Questions and Answers: Outsourcing Facility Registration
How does registration as a human drug compounding outsourcing facility under section 503B work?
To register as an outsourcing facility, a compounder must use the electronic registration system unless granted a waiver. It must provide the following information: name; place of business; unique facility identifier; point of contact email address; an indication of whether the facility intends to compound products on FDA’s drug shortage list; an indication of whether the facility compounds from bulk drug substances, and if so, whether it compounds sterile drugs from bulk drug substances.
Once FDA receives the electronic registration submission, it sends the registrant an invoice for the annual establishment (registration fee) that must be paid at the time of registration. The amount of this fee for each fiscal year is published in the Federal Register
Provided the registrant pays the required fee within 15 calendar days after FDA issues the invoice, FDA sends the entity a confirmation that it is registered as an outsourcing facility. FDA generally updates the list of registered outsourcing facilities on its website to reflect new registrants weekly.
An outsourcing facility must re-register and pay the annual establishment fee for each year that it wishes to remain registered as an outsourcing facility. The annual registration period is from October 1-December 31. An entity that registers during this timeframe will remain registered through December 31 of the following year. Registration is encouraged and can be done at any time during the year.
See FDA’s final guidance, Registration of Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act for more information.
What happens after a facility first registers with FDA as an outsourcing facility under section 503B?
Once an outsourcing facility is registered, the facility will be added to the list of facilities FDA intends to inspect. Outsourcing facilities are to be inspected according to a risk-based schedule. Depending on the number of outsourcing facility registrants and other inspection priorities, FDA expects to inspect newly registered outsourcing facilities within two months of initial registration, if the facility has not been previously inspected.
Subsequent inspections will depend on the findings from the first inspection and other factors including but not limited to: the compliance history of the outsourcing facility; the record, history, and nature of recalls linked to the outsourcing facility; the inherent risk of the drugs compounded at the outsourcing facility; the inspection frequency and history of the outsourcing facility, including whether the outsourcing facility has been inspected within the last 4 years; and whether the outsourcing facility has registered as an entity that intends to compound drugs in shortage.
What does it mean to be registered as a human drug compounding outsourcing facility under section 503B?
Registration means only that FDA has received the information required to register the facility. It does notmean that the facility is making FDA-approved drugs and it does not mean it is in compliance with current good manufacturing practice (CGMP) requirements, the other conditions of section 503B, or other requirements in the Act. Facilities registered as outsourcing facilities:
- are subject to CGMP requirements;
- must report adverse events to FDA; and
- meet certain other requirements.
Outsourcing facilities that comply with the conditions under section 503B are not required to obtain FDA approval of their compounded drug products. Registration of an outsourcing facility does not mean that FDA has determined that the outsourcing facility is in compliance with CGMP requirements or that it has met the conditions for its drug products to qualify for the exemptions under section 503B.
If FDA has inspected an outsourcing facility, can I be sure that the drugs I purchase from that facility are safe?
Drugs made by compounders, including those made at outsourcing facilities, are not FDA-approved. This means that they have not undergone the same premarket review as approved drugs. They lack an FDA review of safety and efficacy and of manufacturing quality. Therefore, when a patient can use an available FDA-approved drug, FDA recommends that practitioners prescribe an FDA-approved drug rather than a compounded drug.
Although the drugs will not be FDA-approved, purchasers of drugs compounded at an outsourcing facility that has had a recent satisfactory FDA inspection will have some assurance that the conditions at that facility met applicable current good manufacturing practice standards at the time of the inspection, and the compounded drugs are labeled with the required information. It should be noted, however, that FDA inspections are just a snapshot in time. Conditions at the facility can change at any time. And FDA only reviews a sample of the records available at a facility during an inspection and must draw conclusions about the conditions and practices at the facility from that sample of records. Purchasers should look at other available information about the facility that can provide them with additional insight with regard to the facility’s operations.
If I purchase drugs from a company that has multiple facilities, how can I be sure about the quality of the specific compounded drugs I purchase?
Registration and inspections are facility specific. Facilities under common ownership and control are inspected individually. Before purchasing drugs from a corporate entity, you should determine that the specific facility in which the drugs are compounded is an outsourcing facility with a satisfactory inspection.
What does an outsourcing facility do?
Under section 503B, outsourcing facilities that compound human drugs must be registered and meet certain other conditions and requirements for their drugs to qualify for the exemptions from the new drug approval requirements, the requirements for labeling with adequate directions for use, and drug supply chain security requirements. Under section 503B, an outsourcing facility is a facility that:
- is engaged in the compounding of sterile drugs (and may also compound non-sterile drugs);
- has elected to register as an outsourcing facility;
- complies with all of the requirements of section 503B;
- is not required to be a licensed pharmacy, but compounding must be by or under the direct supervision of a licensed pharmacist; and
- may or may not obtain prescriptions for identified individual patients.
If a facility was on the list of outsourcing facilities but no longer appears on the list, why was it removed?
A facility is removed from the list if it is no longer registered and therefore no longer an outsourcing facility. For example, a facility could be removed if it withdraws its registration, or if its registration is not renewed during the annual re-registration period of October 1 – December 31. If such a facility is continuing to produce drug products it must be registered under section 510 of the FD&C Act and comply with all of the requirements of the FD&C Act including obtaining drug approval under section 505 of the FD&C Act.