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Defining expectations, such as GMPs, is paramount for sourcing the right biopharmaceutical raw materials.
For biological molecules to be safe and possess both high quality and efficacy, raw material quality control strategies are of the utmost importance. According to an article published by the Parenteral Drug Association (PDA), to achieve safety, quality, and efficacy, the following must be considered (1):
Assessing supply risk, specifically, can include evaluating raw material availability, secondary options for supply, audits, and contractual agreements, while gauging quality risk may include evaluating consistency between lots, according to the PDA article (1). Raw material quality control strategies are essential to help ensure product quality and mitigate adventitious agent contamination risk (1).
Udo Losehand, head of global technical developers, Roquette—a supplier of biopharmaceutical raw materials—as well as Nate Fillipan, senior specialist, quality assurance; Stephanie Walsh, director, supply chain; and Paul Schildgen, director, manufacturing process optimization, all of Catalent Biologics—a manufacturer of biopharmaceutical raw materials—share with BioPharm International how to determine the quality of raw materials, regulatory requirements to be aware of, supply chain challenges, and what factors must be considered when sourcing raw materials.
BioPharm: What is the general procedure for making raw materials?
Losehand (Roquette): Roquette is vertically integrated, and, therefore, performs every step of the manufacturing process in-house. This starts with the selection of appropriate grains and the extraction of starch, through to the manufacture of a high-quality product via enzymatic processing, hydrogenation, purification, packaging, and release testing.
BioPharm: When a client approaches you for raw materials, what is that process like? Do you provide a consult as to whether specific materials are suitable for the client’s intended purpose?
Losehand (Roquette): Indeed, for every customer request we receive, we evaluate the purpose and intended use of the ingredient in detail. This enables us to identify a product from our portfolio that is fit for purpose.
BioPharm: What testing strategies do you have in place to ensure the quality of raw materials?
Losehand (Roquette): We produce our raw materials according to good manufacturing practice (GMP) guidelines using processes validated for the manufacture of United States Pharmacopeia (USP)-compliant products. A combination of testing specifications for every batch, as well as routinely monitoring key performance indicators, means we can ensure the highest quality ingredients possible.
BioPharm: How can the quality of biopharmaceutical raw materials be determined, specifically if it isn’t suitable for an intended application?
Fillipan (Catalent Biologics): Risk assessment and collaboration with the project sponsor [Catalent’s clients] are necessary for all instances where materials may not be suitable for an intended purpose. Specific use-testing, process development activities, and material qualification can be employed to help justify the use and mitigate risk.
BioPharm: What does GMP mean for your company and its products?
Losehand (Roquette): Excipients play a critical role in the manufacture of medicines, helping to preserve the efficacy, safety, and stability of active pharmaceutical ingredients (APIs). That’s why GMP manufacturing is such a significant part of Roquette Pharma Solutions’ DNA, to ensure each and every one of our customers’ products deliver its promised benefits to patients. Roquette has over 50 years of experience in the manufacture of pharmaceutical raw materials, complying with the appropriate GMP, for instance with ICH Q7 [International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use] for the APIs produced by Roquette (2). Meanwhile, our entire portfolio of biopharma raw materials meets GMP requirements for the International Pharmaceutical Excipients Council Federation’s validation of excipients. Our manufacturing site for biopharma raw materials is registered by the French Health Authority and audited regularly by the various regulatory agencies (e.g., FDA) as well.
BioPharm: GMP can mean different things to different suppliers. How can a company ensure a supplier’s GMP standard meets its bioprocessing needs?
Walsh (Catalent Biologics): From a supply chain perspective, providing our suppliers with clear expectations and regular feedback with regard to the GMP standard is critical to assuring that these suppliers will operate in a manner—and supply products—that will meet our needs. We do this at the site level with our material on-boarding process (including impact assessment), material specification process, and supplier complaint process. At the corporate level, expectation-setting and feedback are facilitated through supplier-relationship management (SRM) programs and the global supplier quality management audit process.
BioPharm: When deciding where to source raw materials and what suppliers to work with, what factors must be considered? What could constitute an automatic pass for select raw materials?
Schildgen (Catalent Biologics): Biopharmaceutical manufacturing now includes single-use consumables, which make up the majority of raw materials. Single-use consumables and equipment technologies are interdependent, and identifying a supplier means looking at the capability, reliability, and compliance of both the equipment and supporting consumables.
Fillipan (Catalent Biologics): Generally, for other materials, the highest grade with the most appropriate compendial label claims is often the most desirable. Materials that are sold as research-grade are often much harder to justify because they may not have appropriate controls to prevent ingress of adventitious agents, may lack transparency to the original manufacturer, or are unsupported by change management, which would complicate their use.
Walsh (Catalent Biologics): Normally, we also prefer to purchase directly from the manufacturer of a raw material or consumable. If we end up having to source from a distributor, transparency, with regard to the actual manufacturer, is paramount, as is the ability of the distributor (and manufacturer) to deploy rigorous change controls on the products that they distribute (or manufacture). A major factor in our decision to appoint a new supplier is our routine material impact assessment.
BioPharm: What regulatory requirements do you have to be mindful of when supplying raw materials?
Losehand (Roquette): Alongside GMP manufacturing and compliance with the standard monographs from the USP, Roquette ensures that additional requirements, specific to the needs of the biopharmaceutical manufacturing process, are met. This includes low endotoxin levels as well as the absence of relevant organic impurities, controlled bioburden, and more.
BioPharm: Describe the difference between raw materials standards in the United States vs. globally.
Losehand (Roquette): Typically, regulations for different regions are set by individual medical agencies. For example, the European Medicines Agency in the European Union or FDA in the US. Differences amongst such regulations are largely historical and stem from different manufacturing or quality standards. In recent years, thanks to the ICH program, significant steps have been initiated to standardize monographs as well as analytical methods (3).
BioPharm: What supply chain concerns are present for sourcing raw materials?
Losehand (Roquette): Roquette reduces the potential risk of a fragmented supply chain via its vertical integration, through which we can control every step of the manufacturing process of our biopharma raw materials in-house. In addition, close collaboration with our customers and a global distribution network, with the potential for local stock-keeping, further reduces the risk of a supply chain disruption.
Schildgen (Catalent Biologics): Critical biopharmaceutical raw materials are often proprietary and single-sourced. An effective sales and operations planning process drives appropriate mitigations to any potential supply-chain risks. Managing a reliable supply chain during extreme market volatility is also a critical concern. Keys to success in these challenging times are regular communication to raise awareness, transparency (both internally and externally), adaptive replenishment models, and operational flexibility.
Walsh (Catalent Biologics): Effective and adaptive SRM programs, which include executive-level participation from both the supplier and the customer, where materials are single-sourced are also a means of mitigating potential supply chain challenges. Regular reviews and, if necessary, rapid adjustment to replenishment models are further mitigating actions. With regard to the need for flexibility, I would say that includes actively deploying backup sources of supply or working with what materials are available, versus those in constrained supply. Good internal communications, to raise awareness of situations, can further reduce risks. These should span all functional areas, with customer-facing functions, and even with customers themselves.
Constant and effective communication is necessary for every step of the process for sourcing biopharmaceutical raw materials, along with being aware of GMP guidelines as well as other guidelines (e.g., ICH) and regulatory expectations for different regions. While single-sourced biopharmaceutical raw materials can present supply chain challenges, adaptive replenishment models, operational flexibility, and general flexibility can help to mitigate these risks. But before all of this, it’s important for manufacturers and suppliers to carefully assess the capability, reliability, and compliance of both the equipment and supporting single-use consumables. As in most things in life, communication and upfront research are key.
Meg Rivers is a senior editor for Pharmaceutical Technology, Pharmaceutical Technology Europe, and BioPharm International.
Volume 34, Number 12
When referring to this article, please cite it as M. Rivers, "Ensuring Quality When Sourcing Biopharmaceutical Raw Materials," BioPharm International 34 (12) 2021.