Compounding Inspections and Oversight Frequently Asked Questions
Find answers to frequently asked questions regarding FDA’s inspections of compounding facilities.
- What are the main differences between an FDA inspection of a 503A and 503B compounding facility?
- What is the difference between a surveillance inspection, a for-cause inspection, and a follow-up inspection? How does FDA prioritize inspections?
- How are reinspection fees determined for 503B outsourcing facilities?
- How does FDA coordinate with state regulators on inspections?
- Some states require an FDA inspection to license an outsourcing facility. How can facilities work with FDA to address this need when an inspection has not occurred
- How does a facility request a pre-operational site evaluation?
- How do I know if my FDA inspection was satisfactory? Can an outsourcing facility consist of multiple sites? Can a 503A compounding facility and an outsourcing facility occupy the same physical location?
- If I have a question for FDA about my recent inspection, whom should I contact?
- What is an FDA Form 483 and a warning letter?
- Why has FDA issued warning letters to compounders that produced drugs in accordance with the conditions of section 503A?
- Why do warning letters sometimes cite 503A compounders for violations of CGMP requirements?
- How do I find out when a firm has adequately corrected the violations identified in the warning letter?
- Should FDA actions (e.g., warning letters or FMD-145s) determine whether purchasers use specific outsourcing facilities?
- Where can I find additional information and resources related to compounding inspections and oversight?
1. What are the main differences between an FDA inspection of a 503A and 503B compounding facility?
Sections 503A and 503B of the Federal Food Drug, and Cosmetic (FD&C) Act differentiate between two types of human drug compounders. Section 503A of the FD&C Act applies to human drug compounding by a licensed pharmacist within a state-licensed pharmacy or federal facility, or by a licensed physician, that is not registered with FDA as an outsourcing facility under section 503B. Section 503B applies to human drug compounding within a registered outsourcing facility. Among other differences, compounders operating in accordance with the conditions of section 503A are eligible for an exemption from production in accordance with Current Good Manufacturing Practice (CGMP) requirements. This exemption is not available to outsourcing facilities.
For more information on sections 503A and 503B and their differences, see: FD&C Act Provisions that Apply to Human Drug Compounding.
When FDA inspects a compounding facility seeking to operate under section 503A, these inspections generally cover an evaluation of the firm’s compliance with section 503A, as well as an identification of any insanitary conditions, examples of which are described in the Insanitary Conditions at Compounding Facilities Guidance for Industry.
FDA inspections of 503B outsourcing facilities cover an evaluation of the firm’s compliance with section 503B, as well as an evaluation of insanitary conditions and compliance with CGMP. For reference, CGMP regulations for drug products are found in 21 CFR part 211. FDA has also published a draft guidance on Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act. Once final, this guidance will represent the agency’s current thinking on this topic.
2. What is the difference between a surveillance inspection, a for-cause inspection, and a follow-up inspection? How does FDA prioritize inspections?
FDA conducts surveillance, for-cause, and follow-up inspections of compounders operating under sections 503A and 503B of the FD&C Act.
Surveillance inspections of regulated facilities are used to monitor ongoing compliance with the FD&C Act. FDA routinely conducts surveillance inspections of outsourcing facilities. Surveillance inspections of compounding facilities seeking to operate under section 503A are generally conducted using a risk-based approach to support prioritization, which may consider various factors such as prior complaints.
For-cause inspections occur when FDA believes a facility could have serious problems or to investigate a specific problem or product complaint that has come to FDA’s attention. FDA conducts for-cause inspections in response to complaints, reports of serious adverse events, product quality concerns such as drug contamination, or facility/process concerns.
Follow-up inspections allow FDA to further evaluate whether firms have corrected any previously observed violations, because product safety or quality could be at risk. Follow-up inspections generally aim to verify corrective actions that compounders agreed to implement. These follow-up inspections are considered for-cause inspections.
For-cause inspections, including follow-up inspections, receive a higher priority status.
3. How are reinspection fees determined for 503B outsourcing facilities?
Reinspection of an outsourcing facility is subject to a reinspection fee when (1) the previous inspection identified noncompliance “materially related to an applicable requirement” of the FD&C Act and (2) FDA conducts a subsequent inspection “specifically to determine whether compliance has been achieved to [FDA] satisfaction.”
The reinspection fee is assessed for the fiscal year in which the reinspection takes place. Moreover, a reinspection fee is incurred for each reinspection that occurs until FDA determines that the noncompliant conditions have been adequately addressed.
For more information, see FDA guidance: Fees for Human Drug Compounding Outsourcing Facilities Under Sections 503B and 744K of the FD&C Act.
4. How does FDA coordinate with state regulators on inspections?
Before each compounding inspection, Office of Regulatory Affairs (ORA) generally seeks to invite respective state regulators to participate in inspections of compounders operating under sections 503A and 503B of the FD&C Act.
5. Some states require an FDA inspection to license an outsourcing facility. How can facilities work with FDA to address this need when an inspection has not occurred? How does a facility request a pre-operational site evaluation?
While FDA does not schedule inspections on-demand, FDA can grant requests for pre-operational site evaluations when resources permit. A pre-operational site evaluation is an informal review of a registered outsourcing facility. During the pre-operational site evaluation, FDA may conduct a facility walk-through, ask questions, identify potential deficiencies, and provide guidance for areas of improvement based on regulatory requirements. Outsourcing facilities can submit a formal request for a pre-operational site evaluation to the compounding mailbox at compounding@fda.hhs.gov. These requests are evaluated on a case-by-case basis.
6. How do I know if my FDA inspection was satisfactory?
If FDA does not intend to pursue further action and determines the inspection is closed, the establishment inspection report (EIR) will be shared with the firm as per the Field Management Directive 145 (FMD-145)-Release of the EIR.
In addition, FDA generally issues a letter referring inspectional findings to state regulators when a 503A compounder has committed to taking the necessary corrective actions, and FDA believes those corrective actions can be appropriately overseen by the state regulators.
7. Can an outsourcing facility consist of multiple sites? Can a 503A compounding facility and an outsourcing facility occupy the same physical location?
Section 503B defines an outsourcing facility, in part, as “a facility at one geographic location or address.” As described in FDA guidance, a “facility” may comprise one or multiple suites within a single building, or one or multiple buildings “at one geographic location or address.” Further, a geographic location could include two or more addresses, provided that FDA is capable of inspecting the addresses within a single inspection.
As further discussed in guidance, all drug products compounded in an outsourcing facility are regulated under section 503B and subject to CGMP requirements. An entity that owns or manages an outsourcing facility may compound drugs under section 503A in a separate establishment near the outsourcing facility or in the same building provided the compounding in the 503B outsourcing facility is completely segregated from compounding by the section 503A establishment.
For more information on complete segregation and additional FDA thinking on this matter, see FDA guidance: Facility Definition Under Section 503B of the Federal Food, Drug, and Cosmetic Act.
8. If I have a question for FDA about my recent inspection, whom should I contact?
FDA ORA Office of Pharmaceutical Quality Operations (OPQO) consists of four divisions by geographical area. Your contact email is based on your facility’s geographical location:
- ORAPHARM1_RESPONSES@fda.hhs.gov
- ORAPHARM2_RESPONSES@fda.hhs.gov
- ORAPHARM3_RESPONSES@fda.hhs.gov
- ORAPHARM4_RESPONSES@fda.hhs.gov
9. What is an FDA Form 483 and a warning letter?
An FDA Form 483 lists FDA investigators’ observations from an inspection.
A warning letter advises the compounder of violations of regulatory significance. When FDA considers issuing a warning letter, the agency takes into consideration response(s) the compounder provided in response to the Form FDA 483.
10. Why has FDA issued warning letters to compounders that produced drugs in accordance with the conditions of section 503A?
When a compounder produces drugs in accordance with the conditions of section 503A, the drugs are exempt from only three sections of the FD&C Act:
- section 501(a)(2)(B) – CGMP requirements
- section 502(f)(1) – labeling with adequate directions for use
- section 505 – new drug approval requirements
The drugs remain subject to all other provisions of the FD&C Act, including, for example, section 501(a)(2)(A) – which states that drugs are deemed adulterated if they are prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth or rendered injurious to health.
When FDA issues a warning letter to a firm that produced drugs in accordance with the conditions of section 503A, it is based on violations of federal law from which the drugs were not exempt. Often, such warning letters cite insanitary conditions.
11. Why do warning letters sometimes cite 503A compounders for violations of CGMP requirements?
FDA generally cites compounders for violations of CGMP requirements in two situations:
- First, drugs compounded by entities that are registered with FDA as outsourcing facilities are subject to CGMP requirements. There is no exemption in federal law from CGMP requirements for outsourcing facilities.
- Second, if a licensed pharmacist within a state-licensed pharmacy or federal facility, or a licensed physician, compounds drugs in accordance with section 503A of the FD&C Act, those drugs are exempt from CGMP requirements (as well as from drug approval and certain labeling requirements). However, if the compounder does not produce the drugs in accordance with the conditions of section 503A, the drugs are not eligible for the exemptions and are therefore subject to CGMP requirements.
Note that drugs cannot be prepared, packed, or held under insanitary conditions, regardless of whether they are made in accordance with section 503A or section 503B.
12. How do I find out when a firm has adequately corrected the violations identified in the warning letter?
FDA issues a warning letter close-out letter and posts on this Compounding webpage when FDA has verified the firm has adequately addressed the violations described in the warning letter.
13. Should FDA actions (e.g., warning letters or FMD-145s) determine whether purchasers use specific outsourcing facilities?
Purchasers may consider FDA actions to inform their understanding of a firm’s history of compliance; however, inspections are a snapshot in time, and conditions at the facility can change at any time. FDA reviews and evaluates the facility during an inspection and must draw conclusions about the conditions and practices observed at the time of the inspection. Purchasers should consider other available information about the compounder that may provide them with additional insight about the compounder’s operations.
When a compounded drug is needed because patients cannot be treated with an FDA-approved medication, FDA encourages purchasers to consider obtaining drugs from compounders that are registered with FDA as outsourcing facilities, as these facilities are subject to routine FDA inspections according to a risk-based schedule and CGMP requirements
14. Where can I find additional information and resources related to compounding inspections and oversight?
- For information on FDA compounding inspections and outcomes:
- For webinars on FDA inspection and post-inspection processes:
- On-demand training courses are freely available to the public:
- Additional human drug compounding resources: