Evaluate 503B Outsourced Compounding Vendors


June 2021 - Vol.18 No. 6 - Page #24

Pharmacy Purchasing & Products recently held a webinar entitled:
Evaluate 503B Outsourced Compounding Partners
The following questions were submitted by attendees.
The webinar slides and full presentation can be downloaded at pppmag.com/webinars.

Q: What is the key data to review when considering a new 503B vendor?

A: When choosing a new 503B vendor, you should feel confident that they will be the right fit for your organization. Start by learning how the vendor operates. The first step is ensuring the potential vendor’s licensure is in place. Then, familiarize yourself with their regulatory history (eg, any FDA inspections with a classification of Official Action Indicated [OAI]), review the number of SKUs they report in a six month period, and examine any recall information. It is also important to verify they are doing an annual drug review for the FDA, as this is a current good manufacturing practice (CGMP) requirement. Finally, checking references from customers with operations similar to your own can also help in your decision-making process.

Q: Do you recommend conducting an onsite inspection of a potential 503B vendor?

A: If there is an opportunity to do so, an onsite inspection can provide context and perspective as to how the 503B vendor operates. To use your visit effectively, you must know ahead of time what to look for. Although some of the activities are similar, remember that their operation may not resemble what you see every day in your pharmacy. Because of FDA regulations, expect to see sterile “bunny suits,” workers moving deliberately and slowly, and workers utilizing many different rooms. If your only option is a paper-based audit, you will still have the opportunity to speak with the vendor’s leadership and ask questions. Many pharmacists may not be familiar with GMP requirements, so I recommend beginning with a review of the FDA’s current draft Guidance Document for 503B Outsourcing Facilities, which is the FDA’s inspection classification database. Reviewing this can provide greater insight into the number, the type, and the seriousness of any 483 observations received by the vendor.

Q: Should different questions be asked when onboarding a new 503B vendor versus an annual review of an existing vendor?

A: In my opinion, there is no need to ask different questions for onboarding a 503B versus conducting an annual review. Once you have established that the 503B vendor can meet your sterile compounded medication needs, your evaluation of them should be focused on their quality systems and their compliance to the critical quality attributes required by the CGMPs, 21 CFR Part 211, as well as the 503B specific CGMPs, revision 2 (issued in January 2020).

Q: What data should be examined in the annual re-evaluation of your 503B vendor?

A: Your annual re-evaluation should include the following key steps:

  • Review required filings with the FDA (eg, annual registration, semi-annual product filings, and annual drug review)
  • Quantify all of the quality release tests and checks performed on compounded medications before being released for distribution
  • Detail the number of sterility failures (if any), investigations, and batch disposition
  • Review out-of-specification (OOS) investigations
  • Review deviation investigations (with particular attention to endotoxin deviations)
  • Examine environmental monitoring excursions, particularly action-level investigations
  • Examine batch rejections and subsequent investigations into the rejections

Q: How do you utilize response letters when reviewing a 503B vendor?

A: If a 503B vendor is inspected, they will likely receive a 483 observation. Understanding what the observation encompasses, how it was addressed, whether there were repeat observations, and the severity or the type of issues can assist in the evaluation process. Ask your vendor how they responded to the agency and how they addressed the concerns that were raised. Depending on the adequacy and acceptability of the vendor’s response to the 483, observations may result in additional actions from the FDA, which can include a follow-up inspection. This is one possible reason a 503B may have repeat observations.

Also, examine any additional activities between the 503B vendor and the FDA, such as a Warning Letter or regulatory meetings. Regulatory meetings indicate that the FDA may be dissatisfied with the 503B’s response to their 483 observation or that there may be issues with the 503B’s GMP compliance level.

Q: What are the benefits of having a quality agreement in place with an outsourcer?

A: A quality agreement defines and establishes each party’s roles and responsibilities with respect to ensuring that drug substances and drug products are manufactured in accordance with CGMP. With this approach, you will be alerted proactively if something has changed with your vendor; thus eliminating the element of surprise. Establishing this as an addition to your contract can help ensure that the 503B provider is operating in your best interest.

Q: Is it appropriate to request responses to inspectional observations from the 503B vendor?

A: A good 503B vendor should be fully transparent. It is reasonable to ask for these documents and for some explanation if needed. While you can visit the FDA’s website monthly to look for recalls, talk directly to your 503B vendor about obtaining quality assurance data for events such as sterility failures and environmental excursions in the ISO-5 environment.

Q: Does the FDA encourage sterile-to-sterile compounding?

A: The FDA distinctly encourages sterile-to-sterile compounding. According to the Drug Quality and Security Act, 503B vendors should be using approved products and compounding sterile-to-sterile; only in the event of a drug shortage or a clinical need should bulk API be used. There have been many 483 observations regarding firms using API for products that are already commercially available.


Eric S. Kastango, MBA, RPh, FASHP, is vice president and managing partner of the Kastango Consulting Group, a TRC Healthcare Company.

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