Conventional and robotic automation inside closed systems reduces risk.

Automating Aseptic Manufacturing

Evolving equipment designs meet the needs of continuous processing techniques.

Adopting Continuous Manufacturing for Solid-Dose Drug Products

Stability programs for biologics are far more complex than small-molecule drugs.

Determining Shelf Life: Reading the Stability Testing Data

Reformulation strategies are useful tools for more than just stretching out return on investment.

Considering Bio/Pharma Reformulation Strategies

Almost half of pharmaceutical industry profits continue to come from biopharmaceuticals.

Trends Affecting Biopharmaceutical Manufacturing

AstraZeneca’s AZD7442 Clinical Trial Meets Primary Endpoint

FDA Advisory Council Unanimously Supports Moderna COVID-19 Booster EUA

Pharma strategizes to reduce its environmental footprint while optimizing output.

Greener API Manufacturing

In conjunction with National Chemistry Week (Oct. 17- 23, 2021), Spectrum Chemical Mfg. Corp scientists compiled a list of their top 10 chemicals impacting quality of life, according to the company’s Oct. 2021 press release. This list is based on multiple factors, including contributions to saving lives, ending suffering, and enabling technological advancements that have provided more communication channels, improved access to information, and modernized the healthcare industry.

The “Top 10 Chemicals that Have Impacted Quality of Life”, as selected by Spectrum Chemical Mfg. Corp scientists, are as follows:

“Chemistry plays an essential role in improving the quality of life, as highlighted by the many chemists, scientists, and medical professionals playing a key role in the battle against COVID-19 and other diseases,” said Russell Kneipp, COO, Spectrum Chemical, in the press release.

National Chemistry Week is an annual event to build public awareness of the importance of chemistry to quality of life.

Articles

Spectrum Chemical scientists give a shout-out to 10 chemicals impacting quality of life in conjunction with National Chemistry Week.

Spectrum Chemical Names Top 10 Chemicals Impacting Quality of Life

Pfizer and BioNTech announced favorable results of a Phase III trial evaluating the efficacy of booster doses for their COVID-19 vaccine on Oct. 21, 2021. Participants who were given a booster vaccine in the trial had a disease reduction rate of 95.6% relative to those who did not receive a booster.

The trial included more than 10,000 participants aged 16 years or older. Participants—individuals who were administered the two-dose Pfizer-BioNTech COVID-19 vaccine—were randomized 1:1 to receive either a 30-µg booster dose or placebo. The median time between administration of the second dose and the booster was 11 months.

Symptomatic COVID-19 occurrence was measured from at least seven days after booster or placebo, with a median follow-up of 2.5 months. Five members of the group who received the booster dose contracted COVID-19, while 109 members of the non-boosted group contracted the virus.

“These important data add to the body of evidence suggesting that a booster dose of our vaccine can help protect a broad population of people from this virus and its variants,” said Ugur Sahin, CEO and co-founder of BioNTech, in a Pfizer press release. “Based on these findings we believe that, in addition to broad global access to vaccines for everyone, booster vaccinations could play an important role in sustaining pandemic containment and a return to normalcy.”

 received an Emergency Use Authorization (EUA) from FDA for the use of their COVID-19 vaccine as a booster among certain populations. This week, both 

 also received EUA’s permitting booster doses.

Pfizer and BioNTech’s Phase III trial demonstrated 95.6% booster efficacy relative to participants who received placebo.

Pfizer and BioNTech Release Phase III Trial Data Supporting Efficacy of Booster Doses

Bristol Myers Squibb (BMS) announced on Oct. 21, 2021, that the European Commission (EC) approved its drug Opdivo (nivolumab) as a complementary treatment to fluoropyrimidine- and platinum-based combination chemotherapy in adult patients with certain types of gastric or esophageal cancer. Nivolumab is a programmed death-1 immune checkpoint inhibitor that is designed to use one’s immune system to help restore the anti-tumor immune response.

According to a company press release, EC’s decision was made following a Phase III trial that evaluated nivolumab. The study found a clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) in patients given nivolumab who had unresectable advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. These results were found in patients whose tumors expressed a combined positive score greater than or equal to five.

The study evaluated OS and PFS rates among patients who received nivolumab and chemotherapy relative to patients who received only chemotherapy. According to BMS, median OS was 14.4 months in patients receiving nivolumab vs. 11.1 months in those receiving chemotherapy alone, while median PFS was 8.31 months in patients receiving nivolumab vs. 6.05 months chemotherapy alone.

“This approval marks a great achievement for many patients with gastric, gastroesophageal junction, and esophageal adenocarcinomas, who now have a new treatment option that has demonstrated superior overall survival compared to the long-standing standard of care,” said Ian M. Waxman, development lead, Gastrointestinal Cancers, BMS, in the press release. “With limited advances for [human epidermal growth factor receptor 2]-negative gastric cancers made in the past 10 years, we are especially pleased to move the field forward and introduce this [nivolumab]-based combination for patients in the European Union.”

The EC approved BMS’s Opdivo (nivolumab) as a complementary treatment to chemotherapy for adult patients with certain types of gastric or esophageal cancer.

Bristol Myers Squibb Receives European Commission Approval for Opdivo

Jennifer Markarian is manufacturing editor of Pharmaceutical Technology.

Cellectis, an international, clinical-stage gene editing company, recently opened a manufacturing facility in Raleigh, NC. The new, 82,000-ft

 good manufacturing practice (GMP) facility is purpose-built for manufacturing allogeneic, universal chimeric antigen receptor T-cell (UCART) immunotherapies for oncology. UCART products are manufactured using the T-cells of a healthy donor to make off-the-shelf and ready-to-use gene-edited CAR T-cells. T-cells from one donor, used in one manufacturing batch of UCART, can make hundreds of doses of product, the company reports. 

 GMP facility in Paris, France was opened in 2020 and makes clinical and commercial critical starting materials including plasma DNA, messenger RNA (mRNA), and viral vectors that are used in UCART manufacturing. The two facilities give the company end-to-end in-house manufacturing capabilities for GMP manufacturing of all critical starting materials and cell products for clinical studies and, eventually, commercial distribution. 

The newly opened facility in Raleigh, NC, includes ambient GMP warehousing and cold-storage space, cryogenic storage for incoming white blood cells and for final products, manufacturing spaces, quality control laboratories, utility and maintenance areas, and office areas. Two UCART manufacturing suites each hold a custom designed, four-chamber isolator that encloses all parts of the manufacturing process, including Cellectis’ proprietary electroporation system that enables its TALEN gene editing technology.

“The manufacturing process includes manual steps that operators perform through glove ports in the isolators, which create a Grade A environment,” explains Steve Doares, senior vice-president of US manufacturing and Raleigh site head at Cellectis. “UCART processing can’t use in-process or terminal filter sterilization, so we must maintain an aseptic state from beginning to end. Rather than putting the process equipment inside biosafety cabinets, we chose to completely enclose them in isolators to give the best possible assurance of product quality for the patient.”

A separate filling suite contains a single-chamber isolator with a robotic filling system. Vials are filled, inspected, labeled, and frozen under highly controlled conditions. Doares notes that the manufacturing process uses single-use systems, which he says are most suitable for the scale of this process.

“Having control over the entire development, manufacturing, and production process helps eliminate setbacks in the product development timeline that could hinder delivery of medicines to patients, which is an issue biotech companies have struggled with during the COVID-19 pandemic,” notes Doares.

A new GMP facility in Raleigh, NC, and a starting materials facility in Paris, France, give Cellectis end-to-end, in-house manufacturing capacity for its UCART product candidates.  

Cellectis Opens GMP Manufacturing Facility

UK-based crystal and particle-engineering company, Crystec, and Argentinian company, Biosidus, have joined forces to enhance the delivery and performance of biotherapeutics, it was announced in an Oct. 19, 2021 press release.

Using Crystec’s proprietary modified supercritical antisolvent (mSAS) supercritical fluid particle engineering platform on selected Biosidus products, the companies hope to be able to generate a range of innovative, differentiated medicines. Initially, the partnership will focus on accelerating the development of a dry powder preparation of teriparatide for the treatment of osteoporosis.

Currently, teriparatide typically needs to be administered by daily injections over a two-year period. Crystec and Biosidus are hoping to be able to eliminate the need for daily injections by developing the dry preparation of the drug that can be used in formulations for administration via alternative routes, such as the nose.

“We are passionate about making our vital therapies accessible and convenient for those who require them. Our ultimate ambition is to eliminate the need for daily injections meaning that men, women, and children who suffer from long-term and chronic illnesses are not subjected to additional discomfort in the course of their treatment,” said Marcelo Criscuolo, scientific director at Biosidus, in the press release. “Working with Crystec’s innovative mSAS technology opens up the possibility of maximizing the therapeutic potential of these drugs through retaining improved biological activity levels and enabling ‘needle free’ delivery options for our patients.”

“We are delighted to work with Biosidus in this important area of drug delivery,” added Paul Thorning, CEO, Crystec, in the press release. “Our collaboration provides significant potential to demonstrate the power of the mSAS platform in simplifying biopharmaceutical processing, whilst facilitating the accelerated development of inhaled and nasal products that could be truly transformative for patients.”

Crystec and Biosidus have joined forces to enhance the delivery and performance of biotherapeutics.

Crystec, Biosidus Collaborate on Enhanced Delivery and Performance of Biotherapeutics 

International pharmaceutical company, Ferrer, and clinical-stage biotechnology company, Treeway, have entered into a license agreement for the development and commercialization of an oral formulation of edaravone (TW001/FNP122).

According to an Oct. 20, 2021 press release, the medicine will be used for the treatment of Amyotrophic Lateral Sclerosis (ALS) in certain territories, which will include Europe and some Asian countries. Ferrer will be responsible for advancing the development and commercialization of the drug and will make royalty payments to Treeway once certain milestones have been met.

“Guided by patients, we have developed TW001/FNP122 through the early stages of development,” said Inez de Greef, CEO at Treeway, in the press release. “We are therefore delighted that Ferrer has committed to advance our lead product to the required pivotal Phase III trial and make it available for ALS patients in large parts of the world.”

“Driven by our purpose of bringing transformative products to patients the world over, we are pleased to enter the agreement with Treeway and look forward to patients benefiting from improved treatment options,” added Oscar Pérez, Ferrer’s chief business development and licensing officer, in the press release. “TW001/FNP122 is the perfect fit for Ferrer’s strategy to bring new molecules to late-stage clinical development, registration and market entry in the field of neurological disorders and strengthen our pipeline for the coming years.”

Ferrer and Treeway, have entered into a license agreement for the development and commercialization of an oral formulation of edaravone (TW001/FNP122).

Ferrer, Treeway Partner on Development and Commercialization of ALS Treatment

The European Medicines Agency (EMA) has recommended the marketing authorization of a first-in-class medicine, Trodelvy (sacitusumab govitecan), to treat patients with an aggressive form of breast cancer.

More specifically, it was revealed in an Oct. 15, 2021 press release that the recommendation is for Trodelvy to be used in the treatment of adult patients with unresectable or metastatic triple-negative breast cancer who have already received two or more systemic therapies, with at least one of those treatments being for advanced disease. As patients with this aggressive form of breast cancer tend to be unresponsive to the standard treatment, chemotherapy, there is a high unmet medical need for new treatments in this area to improve patients’ outcomes.

Trodelvy combines a humanized antibody with a type of an antineoplastic agent called topoisomerase I inhibitor, which are intended to inhibit cancer growth, division, and spread. The marketing authorization application for the treatment has been evaluated under an accelerated process in efforts to speed up patient access to the medicine.

The regulatory authority’s recommendation was based on the data from a Phase III clinical trial that evaluated the safety and efficacy of Trodelvy in 529 patients. In the trial, it was found that the therapy helped to prolong the overall survival of patients by approximately five months and progression-free survival by approximately three months.

This recommendation will now be sent to the European Commission for a final decision on marketing authorization for the European Union. If a positive final decision is made, each European member state will make decisions on price and reimbursements for the medicine

EMA has recommended the marketing authorization of Trodelvy (sacitusumab govitecan) to treat patients with an aggressive form of breast cancer.

Trodelvy Gains EMA Nod for Treatment of Aggressive Form of Breast Cancer

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has approved two new manufacturing sites and a ready-to-use formulation of the BioNTech-Pfizer COVID-19 vaccine, Comirnaty.

Announced in an Oct. 18, 2021 press release, the two new manufacturing sites are both located in Italy—one in Monza, operated by Patheon, and the other in Anagni, operated by Catalent Anagni. Both sites are set to manufacture finished product and are expected to be able to produce up to 85 million addition doses of the COVID-19 vaccine to the European Union before the end of 2021.

The ready-to-use formulation that has been approved by CHMP does not require dilution prior to administration and will be available in a 10-vial (60 dose) pack size. The new formulation can be stored at 2–8 °C for up to 10 weeks. Currently, the concentrated formulation of Comirnaty needs to be diluted before use and can only be stored for up to one month at 2–8 °C. So, the new formulation should provide better storage, transport, and logistic options for distribution and administration.

According to the press release, the new formulation will be rolled out in a phased way commencing in early 2022.

EMA's CHMP has approved two new manufacturing sites and a ready-to-use formulation of Comirnaty.

EMA Approves Two New Manufacturing Sites and a New Formulation for Comirnaty

The European Medicines Agency (EMA) has commenced its evaluation of the BioNTech-Pfizer COVID-19 vaccine, Comirnaty, in children who are aged between five years and 11 years old, to determine if it can be authorized for further expanded use.

According to an Oct. 18, 2021 press release, EMA’s Committee for Medicinal Products for Human Use (CHMP) will review available data on the vaccine, which include results from a clinical study involving children between five and 11 years old that is ongoing. Once CHMP has formed a decision on whether or not an extension of the use of Comirnaty is appropriate it will forward all information onto the European Commission for a final decision.

EMA has specified in the press release that it will “communicate on the outcome of its evaluation, which is expected in a couple of months unless supplementary information is needed.”

EMA has started its evaluation of further expanded use of Comirnaty in children aged between five years and 11 years old.

EMA Starts Evaluation of Comirnaty in Children

The government of the United Kingdom has secured two new antiviral treatments for COVID-19, it was revealed in an Oct. 20, 2021 press release. The deals were made by the government’s Antivirals Taskforce and could be rolled out through a national clinical study before the end of 2021.

“I am delighted to confirm we may soon have a new defense in our arsenal with two new antiviral drugs that we have secured,” said Sajid Javid, health and social care secretary for the UK government, in the press release. “Our work is far from done though—and we’ll continue our tireless work to secure more innovative treatments so we can protect as many people as possible from the virus, its variants, and future diseases.”

Primarily, the antivirals—Molnupiravir (MSD) and PF-07321332/ritonavir (Pfizer)—will be used for the most vulnerable patients, including the elderly and those with weakened immune systems. Both treatments will need to be evaluated by the UK’s regulatory body the Medicines and Healthcare products Regulatory Agency (MHRA) before they are authorized.

“This is a very important development in our mission to find antivirals for those exposed to COVID-19, supporting the renowned vaccination program and the [National Health Service] over the coming months,” added Eddie Gray, chair of the Antivirals Taskforce, in the press release. “Should they be approved by the medicines regulator, we could see these treatments rolled out to patients this winter, providing them with vital protection.”

In response to the government’s announcement, Richard Torbett, chief executive of the Association of the British Pharmaceutical Industry commented in a press statement, “Vaccines have already done so much to help break the link between infections and hospitalizations. Antivirals are another line of defense for the most clinically vulnerable and patients who are seriously ill with COVID-19. This is good news, and another example of the pharmaceutical industry and government working together to make sure we have as many effective tools as possible to tackle this pandemic.”

UK government has secured two new antiviral treatments for COVID-19, which may be rolled out in a national clinical study before the end of 2021.