Information Concerning Outsourcing Facility Registration
1. How does registration as a human drug compounding outsourcing facility under section 503B work?
To register as an outsourcing facility, a compounder must send an email or use the electronic registration system to 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.
When FDA receives a submission for registration, FDA will review the submission to determine whether the required information has been provided, and if so, the outsourcing facility will be considered registered. If the information is not complete, FDA will contact the registrant and ask that they provide the necessary information. A firm will not be considered registered until the information is complete.
Beginning October 1, 2014, outsourcing facilities will be required to pay a fee at the time of registration. The amount of this fee and directions for paying the fee will be published in the Federal Register in early August 2014. Facilities for which the proper fee has not been received on or after October 1, 2014 will not be considered to be registered and will be removed from this list of registered outsourcing facilities.
2. What happens after a facility first registers with FDA as an outsourcing facility under section 503B?
Once an outsourcing facility is registered, the facility is subject to inspection by FDA and 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.
3. 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 not mean that the facility is making FDA-approved drugs and it does not mean it is in compliance with current good manufacturing practice requirements, the other conditions of section 503B, or other requirements in the Act. Approval of a drug requires the submission and approval of a new drug application or an abbreviated new drug application. Facilities registered as human drug compounding outsourcing facilities are required to comply with current good manufacturing practice requirements; report adverse events to FDA; label their products with certain information; and meet certain other requirements if they are to qualify for the exemptions from the new drug approval and adequate directions for use requirements of the Act. Outsourcing facilities that comply with the conditions for exemption under section 503B are not required to obtain new drug approvals. Listing of an outsourcing facility on this list does not mean that FDA has determined that the outsourcing facility is in compliance with these requirements or that it has met the conditions to qualify the exemptions under section 503B.
4. If FDA has inspected a human drug compounding outsourcing facility, can I be sure that the drugs I purchase from that facility are safe?
Drugs made by compounders, including those made at human drug compounding 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 an FDA-approved drug is commercially available, FDA recommends that practitioners prescribe the FDA-approved drug rather than a compounded drug unless the prescribing practitioner has determined that a compounded product is necessary for the particular patient and would provide a significant difference for the patient as compared to the FDA-approved commercially available drug product.
Although the drugs will not be FDA approved, purchasers of drugs compounded at a registered 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 small 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 small 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.
5. 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 and do not apply to all facilities under common ownership and control. Before purchasing drugs from a corporate entity, you should determine that the specific facility in which the drugs are compounded is a registered outsourcing facility with a satisfactory inspection.
6. What does an outsourcing facility do?
Under section 503B, outsourcing facilities that compound human drugs may register and meet certain other requirements to qualify for the exemptions from the new drug approval requirements and the requirements for adequate directions for use. Under section 503B, an outsourcing facility is a facility that:
- Is engaged in the compounding of 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
- May or may not obtain prescriptions for identified individual patients
When registering, an outsourcing facility must pay a fee. Registering as an outsourcer means that the compounding pharmacy will be inspected according to a risk-based schedule.
7. Is it safe for me to purchase drugs in shortage from a registered outsourcing facility?
Drugs compounded in registered outsourcing facilities that have had a satisfactory FDA inspection may have more assurance of safety than those made by other non-registered compounders because they are to be made in accordance with current good manufacturing practice standards. However, drugs made by compounders, including those made at human drug compounding 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 an FDA-approved drug is commercially available, or an alternative FDA-approved drug can be used, the FDA recommends that practitioners prescribe the FDA-approved drug rather than a compounded drug unless the prescribing practitioner has determined that a compounded product is necessary for the particular patient and would provide a significant difference for the patient as compared to the FDA-approved commercially available drug product.
For drugs compounded by registered outsourcing facilities that are on the FDA Drug Shortage List, the drug must be compounded after the drug is placed on the drug shortage list and may not be dispensed or administered to a patient after it has been removed from the drug shortage list. Therefore, compounders may place shorter beyond use or expiration dates on such products to ensure that they will be used within this period and compounders and purchasers will not be left with inventory of drugs that cannot be used because they are no longer in shortage.
8. If a facility that was on the list no longer appears on the list, why would it have been removed?
A facility is removed from the list if it is no longer registered. For example, a facility could be removed if it notifies FDA that it no longer wants to be considered registered as an outsourcing facility, or if its registration is not renewed during the annual re-registration period of October 1 – December 31.