Insanitary Conditions at 
Compounding Facilities 
 
Guidance for Industry  
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Office of Compliance 
 
 
November 2020 
Compounding and Related Documents 
 
   
 
Insanitary Conditions at 
Compounding Facilities 
 
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) 
Office of Compliance 
 
November 2020 
Compounding and Related Documents 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  POLICY ............................................................................................................................. 3 
A.  Examples of Insanitary Conditions .............................................................................................. 4 
B.  Preventative and Corrective Actions for Insanitary Conditions ............................................. 10 
C.  Regulatory Action ........................................................................................................................ 12 
 
  Contains Nonbinding Recommendations 
Guidance for Industry1 
Insanitary Conditions at Compounding Facilities 
  
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or the Agency) 
on this topic.  It does not create any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. 
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
I.  INTRODUCTION 
 
Under section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 
U.S.C. 351(a)(2)(A)), a drug is deemed to be adulterated if it has been prepared, packed, or held 
under insanitary conditions whereby it may have been contaminated with filth, or whereby it 
may have been rendered injurious to health . . .2 Drug products prepared, packed, or held under 
insanitary conditions could become contaminated and cause serious adverse events, including 
death.   
 
Under sections 503A and 503B of the FD&C Act (21 U.S.C. 353a and 353b), compounded 
human drug products can qualify for exemptions from specified provisions of the FD&C Act if 
certain conditions are met. However, neither section provides an exemption from section 
501(a)(2)(A) of the FD&C Act. Drugs (including biological products) prepared, packed, or held 
(hereinafter referred to as produced) under insanitary conditions are deemed to be adulterated, 
regardless of whether the drugs qualify for exemptions set forth in sections 503A or 503B of the 
FD&C Act.   
 
This guidance describes examples of insanitary conditions that FDA has observed. This guidance 
specifically addresses drugs (including biological products) produced by pharmacies, federal 
facilities, and outsourcing facilities that compound or repackage drugs, or that mix, dilute, or 
repackage biological products.3 For purposes of this guidance, we refer to such entities as 
compounding facilities.  
                                                 
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. 
 
2 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)). 
3 At this time and based on our current understanding of the risks, FDA generally does not intend to take action 
under section 501(a)(2)(A) against a physician who is compounding a drug product, repackaging an FDA-approved 
drug product, or who is mixing, diluting, or repackaging an FDA-licensed biological product, provided that such 
production by the physician occurs in the physicians office for in-office administration, to his or her individual 
patients.  
 
1       Contains Nonbinding Recommendations 
 
FDA is issuing this guidance to help compounding facilities and state regulatory agencies 
understand some examples of what FDA considers to be insanitary conditions that could cause a 
drug product to become contaminated or rendered injurious to health. These examples are 
intended to help compounding facilities  prevent the occurrence of these and other insanitary 
conditions. This guidance is also intended to help compounding facilities identify and remediate 
such insanitary conditions when they already exist.  
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required.  
 
 
II.  BACKGROUND 
 
FDA has investigated numerous outbreaks of infections and deaths found to be the result of drug 
products that were contaminated because they were produced under insanitary conditions. Most 
notably, in 2012, injectable drug products produced by a compounding facility and shipped 
across the country caused a fungal meningitis outbreak that resulted in more than 750 cases of 
infection and 60 deaths. FDA has investigated numerous other serious adverse events, including 
deaths, associated with contaminated drug products produced by compounding facilities, and it is 
likely that adverse events are underreported.  
 
Since the 2012 fungal meningitis outbreak, FDA has identified insanitary conditions at many of 
the compounding facilities that it has inspected, and numerous compounding facilities have 
voluntarily recalled drug products intended to be sterile and temporarily or permanently ceased 
sterile operations because of those findings. FDA routinely inspects outsourcing facilities.4 There 
are also numerous state-licensed pharmacies in the United States engaged in compounding, 
repackaging drugs, or mixing, diluting, or repackaging biological products that do not register as 
outsourcing facilities with FDA. Generally, state boards of pharmacy have primary responsibility 
for the day-to-day oversight of state-licensed pharmacies that are not registered as outsourcing 
facilities. While FDA conducts inspections of such state-licensed pharmacies, it does not inspect 
the vast majority of them unless, for example, FDA receives a complaint, such as a report of a 
serious adverse event or product quality issue. As a result, the Agency is often not aware of these 
pharmacies, their conditions and practices, and potential problems with the quality and safety of 
their drug products.  
 
Regardless of whether a facility is routinely inspected by FDA, it is critical that both state-
licensed pharmacies and outsourcing facilities prevent the occurrence of insanitary conditions 
within their facilities. Upon identification, insanitary conditions should be remediated before the 
conditions result in drug contamination and patient injury.   
 
                                                 
4 See section 503B(b)(4) of the FD&C Act. 
2       Contains Nonbinding Recommendations 
In addition, to protect the public health, both FDA and state regulatory agencies may take action 
when compounding facilities produce drugs under insanitary conditions. Based on its 
inspections, FDA determines whether compounding facilities produce drugs under insanitary 
conditions in violation of section 501(a)(2)(A) of the FD&C Act, and if so, the Agency may 
initiate regulatory action. However, compounding facilities that are not registered with FDA as 
outsourcing facilities are primarily overseen by the states and, as explained above, generally are 
not routinely inspected by FDA. FDA strongly encourages state regulatory agencies to assess 
during inspections whether compounding facilities that they oversee engage in poor practices, 
including those described below. Where insanitary conditions are identified, FDA encourages 
states to take appropriate action, consistent with state laws and regulations, and to contact FDA. 
 
 
III.  POLICY 
 
Section III.A of this guidance provides examples of conditions that FDA has observed at one or 
more compounding facilities it has inspected and considers to be insanitary conditions under 
section 501(a)(2)(A) of the FD&C Act. These examples do not constitute an exhaustive list of 
insanitary conditions that could be present in a compounding facility; other conditions not 
described in this guidance may also be considered insanitary.   
 
Section III.B of this guidance describes corrective actions that compounding facilities should 
take when they identify insanitary conditions. It also describes actions that are recommended to 
prevent the occurrence of insanitary conditions. Of note, this section includes a list of 
particularly concerning conditions that FDA has observed. When these particular insanitary 
conditions are identified, FDA strongly recommends that a facility immediately recall 
purportedly sterile drugs and cease sterile operations until these insanitary conditions have been 
remediated.  
 
Finally, section III.C of this guidance discusses regulatory actions FDA may take in response to 
insanitary conditions we identify at a compounding facility. Although FDA expects all insanitary 
conditions to be remediated in a timely manner, FDA considers the entire set of conditions at the 
facility, including any aggravating and mitigating factors, as well as evidence of timely and 
appropriate remediation activities, when determining the type of regulatory action to take against 
a compounding facility.  
 
Note that the examples of insanitary conditions described in this guidance for products intended 
to be sterile can exist in cleanroom and associated controlled environments, as well as segregated 
compounding areas (SCAs), as described in United States Pharmacopeia (USP) Chapter <797> 
(USP <797>). FDA has significant sterility assurance concerns regarding sterile compounding 
within an International Standard Organization (ISO) 5 area located within an unclassified space. 
However, at this time and based on our current understanding of the risks, when a compounding 
facility other than an outsourcing facility produces drugs in an SCA, FDA generally does not 
intend to take action with respect to certain conditions described in this guidance identified with 
an asterisk (*), provided that the compounding facility: (1) complies with all criteria for an SCA 
in USP <797>; (2) assigns beyond-use-dates that do not exceed 12 hours when stored at room 
temperature and 24 hours when refrigerated or frozen; and (3) does not have any additional 
insanitary conditions.   
3       Contains Nonbinding Recommendations 
 
A.  Examples of Insanitary Conditions5 
 
Although product sterility is not a requirement for non-sterile drugs, it is possible for non-sterile 
drugs to become contaminated with microorganisms of a type or at a level that can cause patient 
harm. Non-sterile aqueous solutions are particularly susceptible to microbial growth if 
contaminated. Contamination may also include non-viable filth and the presence of unintended 
drug components.  
 
The following are examples of insanitary conditions that have been observed and are applicable 
to both sterile and non-sterile drug production and applicable to the production of sterile drugs 
only. These examples do not constitute an exhaustive list.   
 
1.  Insanitary Conditions Applicable to the Production of Sterile and Non-Sterile Drugs 
 
 
  Vermin (e.g., insects, rodents) or other animals (e.g., dogs) or evidence of their presence 
(e.g., urine, feces) in the production area6 or adjacent areas 
 
  Visible microbial contamination (e.g., bacteria, mold) in the production area or adjacent 
areas 
 
  Foreign matter in the production area (e.g., rust, glass shavings, hairs, paint chips) 
 
  Producing drugs while construction is underway in a nearby area without adequate 
controls to prevent contamination of the production area and product 
 
  Standing water or evidence of water leakage in the production area or adjacent areas 
 
  Handling bulk drug substances or drug products that are hazardous, sensitizing, or highly 
potent (e.g., hormones) with inadequate controls to prevent cross-contamination. This 
includes: 
  inadequate dedication, segregation, and containment (e.g., a powder-containment 
o
hood) of a suite, room, or piece of equipment based on risk;   
  inadequate cleaning of rooms, work surfaces, and equipment (e.g., utensils), 
o
including spills;  
  inadequate segregation of HVAC systems (as appropriate for the operation); and  
o
  inadequate control over the movement of personnel and materials 
o
 
                                                 
5 Note that USP <797> provides descriptions of select terms used in this section, including buffer room and 
anteroom.  
 
6 For the purpose of this guidance, production area includes, with respect to sterile compounding any ISO classified 
area or SCA, and with respect to non-sterile compounding, any room or area in which non-sterile compounding 
occurs. 
 
4       Contains Nonbinding Recommendations 
  Processing of beta-lactams without complete and comprehensive separation from non-
beta-lactam products7 
 
  Using active ingredients, inactive ingredients, or processing aides, that have or may have 
higher levels of impurities compared to compendial or pharmaceutical grade equivalents 
(e.g., ingredients with potentially harmful impurities, ingredients labeled with not for 
pharmaceutical use or an equivalent statement) 
 
2.  Insanitary Conditions Applicable to the Production of Sterile Drugs Only   
 
a.  Gowning and Aseptic Practices  
 
  Engaging in aseptic processing wearing nonsterile gown components (e.g., gloves)   
 
  Putting on gowning apparel in a way that may cause the gowning apparel to become 
contaminated. This includes, for example:  
  gowning in non-classified areas* 
o
  allowing gowning apparel (except for foot covers) to touch the floor, or other 
o
surface area that could cause apparel to be contaminated, or 
  putting on sterile gloves improperly (e.g., touching the outside of a glove with 
o
bare hands) 
 
  Failing to disinfect or change gloves frequently enough given the nature of the operations 
to prevent contamination. This includes, for example, gloves exiting and re-entering the 
ISO 5 area without changing or sanitizing them, touching a non-sterile object and 
returning to compounding without first changing or sanitizing gloves, cleaning up after a 
spill without changing gloves when returning to compounding, and not changing the 
sterile gloves when glove integrity may have been compromised 
 
  Engaging in aseptic processing after leaving the cleanroom and re-entering from a non-
classified area without first replacing gowning apparel (e.g., gowns, mask, goggles, foot 
covers, gloves)8* 
 
  Performing aseptic manipulations with exposed hair or skin (e.g., on hands, wrists, 
forehead, mouth, or legs) 
 
  Performing aseptic manipulations outside of a certified ISO 5 area (or area of higher 
quality air)  
                                                 
7 For the purposes of this guidance, 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 
product's manufacturer and other manufacturer directions consistent with that labeling [at the immediate point of 
dispensing for administration to the intended patient]. 
 
8 Note that personnel moving in and out of the cleanroom without regowning may bring contaminants from non-
classified areas into the cleanroom. 
 
 
5       Contains Nonbinding Recommendations 
 
  Conducting aseptic manipulations in an area where the movement of first air9 in the 
ISO 5 area is blocked or disrupted (e.g., by equipment, supplies, or operator 
manipulations)10,11 
 
  Exposing sterile drugs and materials to lower than ISO 5 quality air. This would include, 
for example, exposing partially stoppered drug products or stock solutions in a 
container/closure system that is not fully closed (airtight), and open packages of sterile 
wipes  
 
  Failing to disinfect containers of sterile drug components or supplies immediately prior to 
opening for any use in operations 
 
  Failure to use pre-sterilized or sterilized primary containers and closures to fill sterile 
products 
 
  Using a non-sterile tool, manually contacting the inner surface of a sterile container or 
closure, or manually touching a product contact surface 
 
  This includes, for example, touching the top of an open container, or the lower 
o
side or bottom of a closure during manual stoppering (e.g., hand stoppering)12 
 
  Moving quickly in a critical area or in an area immediately adjacent to a critical area13 
such that unidirectional airflow is likely to be disrupted14 
 
                                                 
9 First air means air that is from a HEPA filter and that has not yet contacted any items/surfaces. 
 
10 Note that if unidirectional air over the critical surface is blocked, the area is no longer protected. If it is blocked by 
personnel conducting aseptic manipulations, contamination on personnel could be introduced to the critical area.    
 
11 At this time and based on our current understanding of the risks, FDA generally does not intend to object to the 
temporary blocking or disruption of first air in the ISO 5 area when necessary for the safe handling of 
radiopharmaceuticals, such as the placement of a shielding material for the radiopharmaceutical in the ISO 5 area.  
 
12 Note that this could contaminate the drug in the vials even with the use of sterile gloves and appropriate glove 
sanitization. 
 
13 A critical area is an area designed to maintain sterility of sterilized materials.  Sterilized product, containers or 
closures, and equipment may be exposed in critical areas. The ISO 5 area is the critical area, and the terms are used 
interchangeably throughout this guidance. 
 
14 Note that while conducting aseptic manipulations, ISO 5 airflow must be unidirectional to protect the product 
from contaminating particles. Quick movement of personnel disrupts the airflow and increases the risk of bringing 
lesser quality air into the ISO 5 area. At this time and based on our current understanding of the risks, FDA 
generally does not intend to object to the temporary blocking or disruption of first air in the ISO 5 area when 
necessary for the safe handling of radiopharmaceuticals, such as rapid movement, as appropriate to minimize 
radiation exposure. 
 
 
6       Contains Nonbinding Recommendations 
  Staging open sterile vials within the critical area without protective cover longer than 
needed for the process of filling drug product 
 
b.  Equipment/Facilities 
 
  Microbial contamination in the ISO 5 area 
 
  Lack of adequate routine environmental monitoring15 
 
  This includes nonviable airborne particulate sampling; viable airborne particulate 
o
sampling; and surface sampling, including but not limited to equipment, work 
surfaces, and room surfaces 
 
  Lack of adequate personnel sampling (including glove fingertip sampling) 
 
  Lack of routine and rigorous certification of the ISO 5 area, including smoke studies 
performed under dynamic conditions16 
 
  A facility designed or operated in a way that permits the influx of lesser quality air into a 
higher quality air area 
 
  This includes, for example: 
o
  inadequate pressure differentials between areas of higher quality air and 
lower quality air*  
  material flow directly between an unclassified area and a room in which 
sterile compounding is conducted (e.g., unclassified pass-through)* 
  an ISO 5 area open to the surrounding area with minimal or no physical 
barriers separating it from non-aseptic activities (e.g., weighing of non-
sterile materials, gowning, container labeling)*  
  air returns located next to the high efficiency particulate arrestance 
(HEPA) filter rather than near the floor*  
  an open door or series of open doors between an uncontrolled area and the 
room in which sterile compounding is conducted*  
 
  Failure to detect and adequately address a change in air quality (e.g., through the 
environmental monitoring program) of any classified area before there is a loss of 
environmental control that may impact drug sterility 
 
                                                 
15 Note that environmental monitoring provides information on the quality of the aseptic processing environment. If 
the results reflect a poor quality aseptic processing environment, the compounding facility should promptly identify 
potential routes of contamination and perform corrective actions. 
 
16 Note that if the ISO 5 area is not periodically re-certified or does not pass all certification requirements, there is 
insufficient assurance that the ISO 5 area filters are functioning and delivering the quality of air intended.  
7       Contains Nonbinding Recommendations 
  No or infrequent measurement of room pressure differentials during operations to 
demonstrate proper airflow (i.e., airflow from areas of higher quality air to adjacent areas 
with lower quality air)* 
 
  A pattern of frequent or acute pressure reversals from areas of less clean air to areas of 
higher air cleanliness 
 
  A lack of HEPA-filtered air, or inadequate HEPA filter coverage or airflow, over the 
critical area 
   
  HEPA filters that are not sealed around the perimeter17 
 
  Rooms not properly classified for the activities conducted within them  
 
  Unsealed or loose ceiling tiles in production areas 
 
  Production areas or equipment that are difficult to clean or contain porous, particle-
generating, or visibly dirty (e.g., rusty) equipment or surfaces (e.g., shelving, floors, 
walls, doors, ceilings) 
 
  Buffer room or ISO 5 areas that contain overhangs or ledges capable of collecting dust 
(e.g., utility pipes and horizontal surfaces, such as windowsills) 
 
  The presence of sinks, drains, or water sources in the buffer room where the ISO 5 area is 
located; the presence of floor drains in the anteroom18 
 
  The presence of equipment unnecessary for aseptic operations, particularly particle-
generating equipment, in the ISO 5 area 
 
  Equipment within or in close enough proximity to the ISO 5 area that could compromise 
the air in the ISO 5 area  
 
  Exposing sterile products to non-sterile or non-depyrogenated supplies (e.g., transfer 
tubing, temporary bulk containers) 
   
  Using lyophilizers that are not sterilized by routine sterilization cycles and protected from 
contamination by sterilizing filters on vacuum break air lines/vents 
 
                                                 
17 Note that the air entering the cleanroom needs to be HEPA filtered to remove airborne particles.  If HEPA filters 
are not sealed, air that is not HEPA filtered could enter the cleanroom. 
 
18 Note that sinks and drains are sources of microbial contamination.   
8       Contains Nonbinding Recommendations 
c.  Sterilization 
 
  Using a filter for the purposes of product sterilization that is not appropriately graded for 
sterilization, not appropriate for pharmaceutical use, or used in excess of its volume or 
pressure capacity 
 
  Using a filter in drug production whose integrity is compromised; failing to conduct post-
use filter-integrity testing on filters used to sterilize products  
  
  Using a particle-shedding filter in any stage of sterile drug production 
   
  Using parameters for sterilization (e.g., temperature, pressure, and time) that are not 
lethal to resistant microorganisms  
 
d.  Cleaning and Disinfecting 
   
  Using non-sterile disinfecting agents and cleaning pads/wipes in ISO-classified areas 
   
  Lack of, improper, or infrequent use of a sporicidal agent in the facilitys ISO 5 areas and 
other classified areas 
  
  Failing to appropriately and regularly clean and disinfect (or sterilize) equipment located 
in the ISO 5 area 
  
  Lack of disinfection of equipment and/or supplies at each transition from areas of lower 
quality air to areas of higher quality (e.g., from non-classified to first classified room, 
from anteroom to buffer room, from buffer room to ISO 5 area) 
 
  Using disinfectant in a manner insufficient to achieve adequate levels of disinfection 
(e.g., using insufficient disinfectant contact time (also known as dwell time), 
concentration, or coverage of the item/surface being disinfected) 
 
  Using sterile cleaning and disinfecting agents past their expiry date or discard after 
opening date 
 
  Using cleaning and disinfecting agents that may leave residues or not adequately rinsing 
such agents from containers, closures, or equipment that come into direct contact with 
drugs  
 
e.  Other Insanitary Conditions 
 
  Allowing operators with topical or respiratory infections or with open wounds to work 
within compounding operations 
 
9       Contains Nonbinding Recommendations 
  Compounding with components, containers (e.g., in-process or finished), or other 
materials that have not been verified to assure that they do not contribute endotoxin 
contamination that may be objectionable given the products intended use 
 
  Compounding under processing conditions that offer insufficient assurance that the 
finished product will meet an endotoxin specification appropriate for its route of 
administration 
   
  Failure to conduct media fills that closely simulate aseptic production operations under 
the worst-case, most-challenging and stressful conditions 
  
B.  Preventative and Corrective Actions for Insanitary Conditions 
 
It is critical that all compounding facilities prevent the occurrence of any insanitary conditions 
within their facility (including those not included as examples in this guidance). Prevention of 
insanitary conditions begins with the identification of risks associated with a process, procedure, 
or facility. Risk management tools19 offer a way to evaluate risk and to develop controls 
designed to prevent the occurrence of insanitary conditions within a compounding facility. In the 
event that insanitary conditions occur, having adequate monitoring and other management 
controls should facilitate the identification of insanitary conditions before the conditions result in 
drug contamination and patient harm. FDA recommends that compounding facilities consider 
consulting a third party with relevant drug production expertise to conduct this risk assessment 
and to help develop appropriate controls. 
 
Upon identifying insanitary conditions, a compounding facility should immediately assess the 
impact of the insanitary conditions on drug products produced. The compounding facilitys 
assessment should include an evaluation of how widespread the insanitary conditions are and 
over what period of time the conditions have existed, as well as the lots of drug product that 
remain on the market that could be affected.   
 
The compounding facility should also determine whether to cease production of drug products 
until the conditions have been corrected and whether to initiate a recall20 of all potentially 
affected lots on the market within expiry. Below is a list of insanitary conditions that FDA has 
observed and considers to be particularly serious. If any one of these conditions exists, FDA 
strongly recommends that a compounding facility immediately initiate a recall of purportedly 
sterile drugs and cease sterile operations until the condition has been corrected. 
 
  Vermin (e.g., insects, rodents) or other animals (e.g., dogs) in ISO 5 areas or areas 
immediately accessible to production 
 
                                                 
19 Examples of risk management tools can be found in the ICH guidance for industry Q9 Quality Risk Management 
(June 2006) at https://www.fda.gov/media/71543/download. 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.  
 
20 Subpart C of Part 7 of FDA regulations (21 CFR 7.4059) provides guidance for the voluntary recall of products, 
including those recalls initiated by a firm on its own and at FDA's request. 
10       Contains Nonbinding Recommendations 
  Visible microbial growth (e.g., bacteria, mold) in the ISO 5 area or in adjacent areas 
 
  Sources of foreign matter in the ISO 5 area (e.g., rust, glass shavings, hairs, paint chips) 
 
  Performing aseptic manipulations outside of a certified ISO 5 area or area of higher 
quality air 
 
  Personnel aseptic practices that are a contamination hazard to an exposed sterile drug 
product or its constituent sterile components 
 
  Exposing sterile drugs and materials to lower than ISO 5 quality air for any length of 
time. This would include, for example, exposing partially stoppered drug products or 
stock solutions in a container/closure system that is not fully closed (airtight), and open 
packages of sterile wipes.  
   
  Cleanroom areas with unsealed or loose ceiling tiles 
 
  Production of drugs while construction is underway in a nearby area without adequate 
controls to prevent contamination of the production area and product 
 
  A pattern of frequent or acute pressure reversals from areas of less clean air to areas of 
higher air cleanliness 
 
  Using a filter for the purposes of product sterilization that is not appropriately graded for 
sterilization, not appropriate for pharmaceutical use, or used in excess of its volume or 
pressure capacity 
 
  Using parameters for sterilization (e.g., temperature, pressure, time) that are not lethal to 
resistant microorganisms  
 
If a compounding facility decides to initiate a product recall, we recommend that it document the 
implementation of the recall in accordance with the facilitys procedures and immediately notify 
its local FDA Drug Division recall coordinator.21 We also recommend that the compounding 
facility notify the applicable state regulatory body in the state(s) to which the facility ships drugs, 
consistent with state laws and guidance.   
 
In addition to the immediate actions recommended above, if a compounding facility identifies 
insanitary conditions, it should comprehensively assess its operations, including facility design, 
procedures, personnel, processes, materials, and systems, as applicable to prevent the occurrence 
of insanitary conditions within its facility. FDA recommends that the facility consider consulting 
a third party with relevant drug production expertise to conduct this comprehensive evaluation 
and to help implement appropriate corrective actions.   
 
                                                 
21 See guidance for industry Product Recalls, Including Removals and Corrections (March 2020). 
11       Contains Nonbinding Recommendations 
Compounding facilities producing purportedly sterile drug products under insanitary conditions 
should not rely upon or cite a passing sterility test result as an indication of product sterility. 
Microbial contamination, when present, is not uniformly distributed within a batch; therefore, it 
may not be identified in a sterility test.22 Compounding facilities must correct all insanitary 
conditions at their facility regardless of whether the drugs pass a sterility test.23   
 
C.  Regulatory Action 
 
If a compounding facility produces drugs under insanitary conditions, the facility and responsible 
individuals may be subject to several regulatory actions, including, but not limited to, a warning 
letter, seizure of product, or injunction. FDA may also recommend that the facility initiate a 
recall of some or all of its drugs and cease operations until the insanitary conditions have been 
adequately addressed. The applicable state regulatory agency may also pursue regulatory action 
against the facility under applicable state authorities. 
 
                                                 
22 USP Chapter <71> concerning sterility testing states, [t]hese Pharmacopeial procedures are not by themselves 
designed to ensure that a batch of product is sterile or has been sterilized. This is accomplished primarily by 
validation of the sterilization process or of the aseptic processing procedures. 
23 See section 501(a)(2)(A) of the FD&C Act. 
12