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503B Regulations: Complete Guide to FDA Compliance Requirements

A comprehensive overview of 503B outsourcing facility regulations including FDA registration, cGMP requirements, the bulk drug substances list, inspection process, and state vs federal regulatory overlap.

February 8, 2026 7 min read regulations, compliance, cGMP, FDA, 503B, bulk drug substances
FDA regulatory compliance documentation for pharmaceutical facilities
Understanding 503B regulations is essential for both outsourcing facilities and the healthcare providers who source from them.

The regulatory framework for 503B outsourcing facilities is one of the most important — and most frequently misunderstood — areas of pharmaceutical law. Whether you operate a 503B facility, work in compliance, or are a healthcare provider evaluating compounding partners, this guide provides a comprehensive overview of the regulations that govern 503B outsourcing facilities.

Section 503B was added to the Federal Food, Drug, and Cosmetic Act (FD&C Act) by the Drug Quality and Security Act (DQSA) of 2013. Congress enacted the DQSA in response to the 2012 New England Compounding Center (NECC) fungal meningitis outbreak, which killed 76 people and sickened hundreds more from contaminated steroid injections.

The DQSA created a new category of compounding entity — the outsourcing facility — that sits between traditional 503A compounding pharmacies and full-scale drug manufacturers. Outsourcing facilities are exempt from certain FDA requirements (such as new drug application approval) but are subject to others (such as cGMP compliance and FDA inspection).

Key Statutory Requirements

Under Section 503B, an outsourcing facility must:

  1. Register with the FDA as an outsourcing facility and pay associated fees
  2. Report drugs compounded to the FDA, including the names and quantities of drugs compounded during the previous 6-month period
  3. Comply with cGMP requirements under 21 CFR Parts 210 and 211
  4. Submit to FDA inspection on a risk-based schedule
  5. Report adverse events to the FDA within 15 calendar days of receiving information about a serious adverse event
  6. Label products to identify them as compounded in an outsourcing facility
  7. Compound only from eligible bulk drug substances that meet pharmacopeial or other quality standards
  8. Not compound drugs that are essentially copies of commercially available drugs (with certain exceptions)

FDA Registration Process

Initial Registration

To become a registered 503B outsourcing facility, a facility must:

  1. Submit an initial registration to the FDA through the FDA's online registration system
  2. Pay the applicable annual establishment fee
  3. Identify a United States Agent (if the facility is foreign-based)
  4. Provide facility contact information and the types of drugs compounded

Annual Re-registration

Registration must be renewed annually during the FDA's registration period (typically October 1 through December 31). Failure to re-register means the facility loses its 503B status and can no longer operate as an outsourcing facility.

Drug Reporting

Registered facilities must report to the FDA twice per year (June and December) the following information for each drug compounded:

cGMP Requirements

current Good Manufacturing Practice (cGMP) compliance is the most significant regulatory obligation for 503B facilities. cGMP standards are codified in 21 CFR Parts 210 and 211 and cover every aspect of drug manufacturing.

Key cGMP Areas

Personnel and Training

Facilities and Equipment

Production and Process Controls

Laboratory Controls

Packaging and Labeling

Quality Systems

Environmental Monitoring

For facilities that compound sterile products (which is most 503B facilities), environmental monitoring is a critical cGMP requirement. This includes:

For detailed guidance on environmental monitoring, see our guide: Environmental Monitoring Best Practices for 503B Facilities.

The Bulk Drug Substances List

One of the most discussed regulatory topics for 503B facilities is the bulk drug substances list — the list of active pharmaceutical ingredients that outsourcing facilities are permitted to use in compounding.

Category 1, 2, and 3 Substances

The FDA has organized bulk drug substances into categories based on their eligibility for use in 503B compounding:

How the List Works

A 503B facility may compound a drug using a bulk drug substance if:

  1. The substance appears on the FDA's list of bulk drug substances for which there is a clinical need (Category 1), OR
  2. The substance is a component of an FDA-approved drug, OR
  3. The substance appears in the United States Pharmacopeia or National Formulary (USP-NF)

The FDA periodically updates the bulk drug substances list, which can affect which drugs a facility is authorized to compound.

FDA Inspections

Inspection Frequency

The FDA inspects 503B outsourcing facilities on a risk-based schedule. Factors that influence inspection frequency include:

Most 503B facilities can expect to be inspected every 1-2 years, though facilities with prior compliance issues may be inspected more frequently.

What Inspectors Look For

FDA investigators conducting a 503B inspection typically focus on:

  1. Aseptic processing: Proper sterile technique, media fill validations, gowning procedures
  2. Environmental monitoring: Air and surface sampling data, trending, excursion investigations
  3. Laboratory testing: Methods, equipment, data integrity, out-of-specification investigations
  4. Production records: Master batch records, executed batch records, deviations
  5. Quality systems: CAPA effectiveness, complaint handling, change control
  6. Facility and equipment: Cleanroom conditions, equipment qualification, calibration
  7. Personnel: Training records, gowning qualification, competency assessments

Enforcement Actions

Following an inspection, the FDA may take several types of enforcement actions, listed here in escalating order of severity:

  1. No action indicated: The facility is in compliance
  2. Voluntary action indicated: Minor issues identified but formal action not warranted
  3. Official action indicated: Significant issues identified, leading to:

For more on Form 483 observations, see our guide: Understanding FDA Form 483 for 503B Facilities.

For current inspection results, see: 503B Pharmacy FDA Inspection Results 2025-2026.

State vs. Federal Regulation

503B outsourcing facilities operate under a dual regulatory framework:

Federal (FDA) Requirements

State Requirements

In addition to federal requirements, 503B facilities must comply with applicable state laws, which may include:

The interaction between state and federal regulation creates complexity for 503B facilities that distribute products across multiple states.

2025-2026 Regulatory Updates

The regulatory landscape for 503B facilities continues to evolve. Key recent and upcoming changes include:

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