In the ongoing battle to cut costs while delivering quality and technically sound product, the biotech industry has spent the past two decades gradually moving toward single-use pre-sterilized plastic equipment for both clinical batch and, where applicable, production scale manufacturing. Single-use process equipment can be used and then disposed of, eliminating the development time to validate the sterilization and in-facility sterilization downtime, as well as development time to qualify and verify the cleaning and commensurate cleaning downtime. Reducing time to market by eliminating process validation steps, and eliminating downtime needed to conduct these process steps between batches, is key to an economically productive way of working. Biotech and pharmaceutical companies now recognize that single-use plastic equipment, as opposed to traditional stainless steel equipment, is an economic benefit. Single-use equipment offers cost savings in development and manufacturing as well as in facility operations.
As with any paradigm shift, there are new issues that must be addressed. One such issue with single-use equipment is that consumers are concerned about chemicals that might leach out of the plastics into the drugs. While this has always been a concern with plastic membrane filters, tubing, gaskets, etc., the use of plastic bags for liquid storage has elevated the concern. Now that more contact surfaces are plastic polymers and contact time may be longer with storage, there is a lot of uncertainty about chemical leachables, as polymers can have a variety of additives in their formulation to optimize their properties.
From a regulatory perspective, the onus to establish suitability of process equipment is on the drug manufacturer (pharmaceutical manufacturing equipment is not regulated by drug authorities, only their use by the drug manufacturers). Good manufacturing practices (GMPs) and the Food and Drug Administration (FDA) hold the drug manufacturer responsible for proving that any materials that contact the drug in manufacturing are safe and don’t adversely affect the drug or the patient. Thanks to appropriate material selection and qualification by equipment manufacturers, there isn’t much evidence that sterilized plastic materials for process equipment are dangerous (risk factors are much less than with final dosage containers). However, newness breeds doubt, and safety must be verified. Pharmaceutical companies can lessen their distress by testing their selected equipment materials, but without a lot of experience, it’s hard to know if the FDA is going to accept self-validation.
Thus, drug manufacturers would prefer and have begun to request that equipment suppliers do much of the initial qualification testing for extractable materials. Assisting customers in their validation of the equipment and providing materials knowledge, technical support, and documentation is something that suppliers can do to reduce drug development time and cost of regulatory approval — and therefore potentially the cost of the drug. It is the pharmaceutical industry’s belief that it would be more cost-effective and expedient for the equipment suppliers to supply extractables testing as a data package. Sterilizing filter manufacturers have been doing this for decades, and now it is being extended to plastic biocontainers, connectors, tubing, and assembled systems. The reasoning is that equipment manufacturers have better expertise about their own equipment and materials selection. Once the data is assured once, the supplier can then share that with the industry. This would take a lot less time and be more cost-effective than if each drug company had to do it on their own. More significantly, it helps reduce the time it takes for a drug to get to market. The time savings is an even more significant economic factor than the materials and testing cost savings.
For example, it could take six months for a drug company to collect its data, and that holds off approval from the FDA. For a moderately successful drug that ultimately has $365 million a year in sales, every day of delay is a million dollars lost in sales.
In addition to who should test, there has been debate throughout the pharmaceutical industry about which tests to conduct, how to test, how to standardize tests across the industry or for each component or materials, and how to ensure that the FDA will be able to use that data in judging suitability for drugs on a case-by-case basis.
Industry groups like the Bio-Process Systems Alliance (BPSA), BioPhorum Operations Group (BPOG), ASTM International, the Parenteral Drug Association (PDA), and the U.S. Pharmacopeia (USP) have varying views of standardized approaches to testing. As an industry, however, pharmaceuticals are moving toward some consensus on plastic materials extractables and leachables tests. Simultaneously, suppliers are busy generating data, which will reduce end-user time and costs. Both suppliers and users are hopeful that this data will help satisfy the safety concerns of the FDA.
This year’s Healthcare Packaging Expo, co-located with PACK EXPO Las Vegas (Sept. 25-27 at the Las Vegas Convention Center) will provide attendees the opportunity to see the latest innovations in healthcare packaging equipment and technologies. The show will also feature educational sessions on regulatory matters and other industry insights pertaining to the healthcare, pharmaceutical, and biopharmaceutical business. The event is produced by PMMI, The Association for Packaging and Processing Technologies. Together, both shows will feature more than 2,000 exhibitors and draw 30,000 attendees. For more information, visit packexpolasvegas.com or hcpelasvegas.com.
About The Author
Jerry Martin is an independent consultant to pharmaceutical manufacturers and equipment suppliers for filtration, single-use manufacturing, marketing, business development, and regulatory compliance. He was previously SVP, marketing and global scientific affairs, for Pall Life Sciences, where he served the pharmaceutical, biotech, medical device, and vaccine industries for over 37 years. He is currently chairman emeritus of the Bio-Process Systems Alliance, the single-use manufacturing trade association, and a member of the USP Expert Panel on Plastic Systems Used for Manufacturing Pharmaceutical Products. He holds an M.Sc. in microbiology from the University of Toronto.