FDA 483 Observations in 503B Outsourcing Facilities

In this issue, we will continue our review of FDA 483 observations in 503B facilities; specifically, we will look at the "Equipment" section.

EQUIPMENT

• Your firm did not conduct any dynamic smoke studies from dates xx through xx.
• Your firm's smoke studies are inadequate as they do not demonstrate that your hood and/or line is designed to prevent microbiological contamination, or to provide high assurance of product sterility.
• In the cleanroom, HEPA filter air was being blocked by the equipment (repeater pump) within the hood and the video failed to demonstrate laminar airflow around the equipment when open syringes are connected to the filling tubing.
• Cracks and chips were observed on the acrylic view screens of the ISO-5 laminar flow hoods. The crack appeared to be 5 inches in length. A thick and uneven bead of silicone caulk was used to repair the crack on an unknown date - there were no maintenance records for the repair. The crack and uneven caulk surface is not smooth or hard and therefore may be difficult to disinfect and sanitize.
• The smoke study is deficient as it does not continuously show that the air is moving unidirectionally as the smoke is either too faint and/or the smoke source is depleted and there is no smoke present. Also, the smoke study was not conducted while simulating the current manufacturing and operating process.
• You do not evaluate the air velocity at the work surface of your ISO-5 LAF hoods.
• You do not have a system in place to track the repairs made to your HEPA filters.
• The bottom of carts appeared to be rusty.
• Your SOPs do not include information on all the equipment located in the sterile compounding area to assure appropriate monitoring is performed.
• On a walkthrough of your firm's aseptic processing areas, I observed a brown/black residue on the inside of the LFH bottom left panel between the panel and the metal bench table lip edge.
• On a walkthrough of your firm's aseptic processing areas, I observed cracked side panels from the overtightening of two connecting screws in a LAF. In the cracking area around the screws, a brown residue was observed.

More next week.

Compounded drugs can serve an important role for patients whose medical needs cannot be met by an FDA-approved drug. The FDA is continuing our efforts to help preserve access to compounded drugs for patients who have a medical need for them.

We understand that compounded drugs can serve an important role for patients in hospitals and other healthcare settings whose medical needs cannot be met by an FDA-approved product, and that hospital care raises unique considerations and needs. Recognizing this, in 2016 the agency proposed a policy in draft guidance, that described certain flexibilities for hospital and health system pharmacies that distribute compounded drugs within their health system before receiving patient-specific prescriptions.

Since that time, the agency has received many comments on this proposed policy, including regarding a provision about FDA's intent not to take action if a hospital or health system pharmacy distributes compounded drugs to healthcare facilities within a one-mile radius, that are owned and controlled by the same entity that owns and controls the pharmacy. Stakeholders commented that the proposed one-mile policy was not reflective of the structure of health systems, many of which operate under a centralized compounding model and may service facilities at other sites located outside a one-mile radius without similar compounding capabilities.

After considering these comments, to help preserve access to compounded drugs, today, the FDA is revising our draft guidance to, among other things, remove the one-mile radius provision. We are proposing a two-part compliance policy. The policy describes circumstances under which the agency generally does not intend to take action against a hospital or health system pharmacy, that is not an outsourcing facility, that compounds and distributes a drug without first receiving a valid prescription or order for an individual patient. These circumstances include that compounded drugs be administered only to patients within the hospital or health system and the drugs are used or discarded within 24 hours of leaving the pharmacy.

With respect to hospital and health system pharmacies that deviate from these circumstances, the revised draft guidance outlines the FDA's intention to take a risk-based approach to enforcement. Hospital and health system pharmacies can measure their operations against certain factors to assess whether their practices are likely to be an enforcement priority. At this time and based on the agency's current understanding of the risks, the FDA generally intends to consider the following factors for prioritizing risk-based regulatory action:

• poor compounding practices or a lack of sterility assurance
  
  
• non-patient-specific compounded drugs that are not for emergency uses
  
  
• routine, large amounts of non-patient-specific compounded drugs
  
  
• interstate distribution of large amounts of non-patient-specific compounded drugs
  
  
• lack of a procedure to obtain non-patient-specific compounded drugs from an outsourcing facility.