Challenges in Securing the Biopharma Supply Chain
To gain insight on the unique challenges of securing the supply chain for biopharmaceuticals, BioPharm International spoke with Manja Bouman, president, BIO at Patheon and Susan Schniepp, vice-president Quality Regulatory Affairs at Allergy Laboratories about the management of the biopharmaceutical supply chain.
Biopharma Supply Chain Challenges
Schniepp (Allergy Laboratories): There are a number of challenges facing biopharmaceutical companies with respect to managing their supply chain. Today’s supply chain is quite complex and involves transport of ingredients and final product through multiple countries and touch points. Biopharmaceutical companies must understand the culture and dynamics in multiple regions in order to protect their product from theft, diversion, and counterfeiting. Understanding and managing the complexity of their supply chain is probably the biggest challenge facing companies today.
Bouman (Patheon): Lead time for production consumables and materials can be several weeks to months for some custom-made cell culture media. Lead time to manufacture, test, and release a biopharmaceutical drug substance typically takes 15-20 weeks from initiation of batch manufacturing to release of an drug substance for filling. Drug substances and finished biopharmaceuticals are typically cold chain, and there are risks of temperature deviations during transport. The supply chain will likely involve multiple parties and providers so there is a inherent complexity, resulting in a need for planning and project management.
Multiple quality agreements and manufacturing agreements are in place, [and it is] highly desirable to align these requirements and combine all activities as much as possible. For example, have the drug substance manufacturer and final dosage manufacturer in one agreement and under one project manager. Contractors need to be flexible and able to address needs of customers, such as shifting timelines due to delays in other areas of the manufacturing chain, for example.
Bouman (Patheon): The specific steps are essentially around cGMP compliance but with special attention to mitigating cross-contamination risks in a multi-product environment. [There should be] a fully defined supply chain and agreement on how and when product moves from supplier A to supplier B. [Companies should] try to build in flexibility [and have] excellent planning, including risk mitigation and ‘what if’ scenario planning.
Schniepp (Allergy Laboratories): At the recent PDA/FDA/Rx360 conference on the Pharmaceutical Supply Chain (Expanding Your Quality System [Q10] for a Robust, Reliable, and Secure Supply Chain), there were a number of suggestions for protecting products that were offered to attendees, among which were tracking and tracing devices, bar coding of product, hiring of firms that monitor the product and raw materials through shipment. Of all the suggestions offered, the one endorsed the most frequently was that companies needed to accurately map their supply chain and identify the areas where the greatest risk could occur. Once the supply chain is accurately mapped and risks identified, the next step is to try and mitigate the identified risks. If done correctly, the supply chain mapping identifies all the transfer points in the supply chain. It is most often at these transfer points where the product is most vulnerable of being stolen. Bottom line, creating and maintaining a detailed mapping of your supply chain is paramount to understanding your vulnerabilities. When you understand your vulnerabilities you can take steps to mitigate them.
Bouman (Patheon): [Companies should] implement a rigorous supplier qualification and requalification process [and] develop and scale-up GMP compliant manufacturing bioprocesses. Particular attention should be paid to minimizing process variability and exclusion of extraneous agents. [Companies should] validate the supply chain, particularly cold-chain and frozen-chain components; safety, integrity and security of drug product shipments through validation and constant monitoring post-validation. Conduct thorough FMEA on all aspects of the supply chain through from DS/API to shipment to clinic/pharmacy. Involve contractors in this exercise. Identify potential weak points and establish mitigation strategies. Where feasible, establish second suppliers. Manage contractor-contractor to contractor interface closely. Be proactive as far as possible with the issues.
Schniepp (Allergy Laboratories): There were a number of suggestions made [at the 2014 PDA/FDA/Rx360 supply chain conference] for maintaining the security and integrity of the supply chain, but one recommendation stood out as number one: know who you are doing business with. All of the speakers agreed that knowing who you are doing business with is essential to securing the supply chain. They recommended facility audits and personal visits to your product transporters to establish a business relationship and an understanding about expectations for securing the product. They also recommended having a single point of contact, if possible. It was the majority opinion that nothing takes the place of a good working business relationship. When a relationship is open and trusting, the communication is meaningful and immediate because both parties have a vested interest in the outcome.
This [relationship] is critical when dealing with theft and diversion of biopharmaceutical products. The sooner the carrier/supplier informs the client of a shipping problem the sooner the situation can be resolved. The immediacy with which this is done can be enhanced by the established relationship.
Globalization of the Supply Chain
Schniepp (Allergy Laboratories): The globalization of the industry has complicated the supply chain. The materials and APIs that used to be sourced domestically are now sourced from foreign suppliers. The handoffs of materials and product to get to the final user have dramatically increased in the past 10 to 15 years. The industry has had to understand and communicate with different cultures in order to transport their products safely across the globe. In a way, this globalization has forced companies to think about the safety of their products in a new and completely different way. Now that this has happened the industry can expect to see a more secure supply chain and a more efficient importation process that guarantees safe and effective medicines to the patients.
Bouman (Patheon): Globalization has encouraged the development of dual-sourcing of biopharmaceuticals and improved security of supply. Biosimilars and biobetters are now a possibility in some markets due to globalization. Globalization presents increased security and safety risks to shipments, some of which require lengthy and complex international supply routes. [Globalization has] introduced a geographical challenge with regards to logistics and forced the establishment of, for example, shipping/logistics solutions to suit [those] geographies.
Bouman (Patheon): Collaboration and security are critical in maintaining the integrity of supply chains and ultimately the safety and efficacy of any medicinal product. Companies have to balance transparency with the need for safety and security of the supply chain. To ensure transparency, companies should document and disclose adverse events. The effectiveness of corrective and preventative actions should also be available to regulators.
Delivering Drugs Safely to Patients
Schniepp (Allergy Laboratories): Companies need to watch Internet pharmacy sales and make sure the product being sold at a discount on these sites is, in fact, legitimate. In addition, it is important to try and make sure pharmacies are aware when there is a potential for counterfeit or stolen material to enter back into trade. Companies need to provide the lot numbers of stolen product to pharmacies so the pharmacists can prevent the medicine from reaching the patients.
There is no guarantee that the product has been stored under the proper conditions which makes it unsafe to take.
Bouman (Patheon): The main challenges are ensuring the product quality and integrity is not adversely affected by the distribution and storage on route to the patient. Companies should thoroughly risk assess the entire supply chain from factory gates to patients. Companies should consider security and integrity risks to shipments globally as part of their risk mitigation measures. Distribution companies should validate the supply chain from the factory gates all the way to the patient including considerations for worst-case environmental conditions.