Qualifying Raw Materials and Their Vendors for Contract Manufacturing

It’s a mild understatement to say the supply chain integrity game has changed in the past year. With the advent of the Food Safety Modernization Act (FSMA) granting FDA vast authority to evaluate and verify components of foods from foreign suppliers, the days of relying on supplier certificates of analysis (CoA) for raw materials are over. In fact, they have been over for some time due to the establishment of the cGMPs (current good manufacturing practices) of 21 CFR 111. While every company strives to deliver consistent, high-quality products, effort alone is no longer satisfactory in this environment of ever-increasing scrutiny.

A careful analysis of the form 483s and warning letters to dozens of firms from FDA over the past several years after the GMPs were enforced demonstrates an area of great concern. Firms large and small have seen their systems fail when stressed to provide testing data or proper documentation. Quality is no longer optional, but is a substantial budget line item for the new generation of contract manufacturers in the dietary supplement industry. Failure to conduct adequate identification testing is not an option. Failure to generate master batch records with appropriate instructions is not an option. Failure to provide testing protocols and adhere to them on finished products with proper documentation retention is not an option—yet all of these findings are common in FDA citations for deficiencies.

The world is an inherently complex place, and the supply chains that used to be domestic or generate in Europe have transitioned to the Far East and India. Contract manufacturing firms absorbed significant costs onto their balance sheets to invest in the technology, systems and personnel to verify supply chain components and suppliers. While the GMPs allow some level of flexibility to producers of finished goods to set up mechanisms for reduced testing of each lot, companies would be wise to avoid reaching for that “cost relief" too quickly. Producer audits are often expensive to conduct and unfortunately can be “staged" for foreign visitors, so relying solely on a facility audit would not be wise either. The fact remains that former President Ronald Reagan was right when he said, “Trust, but verify." That is the real dilemma of our industry.

From the Bio-Terrorism Act that followed the unfortunate incidents of 9/11, to implementation of the long-awaited GMPs after passage of the Dietary Supplement Health and Nutrition Act of 1994 (DSHEA), to the provisions of FSMA—the dietary supplement contract manufacturer is the first line of defense against supply chain fraud or ambiguity. It is the legal responsibility of the producer of these products to generate adequate material testing protocols, to perform the tests, to validate the processes and equipment, and to constantly challenge the status quo. In many foreign jurisdictions, every box or drum of a material that enters commerce through the world of dietary supplements needs identification testing, not just via a composite sample. This presents a dilemma in that these tests cost time and money to perform, and both often can be in short supply when margins are constantly under assault by a customer base that is not necessarily as well-informed about the regulatory framework as it should be.

The difference in perspective from just a decade ago is enormous. While traceability always has been a hallmark of product safety and quality, the increased concerns of economic adulteration or supply chain tampering have caused greater stresses than ever before. Companies with reputations and reliable service levels used to conduct paper audits involving some modicum of component or process approval. With the advent of GMPs and FSMA provisions, that world is no more. Today, the risks of not testing for pathogenic organisms, heavy metal contamination, pesticide or herbicide residues, and adulterants are serious concerns. Just ask anyone who has had to deal with Proposition 65 in California. The days of a nice-looking laboratory with a microscope, a fume hood, nice beakers, flasks and a hot plate are over. The modern laboratory deploys fourier transform infrared spectroscopy (FTIR), IR, high-performance thin-layer chromatography (HPTLC), HPLC, ultra-performance liquid chromatography (UPLC), gas chromatography (GC), GC mass spectrophotometry, atomic absorption (AA), inductively coupled plasma (ICP), full micro, disintegration testing (DT), dissolution, friability, solubility and a host of other testing profiles. A well-designed laboratory with multiple testing capabilities can cost north of US$2.5 million to properly equip, and that’s before hiring qualified personnel with master’s degree in science or doctorate qualifications.

Concerns over quality are not going away. Trying to test a deficient product into compliance is not a viable option—although it appears some fall to that temptation from time to time. Consumers want better transparency into our world, and they should have it. If there were a regulatory scheme that would call for licensure by FDA or another competent agency to rate the facility where products are made, issue a permit or registration document, and publish the results of routine audits, that would go a long way in helping maintain or restore consumer trust. Much has been made about economic adulteration, and where those cases are discovered, the violators need to be prosecuted to the highest extent of the law. In the meantime, the dietary supplement contract manufacturing community needs to band together to help police the global material supply chain to reduce the uncertainties that remain, and create a cadre of reliable partners who work to improve health worldwide.

Mark A. LeDoux is founder, chairman and CEO of Natural Alternatives International (nai-online.com) Inc., an organization with world-renowned facilities in the United States and Switzerland engaged in the research, design and manufacture of nutritional supplement programs and products for multinational clients.