Journey of an API: Maintaining quality and compliance in API manufacturing

Every stage of an active pharmaceutical ingredient’s (API) journey is unified by a single, overarching objective: quality. While analytical method development, engineering, production, hazard evaluation, and other aspects of API development and manufacturing each come with their own unique goals and success metrics, all components are ultimately focused on developing a product that is safe, effective, and high-quality.

In this blog, we’ll examine quality control (QC) and quality assurance (QA) more closely, defining key goals, success measures, obstacles, and strategies for success.

QC and QA teams are inherently focused on ensuring product and project quality. However, there are several dimensions of quality, and some are far easier to measure than others. Here, we explore these elements in detail:

Quality is assessed against rigorous benchmarks that are critical for the safety and efficacy of APIs. These benchmarks often include specifications for purity, potency and stability, tailored to the API’s therapeutic use. For instance, quality teams might establish a specification of no less than 99.8% purity for the final API using advanced chromatographic techniques, like ultra-performance liquid chromatography (UPLC). Also, quality standards extend beyond purity, considering the API’s performance long after it leaves the facility. For example, stability testing under accelerated conditions ensures the API will maintain its quality attributes throughout its shelf life. No matter the project, skilled QA and QC teams will define the precise standards required by the API and the methodologies required to measure them, ensuring each product is carefully managed from a quality point of view as it moves through the lifecycle.

How it’s measured:

Quality standards are measured using advanced analytical techniques and statistical process control. High-performance liquid chromatography (HPLC) or gas chromatography (GC) can be used to determine the purity and potency of compounds. In addition to evaluating these values at the batch level, quality teams should also consider the percentage of batches that meet exacting standards to affirm that the process is consistently generating high-quality results.

In-process monitoring is a critical method for evaluating quality metrics continuously throughout the manufacturing process. Quality control teams employ in-process testing to monitor critical process parameters such as water content, pH and reaction completion, ensuring they remain within specified limits.

Regulatory compliance is achieved through meticulous adherence to standards such as ICH Q7 and current Good Manufacturing Practice (cGMP). This includes detailed control of the manufacturing process from raw material qualification to final API release. In many cases, regulatory standards inform and overlap with internal quality standards, creating synergy between the two functions. It is important to remember that regional regulatory standards can vary widely, and the QA and QC teams play an important role in navigating the variance between regional standards to shape and uphold a global quality standard. By implementing a Quality by Design (QbD) framework, an organisation can carefully identify and control the variables that affect the API’s quality, ensuring consistent compliance with global regulatory expectations.

How it’s measured:

Regulatory compliance is assessed through detailed documentation reviews, validation of analytical methods, and regular audits. Compliance teams maintain comprehensive records of each manufacturing step to ensure alignment with guidelines from authorities like the FDA, EMA and ICH. Method validation reports are crucial as they demonstrate the analytical accuracy and reproducibility necessary for regulatory submissions. Additional measures include ensuring that all quality-related deviations are thoroughly investigated and resolved, maintaining an effective change control system to manage any changes in the manufacturing process, and conducting regular risk assessments to pre-emptively address potential compliance issues. Regular training programmes for staff also support compliance by ensuring that all personnel are updated on the latest regulatory standards and practices.

While customer satisfaction is a key objective for all teams involved in API development, it holds particular importance for QA and QC teams who often serve as a primary point of contact with customers. These teams play a crucial role in preparing for customer audits, ensuring that documentation and processes not only meet but exceed customer expectations. They are also instrumental in aligning documentation review methodologies and quality standards to cater specifically to the needs and requirements of each customer.

How it’s measured:

While customer satisfaction is often qualitatively assessed, it can also be quantitatively measured through several key indicators. These include the frequency of audits and the timeliness of their resolution, which is a key indicator of the responsiveness and success of QA. In addition, the results of customer audits provide direct feedback on the adequacy and effectiveness of the quality systems in place. Once an API makes its way into the market, post-market surveillance data offers insights into the long-term satisfaction and trust in the API’s quality, indicating how well the product performs in the field and meets the therapeutic needs. Additionally, regular feedback sessions with customers can help QA better understand their evolving needs and refine processes accordingly.

QC and QA teams can face a variety of roadblocks as they work towards their primary objectives, and these hurdles can vary based on the stage of development. Below, we summarise a few of the most common ones.

Processes can change quickly as an API makes its way through development, particularly early on when scalability issues are most likely to surface. A seasoned quality team plays a pivotal role in ensuring that any process changes are properly anticipated, adopted, documented, and reviewed by the customer, all while keeping the project on track. Having an experienced quality team available around the clock and maintaining tight communication loops with customers, enables the quality team to expedite review rounds and avoid significant impacts to project timelines.

The quality team must balance many moving pieces and coordinate across a multitude of stakeholders who contribute to a project’s success. This includes internal project teams, raw material suppliers, and regulatory agencies. For example, when onboarding raw material suppliers, the quality team must ensure that the supplier’s standards meet the project’s quality requirements and that all documentation, such as certificates of analysis, are obtained, reviewed, and vetted for accuracy. When dealing with regulatory agencies, the team must stay updated on the latest requirements and ensure compliance across different regions where the customer may want to market their product. Building strong working relationships with agencies and suppliers can help streamline the process, ensuring that the project maintains high quality and meets regulatory standards from procurement to final product.

Customer expectations and preferences can vary widely based on their size, background, and specific needs. Quality teams are responsible for providing guidance and understanding each customer’s preferred working style. For instance, some customers may prefer to be heavily involved in every step of the documentation review process, while others might only want to engage at key milestones. Adapting work styles to match customer preferences, keeping them informed of any potential changes, and ensuring projects remain on time are critical tasks. Establishing a direct line of communication from project inception and maintaining regular updates can help quality align with customer priorities and manage their expectations effectively.

Quality extends across all stages and components of an API’s journey to market, making a proven and thorough approach to quality imperative. But in addition to the role of QA and QC teams, it is important to note that quality must be considered from multiple perspectives and across multiple teams—from procurement and supply chain optimisation to analytical methods, to the setup of plant-scale manufacturing to equipment maintenance, process optimisation, and more. Through seeking a development and manufacturing partner that has not only demonstrated its commitment to quality through consistently exceptional delivery, but also continues to prioritise a culture of quality across every team, pharmaceutical organisations will maximise project efficiency and success.

At Sterling, our quality teams play an important role across the entire API lifecycle to affirm that the highest standards are consistently upheld. With tightly integrated quality teams, strong relationships with regulatory agencies and raw material suppliers, and an outstanding track record bringing high-quality products to market, we prioritise quality in every aspect of the project lifecycle. Quality is central to everything we do—from our facilities and equipment to the members of our team, to the way we collaborate with our customers, and much more.

If you’re interested in learning more about how we put quality first in our customers’ projects, contact us to speak to an expert or visit our Knowledge Hub to learn more.