New Regulatory Requirement; Know What to You Need to Comply
"Since the beginning of September 2020, CGMP regulations now require all manufacturers of drug products to detect and quantify any methanol present in each lot of alcohol they receive. Assurance of this has most likely been made a high priority for FDA field personnel."
By Eric Foxman, AAHP Secretary
Francis Godwin, Director of the Office of Manufacturing Quality of FDA’s Office of Compliance, presented during the AAHP Summit on Implementing HPUS Guidelines for FDA Compliance on Sept. 30. Mr. Godwin reminded attendees of a new regulatory requirement affecting every company that manufacturers and/or markets homeopathic drug products.
Mr. Godwin explained that, as a result of the present pandemic, there has been a rush by many firms to market hand sanitizers. The most common active ingredient is 70 percent alcohol (ethanol, a.k.a. ethyl alcohol). FDA’s field-test of a number of these products revealed the inclusion of methanol (methyl alcohol, a.k.a. wood alcohol) in these products. The presence of methanol, whether purposeful or inadvertent, not only renders the products adulterated, but also causes these products to have toxic consequences — even when applied topically.
The Agency traced back in the affected supply chain. It uncovered instances of companies selling alcohol contaminated with methanol — in whole or in part — accompanying the shipments with Certificates of Analysis stating the contents are 100 percent “pure” or ”pharmaceutical grade” alcohol!
Because contaminated alcohol shipments in the supply chain can be utilized in many different products, including homeopathic drugs, FDA is rightly concerned. Members of our industry also need to be concerned that these contaminated shipments might end up possibly in our homeopathic drugs.
This summer, the Agency asked that the USP’s Alcohol identity tests add a requirement to also test for the presence of methanol []. After consideration, the USP adopted the new requirement, which took effect Sept. 1, 2020. []. Thus, since the beginning of September, CGMP regulations [] require all manufacturers of drug products to detect and quantify any methanol present in each lot of alcohol received. Assurance of this has most likely been made a high priority for FDA field personnel.
How does this impact you as a homeopathic manufacturer and/or marketer when the HPUS is the compendia that applies to your products?
- The HPUS definition of alcohol specifically states: “Alcohol… must meet the test for identity and purity described in the USP.” The HPUS does not have separate test standards for alcohol; the USP Identification Tests apply to all alcohol used in making homeopathic drug products. Your company is required to ensure compliance with this new requirement.
- If your company engages a contract manufacturer that uses alcohol in any of its manufacturing steps (even if not for your products) your contract with them should be amended to include a proviso they comply with this new requirement. If they do not comply, FDA field personnel will likely consider their facility to be “out of control,” causing disruptions in their operations that can adversely impact their ability to provide you with product. Your company is required to ensure compliance with this new requirement.
How does this impact you as a homeopathic manufacturer and/or marketer if none of your homeopathic products are in liquid form?
- There are few homeopathic drug products that do not use alcohol at some point in their manufacturing process. Approximately 75 percent of the HPUS monographed substances have alcohol in (at least) the first 2–3 attenuation steps, including all botanical tinctures and many chemical solutions. Of the commonly used homeopathic substances, the percentage is likely to be more than 90 percent. If your products contain any of those commonly used homeopathic substances that have alcohol in the first manufacturing steps, your company is required to ensure compliance with this new requirement.
- Some homeopathic tinctures and liquids may be converted into powder intermediate products and further triturated multiple steps; this effectively removes all alcohol from the final product. However the overall manufacturing process does use alcohol at some point; therefore your company is required to ensure compliance with this new requirement — even if your facility never handles the alcohol (see second bullet above).
We thank Mr. Godwin for bringing this to the attention of our industry through the 2020 AAHP Summit. Prompt action based on this information will help your company avoid a difficult inspection observation that could lead to an expensive recall of multiple lots of your product line. I can’t repeat this often enough: Your company must to ensure compliance with this new requirement.
 21 CFR 211.84(d)(l)