SUPAC: Manufacturing 
Equipment Addendum 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
December 2014 
Pharmaceutical Quality/CMC 
 
   
 
SUPAC: Manufacturing 
Equipment Addendum 
 
Guidance for Industry 
 
 
 
 
 
 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 December 2014 
Pharmaceutical Quality/CMC 
  Contains Nonbinding Recommendations 
 
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  DISCUSSION .................................................................................................................... 2 
IV.  SUPAC IR/MR INFORMATION .................................................................................... 3 
A.  Particle Size Reduction/Separation .............................................................................................. 3 
1. Definitions ........................................................................................................................................ 3 
2. Equipment Classifications ............................................................................................................... 4 
B.  Blending and Mixing...................................................................................................................... 6 
1. Definitions ........................................................................................................................................ 6 
2. Equipment Classifications ............................................................................................................... 6 
C.  Granulation .................................................................................................................................... 7 
1. Definitions ........................................................................................................................................ 7 
2. Equipment Classification ................................................................................................................. 9 
D.  Drying ........................................................................................................................................... 11 
1. Definitions ...................................................................................................................................... 11 
2. Equipment Classifications ............................................................................................................. 13 
E.  Unit Dosing ................................................................................................................................... 14 
1. Definitions ...................................................................................................................................... 14 
2.  Equipment Classifications ............................................................................................................. 15 
F.  Soft Gelatin Capsule .................................................................................................................... 16 
1. Definitions ...................................................................................................................................... 16 
2. Equipment Classifications ............................................................................................................. 18 
G.  Coating/Printing/Drilling ............................................................................................................ 19 
1. Definitions ...................................................................................................................................... 19 
2. Equipment Classification ............................................................................................................... 22 
V.  SUPAC-SS INFORMATION ......................................................................................... 24 
A.  Particle Size Reduction/Separation ............................................................................................ 24 
B.  Mixing ........................................................................................................................................... 24 
1. Definitions ...................................................................................................................................... 24 
2. Equipment Classification ............................................................................................................... 25 
C.  Emulsification ............................................................................................................................... 25 
1. Definitions ...................................................................................................................................... 25  Contains Nonbinding Recommendations 
2. Equipment Classification ............................................................................................................... 26 
D.  Deaeration ..................................................................................................................................... 26 
1. Definitions ...................................................................................................................................... 26 
2. Equipment Classification ............................................................................................................... 27 
E.  Transfer ........................................................................................................................................ 27 
1. Definition ....................................................................................................................................... 27 
2. Equipment Classification ............................................................................................................... 27 
F.  Packaging ...................................................................................................................................... 28 
1. Definitions ...................................................................................................................................... 28 
2. Equipment Classification ............................................................................................................... 29  Contains Nonbinding Recommendations 
1
1  Guidance for Industry  
2  SUPAC: Manufacturing Equipment Addendum 
3   
4   
5  This guidance represents the Food and Drug Administrations (FDAs or Agencys) current thinking on 
6  this topic.  It does not create or confer any rights for or on any person and does not operate to bind FDA 
7  or the public.  You can use an alternative approach if the approach satisfies the requirements of the 
8  applicable statutes and regulations.  If you want to discuss an alternative approach, contact the FDA staff 
9  responsible for implementing this guidance using the contact information on the title page of this 
10  guidance.  
11   
12   
13   
14   
15  I.  INTRODUCTION  
16   
17  This guidance combines and supersedes the following scale-up and post-approval changes 
18  (SUPAC) guidances for industry:  (1) SUPAC-IR/MR:  Immediate Release and Modified 
19  Release Solid Oral Dosage Forms, Manufacturing Equipment Addendum, and (2) SUPAC-SS 
20  Nonsterile Semisolid Dosage Forms, Manufacturing Equipment Addendum.2  It removes the lists 
21  of manufacturing equipment that were in both guidances and clarifies the types of processes being 
22  referenced.   
23   
24  A draft guidance, SUPAC: Manufacturing Equipment Addendum, was published on April 1, 2013.  
25  Comments were received and changes were made to address those comments.  
26   
27  This SUPAC addendum should be used in conjunction with the following SUPAC guidances for 
28  industry:3  (1) Immediate Release Solid Oral Dosage Forms  Scale-Up and Post-Approval 
29  Changes: Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo 
30  Bioequivalence Documentation, (2) SUPAC-MR: Modified Release Solid Oral Dosage Forms 
31  Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro 
32  Dissolution Testing and In Vivo Bioequivalence Documentation, and (3) SUPAC-SS:  Nonsterile 
33  Semisolid Dosage Forms, Scale-Up and Post Approval Changes:  Chemistry Manufacturing and 
34  Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation.4   
35   
36  The SUPAC guidances define:  (1) levels of chemistry, manufacturing, and control change; (2) 
37  recommended chemistry, manufacturing, and controls tests for each level of change; (3) 
38  recommended in vitro dissolution and release tests and/or in vivo bioequivalence tests for each 
                                                 
1 This guidance has been prepared by the Office of Pharmaceutical Science in the Center for Drug Evaluation and 
Research (CDER) at the Food and Drug Administration.  
2  For this guidance only, the new document that is a combination of these two guidances will be referred to as the 
SUPAC addendum. 
3 We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA 
Drugs guidance Web page at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
4 For this guidance only, this collective group of guidances will be referred to as SUPAC guidances. 
  1  Contains Nonbinding Recommendations 
39  level of change; and (4) recommended documentation that should support the change for new 
40  drug applications and abbreviated new drug applications.  
41   
42  This SUPAC addendum, together with the SUPAC guidances, is intended to help you, the 
43  manufacturer, determine the documentation you should submit to FDA regarding manufacturing 
44  equipment changes.   
45   
46  FDAs guidance documents, including this guidance, do not establish legally enforceable 
47  responsibilities.  Instead, guidances describe the Agencys current thinking on a topic and should 
48  be viewed only as recommendations, unless specific regulatory or statutory requirements are 
49  cited.  The use of the word should in Agency guidances means that something is suggested or 
50  recommended, but not required.  
51   
52  II.  BACKGROUND 
53   
54  When the SUPAC equipment addenda were published with tables referencing specific 
55  equipment, the tables were misinterpreted as equipment required by FDA.  FDA recognizes 
56  that scientific innovation and technology advancement are commonplace and play a significant 
57  role in pharmaceutical development, manufacturing, and quality assurance, and we are 
58  concerned that such a misunderstanding could discourage advancements in manufacturing 
59  technologies.  Therefore, this revised SUPAC addendum contains general information on 
60  SUPAC equipment and no longer includes tables referencing specific equipment.  This 
61  guidance also includes changes to clarify the types of processes being referenced.  
62   
63  III.  DISCUSSION    
64   
65  The information in this guidance is presented in broad categories of unit operation.  For 
66  immediate or modified release solid oral dosage forms, broad categories include blending and 
67  mixing, drying, particle size reduction/separation, granulation, unit dosage, coating and printing, 
68  and soft gelatin capsule encapsulation.  For nonsterile semisolid dosage forms, broad categories 
69  include particle size reduction and/or separation, mixing, emulsification, deaeration, transfer, and 
70  packaging.  Definitions and classifications are provided.  For each operation, equipment is 
71  categorized by class (operating principle) and subclass (design characteristic).  Examples of types 
72  of equipment, but not specific brand information, are given within the subclasses. 
73   
74  When assessing manufacturing equipment changes from one class to another or from one 
75  subclass to another, you can follow a risk-based approach that includes a rationale and complies 
76  with the regulations, including the CGMP regulations.5, 6  We also recommend addressing the 
77  impact on the product quality attributes of equipment variations (via process parameters) when 
78  designing and developing the manufacturing process.7 
79   
                                                 
5 21 CFR 314.70. 
6 21 CFR 210-211. 
7 L. X. Yu, G. Amidon, M. A. Khan, S. W. Hoag, J. Polli, G. K. Raju, and J. Woodcock, Understanding 
Pharmaceutical Quality by Design. The AAPS Journal. March 2014. 
  2  Contains Nonbinding Recommendations 
80  When making equipment changes, you will need to determine the filing requirement.8  The 
81  SUPAC guidances provide information on how to do so.  FDA will assess the changes based on 
82  the types of equipment changes being considered.  If you choose an approach that exceeds the 
83  SUPAC guidances and addendum, FDA will assess the changes provided they are supported by 
84  a suitable risk-based assessment.  
85   
86  At the time of the equipment change, you should have available the scientific data and rationale 
87  used to determine the type of change and documentation required.  This information is subject to 
88  FDA review at its discretion.  
89   
90  IV.  SUPAC IR/MR INFORMATION 
91   
92  A.  Particle Size Reduction/Separation 
93   
94  1.  Definitions 
95   
96  a.  Unit Operations 
97    
98  i.  Particle Size Reduction:  The mechanical process of breaking particles into 
99  smaller pieces via one or more particle size reduction mechanisms.  The 
100  mechanical process used generally is referred to as milling.  
101   
102  a.  Particle  Refers to either a discrete particle or a grouping of particles, 
103  generally known as an agglomerate. 
104   
105  b.  Particle Size Reduction Mechanisms 
106   
107    Impact - Particle size reduction by applying an 
108  instantaneous force perpendicular to the 
109  particle/agglomerate surface.  The force can result from 
110  particle-to-particle or particle-to-mill surface collision. 
111   
112    Attrition - Particle size reduction by applying a force in a 
113  direction parallel to the particle surface. 
114   
115    Compression - Particle size reduction by applying a force 
116  slowly (as compared to Impact) to the particle surface in a 
117  direction toward the center of the particle. 
118   
119    Cutting - Particle size reduction by applying a 
120  shearing force to a material. 
121   
122  ii.  Particle Separation:  Particle size classification according to particle size 
123  alone. 
124   
                                                 
8 21 CFR 314.70. 
  3  Contains Nonbinding Recommendations 
125  b.  Operating Principles 
126   
127  i.  Fluid Energy Milling 
128   
129  Particles are reduced in size as a result of high-speed particle-to-particle 
130  impact and/or attrition; also known as micronizing. 
131   
132  ii.  Impact Milling 
133   
134  Particles are reduced in size by high-speed mechanical impact or impact 
135  with other particles; also known as milling, pulverizing, or comminuting. 
136   
137  iii.  Cutting 
138   
139  Particles are reduced in size by mechanical shearing. 
140   
141  iv.  Compression Milling 
142   
143  Particles are reduced in size by compression stress and shear between 
144  two surfaces. 
145   
146  v.  Screening 
147   
148  Particles are reduced in size by mechanically induced attrition through a 
149  screen.  This process commonly is referred to as milling or 
150  deagglomeration. 
151   
152  vi.  Tumble Milling 
153   
154  Particles are reduced in size by attrition utilizing grinding media. 
155   
156  vii.  Separating 
157   
158  Particles are segregated based upon particle size alone and without any 
159  significant particle size reduction.  This process commonly is referred to as 
160  screening or bolting. 
161   
162  2.  Equipment Classifications 
163   
164  a.  Fluid Energy Mills 
165   
166  Fluid energy mill subclasses have no moving parts and primarily are distinguished 
167  from one another by the configuration and/or shape of their chambers, nozzles, 
168  and classifiers. 
169   
170    Tangential Jet 
171    Loop/Oval 
  4  Contains Nonbinding Recommendations 
172    Opposed Jet 
173    Opposed Jet with Dynamic Classifier 
174    Fluidized Bed 
175    Fixed Target 
176    Moving Target 
177    High Pressure Homogenizer 
178   
179  b.  Impact Mills 
180   
181  Impact mill subclasses primarily are distinguished from one another by the 
182  configuration of the grinding heads, chamber grinding liners (if any), and 
183  classifiers. 
184   
185    Hammer Air Swept 
186    Hammer Conventional 
187    Pin/Disc 
188    Cage 
189   
190  c.  Cutting Mills 
191   
192  Although cutting mills may differ from one another in whether the knives are 
193  movable or fixed and in the classifier configuration, no cutting mill subclasses 
194  have been identified. 
195   
196  d.  Compression Mills 
197   
198  Although compression mills may differ from one another in whether one or both 
199  surfaces are moving, no compression mill subclasses have been identified. 
200   
201  e.  Screening Mills 
202   
203  Screening mill subclasses primarily are distinguished from one another by the 
204  rotating element. 
205   
206    Rotating Impeller 
207    Rotating Screen 
208    Oscillating Bar 
209   
210  f.  Tumbling Mills 
211   
212  Tumbling mill subclasses primarily are distinguished from one another by the 
213  grinding media used and by whether the mill is vibrated. 
214   
215    Ball Media 
216    Rod Media 
217    Vibrating 
  5  Contains Nonbinding Recommendations 
218   
219  g.  Separators 
220   
221  Separator subclasses primarily are distinguished from one another by the 
222  mechanical means used to induce particle movement. 
223   
224    Vibratory/Shaker 
225    Centrifugal 
226   
227  B.  Blending and Mixing 
228   
229  1.  Definitions 
230   
231  a.  Unit Operations 
232   
233  Blending and Mixing:  The reorientation of particles relative to one another in 
234  order to achieve uniformity. 
235   
236  b.  Operating Principles 
237   
238  i.  Diffusion Blending (Tumble) 
239   
240  Particles are reoriented in relation to one another when they are 
241  placed in random motion and interparticular friction is reduced 
242  as the result of bed expansion (usually within a rotating 
243  container); also known as tumble blending. 
244   
245  ii.  Convection Mixing 
246   
247  Particles are reoriented in relation to one another as a result 
248  of mechanical movement; also known as paddle or plow 
249  mixing. 
250   
251  iii.  Pneumatic Mixing 
252   
253  Particles are reoriented in relation to one another as a result of 
254  the expansion of a powder bed by gas. 
255   
256  2.  Equipment Classifications 
257   
258  a.  Diffusion Mixers (Tumble) 
259   
260  Diffusion mixer subclasses primarily are distinguished by geometric shape and 
261  the positioning of the axis of rotation. 
262   
263    V-blenders 
264    Double Cone Blenders 
  6  Contains Nonbinding Recommendations 
265    Slant Cone Blenders 
266    Cube Blenders 
267    Bin Blenders 
268    Horizontal/Vertical/Drum Blenders 
269    Static Continuous Blenders 
270    Dynamic Continuous Blenders 
271   
272  b.  Convection Mixers 
273   
274  Convection blender subclasses primarily are distinguished by vessel shape and 
275  impeller geometry. 
276   
277    Ribbon Blenders 
278    Orbiting Screw Blenders 
279    Planetary Blenders 
280    Forberg Blenders 
281    Horizontal Double Arm Blenders 
282    Horizontal High Intensity Mixers 
283    Vertical High Intensity Mixers 
284    Diffusion Mixers (Tumble) with Intensifier/Agitator 
285   
286  c.  Pneumatic Mixers 
287   
288  Although pneumatic mixers may differ from one another in vessel geometry, air 
289  nozzle type, and air nozzle configuration, no pneumatic mixer subclasses have 
290  been identified. 
291   
292   
293  C.  Granulation 
294   
295  1.  Definitions 
296   
297  a.  Unit Operations 
298   
299  Granulation:  The process of creating granules.  The powder morphology is 
300  modified through the use of either a liquid that causes particles to bind through 
301  capillary forces or dry compaction forces.  The process will result in one or more 
302  of the following powder properties:  enhanced flow; increased compressibility; 
303  densification; alteration of physical appearance to more spherical, uniform, or 
304  larger particles; and/or enhanced hydrophilic surface properties. 
305   
306  b.  Operating Principles 
307   
308  i.  Dry Granulation 
309   
  7  Contains Nonbinding Recommendations 
310  Dry powder densification and/or agglomeration by direct 
311  physical compaction. 
312   
313  ii.  Wet High-Shear Granulation 
314   
315  Powder densification and/or agglomeration by the incorporation 
316  of a granulation fluid into the powder with high-power-per-unit 
317  mass, through rotating high-shear forces. 
318   
319  iii.  Wet Low-Shear Granulation 
320   
321  Powder densification and/or agglomeration by the incorporation 
322  of a granulation fluid into the powder with low-power-per-unit 
323  mass, through rotating low-shear forces. 
324   
325  iv.  Low-Shear Tumble Granulation 
326   
327  Powder densification and/or agglomeration by the incorporation 
328  of a granulation fluid into the powder with low-power-per-unit 
329  mass, through rotation of the container vessel and/or intensifier 
330  bar. 
331   
332  v.  Extrusion Granulation 
333   
334  Plasticization of solids or wetted mass of solids and 
335  granulation fluid with linear shear through a sized orifice using 
336  a pressure gradient. 
337   
338  vi.  Rotary Granulation 
339   
340  Spheronization, agglomeration, and/or densification of a wetted or 
341  non-wetted powder or extruded material.  This is accomplished by 
342  centrifugal or rotational forces from a central rotating disk, rotating 
343  walls, or both.  The process may include the incorporation and/or 
344  drying of a granulation fluid. 
345   
346  vii.  Fluid Bed Granulation 
347   
348  Powder densification and/or agglomeration with little or no shear 
349  by direct granulation fluid atomization and impingement on 
350  solids, while suspended by a controlled gas stream, with 
351  simultaneous drying. 
352   
353  viii.  Spray Dry Granulation 
354   
  8  Contains Nonbinding Recommendations 
355  A pumpable granulating liquid containing solids (in solution or 
356  suspension) is atomized in a drying chamber and rapidly dried by a 
357  controlled gas stream, producing a dry powder. 
358   
359  ix.  Hot-melt Granulation 
360   
361  An agglomeration process that utilizes a molten liquid as a 
362  binder(s) or granulation matrix in which the active 
363  pharmaceutical ingredient (API) is mixed and then cooled down 
364  followed by milling into powder.  This is usually accomplished 
365  in a temperature controlled jacketed high shear granulating tank 
366  or using a heated nozzle that sprays the molten binders(s) onto 
367  the fluidizing bed of the API and other inactive ingredients.  
368   
369  x.  Melt Extrusion 
370   
371  A process that involves melting and mixing API and an excipient 
372  (generally a polymer) using low or high shear kneading screws 
373  followed by cooling and then milling into granules. Thermal 
374  energy for melting is usually supplied by the electric/water heater 
375  placed on the barrel. Materials are either premixed or fed into an 
376  extruder separately. Melt extruder subclasses primarily are 
377  distinguished by the configuration of the screw. 
378   
379    Single screw extruder 
380    Twin screw extruder   
381   
382  2.  Equipment Classification 
383   
384  a.  Dry Granulator 
385   
386  Dry granulator subclasses primarily are distinguished by the densification force 
387  application mechanism. 
388   
389    Slugging 
390    Roller Compaction 
391   
392  b.  Wet High-Shear Granulator 
393   
394  Wet high-shear granulator subclasses primarily are distinguished by the 
395  geometric positioning of the primary impellers; impellers can be top, bottom, 
396  or side driven. 
397   
398    Vertical (Top or Bottom Driven) 
399    Horizontal (Side Driven) 
400   
  9  Contains Nonbinding Recommendations 
401  c.  Wet Low-Shear Granulator 
402   
403  Wet low-shear granulator subclasses primarily are distinguished by the 
404  geometry and design of the shear inducing components; shear can be induced 
405  by rotating impeller, reciprocal kneading action, or convection screw action. 
406   
407    Planetary 
408    Kneading 
409    Screw 
410   
411  d.  Low-Shear Tumble Granulator 
412   
413  Although low-shear tumble granulators may differ from one another in vessel 
414  geometry and type of dispersion or intensifier bar, no low-shear tumble 
415  granulator subclasses have been identified.   
416   
417    Slant cone 
418    Double cone 
419    V-blender 
420   
421  e.  Extrusion Granulator 
422   
423  Extrusion granulator subclasses primarily are distinguished by the 
424  orientation of extrusion surfaces and driving pressure production 
425  mechanism. 
426   
427    Radial or Basket 
428    Axial 
429    Ram 
430    Roller, Gear, or Pelletizer 
431   
432  f.  Rotary Granulator 
433   
434  Rotary granulator subclasses primarily are distinguished by their structural 
435  architecture.  They have either open top architecture, such as a vertical centrifugal 
436  spheronizer, or closed top architecture, such as a closed top fluid bed dryer. 
437   
438    Open 
439    Closed 
440   
441  g.  Fluid Bed Granulator 
442   
443  Although fluid bed granulators may differ from one another in geometry, 
444  operating pressures, and other conditions, no fluid bed granulator subclasses 
445  have been identified. 
446   
  10  Contains Nonbinding Recommendations 
447  h.  Spray Dry Granulator 
448   
449  Although spray dry granulators may differ from one another in geometry, 
450  operating pressures, and other conditions, no spray dry granulator subclasses have 
451  been identified. 
452   
453  i.  Hot-melt Granulator 
454   
455  Although, hot-melt granulator may differ from one another in primarily melting the 
456  inactive ingredient (particularly the binder or other polymeric matrices), no 
457  subclasses have been identified at this time.  
458   
459  Note: 
460  If a single piece of equipment is capable of performing multiple discrete unit operations (mixing, 
461  granulating, drying), the unit was evaluated solely for its ability to granulate.  If multifunctional 
462  units were incapable of discrete steps (fluid bed granulator/drier), the unit was evaluated as an 
463  integrated unit. 
464   
465  D.  Drying 
466   
467  1.  Definitions 
468   
469  a.  Unit Operation 
470   
471  Drying:  The removal of a liquid from a solid by evaporation. 
472   
473  b.  Operating Principles 
474   
475  i.  Direct Heating, Static Solids Bed 
476   
477  Heat transfer is accomplished by direct contact between the wet 
478  solids and hot gases.  The vaporized liquid is carried away by the 
479  drying gases.  There is no relative motion among solid particles. 
480  The solids bed exists as a dense bed, with the particles resting upon 
481  one another. 
482   
483  ii.  Direct Heating, Moving Solids Bed 
484   
485  Heat transfer is accomplished by direct contact between the wet 
486  solids and hot gases.  The vaporized liquid is carried away by the 
487  drying gases.  Solids motion is achieved by either mechanical 
488  agitation or gravity force, which slightly expands the bed enough to 
489  flow one particle over another. 
490   
491  iii.  Direct Heating, Fluidized Solids Bed 
492   
  11  Contains Nonbinding Recommendations 
493  Heat transfer is accomplished by direct contact between the wet 
494  solids and hot gases.  The vaporized liquid is carried away by the 
495  drying gases.  The solids are in an expanded condition, with the 
496  particles supported by drag forces caused by the gas phase.  The 
497  solids and gases intermix and behave like a boiling liquid.  This 
498  process commonly is referred to as fluid bed drying. 
499   
500  iv.  Direct Heating, Dilute Solids Bed, Spray Drying 
501   
502  Heat transfer is accomplished by direct contact between a highly 
503  dispersed liquid and hot gases.  The feed liquid may be a solution, 
504  slurry, emulsion, gel or paste, provided it is pumpable and capable 
505  of being atomized.  The fluid is dispersed as fine droplets into a 
506  moving stream of hot gases, where they evaporate rapidly before 
507  reaching the wall of the drying chamber.  The vaporized liquid is 
508  carried away by the drying gases.  The solids are fully expanded 
509  and so widely separated that they exert essentially no influence on 
510  one another. 
511   
512  v.  Direct Heating, Dilute Solids Bed, Flash Drying 
513   
514  Heat transfer is accomplished by direct contact between wet solids 
515  and hot gases.  The solid mass is suspended in a finely divided state 
516  in a high-velocity and high-temperature gas stream.  The vaporized 
517  liquid is carried away by the drying gases. 
518   
519  vi.  Indirect Conduction, Moving Solids Bed 
520   
521  Heat transfer to the wet solid is through a retaining wall.  The 
522  vaporized liquid is removed independently from the heating 
523  medium.  Solids motion is achieved by either mechanical agitation 
524  or gravity force, which slightly expands the bed enough to flow one 
525  particle over another. 
526   
527  vii.  Indirect Conduction, Static Solids Bed 
528   
529  Heat transfer to the wet solid is through a retaining wall.  The 
530  vaporized liquid is removed independently from the heating 
531  medium.  There is no relative motion among solid particles.  The 
532  solids bed exists as a dense bed, with the particles resting upon one 
533  another. 
534   
535  viii.  Indirect Conduction, Lyophilization 
536   
537  Drying in which the water vapor sublimes from the product after 
538  freezing. 
  12  Contains Nonbinding Recommendations 
539   
540  ix.  Gas Stripping 
541   
542  Heat transfer is a combination of direct and indirect heating.  The 
543  solids motion is achieved by agitation and the bed is partially 
544  fluidized. 
545   
546  x.  Indirect Radiant, Moving Solids Bed 
547   
548  Heat transfer is accomplished with varying wavelengths of energy.  
549  Vaporized liquid is removed independently from the solids bed.   
550  The solids motion is achieved by mechanical agitation, which 
551  slightly expands the bed enough to flow one particle over one 
552  another.  This process commonly is referred to as microwave 
553  drying. 
554   
555  2.  Equipment Classifications 
556   
557  a.  Direct Heating, Static Solids Bed 
558   
559  Static solids bed subclasses primarily are distinguished by the method of 
560  moving the solids into the dryer. 
561   
562    Tray and Truck 
563    Belt 
564   
565  b.  Direct Heating, Moving Solids Bed 
566   
567  Moving solids bed subclasses primarily are distinguished by the method or 
568  technology for moving the solids bed. 
569   
570    Rotating Tray 
571    Horizontal Vibrating Conveyor 
572   
573  c.  Direct Heating, Fluidized Solids Bed (Fluid Bed Dryer) 
574  
575  Although fluid bed dryers may differ from one another in geometry, operating 
576  pressures, and other conditions, no fluidized solids bed dryer subclasses have 
577  been identified. 
578  
579  d.  Direct Heating, Dilute Solids Bed, Spray Dryer 
580  
581  Although spray dryers may differ from one another in geometry, operating 
582  pressures, and other conditions, no spray dryer subclasses have been identified. 
583  
  13  Contains Nonbinding Recommendations 
584  e.  Direct Heating, Dilute Solids Bed, Flash Dryer 
585  
586  Although flash dryers may differ from one another in geometry, operating 
587  pressures, and other conditions, no flash dryer subclasses have been identified. 
588  
589  f.  Indirect Conduction Heating, Moving Solids Bed 
590   
591  Moving solids bed subclasses primarily are distinguished by the method or 
592  technology for moving the solids bed. 
593   
594    Paddle 
595    Rotary (Tumble) 
596    Agitation 
597   
598    g.  Indirect Conduction Heating, Static Solids Beds 
599   
600  No indirect heating, static solids bed shelf dryer subclasses have been 
601  identified. 
602   
603  h.  Indirect Conduction, Lyophilization 
604   
605  No lyophilizer subclasses have been identified. 
606   
607  i.  Gas Stripping 
608   
609  Although gas stripping dryers may differ from one another in geometry, shape of 
610  agitator, and how fluidizing gas is moved through the bed, no gas stripping dryer 
611  subclasses have been identified. 
612   
613  j.  Indirect Radiant Heating, Moving Solids Bed (Microwave Dryer)  
614   
615  Although microwave dryers may differ from one another in vessel 
616  geometry and the way microwaves are directed into the solids, no 
617  indirect radiant heating, moving solids bed dryer subclasses have been 
618  identified. 
619   
620  Note:  If a single piece of equipment is capable of performing multiple discrete unit operations 
621  (mixing, granulating, drying), the unit was evaluated solely for its ability to dry.  The drying 
622  equipment was sorted into similar classes of equipment, based upon the method of heat transfer 
623  and the dynamics of the solids bed. 
624   
625  E.  Unit Dosing 
626   
627  1.  Definitions 
628   
629  a.  Unit Operation 
630   
  14  Contains Nonbinding Recommendations 
631  Unit Dosing:  The division of a powder blend into uniform single portions for 
632  delivery to patients. 
633   
634  b.  Operating Principles  
635   
636    i.  Tabletting 
637   
638  The division of a powder blend in which compression force is 
639  applied to form a single unit dose. 
640   
641  ii.  Encapsulating 
642   
643  The division of material into a hard gelatin capsule.  Encapsulators 
644  should all have the following operating principles in common:  
645  rectification (orientation of the hard gelatin capsules), separation of 
646  capsule caps from bodies, dosing of fill material/formulation, 
647  rejoining of caps and bodies, and ejection of filled capsules. 
648   
649  iii.  Powder Filling 
650   
651  The division of a powder blend into a container closure system.  
652  2.   Equipment Classifications 
653   
654  a.  Tablet Press 
655   
656  Tablet press subclasses primarily are distinguished from one another by the 
657  method that the powder blend is delivered to the die cavity.  Tablet presses can 
658  deliver powders without mechanical assistance (gravity), with mechanical 
659  assistance (power assisted), by rotational forces (centrifugal), and in two different 
660  locations where a tablet core is formed and subsequently an outer layer of coating 
661  material is applied (compression coating). 
662   
663    Gravity 
664    Power Assisted 
665    Centrifugal 
666    Compression Coating 
667   
668  Tablet press subclasses are also distinguished from one another for some special 
669  types of tablets where more than one hopper and precise powder feeding 
670  mechanism might be necessary. 
671   
672    Multi-tablet press for micro/mini tablet  
673    Multi-layer tablet press (bi-layer, tri-layer) 
674   
675  b.  Encapsulator 
676   
  15  Contains Nonbinding Recommendations 
677  Encapsulator subclasses primarily are distinguished from one another by the 
678  method that is used for introducing material into the capsule.  Encapsulators 
679  can deliver materials with a rotating auger, vacuum, vibration of perforated 
680  plate, tamping into a bored disk (dosing disk), or cylindrical tubes fitted with 
681  pistons (dosator). 
682   
683    Auger 
684    Vacuum 
685    Vibratory 
686    Dosing Disk 
687    Dosator 
688   
689  c.  Powder Filler 
690   
691  Subclasses of powder fillers primarily are distinguished by the method used to 
692  deliver the predetermined amount for container fill. 
693   
694    Vacuum 
695    Auger 
696   
697  F.  Soft Gelatin Capsule 
698   
699  1.  Definitions 
700   
701  a.  Unit Operations 
702   
703  i.  Gel Mass Preparation:  The manufacture of a homogeneous, 
704  degassed liquid mass (solution) of gelatin, plasticizer, water, and 
705  other additives, either in solution or suspension, such as colorants, 
706  pigments, flavors, preservatives, etc., that comprise a unique 
707  functional gel shell formation.  The operation may be performed in 
708  discreet steps or by continuous processing.  Minor components can 
709  be added after the liquid gel mass is made. 
710   
711  ii.  Fill Mixing:  The mixing of either liquids or solids with other liquids 
712  to form a solution; blending of limited solubility solid(s) with a 
713  liquid carrier and suspending agents used to stabilize the blend to 
714  form a suspension; or the uniform combination of dry inert and drug 
715  active substances to form a dry powder fill suitable for 
716  encapsulation.  The reader should refer to the other sections of this 
717  document for dry fill manufacture. 
718   
719  iii.  Encapsulation:  The continuous casting of gel ribbons, with liquid 
720  fill material being injected between the gel ribbons using a positive 
721  displacement pump or, for dry materials being gravity or force fed 
722  with capsule formation using a rotary die. 
723   
  16  Contains Nonbinding Recommendations 
724  iv.  Washing:  The continuous removal of a lubricant material from the 
725  outside of the formed capsule.  The washing operation is unique to 
726  each manufacturers operation and generally uses in-house 
727  fabricated equipment.  This equipment will not be discussed in this 
728  guidance document. 
729   
730  v.  Drying:  The removal of the majority of water from the capsules 
731  gel shell by tumbling and subsequent tray drying using conditioned 
732  air, which enhances the size, shape, and shell physical properties of 
733  the final product.  The drying operation is unique to each 
734  manufacturers operation and generally uses in-house fabricated 
735  equipment.  This equipment will not be discussed in this guidance 
736  document. 
737   
738  vi.  Inspection/Sorting:  The process wherein undesirable capsules are 
739  removed, including misshapen, leaking, and unfilled capsules as 
740  well as agglomerates of capsules. 
741   
742  vii.  Printing:  The marking of a capsule surface for the purpose of 
743  product identification, using a suitable printing media or method. 
744   
745  b.  Operating Principles  
746   
747    i.  Mixing 
748   
749  The combination of solid and liquid components, including 
750  suspending aid(s) at either ambient or elevated temperatures to 
751  form a solution, suspension, or dry powder blend for the 
752  manufacture of gel mass or fill material.  Mixing also includes 
753  the incorporation of minor components into the liquid gel mass. 
754   
755  ii.  Deaggregation 
756   
757  The removal of aggregates using a suitable homogenizer/mill to 
758  provide a pumpable fill material.  The procedure has minimal 
759  effect on the particle size distribution of the initial solid 
760  component(s), and is viewed as a processing aid.9
 
761   
762  iii.  Deaeration 
763   
764  The removal of entrapped air from either the gel mass or fill 
765  material, solution or suspension.  This process can take place in 
766  either the mixing vessel, through the application of vacuum, or 
767  a separate off-line step. 
768   
                                                 
9 Carstensen, J. T., Theory of Pharmaceutical Systems, Volume 11 Heterogeneous Systems, Academic Press, New York, 
NY, 1973, p 51. 
  17  Contains Nonbinding Recommendations 
769  iv.  Holding 
770   
771  The storage of liquid gel mass or fill material in a vessel, with 
772  a mixer or without, prior to encapsulation, which also may be 
773  equipped with a jacket for either heating or cooling. 
774   
775  v.  Encapsulation 
776   
777  The formation of capsules using a rotary die machine.10
 
778   
779  vi.  Inspection/Sorting 
780   
781  The physical removal of misshapen, leaking, or 
782  agglomerated capsules, using either a manual or automatic 
783  operation. 
784   
785  vii.  Printing 
786   
787  The user of this document is asked to refer to the coating/printing 
788  section, in which the use of various pieces of equipment are defined 
789  and categorized. 
790   
791  2.  Equipment Classifications 
792   
793  a.  Mixers and Mixing Vessels 
794   
795  Mixer and mixing vessel subclasses primarily are distinguished by the mixing 
796  energy, mixer type, and whether a jacketed vessel with vacuum capabilities is 
797  used in conjunction with a specific mixer. 
798   
799    Low Energy Mixer 
800    High Energy Mixer 
801    Planetary 
802    Jacketed Vessel With and Without Vacuum 
803   
804  b.  Deaggregators 
805   
806  Deaggregator subclasses primarily are distinguished by the type of 
807  mechanical action imparted to the material. 
808   
809    Rotor/Stator 
                                                 
10 Lachman, L., H. A. Lieberman, and J. L. Kanig (Eds.), The Theory and Practice of Industrial Pharmacy, 
Chapter 3,  p. 359 (Stanley, J. P.),  Philadelphia  Lea & Febiger, 1971; Tyle, P. (Ed.), Specialized Drug 
Delivery Systems, Manufacturing and Production Technology, Chapter 10,  p. 409 (Wilkinson, P.K. and F.S. 
Hom), New York;  M. Dekker, 1990;  Porter, S., Remingtons Pharmaceutical Sciences, Edition 18, Chapter 
89, pp. 1662 - 1665, Easton, Penn.:  Mack Publishing Co. 
  18  Contains Nonbinding Recommendations 
810    Roller 
811    Cutting Mills 
812    Stone Mills 
813    Tumbling Mills 
814   
815  c.  Deaerators 
816   
817  Deaerator subclasses primarily are distinguished by the air removal path, either 
818  through the bulk or through a thin film, and whether it is a batch or in-line 
819  process. 
820   
821    Vacuum Vessel 
822    Off Line/In Line 
823   
824  d.  Holding Vessels 
825   
826  Although holding vessels may differ from one another, based upon whether they 
827  are jacketed, with and without integrated mixing capabilities, no holding vessel 
828  subclasses have been identified. 
829   
830    Jacketed vessel with and without mixing system 
831   
832  e.  Encapsulators 
833   
834  Encapsulator subclasses primarily are distinguished by the method used to inject 
835  the fill material. 
836   
837    Positive Displacement Pump 
838    Gravity or Force Fed 
839   
840  f.  Inspection/Sorting 
841   
842  Inspection/sorting equipment subclasses primarily are distinguished by the 
843  method used to present the capsule for viewing and mechanical method of 
844  separation. 
845   
846    Belt 
847    Vibratory 
848    Roller 
849    Rotary Table 
850    Electromechanical 
851   
852  G.  Coating/Printing/Drilling 
853   
854  1.  Definitions 
855   
  19  Contains Nonbinding Recommendations 
856  a.  Unit Operation 
857   
858  i.  Coating:  The uniform deposition of a layer of material on 
859  or around a solid dosage form, or component thereof, to: 
860   
861  a.  Protect the drug from its surrounding environment 
862  (air, moisture, and light), with a view to improving 
863  stability. 
864  b.  Mask unpleasant taste, odor, or color of the drug. 
865  c.  Increase the ease of ingesting the product for the patient. 
866  d.  Impart a characteristic appearance to the tablets, which 
867  facilitates product identification and aids patient 
868  compliance. 
869  e.  Provide physical protection to facilitate handling.  This 
870  includes minimizing dust generation in subsequent unit 
871  operations. 
872  f.  Reduce the risk of interaction between incompatible 
873  components.  This would be achieved by coating one or 
874  more of the offending ingredients. 
875  g.  Modify the release of drug from the dosage form.  This 
876  includes delaying, extending, and sustaining drug substance 
877  release. 
878  h.  Modify the dosage form by depositing the API or drug 
879  substance on or around a core tablet, which could be a 
880  placebo core tablet or a tablet containing another drug or a 
881  fractional quantity of the same drug. 
882   
883  The coating material deposition typically is accomplished 
884  through one of six major techniques: 
885   
886  a.  Sugar Coating - Deposition of coating material onto 
887  the substrate from aqueous solution/suspension of 
888  coatings, based predominately upon sucrose as a raw 
889  material. 
890  b.  Film Coating - The deposition of polymeric film onto 
891  the solid dosage form. 
892  c.  Core Enrobing - The gelatin coating of gravity or force 
893  fed pre- formed tablets or caplets. 
894  d.  Microencapsulation - The deposition of a coating material 
895  onto a particle, pellet, granule, or bead core.  The 
896  substrate in this application ranges in size from submicron 
897  to several millimeters.  It is this size range that 
898  differentiates it from the standard coating described in 1 
899  and 2 above. 
900  e.   Compression Coating (also addressed in the Unit Dosing 
901  section) - A coating process where a dry coatings blend is 
902  applied on a previously compressed core tablet using a 
  20  Contains Nonbinding Recommendations 
903  tablet compression machine.11 Therefore, this process is 
904  also known as a dry coating process that does not involve 
905  any water or any other solvent in the coating process. 
906  f.  Active/API coating - Deposition of active pharmaceutical 
907  ingredient (API or drug substance) on or around a core 
908  tablet utilizing any of the above five coating techniques. 
909   
910  ii.  Printing:  The marking of a capsule or tablet surface for the 
911  purpose of product identification.  Printing may be accomplished 
912  by either the application of a contrasting colored polymer (ink) 
913  onto the surface of a capsule or tablet, or by the use of laser 
914  etching. 
915   
916  The method of application, provided the ink formulation is not 
917  altered, is of no consequence to the physical-chemical properties of 
918  the product. 
919   
920  iii.  Drilling:  The drilling or ablating of a hole or holes through the 
921  polymeric film coating shell on the surfaces of a solid oral dosage 
922  form using a laser.  The polymeric film shell is not soluble in 
923  vivo.  The hole or holes allow for the modified release of the drug 
924  from the core of the dosage form. 
925   
926  b.  Operating Principles  
927   
928      i.  Pan Coating 
929  The uniform deposition of coating material onto the surface of a 
930  solid dosage form, or component thereof, while being translated via 
931  a rotating vessel. 
932   
933  ii.  Gas Suspension 
934   
935  The application of a coating material onto a solid dosage form, or 
936  component thereof, while being entrained in a process gas stream. 
937   
938  Alternatively, this may be accomplished simultaneously by 
939  spraying the coating material and substrate into a process gas 
940  stream. 
941   
942  iii.  Vacuum Film Coating 
943   
                                                 
11 W.C. Gunsel & R.G. Dusel. Compression-coated and layer tablets.  In H.A.Lieberman, L. Lachman & B. 
Schwartz (Eds), Pharmaceutical Dosage Forms: Tablets Vol 1, 1989,  pp. 247-249. Mercel Dekker, Inc.  
  21  Contains Nonbinding Recommendations 
944  This technique uses a jacketed pan equipped with a baffle system. 
945  Tablets are placed into the sealed pan, an inert gas (i.e., nitrogen) 
946  is used to displace the air and then a vacuum is drawn. 
947   
948  iv.  Dip Coating 
949   
950  Coating is applied to the substrate by dipping it into the 
951  coating material.  Drying is accomplished using pan coating 
952  equipment. 
953   
954  v.  Electrostatic Coating 
955   
956  A strong electrostatic charge is applied to the surface of the 
957  substrate.  The coating material containing oppositely charged ionic 
958  species is sprayed onto the substrate. 
959   
960  vi.  Compression Coating 
961   
962  Refer to the Unit Dosing section of this document.  
963  vii.  Ink-Based Printing 
964  The application of contrasting colored polymer (ink) onto 
965  the surface of a tablet or capsule. 
966   
967  viii.  Laser Etching 
968   
969  The application of identifying markings onto the surface of a 
970  tablet or capsule using laser-based technology. 
971   
972  ix.  Drilling 
973   
974  A drilling system typically is a custom built unit consisting of a 
975  material handling system to orient and hold the solid dosage form, 
976  a laser (or lasers), and optics (lenses, mirrors, deflectors, etc.) to 
977  ablate the hole or holes, and controls.  The drilling unit may include 
978  debris extraction and inspection systems as well.  The sorting, 
979  orienting, and holding equipment commonly is provided by dosage 
980  form printing equipment manufacturers, and is considered ancillary 
981  in this use. 
982   
983  2.  Equipment Classification 
984   
985  a.  Pan Coating 
986   
987  Pan coating subclasses primarily are distinguished by the pan configuration, the 
988  pan perforations, and/or the perforated device used to introduce process air for 
  22  Contains Nonbinding Recommendations 
989  drying purposes.  Perforated coating systems include both batch and continuous 
990  coating processes. 
991   
992    Non-perforated (conventional) Coating System 
993    Perforated Coating System 
994   
995  b.  Gas Suspension 
996   
997  Gas suspension subclasses primarily are distinguished by the method 
998  by which the coating is applied to the substrate. 
999   
1000    Fluidized Bed with bottom spray mechanism 
1001    Fluidized Bed with tangential spray mechanism 
1002    Fluidized Bed with top spray mechanism 
1003    Fluidized Bed with Wurster column  
1004    Spray Congealing/Drying 
1005   
1006  c.  Vacuum Film Coating 
1007   
1008  Although there may be differences in the jacketed pan, baffle system, or 
1009  vacuum source, no vacuum film coating subclasses have been identified. 
1010   
1011  d.  Dip Coating 
1012   
1013  Because of the custom design associated with this class of coating, no dip 
1014  coating subclasses or examples have been identified. 
1015   
1016  e.  Electrostatic Coating 
1017   
1018  Because of the custom design associated with this class of coating, no 
1019  electrostatic coating subclasses or examples have been identified. 
1020   
1021  f.  Compression Coating 
1022   
1023  Refer to the Unit Dosing section of this document. 
1024   
1025  g.  Ink-Based Printing 
1026   
1027  Ink-based printing subclasses primarily are distinguished by the method by which 
1028  the marking is applied to a capsule or tablet surface. 
1029   
1030    Offset 
1031    Ink Jet 
1032   
1033  h.  Laser Etching (Printing) 
1034   
  23  Contains Nonbinding Recommendations 
1035  Although laser etching systems may differ from one another, no laser 
1036  etching subclasses have been identified. 
1037   
1038  i.  Drilling 
1039   
1040  The method of producing the laser pulse that ablates the hole(s) is of no 
1041  consequence to the physical-chemical properties of the product.  Therefore, no 
1042  dosage form drilling equipment subclasses have been identified. 
1043   
1044  V.  SUPAC-SS INFORMATION 
1045   
1046  A.  Particle Size Reduction/Separation 
1047   
1048  The same definition and classification applies as described in section IV. A. for IR/MR 
1049  products. 
1050   
1051  B.  Mixing 
1052   
1053  1.  Definitions 
1054   
1055  a.  Unit Operation 
1056   
1057  Mixing:  The reorientation of particles relative to one another to achieve 
1058  uniformity or randomness.  This process can include wetting of solids by a liquid 
1059  phase, dispersion of discrete particles, or deagglomeration into a continuous 
1060  phase.  Heating and cooling via indirect conduction may be used in this operation 
1061  to facilitate phase mixing or stabilization. 
1062   
1063  b.  Operating Principles 
1064   
1065  i.  Convection Mixing, Low Shear:  Mixing process with a repeated 
1066  pattern of cycling material from top to bottom, in which dispersion 
1067  occurs under low power per unit mass through rotating low shear 
1068  forces. 
1069   
1070  ii.  Convection Mixing, High Shear:  Mixing process with a repeated 
1071  pattern of cycling material from top to bottom, in which dispersion 
1072  occurs under high power per unit mass through rotating high shear 
1073  forces. 
1074   
1075  iii.  Roller Mixing (Milling):  Mixing process by high mechanical 
1076  shearing action where compression stress is achieved by passing 
1077  material between a series of rotating rolls.  This is commonly 
1078  referred to as compression or roller milling. 
1079   
  24  Contains Nonbinding Recommendations 
1080  iv.  Static Mixing:  Mixing process in which material passes through a 
1081  tube with stationary baffles.  The mixer is generally used in 
1082  conjunction with an in-line pump. 
1083   
1084  2.  Equipment Classification 
1085   
1086  a.  Convection Mixers, Low Shear 
1087   
1088  This group normally operates under low shear conditions and is broken down by 
1089  impeller design and movement.  Design can also include a jacketed vessel to 
1090  facilitate heat transfer. 
1091   
1092     Anchor or sweepgate 
1093     Impeller 
1094     Planetary 
1095   
1096  b.  Convection Mixers, High Shear 
1097   
1098  This group normally operates only under high shear conditions.  Subclasses are 
1099  differentiated by how the high shear is introduced into the material, such as by a 
1100  dispersator with serrated blades or homogenizer with rotor stator. 
1101   
1102     Dispersator 
1103     Rotor stator 
1104   
1105  c.  Roller Mixers (Mills) 
1106   
1107  No roller mixer subclasses have been identified. 
1108   
1109  d.  Static Mixers 
1110   
1111  No static mixer subclasses have been identified. 
1112   
1113   
1114  Note:  If a single piece of equipment is capable of performing multiple discrete unit operations, 
1115  it has been evaluated solely for its ability to mix materials. 
1116   
1117  C.  Emulsification 
1118   
1119  1.  Definitions 
1120   
1121  a.  Unit Operation 
1122   
1123  Emulsification:  The application of physical energy to a liquid system consisting of 
1124  at least two immiscible phases, causing one phase to be dispersed into the other. 
1125   
1126  b.  Operating Principles 
1127   
  25  Contains Nonbinding Recommendations 
1128  i.  Low Shear Emulsification:  Use of low shear energy using 
1129  mechanical mixing with an impeller to achieve a dispersion of the 
1130  mixture.  The effectiveness of this operation is especially dependent 
1131  on proper formulation. 
1132   
1133  ii.  High Shear Emulsification:  Use of high shear energy to 
1134  achieve a dispersion of the immiscible phases.  High shear can 
1135  be achieved by the following means: 
1136   
1137  a.  Stirring the mixture with a high speed chopper or 
1138  saw-tooth dispersator. 
1139   
1140  b.  Passing the mixture through the gap between a high-
1141  speed rotor and a stationary stator. 
1142   
1143  c.  Passing the mixture through a small orifice at high pressure 
1144  (valve- type homogenizer) or through a small orifice at high 
1145  pressure followed by impact against a hard surface or 
1146  opposing stream (valve-impactor type homogenizer), 
1147  causing sudden changes of pressure. 
1148   
1149  2.  Equipment Classification 
1150   
1151  a.  Low Shear Emulsifiers 
1152   
1153  Although low shear emulsification equipment (mechanical stirrers or impellers) 
1154  can differ in the type of fluid flow imparted to the mixture (axial-flow propeller or 
1155  radial-flow turbines), no subclasses have been defined. 
1156   
1157  b.  High Shear Emulsifiers 
1158   
1159  Subclasses of high shear emulsification equipment differ in the method used 
1160  to generate high shear. 
1161   
1162     Dispersator 
1163     Rotor stator 
1164     Valve or pressure homogenizer 
1165   
1166  Note:   If a single piece of equipment is capable of performing multiple discrete unit  
1167  operations, the unit has been evaluated solely for its ability to emulsify materials. 
1168   
1169  D.  Deaeration 
1170     
1171  1.  Definitions 
1172   
1173  a.  Unit Operation 
1174   
  26  Contains Nonbinding Recommendations 
1175  Deaeration:  The elimination of trapped gases to provide more accurate 
1176  volumetric measurements and remove potentially reactive gases. 
1177   
1178  b.  Operating Principles 
1179   
1180  The use of vacuum or negative pressure, alone or in combination with mechanical 
1181  intervention or assistance. 
1182   
1183  2.  Equipment Classification 
1184   
1185  a.  Deaerators 
1186   
1187  Deaerator subclasses differ primarily in their air removal paths, either through the 
1188  bulk material or through a thin film, and in whether they use a batch or in-line 
1189  process. 
1190   
1191     Off-Line or in-line 
1192     Vacuum vessel 
1193   
1194  Note:  If a single piece of equipment is capable of performing multiple discrete unit operations, 
1195  it has been evaluated solely for its ability to deaerate materials. 
1196   
1197  E.  Transfer 
1198   
1199  1.  Definition 
1200   
1201  a.  Unit Operation 
1202   
1203  Transfer:  The controlled movement or transfer of materials from one location to 
1204  another. 
1205   
1206  b.  Operating Principles 
1207   
1208  i.  Passive:  The movement of materials across a non-mechanically-
1209  induced pressure gradient, usually through conduit or pipe. 
1210   
1211  ii.  Active:  The movement of materials across a mechanically-
1212  induced pressure gradient, usually through conduit or pipe. 
1213   
1214  2.  Equipment Classification 
1215   
1216  a.  Low Shear 
1217   
1218  Active or passive material transfer, with a low degree of induced shear 
1219   
1220     Diaphragm 
1221     Gravity 
1222     Peristaltic 
1223     Piston 
1224     Pneumatic 
1225     Rotating lobe 
1226     Screw or helical screw 
1227   
1228  b.  High Shear 
1229   
  27  Contains Nonbinding Recommendations 
1230  Active or mechanical material transfer with a high degree of induced shear 
1231   
1232     Centrifugal or turbine 
1233     Piston 
1234     Rotating gear 
1235   
1236  Note:  This section is intended to deal with the transfer of shear sensitive materials, including 
1237  product or partially manufactured product.  A single piece of equipment can be placed in either a 
1238  low or high shear class, depending on its operating parameters.  If a single piece of equipment is 
1239  capable of performing multiple discrete unit operations, the unit has been evaluated solely for its 
1240  ability to transfer materials. 
1241   
1242  F.  Packaging 
1243   
1244  1.  Definitions 
1245   
1246  a.  Unit Operation 
1247   
1248  i.  Holding:  The process of storing product after completion of 
1249  manufacturing process and prior to filling final primary packs. 
1250   
1251  ii.  Transfer:  The process of relocating bulk finished product from 
1252  holding to filling equipment using pipe, hose, pumps and/or other 
1253  associated components. 
1254   
1255  iii.  Filling:  The delivery of target weight or volume of bulk finished 
1256  product to primary pack containers 
1257   
1258  iv.  Sealing:  A device or process for closing and/or sealing primary 
1259  pack containers following the filling process. 
1260   
1261  b.  Operating Principles 
1262   
1263  i.  Holding:  The storage of liquid, semi-solids, or product 
1264  materials in a vessel that may or may not have temperature 
1265  control and/or agitation. 
1266   
1267  ii.  Transfer:  The controlled movement or transfer of materials 
1268  from one location to another. 
1269   
1270  iii.  Filling:  Filling operating principles involve several associated 
1271  subprinciples.  The primary package can be precleaned to remove 
1272  particulates or other materials by the use of ionized air, vacuum, 
1273  or inversion.  A holding vessel equipped with an auger, gravity, or 
1274  pressure material feeding system should be used.  The vessel may 
1275  or may not be able to control temperature and/or agitation.  Actual 
1276  filling of the dosage form into primary containers can involve a 
1277  metering system based on an auger, gear, orifice, peristaltic, or 
1278  piston pump.  A head-space blanketing system can also be used. 
  28  Contains Nonbinding Recommendations 
1279   
1280  iv.  Sealing:  Primary packages can be sealed using a variety of 
1281  methods, including conducted heat and electromagnetic 
1282  (induction or microwave) or mechanical manipulation (crimping 
1283  or torquing). 
1284   
1285  2.  Equipment Classification 
1286   
1287  a.  Holders 
1288   
1289  Although holding vessels can differ in their geometry and ability to control 
1290  temperature or agitation, their primary differences are based on how materials 
1291  are fed. 
1292   
1293     Auger 
1294     Gravity 
1295     Pneumatic (nitrogen, air, etc.) 
1296   
1297  b.  Fillers 
1298   
1299  The primary differences in filling equipment are based on how materials 
1300  are metered. 
1301   
1302     Auger 
1303     Gear pump 
1304     Orifice 
1305     Peristaltic pump 
1306     Piston 
1307   
1308  c.  Sealers 
1309   
1310  The differences in primary container sealing are based on how energy is 
1311  transferred or applied. 
1312   
1313     Heat 
1314     Induction 
1315     Microwave 
1316     Mechanical or crimping 
1317     Torque 
1318   
1319   
  29