During the recent pandemic, conducting in-person biologics manufacturing facility inspections has been a challenge and has forced FDA to look for innovative ways to maintain the quality of its oversight of drug manufacturing.

In addition to remote assessments and other non-traditional methods to ascertain the quality and compliance of manufacturing facilities, the agency further explored a process that had been in place but not leveraged—the integration of application reviews and facility inspections.

[Related: What is your likelihood of receiving a 483 observation following a pre-approval inspection? Click here to access a recording, including slides, of our August 2022 webinar featuring Redica Systems CEO Michael de la Torre.]

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At the GMP by the Sea annual conference in Cambridge, Md., in August, FDA Office of Pharmaceutical Manufacturing Assessments (OPMA) deputy director Derek Smith explained that a team-based approach with Office of Pharmaceutical Quality (OPQ) and OPMA reviewers joined by ORA investigators would provide “comprehensive oversight of the facility, process, and product at the time of licensure and throughout the product lifecycle.”

In addition to being OPMA deputy director, Smith is a co-chair of New Inspection Protocol Project (NIPP), oversees OPQ’s biologics inspection program, and is the CDER lead for manufacturing inspections during the COVID-19 pandemic.

Our coverage of Smith’s presentation at the August conference is in three parts:

  • Part I below includes background and the rationale behind the inclusion of reviewers and investigators from different offices in FDA and how a partnership between OPQ and ORA improves the efficiency of the process and leverages each team member’s expertise.
  • Part II  will examine the current state and future anticipated states of inspections of biologics regulated by CDER.
  • Part III will focus on the model used to evaluate whether biologics manufacturing site assessments should be conducted remotely or in person.

OPQ and ORA Join Forces to Improve Inspection Coverage

To help decrease the backlog of surveillance inspections for human biologic products brought about by the recent pandemic, investigators from FDA’s Office of Regulatory Affairs (ORA) will join inspection teams reviewing BLAs at manufacturing facilities. This team effort will allow more thorough coverage and leverage the usefulness of each event by including surveillance coverage in conjunction with prelicensing inspections.

Smith explained that OPMA was formerly known as the Office of Process Facilities, charged with ensuring the quality of pharmaceutical commercial manufacturing processes and facilities over the product lifecycle.

[Related: Did you know there have been 113 FDA GMP inspections of biologics sites this year? Learn more about how Redica Systems can help you stay on top of inspection trends involving biologics manufacturing sites.]

Biologics Inspections

With the creation of OPQ, specific disciplines within the application process—the drug substance, drug product, biopharmaceutics, and microbiology—were brought together to maximize each team member’s expertise.

This concept is applied across all three application programs that CDER regulates—NDAs, ANDAs, and BLA—as well as the post-marketing for those programs.

In OPMA, he said, “we focus on the manufacturing elements of the team-based review. We conduct an application assessment in coordination with a pre- and post‐approval inspection to ensure that manufacturing is adequate to deliver quality products for the patient.”

“We also conduct a scientific review and quality evaluation of the manufacturing process, microbiology, and facilities for INDs, NDAs, ANDAs, BLAs, and supplements. This includes an assessment focused on the manufacturing process, sterility assurance, and facilities.”

ConOps Bears Fruit

The evolution of the team inspection process began with the Concept of Operations (ConOps) that CDER and ORA announced in 2017, describing how they would collaborate to drive integration of the manufacturing facility evaluation and inspection for human drugs.

In OPMA, it was not a new paradigm. As a part of the BLA assessment program, for years prior to ConOps, Smith said, review and inspection components were integrated such that the reviewers were leading pre-license inspections for BLA products.

“We took the lessons learned and applied them to ANDAs and NDAs to have a holistic confidence in assessment,” he reported.

Review team members participate in inspections “to support enhanced regulatory understanding and oversight. This results in comprehensive inspection coverage through expert knowledge of process and product-specific risks based partly on the application assessment and provides for real-time communication with the manufacturing facility.”

In the BLA program, he explained, “a lot of times the investigators will go out on the review team and be able to talk through things at the facility and better understand what the goal of the company’s strategy is and how things are made to ensure total quality. And we find that really has helped us understand a lot about how new operations work.”

For prelicense inspections, a team-based approach is used, with product quality reviewers from OPQ and microbiology quality reviewers from OPMA. “We are typically leading these inspections on the pre-license side,” Smith explained.

Part II will include an analysis on the current state of biologics inspections and implications for future inspections.

Using Redica Systems for Due Diligence

An important part of deciding which suppliers, Contract Manufacturing Organizations (CMOs), and other GMP partners to do business with is learning about and evaluating any compliance issues they may have had in the past.

Designed to unearth an actionable level of detail from our vast collection of inspection documents, Redica Systems expert models reveal compliance issues found in both FDA warning letters and a 20-year collection of 483s issued to FDA-regulated companies.

Contact Redica Systems to find out how we can help you with this facet of your due diligence activities.

Additional Resources

FDA Expanding its Sterile Drug NIPP Inspection Pilot to Include Other Dosage Forms

FDA OMQ Regulatory Actions Increase Dramatically in FY2020

89 Products Filed as NDAs Now BLAs Under Regulation Change

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