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Gmp Compliance

AIDP

As June marks complete industry compliance with FDA GMPs, NIE talks to suppliers, manufacturers and certifiers about their experiences, what GMPs mean to the industry and missteps companies must avoid
WHen Sunil Kohli’s company began examining the facilities where its psyllium health supplement products were being contract manufactured, Kohli said he was shocked by what was discovered.

Not only did the company have no control on the timing of delivery, but the facilities were “terrible.” “Everything was handled like a foodservice facility and there was no accountability for any previous production,” said Kohli, COO of Health Plus Inc. (Chino, CA). He explained that Health Plus committed to building its own manufacturing facility to ensure that it applied and received any specific certifications of safety, reliability and quality. “We knew the benefits would be long-lasting and compounding: we would cut costs, we could control and improve upon the quality and also perform any product runs we needed to better manage our inventory. It was the ideal decision.” That was back in 1988. There was no set dietary supplement standard or good manufacturing practice (GMP) at the time, so Health Plus went straight to the regulating source—the Food and Drug Administration (FDA)—to obtain a drug manufacturing license. Working with the California food and drug agency, the company was able to start manufacturing its own supplements by 1989.

In 2000, Soft Gel Technologies, Inc. (Los Angeles, CA) sought GMP certification through the NNFA’s (National Nutritional Foods Association, now Natural Products Association) GMP program, which was launched in January 1999 and designed to review and ensure that the manufacturing facility’s processes are controlled in order for products to meet their purported quality.

The company took its commitment to quality a step further by being certified in 2007 by NSF International (Ann Arbor, MI), whose program is based on a proposed set of GMPs developed by four industry trade associations that were submitted to the FDA in 1995.

The point? GMPs are not a new concept to the dietary supplement industry.

It has had its eye on quality for some time, realizing that individual companies as well as the industry as a whole’s reputations were on the line.

“We considered the NNFA to be heading in the right direction in terms of starting to really regulate the industry and provide a consistent, recognizable standard of quality,” said Steve Holtby, Soft Gel president and CEO. “We have obtained GMP registration through NSF’s Dietary Supplement Certification program and the Natural Products Association (NPA), and have held these certifications for many years prior to the emergence of the FDA GMPs. These internationally-recognized certifications help assure our customers that the products we manufacture are up to the standards they demand in ensuring their purity, potency and quality.” But according to George Pontiakos, president and CEO of BI Nutraceuticals (Long Beach, CA), the FDA’s issuance of mandatory GMPs was, in fact, a wakeup call for the industry.

“This is a passionate industry intent on improving lives. Manufacturers put a great deal of effort into researching their formulas and their knowledge of efficacy is unique,” he said. “But it was a real shock to the industry when it realized that the supply chain wasn’t as ethical as they were, which is why we now have GMPs.” Manufacturers at the Forefront FDA GMP regulations (21 CFR part 111) require that the processes by which dietary supplement products and ingre.

Dients are produced are safer and free of possible contamination. This includes all aspects of the manufacturing process, from raw material control to finished product release, as well as employee training, validation of testing equipment, product traceability and facility maintenance.

“The regulation is aimed specifically at manufacturers of finished dietary supplements that are intended for distribution in the US market. This includes all manufactured products that are also produced outside of the US,” explained Ed Wyszumiala, general manager of NSF International Dietary Supplement Certification Programs. “The regulation indirectly affects ingredient suppliers.

As manufacturers look to qualify their suppliers, FDA has implied they expect industry to also audit their supply chain.

GMP certification is a key tool to help a company make sourcing decisions.” While the onus falls to manufacturers, they aren’t alone if they choose their supply partners wisely. It’s something BI’s Pontiakos has been preaching for some time, but with the advent of the FDA’s GMPs, he pointed out that manufacturers across the board really began to query. And as those questions came to the forefront, ingredient suppliers whose operations were in line began seeing an upswing in business as manufacturers became cognizant of any poor relationships they had formed.

“We’ve seen an uptake in demand over the three years [since the FDA phases began]. My customer base was able to accelerate compliance and maintain far more cost effective compliance protocol than if they had to invest on their own,” said Pontiakos. “When you buy from BI, you buy compliance data (i.e., audit trail, knowledge of vendor, certificate of analysis, etc.). Many customers were surprised how quickly we’re able to provide these materials for their businesses—we’re a force multiplier to our customers; we enable them to grow.” ESM Technologies (Carthage, MO), supplier of eggshell and eggshell membrane ingredients, sought its certification precisely so it could be a better partner to its customers.

“Dealing with finished products manufacturers has become much easier now that we are cGMP compliant,” said Micah Osborn, ESM president. “There has been a difference in the amount of and type of questions being asked since the establishment of 21 CFR part 111.

Having gone through the process of cGMP certification makes answering those questions much easier, and our customers can rest assured that a trusted third party has inspected our facilities on a regular basis.” “Although the FDA’s GMP rules essentially make ingredient suppliers the manufacturers’ responsibility, going that extra step is in keeping with our belief that for a quality finished product, you have to start with ingredients from a responsible and reliable supplier,” said Shaheen Majeed, marketing director for Sabinsa Corporation (East Windsor, NJ).

“Although the industry knows that our manufacturing facilities in India are top notch, having the certification independently verifies that; the National Sanitation Foundation (NSF) certification came through early this year. More recently, our Kunigal plant received Bureau Veritas ISO 22000 Certification.” Avoiding the Pitfalls As the industry has been forced to examine its operating procedures and manufacturing practices to comply with the FDA, it seems widely recognized there are three main pitfalls manufacturers need to avoid: not having the right documentation, not doing their due diligence when dealing with foreign suppliers and using price as the deciding factor.

Documentation According to NSF’s Wyszumiala, fully implementing and documenting standard operating procedures (SOPs) is one of the common missteps he’s seen companies make.

“The SOPs are your company’s internal requirements. Following and documenting your activities is essential,” he said.

“The correlating documentation is your record of compliance; poor documentation, lack of documentation or incomplete documentation are all red flags that can lead to major issues. If it isn’t fully documented, it does not exist.” “For manufacturers unaccustomed to the regulations required for GMP compliance, it may seem overwhelming and require a major overhaul of procedures,” said Soft Gel’s Holtby. “Good preparation includes establishing written SOPs, which detail specific instructions for manufacturing products, and formal training programs to ensure that personnel have a thorough knowledge and follow them. It also includes validation of all procedures, including manufacturing, packaging, laboratory testing and cleaning procedures.” Holtby noted that this also goes for supplier qualifications, as “complete and detailed batch records need to be maintained for traceability purposes.” “The regulation mandates 100 percent identity testing, and that doesn’t mean do it 50 percent of the time,” Wyszumiala concurred. “Identity testing is a major issue, which is spelled out in the regulations.

Finding the Right Foreign Partners It’s unmistakable that many useful ingredients can’t be found within the US, so aligning with the right partner overseas is imperative.

“I think a lot of raw material suppliers importing or foreign suppliers are still struggling with how to get GMP compliant,” said Lauren Clardy, president of NUTRIMARKETING (Santa Rosa, CA).

“Quite a few foreign suppliers I have been in contact with are still working out the process and logistics. The issue is that it is an extremely competitive market and if a supplier is not compliant and doesn’t have a process in place, it is easy to move on to the next one that does.” And Sabinsa’s Majeed expressed when red flags are raised, moving on is a manufacturers only course of action.

“We are a foreign supplier in terms of where our products are manufactured, and our US manufacturing customers appreciate that Sabinsa’s facilities are as fine as anywhere in the world,” he said.

“But if a company is having trouble getting any supplier to meet their needs, with GMP requirements or in other ways, it’s time to interview other suppliers.” NPA established its China office in Beijing in 2006 specifically because China is the leading ingredient supplier and a market with great growth potential.

The office has been working to educate Chinese suppliers on the importance of quality assurance, GMP standards and US importing regulations.

“To help Chinese companies meet US standards, NPA has been offering two programs to suppliers: the ingredient testing program (in partnership with the US Pharmacopeia) and a GMP certification program, which allows Chinese suppliers to become US FDA compliant and certified by NPA,” said Jeff Crowther, executive director of NPA China (Beijing, China).

While the NPA has certified 70 companies globally, Crowther admits the process is challenging. “Because NPA’s programs are voluntary, it is challenging to convince Chinese suppliers to invest in them. NPA and the US industry have to rely on two forces working together to make these programs more successful,” he said. “One is working with suppliers that understand the perception of Chinese ingredients and want to do all they can to reassure their US and potential partners that they are producing quality ingredients and products.

The other pressure has to come from US buyers. If Chinese suppliers feel that they could lose business due to lack of US compliance, they will certainly participate in quality assurance programs or lose out.” NSF’s Wyszumiala noted that GMP certification has been well received by both global suppliers and regulators.

“China and India especially have been looking for an accredited, third-party certifier to offer GMP certification services, and NSF is pleased to be their partner,” he said. “The majority of companies overseas that have earned NSF GMP certification have been ingredient suppliers, which comprise approximately 75 percent of the growth in these markets for NSF. To meet this growing demand, we have opened offices in Shanghai, Delhi and Bangkok as our hubs for calibrated auditing of staff in these countries.” Nutratech, Inc. (West Caldwell, NJ), exclusive distributor of its patented bit.

Ter orange (Citrus aurantium) extract Advantra Z, started working with its Asian suppliers 15 years ago to meet GMP standards, according to Bob Green, company president. “From the beginning, we have worked exclusively with foreign suppliers who were willing to get in line with US GMPs,” he said, but cautioned that it’s a situation where vigilance is absolutely necessary. “We have found and maintained credible suppliers through regular supplier visits.

Nutratech’s whole sourcing strategy requires careful and diligent verification of the GMP manufacturing practices and quality control procedures of our partners,” he said, explaining that the company audits every factory it deals with and insists strict quality standards are adhered to.

Letting Cost Dictate BI’s Pontiakos offered that while the bulk of the industry is focused on efficacy, marketing, formulation and sales, the knowledge base of sterilization and identification is what’s lacking. “The wheels came off when manufacturers assumed the supply chain had their same interests, when all it really cared about were cents per kilo,” he said.

“The moment you have that problem and abrogate that responsibility to a supplier, then you get adulteration and corruption in this industry.” Green said that he’s seen manufacturers use price as the deciding factor, and considers it one of the biggest mistakes a company can make.

“In the past, some companies were reluctant to use Advantra Z because they were concerned about price. But now that they’re forced to look more closely, they’ve seen that generics don’t succeed on price and that the price difference between Advantra Z and generic bitter orange is negligible,” he said.

“It boils down to an average of onethird of one penny for every capsule, tablet or powdered serving—an insignificant amount considering Advantra Z’s product quality and added value.

“Strict GMPs play a key role in ensuring Advantra Z’s quality, consistency and reliability. Those manufacturers who use generic bitter orange are probably having a harder time because many have shopped for price alone,” added Green. “With the new GMPs, quality must come first.” And cost can often be a factor for companies trying to decide if it wants to manufacture its own products or subcontract with an outside vendor.

“Increasing costs and a lack of manufacturing acumen may be a couple of the variables that drive the decision to utilize a contract manufacturer,” said Holtby. “In the recent past, increasing costs were most directly attributed to shipping costs from rising gas prices.

Other than gas prices, manufacturing costs, employee wages, increased consumption of nutraceuticals leading to decreased supply and the costs for FDA GMP compliance are all factors for increasing prices of products. While there are numerous benefits associated with using a contract manufacturer, there are also many factors to consider when searching and choosing the right contract manufacturer.” Conclusion In the end, it comes down to solid relationships built on, sad to say, mistrust.

“All manufactures should audit or be audited at least once per year,” said Chris Haynes, director of sales for ESM.

“This can be very difficult for most brands and manufacturers. It is time consuming, costly for travel and expertise, and many companies could have over 200 vendors of various materials.

But, it should be done to ensure supply chain quality.” And those relationships cannot be dictated by cost or convenience because, ultimately, when a company’s marquis is on the line, the price is too high.