Paula Brown06.01.11
My last column (April 2011) was a tough one to write, however the process of stepping back shook cobwebs off some interdisciplinary synapses and got me thinking about aspects of quality beyond those involving analytical chemistry—in particular, the roles of knowledge and ignorance in supply chain management and how these pertain to quality. I’ll concentrate on the three P’s for now: Provenance, Processing & Production.
Take a minute and think about everything these three terms imply—all movement and storage of raw materials, in-process materials and finished products from manufacture through to the consumer. Consider the level of knowledge and detail you actually need to have about all of these elements to ensure a high quality product is delivered.
In analytical science, we know that every measure or variable (such as weighing, pipetting, loss during transfer, etc.) has uncertainty associated with it, and these errors propagate. Add enough steps to any process and even very small errors associated with each can accumulate in a hurry.
In a previous column, the SIDI protocol (Standardized Information on Dietary Ingredients) was introduced (“Quality Focus,” November 2009). To recap, it provides a checklist for purchasers to use when sourcing raw materials. The template for botanicals includes a section called “Botanical Manufacturing Information” with places to enter the name and address of the manufacturer, the mode of manufacturing, agricultural process, manufacturing process, GMP compliance sterilization or fumigation method, and known or potential sources of impurities and/or contaminants. The agricultural process section gives guidance on what sorts of information to enter, such as method(s) of cultivation (e.g., sustainably-wildcrafted or cultivation method), identification, harvest, handling and post-harvest processing.
In order to manage the supply chain, the SIDI checklist would have to be filled out each time the material changes hands. The provenance of the material would be tracked by a form from the collector or farmer and a form from for the purchasing center that buys and compiles material from small farms/collectors. Throughout the processing there would be forms—from the facility that processes material, ships the material, extracts material, the bulk packager, maybe another shipper. After all these stages the dietary supplement ingredient goes into production and there could be more forms for the finished product manufacturer, packager, labeler and distributor. While there may be fewer or more steps, the point is there are numerous steps requiring documents to trace materials from field to finished product.
As a manufacturer, perhaps you will see a single checklist from the raw material supplier and one would hope it reflects the information from all the other checklists that have been accumulating. The intent here isn’t to suggest we print redundant certificates but rather to point out the level of detail that can exist for every stage of every component in a finished product, despite whether the information is known or not. Rather than blather on about forms and how “what we don’t know may in fact hurt us,” let’s consider an example or two...
Provenance
The SIDI form gives the supplier the opportunity to determine whether the material was wild collected or cultivated, as well as the place (country, farm, GPS coordinates) from which it was collected. The geographic origins of a material can provide volumes of information over and above simply knowing where something was grown.
There can be tremendous implications to quality through informing manufacturers about the likelihood of a particular contaminant, such as the use of DDT to combat malaria in some countries. USDA’s Animal and Plant Health Inspection Service (APHIS) can and will stop botanical raw material at the border if it comes from a country that is known to harbor a plant pathogen, while the same material from a non-infested country is allowed.
Processing
Processing and preservation techniques vary from supplier to supplier. Simple drying of materials can range from lying out in the sun, wood or charcoal fires to a temperature-controlled vacuum oven. Knowing how a material was dried is critical information when considering potential risk associated with that material. For example, sun-dried materials in warm climates may be at risk for mold growth on wet biomass. Molding of root materials, such as ginseng, can lead to unacceptable levels of mycotoxins. Biomass dried with the assistance of open fire may cause the material to be high in potentially cancer-causing polyaromatic hydrocarbons (PAH).
Production
Botanicals (and other dietary supplement ingredients) can be contaminated or otherwise sullied by the manufacturing process just as easily as in any other part of the supply chain. Many sensory and/or pharmacologically relevant compounds can be degraded with light, heat or even changes in pH. Spray-drying an extract for too long or at too high a temperature could turn a nice, aromatic, light-gray green material into a charred mess. Even an over zealous tablet compression could generate enough heat to decrease the quality of a finished product. The selection of the excipients could also lead to contamination and impact quality.
Summary
This column was not intended to be a laundry list of areas that can introduce risk and potentially decrease product quality. Obviously we cannot know everything and we cannot control everything. But making decisions throughout the supply chain to allocate resources based on potential risk is just good business management.
That being said, just identifying risks seems to lead back to a massive laundry list that gets longer and longer with the number of components, ingredients and products a company deals with in manufacture. Perhaps more significant than all the potential sources of risk in a supply chain are the consequences of failures. I believe FDA has made it clear where it feels the consequence of failure poses too great a risk through enactment of the 100% Identity Rule.
Take a minute and think about everything these three terms imply—all movement and storage of raw materials, in-process materials and finished products from manufacture through to the consumer. Consider the level of knowledge and detail you actually need to have about all of these elements to ensure a high quality product is delivered.
In analytical science, we know that every measure or variable (such as weighing, pipetting, loss during transfer, etc.) has uncertainty associated with it, and these errors propagate. Add enough steps to any process and even very small errors associated with each can accumulate in a hurry.
In a previous column, the SIDI protocol (Standardized Information on Dietary Ingredients) was introduced (“Quality Focus,” November 2009). To recap, it provides a checklist for purchasers to use when sourcing raw materials. The template for botanicals includes a section called “Botanical Manufacturing Information” with places to enter the name and address of the manufacturer, the mode of manufacturing, agricultural process, manufacturing process, GMP compliance sterilization or fumigation method, and known or potential sources of impurities and/or contaminants. The agricultural process section gives guidance on what sorts of information to enter, such as method(s) of cultivation (e.g., sustainably-wildcrafted or cultivation method), identification, harvest, handling and post-harvest processing.
In order to manage the supply chain, the SIDI checklist would have to be filled out each time the material changes hands. The provenance of the material would be tracked by a form from the collector or farmer and a form from for the purchasing center that buys and compiles material from small farms/collectors. Throughout the processing there would be forms—from the facility that processes material, ships the material, extracts material, the bulk packager, maybe another shipper. After all these stages the dietary supplement ingredient goes into production and there could be more forms for the finished product manufacturer, packager, labeler and distributor. While there may be fewer or more steps, the point is there are numerous steps requiring documents to trace materials from field to finished product.
As a manufacturer, perhaps you will see a single checklist from the raw material supplier and one would hope it reflects the information from all the other checklists that have been accumulating. The intent here isn’t to suggest we print redundant certificates but rather to point out the level of detail that can exist for every stage of every component in a finished product, despite whether the information is known or not. Rather than blather on about forms and how “what we don’t know may in fact hurt us,” let’s consider an example or two...
Provenance
The SIDI form gives the supplier the opportunity to determine whether the material was wild collected or cultivated, as well as the place (country, farm, GPS coordinates) from which it was collected. The geographic origins of a material can provide volumes of information over and above simply knowing where something was grown.
There can be tremendous implications to quality through informing manufacturers about the likelihood of a particular contaminant, such as the use of DDT to combat malaria in some countries. USDA’s Animal and Plant Health Inspection Service (APHIS) can and will stop botanical raw material at the border if it comes from a country that is known to harbor a plant pathogen, while the same material from a non-infested country is allowed.
Processing
Processing and preservation techniques vary from supplier to supplier. Simple drying of materials can range from lying out in the sun, wood or charcoal fires to a temperature-controlled vacuum oven. Knowing how a material was dried is critical information when considering potential risk associated with that material. For example, sun-dried materials in warm climates may be at risk for mold growth on wet biomass. Molding of root materials, such as ginseng, can lead to unacceptable levels of mycotoxins. Biomass dried with the assistance of open fire may cause the material to be high in potentially cancer-causing polyaromatic hydrocarbons (PAH).
Production
Botanicals (and other dietary supplement ingredients) can be contaminated or otherwise sullied by the manufacturing process just as easily as in any other part of the supply chain. Many sensory and/or pharmacologically relevant compounds can be degraded with light, heat or even changes in pH. Spray-drying an extract for too long or at too high a temperature could turn a nice, aromatic, light-gray green material into a charred mess. Even an over zealous tablet compression could generate enough heat to decrease the quality of a finished product. The selection of the excipients could also lead to contamination and impact quality.
Summary
This column was not intended to be a laundry list of areas that can introduce risk and potentially decrease product quality. Obviously we cannot know everything and we cannot control everything. But making decisions throughout the supply chain to allocate resources based on potential risk is just good business management.
That being said, just identifying risks seems to lead back to a massive laundry list that gets longer and longer with the number of components, ingredients and products a company deals with in manufacture. Perhaps more significant than all the potential sources of risk in a supply chain are the consequences of failures. I believe FDA has made it clear where it feels the consequence of failure poses too great a risk through enactment of the 100% Identity Rule.
