Formulation and Development Considerations for Biologics

As the numbers of biologics in development continue to rise, it is becoming ever more pressing to fully comprehend the potential issues with primary packaging, the optimal route of development, and how to create a patient-centric solution to ensure market success. To understand more about how drug development approaches, primary packaging choices, and regulations impact injectable biologics developers, Pharmaceutical Technology spoke with Janina Lehmann, senior director, Technical Customer Support, North America & Europe at West Pharmaceutical Services.

Important considerations

PharmTech: What are the major formulation and development considerations for biologics?

Lehmann(West): In drug development, the molecule defines the dosage form. The number of biological therapies in development has continuously risen throughout the past few years, and as a result the subsequent complexity from longer-acting formulations, larger injection volumes, and longer injection durations has also increased. The quality and efficacy of a protein-based drug product formulation strongly depends on the compatibility with the primary container. Therefore, a good understanding of the physicochemical properties of the primary packaging material and validation of its suitability for use is necessary. 

Generally speaking, maintaining drug product quality, efficacy, and safety over shelf-life is pivotal when approaching biologics formulation. Protein-based drug product formulations in particular pose new challenges to primary packaging. Therefore, developing an effective protein-based drug product formulation requires comprehensive compatibility testing of the primary packaging. This includes testing of extractables and leachables, as well as elemental impurities. 

Large biomolecules tend to form aggregates under certain storage and transportation conditions; analyzing the interaction of the drug product and container surface under these conditions is recommended. Foreign particulates present in the drug product (e.g., silicone oil) can also cause protein aggregation or adsorption. Using qualified packaging materials that meet compendial standards minimizes the quality risk. 

Additionally, the viscosity and injection volume of protein-based drug formulations have an impact on the design of an injection device. There are various self-injectors and wearable injectors available that increase patient and healthcare professional convenience in the administration of high-volume and viscous injectable drug products.

Patient-centricity

PharmTech: How important is a patient-centric approach to developing injectables, and are there any noticeable trends occurring in the industry?

Lehmann(West): Understanding patient needs is essential to the pharmaceutical quality-by-design (QbD) concept. QbD is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and control based on sound science and quality risk management. To ensure that quality and design of a combination product meet patient needs, critical quality attributes (CQAs) and essential performance requirements (EPRs) must be defined. 

The increasing trend of patient self-medication, and the increasing number of biological therapies (including gene and cell therapies), are driving innovation in containment and delivery systems for injectable drug products. Self-injectors and wearable injectors increase patient convenience and patient adherence. Increasing the availability of smart, connected devices, likewise improves healthcare decision-making and better patient outcome.  

Regulatory reflections

PharmTech: Could you highlight some of the most important regulatory considerations that impact the injectable drug dosage form decision during formulation and development?
Lehmann(West): Injectable drug products, like any pharmaceutical dosage form, must meet the pharmaceutical quality standards as described in pharmacopeias, and be safe for the intended purpose of use. Likewise, they are required to be free from viable microorganisms, pyrogenic substances, and visible particulates over the product shelf-life. 

A main challenge for injectable drug products is to achieve good compatibility with the primary container. High-quality container closure systems that meet regulatory requirements reduce the risk of leachables and adsorption and provide container closure integrity. 

New regulations, such as the 2020 Annex I, EU MDR in Europe, are increasingly focusing on quality risk management in developing and manufacturing sterile drug products and injectable devices. Selecting high-quality drug packaging will reduce quality risks and minimize total cost of ownership.

Benefits of collaboration

PharmTech: How can companies benefit from employing an outsourced partner for formulation and development of injectable drug dosage forms? 

Lehmann(West): For development of injectable drug dosage forms, pharmaceutical companies will benefit from employing an outsourced partner that understands primary packaging and devices, analytical and regulatory requirements, and the drug development process. If a drug manufacturer collaborates with a packaging supplier early on in the development process that can prove beneficial. The packaging technology partner can reduce the development risks by demonstrating the packaging system suitability for its intended use early in drug development. Later in drug development, the packaging partner can help to generate compatibility and performance verification data to support the drug manufacturer’s regulatory submission. 

Partners should provide integrated solutions for pre-screen, compatibility, and clinical phases I, II, and III. Essentially, partnering should simplify the pharmaceutical company’s journey from molecule to market by reducing development and supply risk, minimizing total cost of ownership, accelerating path to market, and improving the patient experience. 

Experts from West Pharmaceutical Services will be available to discuss this topic and more during CPhI Worldwide in Frankfurt, Germany from Nov. 5–7, 2019-Hall 11.1 Stand 111F62.