Point-of-use sterilizing grade filtration has been used reliably for years to achieve sterile fluid fill.It is currently the only alternative for biologics, which would be damaged by heat sterilization.Over the years, the dependability of this critical aseptic processing step has been improved with the introduction of new filter materials and designs, and the adoption of single-use technology in closed unit operations.Moreover, the sterilizing grade filters and related processes are validated to test their performance under process conditions to help ensure that they perform as specified (1–3).Nondestructive tests (e.g., bubble point, diffusive flow, or pressure decay), which have been in use since the mid-1970s, are typically used for filter integrity assessments, which can be done in the following ways:

Maik W. Jornitz is CEO of G-CON Manufacturing, Inc.

Pharmaceutical Technology's Biologics and Sterile Drug Manufacturing


eBook: Biologics and Sterile Drug Manufacturing, May 2021
May 2021
Pages: 4–12

When referring to this article, please cite it as M. W. Jornitz, “Sterile Filtration: Reducing Risk, Ensuring Safety,"

 Pharmaceutical Technology Biologics and Sterile Drug Manufacturing eBook 

Articles

Manufacturing

A task force established by PDA and BioPhorum is establishing scientific data for integrity test activities.  

Sterile Filtration: Reducing Risk, Ensuring Safety

With the increase in drug products targeted to specific patient groups, including orphan drugs and even individualized medicine, manufacturers must consider how to optimize the manufacturing process for aseptic fill/finish of drugs in small batch sizes. 

 spoke with Joerg Zimmermann, vice-president of Development Service and External Affairs at Vetter, about these challenges and the equipment and facility options to consider.

Jennifer Markarian is manufacturing editor of 


eBook: Biologics and Sterile Drug Manufacturing, May 2021
May 2021
Pages: 14–17

When referring to this article, please cite it as J. Markarian, “Filling Small Batches

" Pharmaceutical Technology Biologics and Sterile Drug Manufacturing eBook 

Advances in automation and cleanroom technology improve efficiency for small commercial quantities of aseptically filled drug products.  

Filling Small Batches

Vaccine doses are often wasted due to challenges in maintaining cold storage from the manufacturing site to the patient. Aseptic spray drying offers a technology alternative to manufacture thermally stable vaccines, which can help ensure the stability and effectiveness of vaccines, extend shelf life, and reduce the potential for waste of these crucial products.

Sam de Costa is stabilization projects manager, Nova Laboratories Limited.

When referring to this article, please cite it as S. de Costa, “Breaking the Cold Chain for Vaccines," 

Pharmaceutical Technology Biologics and Sterile Drug Manufacturing eBook

Aseptic spray drying offers a technology alternative to manufacture thermally stable vaccines.

Breaking the Cold Chain for Vaccines

The accelerated pace of gene therapies is a sign of enhancements in our understanding of genetics and viral engineering as well as innovation in manufacturing processes. Despite this progress, gene therapy development is not a perfect science, and manufacturers must be careful to monitor the quality of their products before they reach patients. The sensitivity of droplet digital PCR (ddPCR) helps manufacturers detect 

 contamination in adeno-associated vector-based gene therapy products.

Mark White, PhD, is associate director, Biopharma Product Marketing, at Bio-Rad Laboratories.

 Biologics and Sterile Drug Manufacturing

When referring to this article, please cite it as M. White, “Using ddPCR to Detect 

Pharmaceutical Technology Biologics and Sterile Drug Manufacturing

Analytics

The sensitivity of droplet digital PCR helps manufacturers detect Mycoplasma contamination in AAV-based gene therapy products.

Using ddPCR to Detect Mycoplasma Contamination

The COVID-19 pandemic brought on new challenges for the pharmaceutical industry, prompting regulators to quickly develop temporary guidelines to address pharmaceutical manufacturing during the health crisis. When it comes to sterile manufacturing, the urgency of COVID-19 vaccine production has showed how important the use of technology is to add capacity when needed, according to the Parenteral Drug Association (PDA) COVID-19 Task Force, including the use of mobile manufacturing platforms. So, how will these production challenges and short-term regulations impact the future of the industry?

There are principles found in these guidance documents that may be applicable to pharmaceutical development and manufacturing after the pandemic has ended, according to the PDA COVID-19 Task Force. Specifically, FDA’s Remote Interactive Evaluations for Oversight of Drug Facilities During COVID-19 may be useful in the long term for fast-tracking medicines that fulfill unmet needs (1). Data gained from the agency’s guidance on container closures (2) may be used to gain insight on how efficiencies and principles could be more widely applied, according to the Task Force, leading to revised or new guidance documents.

FDA’s guidance on potential transmission of COVID-19 in cell and gene therapies (CGT) (3) raises risk assessment and cross-contamination questions that may need to be answered because of supply chain changes, the Task Force noted, especially the use of sterile fill/finish facilities that manufacture live viral vectors. Cross-contamination from a variety of areas (e.g., employees, materials, and equipment) also should be reviewed.

Kelly Davis-Claeys, director, regulatory affairs at Catalent Bloomington, and Mo Heidaran, vice president, technical at Parexel Consulting, provide additional insight into the future impact of these pandemic challenges and short-term regulations in the following.


eBook: Biologics and Sterile Drug Manufacturing, May 2021
May 2021
Pages: 34-37

When referring to this article, please cite it as S. Haigney, “The Impact of COVID-19 on Biologics Regulations,"

Quality/Regulations

Industry experts discuss how FDA’s response to COVID-19 and related pandemic-related guidance documents may impact the biologics industry long term.

The Impact of COVID-19 on Biologics Regulations

Contract packaging organizations for clinical trial materials are increasingly handling biologic drugs, which are typically delivered by injection and have more stringent packaging requirements than other drug forms. In addition to the shift to biologics, the trend to direct-to-patient shipping affects how materials are packaged and makes tracking even more important. Careful consideration of primary packaging materials, kit design, and distribution is crucial for optimizing packages that balance user requirements, protection of drug product quality, and efficiency.


eBook: Biologics and Sterile Drug Manufacturing, May 2021
May 2021
Pages: 44–48

When referring to this article, please cite it as J. Markarian, “Packaging Biologic Drugs for Clinical Trials

Operations

Contract packaging organizations packaging biologic drugs for clinical trials use technologies that meet the unique requirements of each study. 

Packaging Biologic  Drugs for Clinical Trials

Now that COVID-19 vaccines have received regulatory authorizations and vaccine manufacturers are providing a steady and increasing supply, the focus is on distributing doses. Vaccine manufacturers worked closely with cold-chain distribution experts to plan for maintaining and monitoring the cold chain for these crucial drug products. 

spoke with Mahesh Veerina, CEO of Cloudleaf, and Gisli Herjolfssonn, CEO and cofounder of Controlant, about supply-chain visibility systems for maintaining the cold chain.


eBook: Biologics and Sterile Drug Manufacturing, May 2021
May 2021
Pages: 38–43

When referring to this article, please cite it as J. Markarian, “Tracking Technologies Safeguard Vaccine Cold Chain

Supply-chain visibility systems are proving their worth in the distribution of COVID-19 vaccines and may see broader use in the future.

Tracking Technologies Guard Vaccine Cold Chain

Sterile fill/finish manufacturing is expected to experience significant growth over the coming years, with some market research analysts predicting the field to be worth $12.1 billion by 2025 (1). Expanded drug development pipelines, incorporating more complex, large-molecule products and therapies that require sterile production, form part of the driving force for this rising demand for fill/finish services.

Ophthalmic therapeutics, in particular, require heightened expertise due to the fact that they are administered to the eyes, which are extremely sensitive and important organs. To learn more about the intricacies of sterile fill/finish manufacturing, specifically pertaining to ophthalmics, 

 spoke with Daniel Kehl, chief executive officer at swissfillon—a fill/finish specialist based in Switzerland.

Felicity Thomas is the European editor for Pharmaceutical Technology Group.


eBook: Biologics and Sterile Drug Manufacturing, May 2021
May 2021
Pages: 49–53

When referring to this article, please cite it as F. Thomas, “Eyeing Up Success in Fill/Finish,” 

Pharmaceutical Technology Biologics and Sterile Drug Manufacturing eBook

Certain therapeutics, such as ophthalmics, must be provided as a sterile dosage form but can pose fill/finish challenges due to the small batch sizes required and the fact that the products used are difficult to fill and of high value.

Eyeing Up Success in Fill/Finish

Blow-fill-seal (BFS) technology presents an economical option for single-unit dose delivery of vaccines. Currently used for over-the-counter products, prescription medicines, and more than 50 injectable products, the authors present the case for using BFS for prefilled syringes. Factors including drug formulation, material compatibility, extractables and leachables, sterilization, and regulatory approval must be considered.

Beth Totin is chief commercial officer, and Marcus Webb is director of communications, both with ApiJect Systems, Corp.

When referring to this article, please cite it as B. Totin and M. Webb, “Reducing Packaging Costs for Prefilled Syringes," 

Blow-fill-seal (BFS) technology presents an economical option for single-unit dose delivery of vaccines. 

Reducing Packaging Costs for Prefilled Syringes

Biologics facilities have expanded and advanced within the past few months in terms of significant investments, construction on new facilities, and acquisitions of new locations. The following are a sampling of these advances. 


eBook: Biologics and Sterile Drug Manufacturing, May 2021
May 2021
Pages: 60–62

When referring to this article, please cite it as L. Lavelle, “Biologics Facilities Expand and Establish New Locations in 2021,"

The latest news about biologics facilities includes various expansions, new locations, and acquisitions in the bio/pharmaceutical space. 

Pharmaceutical Technology-05-15-2021