Oral Drug Products 
Administered Via Enteral 
Feeding Tube: In Vitro Testing 
and Labeling Recommendations 
Guidance for Industry 
 
 
 
DRAFT GUIDANCE 
 
  This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance. Submit electronic comments to https://www.regulations.gov. Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD  20852. All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (CDER) Mohamed Ghorab at 240-402-8940 
or (CDRH) CDRH product jurisdiction officer at CDRHProductJurisdiction@fda.hhs.gov.  
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Devices and Radiological Health (CDRH) 
 
June 2021 
Pharmaceutical Quality/CMC  
 
23257339dft.docx 
06/03/21   
Oral Drug Products 
Administered Via Enteral 
Feeding Tube: In Vitro Testing 
and Labeling Recommendations 
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 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: druginfo@fda.hhs.gov  
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs  
  
and/or 
 
Office of Policy 
Center for Devices and Radiological Health 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 66, Room 5431 
Silver Spring, MD 20993-0002 
Email: CDRH-Guidance@fda.hhs.gov 
https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-
medical-devices-and-radiation-emitting-products  
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Devices and Radiological Health (CDRH) 
 
June 2021 
Pharmaceutical Quality/CMC  
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 3 
III.  IN VITRO TESTING RECOMMENDATIONS TO EVALUATE DRUG 
PRODUCT SUITABILITY FOR ADMINISTRATION VIA ENTERAL TUBE ...... 4 
A.  In Vitro Testing Development Considerations ............................................................................ 5 
1. Selection of Enteral Tubes ............................................................................................................... 5 
2. Dispersion Media and Dispersion Preparation ............................................................................... 6 
3. In Vitro Method Development .......................................................................................................... 7 
B.  Testing Type Recommendations ................................................................................................... 8 
1. Recovery Testing .............................................................................................................................. 8 
2. Sedimentation Volume and Redispersibility Testing ........................................................................ 8 
3. In-Use Stability in Designated Dispersion Media ........................................................................... 9 
4. Particle Size Distribution Study ..................................................................................................... 10 
5. Acid Resistance Testing for Drug Products With an Enteric Coating ........................................... 10 
6. Dissolution Testing for Extended-Release Drug Products ............................................................ 10 
C.  Data Submission for Drug Product Applications...................................................................... 11 
1. Additional Considerations for NDA Submissions .......................................................................... 11 
2. Additional Considerations for ANDA Submissions ....................................................................... 11 
IV.  LABELING RECOMMENDATIONS.......................................................................... 13 
A.  Oral Drug Product Recommended for Administration Via Enteral Tube ............................. 13 
B.  Oral Drug Product NOT Recommended for Administration Via Enteral Tube ................... 16 
GLOSSARY................................................................................................................................. 17 
REFERENCES ............................................................................................................................ 18 
APPENDIX: RECOMMENDED REPORT FORMAT FOR SUBMISSION OF IN  
VITRO TESTING RESULTS TO SUPPORT ENTERAL TUBE ADMINISTRATION ... 19 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Oral Drug Products Administered Via Enteral Feeding Tube:  
2  In Vitro Testing and Labeling Recommendations 
3  Guidance for Industry1 
4   
5   
6   
7   
8  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
9  Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not 
10  binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the 
11  applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible 
12  for this guidance as listed on the title page.  
13   
14   
15   
16   
17  I.  INTRODUCTION  
18   
19  This guidance provides recommendations regarding in vitro testing of oral drug products, other 
20  than solutions, administered via enteral feeding tube (hereinafter enteral tube). These products 
21  represent a wide range of oral dosage forms including, but not limited to, granules, pellets, 
22  powders, suspensions, capsules, and tablets. The recommendations for in vitro testing apply to 
23  products that are subject to the following and submitted under section 505 of the Federal Food, 
24  Drug, and Cosmetic Act (21 U.S.C. 355) and 21 CFR parts 312 and 314:2  
25   
26    New drug applications (NDAs) (original or supplemental) where applicants are seeking 
27  and/or revising enteral tube administration instructions and related information in 
28  labeling 
29   
30    Abbreviated new drug applications (ANDAs) where the reference listed drug (RLD) 
31  contains enteral tube administration instructions and related information in labeling 
32   
33    Investigational new drug applications where the investigational drug product is 
34  administered or planned for administration via enteral tube 
35   
 
1 This guidance has been prepared by the Office of Pharmaceutical Quality in the Center for Drug Evaluation and 
Research in cooperation with the Center for Devices and Radiological Health at the Food and Drug Administration. 
 
2 The principles and recommendations in this guidance may also be relevant to products that are subject to biologics 
license applications that are developed or marketed as oral dosage forms (other than solutions) where the applicant is 
seeking labeling instructions for administration via enteral tube. Applicants seeking licensure for these products are 
encouraged to contact the Agency regarding their development plans. 
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Draft  Not for Implementation 
36  Specifically, the guidance covers:  
37   
38    In vitro testing recommendations to ensure oral drug product quality and, as applicable, 
39  bioequivalence to the RLD when evaluating a drug products suitability for 
40  administration via enteral tube 
41   
42    Appropriate content and format for submission of in vitro testing results regarding 
43  administration via enteral tube  
44    
45    Recommendations on how to incorporate information about administration via enteral 
46  tube in drug product labeling when supported by in vitro testing results3  
47   
48  The guidance does not cover recommendations involving: 
49   
50    Oral solutions, which do not present the same risk of forming occlusions when 
51  administered via enteral tube as other oral dosage forms containing solid or insoluble 
52  components 
53   
54    Clinical study design to support enteral tube administration  
55   
56    Physical characteristics of enteral tubes (e.g., connector design), which are covered in the 
57  guidance for industry Safety Considerations to Mitigate the Risks of Misconnections with 
58  Small-bore Connectors Intended for Enteral Applications (February 2015)4 
59   
60  Providing recommendations for in vitro testing of oral drug products administered via enteral 
61  tube will support the development of clear, product-specific enteral tube administration 
62  instructions in labeling for administration to patients unable to ingest oral drug products. The 
63  goal is to establish applicable in vitro methodology and provide information in drug product 
64  labeling for safe and effective administration of oral drug products through enteral tubes. 
65   
66  Applicants5 are encouraged to discuss testing approaches that differ from those recommended in 
67  this guidance with the applicable review or assessment staff before conducting the studies.  
68   
69  The contents of this document do not have the force and effect of law and are not meant to bind 
70  the public in any way, unless specifically incorporated into a contract. This document is intended 
71  only to provide clarity to the public regarding existing requirements under the law. FDA 
72  guidance documents, including this guidance, should be viewed only as recommendations, unless 
 
3 The recommendations in this guidance are limited to applicants for drug products seeking or bearing labeling 
instructions for administration via enteral tube. As of the time of publication of this guidance, no nonprescription 
drug product is labeled for administration via enteral tube. Therefore, with respect to nonprescription drug products, 
only those applicants seeking such labeling statements should follow the recommendations for in vitro testing to 
evaluate the drug products suitability to be administered via enteral tube. 
 
4 We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
5 For the purposes of this guidance, the term applicant includes application holder, manufacturer, and sponsor. 
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
73  specific regulatory or statutory requirements are cited. The use of the word should in Agency 
74  guidance means that something is suggested or recommended, but not required. 
75   
76   
77  II.  BACKGROUND 
78   
79  Enteral tubes are critical for patients who are unable to swallow oral dosage forms because of 
80  medical conditions or therapies that may compromise swallowing or the function of the proximal 
81  gastrointestinal system (e.g., feeding disorders, severe intellectual disabilities, neurological 
82  disorders, cancers). These patients rely on enteral tubes for their nutrition and drug treatment 
83  needs. This need spans patient care settings from intensive care units and other acute care 
84  settings to chronic residential care facilities and patients homes. Enteral tube feeding at home is 
85  becoming widespread, with an estimated patient prevalence of 1,385 per 1 million U.S. 
86  inhabitants (Mundi et al. 2017). It is essential that each drug product administered via enteral 
87  tube is delivered in a manner that preserves the correct dose and the drugs expected safety and 
88  effectiveness profile, including any labeled modified-release6 characteristics, and does not 
89  compromise the integrity of the tube. Although some FDA-approved drug products include 
90  instructions for enteral tube administration in their labeling, the administration instructions and 
91  in vitro testing to support administration via enteral tube are not sufficiently widespread or 
92  consistent (Ren et al. 2017). 
93   
94  Enteral tubes differ in tube diameter (inner and outer), tube composition, inner tube geometry, 
95  tube length, port number, connector type, port geometry (closed versus open distal tip), and 
96  number and location of eyes. Enteral tubes are composed of a variety of materials, including 
97  polyurethane, polyvinylchloride, and silicone. Table 1 summarizes common enteral tube types 
98  and their typical size ranges. In general, enteral tube size is designated by the diameter of the 
99  outer tube in French (Fr) units. Some enteral tubes can be inserted through the nose and are 
100  intended for short-term use, typically less than 4 weeks. Enteral tubes for chronic use (greater 
101  than 4 weeks) are placed percutaneously into the stomach or jejunum using an open surgical, 
102  endoscopic, or radioimaging technique.  
103   
104  Table 1. Types and Characteristics of Enteral Tubes 
Type  Outer Tube Diameter (Fr*,**) 
Nasogastric  5-18 
Nasoduodenal  3.5-12 
Nasojejunal  3.5-12 
Gastrostomy  12-30 
Gastrojejunal  12-22 
Jejunostomy  12-18 
105  * Fr = French 
106  ** 3 Fr = 1 millimeter 
107   
108  Clinical data suggest enteral tube occlusions and clogs occur in 23 to 35 percent of cases during 
109  routine use (Bourgault et al. 2003; Dandeles and Lodolce 2011; Blumenstein et al. 2014). The 
 
6 Terms that appear in bold type upon first use are defined in the Glossary. 
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
110  risks of enteral tube occlusion increase under a number of conditions, including, but not limited 
111  to, the following (Bourgault et al. 2003; Shipley et al. 2016):  
112   
113    Presence of insoluble ingredients  
114    Aggregation in dispersion media  
115    Selection of an inappropriate vehicle to serve as the dispersion media7  
116    Inadequate flushing of the enteral tube before and after drug product administration  
117    Inadequate drug product dispersion before administration  
118    Larger particle size  
119    Drug product-enteral tube interactions  
120    Departures from drug product labeling or enteral tube instructions 
121   
122  The Agency recognizes the need for consistent in vitro testing to ensure safe and effective 
123  delivery of drug products that may be administered via enteral tube and to identify drug products 
124  that cannot be administered through an enteral tube without altering the safety and effectiveness 
125  profile of the drug product or compromising the integrity of the tube. 
126   
127   
128  III.  IN VITRO TESTING RECOMMENDATIONS TO EVALUATE DRUG 
129  PRODUCT SUITABILITY FOR ADMINISTRATION VIA ENTERAL TUBE  
130   
131  Given the inherent challenges of administering oral drug products via enteral tubes, it is critical 
132  that in vitro testing to evaluate drug product suitability for enteral tube administration be 
133  completed before the initiation of any clinical studies intended to support enteral tube 
134  administration claims in labeling. Performing controlled in vitro testing before the initiation of 
135  clinical studies will aid in developing appropriate administration instructions for clinical studies 
136  and potentially identify drug product-specific risks associated with enteral tube administration.  
137   
138  The in vitro testing recommended in this guidance should be performed for oral drug products 
139  other than solutions by: (1) applicants for new drugs, whether by original or supplemental 
140  application, seeking to add labeling instructions for administration via enteral tube; and (2) 
141  applicants for generic drugs where the RLD labeling includes instructions for administration via 
142  enteral tube. The results of in vitro testing to support the use of enteral tube administration 
143  should be submitted to the Agency as part of original or supplemental drug applications in which 
144  enteral tube administration labeling claims are sought. Completion of the recommended testing 
145  should demonstrate whether or not a drug product is suitable for enteral tube administration. 
146  More evidence may be needed to demonstrate suitability and/or compatibility for administration 
147  via enteral tube for a solid oral dosage form known to contain insoluble components than for an 
148  oral drug product that completely dissolves in the directed dispersion media. 
149   
150  Applicants seeking labeling instructions for administration via enteral tube should consider 
151  multiple factors when determining how to perform in vitro enteral tube administration testing 
152  during drug product development including:  
 
7 See the draft guidance for industry Use of Liquids and/or Soft Foods as Vehicles for Drug Administration: General 
Considerations for Selection and In Vitro Methods for Product Quality Assessments (July 2018). When final, this 
guidance will represent the FDAs current thinking on this topic.  
  4  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
153   
154    The active pharmaceutical ingredients (APIs) site of absorption from the 
155  gastrointestinal tract 
156   
157    Whether the drug has a narrow therapeutic index 
158   
159    Whether the drug product is a delayed-release or extended-release dosage form8 
160   
161    The aqueous solubility of the API and inactive ingredients  
162   
163    Whether the API or inactive ingredients may adhere to the enteral tube material (Jory et 
164  al. 2017) 
165   
166  The Agency recommends applicants consider the following test development recommendations 
167  and test types when conducting testing to demonstrate that oral drug products are suitable for 
168  administration via enteral tube. The data generated from the following studies should be included 
169  in a report to support enteral tube administration as a valid alternative method of drug product 
170  delivery.9  
171   
172  A.  In Vitro Testing Development Considerations 
173   
174  The following testing recommendations are based on an expectation that the drug product will be 
175  prepared for in vitro testing in the same manner as it will be prepared for administration via 
176  enteral tube to a patient in planned clinical studies, or prepared as described in labeling submitted 
177  for approval, as applicable.  
178   
179  1.  Selection of Enteral Tubes 
180   
181  If an applicant intends to recommend multiple tube types (e.g., nasogastric (NG), gastrostomy 
182  (G)) or sizes (e.g., Fr 10-16) for administration of its drug product, the recommended testing 
183  should, at minimum, be performed with the smallest intended enteral tube size for each type of 
184  material or design (see section III.B.4., Particle Size Distribution Study, for testing data that may 
185  be helpful in the selection of tube size). For example, if an applicant intends the labeling to 
186  include instructions for drug product administration with both NG (Fr 8 and above) and G tubes 
187  (Fr 12 and above), NG tubes should be tested at Fr 8 and G tubes should be tested at Fr 12. 
188    
189  Enteral tubes may be made with different materials (e.g., polyvinylchloride, silicone, 
190  polyurethane) and different designs (e.g., various numbers of ports and/or eyes, retention 
 
8 The term modified-release is defined in United States Pharmacopeia (USP) General Chapter <1151> 
Pharmaceutical Dosage Forms. Modified-release is a term used when the rate and/or time of release of the drug 
substance is altered as compared to what would be observed or anticipated for an immediate-release product. Two 
modified-release profiles, delayed-release and extended-release, are recognized.  
 
9 The studies described in this guidance may be suitable for inclusion in various sections of the electronic common 
technical document, depending on the context of the submission. Therefore, the Agency recommends inclusion of a 
summary report in Module 2, with a link to the full testing report. See also the Appendix of this guidance for test 
report format. 
  5  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
191  balloons, open or closed distal end). Such differences may affect the inner tube diameter and/or 
192  flow of material through the tubes (Kurien et al. 2015). For in vitro testing, applicants should 
193  consider the material and design of the various enteral tubes that may be used for drug product 
194  administration, and test a representative selection of tubes to ensure complete delivery of the 
195  drug product in the recovery test. FDA recommends that applicants test at least three different 
196  enteral tube configurations for all tube types proposed in the labeling and provide justification 
197  for the enteral tubes selected for testing. Note that for G tubes, at least one tube should be tested 
198  with an inflated balloon configuration.  
199   
200  2.  Dispersion Media and Dispersion Preparation 
201   
202  Various dispersion media such as purified water, apple juice, milk, and liquid nutritional 
203  supplements may be used as vehicles for oral drug product administration and to flush enteral 
204  tubes. The properties of the dispersion media may vary between brands or formulations. 
205  Variations may include pH, concentration, ingredients, and preparation method, among others. 
206  Therefore, applicants should consider the different types and properties of the vehicles that may 
207  be used for drug product administration and evaluate the risk due to potential variations in the 
208  dispersion media used. This analysis should form part of the basis for justifying the 
209  administration conditions, including dispersion media. Detailed instructions describing how the 
210  drug product is prepared for enteral tube administration should be documented including: 
211   
212    Dispersion medium (e.g., type of water such as purified water (including distilled water 
213  and water for injection); type of liquid food; brand of juice)10 
214   
215    Volume and temperature of the dispersion medium 
216   
217    Holding/soaking time between dispersion and administration through the enteral tube 
218   
219    Number of potential administrations through the tube based on proposed administration 
220  instructions (e.g., once per day, every four hours) 
221   
222    Details regarding the preparation and dispersion method of the drug product (e.g., crush, 
223  suspend, dissolve, shaking method), including any equipment used in preparation or 
224  dispersion 
225   
226    The pH of the medium before and after dispersion 
227   
228    Flush volume used before and after drug product administration 
229   
230    Tube and syringe used (e.g., brand item number, material, brand, inner and outer tube 
231  diameter, with or without balloon (filled according to the tube manufacturers 
232  instructions), number of eyes, length of the tube, syringe tip type) 
233   
 
10 Tap water is not recommended as a dispersion medium in the laboratory setting due to its variability as described 
in this guidance. 
  6  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
234    Holding position of the tube and holding position of the syringe (e.g., horizontal, 
235  vertical)  
236   
237    Method, analytical site, and testing dates for each of the tests  
238   
239  The pH for different types of water (e.g., distilled, sterile, and other types of bottled water) may 
240  vary between 5.5 to 8.5. When water is used as the dispersion medium, particularly for modified-
241  release dosage forms or for products containing pH-sensitive coating excipients, the pH within 
242  the preparation container, oral syringe, or enteral tube might adversely affect the integrity of the 
243  enteric coating or dissolution of drug products. Therefore, in these cases, we recommend testing 
244  using water with different pH values (e.g., pH 5.5, 7.0, 8.5) for in vitro enteral tube studies even 
245  if labeling will specify a particular type of water. Similarly, when juice is used as the dispersion 
246  medium, multiple types of juice should be studied, even if labeling will specify a particular type 
247  of juice. 
248   
249  3.  In Vitro Method Development 
250   
251  Development of in vitro methods should follow a risk-based process. In vitro testing conditions 
252  should be justified based on the drug product formulation and its proposed method of 
253  administration. For example, successful testing on the smallest tubing diameter recommended for 
254  use in the drug product labeling would obviate the need to perform testing through tubing with 
255  larger diameters. Likewise, performing the testing at the initial (time zero) and final time points 
256  proposed before administration (e.g., holding/soaking time) would also reduce the need for 
257  testing holding/soaking time points that fall between those two extremes. Applicants should also 
258  consider the dose strengths of their drug products to select the formulation at highest risk of 
259  forming occlusions for testing and should provide their rationale.  
260   
261  The following is a general overview of the in vitro testing method recommendations: 
262   
263    The enteral tube should be prepared according to the tube manufacturers instructions 
264  (e.g., flushing the tube or inflating the balloon). 
265   
266    The drug product (e.g., granules from capsule, tablet (crushed or not)) should be prepared 
267  in the dispersion medium (e.g., purified water, apple juice, or milk), and rotated gently 
268  until the drug product is completely dispersed with no particles visible that are large 
269  relative to the tube inner diameter.  
270   
271    The drug product dispersion should be transferred into an oral syringe, the oral syringe 
272  (or funnel, if applicable) should be connected to the enteral tube, and the dispersion 
273  should be passed through the enteral tube into a collection container. After administration 
274  of the dispersion using the enteral tube, the enteral tube and syringe should be flushed 
275  with a specified amount of the dispersion medium.  
276   
  7  Contains Nonbinding Recommendations 
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277  B.  Testing Type Recommendations 
278   
279  The type and extent of testing should be a risk-based decision focused on the characteristics of 
280  the individual drug product. For example, if additional procedures are needed during testing to 
281  demonstrate that the drug product can be delivered by enteral tube, the applicant should provide 
282  a detailed description of these procedures.  
283   
284  There are additional testing considerations for modified-release dosage forms. In vitro testing of 
285  modified-release products should demonstrate that preparation of the drug product for 
286  administration via enteral tube does not adversely affect the drug content assay or release 
287  characteristics (e.g., dissolution), where appropriate.  
288   
289  These testing recommendations do not replace conventional drug product quality 
290  characterization studies or in vivo bioequivalence studies for the drug product that are typically 
291  conducted. 
292   
293  1.  Recovery Testing 
294   
295  The purpose of recovery testing is to determine the percentage of a dose of a drug that 
296  successfully passes through an enteral tube when the drug product is prepared and administered 
297  as specified or proposed in the product labeling. Recovery testing should be performed to 
298  support enteral tube administration. Applicants should determine the percentage of drug 
299  recovered at the tube exit relative to the initial dose of the drug product using a validated 
300  analytical method. The study should be conducted using an adequate number of samples and 
301  justification for the selected sample size should be provided. The tube and syringe should be 
302  examined visually, and any aggregation, buildup, clogging, or other observations should be 
303  recorded. The percentage of drug recovered at the tube exit relative to the initial dose should 
304  meet appropriate drug product release specifications for new drugs. For generic drugs, the 
305  percentage should be calculated as described in section III.C.2., Additional Considerations for 
306  ANDA Submissions. Applicants should provide video or photographs of the contents of the 
307  syringe and tube before, during, and after testing.  
308   
309  If a drug product will be administered multiple times in a 24-hour period, applicants should 
310  mimic the directed dosing regimen and record drug recovery after each individual administration 
311  (i.e., the same tube should be used for sequential administrations of the drug product). 
312   
313  If the dispersion medium is water, recovery testing should be performed with material recovered 
314  from the enteral tube using water with different pH values (e.g., pH 5.5, 7.0, 8.5) and various 
315  soaking times to support the intended delivery time. The pH values of the drug product 
316  dispersion should be measured upon initial dispersion and after delivery through the enteral tube.  
317   
318  2.  Sedimentation Volume and Redispersibility Testing 
319   
320  Sedimentation volume and redispersibility testing should be performed to assess the 
321  sedimentation potential of a drug product within an enteral tube to support enteral tube 
322  administration. Insoluble components of a drug product have the potential for sedimentation that 
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Draft  Not for Implementation 
323  may increase the risk of clogging. For convenience, instead of an enteral tube, a syringe can be 
324  used for this test. To test sedimentation volume, the syringe should be loaded with drug product 
325  dispersion and allowed to settle. Applicants should record the sedimentation volume and 
326  duration of test (e.g., holding/soaking time). Markings on the syringe can be used for the 
327  measurement. 
328    
329  Redispersibility of the drug product dispersion should be evaluated to determine if settled solids 
330  can be redispersed for administration (e.g., by shaking after the maximum directed soaking 
331  time). The syringe that was used for the sedimentation volume test above should be used to test 
332  redispersibility. Applicants should provide a qualitative description of the test product (e.g., 
333  particle aggregation and particles adhering to the syringe walls). Representative photographs of 
334  the syringe contents should be taken at various intervals throughout the testing process.  
335   
336  Sedimentation volume and redispersibility tests performed during product development or 
337  included as part of routine testing of the drug product (e.g., for oral suspensions) may be 
338  sufficient to serve as the sedimentation volume and redispersibility tests recommended in this 
339  guidance to support enteral tube administration.   
340   
341  3.  In-Use Stability in Designated Dispersion Media 
342   
343  When labeling instructions for administration via enteral tube specify an in-use holding/soaking 
344  time before administration via enteral tube, in vitro testing as described in this guidance should 
345  include in-use stability testing through this in-use period.11 Applicants should perform in-use 
346  stability testing in the proposed dispersion media to demonstrate that the drug product dispersion, 
347  when prepared for enteral tube administration, is chemically and physically stable (i.e., as 
348  indicated by the dissolution profile) throughout the specified soaking time at the recommended 
349  or proposed storage conditions. Chemical stability of the drug product dispersion under proposed 
350  storage conditions for enteral tube administration should be monitored at predetermined time 
351  intervals. The drug content and degradation products of the API should be determined using a 
352  stability-indicating method or methods. The results of the stability studies should provide 
353  assurance for the stability of the drug product dispersion during the proposed soaking period.  
354   
355  For extended holding times before administration of over 4 hours at room temperature or over 24 
356  hours under refrigeration, applicants should include microbiological studies in support of the 
357  proposed storage conditions. For microbial testing and acceptance criteria for non-sterile aqueous 
358  drug products for oral use, see United States Pharmacopeia (USP) General Chapter <1111> 
359  Microbiological Examination of Nonsterile Products: Acceptance Criteria for Pharmaceutical 
360  Preparations and Substances for Pharmaceutical Use, USP General Chapter <61> 
361  Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests, and USP 
362  General Chapter <62> Microbiological Examination of Nonsterile Products: Tests for Specified 
363  Microorganisms. 
364   
 
11 See the ICH guidance for industry Q1A(R2) Stability Testing of New Drug Substances and Products (November 
2003) for additional information about in-use stability testing.  
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365  4.  Particle Size Distribution Study 
366   
367  Particle size is a key attribute affecting the passage of a drug product through an enteral tube 
368  during administration. The particle size distribution study evaluates one mechanism by which a 
369  formulation could block the tube and predicts the risk of blockage. Particle size distribution 
370  studies should be conducted for modified-release dosage forms and other formulations where 
371  particle size may indicate a high risk for forming tube occlusions. Following the enteral tube 
372  preparation procedure outlined in section III.A.3., In Vitro Method Development, applicants 
373  should determine the particle size of the drug suspension before and after delivery through the 
374  enteral tube. Particle size should be determined using a validated method that is sufficiently 
375  reproducible and sensitive (e.g., laser diffraction method with the particle size data at the D10, 
376  D50, and D90 levels).  
377   
378  5.  Acid Resistance Testing for Drug Products With an Enteric Coating 
379   
380  Acid resistance testing is used to ensure the integrity of the enteric coating of delayed-release 
381  dosage forms during administration via enteral tube.12 Acid resistance testing should be 
382  performed on drug products with an enteric coating. The test should be performed under acidic 
383  conditions (pH 1.2 or 0.1 N HCl for 12 hour(s) per drug product release specification) after the 
384  drug product is incubated in the dispersion medium and delivered through the enteral tube. The 
385  percentage of drug released into the acidic medium should conform to the acceptance criteria set 
386  in the drug product specification. Applicants should consider the potential for degradation of the 
387  API if it is acid-labile.  
388   
389  6.  Dissolution Testing for Extended-Release Drug Products 
390   
391  Dissolution testing should be performed for extended-release dosage forms to demonstrate that 
392  preparation and delivery via enteral tube does not affect the timing of drug release from the 
393  dosage form. Dissolution testing should be performed after administration through a combination 
394  of an oral syringe and an enteral tube in dissolution media specified in the drug product 
395  specification. The pH values of the drug product dispersion should be measured before and after 
396  delivery through the enteral tube. The amount of drug released into each recommended 
397  dispersion medium should also be quantitated after passing through the enteral tube. After 
398  collection of the drug product dispersion at the enteral tube exit, the particulates collected into a 
399  dissolution vessel should be transferred using the testing conditions specified in the drug product 
400  specification and the amount of drug released should be determined at time points per the drug 
401  product specification. The amount of drug released (after passage through the enteral tube) 
402  divided by the labeled content of the drug product and expressed as a percentage should conform 
403  to the acceptance criteria set in the drug product specification.  
404   
 
12 A tablet that is enteric-coated would not likely be appropriate for enteral tube administration because crushing to 
disperse the drug would disrupt the function of the enteric coating, whereas a capsule containing enteric-coated 
beads may be suitable for enteral administration. 
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405  C.  Data Submission for Drug Product Applications 
406   
407  In addition to the test results, applicants should submit test protocols and the analytical methods 
408  used for the in vitro enteral tube studies recommended in section III.B., Testing Type 
409  Recommendations. The test protocols should incorporate the recommendations in section 
410  III.A.2., Dispersion Media and Dispersion Preparation. Detailed method validation reports for 
411  the analytical techniques used should be submitted to demonstrate adequacy for the intended 
412  purpose. If the method validation reports for the analytical techniques used are provided 
413  elsewhere in the application, a link or reference to that location in the submission should be 
414  provided. Individual data, mean values, standard deviations, and coefficients of variation (CV %) 
415  for each test should be submitted. Test results should be submitted in the format described in the 
416  Appendix. 
417   
418  The tubing and syringe used for in vitro testing should be examined visually for any aggregation, 
419  adherence, or clogging, and the observations reported with supporting visual information (video 
420  and/or photographs). For recovery studies, applicants can provide videos that document the 
421  testing process and associated observations. If application of additional force to the syringe 
422  compared to that used for initial flushing with dispersion medium is needed during the testing to 
423  ensure complete recovery, it should be documented, and an explanation should be provided.  
424   
425  1.  Additional Considerations for NDA Submissions 
426   
427  For NDAs, the in vitro testing recommendations provided in section III.B., Testing Type 
428  Recommendations, are intended as the initial step to demonstrate that a new drug product is 
429  suitable for administration via enteral tube. Clinical studies involving enteral tube administration 
430  of a new drug product are outside the scope of this guidance, but if applicable, generally should 
431  be conducted after the recommended in vitro studies demonstrate the suitability of a new drug 
432  product for enteral tube administration and the appropriate administration instructions have been 
433  established. For a new drug product seeking labeling instructions for administration via enteral 
434  tube, the proposed labeling statement in the DOSAGE AND ADMINISTRATION section 
435  should be developed based on, and be supported by, the results of enteral tube administration 
436  testing. To ensure adequate investigations, FDA encourages early communication with the 
437  review division to discuss in vitro testing and any clinical study protocol design. When 
438  submitting the in vitro test and any clinical study results, applicants should provide the enteral 
439  tube administration instructions, including the recommended enteral tube type, size, brand, part 
440  number, and the size of the oral syringe used. This information should be submitted at the time 
441  the claim for enteral tube administration is sought (e.g., in the original NDA submission, or in a 
442  supplement if clinically indicated).   
443   
444  2.  Additional Considerations for ANDA Submissions 
445   
446  For ANDAs, the in vitro testing recommendations provided in section III.B., Testing Type 
447  Recommendations, are intended to demonstrate that a generic drug product is therapeutically 
448  equivalent to the RLD when administered according to the RLD product labeling enteral tube 
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449  administration instructions.13 The enteral tube administration instructions provided in the 
450  DOSAGE AND ADMINISTRATION section of labeling for the RLD should guide development 
451  of the in vitro enteral tube administration testing procedures for the planned generic drug 
452  product. If the RLD is discontinued and the reference standard (RS) is being used for 
453  bioequivalence testing, the enteral tube administration instructions in the labeling of the RS 
454  should guide development of the in vitro enteral tube administration testing procedures.14 
455   
456  When performing the recommended in vitro testing to ensure bioequivalence to the RLD (or RS 
457  if the RLD is discontinued or otherwise unavailable) after administration via enteral tube, 
458  applicants should describe the testing conditions including: the number of units of the test and 
459  reference drug products used; enteral tube type, size, brand, and part number; and the size of the 
460  oral syringe used.  
461   
462  For comparative in vitro testing (e.g., recovery testing, acid resistance testing, and sedimentation 
463  testing), applicants should prepare the enteral tube studies based on the procedure outlined in the 
464  most current FDA-approved drug product labeling using 12 units each of the test (T) and 
465  reference (R) drug products dispersed in the dispersion medium for 0 minutes and for the 
466  maximum allowable holding/soaking incubation time in accordance with the drug product 
467  labeling, unless the testing conditions set forth in the relevant product-specific guidance for 
468  generic drug development state otherwise. All in vitro enteral tube tests should be performed on 
469  unexpired T and R batches of the drug product. When labeling instructions specify immediate 
470  administration after preparation, the Agency recommends performing comparative in vitro 
471  enteral tube testing at both 0- and 15-minute soaking times. For recovery testing, applicants 
472  should determine the percentage of drug recovered at the tube exit relative to the initial dose for 
473  both the T and R products using a validated analytical method. Applicants should calculate the 
474  T/R recovery ratio and the 90 percent confidence interval of the T/R recovery ratio. 
475   
476  This information should be provided in the original ANDA submission. For additional insight on 
477  the recommended in vitro testing reporting format, see the Bioequivalence Summary Tables for 
478  In Vitro Feeding Tube Testing.15 Any recommendations for in vivo bioequivalence studies 
479  involving administration via enteral tube will be communicated in the respective product-specific 
480  guidance for generic drug development.16 
481   
482   
 
13 The regulations under 21 CFR 314.3 define therapeutic equivalents as follows: approved drug products that are 
pharmaceutical equivalents for which bioequivalence has been demonstrated, and that can be expected to have the 
same clinical effect and safety profile when administered to patients under the conditions specified in the labeling. 
 
14 See the draft guidance for industry Updating ANDA Labeling After the Marketing Application for the Reference 
Listed Drug Has Been Withdrawn (July 2016). When final, this guidance will represent the FDAs current thinking 
on this topic. 
 
15 https://www.fda.gov/media/98853/download  
 
16 Product-specific guidances are published on the Product-Specific Guidances for Generic Drug Development web 
page at https://www.accessdata.fda.gov/scripts/cder/psg/index.cfm.  
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483  IV.  LABELING RECOMMENDATIONS  
484   
485  A.  Oral Drug Product Recommended for Administration Via Enteral Tube 
486   
487  If there are adequate data that support administration of the drug product via enteral tube, the 
488  drug product labeling should include sufficient information to ensure that the health care 
489  provider, patient, and/or caregiver have the essential information to administer the drug product 
490  safely and effectively via enteral tube. The DOSAGE AND ADMINISTRATION section of 
491  labeling should include, as applicable:17 
492   
493    Information on which dosage form(s) and strength(s) are suitable for administration via 
494  enteral tube. 
495   
496    Recommended enteral tube characteristics, such as the following:  
497   
498    Type (e.g., NG, G) 
499   
500    Size range (expressed in French units) 
501   
502    Any other tube characteristic that affects passage of the drug product dispersion 
503  through the tube (e.g., material composition)  
504   
505    Recommended drug product and enteral tube preparation instructions before 
506  administration. For example: 
507   
508    Dispersion media (e.g., type of water, milk, apple juice) 
509   
510    Details regarding the method of drug product dispersion (e.g., crush to a fine powder, 
511  suspend, dissolve, shaking method) 
512   
513    Volume of dispersion media and soaking time of drug product dispersion before 
514  administration 
515   
516    Preparation of the enteral tube (e.g., flushing the tube) 
517   
518    Other recommended preparation information (e.g., shaking the syringe immediately 
519  before administering the drug product dispersion, a physical description of the desired 
520  dispersion) 
521   
522    Recommended administration instructions. These can include, but are not limited to: 
523   
524    Volume and rate of administration of the drug product dispersion for each strength (if 
525  different) 
 
17 See the guidance for industry Dosage and Administration Section of Labeling for Human Prescription Drug and 
Biological Products  Content and Format (March 2010). 
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526   
527    Holding positions of the syringe and tube during administration 
528   
529    Instructions regarding any residual drug product in the mixing container, syringe, or 
530  enteral tube  
531   
532    Information regarding the timing of administration, such as in relation to continuous 
533  enteral feeding or the appropriate interval prior to the administration of a different 
534  drug product. 
535   
536    Instructions on maintenance of the enteral tube following administration (e.g., flushing of 
537  the tube) 
538   
539    Instructions for storage of residual drug product dispersion during the in-use period, if 
540  applicable. 
541   
542  Clinically relevant information about dispersion media, preparation procedures, syringe 
543  characteristics, soaking times, and enteral tube characteristics that adversely affect drug delivery, 
544  if applicable, should be presented in the appropriate section(s) or subsection(s) of labeling (e.g., 
545  DOSAGE AND ADMINISTRATION section, WARNINGS AND PRECAUTIONS section, 
546  Pharmacokinetics subsection of the CLINICAL PHARMACOLOGY section). 
547   
548  If applicable, the DOSAGE AND ADMINISTRATION section should cross-reference the 
549  Pharmacokinetics subsection of the CLINICAL PHARMACOLOGY section of labeling, where 
550  a succinct summary of the relevant data (e.g., enteral tube characteristics, dispersion media or 
551  soaking times) that affect the pharmacokinetics of the drug product should be included.18  
552   
553  Provided below are examples of instructions for the preparation and administration of a drug 
554  product dispersion via enteral tube in the DOSAGE AND ADMINISTRATION section of 
555  labeling. 
556   
557  Example 1 
558   
559  To administer DRUG-X tablets (all strengths) via nasogastric tube (French size 8 or 
560  larger) follow these steps [see Clinical Pharmacology (12.3)]:  
561   
562    Place one tablet in a catheter-tip syringe and draw up 20 mL of distilled water. 
563   
564    Shake gently to allow for a quick dispersal. 
565   
566    After the tablet has dispersed, swirl the catheter-tip syringe gently to keep the 
567  microgranules from settling, and immediately inject the mixture through the 
 
18 See the guidance for industry Clinical Pharmacology Section of Labeling for Human Prescription Drug and 
Biological Products  Content and Format (December 2016). 
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568  nasogastric tube into the stomach. Do not save the water and microgranule mixture 
569  for later use. 
570   
571    Refill the catheter-tip syringe with approximately 10 mL of distilled water, shake 
572  gently, and flush the tube. 
573   
574    Refill the catheter-tip syringe again with 10 mL of distilled water, swirl gently, and 
575  administer. 
576   
577  Example 2 
578   
579  To administer DRUG-X capsules via nasogastric (French size 8 or larger) or gastrostomy 
580  tube (French size 12 or larger): 
581   
582    Open the capsule and empty the entire contents of the capsule into a clean container 
583  with 30 mL of distilled water. 
584   
585    Gently swirl the mixture in the container for 30 seconds or longer until all of the 
586  powder is uniformly dispersed in the liquid.  
587   
588    After the capsules contents have dispersed, draw up the mixture into a catheter tip 
589  syringe. Apply steady pressure to dispense the contents of the syringe into the 
590  nasogastric or gastrostomy tube within 15 minutes of preparation. Do not keep the 
591  mixture for later use. 
592   
593    If residual drug remains in the syringe or tube, draw up 10 mL of distilled water into 
594  the syringe, swirl it around, and administer through the tube. 
595   
596    Flush the tube with at least 10 mL of distilled water. 
597   
598  If applicable, FDA-approved patient labeling (e.g., Instructions for Use19) should include 
599  detailed patient-use instructions for the preparation, administration, handling, storage, and 
600  disposal of the drug product dispersion administered via enteral tube.20  
601   
 
19 See the draft guidance for industry Instructions for Use  Patient Labeling for Human Prescription Drug and 
Biological Products and Drug-Device and Biologic-Device Combination Products  Content and Format (July 
2019). When final, this guidance will represent the FDAs current thinking on this topic. 
 
20 The Instructions for Use are considered part of the drug product user interface. As such, additional data, such as 
data from human factors studies, could be used to inform the development of the instructions for use for an NDA 
drug product. The discussion of human factors considerations is outside the scope of this guidance. For additional 
information on development of the user interface and human factors considerations, see the draft guidance for 
industry and FDA staff Human Factors Studies and Related Clinical Study Considerations in Combination Product 
Design and Development (February 2016). When final, this guidance will represent the FDAs current thinking on 
this topic. 
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Draft  Not for Implementation 
602  B.  Oral Drug Product NOT Recommended for Administration Via Enteral 
603  Tube 
604   
605  If, in the development of an oral drug product intended for administration via enteral tube, 
606  testing identifies no successful method for preparation and administration of the drug product via 
607  enteral tube, then the DOSAGE AND ADMINISTRATION section of labeling should state this 
608  and provide a brief rationale, if appropriate. As applicable, relevant information supporting the 
609  recommendation against enteral tube administration should be succinctly summarized in other 
610  subsections or sections of labeling (e.g., DESCRIPTION section, Pharmacokinetics subsection 
611  of the CLINICAL PHARMACOLOGY section) and a cross-reference to that information should 
612  be provided in the recommendation.  
613   
614  Provided below are examples of statements recommending against administration of an oral drug 
615  product via enteral tube in the DOSAGE AND ADMINISTRATION section of labeling. 
616   
617  Example 1 
618   
619  Do not administer DRUG-Y via nasogastric, gastrostomy, or other enteral tubes because 
620  it may cause obstruction of enteral tubes. 
621   
622  Example 2 
623   
624  Do not administer DRUG-Y for Oral Suspension via nasogastric, gastrostomy, or other 
625  enteral tubes, because its chemical constituents may interact with the device material [see 
626  Description (11)]. 
627   
628  If applicable, FDA-approved patient labeling (e.g., Instructions for Use,21 Medication Guide,22 
629  Patient Package Insert) should include patient-use instructions that the drug product should not 
630  be administered via enteral tube along with the reason why not. 
631   
 
21 See footnote 19. 
 
22 21 CFR part 208 
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632  GLOSSARY 
633   
634  Delayed-release: A formulation that achieves a delay in the release of the drug substance for 
635  some period of time after initial administration. 
636   
637  Dispersion media: A qualified liquid substrate used to disperse a drug product for delivery 
638  through an enteral tube.  
639   
640  Enteric coating: A polymer barrier applied on drugs intended for oral administration that 
641  prevents their dissolution or disintegration in the gastric environment. 
642   
643  Extended-release: A formulation that makes the drug available over an extended period of time 
644  after ingestion. This allows a reduction in dosing frequency as compared to that presented by a 
645  conventional dosage form (e.g., a solution or an immediate-release dosage form).  
646   
647  Flush volume: A predetermined quantity of liquid used to purge an enteral tube before and/or 
648  after the administration of a drug product in the directed dispersion media. 
649   
650  Holding position of the syringe: The specific orientation (e.g., horizontal, vertical) at which a 
651  syringe must be maintained to ensure adequate administration of a drug product in the directed 
652  dispersion media.  
653   
654  Holding position of the tube: The specific orientation (e.g., horizontal, vertical) at which an 
655  enteral tube must be maintained to ensure adequate administration of a drug product in the 
656  directed dispersion media. 
657   
658  Modified-release: When the rate and/or time of release of the drug substance is altered as 
659  compared to what would be observed or anticipated for an immediate-release product. Two 
660  modified-release profiles, delayed-release and extended-release, are recognized.  
661   
662  Soaking time: A qualified duration of time that demonstrates adequate dispersion of an oral 
663  dosage form in the specified dispersion media.  
664   
665  Therapeutic index: A ratio of the median toxic dose to the median effective dose of a specific 
666  drug product.  
667   
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668  REFERENCES 
669   
670  Blumenstein I, YM Shastri, and J Stein, 2014, Gastroenteric Tube Feeding: Techniques, 
671  Problems and Solutions, World J Gastroenterol, 20:85058524. 
672   
673  Bourgault AM, DK Heyland, JW Drover, L Keefe, P Newman, and AG Day, 2003, Prophylactic 
674  Pancreatic Enzymes to Reduce Feeding Tube Occlusions, Nutr Clin Pract, 18:398401. 
675   
676  Dandeles LM and AE Lodolce, 2011, Efficacy of Agents to Prevent and Treat Enteral Feeding 
677  Tube Clogs, Ann Pharmacother, 45:676680. 
678   
679  Jory C, R Shankar, K Oak, J Oates, and M Wilcock, 2017, Going Down the Tubes! Impact on 
680  Seizure Control of Antiepileptic Medication Given Via Percutaneous Feeding Tubes, Epilepsy 
681  Behav, 74:114118. 
682   
683  Kurien M, H Penny, and DS Sanders, 2015, Impact of Direct Drug Delivery Via Gastric Access 
684  Devices, Expert Opinion on Drug Delivery, 12:3, 455-463 (doi: 
685  10.1517/17425247.2015.966683). 
686   
687  Mundi M, A Pattinson, MT McMahon, J Davidson, and RT Hurt, 2017, Prevalence of Home 
688  Parenteral and Enteral Nutrition in the United States, Nutr Clin Pract, 32:799805. 
689   
690  Ren P, Cui M, Anand O, Xia L, Zhao ZJ, Sun D, Sharp T, Conner DP, Peters J, Jiang W, Stier E, 
691  and Jiang X, 2017, In Vitro Approaches to Support Bioequivalence and Substitutability of 
692  Generic Proton Pump Inhibitors Via Nasogastric Tube Administration, AAPS J, 19(6):1593
693  1599. 
694   
695  Shipley K, AM Gallo, and WL Fields, 2016, Is Your Feeding Tube Clogged? Maintenance of 
696  Gastrostomy and Gastrojejunostomy Tubes, Medsurg Nurs, 25:224228. 
697   
698   
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699  APPENDIX: 
700  RECOMMENDED REPORT FORMAT FOR SUBMISSION OF IN VITRO TESTING 
701  RESULTS TO SUPPORT ENTERAL TUBE ADMINISTRATION 
702   
703  Test Report Information 
704   
705  Complete test reports for nonclinical in vitro testing should include: the objective of the test, 
706  description of the test methods and procedures, predefined pass/fail criteria, test results, and 
707  discussion of conclusions.  
708   
709  A. Summary Table 
710   
711  To facilitate the assessment of submissions, FDA recommends that all submissions containing in 
712  vitro testing reports also include a tabular summary of the testing performed and results obtained, 
713  following the list in B. Test Reports.  
714   
715  B. Test Reports  
716   
717  Complete test reports should include clear, detailed descriptions of: 
718   
719  1.  Test performed  
720   
721  2.  Test objectives  
722   
723  3.  Test methods and procedures. The following should be included: 
724   
725  a.  Test sample information  
726   
727  The sample tested should be described. 
728    
729  b.  Test sample size/selection  
730   
731  The report should provide a scientific rationale to support the number of samples 
732  tested. The test sample selection should consider both inter- and intra-lot variability 
733  (e.g., by examining multiple manufacturing lots if appropriate).  
734   
735  c.  Test protocol  
736   
737  The test protocol should contain enough detail that an individual familiar with the 
738  testing will be able to interpret the purpose of the test, how the test was performed, 
739  and whether the test protocol and method are appropriate to evaluate the results of the 
740  testing. The test protocol should describe the test parameters, including an 
741  explanation of and rationale for critical test parameters. The test protocol should also 
742  include acceptance criteria with scientific or clinical justification for the relevancy of 
743  the acceptance criteria.  
744   
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745  Inclusion of the test protocol is unnecessary if FDA-recognized consensus standards 
746  that include test methods are used during testing even when a Declaration of 
747  Conformity to the standard is not provided.1 Instead, the report should include a full 
748  citation for the standard including the version, the extent to which the standard was 
749  followed, and any deviations from the standard. If the FDA-recognized consensus 
750  standard includes testing options (e.g., what to test, which test methods to use, 
751  performance limits to assess conformity), applicants should include explanations for 
752  the choices and selections made.  
753   
754  4.  Predefined pass/fail criteria  
755   
756  The report should include all specifications or acceptance and rejection criteria used as 
757  well as a clinical or scientific justification for the specifications or acceptance and 
758  rejection criteria.  
759   
760  5.  Test results  
761   
762  The report of test results should include: 
763    
764  a.  Data points  
765   
766  The report should include all data points collected for the tests performed and a 
767  summary of the data (e.g., minimum, maximum, average, and standard deviation). 
768  Applicants should consider using consistent units throughout the testing. If data 
769  values are rounded, then the significant digit to which they were rounded should be 
770  specified.  
771   
772  b.  Data analysis  
773   
774  Applicants should analyze the data, including any outlying points and anomalous 
775  results, and explain whether the data meet acceptance criteria. FDA recommends that 
776  applicants conduct data analyses for the test results using statistical analyses, when 
777  appropriate, and specify whether the acceptance criteria were met. If the data analysis 
778  demonstrates that the acceptance criteria were not met for either individual samples or 
779  entire sample populations, applicants should: discuss the potential reasons for test 
780  failure; determine if re-testing is appropriate; identify risk mitigation measure(s); and 
781  provide justification for why the testing results should be considered acceptable and 
782  supportive of the proposed labeling regarding administration via enteral tube.  
783   
 
1 See the guidance for industry and FDA staff Recognition and Withdrawal of Voluntary Consensus Standards 
(September 2020). We update guidances periodically. For the most recent version of a guidance, check the FDA 
guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.  
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784  c.  Protocol deviations  
785   
786  The report should describe any protocol deviations, the activities executed to 
787  determine the source of the deviation, and any effect on the test results and their 
788  interpretation.  
789   
790  6.  Discussion of conclusions  
791   
792  Applicants should describe the conclusions drawn from the test results and the clinical 
793  significance of the conclusions. 
  21