API Manufacturing: What Are 5 Best Practices in Qualifying Suppliers?


Suppliers are the lifeblood of drug development and manufacturing. Whether the project requires off-the-shelf or customized ingredients, a reliable supply of high quality materials is essential. Contract Manufacturing Organizations (CMOs) need to be on top of their supply chain from beginning to end.

Sign up for our Blog Subscription and get the latest News and Insight right in your inbox

First of all, it’s required. All suppliers must be qualified as part of the regulated Pharmaceutical Quality System that must be implemented in Current Good Manufacturing Practices (cGMP).  Every manufacturer of drug products and active pharmaceutical ingredient (API) has to comply.

What is entailed in supplier qualifications? By its definition, supplier qualification refers to the overall quality management of outsourced materials and/or activities as they relate to drug product and API manufacturing.  In “activities,” regulators include contract manufacturing and lab testing.

This article presents some background into how PCI Synthesis qualifies our suppliers in order to provide a sense of transparency.

Main reason for qualifying suppliers

In addition to complying with regulatory requirements, there is one overarching reason for carefully and thoroughly qualifying suppliers: our sponsors’ business depends on it. It is sponsors who are held accountable by the FDA for any quality problems that could adversely impact patient safety.

It behooves us, their CMO, to prevent problems—and that starts with qualifying all suppliers.

We have heard about all kinds of problems related to outsourced materials, from our many interactions in the industry. PCI Synthesis CEO Ed Price serves as co-chair of the New England CRO/CMO Council. He sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst and is a long-standing member of the American Chemical Society. He also advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA). Our scientists also have numerous industry affiliations.

5 supply chain problem areas

The unhappy stories we have heard through the years tend to fall into these 5 categories:

  1. Pharmaceutical companies can’t supply the market due to supply-related delays
  2. Pharmaceutical companies have their programs delayed for regulatory reasons
  3. FDA inspections raising quality control issues, causing program delays
  4. Clinical trials halted or amended
  5. Additional review cycles required due to quality concerns

No sponsor wants their CMO to receive an FDA Form 483 indicating problems found during an  inspection, FDA warning letters issued, or a host of other potential issues that could impact patient safety.

5 Best practices in qualifying suppliers

Good manufacturing has always been about paying attention to the details, which we discuss in Embracing the Good and Avoiding the Bad and the Ugly in Pharma Manufacturing.

Focused as we are on timely delivery of quality small molecule APIs or New Chemical Entities (NCEs), we make every effort to minimize the number of issues that can disrupt project completion.

Because the stakes are so high for our sponsors, we take extra care in selecting and managing suppliers of raw materials and outsourced services.

Prior to selecting suppliers of goods and services, PCI Synthesis carefully assesses the suppliers by:

  1. Requiring every supplier to complete a self-evaluation questionnaire
  2. Based on the responses, determining the supplier’s suitability and compliance cGMP’s or their own internal quality systems.
  3. Perform on site evaluations

For suppliers of mission-critical supplies, PCI Synthesis also:

  1. Performs periodic on-site quality audits of the supplier’s facility, operations and quality systems
  2. Establishes long-term oversight of a supplier’s commitment to quality

In the event an on-site audit is not feasible, PCI Synthesis may accept recent evidence of a quality system inspection by a regulatory body such as the FDA, European Medicines Agency (EMA) or other as a substitute for its own on-site visit.

The FDA’s recent changes create challenges for CMOs

For many years careful selection and management of suppliers applied primarily to finished drug product manufacturers as they sourced APIs and excipients for their formulations.

In recent years the FDA’s thinking on this subject expanded, with particular scrutiny extended further up the supply chain to those providing raw materials and critical reagents used in the manufacture of APIs.

The FDA’s requirement that suppliers be qualified earlier and earlier in the drug synthesis process makes the regulatory burden on CMOs and sponsors exceptionally challenging.

Producers of commoditized raw materials are neither easily reached nor willing to divulge their proprietary manufacturing processes. It can sometimes take a month to piece together the information required for a regulatory submission.

Risk/benefit ratio

We’re not sure obtaining this information so upstream in the drug development process makes sense from a risk/benefit standpoint. The effort seems to outweigh the benefit.

Whether or not regulations and enforcements are relaxed by the FDA in the future, we believe in adhering to current best practices in qualifying suppliers, and will continue to do so.

What to look for in suppliers

In light of the regulatory challenges, it’s important to have a deep bench of suppliers. We source materials from all over the world, favoring suppliers who can supply us reliably, at a high level of quality, and who are willing to provide the information needed for regulatory filings.

Communication is key

Readers of our blog know how much emphasis we place on open and frequent communication between CMO and sponsor teams. It is critical in all aspects of drug development and manufacture, and no less so if suppliers need to be changed for any reason whatsoever or if other supply issues should arise.

We make it a practice of holding weekly/biweekly meetings or teleconferences with our sponsors to go over everything from process improvements to production schedules and that includes status of supplies if there’s even an inkling of a problem.

We also maintain frequent communication with our suppliers and in the event changes need to be made, we can often do so reasonably and quickly.