Process and plasmid design optimization, disposable equipment, and flexible platform processes all play important roles.

Achieving High Yields in Upstream Processing of Plasmids

Decreasing vein to vein time saves lives.

High-titer Vector Producing Cells

There is growing pressure for robust and economically scalable viral-vector manufacturing technologies.

Tactics and Strategies for Designing an Ideal Lentiviral Vector Platform

Shifts in pharmaceutical packaging have spurred tremendous growth in the pre-filled syringe fill/finish industry.

Automated Inspection of Pre-filled Syringes and Biologics During Fill/Finish

Considerable efforts have been made over the years to resolve the key issues of stability and delivery of RNA-based therapeutics.

The Marriage of RNA and Mass Spectrometry

The bio/pharma outsourcing industry continues to be integral in the development and manufacture of medicines.

Outsourcing Still Vital

The trends shaping the growth of the biologics outsourcing industry demand attention.

The Logistics of Outsourcing Biologics

Grant Playter is the Assistant Editor for 

Pfizer and Seagen, a global biotechnology company specializing in antibody-drug conjugates (ADC), announced a definitive merger agreement on March 13, 2023. The deal will see Pfizer acquire all outstanding shares of Seagen for a total of $43 billion. The companies expect to complete the transaction in late 2023 or early 2024, subject to approval of Seagen’s stockholders and receipt of required regulatory approvals.

According to a company press release, Seagen’s portfolio includes four approved medicines that are first- or best-in-class in their respective indications across solid tumors and hematologic malignancies: three of these, Adcetris (brentuximab vedotin), Padcev (enfortumab vedotin), and Tivdak (tisotumab vedotin), are ADCs. The company’s technology is used in four of the twelve total FDA-approved and marketed ADCs.

In the release, Seagen stated that it expects to generate approximately $2.2 billion of revenue in 2023, representing 12% growth relative to 2022. Additionally, Pfizer indicated it believed that Seagen could contribute more than $10 billion in risk-adjusted revenues by 2030, as well as provide potential significant growth beyond that.

“Pfizer is deploying its financial resources to advance the battle against cancer, a leading cause of death worldwide with a significant impact on public health,” said Albert Bourla, chairman and CEO, in the release. “Together, Pfizer and Seagen seek to accelerate the next generation of cancer breakthroughs and bring new solutions to patients by combining the power of Seagen’s ADC technology with the scale and strength of Pfizer’s capabilities and expertise. Oncology continues to be the largest growth driver in global medicine, and this acquisition will enhance Pfizer’s position in this important space and contribute meaningfully to the achievement of Pfizer’s near- and long-term financial goals.”

“Pfizer shares our steadfast commitment to patients, and this combination is a testament to the passion, dedication and talent of the Seagen team to achieve our mission to discover, develop, and commercialize transformative cancer medicines that make a meaningful difference in people’s lives,” said David Epstein, CEO, Seagen, in the release. “The proposed combination with Pfizer is the right next step for Seagen to further its strategy, and this compelling transaction will deliver significant and immediate value to our stockholders and provide new opportunities for our colleagues as part of a larger science-driven, patient-centric, global company.”

Articles

Pfizer will acquire all outstanding shares of Seagen for a total of $43 billion.

Pfizer to Acquire Seagen in $43 Billion Blockbuster Deal

The Biden-Harris administration, through the Centers for Medicare & Medicaid Services (CMS), announced on March 15, 2023 a list of prescription drugs for which Part B beneficiary coinsurances may be lower. Taking effect from April 1, 2023 to June 30, 2023, Medicare recipients may save between $2 and $390 per average dose on affected medications, although drugmakers will not be expected to pay these rebates until 2025.

According to the agency press release, these price controls, instituted on 27 different drugs, are set to hit drugs whose price increases have outpaced the rate of inflation. The 

 (1) notably includes heavy-hitters such as AbbVie’s Humira (adalimumab) and Astellas Pharma’s and Seagen’s Padcev (enfortumab vedotin). Other affected companies include Gilead Sciences, Johnson &Johnson, and Pfizer; Pfizer, had the most drugs named of any other company, with five drugs on the list,.

“The Biden-Harris Administration believes people with Medicare shouldn’t be on the hook when drug companies inexplicably jack up the prices of their drugs,” said Health and Human Services Secretary Xavier Becerra in a CMS press release. “President Biden made lowering prescription drug costs for Americans a top priority, and we’re using every lever we have to deliver results. With the inflation rebate program, we are fighting to ensure seniors can afford the treatments they need, taxpayers aren’t subsidizing drug company excess prices, and the Medicare program is strong for millions of beneficiaries now and in the future.”

1. CMS, “Reduced Coinsurance for Certain Part B Rebatable Drugs under the Medicare Prescription Drug Inflation Rebate Program,” Press Release, March 15, 2023.

27 drugs within Medicare will face penalties for having their prices raised faster than the rate of inflation. 

First Drugs Hit by Inflation Reduction Act Price Controls

Mike Wilson, QA/QC Strategy, Waters Corporation

Facing new global challenges, pharmaceutical company leaders are looking to prioritize operational strategies to remain competitive in this rapidly evolving business environment. Recent events that range from the COVID-19 pandemic to new regulatory guidelines to economic inflation have required pharma manufacturers to find new ways to streamline workflows and minimize risks. Disruptions caused by the pandemic and related restrictions continue to impact supply chains and logistics worldwide. Additionally, many companies have shifted toward remote and hybrid working, and have increased their use of digital technologies to maintain business continuity and protect the health of employees.

Mitigating Human Error and Supporting Compliance with Smart Technology

These changes are accelerating the need for new innovations. One solution is the use of intelligent informatics in the pharmaceutical quality control (QC) laboratory to improve the quality and safety of drugs and reduce the risk of costly errors and recalls. However, while technology can simplify many workflows, it also comes with a learning curve and new burdens may be placed on its users. Pharma companies must determine the effectiveness of technological advancements and the potential challenges they may introduce in an environment like pharmaceutical quality assurance/quality control (QA/QC).

BioPharm International’s March 2023 Quality and Regulatory Sourcebook eBook.

When referring to this article, please cite it as Wilson, M. Mitigating Human Error and Supporting Compliance with Smart Technology. 

BioPharm International’s Quality and Regulatory Sourcebook eBook 

Technological advances hold promise for mitigating human error in the pharmaceutical industry, especially in quality assurance/quality control, by reducing the incidence of, and risk associated with, mistakes.

Paul Van Tilborg is director of analytical sciences at Ardena.

Progressing a drug candidate from research to commercialization requires huge sums of money (approximately US$1.5 billion–$4.5 billion) (1) and is inherently high risk due to the high attrition rate. Only approximately 10% of total drug attrition is because of poor strategic planning or a lack of commercial needs (2). Highlighting solid strategy and funding alone is not enough to take a drug to market. Approximately 70–80% of clinical failures can be attributed to a lack of clinical efficacy or toxicity (3), and the majority of drug failures occurring in pre-clinical and Phase I are due to pharmacokinetics or toxicity issues (4).

When referring to this article, please cite it as Van Tilborg, P. Phase-appropriate Analytical Methodology. 

A phase-appropriate analytical development strategy is crucial, especially for complex (formulated) drug substances.

Phase-appropriate Analytical Methodology

Amanda Guiraldelli is scientific affairs manager at the United States Pharmacopeia.

Jane Weitzel is an independent consultant and chair of the US Pharmacopeia Expert Committee on Measurement and Data Quality.

In parallel to the evolution of compendial and regulatory approaches addressing new quality paradigms for analytical procedure validation (discussed in Part I of this article), fundamentals of the quality-by-design (QbD) concept have been incorporated into the new International Council for Harmonisation (ICH) Q14 and ICH Q2(R2), which were recently released for public consultation. This article focuses on drawing parallels between ICH Q14/Q2(R2), 

) <1220>, and International Organization for Standardization/International Electrotechnical Commission (ISO/IEC) 17025:2017.

Evolution of Analytical Procedure Validation Concepts: Part II

Evolution of Analytical Procedure Validation Concepts: Part I

Quality and Regulatory Sourcebook eBook March 2023

BioPharm International’s Quality and Regulatory Sourcebook

Amanda Guiraldelli is scientific affairs manager at the United States Pharmacopeia.
Jane Weitzel is an independent consultant and chair of the US Pharmacopeia Expert Committee on Measurement and Data Quality.

When referring to this article, please cite it as Guiraldelli, A. and Weitzel, J. Evolution of Analytical Procedure Validation Concepts: Part 2. 

BioPharm International Quality and Regulatory Sourcebook

This article focuses on drawing parallels between ICH Q14/Q2(R2), United States Pharmacopeia (USP) <1220>, and International Organization for Standardization/International Electrotechnical Commission (ISO/IEC) 17025:2017.


A safety surveillance strategy is a requirement for pharmaceutical companies to monitor product safety in the post-marketing environment, as well as to keep physicians informed on product risks and how to prescribe appropriately. This is usually seen as a labor-intensive cost center that often overburdens teams with work, making it difficult to retain talent. As the industry becomes more cost-conscious and is handling more real-world data sources than ever, companies are seeking ways to improve the efficiency and effectiveness of their pharmacovigilance (PV) activities. Automation offers the solution for organizations prepared to embrace it and to do the hard work required to support digital transformation.

Why automation is vital in pharmacovigilance

Many reasons exist to support the adoption of automation in drug safety surveillance. Using artificial intelligence (AI) in safety surveillance can automate many aspects of the process, including non-electronic data collection, processing of inbound data, and triaging data according to its source. With these applications, companies can increase productivity, lower their technology costs, and reduce their reliance on manual labor.

Read this article in the Quality and Regulatory Sourcebook 2023 

Updesh Dosanjh is a practice leader for technology solutions at IQVIA.

When referring to this article, please cite it as U. Dosanjh, "Pharmacovigilance Automation," 

BioPharm International's Quality and Regulatory

Organizations can better understand the maturity of AI-driven automation technology across their organization’s IT landscape through effective pharmacovigilance.

Pharmacovigilance Automation

In recent years, regulatory agencies have placed an increased emphasis on pharmaceutical process understanding through adoption of quality-by-design (QbD) principles by launching a series of initiatives to encourage the pharmaceutical industry to adopt QbD in the manufacturing process. A key component of this transformation is the evolution of validation concepts to a life cycle risk-based approach driven by analytical quality by design (AQbD) principles. Different pharmacopoeias have been developing compendial approaches to support the implementation of analytical procedure life cycle (APLC) risk-based approach. Additionally, the International Council for Harmonisation (ICH) released in March 2022 two draft guidelines for public consultation which outline QbD principles: ICH Q14 (procedure development) (1), and the ICH Q2(R2) (procedure validation) (2). In a series of two articles, the authors will provide an overview of the validation concept principles evolution with a focus on compendial perspectives (Part I) and draw a parallel between ICH Q14 and Q2(R2) and 

) General Chapter <1220> and the ISO/IEC 17025:2017 (Part II).

Evolution of Analytical Procedure Validation Concenpts: Part II

BioPharm International
eBook: Quality and Regulatory Sourcebook 2023
March 2023
Pages: 14–21

When referring to this article, please cite it as Guiraldelli, A. and Weitzel, J. Evolution of Analytical Procedure Validation Concepts: Part I. 

This article provides an overview of validation concept principles evolution to a life cycle risk-based approach with focus on compendial perspectives.


Cliff Campbell is senior consultant at KPC.

Biopharma systems and processes are outlined in the introductory section of this monograph. A new knowledge management (KM) paradigm is then described, beginning with an analysis of United States and European Union regulatory requirements, and of prevailing commissioning and qualification (C&Q) and quality risk management (QRM) guidance from the International Society for Pharmaceutical Engineering (ISPE) and International Council for Harmonisation (ICH).

Points to Consider for Knowledge Management Acceleration

The KM paradigm is a response to the expectation that C&Q and QRM be integrated and accelerated, on urgent fast-track projects (the new normal) in particular. It is based on pattern recognition, and on the insight that process-related critical quality attributes (CQAs) and critical process parameters (CPPs), and plant-related critical aspects (CAs, or functions) and critical design elements (CDEs, or components), are best managed via a previously unrecognized fundamental object called quality quartet, comprising CQA:CPP:CA:CDE parts. Several well-established and universally accepted benchmarks are listed in support of the paradigm.

When referring to this article, please cite it as Campbell, C. Points to Consider for Knowledge Management Acceleration. 

Quality quartets support an integrated and stable combination of
commissioning and qualification and quality risk management processes.

On March 9, 2023, FDA announced that it is requesting $7.2 billion as part of the president’s fiscal year 2024 budget. The request includes an increase of $372 million in budget authority and a $150 million increase in user fees.

The funding will allow the agency to continue to leverage new and emerging technologies, recruit and support a skilled workforce, and adapt oversight to new production and business models. This would have an immediate impact on food, tobacco, and medical product safety in the United States, while also preparing the agency to address rapid innovation across the food and medical products fields.

“This year’s funding request builds on our accomplishments and lessons learned over the past year and adds new funding to continue modernizing [FDA] and its capabilities for the future. We continue to deliver on a wide range of priorities and have strategically focused our request to ensure our program areas have the funding they need to operate with the highest success for the good of public health,” said FDA Commissioner Robert M. Califf in a press release. “Our investments to strengthen medical product safety and availability, along with funding for vital oversight of tobacco products continue to be a central focus. The budget also provides a historic investment to strengthen [FDA’s] food safety and nutrition capacity—especially for infants and young children, demonstrating the Administration’s ongoing commitment to these responsibilities. As always, our foremost focus is on the well-being of patients and consumers, and we look forward to continuing our work with Congress to help meet the critical public health challenges ahead.”

FDA is seeking $7.2 billion to enhance food safety and advance medical product availability. 

FDA Seeks $7.2 Billion to Protect and Advance Public Health

Sumitovant Biopharma announced on March 10, 2023 that it has completed its acquisition of Myovant Sciences. Sumitovant has acquired all outstanding shares of Myovant not already owned by Sumitovant in an all-cash deal with a total transaction value of approximately $1.7 billion. Myovant will now be delisted from the New York Stock Exchange, and its shares will no longer by publicly traded.

“We are excited to have officially completed our acquisition of Myovant and look forward to working together to address unmet needs in women’s health and prostate cancer,” said Myrtle Potter, CEO of Sumitovant, in a company press release. “By combining our unique expertise, platforms, and resources, we will be better positioned to drive the growth of Myovant’s products and accelerate the development of our robust combined pipeline.”

“I am confident that bringing together the capabilities and strengths of Sumitovant and Myovant will best position us to continue delivering innovative therapies to patients sooner and accelerate the potential opportunities for ORGOVYX and MYFEMBREE,” said Hiroshi Nomura, CEO of Sumitomo Pharma, in the release.

“I look forward to all we will be able to achieve with the support of Sumitovant and Sumitomo Pharma to expand the impact of our differentiated therapies and advance our clinical programs,” said David Marek, CEO of Myovant, in the release. “We remain steadfast in our commitment to advance life-changing medicine and health equity for the patient communities we serve.”

Sumitovant Bipharma has completed its acquisition of Myovant Sciences for approximately $1.7 billion.

Sumitovant Acquires Myovant for $1.7 Billion

On March 10, 2023, Silicon Valley Bank (SVB) was closed by the California Department of Financial Protection and Innovation, with the Federal Deposit Insurance Corporation (FDIC) as appointed receiver. Biotechnology companies made up a substantial part of the bank’s client base, with 12% of the bank’s $173 billion in deposits coming from life sciences and healthcare, according to SBV’s 

SVB was also a critical partner for many startups and young biotechnology companies. Many companies have issued statements regarding their lack of affiliation with the bank. ONWARD Medical N.V. issued a 

 statement on March 13, 2023, stating, “ONWARD has no business arrangements nor known exposure to SVB. All banks currently holding cash deposits and securities on behalf of ONWARD carry Moody’s Investors Service ratings of A1/P-1 or higher on long/short-term deposits,” (2).

 statement on March 13, 2023, stating, “Autolus Therapeutics…following recent events with Silicon Valley Bank, announced that the company has no business relationships with Silicon Valley Bank past or present,” (3). 

 from the FDIC, “all deposits—both insured and uninsured— … [have been transferred] to a newly created, full-service FDIC-operated ‘bridge bank’ in an action designed to protect all depositors of Silicon Valley Bank. Depositors will have full access to their money beginning this morning, [March 13, 2023], when Silicon Valley Bank, N.A., the bridge bank, opens and resumes normal banking hours and activities, including online banking.”

Some biotechnology companies who have had relations with SVB are beginning to reassess their approach, with Agenus announcing in a 

 that “it has cancelled its conference call on Monday, March 13 to discuss its minority cash holdings at Silicon Valley Bank in light of the government’s SVB deposit access announcement,” (4).

Ventyx Biosciences provided an update in a 

, stating, “A portion of our cash is deposited in accounts with SVB and custodial accounts managed by SVB, and Ventyx may not have full access to these funds in the near-term. We do not see a material impact to our liquidity position or our ongoing operations as a result of this event,” (5).

1. SVB. Q4 2022 Financial Highlights. Jan. 19, 2023.

2. ONWARD. ONWARD Does Not Hold Cash Deposits at Silicon Valley Bank. Press release. March 13, 2023.

3. Autolus Therapeutics. Autolus Therapeutics Has No Business Relationship with Silicon Valley Bank. Press release. March 13, 2023.

4. Agenus. Agenus Cancels Conference Call to Discuss the Company’s Minority Cash Holdings at SBV in Light of Government’s SBV Deposit Access. Press release. March 12, 2023.

5. Ventyx Biosciences. Ventyx Biosciences Provides Update on Silicon Valley Bank Financial Exposure. Press release. March 11, 2023.

Silicon Valley Bank has collapsed, leaving many biotechnology companies unsure of the future. 

Biotech Companies Deal with Silicon Valley Bank Collapse

 Washington Editor, jillwechsler7@gmail.com.

After more than a decade of delay tactics, it appears that FDA may finally bring about the withdrawal of its earlier approval of the controversial drug to prevent preterm birth. Even after an FDA 

advisory panel voted 14–1 in October 2022 

to remove the drug, Makena manufacturer Covis Pharma continued to press for some continued access to the therapy. In a long submission, the firm’s attorneys argued that the weak trial results were inconclusive and that more studies should be done, and that there is no other drug available to prevent preterm birth, so Makena is better than nothing.

Officials at the Center for Drug Evaluation and Research (CDER) disagreed, 

stating that it undermines public health to offer a drug to patients that offers only risks and no benefits and that Makena should exit the market immediately

. FDA explains that Makena was approved under the accelerated approval process, but that postmarketing clinical studies had failed to confirm its effectiveness in reducing the risk of premature birth in its target patient population. Therefore, CDER analysts urge Commissioner Rob Califf and the agency’s chief scientist, who are charged with deciding the issue, to support immediate withdrawal of the drug and any generic versions to avoid exposing patients to further risk. And in specific response to Makena’s proposal to continue treatment for those patients already using the drug, agency experts emphasize that there is no evidence of patient harm from discontinuing Makena, and only further risks from continued treatment.

The 12-year Makena saga illustrates how difficult it is for FDA to cancel marketing of an approved therapy, even when test data fails to confirm efficacy, and the need for reform of the accelerated approval process to ensure patient use of effective treatments. An FDA advisory committee that met in October 2019 was divided on whether to withdraw the drug. Even though postapproval studies of Makena by then-manufacturer AMAG Pharmaceuticals failed to confirm substantial evidence of effectiveness, some panel members supported leaving the product on the market pending further evidence. The company objected to additional trials, and FDA proposed to remove the drug from the market in October 2020.

That led to the more recent advisory committee meeting in October 2022. With little new evidence to support the drug’s efficacy, this time the panel voted unanimously that a confirmatory study showed no benefit, and it agreed 14–1 to remove Makena from the market. Covis 

initially objected to that course of action

 and sought to continue to make the drug available to very high-risk patients. Only when FDA issued a much harsher report this month did the company agree on March 7, 2023 to “voluntarily withdraw the product” in an “orderly wind-down,” said

 Covis Chief Innovation Officer Raghav Chari

Just how long that “wind-down” takes remains to be seen. Covis continues to point to the lack of any alternative treatment to prevent miscarriage, and that that some treatment—even its ineffective one—is better than nothing. And the company has highlighted the higher rates of miscarriage among black women, and that removing the drug discriminates against this minority patient group.

FDA and the research community, however, recognize that it’s impossible to conduct any placebo-controlled study if any approved treatment is available to patients. Leaving the drug on the market all these years now is seen as a deterrent to developing more effective therapies for this condition. But the therapy generated some $1.5 billion in sales since its approval in 2011, according to press reports. If Califf and his staff agree with CDER’s recommendations, the marketing of Makena may finally end.

Even after an FDA advisory panel voted 14–1 in October 2022 to remove the drug, Makena manufacturer Covis Pharma continued to press for some continued access to the therapy.