Aseptic Manufacturing with State-of-the-Art Technologies

The continued growth of biologic drugs and the recent COVID-19 pandemic are driving an ever greater need for expanded sterile manufacturing capacity and capabilities across the globe. Pharmaceutics International, Inc. (Pii) has proactively expanded its highly flexible aseptic filling capacity with proven isolator–barrier and automated technologies that enable processing of conventional as well as toxic and cytotoxic drug products, under highly sterile, contained conditions.

Many Drivers for Outsourcing of Aseptic Fill/Finish

Growth of the sterile injectables market is predicted to exceed 11% per year on average through the middle of this decade. The value for the global market is estimated to reach $779 billion by 2024¹ and just over $900 billion by 2025.² The global vaccines market — before the COVID-19 pandemic developed — was projected to reach a value of $100 billion by 2025.³

As the number of biologic drugs in the pharmaceutical pipeline increases and more biopharmaceuticals receive marketing authorizations/approvals, demand for contract aseptic fill/finish services has also risen. Sterile manufacturing is required for parenteral drugs (both small and large molecule), viral vectors for cell and gene therapy manufacturing, and vaccines.

Many novel biologics and other products that require sterile fill/finish are developed by emerging/small biotech companies with no, or limited, manufacturing capacity. Large biopharma firms also often outsource portions of their portfolios to access specialized capabilities and/or reduce supply chain risks.⁴ 

In a survey conducted by HighTech Business Decisions, nearly all respondents (96%) reported that their companies outsource aseptic filling activities to some degree.⁴ In addition, more than two-thirds (72%) of survey participants outsource lyophilization. Overall, the survey revealed that 89% of companies have difficulty accessing outsourced capacity, particularly for antibody-drug conjugates, live viruses, cytotoxics with slow-release formulations, and small-volume projects.

Consequently, the global contract manufacturing market for fill/finish services for biologics is anticipated to expand at an annualized rate of >10% to reach $4.2 billion by 2030.⁵ The global vaccine contract manufacturing market, before the COVID-19 pandemic, was estimated to be expanding at a CAGR of 9.3% to reach a similar value of $4.0 billion.

Unique Synthesis of Pharmaceutics Experience, Service Excellence, and Entrepreneurial Adaptability

The foundational premise of Pii is our pharmaceutics know-how. We are a science-driven CDMO providing dosage form development and cGMP manufacturing services to the global pharmaceutical industry. We offer unparalleled scientific insight and depth of product knowledge while supplying high-quality dosage forms that enhance the lives of patients worldwide.

For over 25 years, Pii has been supporting our pharmaceutical partners (from virtual to multinational) with extensive technical capabilities and expertise, including preformulation studies, formulation development, and lyophilization cycle development, as well as the clinical and commercial cGMP manufacturing of parenterals, oral liquids, and solids, including soft gels, tablets, and capsules. We also provide clinical packaging and labeling, clinical trial kit building and distribution services, and full analytical and regulatory support and have the capability to handle potent drugs and Schedules I–V controlled substances.

Our focus is on small- to medium-scale processes, which we support with a unique combination of agility, flexibility, and responsiveness, whether those products are conventional small molecule drug substances and drug products, biologics, or other challenging products. Our specialized capabilities, multi-product facilities, and knowledge base allow us to work with potent compounds and hormones, develop complex dosage forms, and support varied manufacturing processes. All of our efforts are supported by our extensive pharmaceutics know-how, which includes formulation, process and manufacturing, commercial quality, process management, and regulatory expertise.

The goal is always to help our pharma partners get to the clinic as quickly as possible without any issue. Pii prides itself on delivering on both of these critical requirements through the application of innovative, flexible, and efficient sterile product filling solutions. No matter what the program or its inherent challenges, Pii never says “no” — we say, “let’s find a solution together.”

Extensive Aseptic Manufacturing Capabilities

Aseptic manufacturing is a complex process that requires extensive knowledge and understanding of drug substance properties, numerous novel product formats, and highly advanced containment and filling systems. 

Pii’s aseptic capabilities position us to deliver quality and on-time drug product for both clinical and commercial projects. Our cleanrooms range from class 100 to 100,000, and we use disposable consumables and contact parts wherever possible to minimize the risk of contamination. We have experience with products that are difficult to develop and manufacture, such as highly viscous liquids/suspensions and highly sensitive formulations. 

We have two suites with a wide range of filling options, including vials, prefilled syringes, cartridges, and lyophilization. “Aseptic 1” is designed for development to small-scale commercial projects, with batch sizes from 1—300 L. Both terminal sterilization and aseptic liquid fill/finish processes can be accommodated, with vial sizes of 3–100 mL (at fill rates of 40–50 and 608 vials/minute, respectively) and syringe volumes of 1–10 mL (fill rates of 32, 20, and 8–10 syringes per minute for 1-, 5-, and 10-mL syringes, respectively). Lyophilization can also be performed in this suite, with up to 16,000 3-mL vials or 2,100 100-mL vials per load.

“Aseptic 2” supports development to large-scale commercial projects, with batch sizes of 1–1000 L and up to 150,000 vials (2–100 mL with fill rates of 100–160 and 30–40 vials per minute, respectively). It, too, can accommodate processes that involve terminal sterilization or liquid fill/finish.

Recently, we expanded our capability to provide lyophilization cycle development services. Today, we support customers in the early-phase development of this technically challenging pharmaceutical process, providing them with a solution that can be readily transferred and scaled up for commercial manufacturing. 

Long Track Record of Performance

With more than 400 development programs completed, Pii is a leader in pharmaceutical product development. Our scientific team has extensive experience working with drug substances representing a range of physicochemical characteristics (and challenges).  

In 2019 alone, we added three new commercial parenteral products. In March, we launched Busulfan Injection, 6 mg/mL in 10mL vials, in partnership with Athenex Pharmaceuticals, Sungen Pharma, and Chemwerth. In September, Pii announced the commercial supply of Fulvestrant Injection 250 mg/5 ml drug product, which was recently approved by the U.S. FDA. The product is marketed and distributed in the United States by Sagent Pharmaceuticals. In October, Pii received FDA approval of a prior approval supplement for Bretylium Tosylate Injection, USP 500 mg/10 ml (50 mg/ml), which we are producing for ANI Pharmaceuticals, Inc. These diverse manufacturing contracts reflect our wide-ranging capabilities for sterile drug production.

More recently, Pii was recognized with multiple 2020 CMO Leadership Awards as presented by Life Science Leader. These awards — for Compatibility (Big Pharma), Quality (Overall, Big Pharma), Reliability (Overall, Big Pharma), and Service (Overall) — reflect the commitment and accomplishments of our highly skilled personnel and their experience in development and production using our extensive range of innovative technologies. 

Investing for the Future

Meeting the needs of our customers today and into the future also requires continual investment in new technologies and capabilities. Recognizing the growing need for additional sterile fill/finish outsourcing capacity, PII recently expanded our aseptic filling capabilities with the addition of a fully robotic filling line. The GENiSYS R filling machine from Automated Systems of Tacoma, LLC (AST), processes pre-sterilized, ready-to-fill vials, syringes, and cartridges on a single machine specifically designed for small- to medium-scale aseptic manufacturing under cGMP. The highly efficient, flexible, and adaptable line can be used to produce anywhere from a few hundred to 50,000 vials per day.

Integration of proven isolator-barrier and automated technologies provides a balance of flexibility and advanced system features, enabling the processing of aseptic, toxic, and cytotoxic drug products. Automated bag and tub opening, statistical and 100% in-process fill weight verification, and vial capping completely automate the aseptic fill/finish process. Operations downstream can include lyophilizer loading and unloading and vial capping, depending on product and application requirements.

The addition of this automated solution enhances system productivity and controls contamination risk by minimizing operator intervention to the greatest extent possible, while providing unrivaled flexibility for aseptic filling of medium-sized clinical and commercial batches. Pii customers can benefit from the scalability of processes developed for the GENiSYS machine because, as products progress through the clinic, the aseptic filling process can be scaled to larger filling lines with minimal tech transfer. 

​The new line was fully qualified to support vial and syringe operations by the end of Q1 2020, just one year after the initial purchase order was placed. Multiple programs in early- to late-stage development have already been identified as candidates for transition to the new line. 

Future manufacturing capacity expansions for aseptic product development and commercial capabilities are also in the planning stages. An existing solid dose R&D and GMP manufacturing space will be converted to three incremental aseptic manufacturing areas with additional capacity of 15 million doses/unit or 45 million doses annually when operating three shifts per day five days per week. As a result, our total future manufacturing capacity will reach up to 65 million doses annually.

Ready to Partner on Challenging Aseptic Projects

As a CDMO that has had experience developing and manufacturing our own products, we offer our customers the added value of seeing challenges and opportunities from their perspective. This understanding is driving our strategies for the future, which will continue to emphasize the early adoption of advanced technologies and investment in leading-edge solutions, such as the GENiSYS R filling machine.

The actions we are taking today are preparing Pii to successfully manage our growing customer base. With the right combination of people, processes, and geographic distribution and by continuing to leverage our pharmaceutics know-how, extensive experience, and customer service excellence, we will be supporting many more customers with the same high level of competence and service excellence as we do today.

We are particularly excited to embark on projects that make use of our aseptic production capabilities and our fully robotic filling line, including novel therapies and vaccines that target SARS-CoV-2, the virus that causes COVID-19. We wish to engage with customers that are inspired by what we do in the pharmaceutical industry. At Pii, we want to help develop and manufacture products that fill such unmet medical needs and make a real difference in people’s lives

References

1. Global Sterile Injectable Drugs Market Set for Rapid Growth. To Reach Around USD 779.9 Billion By 2024. Rep. Zion Market Research. 2 Jan. 2019. Web. 

2. Sterile Injectable Drugs Market Global Insights. Clinical Aspect and Industry Detailed Analysis Report 2020- Baxter International. Sanofi. Novartis. AstraZeneca. Merck. Market Insight Reports. 2 Apr. 2020. Web. 

3. Global Vaccine Contract Manufacturing Market 2019-2030 by Service Portfolio. Expression System Used. Scale of Operation. Size of Manufacturers. Geography. Research and Markets. 8 Aug. 2019. Web. 

4. Liu, Cindy and William Downey. “Biopharma Contract Fill-and-Finish Market Trends.” Contract Pharma. 6 Mar. 2019. Web. 

5. The Contract Fill / Finish Services Market for Biologics is Anticipated to be Worth USD 4.2 Billion by 2030. Growing at Annnualized Rate of Over 10%. Predicts Roots Analysis. Roots Analysis. 18 Jul. 2019. Web. 

6. Vaccine Contract Manufacturing Market Size, Share and Research Report by 2025. Grand View Research. 1 Nov. 2019. Web.