PDA Technical Report No. 39 (TR 39) provides essential, consensus-based guidance for maintaining the quality of temperature-sensitive medicinal products during transportation, focusing on environmental monitoring, risk management, and packaging qualification. As a foundational document for Good Distribution Practices (GDP), it aligns with regulatory standards to prevent product degradation from heat, cold, or light during the shipping process. More information is available on the Parenteral Drug Association website. Cold Chain Guidance for Medicinal Products | PDF - Scribd
A common observation (Form 483) cites failure to follow TR 39’s guidance on “worst-case route selection” or “lack of seasonal mapping.” In one notable case, a company received a Warning Letter because their shipping qualification used a benign springtime route, while their commercial shipments crossed the desert in summer—a direct violation of TR 39 principles.
In the world of pharmaceutical manufacturing and supply chain management, few documents carry as much weight in the quiet, often-overlooked realm of temperature control as (TR 39). Officially titled "Guidance for Temperature-Controlled Medicinal Products: Maintaining the Quality of Temperature-Sensitive Medicinal Products through the Transportation Environment," this report has become the industry standard for managing cold chain processes. pda technical report 39
Before TR 39, there was significant variability in how companies validated filters. Questions regarding filter area, extractables, and integrity test limits were often answered inconsistently. TR 39 established a scientific baseline, utilizing the risk-based approach that would later become a hallmark of ICH Q9.
| Step | Action | |------|--------| | | Verify shipper is qualified for season & route. | | During packing | Place data logger(s) near product, not just in air space. | | Before dispatch | Check logger is armed, batteries OK, alarm set. | | In transit | Monitor alarms remotely if possible. | | On receipt | Download data immediately; hold product until review. | | Excursion? | Follow SOP: assess vs. stability data, document decision. | | Annual review | Re-evaluate lanes, packaging, and partner performance. | PDA Technical Report No
: Using stability data to determine how long a product can safely withstand excursions.
The report strongly discourages automatic rejection of product based solely on a temperature spike. Instead, it promotes a science-based evaluation considering: More information is available on the Parenteral Drug
Move away from "three successful runs" as validation. TR 39 calls for that simulate:
This is the oldest and most direct method. It relies on the principle that a liquid-wetted membrane has a surface tension that holds liquid in the pores. Gas pressure is increased until the liquid is expelled from the largest pore, causing a steady stream of bubbles.
Before designing any process, identify hazards:
: Guidance on designing specialized packaging systems (active or passive shippers) and qualifying them through rigorous testing.