From the 1970s to 2009, Syms was a popular, well-known off-label regional clothing retailer in the U.S., Syms sold high quality goods and designer clothing at reasonable prices, attracting a large and loyal customer base. Their famous motto, used in every commercial across four decades was, “An educated consumer is our best customer.” Syms customers understood that when they bought at Syms, they were getting good value.
We have always believed the Syms motto applies equally well to Seqens North America. Like Syms, our best customers are those sponsors who are knowledgeable about all aspects of API development, particularly the all-important regulatory requirements. They understand the value of working with a CDMO that develops and manufactures APIs with a laser-sharp focus on quality and purity, which generally saves a great deal of time and money in the long run.
This article will focus on where CDMOs add the most value as it pertains to regulations that must be adhered to.
Every project starts and ends with the regulators
Whether it’s ICHQ7, CFR Part 11 or other requirements in the vast regulatory landscape promulgated by the FDA, EMA and ICH, the end goal, approval, is the starting point of any program. Each of our projects begins with a look toward the goal post: the submission to a regulatory agency somewhere in the world. That entails assuring that everything—from purchasing and storing raw materials to each step along the way—is appropriately executed and documented so that the submission is complete, and guidelines met.
Our most knowledgeable sponsors are fully aware that if we suggest work, it’s not because we want to keep the meter running, but because we know that doing things right the first time is the quickest, least expensive route to regulatory approval.
Sometimes sponsors who may not fully understand the regulatory requirements focus primarily on budgets. That’s a mistake that can cause them difficulty in two ways:
- The regulatory agency will reject their application if the science is lacking or not thorough enough.
- Lose a year because the work has to be repeated—and incur the cost of doing the same work twice.
Impurities are the main focus
ICH guidelines are worldwide standards adhered to by the entire pharmaceutical industry. For active ingredients, ICH sets minimum specifications that need to be met. We have found that it pays to home in on impurities, especially in early stages of a program. We want to identify not only total known impurities, but also potential unknown impurities, remediating any issues as early in the project as they materialize.
Meeting ICH guidelines is no walk in the park. The ICH sets very high standards for impurities—a drug substance must be greater than 99% pure. There are specific limits set for known, unknown, elemental and genotoxic impurities.
Looking down the field at the goal post we’re aiming for, we want to make sure from the beginning that we document every effort made to assure the API’s purity during its development and manufacturing, meeting standards that make it safe for clinical trial subjects anywhere in the world.
Data integrity—make no mistakes about it
Regulators can come down hard on sponsors whose data integrity is questionable. This issue came to the fore a few years ago when dozens of people died after taking adulterated Heparin produced in China, a case that generated a lot of media attention. Investigations into this tragedy found systemic failures, including inadequate quality controls, in plants operating outside the U.S. that supplied the raw materials, which resulted in submission of bad data.
It used to be the practice that samples were taken and tested multiple times and an average of the results submitted. However, some unscrupulous labs threw out data points that pulled the average out of spec. After the Heparin debacle, data integrity became one of the biggest issues for the industry.
Much of today’s guidance was published in the aftermath of the Heparin-related deaths to assure that any out of spec results are investigated and resolved. As a CFR 11-compliant GMP facility, Seqens North America is subject to inspections by the FDA. Consequently, our Quality Control (QC) department follows very specific rules on manipulation of data and data integrity, knowing how critical good data is to a program’s success.
Such compliance results in a need to do more testing, and for customers it means needing to spend more for analytical work than they had in the past. If the cost of analytical work was $150,000 to $200,000 six or seven years ago, it now costs $400,000 due to the added work and increase in personnel involved.
The pharmaceutical industry is not unique in this. After the 2008-2009 financial crash, regulations were put into place to avoid another crash. An entire industry was born to run stress tests and assure that large financial institutions were in compliance with the new regulations.
Preparing for submission and working with the FDA, EMA and other world regulatory bodies requires a copious amount of work. It’s best to adhere to a “right first time” approach, avoiding glitches and delays in regulatory submissions that can hinder a sponsor’s progress in bringing a new drug to market—and help its competitors.
The bottom line
The need for the smooth regulatory path to get a drug to market is the main reason pharmaceutical companies look closely at a CDMO’s track record with regulators. With all humility, ours is one of the best. There’s a great deal that goes into meeting regulatory requirements. Whether it’s a drug substance, generic, nutraceutical or other substance that must meet guidelines, make sure your CDMO knows what regulators are looking for. There’s great value to that.
For more on this, check out: “Avoiding FDA Drug Rescissions: Sponsors Seek CDMOs With Strong Regulatory Track Records Data from regulatory-minded CDMOs keeps approvals on track,” “Why the FDA and EMA want you to implement QbD Quality by Design – 9 basics and what’s in it for sponsors,” and “Best practices in following ICH guidelines for APIs Since understanding regulations is a key part of our business, this blog takes a brief look at the origins of the International Conference of Harmonization (ICH), and the implications of a unified regulatory framework.” We’re happy to talk about this; call us at (978) 462-5555 or email us at info@pcisynthesis.com.