Pharmaceutical Technology Editors

The recently formed scientific advisory board (SAB) of contract research organization, Europital, anticipates that a deficit in the clinical knowledge of smaller biotechs may lead to slow biotech development in 2021.

According to a Feb. 8, 2021 press release, the SAB, which comprises a group of clinical key-opinion leaders and specialized industry experts, forewarns of a slowing of trials in 2021 due to the clinical knowledge deficit. Additionally, the board believes that investment communities will start to take a holistic look at biotechs and partners to ensure there is deep therapeutic expertise available.

“The drug discovery pipeline is increasingly made up of smaller and more nimble innovators with limited clinical experience in-house. Yet, with many of the low hanging fruit already having been developed, molecules and biologies are becoming ever more complex,” said Dr. Mohamed El Malt, chief medical officer of Europital, in the press release. “The challenge for small and medium pharma and biotechs is how to access appropriate high-quality clinical knowledge—and this clinical deficit over the next few years is set to be a critical factor in any candidates advancement.

“It’s no secret that unlike the larger pharma companies that can pull in the best resources from the largest CROs, smaller companies must increasingly compete to ensure they can access the best clinical knowledge, as this can be the difference between delays due poor trial management and planning, and even, a project’s potential success or failure,” added El Malt.

Articles

The recently formed scientific advisory board of Europital anticipates that a deficit in the clinical knowledge of smaller biotechs may lead to slow development in 2021.

Europital’s Scientific Advisory Board Predicts Clinical Deficit May Slow Biotech Advancement

Bristol Myers Squibb (BMS) announced on Feb. 5, 2021 that FDA has approved Breyanzi (lisocabtagene maraleucel; liso-cel), BMS’ chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory large B-cell lymphoma.

According to a BMS company press release, the cell therapy will be manufactured for each individual patient at BMS’ immunotherapy manufacturing facility in Bothell, WA, and will be launched across a network of treatment centers.

“Breyanzi, a CAR T cell therapy, will have an important role in clinical practice, offering people living with relapsed or refractory large B-cell lymphoma the chance for sustained response with an individualized treatment experience,” said Samit Hirawat, MD, chief medical officer, Bristol Myers Squibb, in the press release. “Today’s FDA approval reflects our deep commitment to advancing cell therapy research, developing innovative treatments, and supporting patients at every step of their treatment journey.”

The cell therapy will be manufactured for each individual patient at BMS’ immunotherapy manufacturing facility in Bothell, WA, and will be launched across a network of treatment centers. 

FDA Approves Bristol Myers Squibb’s CAR T Cell Therapy Lymphoma Treatment

How have biopharma companies responded and adjusted to pandemic issues? What lessons learned under fire may lead to more effective and efficient bioprocessing practices going forward? Eric Langer, managing partner, BioPlan Associates, Inc., shared research and expert insight in Delivering on the Promise: Overcoming Biopharma Development and Manufacturing Challenges.

 editors was recorded during the 2020 Bio/Pharma Virtual Congress on Nov. 11, 2020.

Videos

Lessons learned from the pandemic can advance future biologic drug development and manufacturing.

Pandemic Response Lessons

 sent to Allay Pharmaceuticals by FDA on Jan. 27, 2021 details violations of current good manufacturing practices (CGMPs) found at the company’s Hialeah, FL site during an agency inspection conducted from May 5–15, 2020. Investigators found a variety of quality control failures and a lack of written production and process control procedures.

Specifically, FDA stated in the letter that the company had not adequately validated manufacturing processes. “You lacked adequate data to show homogeneity of your drug product during manufacturing. During your process performance qualification (PPQ), blend samples were 

, it potentially masks the variability of your blend. In addition, you obtained an out-of-specification (OOS) assay result for one of the active ingredients, 

.” FDA also found samples collected from the company’s process validation lots to have sub-potent API.

“Your manufacturing failures indicate that you do not have an adequate ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality,” the letter stated. FDA requested the company provide the agency with a “data-driven and scientifically sound analysis” of sources of variability; a summary of the company’s validation program; a process performance qualification timeline for its products; and process performance protocols and written procedures for equipment and facility qualification.

The agency also stated that the company failed to thoroughly investigate out-of-specification (OOS) assay results found after FDA testing of one lot of tablets. “Your investigation into the OOS sample result was inadequate and did not identify CAPA. Furthermore, an investigation was not performed to ensure that previously released lots met your revised assay specifications. FDA investigators found 13 lots within expiry that exceeded your new assay specification during release or stability testing. These lots should have been identified in your investigation,” the agency stated in the letter. FDA requested the company provide a review and risk assessment of products to determine if specifications are appropriate; updated procedures for routine review of product specifications; an independent assessment of its system for investigating OOS results and deviations; and an action plan with timelines and summary results from retain sample testing of product.

In the letter, the agency also stated that the company had failed to establish and follow a written testing program for assessing stability characteristics. The company’s quality control unit also failed to ensure that products were manufactured in compliance with CGMPs, according to FDA. Specifically, according to the agency, the company did not adequately evaluate variability in supplier API assay results compared with the company’s testing. “The variability observed may compromise the assay and content uniformity of your finished product. For example, your firm’s test results for API lot 

, had a difference of 7.8% from the API manufacturer’s certificate of analysis (COA). Your firm used your assay result to formulate the finished product. Additionally, the FDA sampled lot 

 and the sample results failed to meet the USP assay specification for active ingredient, 

FDA sent a warning letter to Allay Pharmaceuticals for inadequate written procedures; inadequate out-of-specification testing; inadequate stability testing; and inadequate quality control oversight.

Florida Manufacturer Warned for Inadequate Written Procedures 

The recent discovery of probable carcinogens in widely used APIs triggered a wave of drug recalls, increased regulatory oversight, and new testing procedures. Advanced analysis of excipients may reveal previously unknown ingredients; however, such a discovery prompts the need for better understanding of excipient components, the source and safety profiles of the materials, and the role they play in drug performance.

In this Editors’ Series session, moderated by the editors of 

 an expert panel discusses the characterization of excipient components, understanding regulatory and compendial implications of excipient composition, the global supply chain, effective quality programs and prospects for preapproval of novel excipients.

The panel, featuring Nigel Langley, global technology director, Pharma Solutions, BASF Corporation; David R. Schoneker, president/owner/consultant, Black Diamond Regulatory Consulting, LLC; and Joseph Zeleznik, technical product manager, IMCD US, was recorded during the 2020 Bio/Pharma Virtual Congress on Nov. 11, 2020.

The importance of characterizing excipients, supply chain security, and the role of novel excipients are explored.

Excipient Quality and Impact on Formulation

The bio/pharma industry has demonstrated its R&D capabilities by accelerating development of vaccines and therapeutics to combat COVID-19. At the same time the industry faced intense scrutiny and political pressure. What are the short-, medium-, and long-term implications for bio/pharma development and manufacturing?

Panelists James Mayne, PhD, vice-president, Science & Regulatory Advocacy, PhRMA and Phyllis Arthur, vice-president for infectious diseases and diagnostics policy, Biotechnology Innovation Organization (BIO) shared insights during this Editors’ Series discussion moderated by editors of 

. The discussion was recorded on Nov. 11, 2020, during the 2020 Bio/Pharma Virtual Congress.

Representatives of industry organizations discuss crucial business, regulatory, science-based issues facing the industry.