Outsourcing facilities, which were developed following passage of the Drug Quality and Security Act of 2013, present an important opportunity for ASCs to boost the quality and efficiency of their care.
However, it is important to select a 503B outsourcing partner with the right experience and expertise to reliably support ASC needs. Below, Fagron Sterile Services President Carl Woetzel, Global Quality Director Jason McGuire, and Vice President of Operations Jason Winfield outline key considerations for ASCs as they select outsourcing facility partners.
Question: What is a 503B outsourcing facility?
Carl Woetzel: Outsourcing facilities are a relatively new creation that provide a necessary element in the patient care continuum. These facilities fit in perfectly between traditional pharmaceutical manufacturers and traditional pharmacies to serve provider and patient needs by preparing and distributing drug products that are not otherwise commercially available.
Outsourcing facilities strictly adhere to FDA regulatory standards, called current Good Manufacturing Practices (cGMP), in a manner that is very similar to a pharmaceutical manufacturer. Outsourcing facilities fulfill a market need because they provide the safety and reliability of a drug manufacturer but can take a much more nimble approach to creating customized options for their customers.
Jason McGuire: Upon the development of the Drug Quality and Security Act in 2013, the FDA created the new section 503B which defines an outsourcing facility’s role and responsibility for producing pharmaceutical products.
Under the new law, a 503B outsourcing facility was given the exclusive opportunity to manufacture drug products that are not commercially available from traditional pharmaceutical manufacturers. The focus of the law is on how the facility maintained and followed applicable cGMP and best practices, especially as it relates to aseptic processing and the necessary critical control parameters.
Jason Winfield: This new 503B designation increased the level of quality and compliance associated with the manufacturing facilities, processes and practices. By creating outsourcing facilities, Congress gave hospitals and other facilities the opportunity to safely outsource manufacturing services associated with the sterile production of injectable and parenteral medicines.
Q: How can a reliable 503B outsourcing partner bring stability to ASC supply chains?
CW: A reliable 503B outsourcing partner such as Fagron Sterile Services stabilizes ASC supply chains by ensuring that the medications needed are always in stock and ready to ship. This is best done through a supply agreement where drug manufacturing production is based on projected and historical demand levels with a margin for seasonal adjustments. Additionally, new products can be identified and added to the 503B’s portfolio based on the needs of the ASC.
JW: Fagron’s products are delivered in sterile, ready-to-use presentations with labels meeting ISMP standards, eliminating the need for pharmacist, nurse, or other practitioner manipulation. Some examples include: separating multi-dose vials into single syringes, aspirating from glass vials or ampules into a syringe, and reconstituting lyophilized powders with sterile diluents. All Fagron products undergo extensive sterility and stability protocols and testing to ensure the sterility, quality, and potency from receipt of the product and through the products shelf life.
Q: Should an ASC choose sterile-to-sterile or API-to-sterile compounding?
CW: This often comes down to customer preference. However, I believe there are several advantages to API-to-sterile compounding.
For instance, drug shortages often affect the availability of a medication needed in an ASC. If an ASC chooses to partner with a 503B that prepares drug products from API, the likelihood of experiencing supply interruptions in the face of a drug shortage can be reduced. We have seen this recently with the unavailability of sedatives and muscle relaxants for COVID-19 patients requiring mechanical ventilation. Drug manufacturers and sterile-to-sterile outsourcing facilities have not been able to supply market needs, whereas API-tosterile outsourcing facilities have been successful in providing those needed drug products.
Another advantage is that the API-to-sterile manufacturing process is more efficient and requires fewer steps. 503Bs that only perform sterile-to-sterile compounding are required to purchase finished pharmaceutical goods which have been manufactured by a pharmaceutical company, shipped to a wholesaler, ordered by the 503B, and then repackaged and sold to the customer.
The sterile-to-sterile compounding process requires more manipulations and is less efficient than API-to-sterile compounding. While both sterile-to-sterile and API-to-sterile compounding processes result in the production of safe products, we believe that the safety, efficiency, and invulnerability to drug shortages inherent in API-tosterile compounding renders it a worthwhile choice for ASCs.
JW: Hospitals and ASCs should prefer and expect their 503B partners to offer, or at least have available, an API-to-sterile presentation component in their portfolios. Sterile-to-sterile compounding requires sourcing of vials or ampules of manufactured finished drug products, which generally will drive costs higher and result in lack of availability during drug shortages.
API-to-sterile compounding is safe and effective. Any suggestion to the contrary is simply untrue.
• API is sourced from FDA registered vendors, who are audited by Fagron on a regular basis. Additionally, all APIs are qualified and tested in accordance to their USP monograph prior to release for use in the commercial manufacturing process.
• Manufacturing processes are engineered, validated, and proceduralized for robustness and consistency. Every detail of the process is defined in Standard Operating Procedures (SOPs), as well as Master Batch Records (MBRs) which are unique for each process. SOPs and MBRs are followed and any deviation from these processes results in a deviation investigation to determine root cause and impact prior to batch disposition.
• The manufacturing environment is continuously monitored and people are routinely monitored on a batch-specific basis.
• All batches are sterile filtered, and filter integrity tests confirm successful terminal filtration.
• Each batch undergoes rigorous quality inspection, critical system confirmation, sterility, potency and other required compendial testing which is product-specific.
• Quality and aseptic processes are routinely monitored to confirm adherence to all site procedures.
Q: How can 503B outsourcing reduce an ASC’s regulatory burden?
CW: Much like all healthcare facilities, ASCs are subject to ever increasing regulatory requirements. These requirements include measures aimed at ensuring the safety and effectiveness of medication use. Medication use includes ordering, compounding, labeling, administering and documenting.
A 503B can help to alleviate some of the regulatory burden by providing customized, convenient, safe and effective medication in ready-to-use containers. Medications that come from a 503B to an ASC are labeled pursuant to ISMP standards with labels that are easy to read and color coded to ensure medication safety, particularly in high-acuity situations.
Medications obtained from a 503B also eliminate the need for providers to compound medications on-site, sometimes in less-than ideal conditions for aseptic manipulations. Instead, providers can simply administer the ready-to-use medication directly.
JM: The ASC auditing bodies are verifying their vendors maintain the necessary compliance standards. So long as we keep our house in order, then it makes it easier for ASCs to respond to questions in the event of audit at their site.
JW: If properly managed, a significant portion of regulatory burden can be leveraged onto the 503B. Our sites are inspected annually, and sometimes semi-annually, by FDA, DEA, and various state boards of pharmacy. In addition, we host not less than 15 to 20 customer audits and inspections throughout the year and are subject to internal quality audits by both department and job function.
Q: 503B suppliers must comply with all FDA and DEA quality regulations to operate, but what should ASCs expect from a top tier 503B partner?
CW: A top-tier 503B partner will have an impeccable safety record. They will have a quality program that ensures that all medications are extensively tested before being shipped to their customers. They will have excellent customer service and a portfolio of products that fit the needs of an ASC. A top-tier 503B will also ensure that all medications needed by the ASC are always stocked and ready to ship. They are able to fulfill orders within a day and offer rapid shipping options.
JW: Fagron maintains a greater than 97 percent fulfillment rate, meaning that more than 97 percent of the time an order is placed that order is filled the same day. Organizations that experience recurrent unexpected delays in shipping, batch rejections that impact fulfillment rates, or frequent finished goods inventory shortages is a signal of lack of operational discipline and poor quality in operations.
Q: What are the advantages of a 503B in-house quality testing lab versus outsourced testing through a third party vendor?
CW: There are advantages to a 503B having its own in-house quality control lab. The most significant benefit that an in-house lab provides is additional control over quality. This includes the ability to develop robust procedures and conduct thorough investigations when necessary.
Additional benefits include cost and turnaround time. When a 503B tests their own products, they avoid the additional costs of outsourced lab testing and can pass that savings on to the customer. They are also able to release commercial batches faster, resulting in quicker customer access to needed medications. Typically, testing samples can be delivered and put on test the same day they are received in house, as opposed to a contract lab which requires shipping and may experience other delays.
JM: The most critical advantages revolve around regulatory, speed to market, and on-time delivery to ASCs and other customers. The FDA and other auditing bodies appreciate having quality control data and access to the lab when they are on-site.
When using an outsourced laboratory, there can be communication challenges and delays in obtaining requested information. Additionally, outsourced labs can run into issues with their own inspections, which may create problems for 503B facilities and their customers. Regarding speed to market, we have the ability to prioritize which test methods need to be developed sooner without being beholden to the often-long queues at the outsourced lab. In some cases, we can save months in bringing a product online for our customers.
Q: What are the three most important criteria for an ASC to consider when choosing a 503B outsourcing partner?
CW: Quality and reputation in the industry; this is the most important aspect, because the quality of care at the ASC is affected by the quality and safety of its medications. Reliability of supply; this is important as well. You need to be able to count on your 503B partner to produce the medications you need when you need them. Customer Service; when you place an order or make a phone call, how are you treated? Is the process easy and straightforward?
JW: I would also add honesty and transparency, specifically, with business ethics and quality operations. Do what you say, and say what you do – interestingly, this is also a fundamental of cGMP. Additionally, cGMP experience and subject matter expertise with 21 CFR Parts 210 and 211 are crucial.
Fagron has purposefully hired expertise in cGMPs and sterile pharmaceutical manufacturing, quality operations and technical services to uniquely position us to support hospitals, health systems and their leadership in delivering cost-effective, high-quality and reliable ready-to-use sterile injectables.
Q: What are the advantages of 503B outsourcing versus compounding in-house?
JM: There are several advantages to outsourcing from 503Bs. The first is a reduced risk profile. Compounding is as much science as it is art. You need to understand product development, process qualification, and most importantly how to train individuals to be qualified to operate in an extremely controlled environment.
Second is consistency. When using an outsourcing facility, most likely they are producing thousands of the same units daily or weekly. Therefore, they know intimately how to maintain the necessary critical process parameters to ensure each batch is produced the same way with the highest quality control.
CW: I believe that partnering with outsourcing facilities improves the safety and reliability of medication use and optimizes the use of health system, hospital and ASC resources.
Patient safety is enhanced using ready-to-use products with enhanced labeling, extended dating that is backed up by real data, tailored and individualized dosing, and extensive product testing before release.
The utilization of resources is optimized by eliminating medication preparation and compounding steps for hospital and ASC staff.
This article was sponsored by Fagron Sterile Services US.