFs is normally prescribed in the company operation order. The authority to call for these fires may be delegated to the platoon leader of a forward rifle platoon. Final protective fires are ceased on order.

a. Signals. Arm-and-hand signals, voice commands, or pyrotechnic devices may be used in calling for these fires.

b. Rates of Fire. When firing FPFs, the rapid rate of fire is used unless it is obvious that a different rate is necessary to accomplish the mission. When engaging other preselected target areas, the rapid rate of fire is used until commanded to cease fire.

6-9. APPLICATION OF FIRE

To be effective, machine gun fire must be distributed over the entire target area. Improper distribution of fire results in gaps which allow the enemy to escape or use weapons against friendly positions without effective opposition.

a. The method of applying fire to a target is generally the same for either a single gun or a pair of guns. Direct laying is pointing the gun for direction and elevation so that the sights are aligned directly on the target. Fire is delivered in width, depth, or in a combination of the two. To distribute fire properly, the gunners must know where to aim, how to adjust their fire, and the direction to manipulate the gun. The gunner must aim, fire, and adjust on a certain point of the target. Binoculars may be used by the leader to facilitate fire adjustment.

b. The gunner ensures throughout his firing that the center of the beaten zone is maintained at the center base of the target for maximum effect from each burst of fire. When this is done, projectiles in the upper half of the cone of fire will pass through the target if it has height, and the projectiles in the lower half of the beaten zone may ricochet into the target (Figure 6-17).

c. The gunner must move his beaten zone in a certain direction over the target. The direction depends on the type of target and whether the target is engaged with a pair of guns or a single gun. When engaging targets other than point targets with a pair of guns, the targets are divided so that fire is evenly distributed throughout the target area. Fire delivered on point targets or a specific area of other target configurations is called concentrated fire.

6-10. FIRE ADJUSTMENT

Machine gun fire is adjusted by observing the strike of the rounds, observing the flight of tracers, frequently re-laying the gun, or by a combination of these. Adjustment by observation of fire is the most important element of fire control if it is bold, aggressive, rapid, and continuous throughout the action.

a. The gunner is trained to observe and adjust his gun's fire without command. He is trained to anticipate the action of the enemy after the initial burst, and is prepared to shift his fire to cover any change in formation or movement of his target. If the gunner fails to accomplish this, the fire unit leader must promptly correct him by announcing or signaling subsequent fire commands. This responsibility to adjust fire continues through the chain of commands.

b. When subsequent fire commands are given, the gunner makes the required corrections and continues to engage the target without any further command to fire. If the gun is fired on the tripod mount, subsequent commands are given to make changes in direction, elevation, and the rate of fire. These changes are given orally as SHIFT RIGHT, SHIFT LEFT, ADD, or DROP. (For arm-and-hand signals see FM 21-60.) When making these announced changes, mils may be used to indicate the amount of desired shift; for example, SHIFT RIGHT 5 or SHIFT LEFT 7. When making changes in elevation, mils are not used, as it is normally difficult to determine just how high or low the center of the beaten zone is striking the ground in relation to the target.

(1) Observation. When firing on the 10-meter range, the strike of the bullets is visible on the target. When firing at greater distances, the strike of the bullets on the ground may cause dust to rise, which is visible to the gunner; however, during wet weather the strike cannot always be seen. In this event, the tracers will allow the gunner or crew leader to note the strike of the burst in relation to the target.

(2) Adjustment. Using the mil relation, one click of the traversing handwheel or elevating handwheel moves the strike of the bullet 1/2 inch on the target at a range of 10 meters.

(a) When firing on the 10-meter range, adjust by moving the shot group a required number of centimeters vertically or horizontally until the center of the group is on the aiming paster. Should the gunner's initial burst strike the target 2 centimeters to the left and 3 centimeters below the aiming paster, he adjusts his fire by traversing right 4 clicks and elevating 6 clicks before firing again.

(b) When firing on field targets, adjust by moving the burst into the target. One click (mil) on the traversing handwheel will move the strike 1/2 meter at 500 meters or 1 meter at 1,000 meters; however, the distance 1 click (mil) in the elevating handwheel will move the strike depends on the range to the target and the slope of the ground. The gunner determines the number of mils necessary to move the center of the strike into the target, and he manipulates the gun the required number of mils. This does not require the use of sights. For example, should the gunner fire on a target at 500 meters and observe the strike 10 meters to the right of the target and short about 50 meters, he would traverse the gun to the left 20 clicks (mils) and add one or more clicks (mils), depending on the slope of the ground.

(c) The gunner may use the adjusted aiming point method to adjust the fire. In this method the gunner must use his sights. He selects an aiming point that will place the next burst on the target. For example, should the gunner fire on a target at 500 meters and estimate that the strike is 20 meters short and 10 meters to the right of the target, he would rapidly select an aiming point approximately 20 meters beyond the target and 10 meters to the left of the target, lay on that aiming point, and fire.

6-11. ANTIAIRCRAFT GUNNERY

The MG can provide units with a self-defense capability against hostile low-flying, low-performance aircraft. These guns are employed in the air defense role as part of the unit's local defense. The MGs are not components of an integrated and coordinated air defense system. Unless otherwise directed, hostile aircraft within range of the gun (about 800 meters maximum effective range) should be engaged. The decision will be made by the commander. Typical targets are surveillance, reconnaissance, and liaison aircraft; troop carriers; helicopters; and drones.

a. Engagement and Employment. The mission is to impose maximum attrition upon the attacking enemy, such as low-flying, low-performance aircraft. Employment of MGs used for air defense is guided by the following defense design factors:

• Defense design should produce an equally balanced defense that is effective in all directions, unless a forced route of approach exists.
• Machine guns should be sited so that the maximum number of targets can be engaged, continuous fire can be delivered, and the most likely routes of approach are covered.
• Machine guns used to defend march columns should be interspersed in the convoy, with emphasis on the lead and rear elements (Figure 6-18).

b. Target Selection and Engagement Control. These actions depend upon visual means. The sites selected for the guns must provide maximum observation and unobstructed sectors of fire. Units furnished MGs in sufficient numbers should site them within mutual support distances of 90 to 360 meters. Each gun is assigned a primary and secondary sector of fire. Weapon crews maintain constant vigilance in their primary sectors of fire, regardless of the sector in which the guns are actually engaged.

Section III. LIMITED VISIBILITY

The machine gun is provided with a stable tripod mount, M3, and a traversing and elevating mechanism. By manipulating the T&E mechanism, gun crews can record target data during good visibility and engage the same targets in poor visibility. This section provides guidance on machine gun firing techniques and terms used during limited visibility, which includes darkness, smoke, fog, rain, or snow.

6-12. DIFFICULTIES

Crewmembers encounter difficulties while defending during limited visibility, which preclude the use of many of the daylight techniques of engaging targets.

a. During limited visibility, the machine gunner's sector of responsibility cannot be observed in depth; therefore, targets are difficult or impossible to detect.

b. Visibility may be so limited that the leader cannot control the fires of his guns by selecting and directing fire on targets as he would during good visibility. Oral commands are not dependable, arm-and-hand signals may not be seen, and personal contact with the gunner is difficult.

c. At night, machine gunners have a tendency to fire indiscriminately at noises and suspected enemy locations.

To overcome these difficulties, special techniques must be developed for engaging targets and delivering preplanned fires by the use of range cards. (See Appendix E.)

6-13. TERMINOLOGY

The following terms must be familiar to MG crews for them to complete their missions in poor visibility.

a. Sector of Fire. An area (to be covered by fire) assigned to an individual or unit. Machine guns are normally assigned two sectors of fire, a primary and a secondary sector.

b. Final Protective Line. A predetermined line along which grazing fire is placed to stop an enemy assault. The FPL is fixed as to direction and elevation; however, a few mils of search are employed during firing to compensate for irregularities in the terrain. The FPL can be delivered regardless of visibility conditions. The FPL is always the inner limit of the primary sector, which is assigned close to the forward line of troops area. When terrain permits, FPLs are assigned to machine guns along the FLOT as a part of the final protective fires of the defending unit.

c. Principal Direction of Fire. A PDF is a priority direction of fire that marks a specific area assigned to a weapon. This area may extend from the gun position to the maximum effective range of the weapon and therefore is not fixed for elevation. Visible targets appearing in the PDF take priority over targets that may appear elsewhere in the sector. A PDF may be assigned to cover an area that provides good fields of fire, is a likely avenue of foot approach, or mutually supports an adjacent unit.

d. Sector of Graze. A wedge-shaped area formed by assigned sector limits that afford grazing fire (one meter high, maximum) from the muzzle of the weapon to the first major break in the terrain. The sector of graze is fired using swinging traverse in the primary sector of fire. It can be fired in the secondary sector in conjunction with field expedients by freeing the T&E mechanism and using the mount as a pivot. A sector of graze can be delivered regardless of the condition of visibility.

e. Area of Graze. This is an area, other than the sector of graze, within a sector of fire that is covered by grazing fire. Grazing fire need not be continuous from the muzzle of the weapon to the area over which grazing fire is desired.

The Division Difference Dmg To Target Out Of Cover Range Chart

6-14. TARGET ENGAGEMENT

A gunner's ability to detect and identify targets during limited visibility will vary, depending upon the amount of natural and artificial light and the types and numbers of sensors used. All tracer ammunition allows a gunner to more effectively engage visible targets during limited visibility; it should be used when possible. Gunners must be trained to fire low initially and adjust up when engaging targets during limited visibility. This helps them overcome the tendency to fire high during these conditions. The types of point targets machine gunners will be concerned with during limited visibility, particularly at night, are enemy automatic weapons and assaulting enemy personnel.

a. Point targets such as automatic weapons may be identified during limited visibility by their muzzle flashes. To effectively engage these targets, fire should be delivered in a heavy volume and adjusted by observing the tracer stream.

b. During the final stage of an enemy assault, machine guns normally fire at personnel on an FPL; they may be assigned a PDF. Both are considered as final protective fires and should be planned for and coordinated as such. If individual enemy soldiers are observed in the proximity of the gun position, they must be neutralized by someone other than the machine gunner (by the other crewmembers or by security forces of the supported unit). The FPFs are fired according to the order or SOP, and the machine gunner is not allowed to stop firing them except in accordance with those orders or SOP.

6-15. FIRE CONTROL

During limited visibility, the leader cannot direct the fires of his guns as effectively as with good visibility. Consequently, initiative is required of the gunners. When targets within their sectors become visible to gunners, they must engage such targets without command and continue to fire until the targets have been neutralized. Gun crews engage targets only when they can identify them, unless ordered to do otherwise. For example, if one gunner detects a target and engages it, the other gunners will observe the area in which fire is being placed. They will add their fire only if they can identify the target or are ordered to place fire in the area.

6-16. PREPLANNED FIRES

In addition to engaging appropriate visible targets, the gunner must be able to deliver preplanned fires during limited visibility. These fires are used to cover target areas of tactical significance (such as routes, avenues of approach, anticipated enemy supporting weapons positions, and probable enemy assault positions) and to establish sectors of graze and final protective lines. For maximum effect in all preplanned target areas, grazing fire should be obtained when possible.

a. Obtaining Maximum Extent of Grazing Fire Over Level or Uniformly Sloping Terrain. The machine gunner sets the rear sights at 700 meters; selects a point on the ground, which he determines to be at a range of about 700 meters; and lays, fires, and adjusts on this point. If the gunner cannot obtain 700 meters of grazing fire because of a major break in the ground at a range of less than 700 meters, he places the range to the break on his sight and lays, fires, and adjusts at that point.

b. Determining the Extent of Grazing Fire on the Final Protective Line. The extent of grazing fire on the FPL is determined using the techniques described above. Any intermediate breaks in the terrain along this line that cannot be covered by grazing fire from a gun firing along the line is considered dead space.

c. Determining the Extent of Grazing Fire in the Sector of Graze. The ranges to the extent of grazing fire in a sector of graze are determined by observing the terrain and by observing the tracer stream from behind or from a flank of the gun position. Normally, the extent of grazing fire within this area will be much less than on an FPL and will form an irregular pattern.

d. Determining the Amount of Grazing Fire in an Area of Graze. The same procedures used in paragraph 6-8a are used in determining the extent of grazing fire in an area of graze. The ranges to areas of grazing fire are determined by observing the flight of tracer ammunition from behind or from the flank of the gun position. The gunner determines the lateral extent of areas of graze by selecting and engaging successive aiming points in the area believed to afford grazing fire, using the same range setting as when determining the range to the extent of grazing fire.

6-17. NBC CONSIDERATIONS

During this phase of training, the gunner is introduced to firing the machine gun while in MOPP, keeping in mind that engagement of some targets in MOPP is a qualification requirement. Firing weapons is only part of the overall NBC training. Soldiers must first be familiar with the NBC equipment, its use, and proper wear before they progress to learning the techniques of MOPP firing. Although there is no different technique required to fire the MG, there are certain fundamentals that may be slightly impaired.

a. Immediate Action. Under normal conditions, a gunner should be able to clear a stoppage in two to four seconds; however, under full MOPP, this may take a few seconds longer. Dry-fire practice under these conditions is necessary to reduce time and streamline actions. When practicing with the hood/mask and gloves, care must be taken not to snag or damage the gloves or dislodge the hood/mask during movement. Trainers should apply immediate action to a variety of stoppages during dry fire until the gunners are able to instinctively do it without compromising their NBC environment.

b. Target Detection. Techniques and principles of target detection and target acquisition still remain valid during NBC conditions, but considerations must be made for limiting factors imposed by MOPP equipment. For example, vision is limited to what can be seen through the mask's lens/faceplate. Peripheral vision is severely restricted. The lens/faceplate may be scratched or partly fogged, thus further restricting vision. Gunners requiring corrective lenses must be issued insert lenses before training. Scanning movements may be restricted by the hood/mask. Any of these factors could adversely affect the gunner's ability to quickly and accurately detect targets. Extra skill practice should be conducted.

c. Efficient Performance. The trainer must keep in mind that although movements are slowed, tasks take longer, and function checks, loading, unloading, and cleaning are affected by MOPP, it is a must that the gunner avoid damaging MOPP gear and risk possible exposure to lethal agents. Because of the great difference between no MOPP and MOPP4, gunners must be trained in all aspects of operation and maintenance of the weapon while practicing at the highest MOPP level. Only through repeated training and practice can the soldier be expected to perform all tasks efficiently.

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(February 18, 1997)

All NDA, ANDA, and AADA Holders

Dear Sponsors:

On November 30, 1995, the Scale-up and Post-Approval Changes Guidance for Immediate Release Products (SUPAC-IR) was published. Since then a number of questions have arisen in interpreting the Guidance as it applies to specific situations encountered or that could be encountered in the pharmaceutical industry. The purpose of this letter is primarily to share with you the questions that have been asked most frequently or that we consider the most significant. Also included are the Center's responses to these questions. The responses were developed and concurred with by the Office of New Drug Chemistry and Office of Generic Drugs, Center for Drug Evaluation and Research (CDER). We believe the sharing of the information will result in furthering the use of the Guidance to increase regulatory flexibility for industry.

In addition, the Center's Chemistry and Manufacturing Controls Coordinating Committee (CMC CC) has met and reconsidered two SUPAC-IR issues which have been of great concern and interest to industry. The following information on stand alone packaging operation site changes and stand alone analytical site changes represents a re-assessment of how SUPAC-IR should be interpreted on these issues.

STAND ALONE PACKAGING OPERATIONS SITE CHANGES

For immediate release solid oral dosage forms, a stand alone packaging operations site change, utilizing container(s)/closure(s) in the approved application, may be submitted as a Changes Being Effected supplement. The facility should also have a current and satisfactory cGMP compliance profile with FDA for the type of packaging operation in question before submitting the supplement. The supplement should contain written certification from the packaging facility stating that it is in conformance with cGMP's. If the facility has not received a satisfactory cGMP inspection within the previous two years for the type of packaging operation involved, a prior-approval supplement with the same commitment for stability is recommended.

The supplement should also contain a commitment to place the first production batch of the product on long-term stability studies using the approved protocol in the application and to submit the resulting data in annual reports. Where the product is available in more than one strength, size, or container/closure system, one batch of each combination should be placed on long-term stability studies. Bracketing or matrixing is allowed only if it has been approved previously by FDA. Any changes to an approved stability protocol should have a supplemental approval prior to the initiation of the stability study. Batches should be tested annually as per the stability commitments in the approved application.

STAND ALONE ANALYTICAL TESTING LAB SITE CHANGES

For immediate release solid oral dosage forms, a stand alone analytical testing laboratory site change may be submitted as a Changes Being Effected supplement, if the new facility has a current and satisfactory cGMP compliance profile with FDA for the type of testing operation in question. The supplement should contain a commitment to use the same SOP's and test methods employed in the approved application, written certification from the testing laboratory stating that they are in conformance with cGMP's, and a full description of the testing to be performed by the testing lab. If the facility has not received a satisfactory GMP inspection within the previous 2 years for the type of testing involved, a prior-approval supplement is recommended.

The CMC CC and the Center intend that the SUPAC-IR Guidance will be revised to further clarify and update its recommendations and to assure good correspondence between these recommendations and those of other SUPAC documents in preparation. In the meantime, we hope these questions and answers will help clarify the application of the Guidance.

Sincerely yours,

/s /

Roger L. Williams, M. D.
Deputy Center Director for Pharmaceutical Science
Center for Drug Evaluation and Research

Enclosure

SUPAC-IR: QUESTIONS AND ANSWERS

(To the extent these questions and answers provide guidance, that guidance was prepared by the Chemistry, Manufacturing, and Controls Coordinating Committee in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration. Although this guidance does not create or confer any rights for or on any person and does not operate to bind the FDA or the industry, it does represent the Agency's current thinking on questions related to the Scale-Up and Post-Approval Changes Guidance for Immediate Release Products (SUPAC-IR). An electronic version of these questions and answers are also available via Internet using the World Wide Web (WWW). To access the document on the WWW, connect to the CDER Home Page and go to the 'Regulatory Guidance' section.)

COMPONENT AND COMPOSITION CHANGES

1. Q: May one color be replaced with another by placing the batch on concurrent stability and reporting it in the annual report?A: A change from one color to another should be submitted as a prior approval supplement.2. Q: Can color be changed under SUPAC-IR?A: Yes. A change in color, either in amount or from one color to another, is a level 3 component and composition change which calls for a prior approval supplement. However, if the color is merely being removed, it is a level 1 change and can be reported in the next annual report.3. Q: What is the full definition of a change in 'technical grade' of an excipient? Does this only mean a change in excipient specifications that may impact functionality or does it include a change in supplier even if all applicable specifications remain the same? A: Technical grades of excipients differ in their specifications and intended use. Technical grades may differ in: 1) specifications and/or functionality; 2) impurities; and 3) impurity profiles. If a supplier of an excipient changes but its technical grade AND specifications remain the same, the agency should be notified in an annual report.4. Q: How does one apply SUPAC-IR to multifunctional excipients, e.g., starch?

A: SUPAC-IR composition changes are based on being able to define the use or action of the particular excipient in the product. This rationale should be included by the applicants as part of their original applications. Not all multifunctional excipients are listed in the guidance. However, if an excipient was utilized to provide multiple functions such as pregelatinized starch as a filler, starch as a disintegrant, starch paste as a binder, then the most conservative recommended change should be followed (e.g., for an excipient that is a filler, disintegrant and binder, the recommended limit for a Level 2 change is ' 0.5 percent, see page 7, SUPAC-IR). An applicant may wish to add an explanation of how the change will affect other functions of the excipient in the product. If this information was not included in the original application, the review division should be consulted before filing such a SUPAC change, either through a CBE or annual report.

5. Q: What is the reference source for defining the action of an inactive ingredient, for example, lubricant versus glidant? What if the action is defined differently in two sources?A: An applicant should be able to justify the choice and the basis for the selection of a particular excipient, i.e., its expected function in the drug product. It may be useful to cite a source. The action may depend on the specific product.6. Q: Does SUPAC-IR cover changes in granulating solution volume outside the range in an application?A: Changes in granulating solution volume are not covered under SUPAC-IR. Minor changes are considered as normal operating procedure and should be included in the executed batch record. However, if this represents a permanent change, such a change may be described in the annual report along with the data to justify that the formulation quality and performance (i.e., drug product is within the approved specifications) was not altered.7. Q: To what category does a change in granulation solvent in a wet granulation process belong?A: A change in granulating solvent (e.g., alcohol to water) would alter the composition of the drug product, both qualitatively and quantitatively, even though it may be removed during manufacture of the drug product. Because such a change may have significant impact on formulation quality and performance, it is a level 3 composition change that needs a prior approval supplement.8. Q: The NDA includes validated/approved ranges for excipients in the formulation. We would like to move the target formula amount of one of the fillers to the upper value in the range. Will this be a level 1 change in composition?A: All changes are predicated on the target approved in the original application or through a prior approval supplement for a formulation change. For products approved with only a range for an excipient, the target may be assumed to be the mid-point of the approved range. If the new target is within the validated range, the change will be a level 1 or 2 change depending on the specific excipient changed and the percent change (see the SUPAC-IR guidance document). The target originally approved remains the target of record; i.e., Level 1 or Level 2 component changes made under SUPAC- IR do not change the target. If the new target is not within the validated range, the proposed target will need a prior approval supplement.9. Q: When microcrystalline cellulose is increased by 5%, the tablet weight increases. Can this still be a level 1 change?A: After the SUPAC-IR change, if the new target weight is still within the range in the approved original application, it is a level 1 change. Otherwise, it is a Level 2 or 3 change, both of which are to be submitted as a prior approval supplement.10. Q: If one component in a formulation is decreased, must another be increased so that the final weight can remain the same?A: No. The amount of a single component in the formulation may be changed independent of any other changes. (See 9 above)

11. Q: It is my understanding that the development report should cover ranges of processing parameters. Further, the validation report should cover the target parameters for production. If this is true, when level 1 changes are made, how can the validation cover ranges? For future validation reports, is it acceptable to vary processing parameters to prepare for future SUPAC changes?

A: The validation report should cover the target production parameters; however, it is not restricted to these only. If a range is specific, it needs to be validated. This can involve manufacturing batches of product at the extremes of the desired range(s), with appropriate testing to assure that the extreme range batches continue to meet all quality attributes, including dissolution and possibly in vivo bioequivalence tests. For future validation reports, it is acceptable to vary processing parameters. However, it should be understood that the Center's chemists do not review validation data collected by applicants, post-approval, on the first three production batches, because such information is checked by the Field investigators as part of the cGMP requirements. Thus, a summary of validation data on the test (bioavailability/bioequivalence) batch(es) submitted in the original application for approval is the basis for setting acceptable ranges of processing parameters for manufacture of the IR dosage form. These data may include parameters such as mixing time, mixing speed, and blend assays. Thus, for future level 1 SUPAC-IR changes, applicants should use the approved validation ranges as described in the application.12. Q: What is the guidance to determine if a new drug falls into the category of narrow therapeutic range?

A: Appendix A of the SUPAC-IR guidance lists a number of such drugs. In addition, 21 CFR 320.338 describes how to determine if a drug falls into this category.

13. Q: Is a change in gelatin capsule size considered a SUPAC-IR component and composition change?A: Issues related to empty gelatin capsules are not covered in the SUPAC-IR guidance. Only the component categories discussed in the document are covered. Changes for other components should be submitted in accordance with the provisions of 21 CFR 314.70.14. Q: When making a component or composition change according to SUPAC-IR, and the approved application has a range and target for a specific component, does the range move when the target changes?A: No. The range remains the same even when the target changes. Such changes are predicated on the target approved in the original application or through prior approval supplement for a formulation change. Changes to the approved range should be made by prior approval supplements in accordance with the provisions of 21 CFR 314.70.15. Q: Are wetting agents covered under SUPAC-IR?A: No. Only components included in categories spelled out in the guidance qualify as SUPAC-IR changes. Thus, wetting agents are not covered.16. Q: Can inks be changed under SUPAC-IR? If so, how?A: If the new ink has been used in other approved products the change is allowed under SUPAC-IR as a level one change. Alternatively, if all of the components of the ink have been used in approved drug products, the switch also can be made under SUPAC-IR. A justification should be given; reference should be made to the approved product(s) where the ink and/or the components are already used.17. Q: Can inks be eliminated under SUPAC-IR?

A: Ink can be eliminated as a level 1 change.

MANUFACTURING SITE CHANGES

1. Q: Must the inspection which is required for a site transfer have been conducted for the same dosage form?A: Yes. 2. Q: What is the meaning of 'same environmental conditions'?A: 'Same environmental conditions' refers to such conditions as the same temperature range, the same humidity control range, and the same lighting intensity.3. Q: Is moving to/between contract manufacturers covered by SUPAC-IR?A: Yes. The guidance defines site changes as a change in location of the site of manufacture for both company-owned and contract manufacturing facilities.4. Q: If a foreign firm moves to a new manufacturing site (new building) how would they initiate the inspection of that facility?A: The answer is the same whether the new site is foreign or domestic. The submission of a supplement (changes being effected or prior approval) for the site change will trigger an inspection request from the reviewing division. The move to a new manufacturing site may qualify as a level 1 change in which case the proper submission would be an annual report. In either case an applicant could ask the Field to evaluate their facility. Any site change under SUPAC-IR calls for the new site to be in compliance with cGMP regulations. Should the firm wish to schedule an inspection prior to submission of the site change information to the application, a foreign firm should contact the Foreign Inspection Team in the Division of Manufacturing and Product Quality, Office of Compliance, CDER. Domestic firms should contact their local district office.5. Q: Some investigators have stated that any 483 observations (no matter how minor) means that the inspection is 'violative' for the company. Should a firm assume that if they receive a 483 observation that they are 'violative'?A: The districts use three classifications, NAI (no action indicated), VAI (voluntary action indicated), and OAI (official action indicated). Generally, a firm classified NAI has no findings or a few insignificant findings and is considered to be in compliance and therefore not violative. A firm classified VAI usually has several violations that can be significant if they are not corrected as soon as possible. If the corrections and commitments appear adequate the firm is not considered to be violative. Generally, when a firm is classified OAI the findings are significant and should result in some or all of the following: withhold approval of an application, a warning letter, or an injunction, seizure, and/or prosecution. A firm will remain OAI until they have corrected the deficiencies.6. Q: If a site change described in Section IV includes manufacturing, packaging, and testing together, is it covered?A: Yes.7. Q: When packaging (or testing) is the only part of the manufacturing process which is being moved, is this situation covered by SUPAC-IR?A: Yes. Originally, only packaging (or testing) site changes which were part of a site change for complete manufacturing operation as described in #1 above were covered by SUPAC-IR. However, that position was recently reassessed by FDA. Packaging or testing site changes separate from the rest of the manufacturing operation are acceptable under SUPAC-IR as described in the cover letter.8. Q: Does the Center require any communication from the Field when a company reports a site change in the annual report?A: The facility should have had a successful cGMP inspection within the past two years and the Center does not expect to hear from the Field at the time of submission of the annual report. A firm may request an assessment of a proposed site change from the appropriate FDA district office.9. Q: Does Section IV apply to the addition of facilities not previously listed, or is it limited to sites already listed in the location of operations section?A: SUPAC-IR section IV does include site changes to facilities not already listed in the NDA/ANDA/AADA. For CBE supplements, a new manufacturing site should have an acceptable cGMP status, as previously discussed.10. Q: Are build-outs (extensions of a building) considered a SUPAC-IR level 1 site change?A: At the current time, the Center's position is that build-outs qualify as level 1 site changes. The change should be reported in the annual report as long as the facility has had a satisfactory cGMP inspection within the last two years.11. Q: Is it possible to have a site change covered under SUPAC-IR when the change results in different/revised SOPs?A: If SOPs are different, the implication is that the manufacturing process has also changed. Thus, this site change is not covered under SUPAC-IR. A prior approval supplement is required under 21 CFR 314.70 (b) (2) (vi).12. Q: What is meant by 'personnel common to both manufacturing sites' under part IV. Manufacturing?

A: This means personnel 'already working on the campus who have suitable experience with the manufacturing process.'

MANUFACTURING PROCESS CHANGES

1. Q: If no range was established through validation studies for mixing time, is it possible to make a level 1 change in mixing times?A: This situation does not qualify as a level 1 change.2. Q: If a parameter is not specified in the application (e.g. mixing speed), and you want to change it, is the change within range or outside?

A: If the approved application does not contain the necessary details (e.g., mixing speed), and one wants to change the method of manufacture of the drug product (i.e., equipment and/or process with associated parameters), a prior approval supplement should be filed.

MANUFACTURING EQUIPMENT CHANGES

1. Q: When going from equipment of one scale to one which is 2 or 1/10 the scale, the operating parameters will always change (e.g., airflows will decrease, spray rates will decrease). It is unlikely that the parameters will have been previously validated. Therefore, it would appear that any such change will be a level 2 change. Please comment.

A: If a scale-down of the production batch to 2 or 1/10 the size is needed, operating parameters that would fall within the range established for manufacture of the test batch and the first three production batches (i.e., validation batches) will be regarded as a level 1 change. If they fall outside the validation ranges the change would be permitted under SUPAC IR as a level 2 change. Regardless, SUPAC IR does not address scale-down below 100,000 units.

2. Q: Is a change in mill screen size (to improve flow during formulation) a level 1 change?A: A screen size change to an alternate screen of the same design (holes) and operating principle (sifting) but different diameters to facilitate flow of powder will be regarded as a level 1 change, provided the alternate screen has not altered the particle size distribution of the screened material. Under such conditions, the information can be filed in the annual report.3. Q: Must the equipment be moved from the old site to the new one when the manufacturing site is changed?

The Division Difference Dmg To Target Out Of Cover Ranges

A: A company need not move equipment for a SUPAC-IR site change. However, any equipment should be of the same design and operating principle as the old equipment, and the SOPs and formulation should be the same.

IN VITRO DISSOLUTION

1. Q: Can the equation for profile dissolution be used for comparing a generic product with the reference listed drug product?A: Yes. The equation can be used in this situation. However, under SUPAC-IR, dissolution testing is generally conducted on the applicant's product before and after a particular change is made.2. Q: For Case C testing, specific media are cited. Can other media or other pH's be used?A: The five media indicated for Case C dissolution testing are presented as examples only. Other media, as appropriate for a particular drug product, if properly justified, may be used. Such a situation could involve using different solution compositions to attain a certain pH, as well as some at different pH conditions.3. Q: For SUPAC-IR changes which require multi-point dissolution in several media, is this required of AA drug products? A: For AA drugs (i.e., those drugs identified in the Approved Drug Products With Therapeutic Equivalence Evaluations or the 'Orange Book' as not presenting bioequivalence problems) when the original application only required multi-point single medium dissolution testing for approval, then a multi-point single medium dissolution will be satisfactory where Case C is specified in the SUPAC-IR guidance.4. Q: The inclusion of 'n' in the f2 formula implies that the number and time of the pulls is left to the discretion of the FDA investigator. Choosing points late in the curve could insure a high f2. How will this be avoided?A: It is recommended that only one point past the plateau of the profiles be used.5. Q: Are the points for dissolution profiles listed in the document just guides, or do you expect to see those specific points? For a quickly dissolving drug, points at 10, 20, 30, and 40 may be more appropriate.A: The points listed should be considered to be examples. Others points can be used with justification. It is suggested that at least 4 points (other than zero), equally spaced, be utilized.6. Q: What options are available if f2 fails?A: If an applicant believes the profiles are similar even if dissolution profiles fail f2, the firm may present a scientific justification as to why the observed difference is not due to the proposed change, and could not have significant impact beyond what is normally seen for batches prepared without the change.7. Q: For case C testing, if all of the media are not ones typically used, must the dissolution procedure be validated using these media?A: Yes. All of the methods used should be validated.8. Q: What methods, other than Dr. Amidon's are acceptable?A: This is an evolving area or research. 'Extent of absorption' may be an appropriate alternative, as indicated in the guidance. Full documentation of permeability may require special clinical testing. Physicochemical and in vitro predictors of permeability are being assessed at the FDA. Pending availability of these methods, firms may rely on literature data from pharmacokinetic/mass balance studies that suggest high extent of absorption of a drug across the gastrointestinal mucosa. Absent this information, firms should assume that a drug substance has low permeability and follow the recommendations in the SUPAC-IR guidance accordingly. 9. Q: How exactly is the industry expected to determine or know the permeability of their drug?A: One source of permeability information is the current research being conducted and sponsored by FDA. This information, for other drugs, could be experimentally determined by an applicant. Other alternative methods, related to permeability, may also be useful.10. Q: Are we allowed to monitor the metabolites and sum all the components?A: For determination of extent of absorption related to permeability, it may be appropriate to consider the sum of all components. As described in the guidance, this is 'in the absence of documented instability in the gastro-intestinal tract.' In general, it is appropriate to sum all of the components if the formation of the metabolite occurs following permeation through the gastrointestinal mucosa.11. Q: What constitutes an acceptable in vivo/in vitro correlation? Does 'verified' mean validated?

A: Verified may be thought of as synonymous with validated. The Biopharmaceutics Coordinating Committee in CDER is developing guidance that addresses the general question. Pending availability of this guidance, firms should refer to published literature for information on establishing in vitro/in vivo correlations.

IN VIVO BIO STUDIES

1. Q: If the highest strength was the biobatch strength, and waivers were used for the other strengths, does supporting documentation for SUPAC-IR changes refer to all strengths? Does the answer differ depending on whether the strengths are dose/weight proportional?A: For SUPAC-IR bioequivalence recommendations, the recommended tests apply to all strengths. Regarding bio-requirements, the supporting documentation normally is needed for all strengths. If a bioequivalence study is recommended, then the compositional proportionality of the various strengths may determine if all strengths need to be tested for bioequivalence, or if a strength can be waived. However, this is not the standard comparison that is in the SUPAC-IR Guidance.2. Q: Will many small changes prompt the Agency to require a biostudy?A: Generally, a biostudy will not be requested simply because many changes which individually would not normally require a biostudy, are performed.3. Q: For SUPAC-IR changes which require an in-vivo bioequivalence test, is this requirement also intended for AA drugs which were exempt from bioequivalence testing when originally approved?A: The Center did not intend for SUPAC-IR to impose additional bioequivalence requirements for AA drugs beyond those in an original application. (AA drugs are those identified in the Orange Book as not presenting bioequivalence problems.) Therefore, if bioequivalence testing was not required originally, it will not be required under SUPAC-IR for AA drugs.

4. Q: Would an in vivo bioequivalence study be needed for an AAA@ or non-bioequivalence problem DESI drug even if it one would be needed according to SUPAC?

A: No, since that would conflict with the agency's current bioequivalence policy. 5. Q: When a bio study is required under SUPAC-IR, to what product should a generic product be compared - the Reference Listed Drug or the generic product approved prior to the SUPAC change.

The Division Difference Dmg To Target Out Of Cover Ranger

A: An innovator product should be compared to itself. A generic should be compared to the reference listed drug for that drug product.

STABILITY/CHANGE IN BATCH SIZE

1. Q: When the documentation for a change is one batch on long term stability, is there a time limit between implementation of the change and initiation of the stability study?A: No. But the stability study should start as soon as possible after the drug product is prepared in the market container.2. Q: What is the stability requirement for a level 3 change involving a product with multiple strengths packaged in bottles and blisters? SUPAC-IR states one batch. Can we bracket?A: Testing and data collection involving the use of product bracketing are not the subject of SUPAC-IR. Bracketing may be used with prior approval of the Agency. The amount of data required depends on the type of change and whether or not there is a significant body of data available. If an applicant plans to bracket, the proposed protocol should be submitted to the Agency. This plan should include a protocol for each product. It should indicate all of the approved packaging configurations, and what strengths are approved for each of these. It also should include the approved stability test protocol.3. Q: Who determines how many batches are required for stability when the documentation requests 1-3?A: The answer will be dependent on the specific drug product and the amount of data already available. The appropriate review division should be contacted for further guidance.4. Q: When accelerated stability data are required, is that comparative data?

A: Yes. Historical data may be used for comparison.

MISCELLANEOUS ISSUES

1. Q: The recommended documentation for several SUPAC-IR changes indicates that 'batch records' or 'updated batch records' be submitted. Should copies of batch records be submitted with the appropriate filing? Is batch record defined as the actual blank floor work order or can another manufacturing process description be used? In which cases should the batch records be executed batch records?A: Wherever 'batch record' occurs in the SUPAC-IR guidance, it means executed batch records. These records should be submitted in the designated filing.2. Q: What does the Agency intend by 'notification of change'? Should there be a separate communication to the Agency in addition to the annual report?A: The Agency should be notified of changes by the appropriate submission as described in the guidance..3. Q: May a firm make a SUPAC-IR change immediately after approval of the original application, or is there a waiting period?A: There is no waiting period. SUPAC-IR changes may be made as soon as the application is approved provided the appropriate data are available and filing criteria are addressed.4. Q: When there is a time lag between when changes are made under SUPAC and the submission of the annual report, what evidence is needed to show that an appropriate change will be submitted in the next annual report? What will the FDA investigator expect to see?A: The regulations at 21 CFR 314.70 (d) govern the filing of annual reports. Changes are made according to the applicant's change policy/procedures; these are part of the cGMP requirements. Because all changes should be approved by the appropriate quality unit, some set of documentation (e.g., development protocols, validation runs, batch records, etc.) should exist before the change is made. The investigator would expect to see this documentation.5. Q: Should the information described under 'documentation' be submitted in the filing, or does having the appropriate information on site for the inspection satisfy the requirement?A: The documentation should be included in the designated filing regardless of whether a supplement (prior approval or changes being effected) or annual report is used.6. Q: Are changes such as tablet shape and size covered under SUPAC-IR?A: In general, changes involving size and/or geometry of the tablet are not covered under SUPAC-IR, and would need prior approval supplements. However, changes in thickness due to a composition change may be covered under SUPAC-IR 7. Q: What does the Center expect relative to validation for SUPAC-IR changes?A: A summary of the validation data should be included in submissions describing process changes.8. Q: What is meant by 'validated range'?A: Validated ranges mean the upper and lower limits are validated for a particular manufacturing process. An example of this is the time required during mixing of bulk powders which supports the minimum and maximum time needed to optimize mixing of the contents9. Q: Based on the SUPAC video, it appears that a certificate of analysis and dissolution data need not be submitted in annual reports, but should be held on site. Is this correct?A: These data should be submitted in the annual report.10. Q: A 'significant body of data' is mentioned in several places in the SUPAC-IR guidance. What does this mean?A: If an applicant for a new molecular entity has at least five years of post-approval manufacturing experience, or if the applicant for a new dosage that is an immediate release solid oral, has at least three years of post-approval manufacturing experience, the Center believes that a 'significant body of information' exists for that product.11. Q: In the SUPAC-IR guidance document, what is meant by a 'short period of time'?A: Because it is difficult to specify a single time frame which could be applied to all situations for drug products, the appropriate chemistry team leader should be consulted. Each situation will be defined on a case by case basis.12. Q: If a new dosage form of a product that has been marketed for a number of years is accepted for filing as a generic product through the suitability petition process, will it be considered to have a 'significant body of information'?A: No, it would not. As noted in the definition for significant body of information, a significant body of information is likely to exist after three years of commercial experience for new dosage forms.

Date created: February 19, 1997; last update: July 6, 2005

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