Paula Brown04.01.11
“Quality has to be caused, not controlled.”—Philip Crosby, 1926-2001
As we transition into 2011 and look back over the last couple years of columns, I have decided it is time to take a break. No, I won’t stop writing just yet; rather I will steer away from the GMP for this one column to consider the very nature of the column’s subject matter: quality. The past few columns have tended toward discussions of testing, but as any good quality assurance expert will tell you, you can’t test quality into a product. Establishing quality is a top-to-bottom process that assures that whatever goals you set for yourself in terms of making the product are met. Testing is only one part of the process. So if an HPLC chromatogram is the sole determinant of product quality, then I fear we are setting the bar pretty low.
“Even though quality cannot be defined, you know what quality is.” —Robert M. Pirsig, b. 1928
When judging an apple, we as consumers might look at it and consider the color, shape, lack of blemishes and surface dirt. If those are acceptable, we’d take a bite out of it and evaluate crispness, flavor, maybe the feeling of satiation. We would then say either “Mmmm” or “Yuck.” As apple growers, we would be careful with harvest and transport, perhaps check for blemishes and divert those apples deemed unsuitable to further processing. As distributors or retailers, we would rotate our apple stock so that old apples were sold before they got mushy and rotted.
Regulatory changes and even consumer demands of quality above freshness, appearance and taste, have moved to include a lack of pesticides and pathogens, as well as labeling that designates the apple variety and even Country of Origin. Apple producers can manage these requirements by using approved pesticides as directed or not using pesticides at all, by only selling fruit that is picked directly from the tree and not off the ground where they may come in contact with animal waste, and by maintaining clean storage facilities and transport (these are elements of Good Agricultural Practice, perhaps another time). However, none of these controls involves analytical testing. My point is that the savvy consumer can tell a good apple from a bad when it’s presented as fresh whole fruit, just as they can distinguish fresh ground espresso and freeze-dried instant coffee.
“Customers pay only for what is of use to them and gives them value. Nothing else constitutes quality.” —Peter F. Drucker, 1909-2005
In considering aspirin, there are superficial quality indicators that consumers can use to judge “quality”: Are the tablets all the same size, weight and color? Are they intact? Do they smell like vinegar? Those who remember the 1982 episode of poisoned acetaminophen will be concerned about packaging and more recent recalls may prompt concerns about over-potent products. Most important, perhaps, is the matter of whether or not the aspirin worked. Did your headache go away? Sensory evaluation coupled with easily discerned efficacy, are important hallmarks of aspirin quality. However, the health consequences of consuming poorly made drugs intended to work over long periods of time to reduce risk, such as statins, may not be observed for years. Your doctor may measure biomarkers of cardiovascular risk like cholesterol, but it’s difficult to collect evidence of “not having the heart attack that you might otherwise have had,” so efficacy is harder to judge than in the aspirin example.
The U.S. Congress (with FDA oversight) requires that companies ensure that drugs “work” before they can be marketed, and drug GMP potency testing is built in to make sure there’s enough (but not too much) of the active substance in the product. How do manufacturers make sure the product will meet the specification for potency? Well, they take all the necessary steps to ensure the right ingredients in the right amounts are employed, and then test to make sure that everything went as planned.
According to FDA’s MedWatch recall notice list-serve, most drug recalls result from GMP problems rather than from inherent safety issues. The former can cause therapeutic failure, while the latter can cause dangerous overdose. Drug GMP regulations don’t mention efficacy, because that is presupposed from the drug licensing process. However, controlling for and testing potency are vital to pharmaceutical manufacturing. For drugs the efficacy element is added to the general criteria for appearance, odor and taste that we cited in the apple example (i.e., there were no efficacy criteria in the food quality definition).
“Quality is never an accident; it is always the result of intelligent effort.”— John Ruskin, 1819-1900
Although classified as a special category of food, consumers may be challenged to judge the quality of dietary supplements by their senses, so quality must be built in and evaluated by the manufacturer. In this respect, quality assurance for supplements is similar to drugs, although with most supplements intending to convey mild benefit over long periods of time, there is no instant efficacy feedback. With measures for short- and long-term efficacy harder to come by, defining and measuring quality in dietary supplements is more challenging. Interestingly, you can peruse the final GMP rule and its voluminous preamble without finding efficacy mentioned anywhere. Lacking information on the appropriate amount of active substance (herb, etc.) that should be contained in each product, FDA does not use the word “potency” in the GMP, but instead uses “strength” and mandates that experts (i.e., the manufacturers) set science-based specifications for strength as well as identity, purity and composition.
The more prescriptive elements of the GMP deal with safety, such as the identity testing requirement that evolved from FDA’s concern from the substitution of foxglove (poisonous) for plantain (not poisonous) in the 1990s. Rules about testing for “reasonably anticipated contaminants” came about from FDA reports of adulteration with pharmaceutical drugs and contamination with pesticides, microbials and heavy metals. Cases of manufacturers being less than punctilious about the exact locations of decimal places in formulating products led to the need for having Master Manufacturing Records and documentation that the recipes therein were followed. And so on.
“It is easier to do a job right than to explain why you didn't.”—Martin Van Buren, 1782-1862
The intention of this column was to consider the nature of quality, but the process by which you assure quality is very much a part of GMP, so I might as well follow through with the FDA definition of quality: “the dietary supplement consistently meets the established specifications for identity, purity, strength, and composition and limits on contaminants, and has been manufactured, packaged, labeled, and held under conditions to prevent adulteration under sections 402(a)(1), (a)(2), (a)(3), and (a)(4) of the act” [referring to the Federal Food, Drug, and Cosmetic Act] (see 21 CFR 111.3).”
There are many different approaches to manufacturing in the GMP environment, two of which I wouldn’t recommend if a quality product is the endgame. First, you can save money in the short-term by avoiding the time consuming and expensive controls, oversight, paperwork and testing, right up until the FDA shuts you down. Second, you can do the above, but test at the end to see if your specifications are met. While you may save money in the short-term, your chances of a product failing go way up and you are likely to reach the same endpoint with FDA. The third alternative is to have careful written processes and controls in place, and documentation to support they are being followed, and to test the finished product to make sure everything went as planned. In the long run the cost of production, without controls in place, is surely greater than carefully controlled production that results in the expected product.
So, when all is said and done, ensuring quality within the context of the dietary supplement GMP comes down to three things: 1. Making sure you have the right component (whether ingredient, excipient or packaging) and it is clean; 2. You have a recipe and you can prove you followed it; and 3. You have the tools to prove your product is what you claim it to be. While “quality” for dietary ingredients is not easily defined, it is hopefully based on the substantiation information you have on file for your ingredients and your finished product.
“Quality means doing it right when no one is looking.”—Henry Ford, 1863-1947
To the consumer, quality means the product is and does what it says. Most finished dietary supplement products can’t be evaluated by taste, appearance or smell, and many cannot be evaluated based on an immediate effect. Quality endpoints for drugs and foods are relatively simple compared to endpoints for supplements. For drugs, the endpoints are “no more dangerous than it has to be” and “it works.” For foods, quality endpoints are “it doesn’t make us sick” and “it tastes good.” Supplements don’t necessarily have to taste good, but they shouldn’t make us sick and they should do what they claim to do. The supplement GMPs take care of the “don’t make us sick” part but put most of the responsibility for “does what it claims to do” on the manufacturer. So outside the descriptors of quality required by the GMP rule, quality will be based on the rigor and integrity of your substantiation data and integration of that data into your recipes and testing protocols.
“You can't fake quality any more than you can fake a good meal.”—William S. Burroughs, 1914-1997
GMP compliance can be verified by a lack of FDA warning letters to your company, but in the end consumers buy based on trust—trust that the manufacturer knows its business and takes pride in the connection of the products to nature and healing, not just the factory. Sort of like the farmer’s apples, quality is not really about testing; it is about the recipe. This is true for all good products from the apple to the drug. Just because Nana bakes her pie from memory, doesn’t mean there isn’t a recipe and if she screw’s up (sorry, Nana) the feedback will be pretty immediate when you take a bite. In industrial settings, your brand’s reputation can be worth millions to your bottom line, and that reputation hinges on consumer perceptions of quality.
As we transition into 2011 and look back over the last couple years of columns, I have decided it is time to take a break. No, I won’t stop writing just yet; rather I will steer away from the GMP for this one column to consider the very nature of the column’s subject matter: quality. The past few columns have tended toward discussions of testing, but as any good quality assurance expert will tell you, you can’t test quality into a product. Establishing quality is a top-to-bottom process that assures that whatever goals you set for yourself in terms of making the product are met. Testing is only one part of the process. So if an HPLC chromatogram is the sole determinant of product quality, then I fear we are setting the bar pretty low.
“Even though quality cannot be defined, you know what quality is.” —Robert M. Pirsig, b. 1928
When judging an apple, we as consumers might look at it and consider the color, shape, lack of blemishes and surface dirt. If those are acceptable, we’d take a bite out of it and evaluate crispness, flavor, maybe the feeling of satiation. We would then say either “Mmmm” or “Yuck.” As apple growers, we would be careful with harvest and transport, perhaps check for blemishes and divert those apples deemed unsuitable to further processing. As distributors or retailers, we would rotate our apple stock so that old apples were sold before they got mushy and rotted.
Regulatory changes and even consumer demands of quality above freshness, appearance and taste, have moved to include a lack of pesticides and pathogens, as well as labeling that designates the apple variety and even Country of Origin. Apple producers can manage these requirements by using approved pesticides as directed or not using pesticides at all, by only selling fruit that is picked directly from the tree and not off the ground where they may come in contact with animal waste, and by maintaining clean storage facilities and transport (these are elements of Good Agricultural Practice, perhaps another time). However, none of these controls involves analytical testing. My point is that the savvy consumer can tell a good apple from a bad when it’s presented as fresh whole fruit, just as they can distinguish fresh ground espresso and freeze-dried instant coffee.
“Customers pay only for what is of use to them and gives them value. Nothing else constitutes quality.” —Peter F. Drucker, 1909-2005
In considering aspirin, there are superficial quality indicators that consumers can use to judge “quality”: Are the tablets all the same size, weight and color? Are they intact? Do they smell like vinegar? Those who remember the 1982 episode of poisoned acetaminophen will be concerned about packaging and more recent recalls may prompt concerns about over-potent products. Most important, perhaps, is the matter of whether or not the aspirin worked. Did your headache go away? Sensory evaluation coupled with easily discerned efficacy, are important hallmarks of aspirin quality. However, the health consequences of consuming poorly made drugs intended to work over long periods of time to reduce risk, such as statins, may not be observed for years. Your doctor may measure biomarkers of cardiovascular risk like cholesterol, but it’s difficult to collect evidence of “not having the heart attack that you might otherwise have had,” so efficacy is harder to judge than in the aspirin example.
The U.S. Congress (with FDA oversight) requires that companies ensure that drugs “work” before they can be marketed, and drug GMP potency testing is built in to make sure there’s enough (but not too much) of the active substance in the product. How do manufacturers make sure the product will meet the specification for potency? Well, they take all the necessary steps to ensure the right ingredients in the right amounts are employed, and then test to make sure that everything went as planned.
According to FDA’s MedWatch recall notice list-serve, most drug recalls result from GMP problems rather than from inherent safety issues. The former can cause therapeutic failure, while the latter can cause dangerous overdose. Drug GMP regulations don’t mention efficacy, because that is presupposed from the drug licensing process. However, controlling for and testing potency are vital to pharmaceutical manufacturing. For drugs the efficacy element is added to the general criteria for appearance, odor and taste that we cited in the apple example (i.e., there were no efficacy criteria in the food quality definition).
“Quality is never an accident; it is always the result of intelligent effort.”— John Ruskin, 1819-1900
Although classified as a special category of food, consumers may be challenged to judge the quality of dietary supplements by their senses, so quality must be built in and evaluated by the manufacturer. In this respect, quality assurance for supplements is similar to drugs, although with most supplements intending to convey mild benefit over long periods of time, there is no instant efficacy feedback. With measures for short- and long-term efficacy harder to come by, defining and measuring quality in dietary supplements is more challenging. Interestingly, you can peruse the final GMP rule and its voluminous preamble without finding efficacy mentioned anywhere. Lacking information on the appropriate amount of active substance (herb, etc.) that should be contained in each product, FDA does not use the word “potency” in the GMP, but instead uses “strength” and mandates that experts (i.e., the manufacturers) set science-based specifications for strength as well as identity, purity and composition.
The more prescriptive elements of the GMP deal with safety, such as the identity testing requirement that evolved from FDA’s concern from the substitution of foxglove (poisonous) for plantain (not poisonous) in the 1990s. Rules about testing for “reasonably anticipated contaminants” came about from FDA reports of adulteration with pharmaceutical drugs and contamination with pesticides, microbials and heavy metals. Cases of manufacturers being less than punctilious about the exact locations of decimal places in formulating products led to the need for having Master Manufacturing Records and documentation that the recipes therein were followed. And so on.
“It is easier to do a job right than to explain why you didn't.”—Martin Van Buren, 1782-1862
The intention of this column was to consider the nature of quality, but the process by which you assure quality is very much a part of GMP, so I might as well follow through with the FDA definition of quality: “the dietary supplement consistently meets the established specifications for identity, purity, strength, and composition and limits on contaminants, and has been manufactured, packaged, labeled, and held under conditions to prevent adulteration under sections 402(a)(1), (a)(2), (a)(3), and (a)(4) of the act” [referring to the Federal Food, Drug, and Cosmetic Act] (see 21 CFR 111.3).”
There are many different approaches to manufacturing in the GMP environment, two of which I wouldn’t recommend if a quality product is the endgame. First, you can save money in the short-term by avoiding the time consuming and expensive controls, oversight, paperwork and testing, right up until the FDA shuts you down. Second, you can do the above, but test at the end to see if your specifications are met. While you may save money in the short-term, your chances of a product failing go way up and you are likely to reach the same endpoint with FDA. The third alternative is to have careful written processes and controls in place, and documentation to support they are being followed, and to test the finished product to make sure everything went as planned. In the long run the cost of production, without controls in place, is surely greater than carefully controlled production that results in the expected product.
So, when all is said and done, ensuring quality within the context of the dietary supplement GMP comes down to three things: 1. Making sure you have the right component (whether ingredient, excipient or packaging) and it is clean; 2. You have a recipe and you can prove you followed it; and 3. You have the tools to prove your product is what you claim it to be. While “quality” for dietary ingredients is not easily defined, it is hopefully based on the substantiation information you have on file for your ingredients and your finished product.
“Quality means doing it right when no one is looking.”—Henry Ford, 1863-1947
To the consumer, quality means the product is and does what it says. Most finished dietary supplement products can’t be evaluated by taste, appearance or smell, and many cannot be evaluated based on an immediate effect. Quality endpoints for drugs and foods are relatively simple compared to endpoints for supplements. For drugs, the endpoints are “no more dangerous than it has to be” and “it works.” For foods, quality endpoints are “it doesn’t make us sick” and “it tastes good.” Supplements don’t necessarily have to taste good, but they shouldn’t make us sick and they should do what they claim to do. The supplement GMPs take care of the “don’t make us sick” part but put most of the responsibility for “does what it claims to do” on the manufacturer. So outside the descriptors of quality required by the GMP rule, quality will be based on the rigor and integrity of your substantiation data and integration of that data into your recipes and testing protocols.
“You can't fake quality any more than you can fake a good meal.”—William S. Burroughs, 1914-1997
GMP compliance can be verified by a lack of FDA warning letters to your company, but in the end consumers buy based on trust—trust that the manufacturer knows its business and takes pride in the connection of the products to nature and healing, not just the factory. Sort of like the farmer’s apples, quality is not really about testing; it is about the recipe. This is true for all good products from the apple to the drug. Just because Nana bakes her pie from memory, doesn’t mean there isn’t a recipe and if she screw’s up (sorry, Nana) the feedback will be pretty immediate when you take a bite. In industrial settings, your brand’s reputation can be worth millions to your bottom line, and that reputation hinges on consumer perceptions of quality.
