Alkemy 101 Newsletter - January 2012

New Year! New Advances!

Welcome to 2012 everyone! This year, we are continuing to expand for more capacity by upgrading our equipments and adding more highly experienced analytical chemists to tackle nonGMP (R&D) and cGMP work. We have also launched a new initiative to help reduce unforeseen testing delays and OOS's due to incomplete methodology or sample information; as a result we will be able to offer reduced turn-around times and pricing for routine sample testing with qualfied HPLC or UPLC methods. Waters ACQUITY UPLC H-Class We just acquired our new UPLC to offer optimization of legacy HPLC methods that have extensive run times. Additionally, we are developing our library for amino acid and peptide analysis in both pure form as well as complex sports nutrition and performance products. While a baseline of experience is critical, efficient method development and/or qualification and validation are critical to long term brand success. Composite Reference Botanicals (CRBs) In 2009 we launched our line of Composite Reference Botanicals for customers developing their own in-house Identity Testing capabilities by HPTLC on incoming raw materials. With approximately 150 CRBs comprised of botanical specimens that have been verified dating back nearly a decade or more, including many to vouchered specimens, we're proud to say that we have the largest offering of reference botanicals for Ingredient Identity purposes available commercially. For a current list, please contact us today! In addition to Identity Testing, many clients have bought our CRB's to assist in the following ways: Product Formulation - Utilzing a CRB as a verified ingredient to start product development and/or improve upon their product formulation. Process Development - CRBs are whole botanicals, but enable customers to evaluate new extraction procedures/techniques with identify confirmed whole raw materials to generate a qualitative profile whether by FTIR, HPTLC or even HPLC. Investigations - CRBs with their specific phytochemical profiles can give insight to potential Supply Chain issues as well as limitations or gaps in testing methodology. Just Send It To Alkemists

Alkemy 101 Newsletter - November 2011

Is your Intellectual Property protected by your Vendor?

- What is in your Confidentiality Agreement or Service Agreement? - Are you getting a deal for the price you are paying or being taken advantage of? - What are the potential gaps in your IP development and protection strategy? Intellectual Property comes in all shapes and sizes, and sometimes companies don't know they even have any IP to protect other than a copyright. At an economic time when companies must adapt their position to best leverage their brand and grow sales, we are finding out quite often that the back door is left wide open. Case in point, a small company selected a particular Contract Manufacturing Organization (CMO) vendor that has an industry recognized seal of GMP compliance and a recognized brand name. After working with the CMO to get the ideal formulation and manufacturing the first several production batches, the company opted for a third-party investigative analysis of their finished product due to a small discrepancy. It was then that the company realized "things" were not what they seemed i.e. their formulation had been changed without their prior approval. Furthermore, because the CMO partner didn't charge the company for development on the final formulation, they would not support the investigation or disclose any details of the ingredients or testing of the product because it was "proprietary" ...to the CMO! In another case, a start-up company engaged in development of Botanical Drug products and related IP sought out a laboratory to contract the isolation and characterization of some new compounds. The contract lab they selected offered the company to do the work at a great rate including delivery of nearly twice the amount of the desired compounds. With compounds in hand, the company went on to the next stages of developing their product. They did not realize the lab they contracted also had their own business interest in the compounds. Because of opting to conduct the work at a lower price compared to some other bids received, they inadvertently waived the rights to the isolation and purification processes, the characterization IP and ultimately the exclusive use of the isolated compounds because these were outside of the Scope of Work. By the time the package was submitted, the various compounds were already on the open market. To help understand, identify and protect your IP, the folks at Ingredient Identity can help!

Alkemy 101 Newsletter - October 2011

Do you have a Quality Agreement with your Contract Manufacturer?

- What is a Quality Agreement, is it needed and how is it different than a Service Agreement? - How are the raw materials in your finished product qualified by your manufacturer routinely? - Should you get copies of test reports from your CMO partner for your finished products? A Quality Agreement is a legally binding document, which outlines specific quality parameters for a service to be rendered and identifies the responsible party (or parties) obligated to uphold those parameters under the Service Agreement. In lamens terms, its the upfront contract you put in place with your manufacturer in addition to the Service Agreement, to make a product in accordance with your standards and current regulations. A Quality Agreement defines all the aspects of a service or product relating to how identity, purity/potency, quality and overall safety of a given product is manufactured and maintained. Whereas the Service Agreement typically defines the legalese and scope of a project as well as deliverables for a set price, it does not usually address "HOW" the partner will accomplish the service; hence, the Quality Agreement. A well drafted Quality Agreement offers you protection should your contract manufacturer not uphold the terms therein. For example, if an agreed upon quality testing regimen is not followed or disregarded altogether, you may very well have legal leverage to change certain terms or dismiss the Service Agreement altogether. Same thing applies if your contract manufacturer is found operating not under cGMP compliance or changes raw material suppliers without your permission or appropriate qualifiction. Whether the CMO has an in-house laboratory or contracts with a third-party lab, you should request and have access to all testing records for your raw materials and your finished product on file.

Alkemy 101 Newsletter - September 2011

Why doesn't your HPLC Method Work Right?

- The Method wasn't properly developed or qualified - The "Reference Standard" wasn't really a standard at all - The analytical data was inaccurately interpreted - Wait! The method does work....the raw materials were switched without being properly qualified, etc. There are numerous reasons why an HPLC method might not work for your product, but are you getting the run around as to what the real reasons are, and more importantly what the right solution is? Moreover, how can you identify the right solution for the least amount of money? A strategic understanding of the appropriateness of method qualification should be considered fundamental to any Quality System. All too often, we are engaged in last minute troubleshooting for customers who had little or no early enough investment into the quality management of their products from an analytical perspective. Often, the mindset remains on finding a quick and dirty formulation followed by aggressive marketing of such products without qualifying the supply chain properly or ensuring analytical methods are in place. The resulting production delays, development fees and other costs relating to release testing, cGMP compliance and lastly mitigation of FTC or civil litigation can scale up to be insurmountable and cost-prohibitive in a very short period of time, if critical steps were not taken in the beginning. For more information on how to qualify an HPLC method or to determine if method development is required for your product, give us a call today!

Alkemy 101 Newsletter - August 2011

Identity Testing for Botanical Oils by HPTLC

- Affordable alternative to ID oil ingredients - Run multiple samples in parallel - 5 Day Turn-around Time for routine oils - Accurate chemical profiling of complex oil blends Yes, it's possible and more affordable than other more costly analytical techniques such as GC or GCMS! We've expanded our portfolio of Identity Testing methodologies for more essential and botanical oils used in Food Supplements, Cosmeceuticals and Aromatherapies. For comprehensive ID work of either pure oil ingredients or complex blends, we can profile the sample to confirm identity and compliance with cGMP's.

Alkemy 101 Newsletter - May 2011

Need FDA Inspection Support?

Alkemists Labs has expanded its consultancy services to rapidly tackle more of the challenges with meeting the cGMP's, such as Quality Systems audits, responding to FDA inspections including warning letters or on-site representation and testing complex dietary supplement finished products.

Some areas of support include the following:

• cGMP Compliance Audits of your manufacturing operations/parnters
• General SOP Writing and Guidance
• Scientific Data Review from internal/external contract labs
• Response Letters to FDA
• QC or QA Planning
• Investigative research including study designs
• Sampling and In-Process Testing
• Stability Study Designs & Protocols

Allergen Testing Now Available

Allergen testing for raw material ingredients by PCR Analysis for Allergen botanical ingredients is now available through Alkemists from AuthenTechnologies headed by Danica Reynaud, Ph.D. In an effort to support detection of known allergen contaminants/adulterants botanical raw materials by DNA presence, Alkemists is providing pass-through testing in collaboration with AuthenTechnologies to screen ingredients for customers.

Targeted allergens by PCR analysis from the following:
Almond, Brazil Nut, Hazelnut, Peanut, Pecan, Soy, Walnut and Wheat

Contact Bryan Fine at Alkemists for more information on the types of allergens and testing details.

Quality Initiative Series: An Interview with Elan Sudberg, Lab Manager, Alkemists Labs

Elan Sudberg is the Lab Manager for Alkemists Pharmaceuticals. He has a degree in Chemistry, and a background in business and botany. He began Alkemists Labs with his father, Dr. Sidney Sudberg, who also has a background in analytical chemistry, as well as herbal medicine, chiropractics and acupuncture. Dr. Sudberg was also trained by the Food and Drug Administration.

Alkemists began about 11 years ago, doing identity testing such as High Performance Thin Layer Chromatography (HPTLC). Over the years they’ve picked up clientele from all over the world, and to date have studied over a thousand different species of botanicals. Over the last five years, the lab’s services have increased from microscopic identity and HPTLC identity testing to include HPLC purity analysis tests, and Ultra-violet Visual (UV/VIS). They specialize in botanical analysis, natural product analysis as well as identification and characterization of natural products. Alkemists now boasts 14 employees and doubled its sales since last year.

What instrumentation do you have in house and what is its typical use?

High Performance (or Pressure) Liquid Chromatography (HPLC) with Ultra-violet (UV) and Diode Array Detector (DAD) used for purity & content analysis as well as constituent ID & quantitation. High Performance Thin Layer Chromatography (HPTLC) is used for identity testing, purity analysis and adulteration detection as well as quantitation of marker compounds. Ultra-Violet/Visual (UV/VIS) analysis is another way to test for purity and content analysis. Microscopy is also used for botanical identification and adulteration detection.

What are the limitations of the instruments above?

HPLC/UV-DAD limitations can include not seeing the forest for the trees, meaning that in the attempt to quantify single markers, information on the broader scale will be missed.

Inert adulterants may not be detected. Some sample types are difficult to analyze, such as fats/lipids, as there needs to be a chromophore (the part of a molecule responsible for its ‘color’.) There is always the possibility that the compound of interest will not be separated/resolved completely and hence the values reported will tend to be higher than what they should be as a consequence. Methods for botanical testing are not always available.

HPTLC limitations are that inert adulterants may not be detected, there is a limitation in analyte resolution, methods for botanical analyses are not always available and they can be challenging to quantify.

UV/VIS limitations include; inert adulterants will be missed, limitation in analyte detection, methods for botanical analysis are not always available and quantitation is broad and/or non-specific.

Microscopy’s limitations for identity are that it is not applicable for extracts or liquids.

How do you know a method is ‘suitable for its intended use?’

It should be able to confirm/analyze to the specifications of the material in question & to whatever level of confidence that meets the needs of the intended application of that material e.g. a pharmaceutical drug vs. plant drug or food or other natural products. In other words we don’t need to use LC/MS to analyze for the presence or absence of caffeine to determine the identity of coffee if the same results or better/more complete can be derived with something like HPTLC or microscopy. It would be like driving a nail into a piece of wood with a sledge hammer instead of a carpenters hammer or using your Ferrari to drive to the store around the block when you could have easily walked, etc. unless your trying to impress your friends & neighbors. It would be a waste of time, money & energy to use the ‘overkill’ methods when something else that is sufficient for the intended purpose can do it as well or better in some cases.

A common problem I see facing this industry is the overuse of certain technology in quality control of natural products. We tend to be enamored with technology & frequently use methods that are unmistakably accurate but the level of accuracy achieved with the ‘sexy’ instrumentation does not necessarily increase the value of the data since the more accurate data does not improve the value of the material being tested. There is also no significant advantage to the material/product being tested when the data collected is more accurate since the increase in accuracy does not improve the quality of the material being tested. You cannot test quality into products.

In your opinion, is this straightforward? What are common issues or decisions one must make?

Unfortunately, nothing in natural products is straightforward and one has to constantly be vigilant with every sample, project or material being tested. There are so many variables to manage with every natural product that it is important to pay close attention to data analysis. By doing this, especially with natural products, one can create a data base that will have more and more value over time so that better decisions can be made with respect to the intended use. In business ‘cash is king’ in analysis ‘data is king’. It is essential that if you are in the business of data, that you maintain an active statistical data analysis department to constantly re-evaluate data to be certain that it maintains the highest quality possible.

As an analytical lab, how are your obligations or expectations changing under supplement GMP’s?

We are obligated to provide validated analyses at an affordable price with a fast turn around in order to meet the industry’s needs. Our customers rely on our services to help them move their products through the supply chain efficiently and accurately. We do not overcharge, nor can we take too much time producing results as both would mean the end of our customers’ livelihood. The current pressure, not necessarily expressed from clients, is turnaround time, without an increase in the cost. We know that our clients need results faster and cheaper, without compromising quality. This is the on-going challenge we have and as a laboratory concerned with producing the highest quality data possible, we are constantly reviewing our processes, methods & procedures to become more efficient without a loss of quality.

Do third parties, (i.e. not your customers) contact you for information about test methods and results?

All the time. Unlike many labs, our methods are transparent and are issued on the C of A at no extra charge. We feel this transparency is following the model of scientific research and is ultimately beneficial to the industry as opposed to making everything proprietary and costly and sometimes plain mysterious.

Do your customers ask about your compliance with acceptable practices?

Yes, we are audited by many of our customers to ISO 17025 and/or GLP standards and are striving for ISO 17025 accreditation by 2010.

How do you differentiate your lab and its capabilities and expertise from others?

We are passionate about our work and take the natural product industry very seriously because we know these products, especially if they are made with quality in mind, actually work and can be used effectively if and only if that quality is confirmed. We have specialized in plant identification and characterization for over a decade with a background in natural product science for 30 years before that. Many other labs offer a wide variety of services but do not have a full grasp of plant identification or characterization. An internal herbarium with over 6000 specimens on premises is utilized to verify all incoming samples with multiple specimens of the same plant species and or related species for comparison to add confidence & credibility to our analyses. We are also family owned and operated which gives our team an increased sense of pride and responsibility that goes beyond just getting samples in and out as fast as possible.

What major investments have you made in ‘quality’, QA/QC in the past year?

We have recently brought in the entire line of new HPTLC equipment, made by Camag, which has more automated features and allows more samples to be looked at, at the same time as well as being fully compliant with GLP. We can keep better records of the analyses that we do and this allows us to produce more consistent, reproducible results.

What do you plan in the near future?

We are planning to introduce ‘Measurement Uncertainty’ calculations to our data so that the data we produce has more significance. This will give clients a better understanding of the actual accuracy of their data. It’s really just more academic about the results that we give out, being truthful and upfront about any potential variations or differences in results that can’t be avoided with any measurement. It’s about being as accurate as one can be. We are also planning on adding to our equipment Gas Chromatography and Mass Spec capacity within the next year.

What do you see emerging as a critical QA/QC issue with your services?

How to define 'quality of data' is a major issue with analysis in general with any analytical laboratory. There is a great need for data to be qualified so that the customer has confidence that the data produced in one lab will be equivalent to that produced by any other lab. While method validation may demonstrate that a method ‘works’ for a particular analyte in a specific matrix, it does not guarantee that the lab knows how to use the method properly to get the right/accurate results. Method proficiency testing is a much more useful concept for labs to use to demonstrate ability and credibility of the data produced.

Do you use standards, reference materials and validated methods and are they appropriately used? Where do you get them from?

We always use chemical reference materials/standards and plant reference materials to be able to produce accurate results. Methods are developed so that a minimum level of validation is maintained so that it is ‘fit for purpose’.

We obtain our reference standards from Sigma, Phytolab, Chromadex, Indofine, USP and/or NIST.

Are there questions you wish your clients would ask more frequently?

I would suggest that clients be aware of the fact that data, which is the product that a laboratory produces, must be fully transparent. In other words, if all you are getting is a number with no indication of how the number was produced, then the lab is not being forthcoming. Method information should be freely accessible to all customers so that a method can be reproduced to verify a result in their own lab or by another lab if the need arises so that we are all on a level playing field.

What should the natural products industry know about an analytical lab GMP’s?

They should routinely audit the Quality System used by a lab to know that there are procedures written that take into account all aspects of a lab’s quality assurance.

Do you feel more companies should be using analytical labs that follow certain practices, rather than just any analytical lab?

Yes, it is imperative that an analytical lab pay very close attention to producing the highest quality data possible and that they can back up their data, not just with the most advanced or high tech equipment but with quality control practices that lend credibility to the data produced, whether the data is collected by wet chemistry or the most advanced technology. Unfortunately you can’t just trust a lab in this industry, or any other industry, at face value. Check for references from other clients who’ve used the labs before, and look for testimonials. We have some testimonials on our website from some pretty large companies who are happy with our services, which is great. They wouldn’t give us that testimonial in their name if they weren’t happy with our work. There are labs out there that you can’t just trust, and that’s why references and testimonials are important.

Do you feel that most people have enough knowledge to make good decisions in their choice of analytical labs, or is this something about which more information could be made available to help educate the industry?

I feel that more information needs to be made available to the industry so that they know what the difference between good data & just any data is just because a validated method is used. We recently co-produced a seminar addressing this issue in our area presented by several quality control experts in conjunction with our local chapter of the AOAC at the local FDA labs to address the issue of ‘data quality’ or credibility with industry members. We are planning to offer more of these seminars or workshops in the future so as to bring all interested parties up to speed with respect to quality of data or data integrity. We believe this will ultimately help close the gap between this industry and other related industries that are responsible for the food supply and/or the health and well-being of the public.