In light of the fact that drug manufacturers today are expected to exercise greater control and oversight over their suppliers than ever before, supplier audits have become increasingly common and important. Pharmaceutical Manufacturing recently spoke with SGS’s Dr. Eize de Boer, well-versed in the subject, about best practices.
PM: Do you think pharmaceutical manufacturers are being prudent in terms of truly auditing their suppliers? What types of trends have you seen in supply chain auditing within the pharmaceutical industry?
EdB: What we have seen so far is more and more manufacturers are controlling their suppliers by sending their QA auditors to third-party manufacturers and suppliers. Certainly if you make that distinction, it is true that API suppliers of large organizations are really addressing this. What is about to emerge right now is the compliance auditing of excipient producers. Excipient manufacturing audits are now about to emerge even though there is no formal regulation on excipient manufacturing organizations.
That’s true for the real big pharmaceutical organizations again, but what we see today is that smaller pharmaceutical organizations are taking responsibility to audit their suppliers. That’s the trend . . . larger multinationals have already taken their responsibility, but now even the generic manufacturers are investing in audits for their API and excipient producers.
PM: Can you discuss responsibilities supply chain auditors should have and describe a typical audit process?
EdB: (For more details, read Lessons from Heparin).
PM: Do you feel regulatory agencies (especially FDA) have adequately spelled out requirements for supplier audits?
EdB: What we see today, is both the EU and the U.S. are very specific about the obligations that drug manufacturers have to fulfill. It is all perfectly written down. For example, the EU has published a Q&A on what the specific requirements are for manufacturers. There are two points to consider. What we see is that for the smaller manufacturing organizations, these suppliers are not always willing to cooperate during an audit process as they do not feel it necessary.
For instance, some of them may never have been audited so they are reluctant and questioning why an audit is necessary. If that supplier’s quality systems are less than optimal, they will often strongly argue against the audit. Another complication is that suppliers are often represented by agents or brokers. When suppliers have a broker or agent sitting in the U.S., suppliers are in contact with these brokers only and not the manufacturer, and many brokers are opposed to audits. We’ve observed that many feel threatened or that they will be turned down after the audit. Both issues need to be resolved, but a technical sound contract is key always. Both manufac-turer and supplier need to write out the requirements and responsibilities.
PM: How are auditors using ICH guidelines such as Q9 and Q10 as a foundation for efficient auditing procedures?
EdB: ICH’s work is truly important as it establishes global standards of quality for the pharma industry and particularly for auditors. In a global organization, it is extremely important to have access to harmonized standards. If you would like to reach consistency, independency, objectivity, it is very important to work with the harmonized standard.
We are working in Asia, North America, South America, Europe, etc. and it is easier to train a global standard. That way you will make sure that people in different regions receive the same training. We need to ensure a worldwide consistent quality approach which can be applied to manufacturing organizations to make sure the auditing systems are consistent as we deploy them globally. That’s why we are promoting this work and carefully checking what ICH is doing. Q10, for example, is in draft, so as soon as the document has been finalized, we will seriously consider turning this into an auditing guide.
PM: Can you share other best practices in terms of how manufacturers can ensure that their partners are legit?
EdB: The contract is key, but there is another item that is really of importance at the level of suppliers: training. The moment a manufacturer starts working with a supplier, that manufacturer is able to show the internal procedure to the supplier organization and tell them about the particular GMP requirements in their field of interest and they can do that through training.
So besides the formal arrangement, as laid down in the contract, training is a very good tool to develop quality awareness at the level of the supplier. Typically companies have to go out to their supplier, even if they are in China, to make sure that you show them the procedure, the best practices, the relevant GMP regulations, etc. Before we start an auditing program for a client of a particular supplier, typically we start off with a training session.
Normally we organize this in-house. During this training session you can dedicate your course content to the specifics of the supplier manufacturing organization in relation to GMP, correct procedures, best practices, etc. That should be the order: Contract, training sessions, and the actual auditing program. The training stage is extremely important.
The following are some contract manufacturers on the grow and making news:
Aptuit (Greenwich, Conn.) features 18 global sites and specializes in a variety of clinical and commercial operations, with a focus on the development process. A claim to fame is its paperless operations. It has invested more than $50 million to convert paper-based processes into an electronic system that is web-accessible to clients. By linking data, projects and contracts with clients in real-time, Aptuit aims to enable quick decision-making and reduced cycle times. www.aptuit.com.
DSM Pharmaceutical Products (Parsippany, N.J.) is a global provider of custom clinical and commercial manufacturing. DSM works in the areas of steriles, and orals and topicals, including dose form manufacturing, scheduled drugs, clinical manufacturing, fill/finish manufacturing, and lyophilization services. It also specializes in cytotoxics. www.dsm.com.
Baxter BioPharma Solutions (Round Lake, Ill.) specializes in formulation, clinical and commercial biologic API manufacturing, monoclonal antibodies and recombinant proteins, and form/fill/finish services with recently enhanced lyophilization capabilities. www.baxterbiopharmasolutions.com.
Ben Venue Laboratories (Bedford, Ohio) develops and manufactures sterile products, in particular sterile liquid products filled into vials and ampules. Its core competencies also include lyophilization and vacuum-drying of parenterals. It boasts among its clients the National Cancer Institute. www.benvenue.com.
DPT Labs (San Antonio, Texas) offers integrated contract drug development, packaging and manufacturing. Its development expertise lies in pre-formulation and formulation, analytical method development, process development, validation, and stability studies. www.dptlabs.com.
At its sites in Germany, Switzerland, and New Jersey, Glatt Pharmaceutical Services (Ramsey, N.J.) offers clinical to full-scale manufacturing as well as turnkey engineering. The CMO specializes in proprietary delivery technologies such as controlled release and site-specific delivery.
Hospira (Lake Forest, Ill.) has been manufacturing parenterals for some 70 years, the last 20 as a contractor as well. The company specializes in partnering with clients from development through scaleup and commercialization.
PacificGMP (San Diego, Calif.) is a pioneer in single-use bioprocessing, affording clients cost effectiveness and rapid turnaround times. The facility will host its 2nd annual open house on October 9. www.pacificgmp.com.