Compounding Certain 
Beta-Lactam Products 
in Shortage Under 
Section 503A of the 
Federal Food, Drug, 
and Cosmetic Act  
 
Immediately in Effect Guidance 
for Industry 
 
FDA is issuing this guidance for immediate implementation in accordance with 21 CFR 
10.115(g)(2).  Comments may be submitted at any time for Agency consideration.  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. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
November 2022 
Compounding 
 
    
Compounding Certain 
Beta-Lactam Products 
in Shortage Under 
Section 503A of the 
Federal Food, Drug, 
and Cosmetic Act 
 
Immediately in Effect 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 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
November 2022 
Compounding 
 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  DISCUSSION .................................................................................................................... 3 
i  Contains Nonbinding Recommendations 
 
1  Compounding Certain Beta-Lactam Products in Shortage Under 
2  Section 503A of the Federal Food, Drug, and Cosmetic Act 
3  Immediately in Effect Guidance for Industry1 
4   
5   
6  This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
7  this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
8  can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
9  To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
10  title page.   
11   
12   
13   
14   
15  I.  INTRODUCTION  
16   
17  This guidance describes the Food and Drug Administrations (FDA or the Agency) regulatory 
18  and enforcement priorities regarding preparation of beta-lactam oral antibiotic suspension 
19  products that appear on FDAs drug shortage list by a licensed pharmacist in a State-licensed 
20  pharmacy or Federal facility.  There is currently an acute shortage of amoxicillin oral antibiotic 
21  powder for suspension.  Amoxicillin oral antibiotic powder for suspension products currently 
22  appear on FDAs drug shortage list.  Amoxicillin is widely used for the treatment of bacterial 
23  upper and lower respiratory infections in the pediatric population, among other uses.  As a result 
24  of this shortage, there is an urgent need to increase the supply of these beta-lactam oral 
25  suspension products.  FDA has received a number of reports related to increased demand for 
26  amoxicillin oral antibiotic suspension products in particular.  FDA has also received requests for 
27  clarification about preparation of compounded versions of those products from FDA-approved 
28  tablets and capsules.     
29   
30  This guidance is being implemented without prior public comment because FDA has determined 
31  that prior public participation for this guidance is not feasible or appropriate (see section 
32  701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 
33  10.115(g)(2)).  This guidance document is being implemented immediately because of the public 
34  health need for amoxicillin oral antibiotic suspension products, but it remains subject to 
35  comment in accordance with the Agencys good guidance practices. 
36   
37  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
38  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
39  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
40  the word should in Agency guidances means that something is suggested or recommended, but 
41  not required.  
 
1 This guidance has been prepared by multiple offices in the Center for Drug Evaluation and Research, in 
consultation with the Office of Regulatory Affairs, at the Food and Drug Administration.  
  1  Contains Nonbinding Recommendations 
 
42   
43  II.  BACKGROUND 
44   
45  Compounded drug products are not FDA-approved, which means they have not undergone FDA 
46  premarket review for safety, effectiveness, and quality.  Section 503A of the FD&C Act (21 
47  U.S.C. 353a) provides that a drug product compounded by a licensed pharmacist in a State-
48  licensed pharmacy or a Federal facility or by a licensed physician can qualify for exemptions 
49  from requirements under three other sections of the FD&C Act: adequate directions for use 
50  (section 502(f)(1) (21 U.S.C. 352(f)(1)), new drug approval requirements (section 505 (21 
51  U.S.C. 355)), and current good manufacturing practice (CGMP) requirements (section 
52  501(a)(2)(B) (21 U.S.C. 351(a)(2)(B))) if all of the conditions in section 503A are met.   
53   
54  One of the conditions in section 503A of the FD&C Act is that each drug product must be 
55  compounded for an identified individual patient based on the receipt of a valid prescription order 
56  or a notation, approved by the prescribing practitioner, on the prescription order that a 
57  compounded product is necessary for the identified patient.2  If an FDA-approved drug product 
58  is on FDAs drug shortage list, it may be compounded by an outsourcing facility in accordance 
59  with section 503B of the FD&C Act or by a licensed pharmacist in a State-licensed pharmacy or 
60  Federal facility in accordance with section 503A of the FD&C Act.3   
61   
62  Under the FD&C Act, a drug is adulterated if it has been prepared, packed, or held under 
63  insanitary conditions whereby it may have been contaminated with filth, or whereby it may have 
64  been rendered injurious to health (section 501(a)(2)(A) of the FD&C Act (21 U.S.C. 
65  351(a)(2)(A)) (insanitary conditions provision).  Section 503A of the FD&C Act does not 
66  provide an exemption from the insanitary conditions provision.4  Drug products prepared, 
67  packed, or held under insanitary conditions could become contaminated and cause serious 
68  adverse events, including death.  Processing of beta-lactam drugs without complete and 
 
2 See section 503A(a) of the FD&C Act. See also FDAs guidance for industry Prescription Requirement Under 
Section 503A of the Federal Food, Drug, and Cosmetic Act (December 2016).  We update guidances periodically. 
For the most recent version of the guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents. 
3 The provision in section 503A of the FD&C Act that applies to compounding a drug product that is essentially a 
copy of a commercially available drug does not apply to compounding a drug on FDAs drug shortage list because 
FDA does not consider products on FDAs drug shortage list to be commercially available.  See section 
503A(b)(1)(D) of the FD&C Act, and FDAs guidance for industry Compounded Drug Products That Are 
Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and 
Cosmetic Act (January 2018).   
4 Insanitary conditions are conditions that could cause a drug to become contaminated with filth or rendered 
injurious to health. The drug itself need not actually be contaminated.  A drug that is actually contaminated with any 
filthy, putrid, or decomposed substance is deemed to be adulterated under section 501(a)(1) of the FD&C Act (21 
U.S.C. 351(a)(1)). 
  2  Contains Nonbinding Recommendations 
 
69  comprehensive separation5 from non-beta-lactam products is an example of an insanitary 
70  condition that FDA has observed.6   
71   
72  In addition to penicillin, all beta-lactam drugs can be sensitizing agents; therefore, cross-
73  contamination between any beta-lactam drug and other drugs could initiate the same types of 
74  drug-induced life-threatening allergic reactions that penicillins can trigger.  Therefore, any 
75  handling of any beta-lactam drugs should be done in a manner to prevent cross-contamination 
76  with non-beta-lactam drugs, thereby reducing the potential for drug-induced, life-threatening 
77  allergic reactions.  
78   
79  The current shortage of amoxicillin oral antibiotic powder for suspension products and increased 
80  demand for beta-lactam oral antibiotic suspension products could lead to potentially serious or 
81  life-threatening situations in particular in the pediatric population, especially during the 
82  upcoming fall and winter months when the incidence of upper and lower respiratory infections is 
83  expected to peak.  Therefore, based on risk management principles, in order to address access 
84  concerns while also minimizing the potential for cross-contamination and the resulting 
85  hypersensitivity or allergic reactions, FDA intends to prioritize its regulatory and enforcement 
86  actions regarding the preparation of beta-lactam oral antibiotic suspension products that appear 
87  on FDAs drug shortage list by compounders under section 503A as described below.     
88   
89  III.  DISCUSSION 
90   
91  For a licensed pharmacist in a State-licensed pharmacy or Federal facility that has not registered 
92  as an outsourcing facility and that compounds beta-lactam oral antibiotic suspension products 
93  that appear on FDAs drug shortage list, the Agency intends to prioritize its regulatory and 
94  enforcement actions with respect to the insanitary conditions provision to focus on the potential 
95  for harm to the public health, taking into consideration the public health need for beta-lactam 
96  oral antibiotic suspension products at this time.   
97   
 
5 Complete and comprehensive separation refers to a cross-contamination prevention strategy that consists of: (1) the 
complete physical separation of beta-lactam production area(s) (including separate air handling system(s)) from 
production areas for other drugs; and (2) additional design and procedural controls for facilities, equipment, 
material, and personnel that are necessary to support and maintain the integrity of the physical separation (e.g., 
dedicated equipment; utilities management (waste flow, including the potential for beta-lactam production exhaust 
to contaminate an adjacent building air intake, vacuum systems); people/material/equipment flow; personnel 
gowning; decontamination; monitoring containment; testing; compliance with procedures; investigations).  Although 
separate buildings could ensure separation of beta-lactam operations from non-beta-lactam operations, it is feasible 
for one building to contain a dedicated area for beta-lactam production that is completely isolated and sealed off 
from the rest of the building.  For example, separate entries and exits to the beta-lactam segment of the building 
would be necessary to ensure comprehensive separation.  In the limited cases in which this design concept could be 
considered, a risk assessment should demonstrate that the design provides as much protection against cross-
contamination as is achieved by producing in a separate building. 
6 See FDAs guidance for industry on Insanitary Conditions at Compounding Facilities.  The guidance explains that 
processing of beta-lactams does not refer to mixing, reconstituting, or other such acts that are performed in 
accordance with the directions contained in approved labeling provided by the products manufacturer and other 
manufacturer directions consistent with that labeling, at the immediate point of dispensing for administration to the 
intended patient. 
  3  Contains Nonbinding Recommendations 
 
98  As noted above, FDAs insanitary conditions guidance describes the processing of beta-lactams 
99  without complete and comprehensive separation from non-beta-lactam products as an example of 
100  an insanitary condition the Agency has observed.  However, during the time that beta-lactam 
101  antibiotic powder for oral suspension products are on the FDA shortage list (or for such shorter 
102  time as FDA may announce by updating or withdrawing this guidance based on evolving needs 
103  and circumstances), based on the Agencys current understanding of the potential for risk of 
104  contamination, compounders under section 503A of the FD&C Act that prepare beta lactam oral 
105  antibiotic suspension products that appear on FDAs shortage list without complete and 
106  comprehensive separation from non-beta-lactam products should take at least the following 
107  minimum steps to mitigate the potential risk of cross-contamination and reduce risk to patients.  
108  FDA generally intends to prioritize its regulatory and enforcement actions if the following steps 
109  are not all followed when preparing beta-lactam oral antibiotic suspension products that appear 
110  on FDAs shortage list without complete and comprehensive separation from non-beta-lactam 
111  products: 
112   
113  1.  Use of FDA-approved beta-lactam tablets and capsules instead of bulk drug substances to 
114  compound the beta-lactam oral antibiotic suspension product; 
115  2.  Temporal segregation of the compounding of these oral suspensions from non-beta-
116  lactam products; 
117  3.  Use of dedicated or disposable equipment, utensils, and personal protective equipment 
118  (e.g., gowns, gloves);   
119  4.  Segregation and storage in a separate area of any equipment, utensils, and personal 
120  protective equipment used in the compounding of these oral suspensions (e.g., glassware, 
121  mortar and pestle) from equipment, utensils, and personal protective equipment not used 
122  in beta-lactam compounding; 
123  5.  Trituration of the FDA-approved product after wetting it with a quantity of the 
124  suspension vehicle sufficient to eliminate formation of product dust;  
125  6.  Use of proper cleaning procedures after completing compounding, including use of 
126  peroxide or bleach solutions to deactivate the beta-lactam ring of any drug residue on 
127  surfaces.  The use of strong oxidizers should be followed by neutralizers and volatile 
128  cleaning agents (e.g., purified water, isopropanol) to minimize damage to these surfaces;  
129  7.  Containment and remediation of spills; 
130  8.  The beyond-use-date assigned to the compounded oral suspension does not exceed the 
131  beyond-use-date of the related reconstituted FDA-approved beta-lactam antibiotic 
132  powder for oral suspension product that is on FDAs drug shortage list, as found on the 
133  approved labeling; and 
134  9.  Storage conditions used for the compounded oral suspension are consistent with those for 
135  the related reconstituted FDA-approved beta-lactam antibiotic powder for oral suspension 
136  product that is on FDAs drug shortage list, as found on the approved labeling. 
137  Health care providers may also consider FDA-approved alternatives to the product in shortage.   
138   
139  FDA also recommends monitoring for reports of allergic reactions, including anaphylactic shock, 
140  that might be related to unintentional beta-lactam exposure from the use of non-beta-lactam 
141  drugs.  If such reports are confirmed, the pharmacy should take appropriate action, which may 
142  include notifying patients and medical providers.  If there are reports of anaphylactic shock or 
  4  Contains Nonbinding Recommendations 
 
143  allergic reactions related to unintentional exposure, the pharmacy should stop compounding beta-
144  lactam products.  
145   
146  FDA encourages consumers, patients, and health care professionals to report adverse events or 
147  quality problems experienced with the use of compounded drugs to FDAs MedWatch Adverse 
148  Event Reporting program: 
149    Complete and submit the report online at MedWatch: The FDA Safety Information and 
150  Adverse Event Reporting Program; or 
151    Download and complete the form, then submit it via fax at 1-800-FDA-0178. 
  5