USP<62>MICROBIOLOGICAL EXAMINATION OF NONSTERILE PRODUCTS: TESTS FOR SPECIFIED MICROORGANISMS

USP General Chapter <62> establishes the harmonized compendial procedures for determining the absence of specific, objectionable microorganisms in non-sterile pharmaceutical products and raw materials.

While its partner chapter (USP <61>) focuses on quantitative enumeration, USP <62> is a qualitative (Presence/Absence) test. It uses selective enrichment broths and diagnostic agar media to determine if a specific pathogen is present in a defined quantity of product (typically 1 g or 10 g).

Harmonization Status: This chapter is fully harmonized with Ph. Eur. 2.6.13 and JP 4.05 under the Pharmacopoeial Discussion Group (PDG).

1. Scope and Applicability This chapter applies to:

Non-sterile Drug Products: Oral liquids, tablets, topicals, and nasal sprays.

Raw Materials & Excipients: Used in both non-sterile and sterile manufacturing (upstream bioburden control).

Nutritional and Dietary Supplements.

2. The "Specified" Microorganisms The chapter provides specific detection protocols for pathogens deemed "objectionable" based on the route of administration. The standard list includes:

• Staphylococcus aureus
• Pseudomonas aeruginosa
• Escherichia coli
• Salmonella spp.
• Bile-tolerant Gram-negative bacteria (BTGNB)
• Candida albicans

3. The Testing Workflow The method relies on a stepwise stress-recovery and selection process:

Sample Preparation: Preparation of a 1:10 dilution (usually in Tryptic Soy Broth) with appropriate neutralizers if the product has antimicrobial activity.

Pre-Enrichment: Incubation to revive stressed microorganisms.

Selective Enrichment: Transfer to selective broths (e.g., Rappaport-Vassiliadis for Salmonella) to favor the target organism over background flora.

Selective Plating: Subculture onto diagnostic media such as:

• Cetrimide Agar (P. aeruginosa)
• Mannitol Salt Agar (S. aureus)
• MacConkey Agar (E. coli/BTGNB)
• XLD Agar (Salmonella)
• Sabouraud Dextrose Agar (C. albicans)

Confirmation: Suspect colonies are confirmed using:

• Gram staining
• Biochemical identification
• Pattern of growth on selective media

4. Method Suitability (Validation) Before routine testing, the laboratory must demonstrate "Method Suitability."

Requirements:

• Spike each target organism at ≤ 100 CFU into the product.
• Demonstrate recoverability compared with a positive control (product-free).
• Recovery criteria are defined in <62> and aligned with harmonized PDG expectations.
• Needed whenever formulation, preservative system, or raw materials change.