Case Studies

Agenus: Quality alignment after acquisition.

Growth through acquisition is an SOP for the biopharmaceutical industry. Once a deal is done, however, the hard work of operational integration and quality management is essential for realizing the expected benefits.

Agenus

In early 2016, a company based in Lexington, Massachusetts acquired an established GMP antibody manufacturing pilot plant in Berkley, California. It was a strategic acquisition that added important capacity to make antibodies for the Lexington company’s growing immuno-oncology clinical programs.

The acquired plant’s experienced chemistry, manufacturing, and controls (CMC) team remained with the merged company to operate the facility and adapt their processes to support new programs. “We recognized that there was a need to develop and align quality management systems (QMS) between the two manufacturing sites while maintaining industry standards and best practices,” said the senior director of quality assurance for the merged company.

The QA director had worked with ICQ President Michael Bogan in the past, so she reached out for help with the QMS project. ICQ launched our effort in 2018 with a three-person team to conduct a rapid, but comprehensive audit of their quality procedures and programs at the manufacturing sites in California and Massachusetts.

“Even though everyone has to play by the same rules, GMP facilities will generally have their own way of doing certain things,” Michael Bogan said. “So, it is essential to take a comprehensive approach, identify areas that diverge, and align systems within a unified quality management framework.”

The results of the ICQ audit became the basis for an implementation plan that aligned the quality and validation processes at both sites, raising the bar in some cases to meet current best practices. Institutional knowledge among both teams was respected and synthesized into a new company-wide quality management program.

“ICQ consultants performed an audit of our facilities, quality systems and operational readiness and outlined a simple yet thorough executable and effective strategy,” the QA director said. “They proceeded through the execution plan that exceeded expectations.”

Genzyme: It had to be perfect, the first time.

The entire biopharmaceutical industry was watching. As were the regulators, investors, and most importantly, the patients who depended on the life-saving drugs that would soon be in short supply. This was 2009 when Genzyme confirmed that the decreasing yields it was tracking of two drugs made at its Allston Landing Plant in Boston was the result of viral contamination.
Genzyme

What happened next was widely documented in the media. Genzyme suspended production in Allston of Cerezyme® for Gaucher disease and Fabrazyme® for Farby disease and began an unprecedented effort to sanitize the plant and rebuild not only its operating procedures but also public confidence, ultimately working under a consent decree.

Concurrently, Genzyme was planning to expand its biomanufacturing facility in Framingham, Massachusetts. And while there was no viral contamination in Framingham, the company made the strategic decision to apply its top-to-bottom restoration approach there as well. In that effort,

ICQ was engaged by Genzyme to develop a new commissioning and qualification program, reflecting the latest best-practices, informed by the contemporary regulatory frameworks promulgated by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

For nearly a year, a six-person team from ICQ, led by company president Michael Bogan, worked closely with Genzyme’s engineering and quality teams to build and deploy a new program. Nothing was taken for granted. The standard set by ICQ was simultaneously simple and intense— get it 100 % right, the first time, in all cases.

After months of collaborative development, ICQ deployed the Commissioning and Qualification program on Genzyme’s new Cell Culture Process Train and associated utility improvement project.  “As Senior Director of Engineering, I was responsible for implementing a new commissioning and qualification Program to comply with the consent decree remediation requirements and support our strategic capital program” said Jim Rice at Genzyme. “Ultimately, ICQ Consultants produced extraordinary results by maintaining 100% right first-time metrics, helping to end the consent decree and completing all assigned scope one month early.”

The new Framingham manufacturing facility was approved by the FDA and the EMA in January of 2012. The first batch of Fabrazyme made there shipped in March of 2012.

“Everyone understood what was at stake in this project,” Michael Bogan said. “The resolute commitment of the Genzyme team to succeed and get patients the medicine they need, was essential to ICQ’s ability to help.”

Mannkind: Getting a new facility back on track.

Growing from a discovery company to a biologics manufacturing company can be a treacherous path. Construction of GMP facilities is often chaotic, with multiple contractors and suppliers involved. Specialized project management focused on quality throughout construction is essential for the successful commissioning and validation of the facility.
MannKind

This was the situation that MannKind Corp. faced when building its own 240,000 square-foot biomanufacturing plant to make its innovative inhalable insulin product Afrezza. “During the new facility build-out we found ourselves behind schedule in completing the validation deliverables and  the project was in jeopardy of being severely over budget,” said Kimberly Byrd, Associate Director for Validation at MannKind during this time.

In immediate need of expert validation support, Ms. Byrd reached out to ICQ. At the time of ICQ’s involvement, construction of the plant in Danbury, Connecticut was well underway. The building shell was up, utilities were being installed, and equipment was arriving on site. ICQ’s team of validation engineers quickly assessed the issues causing delays, and cost over-runs and developed a plan to implement solutions.

“ICQ implemented a complete set of project controls that included tools for reporting metrics, determining accurate staffing plans and managing budget estimates, as well as, providing an overall execution plan that very quickly turned the project around and enabled my team to get things back on track,” Ms. Byrd said. “In the end, the biologics manufacturing facility was commissioned and qualified with no issues noted during the FDA inspection.”

Building a GMP facility means focusing on the details. Every major Biopharma project, whether a brand-new facility or a major renovation, will have some challenges. Leveraging our decades of combined experience over many GMP build-outs helps ICQ teams to plug-in to a construction project at any stage to solve problems or lead CQV management.

“Our goal is always to help clients solve the challenges in front of them,” said Michael Bogan, ICQ president. “We operate in an intensely regulated environment, and the fundamental first step for these companies is to have a manufacturing facility that meets all its marks, with rigorous quality management systems in place to maintain equipment and systems in a validated state and to ensure adherence to Quality requirements over time.”

Shire: Expertise and the staff to implement.

Success can create its own set of challenges. Through in-house R&D and strategic acquisitions, this client became a global force, commercializing a series of transformative biologics for rare diseases that simultaneously saved lives, fueled corporate growth, and strained some of the company’s manufacturing procedures.

Shire

At their Massachusetts facility, the validation and quality teams do outstanding work. So, they understood the magnitude of the challenges they faced after a regulatory audit illuminated several areas that needed attention. To assist, the company engaged ICQ to provide the expertise and resources needed to ensure compliance and improve procedures, all while working in real time, with live product in production.

A multi-year project ensued, led by ICQ Principal Michael Gatta, focused on a comprehensive assessment and redevelopment of the company’s Analytical Instrument Qualification (AIQ) and Commissioning, Qualification and Validation (CQV) programs. Multidisciplinary teams from ICQ worked on the rolling engagement, first assessing the operating status-quo then crafting new plans and writing the myriad of standard operating procedures (SOPs) needed.

“ICQ was instrumental in the development of our CQV and AIQ programs, from providing leadership and guidance of the high-level principles and procedures, to the actual generation of standard operating procedures,” said the company’s senior director of validation. “These programs and procedures provided compliance and efficiencies as well as a consistent approach and methodology. Additionally, ICQ generated comprehensive site Validation Master Plans which outlined our CQV strategy and documentation for each of our manufacturing facilities.”

As many as 25 people from ICQ were stationed at the company for months at a time to provide the extra hands-on-deck needed to finalize and implement the new programs. Over time, all the audit findings were satisfactorily addressed, and improved programs created, without interrupting any production schedules.

“It’s all about developing the right plans and procedures, classifying and assessing systems properly, then getting everyone working to those plans,” Michael Gatta said. “You want to be able to show that you are better today than you were yesterday, and you have a sustainable program in place that is tied to the relevant regulations.”

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