Pharmaceutical Technology Editors

FDA announced on June 15, 2022 that it has published the International Council for Harmonisation’s (ICH) 

draft guidance document. The draft version details the general quality risk management (QRM) process including risk assessment, risk control, risk communication, and risk review. It also discusses methodology for risk management and risk-based decision making.

The integration of QRM into the industry and regulatory operations is also discussed. The document includes two annexes. Annex I provides information on QRM methods and tools such as failure mode effects analysis, fault tree analysis, hazard analysis and critical control points, and more. Annex II breaks down QRM as parts of integrated quality management.

“In the pharmaceutical sector, the principles and framework of ICH Q9, coupled with the official ICH training material that supports this guideline, are instrumental in enhancing the application of effective quality risk management by industry and regulators. The importance of quality systems has been recognized in the pharmaceutical industry, and it is evident that quality risk management is a valuable component of an effective quality system,” the agency stated on its website.

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The draft ICH Q9(R1) document details the importance of quality risk management principles.

FDA Publishes Draft Quality Risk Management Guidance

FDA published draft guidance on June 15, 2022 that describes the Center for Biologics Evaluation and Research’s (CBER) standards recognition program for regenerative medicine therapies (SRP-RMT) to identify Voluntary Consensus Standards (VCS) for the development of regenerative medicine therapy (RMT) products. CBER states that the use of VCS can assist stakeholders in meeting regulatory requirements. “By leveraging stakeholders’ efforts to develop standards, FDA can eliminate costs to the Federal government associated with the development of government-unique standards and promote international harmonization of standards that are acceptable to FDA,” FDA states in the guidance. 

The document describes the procedures for evaluating VCS and documenting the use of a standard recognized by CBER. It also answers industry questions about VCS and SRP-RMT.

The new draft guidance describes a standards recognition program for regenerative medicine therapies.

FDA Publishes Guidance on Regenerative Medicine Therapies

Yourway, an integrated courier and clinical packaging company, announced the construction of a new flagship European depot in Dublin, Ireland on June 8, 2022. The new good manufacturing practice facility will support Yourway’s clinical trials offering, including courier services, primary and secondary packaging, and temperature-controlled storage.

According to a company press release, Yourway chose the Dublin Airport Logistics Park site because it’s convenient for major pharma and biopharma companies in Ireland. The facility will also offer easy access to a significant domestic clinical trials market. It is scheduled to be audit ready by Q4 2022.

“With Ireland’s strength in biopharma, Yourway has operated there for over 15 years, which contributed to our decision to build our flagship depot in Dublin,” said Gulam Jaffer, founder and president, Yourway, in the press release. “We’re anticipating notable market growth in Europe, and Yourway will be perfectly placed to support it.”

The site will be supported by the company’s other European depots in London, UK; Kyiv, Ukraine; Minsk, Belarus; and Moscow, Russia. The company’s global depot network exists across these locations as well as sites in 15 other countries across the world.

Yourway intends to construct a new manufacturing facility in the Dublin Airport Logistics Park.

Yourway Announces New European Depot in Dublin

Spectrum Chemical, a provider of fine chemicals, laboratory equipment, and supplies, announced a new distribution arrangement on June 9, 2022 with ANGUS Chemical Company, a specialty ingredients manufacturer. The deal will see Spectrum market and distribute ANGUS’ tris(hydroxymethyl)aminomethane (TRIS) buffers in the United States and Canada.

According to a company press release, Spectrum will work with the TRIS AMINO Advanced Crystal and BIS-TRIS biologics grade buffers. These products are used as buffering agents in cell culture and bioprocessing applications and in the purification of biological molecules in downstream processing.

“The addition of these essential ANGUS-branded TRIS and TRIS derivative products to our product offering broadens our capability to deliver best-in-class solutions to our biopharmaceutical and life sciences research customers,” said Jim Luchsinger, vice-president, business development, Spectrum Chemical, in the press release. “We are committed to delivering the fullest range of high-quality chemicals necessary for every bioprocessing stage, from development through commercialization.”

“Through Spectrum Chemical’s deep experience in serving the U.S. and Canadian research markets, we look forward to enhancing our supply and delivery capabilities for customers in the region supported by ANGUS’ commitment to providing 100% traceability and the most secure, sustainable supply of these essential chemistries,” said Doug Ward, North American sales director, ANGUS, in the press release.

The deal will see Spectrum market and distribute ANGUS’ biologics grade buffers in the United States and Canada.

Spectrum Chemical Strikes Buffers Distribution Deal with ANGUS Chemical Company

Precision BioSciences, a clinical-stage biotechnology company, released new clinical data for its lead candidate, PBCAR0191, a potential first-in-class allogenic B-lymphocyte antigen CD19 (CD19) chimeric antigen receptor (CAR) T-cell therapy, on June 8, 2022. PBCAR0191 is intended as a treatment for patients with autologous CAR T relapsed aggressive lymphomas.

The company found that PBCAR0191 produced high clinical response rates in patients who received a median of five prior lines of therapy. Evaluable subjects had a 100% (11/11) overall response rate, a 73% (8/11) conversion rate, and a 50% (3/6) durable response rate.

“We are pleased that our manufacturing process is yielding improved product attributes, which enable us to deploy a lower dose of lymphodepletion in this fragile and heavily pre-treated CAR T relapsed patient population,” said Alan List, chief medical officer, Precision BioSciences, in a company press release. “We believe these improvements contributed to a faster and improved hematologic recovery without compromising efficacy.”

List also noted that the cell expansion observed with PBCAR0191 cells at dose level 4b (DL4b) lymphodepletion matched the median autologous CAR T peak expansion in subjects who achieved a long durable response in the Phase I/II trial (ZUMA-1). The company believes this to be a first for allogeneic CAR T therapy studied in any population (earlier lines or more heavily pre-treated).

“We are optimistic that, if approved, this could potentially help patients with aggressive lymphomas that relapse after CAR T treatment,” said Michael Amoroso, CEO, Precision BioSciences, in the release. “We believe this data is timely and highly relevant. Today, patients who relapse after CAR T treatment remain highly underserved with no approved standard of care and a progression free survival of only one to two months.”

The company plans to continue dosing subjects with optimized PBCAR0191 in this CAR T relapsed patient population while further reducing the lymphodepletion dose to standard levels to improve overall therapeutic index. They plan to meet with FDA to review data for future guidance.

The company also released details concerning allogeneic CAR T therapy candidates PBCAR19B and PBCAR269A in the release. PBCAR19B, an anti-CD19 targeting allogeneic CAR T candidate intended to treat non-Hodgkin lymphoma, has been administered to three subjects with relapsed or refractory (R/R) diffuse large B-cell lymphoma.

The company also continues to enroll subjects in a Phase I/IIa study featuring PBCAR269A in combination with nirogacestat, a gamma secretase inhibitor developed by SpringWorks Therapeutics. The goal of this study is to produce an allogeneic alternative to autologous CAR T therapies targeting B-cell maturation antigen for R/R multiple myeloma.

Precision BioSciences has released clinical trial data on CAR T therapy candidates PBCAR0191, PBCAR19B, and PBCAR269A.

Precision BioSciences Releases Data on CAR T Therapy Candidates

Moderna released new data concerning its Omicron-containing bivalent COVID booster candidate, messenger RNA (mRNA)-1273.214, on June 8th, 2022. A 50-µg booster dose of the candidate exhibited a superior neutralizing antibody response against the Omicron variant one month after administration relative to the original mRNA-1273 vaccine booster. The bivalent booster raised neutralizing geometric mean titers (GMT) against Omicron approximately eight-fold above baseline levels.

According to a company press release, the booster candidate met all pre-specified endpoints of the Phase II/III clinical trial, including superiority to the Spikevax booster. The candidate was generally well-tolerated in the 437 study participants, who had side effects comparable to a booster dose of mRNA-1273.

Among seronegative participants one month after administration, the neutralizing GMT against ancestral SARS-CoV-2 for mRNA-1273.214 was 5977, compared to a GMT of 5649 for mRNA-1273. Among Omicron-specific variants, mRNA-1273.214 had a GMT of 2372 and mRNA-1273 a GMT of 1473. Additionally, binding antibody titers were found to be significantly higher against all other variants of concern for mRNA-1273.214 relative to mRNA-1273.

"We are thrilled to share the preliminary data analysis on mRNA-1273.214, which is the second demonstration of superiority of our bivalent booster platform against variants of concern and represents an innovation in the fight against COVID," said Stéphane Bancel, CEO, Moderna, in a company press release. "Looking at these data alongside the durability we saw with our first bivalent booster candidate, mRNA-1273.211, we anticipate more durable protection against variants of concern with mRNA-1273.214, making it our lead candidate for a Fall 2022 booster.”

According to the release, Moderna plans to submit preliminary data and analysis to regulators with hopes that the booster will be available by late summer.

Moderna’s mRNA-1273.214 booster candidate exhibited an eight-fold boost in neutralizing geometric mean titers against Omicron.