FDA Inspection

cGMP Certified Isnt Enough

Ten questions to ask a cGMP-certified manufacturer to ensure they go beyond the minimum federal manufacturing requirements.

Selection of a contract manufacturer is potentially the most important decision a brand owner can make. A contract manufacturer is more than a service provider; it is a partner. This is an important distinction. While a poor service provider may cause frustration, a poor partner can sink a business. Think Im being overly dramatic? Ask one of the many who have failed a FDA cGMP(current good manufacturing practice) audit, and they will likely say a lack of a partnership with thier contract manufacturer played a significant role in their demise.

Look Beyond Third-Party  cGMP Certification

Its a common misconception that all cGMP-certified manufacturers operate with the same or similar level of cGMP compliance. As with any business/profession, there are varying degrees of experience, expertise and regulatory compliance. For example, just because someone has a degree from a medical school does not mean they are an excellent doctor. It simply means they have met the basic standards required to practice medicine.

The bottom line is that while cGMP certification is one of the first things to look for, it is by no means the last. There is no shortage of cGMP-certified facilities. Many facilities have the capital and equipment necessary to appear compliant. The key word here is appear." In order to determine the true level of cGMP compliance, customers and/or potential customers must look beyond third-party certification. In doing so, a brand owner is sure to find dramatic and sometimes unsettling differences between cGMP-certified facilities. 

High-level cGMP compliance and true finished goods quality requires a combination of exceptional process/production controls and extensive qualitative/quantitative laboratory testing. One without the other is not enough.

Qualitative and Quantitative Lab Operations

Many customers and/or potential customers are familiar with cGMPs as they relate to the production process. However, many are less than familiar with cGMPs as they relate to laboratory operations.

Here are 10 questions to ask a cGMP-certified manufacturer:

1. What makes your facility different than other cGMP-certified manufacturers?

Appropriate response:  Testing, testing, and more testing. While many companies claim to provide  quality, only a few have the laboratory equipment and expertise to do so. Unfortunately, only a handful of manufacturers perform the extensive raw material and finished goods testing required for high-level cGMP compliance. The proof is in the pudding. Facilities that embrace cGMPs are facilities that test.

2. Please estimate the investment your company has made in laboratory equipment and personnel to ensure high level cGMP compliance.

Appropriate response:  While many companies make bold statements about their quality, few have made the large financial investment in laboratory equipment and personnel. cGMPs allow for the use of third-party contract laboratories. However, it's good to also have in-house analytical expertise and experience. A full-scale in-house analytical laboratory expedites and facilitates high-level cGMP compliance.

3. What are your in-house laboratory capabilities?

Appropriate response:  Depending on specific needs and product type, a contract manufacturers laboratory should include most if not all of the following:  

  • UV-Vis (ultraviolet-visible spectrophotometry)
  • HPLC/UPLC (high pressure or ultra-high pressure liquid chromatography)
  • ICP-MS (inductively coupled plasma mass spectrometry); If you sell in California, this is a must-have piece of equipment.
  • GC (gas chromatography)
  • FTIR, mid-IR and/or NIR (infrared spectroscopy)
  • Drying ovens and/or Karl Fischer titration equipment necessary to determine the moisture/water  content
  • Accelerated stability (shelf life) chambers
  • Microbiological (plating, incubation, etc.)
  • pH meters
  • Brix meters

4. Do you perform skip lot testing?

Appropriate Response: No. Skip lot and/or supplier qualification involves a schedule of testing wherein a manufacturer may test the first few lots of a raw material(s) received from a supplier. If the materials are within specification, it may consider that supplier qualified. Then, based on the qualified supplier status, facilities may choose to skip testing on some future lots. Skip lot testing is performed to save time and money. A brand owner has to ask itself if the savings is worth the time and expense of an out-of-spec batch or recall.

Additionally, in todays volatile raw material marketplace, the raw material supplier is not always the raw material manufacturer. Therefore, while a contract manufacturer may have qualified a supplier, it may not have qualified the raw material manufacturer. If the qualified supplier provides material from a different manufacturer, the qualification is worthless. Further, the use of skip lot testing will not identify the material difference until its too late, i.e., the blend or finished product is out of specification.

5. What qualitative tests are performed as part of the raw material and component approval process?

Appropriate response:  Qualitative analysis is performed on all incoming raw materials and components: Routine qualitative tests include, but should not be limited to the following:   

  • FTIR, mid-IR and/or NIR
  • Organoleptic analysis: taste, color, odor, appearance, feel (when applicable)
  • Specific gravity (when applicable)
  • While not technically qualitative, the following are often lumped into the qualitative category:
  • Brix
  • pH
  • Moisture/water content
  • Mesh size
  • TDS etc.

6. What is your protocol for analytical/quantitative analysis of incoming raw materials, i.e., how do you determine the activity and/or purity of raw materials?

Appropriate response:  Analytical/quantitative analysis of all incoming vitamins, minerals, standardized botanicals and/or all other materials that carry a potency/activity label claim and/or that contribute to the total amount of another ingredient on the label. For example, Gurana contains caffeine. As such, this raw material should undergo a quantitative assay to determine the actual caffeine content. In short, a manufacturers standard testing protocol should include a wide variety of quantitative raw material assays to determine that the activity, potency and/or purity are within specifications.

7. Are you aware of Californias Prop 65, and are you prepared to produce products in accordance with those regulations?

Appropriate response:  Yes, were aware, and we have made the investment in ICP-MS. This equipment is able to detect heavy metals such as lead, mercury, arsenic, cadmium and others at parts per million (ppm) and/or parts per billion (ppb) levels necessary to ensure compliance with Prop 65.

8. What is your standard protocol for microbiological analysis of incoming raw materials?

Appropriate response:  Full microbial analysis of all incoming raw materials that should include, but may not be limited to the following:  

  • Total aerobic bacteria
  • Staphylococcus
  • E. Coli
  • Salmonella
  • Yeast and mold
  • Coliforms
  • Enterobacteriaceae

9. What is your procedure for finished goods testing?

Appropriate response:  A myriad of qualitative and quantitative finished goods testing is performed on all lots. Finished goods testing includes, but should not be limited to the following:

High/low quantitative assay on each finished good in order to validate the homogeneity of the blended and previously assayed ingredients.  For example: if the formula contains 100 mcg of selenium and 1000 mg of calcium, a lab would like to see a quantitative finished goods assay for each of those ingredients as it provides some validation to the blend uniformity.

  • FTIR Mid-IR and/or NIR
  • Organoleptic analysis: taste, color, odor, appearance and feel (when applicable)
  • Microbiological analysis: Aerobic bacteria, staphylococcus, E. coli, salmonella, yeast, mold, coliforms, enterobacteriaceae, sometimes pseudomonas and/or others as necessitated by the formulation and its components
  • Viscosity (when applicable)
  • pH
  • Specific gravity
  • Brix

10. Will we be provided with copies of the raw material and finished goods test results, and may we see examples of the raw material, in-process and finished goods testing that have been performed within the last week?

Appropriate response: Yes, wed be happy to. Please note that you should receive tests results for raw materials, in-process goods and finished goods. 

Matt Martin is president and partner of Healthy Solutions LLC, a liquid supplement manufacturer. He has nearly 10 years of experience with liquid supplement and skincare manufacturing as well as with regulatory compliance.

Eric Manfull is partner, chief operating officer (COO) and senior engineer at Healthy Solutions LLC. He has more than 10 years of experience with dairy, beverage and supplement manufacturing.

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