CDMO eBook

Strategies to Streamline & Optimize Formulation

Health Inspired, Quality Driven.

Table of Content

Introduction Chapter 1: The benefits of working with a CDMO Chapter 2: Pitfalls in formulation development Chapter 3: Finding the right dosage form for your API Chapter 4: Pros and cons of early formulation

01 02

Introduction

this risk. Possibly the most critical point that a CDMO can enter the product development cycle to add value is the formulation phase. In this e-Book, we will detail ways in which working with an experienced CDMO can help you streamline and optimize your formulation process. • Chapter 1: The benefits of working with a CDMO • Chapter 2: Pitfalls in formulation development • Chapter 3: Finding the right dosage form for your API • Chapter 4: Pros and cons of early formulation – coming soon

There is a great deal of risk associated with developing and launching a successful drug product. Some pharma and biopharma companies may not have access to the specialized expertise, in-depth regulatory knowledge, or sufficient funding for capital equipment required to successfully bring an innovative, new product from development to market in house. Contract development and manufacturing organizations (CDMOs) support drug development companies with outsourcing solutions to help bring products to market faster, more efficiently and cost-effectively. These services can range from formulation development and analytical testing to clinical trial and commercial manufacturing. Working with an experienced CDMO can provide many benefits that help pharmaceutical companies reduce

Chapter 1: The Benefits of Working with a CDMO

production needs or are launching new products. • SGS Quay Pharma offers drug product development services in the small molecule and microbiome spaces, from early phase discovery through to niche scale commercial manufacturing. We work with a variety of dosage forms including oral liquids, solid oral doses, topicals and more in both the small molecule and microbiome spaces. INCREASED EFFICIENCY AND COST SAVINGS: By partnering with a CDMO, a company can access the resources and expertise they need without having to invest in them themselves. This can lead to increased efficiency and cost savings for the company. For SMEs and start-up companies, the benefits provided by CDMOs can be pivotal in supporting the growth and progress of a business. • SGS Quay Pharma provides scalability, expertise and facilities for our clients, which mean there is no need

Working with an experienced CDMO can provide many benefits that help pharmaceutical companies reduce this risk, also while accelerating timelines. These benefits include: ACCESS TO SPECIALIZED EXPERTISE AND EQUIPMENT: CDMOs often have specialized expertise and equipment that a company may not have in-house. This can include expertise in specific drug development and manufacturing techniques, as well as specialized equipment for producing and testing drug products. • SGS Quay Pharma has more than 20 years of experience with formulation development and has supported a plethora of products through both the clinical and commercial phases of development. FLEXIBILITY AND SCALABILITY: CDMOs can provide a flexible and scalable solution for a company's drug development and manufacturing needs. This can be especially useful for companies that have fluctuating

SPEED TO MARKET: A qualified CDMO can help drug companies accelerate their timelines to market, which can be especially important in highly competitive markets. • SGS Quay Pharma has the experience and resources to help companies bring their products to market quickly with our comprehensive service offering from formulation to manufacturing, as well as our access to specialized expertise, state-of-the-art equipment and deep regulatory knowledge.

for a client to endure the process of commissioning and qualifying both the necessary facilities and equipment. This also delivers considerable risk mitigation as the usual sizable upfront investment at the early stages of drug development is not required. REDUCED REGULATORY BURDEN: The regulatory landscape is constantly changing with new regulations and increasing complexities. An experienced CDMO can support a company by navigating the complex regulatory landscape associated with drug development and manufacturing. • SGS Quay Pharma continuously monitors the regulatory landscape and is actively involved in industry groups, forums and regulatory committees that drive and define these regulations. With this knowledge and insight, our team can assist clients in understanding and implementing any changes in regulations that may impact their products.

How SGS Quay Pharma Can Help

Our comprehensive, flexible range of services enables with state-of-the-art instrumentation to help clients bring drug products through the various stages of clinical development; from pre-formulation work to formulation, dosage form design and optimization. Through our global network of laboratories and clinical trial facilities, we offer integrated services and expertise that provide knowledge, flexibility and ability to scale.

Chapter 2: Pitfalls in Formulation Development

FAILURE TO CONSIDER THE INTENDED ROUTE OF ADMINISTRATION CAN NEGATIVELY IMPACT THE API'S STABILITY AND SOLUBILITY Carefully considering the intended route of administration and its effects on the API's stability and solubility and selecting appropriate excipients accordingly. SGS Quay Pharma provide cost-effective screening platforms using solvents and/or excipients that are tailored to each API, considering key aspects such as indication, route of administration and intended species. We include PK assessments in the service, enabling formulation comparisons and PK/dose prediction modelling in our pre-clinical services. INADEQUATE TESTING OF THE FORMULATION'S STABILITY AND COMPATIBILITY WITH OTHER INGREDIENTS CAN LEAD TO EXCIPIENT INTERACTIONS OR DEGRADATION OF THE API Thoroughly testing the formulation's stability and compatibility with other ingredients via excipient

There are several potential pitfalls in finished product development that if not addressed during the formulation process, can lead to costly delays in product launch, including: INSUFFICIENT CHARACTERIZATION OF THE ACTIVE PHARMACEUTICAL INGREDIENT (API) CAN LEAD TO POOR STABILITY AND BIOAVAILABILITY OF THE API IN THE FINAL FORMULATION. Thoroughly characterizing the physicochemical properties of your key starting materials, excipients and finished products is vital when making decisions regarding processing equipment, packaging materials and environmental conditions. Adequate quantitative and qualitative testing methods provides a baseline to work from to inform the drug product development process. Without this deep knowledge there can be a significant impact on efficacious dosage form and/or long-term drug performance.

process validation to ensure consistency and quality of the final product is key when reaching the later stages of development prior to commercialization. During the development stages we will work to assess an appropriate scale for clinical manufacturing and make recommendations on process development strategies. INADEQUATE PACKAGING AND STORAGE CONDITIONS CAN CAUSE INSTABILITY AND DEGRADATION OF THE API. Failure to think about the packaging suitability can lead to overprocessing during clinical trials as well as poor patient compliance. Selecting appropriate packaging that takes into consideration the end patient population, trial logistics and the commercial product goal is key. Appropriate selection of storage conditions via adequate stability data ensures robustness of the API increasing the longevity of clinical supplies.

compatibility, forced degradation studies and accelerated stability testing. At SGS Quay Pharma, our work is supported by access to the latest technologies, and all prototype formulations are subject to in-depth screening and stability evaluation in a non-GMP environment. LACK OF REGULATORY COMPLIANCE CAN RESULT IN DELAYS OR REJECTION OF THE FORMULATION DURING THE APPROVAL PROCESS. Ensuring regulatory compliance by following current good manufacturing practices (cGMPs) and consulting with regulatory authorities as needed is key to delivering safe and effective products to patients. FAILURE TO CONSIDER MANUFACTURE PROCESSING & SCALE-UP ASPECTS CAN LEAD TO VARIATIONS IN THE FINAL PRODUCT AND POTENTIAL SAFETY RISKS. Using a Quality by Design (QbD) approach during the development stages minimizes risk, improves quality and looks to increase efficiency while in the product development phase. With advanced facilities and in-house analytics, we provide a framework to enable effortless scaling-up of products for clinical manufacturing beyond phase I. Performing robust

How SGS Quay Pharma Can Help

SGS Quay Pharma has more than 20 years of experience with formulation development and has supported a plethora of products through both the clinical and commercial phases of development. Our consultative and collaborative approach to product formulation helps clients streamline this step in the process to keep projects on track to reach markets quickly and safely. Through extensive experience, SGS Quay Pharma has developed our own robust risk mitigation strategy that is imbedded in our development, manufacturing and quality process to address and resolve these challenges and help clients optimize their product pipeline.

Chapter 3: Which Dosage Form is Right for Your API?

• The appropriate dosage form for an active pharmaceutical ingredient (API) depends on several factors, including the properties of the API, the desired route of administration, and the desired release profile. Some common dosage forms include tablets, capsules, oral solutions, injectables, and transdermal patches. A formulation scientist or a pharmaceutical development team can assist in determining the most appropriate dosage form for a specific API. • Active Pharmaceutical Ingredients (API) can be formulated into various dosage forms for administration. Some of the most conventional include: • Tablets: solid dosage forms that can be taken orally • Capsules: oral dosage forms that contain a powder or granular material within a small, generally hard shell • Solutions: liquid dosage forms that can be taken orally or administered intravenously

• Suspensions: liquid dosage forms that contain insoluble particles suspended in a liquid • Emulsions: liquid dosage forms that contain two immiscible liquids, such as oil and water, that are emulsified to form a homogeneous mixture • Creams and ointments: topical dosage forms that are applied to the skin There are many other forms, such as injections, inhalers, transdermal patches, suppositories, pessaries etc. Finding the correct dosage form for an Active Pharmaceutical Ingredient (API) is critical because it directly affects the safety and efficacy of the drug; yet identifying the most suitable method of administration is complex due to several factors, including: • Properties of the API

• Properties of the dosage form • Desired route of administration • Intended patient population

• Desired release profile • Storage requirements Different dosage forms, such as tablets, capsules, injections, and topical creams, have different properties that can affect how the drug is absorbed, distributed, metabolized, and excreted by the body. It is also important to consider factors such as the intended patient population, route of administration, and storage requirements when selecting the appropriate dosage form. Ultimately, the goal is to find a dosage form that effectively delivers the API to its site of action while minimizing any potential side effects and therefore, all of these factors must be considered carefully and thoroughly.

How SGS Quay Pharma Can Help

SGS Quay Pharma has considerable experience in the development and manufacture of safe, robust conventional dosage forms including tablets, capsules, oral liquids and topical products. We are also used to working with formulations developed by clients or other contract manufacturers, and either optimizing them or simply providing manufacturing support. Where a substance shows particular solubility or bioavailability challenges, we can draw on a wide choice of innovative technologies to overcome the barriers to clinical progress. We can also provide a range of effective modified release technologies.

Chapter 4: The Pros and Cons of Early Formulation Development

programme. By identifying challenges early, companies can save money by avoiding costly formulation changes or even complete product failure later in the development process. • Improved drug performance: An optimized formulation can help improve the drug's therapeutic performance, such as increasing its bioavailability, stability, or patient compliance, resulting in better patient outcomes. • Intellectual property protection: Early formulation development activities can help establish data to support patent protection for the drug product, which is an essential consideration for the long-term viability/commercialisation of a drug product. • Time savings: An optimized/enabled formulation can help speed up the transition between early clinical phases, which ultimately reduces the duration to regulatory approval and the timeframe for return on investment.

Formulation development activities are an essential step in the drug product development process, where the initial formulation is designed and optimized to achieve the desired drug product characteristics. In many cases, it is ideal to perform the formulation step early in the development process; however, it is essential to carefully consider the potential challenges and limitations associated with early formulation development to ensure that it is done efficiently and effectively. Some potential pros and cons of early formulation development include: PROS: • Cost savings: Performing formulation development activities early (particularly pre-formulation studies) can help identify potential challenges with the drug substance such as stability, solubility and permeability (bioavailability). This data allows pharmaceutical companies to design an approach to achieve an optimal formulation for administration, enabling these challenges to be overcome early in the development

CONS: • Resources: Formulation development activities require investment in time, equipment, and expertise, which may be a challenge for small pharmaceutical companies or start-ups, where these factors are not available in-house. • Drug Substance supply: Sufficient quantities of drug substance are necessary to perform the required formulation development activities. The associated cost of the drug substance must be factored into programme budgets. • Unexpected issues: Even with well-designed formulation development activities performed early in a programme to mitigate programme risk, still may result in unexpected issues during the later stages of development, which may require additional formulation/process changes which can impact upon programme timelines. Overall, the pros of performing formulation development activities early in a programme may well outweigh the cons. and if done correctly, will optimize the performance of the drug and ultimately save time and money.

WHEN SHOULD YOU PERFORM FORMULATION DEVELOPMENT ACTIVITIES?

WHEN EARLY FORMULATION DEVELOPMENT IS NOT A FEASIBLE PATH? While formulation development activities are an essential step in drug development, there may be certain situations where it may not be necessary or advisable to perform. Some scenarios where early formulation development may not be appropriate include: • For compound with suitable physicochemical characteristics: Where a compound exhibits studies rather than using simple extemporaneously prepared dosing strategies, can improve clinical outcomes, reduce clinical timelines and provide an earlier insight into commercial considerations such as product cost of goods and process train requirements for scale up. In general, early formulation development activities are part of an iterative process, with regular data evaluations and product modifications as necessary, based upon clinical findings, stability data and refinement of the target product profile throughout a development programme. The goal is to achieve a stable, effective, and safe drug product that can be manufactured consistently and meets regulatory requirements.

Formulation development activities should ideally be performed as early as possible in the drug development process; typically in the preclinical phase, after the lead compound has been identified and characterized for its physicochemical properties. Some key stages of drug development when early formulation development can be performed include: • Following lead compound optimization: Once a lead compound (drug substance) has been identified, early formulation development can be initiated to design the formulation to overcome the challenges associated with the drug substance for improved drug delivery, stability, and efficacy. • Preclinical development: During the preclinical phase, early formulation development can aid dose delivery for toxicology studies and support PK modelling for determination of starting dose and route of administration when considering first in human (FIH) studies. The data gained from these formulations can help to assess the stability of the drug substance/product and identify potential issues with bioavailability and toxicity. • Phase I Clinical development: Performing formulation development activities to support FIH

favourable physicochemical characteristics, enabling formulations may not be necessary to achieve desired clinical outcomes. In this instance simple dosing strategies may be employed in the clinical without the need for extensive formulation development activities to support early clinical evaluation. • Short term clinical focus: Where the strategy of a company is to achieve limited early clinical data (such as safety/tolerability and dose escalation) prior to selling an asset or requiring such data to support further funding requirements, extensive formulation development may not be appropriate. In general, formulation development activities should be performed as early as possible in the drug development process to optimize the efficacy, safety, and stability of the drug product. However, in certain situations where companies need to reach end of Phase I milestones quickly for commercial reasons the strategy adopted for clinical dosing should be considered carefully to marry cost/time/risk against milestone aims.

How SGS Quay Pharma Can Help

With 20 years of experience performing early formulation and associated product development activities for new chemical entities, biologicals, and live biotherapeutics, SGS Quay Pharma has the specialized expertise and equipment needed to successfully support early formulation development. We help clients identify physiochemical properties in the early stages, provide multiple formulation options, and successfully troubleshoot the most challenging formulations.

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