Comparison of 503A versus 503B
Written by: Emma Hammond PharmD. Candidate, Mercer University
What are 503A and 503B facilities?
503A pharmacies are what we would consider compounding pharmacies, that fill individualized patient prescriptions and operate on a relatively small scale. These pharmacies must have prescriptions for individual patients. 503B facilities were created with the Drug Quality and Security Act of 2013 (DQSA). A 503B facility acts more as a drug manufacturer, able of manufacturing large batches of drug products without a prescription required. These are defined as an outsourcing facility that compounds sterile drugs, has registered as an outsourcing facility, and complies with requirements of section 503b.
Chart Comparing 503a and 503b.
| 503a | 503b | |
| Population | Compounding based on the receipt of a valid prescription for an individual patient. Limited batch quantities may be compounded, based on historical use. So, these pharmacies may NOT compound for “office-use”. | Healthcare facilities, to be used in office, with or without prescriptions. They also have the option to fill patient specific prescriptions. |
| Regulation | Must follow respective state board of pharmacy regulations, USP 795 and 797
Must register with state boards of pharmacy and DEA. |
More rigorous requirements.
Board of pharmacy regulations, USP 795, 797, current good manufacturing practices (cGMP). Must register with FDA but is not required to be a registered pharmacy. |
| Federal Requirements | All provisions in FD&C act except for:
if the pharmacy meets the requirements in 503A. |
All provisions in FD&C act expect for:
if the facility meets the requirements in 503B. |
| Compounders | By a licensed pharmacist in a state-licensed pharmacy or federal pharmacy or a licensed physician | Is by or under the direct supervision of a licensed pharmacist in the outsourcing facility.
Is not required to be a licensed pharmacy. |
| Bulk drug substances | Bulk drug substances must have a valid certificate of analysis and manufactured with an establishment registered with FDA under section 510. | |
| Must comply with USP or NF monograph or be a component of an FDA approved drug or appear on the list of bulk drug substances that can be used for compounding developed by the FDA, and the USP chapter on pharmacy compounding. | Bulk drug substances must appear on the list of drug substances that can be used for compounding under 503B or on the FDA drug shortage list at the time of compounding, distribution, and dispensing.
If there is an USP, NF or any other drug monograph recognized by the FDA, it must comply with that monograph. |
|
| Drugs withdrawn from the market | Cannot be compounded if it appears on the list published by the FDA of drugs that have been withdrawn or removed from the market. | |
| Drugs presenting demonstrable difficulties for compounding | Cannot compound if the drug is identified by the FDA as one that presents demonstratable difficulties for compounding that can have an adverse effect on safety or effectiveness of the product. | Cannot compound if the drug or if the category of drugs is identified on the list published by the FDA of those that present demonstratable difficulties for compounding. |
| Copies of available products | Cannot compound drug products that are essentially copies of a commercially available product. | |
| Essentially a copy of an approved drug is defined as a drug that identical or nearly identical to an approved drug that is not subject to section 503(b) and to approval in an application under section 505, unless the approved product is on the FDA drug shortage list at the time of compounding.
The drug products are considered identical or nearly identical if they have the same active ingredient(s), route, dosage form, strength, and excipients as the approved product. |
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| Interstate distribution limitations | Limited to no more than 5 % disturbed out of state.
The FDA extended the memorandum of understanding in August 2021, to last until October 27th, 2022, and will begin to enforce this limit when it is finalized. |
None. |
| Wholesaling | Follows any requirements in FD&C act. | The drug cannot be sold or transferred to an entity other than the outsourcing facility that compounded the drug. This does not apply to administration in a healthcare setting or dispensing the drug with a prescription order. |
| Registration | Follows FD&C act section 510(g). | Must register with FDA as an outsourcing facility. |
| Adverse Event Reporting | None in section 503A | Must submit adverse event reporting to the FDA. |
| Labeling | None in section 503A | Must have required information on label, such as “This is a compounded drug.” Or reasonable alternative. It must also include name, address, and phone number of the facility, the lot or batch number, established drug name, dosage form and strength, quantity, date of compounding, expiration date, storage, and handling instructions, NDC (if available), must state “Not for resale” or “Office Use Only” and a list of active and inactive ingredients.4″>ingredients.
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- What are current good manufacturing practices (cGMP)?
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- Regulations enforced by the FDA that assure the identity, strength, quality, and purity of drug products that manufactures are required to uphold. The purpose of these practices is to ensure that drug products are safe and effective. These are the minimum requirements manufacturers must implement. FDA preforms regular inspections of facilities to assess compliance.
- What are USP 795 and USP 797?
- Standards of practice for compounding non-sterile (795) and sterile (797) drugs.
- When should a facility register as a 503B facility?
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- The facility must compound sterile drugs to be considered and do more than repackaging, compounding non-sterile drugs, drugs for animal use or biological products. Only register as an outsourcing facility if you intend to compound all the facility’s compounded drugs in accordance with 503B requirements.
- To qualify for exemptions from the drug approval process the facility must be in compliance with the registration and reporting requirements, including twice yearly reports regarding drugs that are compounded by the facility and adverse event reporting, meets the bulk drug substance and other ingredients requirements as seen in 503B(a)(2) and 503B(a)(3) respectively, cannot compound drugs that have been withdrawn or removed from market by the FDA, cannot make what are essentially copies of an approved drug, cannot compound drugs on the list of those that have demonstratable difficulties for compounding, must assure safe use of drugs with REMS, the compounded drugs are not sold or transferred by an entity other than the outsourcing facility, paid all required fees, includes the required information on labels and labeling of its products from section 503B(a)(10).
References:
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Section 503A of the Federal Food, Drug, and Cosmetic Act. U.S. Food and Drug Administration. https://www.fda.gov/drugs/human-drug-compounding/section-503a-federal-food-drug-and-cosmetic-act. Published June 21, 2018. Accessed June 10, 2022.
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Center for Drug Evaluation and Research. Information for outsourcing facilities. U.S. Food and Drug Administration. https://www.fda.gov/drugs/human-drug-compounding/information-outsourcing-facilities. Published March 29, 2022. Accessed June 10, 2022.
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Center for Drug Evaluation and Research. Provisions that apply to human drug compounding. U.S. Food and Drug Administration. https://www.fda.gov/drugs/human-drug-compounding/fdc-act-provisions-apply-human-drug-compounding. Published August 13, 2021. Accessed June 12, 2022.
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Text of compounding quality act. U.S. Food and Drug Administration. https://www.fda.gov/drugs/human-drug-compounding/text-compounding-quality-act. Published June 21, 2018. Accessed June 15, 2022.
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Center for Drug Evaluation and Research. Facts about the current Good Manufacturing Practices (cgmps). U.S. Food and Drug Administration. https://www.fda.gov/drugs/pharmaceutical-quality-resources/facts-about-current-good-manufacturing-practices-cgmps. Published June 1, 2021. Accessed June 12, 2022.
