Ensuring Quality Crucial to Industry Viability
The issue of quality control (QC) remains one of profound interest to industry members. Whether in production, sourcing or claims, quality is the goal. Natural Products Industry INSIDER asked several leading industry executives about their quality control procedures and the major problems facing the industry in this field. Here, you'll find their opinions on the major problems with quality control in the natural products industry.
What are the major problems with quality control facing the natural products industry?
Stephen Ashmead, director of research & development, Albion Advanced Nutrition: First, there is no independent certification or validation of companies' quality control procedures. In the animal feed market, AAFCO sponsors a laboratory testing services. In this service, the lab pays a yearly fee and gets a sample on a monthly basis. The lab does not know what it contains, but performs its assays and submits back the results. The results from all laboratories are combined and a report is generated that shows what your score is and how you compare to the average and bias of all the other laboratories. There is no corresponding service for the natural products industry, or even segments of it. This is crucial. The No. 1 reason why there are inaccurate test results is incorrect analytical technique, followed by poor standards. A third-party validation such as the AAFCO feed composition program would expose these problems so they could be corrected. Albion is fortunate in that we are aware of these programs due to our other divisions, and can participate and extend this to our human manufacturing division.
Second, there is a lack of acceptable and universal standards. For a pH test, recognizable standards can be bought from reputable chemical supply houses, and very few people doubt the veracity of that standard. The same can be held for metal standards for ICP, ICP/MS, AA, etc. However, suppose that you want a standard for a botanical. Where do you get it? Generally, you must make your own, and then how do you validate that you have extracted all of the active ingredient to serve as the standard?
Third, there is no recognized independent industry "watchdog" for label claims. Recently, ConsumerLab.com put on its Web site the report of its magnesium study. It lists the magnesium source, but only tested for magnesium content. It did not test for the various forms of magnesium listed on the label. Generally, organics are higher in price than inorganics, but do you know if the product that you purchased really has magnesium citrate, or is it magnesium oxide? In my opinion, ConsumerLab.com and similar testing services are doing a disservice to the industry without that additional information. It is also promoting the cheating of manufacturers to make label claims at all costs.
Finally, there is no verification of quality in conjunction with GMP. Until quality and GMP are tied together, any GMP-certifying agency for finished goods will only promote a false sense of quality and will be used as such. ConsumerLab.com is predominantly quality, but not GMP. NNFA is predominantly GMP (procedures), but not quality. The two aspects need to be tied together.
Todd Norton, president, Sabinsa Corp.: One--the lack of generally accepted assay methods and reporting of active ingredient percentages. There is a significant problem in this industry with companies buying ingredients and relying solely on what is reported on the product certificate of analysis to assure quality. Some ingredients report an assay based on HPLC, and others report it based on UV or gravimetric or something else. Either way, the results are bound to differ. Take guggul extract, for example. Sabinsa offers a minimum 2.5 percent Guggulsterone Z&E content in our Gugulipid product, as shown in clinical studies to be responsible for therapeutic benefits. We measure our guggulsterone content by HPLC to be precise. We compete against other generic guggul extracts that claim to offer 10 percent guggulsterones, yet when pressed on the method of analysis used to determine this percentage, the answer is either by UV, or "I don't know." So, what levels of guggulsterone Z&E do they really contain? And what is it exactly that constitutes the 10 percent assay? Now let's fast forward to the retail shelf. If two guggul products are side by side and one claims 10 percent while the other claims 2.5 percent guggulsterones, assuming they are similarly priced, which one will the consumer likely buy? Some manufacturers, when seeking the higher potency listed on a competitor's label then feel compelled to modify their product also. Does anybody along the way ask the question whether the jump to a higher assay is practical, necessary or possible in the first place? Sadly, the matter is best summed up by a comment made by industry consultant Jay Jacobowitz: "It's remarkable that in our industry it is 'news' when potency matches label claims."
Two--the lack of substantiated agreement on what actives are responsible and in what percentages for certain health benefits in botanicals. Look no further than to the media-beating this industry took over St. John's wort not long ago. After all, as long as it's St. John's wort, it's all the same, isn't it?
And third--too much downward pressure on pricing. I am a firm believer that in most instances you get what you pay for. The trend toward constantly chasing the lowest price is taking an adverse toll on product quality. What is basically happening is the barriers to entry to be a supplier of ingredients keep getting lowered, yet industry manufacturers increasingly expect suppliers to provide more documentation, product testing and marketing support. This is an inverse relationship, and it only can last for so long before something gives.
My father worked in the poultry industry for nearly 20 years. His company adopted the following motto and I think it is appropriate: "The bitterness of poor quality will remain long after the sweetness of low price is forgotten." Sound words of wisdom for any industry, especially one professing to transform the "snake oil" persona that shows up repeatedly in the mass media. Quality, or the lack thereof, does come with a price. It is up to the industry to decide where they will pay.
David Parish, president and chief executive officer, Designed Nutritional Products: I have heard that some companies are willing to generate a certificate of analysis that says whatever the customer needs it to say. This is a deplorable practice and can severely damage an industry already under scrutiny. Companies should be careful not to place too much confidence in a piece of paper until the results can be verified. Furthermore, inability or unwillingness to provide analytical procedures for review should also raise concern.
As someone cross-trained in certain analytical methods, I see another problem associated with creating test methods that generate meaningful data. Even when meaningful data can be obtained, accurate interpretation of this data is also essential. An HPLC assay can report a purity of 101 percent, but what does this really mean? Many people assume that HPLC purity of 99.9 percent can be taken at face value. They fail to realize that HPLC can make garbage look clean if the method is not carefully developed or the standard is not pure. I have seen this both as a result of incompetence and as a deliberate wanton act.
Lastly, possibly the biggest threat to overall quality control is the failure of businesses to totally embrace true quality concepts. Companies can achieve quality registration by going through the necessary steps but still fall short of complete conversion. The sole purpose of quality concepts should be to improve how the final consumer is served. This automatically implies many other benefits, such as lower costs, higher production, faster delivery, a broader customer base, less liability and increased profits. Getting quality certification solely for the perceived marketing value is largely a waste of money and can potentially cost dearly.
Robin Ward, marketing manager, Linnea: First, the focus on price rather than the quality of ingredients. There is currently no obligation in the United States to test raw materials; the certificate of analysis provided with an ingredient is considered sufficient under current legislation. No re-testing is currently required, nor is proof that the product was manufactured under validated GMPs or that the product was tested by a competent and validated laboratory.
Second, testing for what should not be in the product is as important as testing for an active ingredient. The current focus of testing seems to be on the active or marker ingredient. Testing of identity, quantitative and qualitative composition, as well as residual solvents, impurities and microbiological content, should form part of the quality control function. Again, the focus on price and not quality of an ingredient is a barrier.
Finally, the lack of uniform industry standards for the testing of materials. The ongoing work of organizations like the U.S. Pharmacopoeia and NSF is critical in this regard.
Greg St. Clair, vice president, Arizona Nutritional Supplements: 1) Lack of standards for raw material suppliers; 2) Lack of enforceable standards from industry governing bodies; 3) Lack of support from industry/trade individuals and companies.
Walt Jones, president, Caraloe Inc: Identification of actives and the methods used to identify. The testing methods we have developed for our natural products are the same testing methods we developed for pharmaceutical. It is critical that as natural products, we establish base quality standards for identification and also some type of quality standards for our products.
What types of QC certifications do you hold?
Ashmead: We currently do not have any third party certifications. We are preparing for ISO certification and training our personnel for ASQ certification. Until those certifications are in place, we allow our customers to audit our facilities upon request. Our GMP procedures are a hybrid synthesis of proposed FDA dietary supplement GMPs, NNFA GMPs and customer requirements.
Jones: We hold ISO 9001/2000, cGMP for drugs and certification for organic raw material.
Norton: Sabinsa is the sales and marketing arm for our manufacturing operation SAMI Labs Inc., which is located outside the United States. SAMI Labs recently obtained World Health Organization (WHO) certification for its manufacturing operations.
Parish: Designed Nutritional is ISO 9001:2000 registered. GMP is the next quality certification we will attain.
St. Clair: We hold two GMP certifications. One is through the NNFA and the other is through NSF.
Ward: Linnea adheres to pharmaceutical standard quality assurance systems combined with strict pharmaceutical GMP compliance. Our operations are audited and validated by the IKS, the Swiss version of the FDA, which issues our GMP certification. Pharmaceutical GMP is the top level of certification.
How did you determine whether to hold a QC certification, and what does it offer you and your customers in the marketplace?
Ashmead: The determination is based upon what will serve the majority of our customers, the reputation of the certifying agency and available resources. In my opinion, the current dietary supplement certifying agencies only offer a marketing advantage. They do not offer any assurances to the customer that the manufacturer is not cheating on the supplement, only that the manufacturer is following a set of procedures all the time. It could be said that they only offer a false sense of quality to the customer.
Jones: We manufacture wound care products that are prescription drug and 510k products so we are mandated to use cGMP by FDA. ISO 9001 certification allows our products to carry the CE mark for importation into Europe and other countries throughout the world.
Norton: Sabinsa has a number of agents worldwide that represent our product line, many of which are affiliated with the European Union. We felt that WHO certification would best serve our diverse customer base and be universally recognized in the major international markets where we have a presence.
Parish: Many people misunderstand the purpose and utility of ISO registration. ISO is NOT just saying what you do, doing what you say, and documenting everything. When applied properly, ISO is a powerful business tool that eliminates scrap, increases production, improves efficiencies, decreases costs, establishes accountability, and delivers more value to the customer. All this makes it easier to compete in the marketplace. We selected ISO for the value it brought to our business systems and overall customer satisfaction. Creating barriers to competition is just frosting on the cake. We find that prospects place more confidence in a company willing to adhere to this international standard.
St. Clair: Our volunteering to become GMP certified was a natural progression to our companys growth. We also feel that we must continue to strive for better standards and continue to support our industry. We also work hard to provide quality and assurance through our commitment with the certification programs that ultimately provide efficacy and safety in our products.
Ward: We sell extensively to the pharmaceutical as well as the dietary supplement and cosmetic industries; therefore pharmaceutical GMP certification is a prerequisite. The same exacting standard is applied to the manufacture of all our products whether for the pharmaceutical, dietary supplement or cosmetic industries. Our manufacturing philosophy is based on three pillars--safety, quality and consistency. To this end we invest extensively in manufacturing technology, in-process control and quality assurance. This includes development of fully validated manufacturing process, fully validated analytical methodology and fully validated operating procedures (SOP's). The Linnea label stands for peace of mind and due diligence; effectively we build in the safety, quality and consistency. Many manufacturers of dietary supplements prefer to deal directly with a manufacturer than sourcing anonymously through trading companies. The clich it is not quality that costs but a lack of quality is very pertinent in our industry. Our consistency of product is reflected in our customers product. It provides an assurance of the same quality each and every time. This is very important for our customers when building brand loyalty with the consumer. Our attention to detail also protects our customers brands. From a purely manufacturing perspective a lack of quality and product consistency can also generate expensive delays in tablet or capsule manufacturing, unacceptable variability in the quality of the finished product or even complete rejection of batches.
What do you do to ensure the quality of the raw materials you supply?
Ashmead: Since we are a manufacturer, each raw ingredient is certified as acceptable before it is used in production. It is tested for the requisite parameters when it is received and when it passes the QC specifications, it is released to production. After the production process, the finished product is tested for the parameters specific to the product. The product must pass all specifications before it is released. All tests are conducted by in-house personnel and equipment, with the exception of microbiological assays. Those are sent to a state certified microbiological laboratory.
Jones: All of our raw materials we supply are strictly tested and validated just as if they were pharmaceutical products. Very tight specifications and standards are used to ensure the quality and identification of each item and component.
Norton: People need to remember that we are dealing with plant products that can, and do, change depending on which region they come from and the season in which the are harvested. The Sabinsa/SAMI operation is 100 percent vertically integrated. In some instances we control the cultivation of certain botanicals, and go so far as to provide our farmers with the seedling plants to ensure the right species is grown. When purchasing raw materials from outside sources, such as small villages or collection groups, we have a procurement team that travels with a portable testing equipment to quickly assess the identity and potency. If further testing is required we send the materials to our lab in the corporate office. Based on these results we either purchase or we dont.
Parish: Product specifications are established for every product we buy and sell. Even if we provide a supplier with the testing procedure for product verification, we verify the product specifications through third party independent analysis. Knowledge of the product and potential problems specific to a given product, enable us to look for the right things in the right places. SOPs for equipment cleaning and product handling minimize the likelihood of cross contamination in house.
St. Clair: We have several standard operating procedures (SOPs), from receiving of material to the shipment of finished products that identifies and ensures quality. We also have 20 percent of our staff dedicated to QC throughout the production process and our on site laboratory gives us flexibility of time.
Ward: Strict raw herb sourcing is vital to ensure the efficacy and safety of an herbal extract. Both the pharmacological activity and the safety profile of an extract are species- and genus-specific. Also, botanical species that appear very similar may have vastly different compositions; a healing herb and a toxic plant can easily be confused by the inexperienced eye or careless hand. To insure raw herb integrity and complete supply-chain traceability, we never source raw materials through anonymous trading companies; instead, our raw material procurement specialists rely on their expertise, long-standing relationships with key suppliers, and the raw materials that we grow on our own plantations around the world. Once raw materials arrive at our plant for extraction, they are subjected to further testing (sight, smell, and taste) for species classification before their final chemical analysis in our Quality Assurance laboratories. We also test extensively for pesticide and herbicide residues in our raw materials and finished extracts to insure safety from adulterating and/or potentially harmful substances. Because much of the nature and activity of many botanicals remains undefined, we go further than the basic standardization of extracts. We believe it is important that botanical extracts contain not only the key ingredients and markers, but also the broad range of ingredients characteristic of herb, the unknowns and synergistic compounds vital to the true nature and activity of the herb. Linneas extracts are clearly identifiable from their HPLC fingerprints. This uncompromising approach along with our validated GMP manufacturing process ensures the safety, quality and consistency of the botanical extracts we manufacture.
What types of tests do you conduct on raw materials, and how do you determine the testing methods used?
Ashmead: Our tests include physical examinations, metal content, heavy metal content, identity testing, Kosher certification and other tests to the specification of the ingredient. The methods that we use are published methods such as AOAC, USP, USEPA, etc., that are modified for our specific equipment setup, i.e., Agilent vs. Perkin Elmer.
Jones: Besides the typical HPLC, we also do light refraction, microbiological and comparison to standards.
Norton: The first thing to do is confirm with an identity test, usually thin layer chromatography (TLC), that you have the correct species of plant. Once confirmed, and before production begins on any of our standardized extracts, we first determine the assay value of our starting material. From here we can determine if any modifications are required to our manufacturing process. The whole idea of a standardized botanical extract is to provide the same percentage of active constituents from batch to batch. Testing the finished material varies depending on what the product is standardized for. Wherever possible an HPLC method of analysis is recommended due to the high degree of accuracy and reproducibility it offers. This is a good method to use when you want to identify a specific compound. Some products, however, contain a mixture of compounds that provide the activity. The methods generally used for testing in these instances are UV spectrophotometry or gravimetric. These methods identify compounds that are similar in chemical structure, thereby giving a cumulative percentage of their presence in the material. The methodology used is a function what you are testing for in the product. There are also other sophisticated methods and equipment available that can test for things like residual solvents and pesticide levels.
Parish: Designed Nutritional utilizes published standards of analysis for many compounds. These include IR, HPLC, GC, size exclusion chromatography, X-ray fluorescence, mass spec, NMR, melting point, solubility, titration, microbiological, elemental and heavy metals analysis. Occasionally analytical methods need to be developed for specific purposes. Steps are taken to validate both the methodology and the results. Deciding on which testing to conduct largely depends on the nature of the product, our knowledge of the processing, and the needs of the customer.
St. Clair: Our testing on raw materials is accomplished through several methods (i.e., F.T.I.R.spectrometer and soon our in house H.P.L.C.). These methods provide identification, separation, purification and quantification.
Ward: All Linnea extracts are subjected to extensive testing by our Quality Control laboratories, which employ such analytical capabilities as HPLC, TLC, HPLC mass detection, photometric and colormetric assay. The analysis of raw materials normally requires that two key criteria are met. Product identity, or is the product what you think it is? Not to be confused with testing for a standardized marker or active ingredient as products can be spiked, thus hiding their true identity. An identity test confirms the origin of the extract and/or gives a qualitative profile of the key compounds. Quantitative analysis ensures the key compounds are within the specified upper and lower limits. In the case of bilberry we test for identity by TLC, qualitative analysis is made for profiling of the anthocyanosides by HPLC and the quantitative analysis is made by colourmetric assay. It is also important to analyze for what should not be in the product, including testing to confirm the required low levels of residual solvents, low levels of heavy metals, low or absence of impurities and pharmaceutical standard of microbiological control. At Linnea we also test to ensure consistency of the physical aspects of the product including bulk density testing and laser particle size analysis. All methodology and instrumentation should be validated in accordance with international protocols. The type of analytical method chosen depends on the nature of ingredient and its chemicals composition. Certain ingredients are better suited to analysis by one type of analysis than another. In some case we use the published methods, such as those that appear in Pharmacopoeias, monographs or other peer reviewed sources. In other cases, the methods have been developed and validated by our own laboratories.
Books Review Botanical Standardization, QC Evaluation
CORAL GABLES, Fla.--Farma International is now distributing two new books about quality standards and botanical products. Quality Control of Herbal Drugs reviews extraction and testing procedures, ethnobotany in drug evaluation and analytical profiles of selected medicinal plants. Standardization of Botanicals provides quantitative testing methods, extraction processes, therapeutic functions and more for 25 widely used medicinal herbs. Both books are published out of India, the first from Business Horizons and the later from Eastern Publishers. Farma Distributors can be contacted at (305) 670-4416.