USP Chapter Emphasizes Problems With Revision Process - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

USP Chapter Emphasizes Problems With Revision Process
Inaccuracies in Chapter 91072: of the current USP 29 reveal problems in USP's revision and proofreading process.

Pharmaceutical Technology

The United States Pharmacopia has been recognized for years as an authoritative compendium on drug standards. In recent years, it has paid increasing attention to "microbial purity," i.e., freedom from and control of objectionable bacteria and fungi and included writings on the theory and practice of antimicrobial agents. A reading of Chapter ‹1072› in current USP 29 (Antiseptics and Disinfectants), however, reveals inaccuracies in organic chemistry, proper selection of agents, and ingredient concentrations. Although these errors or inaccuracies do not affect drug purity, they are evidence of a revision process that fails to circulate early drafts to the right people.

Item No. 1: The remarks following Table 3 in Chapter ‹1072› discuss the ionization of weak acids such as phenol and acetic acid, both rarely used in the pharmaceutical plant as microbicides. It is correctly stated that phenol is more active in killing microorganisms below pH 7.0 because it is mostly un-ionized. The same common ion effect would be obtained for acetic acid as well, but the author reverses the equation and states that "acetic acid will be more effective at a pH below 4.0 where it is ionized" (1). The equation is

The pKa of acetic acid is 4.55. By the rule of 2-above-2-below, at pH 6.55 the acid is highly ionized and at pH 2.55 it is practically all un-ionized. At pH 4.0, as cited by the author, it cannot be said to be "ionized;" as a matter of fact, about 90% is just the opposite. Thus, fungi and a few aciduric bacteria will be killed rapidly because the molecule exists mainly as HOAc un-ionized. This pH-dependant lethality is, we believe, what the author tried to convey. But if what is said is not clear, it should not be said.

Item No. 2: Table 2 misspells glutaraldehyde, and Table 4 mistakenly lists glutaraldehyde as an oxidizing agent. Glutaraldehyde exerts its effect by covalent bonding to amino groups or other susceptible sites on nucleic acids or polypeptide chains. In chemistry, a nucleophile (literally, "nucleus lover") is a reagent that forms a chemical bond to its reaction partner (the electrophile) by donating both bonding electrons. Its mechanism is the same as formaldehyde but it is less toxic. No manufacturer of this germicide has ever claimed glutaraldehyde to be an oxidizing agent, like chlorine, nor will any textbook of organic chemistry so state. A common definition of an oxidizing agent is a substance that gains electrons in a redox chemical reaction.

In this same table, ethylene oxide is listed as an oxidizing agent. For classification purposes, it should be grouped with formaldehyde and glutaraldehyde. It is an alkylating agent. Alkylating agents increase the size of a molecule, oxidizing agents generally degrade them.

Item No. 3: In Table 2, "General Classification of Antiseptics, Disinfectants, and Sporicidal Agents," benzalkonium chloride is listed at a use concentration of 200 μg/g. This single concentration does not fit any of the standard marketed products now available that might include this agent. For example, it is too low for use as a disinfectant, for first-aid preparation, or for cosmetic use (the usual range is 1000–3000 μg/g for these uses) and it is too high to be used as an ophthalmic preservative, for which the range is 30–100 μg/g.


blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
| Weekly

Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatcchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Obama Administration Halts Attack on Medicare Drug Plans
Source: Pharmaceutical Technology,
Click here