43146039dft.docx

4/3/2023

Notifying FDA of a Discontinuance or 

Interruption in Manufacturing of 

Finished Products or Active 

Pharmaceutical Ingredients Under 

Section 506C of the FD&C Act 

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DRAFT GUIDANCE 

This guidance document is being distributed for comment purposes only.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) Drug Shortage Staff, 240-402-

7770, or (CBER) Office of Communication, Outreach and Development, 800-835-4709 or 240-

402-8010. 

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

April 2023 

Procedural
Notifying FDA of a Discontinuance or 

Interruption in Manufacturing of 

Finished Products or Active 

Pharmaceutical Ingredients Under 

Section 506C of the FD&C Act 

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 Communication, Outreach, and Development 

Center for Biologics Evaluation and Research

Food and Drug Administration

10903 New Hampshire Ave., Bldg. 71, Room 3128

Silver Spring, MD 20993-0002

Phone: 800-835-4709 or 240-402-8010; Email: ocod@fda.hhs.gov

https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

April 2023 

Procedural
Contains Nonbinding Recommendations

Draft — Not for Implementation

TABLE OF CONTENTS

I. INTRODUCTION............................................................................................................. 1

II. BACKGROUND ............................................................................................................... 2

III. NOTIFYING FDA OF A PERMANENT DISCONTINUANCE OR AN 

INTERRUPTION IN MANUFACTURING .................................................................. 3

A. Who Must Notify FDA and What Products are Subject to the Notification Requirements ...4

B. When To Notify FDA..................................................................................................................... 6

C. What Information To Include in Notifications About Discontinuances or Interruptions in 

Manufacturing of Covered Finished Products............................................................................ 8

D. What Information to Include in Notifications About Discontinuances or Interruptions in 

Manufacturing of API ................................................................................................................. 11

E. How To Notify FDA..................................................................................................................... 12

F. Failure To Notify FDA................................................................................................................. 12

IV. HOW FDA COMMUNICATES INFORMATION ABOUT DRUGS AND 

BIOLOGICAL PRODUCTS IN SHORTAGE ............................................................ 13
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1 

1 Notifying FDA of a Discontinuance or Interruption in 

2 Manufacturing of Finished Products or Active Pharmaceutical 

3 Ingredients Under Section 506C of the FD&C Act

Guidance for Industry1 4 

 5 

6 

7 This draft guidance, when finalized, will represent the current thinking of the Food and Drug 

8 Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not 

9 binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the 

10 applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible 

11 for this guidance as listed on the title page.

12 

 13 

 14 

15 I. INTRODUCTION

 16 

17 FDA is issuing this guidance to assist applicants and manufacturers in providing FDA timely, 

18 informative notifications about changes in the production of certain finished drugs and biological 

products2 as well as certain active pharmaceutical ingredients (API)3 19 that may, in turn, help the 

20 Agency in its efforts to prevent and mitigate shortages. 

 21 

22 The guidance discusses the notification requirements under section 506C of the Federal Food, 

23 Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 356c) and FDA’s regulations. Generally, 

24 section 506C of the FD&C Act requires applicants and manufacturers of certain finished drugs 

25 and biological products to notify FDA of (1) a permanent discontinuance in the manufacture of 

26 such products, (2) an interruption in the manufacture of such products that is likely to lead to a 

27 meaningful disruption in supply of those products in the United States, (3) a permanent 

28 discontinuance in the manufacture of API for such products, or (4) an interruption in the 

29 manufacture of API for such products that is likely to lead to a meaningful disruption in the 

30 supply of the API for those products. This guidance recommends that applicants and 

31 manufacturers provide additional details and follow additional procedures to ensure FDA has the 

32 specific information it needs to help prevent or mitigate shortages. In addition, the guidance 

1 This guidance has been prepared by the Drug Shortage Staff and the Office of Regulatory Policy in the Center for 

Drug Evaluation and Research (CDER), in conjunction with the Office of Compliance and Biologics Quality in the 

Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration. 

2 For purposes of this guidance, a finished drug or biological product refers to a specific strength, dosage form, and 

route of administration of a drug or biological product. See 80 FR 38915 at 38919 and 38928; see also section 

506C(h)(1) of the FD&C Act (defining “drug” for purposes of section 506C).

3 For purposes of this guidance, active pharmaceutical ingredient means any substance that is intended for 

incorporation into a finished drug product and is intended to furnish pharmacological activity or other direct effect in 

the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the 

body. Active pharmaceutical ingredient does not include intermediates used in the synthesis of the substance (see 21 

CFR 207.1). 
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33 explains how FDA communicates information about products in shortage to the public. When 

34 finalized, this guidance will replace the March 2020 guidance for industry Notifying FDA of a 

35 Permanent Discontinuance or Interruption in Manufacturing Under Section 506C of the FD&C 

Act. 36 

37 

38 In general, FDA’s guidance documents do not establish legally enforceable responsibilities. 

39 Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only 

40 as recommendations, unless specific regulatory or statutory requirements are cited. The use of 

41 the word should in Agency guidances means that something is suggested or recommended, but 

42 not required. 

 43 

44 II. BACKGROUND

 45 

46 Title X of the Food and Drug Administration Safety and Innovation Act (FDASIA), enacted on 

July 9, 2012,4 47 and section 3112 of the Coronavirus Aid, Relief, and Economic Security Act 

(CARES Act), enacted on March 27, 2020,5 48 amended the FD&C Act to help the Agency address 

49 the problem of drug shortages in the United States, including by adding requirements related to 

50 notifying FDA about finished product and API manufacturing discontinuances and interruptions. 

51 While some supply disruptions and product shortages cannot be predicted or prevented, early 

52 communication and detailed notifications from manufacturers to the Agency play a significant 

53 role in decreasing the incidence, impact, and duration of supply disruptions and product 

54 shortages. Timely notifications that include specific information about the situation allow the 

Agency to evaluate the situation and determine an appropriate course of action. 55 6 When FDA 

56 does not receive timely, informative notifications, the Agency’s ability to respond appropriately 

57 is limited.

 58 

59 Please note that notifications regarding discontinuances or potential manufacturing issues that 

60 are sent to FDA to meet other reporting requirements, for example, under section 506I of the 

61 FD&C Act (reports of marketing status) or 21 CFR 314.81(b)(1) (field alert reports), are not a 

62 substitute for the notifications required under section 506C of the FD&C Act. It is important that 

63 notifications pursuant to section 506C contain detailed information and be submitted to the 

64 appropriate staff in the Center for Drug Evaluation and Research (CDER) and the Center for 

65 Biologics Evaluation and Research (CBER) (as described in section III.E) to enable timely 

66 review and action by the Agency. 

4 Public Law 112-144. The FDASIA amendments to section 506C of the FD&C Act took effect on July 9, 2012.

5 Public Law 116-136. The CARES Act amendments to section 506C of the FD&C Act took effect on September 

23, 2020.

6 See CDER’s Manual of Policies and Procedures (MAPP) 4190.1 Drug Shortage Management for information 

about CDER’s policies and procedures for evaluating and managing drug shortage situations. CDER MAPPs can be 

found on the Manual of Policies and Procedures web page at https://www.fda.gov/about-fda/center-drug-evaluationand-research/cder-manual-policies-procedures-mapp. See CBER’s Standard Operating Procedures and Policies 

(SOPPS) 8506 Management of Shortages of CBER-Regulated Products for information about CBER’s policies and 

procedures for evaluating and managing shortage situations. CBER SOPPs can be found on the Biologics 

Procedures web page at https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatoryinformation-biologics/biologics-procedures-sopps. 
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67

68

69 III. NOTIFYING FDA OF A PERMANENT DISCONTINUANCE OR AN 

70 INTERRUPTION IN MANUFACTURING

71

Under section 506C of the FD&C Act and FDA’s regulations,

7,8 72 certain persons must notify

73 FDA of (1) a permanent discontinuance in the manufacture of certain finished drug and 

74 biological products, (2) an interruption in the manufacture of certain finished drug and biological

products that is likely to lead to a meaningful disruption9 75 (or, in the case of blood or blood 

components intended for transfusion, a significant disruption10 76 ) in supply of those products in the 

77 United States, (3) a permanent discontinuance in the manufacture of API for certain finished 

78 drugs and biological products, or (4) an interruption in the manufacture of API for certain 

7 Section 506C(i) of the FD&C Act (as amended by FDASIA) required FDA to issue regulations implementing

section 506C of the FD&C Act. On July 8, 2015, FDA issued the final rule, “Permanent Discontinuance or 

Interruption in Manufacturing of Certain Drug or Biological Products” (80 FR 38915) to implement section 506C 

and other drug shortage provisions of the FD&C Act, as amended by FDASIA (see 21 CFR 310.306, 

314.81(b)(3)(iii), and 21 CFR 600.82). Section 506C(i)(3) of the FD&C Act permitted FDA to apply the section, by 

regulation, to biological products (as defined in section 351 of the Public Health Service Act), including plasma 

products derived from human plasma protein and their recombinant analogs, if FDA determined that including these 

products would benefit the public health. FDA’s 2015 final rule extended drug shortage notification requirements to 

applicants of certain biological products, including recombinant therapeutic proteins, monoclonal antibody products, 

vaccines, allergenic products, plasma derived products and their recombinant analogs, blood or blood components 

for transfusion, and cellular and gene therapy products (see § 600.82 and 80 FR 38915 at 38918).

8 As noted above, the CARES Act amended section 506C of the FD&C Act by, among other things, adding 

requirements related to notifying FDA about discontinuances and interruptions in manufacturing of certain 

APIs. Prior to the CARES Act, section 506C contained notification requirements applicable to covered finished 

products (as described below in section III.A) only. As such, the regulations implementing section 506C, which 

FDA promulgated in 2015 (80 FR 38915), contain notification requirements applicable to covered finished products 

only. These regulations do not contain the notification requirements described in this guidance that are applicable to 

API for covered finished products; rather, such API notification requirements arise directly under section 506C, as 

amended by the CARES Act.

9 With respect to finished product notifications under section 506C of the FD&C Act, meaningful disruption means 

a change in production that is reasonably likely to lead to a reduction in the supply of a drug by a manufacturer that 

is more than negligible and affects the ability of the manufacturer to fill orders or meet expected demand for its 

product, and does not include interruptions in manufacturing due to matters such as routine maintenance or 

insignificant changes in manufacturing so long as the manufacturer expects to resume operations in a short period of 

time (see section 506C(h)(3) of the FD&C Act and §§ 314.81(b)(3)(iii)(f) and 600.82(f)).

10 Significant disruption means a change in production that is reasonably likely to lead to a reduction in the supply of 

blood or blood components by a manufacturer that substantially affects the ability of the manufacturer to fill orders 

or meet expected demand for its product, and does not include interruptions in manufacturing due to matters such as 

routine maintenance or insignificant changes in manufacturing so long as the manufacturer expects to resume 

operations in a short period of time (see § 600.82(f)). FDA intends to consider an interruption in manufacturing that 

leads to a reduction of 20 percent or more of an applicant’s own supply of blood or blood components over a 1-

month period to “substantially affect” the ability of the applicant to fill orders or meet expected demand; 

accordingly, such an interruption would be considered a “significant disruption” in supply (see 80 FR 38915 at 

38920-21). 
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finished drugs and biological products that is likely to lead to a meaningful disruption11 79 in the 

80 supply of the API for those products. Notifications under section 506C must include disclosure 

of reasons for the discontinuation or interruption.12 81 The sections below describe the notification 

82 requirements under section 506C in greater detail and provide recommendations about the 

83 notifications, including the timing and contents.

84

85 A. Who Must Notify FDA and What Products are Subject to the Notification 

86 Requirements 

87

88 The persons who must submit notifications under section 506C (collectively referred to in this 

89 guidance as manufacturers) are as follows: 

90

91 • Applicants with approved new drug applications (NDAs) or approved abbreviated new 

drug applications (ANDAs) for certain finished drug products13 92

93

94 • Applicants with approved biologics license applications (BLAs) for certain finished 

biological products other than blood or blood components14 95

96

97 • Applicants with approved BLAs for blood or blood components for transfusion that 

manufacture a significant percentage of the U.S. blood supply15,16 98

99

100 • Manufacturers of certain finished drug products marketed without approved NDAs or 

ANDAs17 101 

102

103 The notification requirement regarding discontinuances and interruptions in manufacturing of

104 API under section 506C of the FD&C Act applies only to the manufacturers that are listed 

105 above; other entities in the supply chain for a drug, including third-party API manufacturers and 

106 suppliers, are not required to submit such notifications. 

11 For purposes of this guidance, and with respect to API notifications under section 506C of the FD&C Act, 

meaningful disruption means a change in production that is reasonably likely to lead to a reduction in supply of an 

API by its manufacturer that is more than negligible and affects the ability of the API manufacturer to fill orders or 

meet expected demand for the API, and does not include interruptions in manufacturing due to matters such as 

routine maintenance or insignificant changes in manufacturing so long as the API manufacturer expects to resume 

operations in a short period of time.

12 See section 506C(a) of the FD&C Act.

13 See § 314.81(b)(3)(iii).

14 See § 600.82(a)(1).

15 See § 600.82(a)(2).

16 FDA intends to consider an applicant that holds a BLA for blood or blood components to be a manufacturer of a 

“significant percentage” of the U.S. blood supply if the applicant manufactures 10 percent or more of the U.S. blood 

supply (see 80 FR 38915 at 38917).

17 See § 310.306, which applies § 314.81(b)(3)(iii) in its entirety to covered drug products marketed without an 

approved NDA or ANDA.
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107

108 The finished products for which notifications must be submitted under section 506C of the 

109 FD&C Act (referred to in the guidance as covered finished products) are prescription drugs and

biological products18 110 (including blood or blood components for transfusion) that are (1) life 

supporting, life sustaining,19 111 or intended for use in the prevention or treatment of a debilitating 

disease or condition,20 112 including any such product used in emergency medical care or during 

113 surgery or any such drug that is critical to the public health during a public health emergency 

114 declared by the Secretary under section 319 of the Public Health Service Act; and (2) not 

radiopharmaceutical drug products or any other products designated by FDA.21,22 115 In addition, the 

116 manufacturers listed above must submit notifications under section 506C of the FD&C Act for 

API of covered finished products.

23 117

118

119 In general, the notification requirements for covered finished products apply to each individual 

120 manufacturer regardless of market share, number of other manufacturers marketing products that 

are therapeutically equivalent, or the amount of product that may be in distribution.24 121 Similarly, 

122 with respect to notifications for an API of a covered finished product, FDA recommends that a 

123 manufacturer consider its current API manufacturer’s supply of the API, regardless of the API 

124 manufacturer’s market share, the number of other API manufacturers marketing the same or 

125 similar APIs, or the amount of the API that may be in distribution. If a manufacturer is not 

126 certain whether the notification requirements under section 506C of the FD&C Act apply to the 

127 products it manufactures or the API(s) for the products it manufactures, we recommend that the 

128 manufacturer contact the Agency as described in section III.E below. 

129

130 In the case of a covered finished product that is marketed under an approved application and API 

131 for such a product, the applicant is solely responsible for submitting notifications to FDA under 

132 section 506C of the FD&C Act concerning the covered finished product or API for the covered 

18 See footnote 2.

19 Life supporting or life sustaining means a product that is essential to or that yields information that is essential to, 

the restoration or continuation of a bodily function important to the continuation of human life (see §§ 

314.81(b)(3)(iii)(f) and 600.82(f)).

20 Intended for use in the prevention or treatment of a debilitating disease or condition means a product intended for 

use in the prevention or treatment of a disease or condition associated with mortality or morbidity that has a 

substantial impact on day-to-day functioning (see §§ 314.81(b)(3)(iii)(f) and 600.82(f)).

21 See section 506C(a) of the FD&C Act; §§ 310.306, 314.81(b)(3)(iii)(a), and 600.82(a).

22 The notification requirement applies regardless of any determination with respect to whether the product is 

medically necessary (see generally CDER’s MAPP 4190.1 Rev. 3). 

23 See section 506C(a) of the FD&C Act.

24 As explained in the preamble to the final rule (80 FR at 38920), “...[T]he rule requires an applicant to report an 

interruption in manufacturing likely to lead to a meaningful disruption in its own supply of a covered drug or 

biological product...Consistent with the statute, the rule does not require an applicant to predict the market-wide 

impact of an interruption in its own manufacturing...” But see above regarding the requirement for blood or blood 

components intended for transfusion which only applies to applicants that manufacture a significant percentage of 

the U.S. blood supply. 
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133 finished product, regardless of whether the product or API is manufactured by the applicant itself 

or for the applicant under contract with one or more different entities.25 134 Accordingly, the 

135 applicant should establish a process with any third-party API suppliers, any relevant contract 

136 manufacturers, and other relevant entities to ensure that the applicant can provide a complete and 

137 accurate notification to FDA within the required time frame. Likewise, for a covered finished 

138 drug product marketed without an approved NDA or ANDA, the manufacturer should establish a 

139 process with any third-party API suppliers, any relevant contract manufacturers, and other 

140 relevant entities to ensure the manufacturer can provide complete and accurate notification to 

141 FDA within the required time frame.

142

143 B. When To Notify FDA

144

145 In general, manufacturers of covered finished products must submit a notification to FDA at least 

146 6 months in advance of (1) a permanent discontinuance in manufacturing of a covered finished 

147 product, (2) an interruption in manufacturing of a covered finished product that is likely to lead 

148 to a meaningful disruption in supply of the product in the United States, (3) a permanent 

149 discontinuance in manufacturing of API for a covered finished product, or (4) an interruption in 

150 manufacturing of API for a covered finished product that is likely to lead to a meaningful 

disruption in supply of the API for the product.

26 151 However, if 6 months’ advance notice is not 

possible, the notification must be submitted as soon as practicable thereafter27 152 ; furthermore, a 

153 notification concerning a permanent discontinuance or interruption in manufacturing of a 

154 covered finished product must be submitted no later than 5 business days after the 

discontinuance or interruption in manufacturing occurs.28 155 

156

157 For covered finished products and API, FDA interprets a permanent discontinuance to be a 

158 decision by its manufacturer to cease manufacturing and distributing its product indefinitely for 

159 business or other reasons. Notification must be provided within the time frame described 

above.29 160 Upon receiving such notifications, FDA assesses the potential public health impact of 

161 the reported discontinuance and, if appropriate, may request further discussion with the reporting 

162 manufacturer. With respect to covered finished products in particular, to the extent possible, 

163 manufacturers should not delay notifying FDA of a permanent discontinuance until after 

164 production has ceased; FDA should be notified well before any decline in supply occurs. 

165

166 In the case of interruptions in manufacturing of a covered finished product, when assessing 

167 whether a meaningful disruption in supply is likely to occur, the relevant analysis is whether a 

168 change in production is likely to lead to a reduction in the supply of a product by the 

169 manufacturer that is more than negligible and would affect the manufacturer’s ability to fill 

25 See §§ 314.81(b)(3)(iii)(a) and 600.82(a)(1).

26 See section 506C(b) of the FD&C Act; §§ 310.306(b), 314.81(b)(3)(iii)(b)(1), and 600.82(b)(1).

27 See section 506C(b) of the FD&C Act.

28 See section 506C(b) of the FD&C Act; §§ 310.306(b), 314.81(b)(3)(iii)(b)(2), and 600.82(b)(2).

29 See section 506C(a) of the FD&C Act; §§ 310.306(b), 314.81(b)(3)(iii)(a), and 600.82(a).
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orders or meet expected demand for its product.30 170 In other words, the assessment is to be based 

171 solely on the reporting manufacturer’s capacity and supply. The manufacturer should not 

172 consider other manufacturers’ or competitors’ capacities or assumed capacities, or what it 

understands about market demand for the product.31 173 To the extent it is possible to do so, 

174 manufacturers must notify FDA of an interruption in manufacturing that is likely to lead to a 

175 meaningful disruption in their own supply of the covered finished product in the United States

prior to the interruption’s occurrence.

32 176 In all cases, manufacturers should notify the Agency

177 before a meaningful disruption in their own supply of a covered finished product occurs. For 

178 example, FDA should not first learn of a meaningful supply disruption resulting from an 

179 interruption in manufacturing when a manufacturer is unable to fill an order. Note that after 

180 providing the initial notification of an interruption in manufacturing of a covered finished 

181 product under section 506C of the FD&C Act, FDA recommends that manufacturers provide 

182 updates approximately every 2 weeks on the situation, including the expected timeline for 

183 resuming normal operations, even if the status remains unchanged. These updates are important 

184 to ensure that FDA remains informed and can act on the most current information. We 

185 recommend that such updates be submitted until the situation has been resolved.

186

187 If a manufacturer is unsure of whether to notify FDA of an interruption in manufacturing 

188 because the firm does not know whether it is likely to lead to a meaningful disruption in its 

supply,33 189 FDA urges the manufacturer to submit a notification anyway. This would allow FDA 

190 to monitor the overall market and take timely steps, as necessary, to help prevent or mitigate any 

191 resulting shortage. In addition, if a manufacturer is considering taking an action that may lead to 

192 a meaningful disruption in the supply of a product (e.g., holding production to investigate a 

193 quality issue or transfer of ownership), FDA requests that the manufacturer notify FDA 

194 immediately through the process explained below in section III.E.

195

30 See 80 FR 38915 at 38920. Manufacturers are not required to report interruptions in manufacturing due to matters 

such as routine maintenance or insignificant changes in manufacturing, so long as the manufacturer expects to 

resume operations in a short period of time (see section 506C(h)(3)(B) of the FD&C Act).

31 See 80 FR 38915 at 38920 (explaining that manufacturers are not required or expected to predict the market-wide 

impact of an interruption in their own manufacturing). But see section III.A (explaining that the regulatory 

requirement for blood or blood components intended for transfusion only applies to applicants that manufacture a 

significant percentage of the U.S. blood supply) (emphasis added). 

32 See section 506C(b) of the FD&C Act; §§ 310.306(b), 314.81(b)(3)(iii)(b), and 600.82(b).

33 See footnote 9.
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196 In the case of interruptions in manufacturing of API, a covered finished product manufacturer is 

197 required to notify FDA of interruptions in the manufacture of the API of such products that are 

198 likely to lead to a meaningful disruption in the supply of API. When assessing whether a 

199 meaningful disruption is likely to occur in this context, the manufacturer should consider

200 whether a change in production of the API is likely to lead to a reduction in the supply of API by 

201 the API supplier that is more than negligible and would affect the API supplier’s ability to fill 

orders or meet expected demand for the API.34 202 As noted in section III.A, to ensure the 

203 manufacturer is able to satisfy the notification requirement with respect to API, manufacturers 

204 should establish a process to ensure they receive sufficient, timely information about changes in 

205 production of their supplier’s API.

206

207 As described above, the notification requirements under the FD&C Act and FDA’s regulations 

208 are triggered by a permanent discontinuance or an interruption in manufacturing that is likely to 

209 lead to a meaningful disruption in supply of certain finished drugs or biological products or API 

210 for those products. However, FDA requests that manufacturers also notify the Agency when they 

211 are unable to meet demand for covered finished products, even in the absence of an interruption 

212 in manufacturing, for example, when there is a sudden, unexpected spike in demand. Though 

213 manufacturers are not required to report this type of situation to FDA, reporting under these 

214 circumstances provides an important signal to the Agency about a potential shortage and allows 

215 FDA to take appropriate steps to address the potential shortage.

216

217 C. What Information To Include in Notifications About Discontinuances or 

218 Interruptions in Manufacturing of Covered Finished Products

219

220 Under section 506C of the FD&C Act and FDA’s regulations, notifications concerning a 

221 permanent discontinuance or interruption in the manufacture of a covered finished product that is 

likely to lead to a meaningful disruption in supply must include, at a minimum:

35 222

223

224 • Name of the product, including the National Drug Code (NDC) number, or, for biological 

225 products, an alternative standard for identification and labeling if one has been 

recognized as acceptable by the Center Director.

36 226

227

228 • Name of the applicant (for approved products) or manufacturer (for unapproved drugs).

229

230 • Whether the notification relates to a permanent discontinuance of the product or an 

231 interruption in manufacturing of the product.

232

233 • Description of the reason(s) for the discontinuation or interruption in manufacturing.

234

34 FDA recommends that a manufacturer consider its current API manufacturer’s supply of the API regardless of the 

API manufacturer’s market share, the number of other API manufacturers marketing the same or similar APIs

(including, for approved products, the number of approved API sources the manufacturer may have), or the amount 

of the API that may be in distribution. 

35 See section 506C(a) of the FD&C Act; §§ 310.306(b), 314.81(b)(3)(iii)(c), and 600.82(c).

36 See § 600.82(c)(1).
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235 • If an API is a reason for, or risk factor in, the discontinuation or interruption, the source 

236 of the API, and any alternative sources for the API known by the manufacturer. 

 237 

238 • Whether any associated device used for preparation or administration included in the 

covered finished product37 239 is a reason for, or risk factor in, the discontinuation or 

240 interruption in manufacturing of the covered finished product. 

 241 

242 • The estimated duration of an interruption in manufacturing of the covered finished 

243 product. 

 244 

245 As noted above, this information is the minimum that manufacturers must provide. However, to 

246 ensure that FDA is better equipped to help prevent or mitigate a drug shortage, FDA 

247 recommends that manufacturers provide additional details about the situation and has included 

248 below a list of types of additional information for manufacturers to consider providing in their 

249 notifications to FDA. This list is not intended to be exhaustive; it provides information that FDA 

250 generally finds helpful in assessing the situation and determining appropriate steps to help 

251 prevent or mitigate a shortage. The more information manufacturers provide, the better FDA will 

252 be able to assist.

 253 

254 We recommend including the following additional information, as relevant to the situation, when 

255 notifying FDA of a permanent discontinuance or interruption in manufacturing concerning a 

256 covered finished product: 

 257 

258 • Whether the notification concerns an unavoidable supply disruption or a supply 

259 disruption that may be preventable. 

 260 

261 • The underlying reason or root cause leading to this notification. (A detailed and thorough 

262 explanation beyond “manufacturing delay” or a recitation of the broad categories of 

263 reasons listed below in section IV is especially important and allows FDA to identify and 

264 use the most appropriate and effective mitigation tools.)

 265 

37 For purposes of the notification requirement under section 506C of the FD&C Act, FDA considers the term any

associated device used for preparation or administration included in the drug to be a device constituent part of a 

covered finished product that is a drug-led, drug-device or biologic-led, biologic-device combination product (i.e., a 

single entity, co-packaged, or cross-labeled combination product, as defined in 21 CFR 3.2(e)). Under section 506J 

of the FD&C Act, manufacturers of certain medical devices are required to notify the Agency of a permanent 

discontinuance in the manufacture of the device or interruption in manufacture of the device that is likely to lead to a 

meaningful disruption in the supply of the device in the United States. For more information about such device 

notifications, see section 506J of the FD&C Act. Regarding the shortage of a device, if you have questions about 

your notification, you can contact the Center for Devices and Radiological Health at

CDRHManufacturerShortage@fda.hhs.gov and include “Question” in the subject line of the email. 
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266 • The estimated date of onset of the interruption in manufacturing or supply disruption for 

267 this product. If a supply disruption has already occurred, provide the estimated 

duration.

38 268

269

270 • The anticipated time frame for all existing product (on hand and in distribution channels) 

271 to be exhausted if the notification is for a permanent discontinuance.

272

273 • The estimated market share for the product and whether the entire market share is 

274 affected by this issue.

275

276 • The estimated volume of historic monthly sales, usage, or demand, as applicable, for this 

277 product.

278

279 • Whether the product is manufactured on multiple lines or in multiple facilities.

280

281 • Amount of current inventory of product at the manufacturing facility or warehouse.

282

283 • If the notification is for an interruption in manufacturing, the date when the last 

284 remaining batch of finished product was or will be released into distribution and how 

285 long the supply is expected to last in the market without additional releases based on 

286 current demand.

287

• Whether there is an emergency or reserve supply of this product and whether allocation39 288

289 of supply on hand or reserve supply is an option.

290

291 • Whether a redundancy risk management plan that identifies and evaluates risks to the 

supply of the drug is in place.40 292

293

294 • Whether public information has been provided or will be provided for stakeholders and 

295 patients regarding this actual or potential shortage (e.g., Dear Healthcare Provider 

296 (DHCP) Letters, supply or shortage information posted on the manufacturer’s website).

297

298 • Whether a proposal is available for FDA to review that may help to expedite availability 

299 of the product or suggestions for FDA actions that may help prevent or mitigate a supply 

300 disruption or shortage.

301

302 Manufacturers need not have all of these additional details available before submitting a 

303 notification; notifications can be updated at any time to include such additional information. 

38 Notifications of interruptions in manufacturing must include the expected duration of the interruption in 

manufacturing. See section 506C(a) of the FD&C Act. See also §§ 310.306(b), 314.81(b)(3)(iii)(c)(5), and 

600.82(c)(5).

39 Allocation generally refers to limiting the quantity distributed to customers to extend the life of the existing 

supply.

40 See section 506C(j) of the FD&C Act.
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304 Manufacturers must provide initial notification within the timeframe described in section 

305 506C(b) of the FD&C Act and applicable regulations (see section III.B for further discussion), 

306 and FDA recommends that manufacturers update their notifications with additional information 

307 as it becomes available. As described further in section IV below, information that is submitted 

308 to FDA will not be disclosed except in accordance with applicable disclosure law, which 

includes restrictions on the release of confidential commercial information and trade secrets.41 309 If 

310 FDA determines that a product is in shortage, the Agency intends to work with manufacturers to 

311 confirm the accuracy and appropriateness of information regarding the shortage before posting 

312 publicly on FDA’s website.

313

314 D. What Information to Include in Notifications About Discontinuances or 

315 Interruptions in Manufacturing of API

316

317 Under section 506C of the FD&C Act, notifications concerning API must include, at a 

minimum:42 318

319

320 • Disclosure of reasons for the discontinuation or interruption in manufacturing of the API.

321

322 • Source of the API and any alternative sources for the API known by the finished product 

323 manufacturer.

324

325 • Expected duration of an interruption in manufacturing of the API.

326

327 To ensure these notifications provide information that is helpful to FDA in assessing the 

328 potential for a supply disruption or shortage, we recommend that manufacturers also include the

329 additional information outlined below:

330

331 • Name(s) of the finished product(s) for which the API is used, including the NDC 

332 number(s), or, for biological products, an alternative standard for identification and 

labeling if one has been recognized as acceptable by the Center Director.

43 333

334

335 • Name of the application holder (for approved products) or manufacturer (for unapproved 

336 drugs) of the covered finished product(s) for which the API is used.

337

• Number of any drug master file associated with the API.

44 338

339

340 • Whether the notification relates to a permanent discontinuance of the API or an 

341 interruption in manufacturing of the API.

342

41 See section 506C(d) of the FD&C Act.

42 See section 506C(a) of the FD&C Act.

43 See § 600.82(c)(1).

44 See § 314.420.
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343 • Estimated date of onset of the interruption in manufacturing or supply disruption for the 

API. If a supply disruption has occurred, provide the estimated duration.

45 344 

 345 

346 • Whether the discontinuance or interruption in manufacturing of the API has impacted or 

347 is expected to impact the supply of the covered finished product or ability to fill orders 

348 for the covered finished product.

 349 

350 E. How To Notify FDA

351 

352 Manufacturers of covered finished products regulated by CDER should submit initial 

notifications about such products46 353 and API for such products either via email to

354 drugshortages@fda.hhs.gov or through the CDER Direct NextGen Portal at https://edm.fda.gov. 

355 Manufacturers of covered finished products regulated by CBER should submit initial 

notifications about such products47 356 and API for such products via email to

357 cbershortage@fda.hhs.gov. All additional updates should be submitted by email to the applicable 

358 Center (CDER or CBER), not through the NextGen Portal. 

 359 

360 Manufacturers should submit a separate notification for each permanent discontinuance or 

361 interruption in manufacturing. A single initial notification may include a list of all affected

covered finished products48 362 or API. Manufacturers should not provide notification about a newly 

363 affected product (e.g., a new strength) in an update, even if the issue is related to a previously 

364 reported interruption in manufacturing. Rather, a separate initial notification should be submitted 

365 to ensure the newly affected product is tracked appropriately. In addition, as explained in section 

366 II, notifications submitted to FDA to satisfy other reporting requirements (e.g., under section 

367 506I of the FD&C Act) are not a substitute for the notifications required under section 506C. 

 368 

369 F. Failure To Notify FDA

 370 

371 If a manufacturer fails to provide notification with respect to covered finished products or API, 

372 as required by section 506C(a) of the FD&C Act and in accordance with the timelines set forth in 

section 506C(b) and the implementing regulations,49 373 FDA will issue a letter to that manufacturer 

stating that the applicable notification requirement was not met (a “noncompliance letter”).

50 374 

375 Note that if FDA determines that an applicant experienced a reportable interruption in 

376 manufacturing that it could not reasonably anticipate 6 months in advance, but the applicant 

45 Notifications of interruptions in manufacturing must include the expected duration of the interruption in 

manufacturing. See section 506C(a) of the FD&C Act. 

46 Notifications for finished products under section 506C of the FD&C Act must be submitted to FDA electronically 

in a format that FDA can process, review, and archive. See §§ 310.306(b), 314.81(b)(3)(iii)(b), and 600.82(b); see 

also 80 FR 38915 at 38922.

47 Ibid.

48 See footnote 2. 

49 Section 506C(b) of the FD&C Act; §§ 310.306(b), 314.81(b)(3)(iii)(b)(1) and (2), and 600.82(b)(1) and (2).

50 See section 506C(f)(1) of the FD&C Act.
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failed to notify FDA “as soon as practicable,” FDA will issue a noncompliance letter.51 377 The 

378 manufacturer must respond to FDA’s letter not later than 30 calendar days after its issuance, 

379 providing the reason for noncompliance and the information on the discontinuance or 

interruption required under section 506C(a) of the FD&C Act.

52 380 Not later than 45 calendar days 

381 after the issuance of the noncompliance letter to the manufacturer, FDA will post that letter and 

any response received on FDA’s website,53 382 with appropriate redactions to protect trade secrets or 

confidential commercial information.54 383 However, FDA will not post the noncompliance letter 

384 and any response it receives if the Agency determines that the noncompliance letter was issued 

385 in error or, after review of the manufacturer’s response, that the manufacturer had a reasonable

basis for not notifying FDA as required.55 386 

 387 

 388 

389 IV. HOW FDA COMMUNICATES INFORMATION ABOUT DRUGS AND 

390 BIOLOGICAL PRODUCTS IN SHORTAGE 

 391 

Consistent with section 506E of the FD&C Act (21 U.S.C. 356e) and FDA’s regulations,56 392 FDA 

393 maintains public, up-to-date lists of finished drugs and biological products that FDA has 

determined to be in shortage in the United States.57 394 These lists include:

 395 

396 • Established name of the product in shortage; brand name of the product in shortage, if 

397 applicable; the NDC number, presentation, strength(s), and package size, as available 

 398 

399 • Name of each application holder (for approved products) or manufacturer (for 

400 unapproved drugs) 

 401 

402 • Name of the distributor, if different from the application holder (for approved products) 

403 or manufacturer (for unapproved drugs) 

 404 

• Reason for the shortage from the following categories:58 405 

51 Ibid.

52 See section 506C(f)(2) of the FD&C Act.

53 Links to noncompliance letters can be found at 

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm403902.htm. 

54 See section 506C(d), (f)(3) of the FD&C Act.

55 See section 506C(f)(3) of the FD&C Act.

56 See section 506E of the FD&C Act; §§ 310.306(c), 314.81(b)(3)(iii)(d)(1), and 600.82(d)(1).

57 See https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm for shortages tracked by CDER; see 

https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/cber-regulated-products-currentshortages for shortages tracked by CBER. 

58 The reason for the shortage identified is determined by FDA using the notification submitted and any 

supplementary information gathered, such as from manufacturing facility reviews conducted by FDA.
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406

407  Requirements related to complying with good manufacturing practices

408  Regulatory delay

409  Shortage of an active ingredient

410  Shortage of an inactive ingredient component

411  Discontinuation of the manufacture of the product

412  Delay in shipping 

413  Demand increase

414  Other reason

415

416 • Estimated duration of the supply disruption or shortage, anticipated date of availability, 

417 and resolution dates (based on information provided by the manufacturer)

418

419 • Any additional information related to the shortage that the manufacturer chooses to share 

420 (e.g., DHCP letters, informed consent forms, or patient letters) 

421

422 FDA updates its lists regularly and strives to communicate in real-time so that patients and 

423 healthcare providers have the most current information on product shortages in the United States. 

424 A product is added to the CDER- or CBER-maintained list only after the Agency determines that 

425 it is in shortage; products are not added to the list(s) immediately upon receipt of a notification 

426 regarding a discontinuance or interruption in manufacturing. In cases where a shortage does not 

427 occur or is prevented through FDA or stakeholder intervention, the product will not be posted on 

428 the list. FDA generally considers a shortage to be resolved and removes the product from the 

429 “current shortage” section of the list based on an evaluation of the entire market, assessing 

430 whether all backorders have been filled and supply is meeting or exceeding demand. In making 

431 this evaluation, FDA may consider, among other factors, affected market share, ability of 

432 alternate manufacturers to cover the demand, and confirmed market stabilization.

433

434 The Agency does not include confidential commercial information or trade secrets in these 

lists.

59 435 In general, FDA works with manufacturers to confirm the accuracy and appropriateness 

436 of information before posting publicly on its website(s). FDA will continue to post information 

437 on its website(s) consistent with section 506E of the FD&C Act and FDA’s regulations, 

438 regardless of any additional information manufacturers provide to the Agency based on the 

439 recommendations in this guidance.

59 See section 506E(c)(2) of the FD&C Act.