Worst-Case Sterilization Cycle Design during Initial Qualification

 The initial qualification must demonstrate that the sterilization process is robust, consistent, and capable of achieving a Sterility Assurance Level (SAL) ≤ 10⁻⁶ under the most challenging conditions. 

Why Worst-Case Conditions?

• To ensure that the most difficult-to-sterilize conditions within the load are validated.
• To confirm uniform lethality across the load, including slowest-to-heat areas.

Examples of Defining Worst-Case Parameters:

1. Temperature and Exposure Time:

   • Use the minimum acceptable temperature and shortest exposure time for the sterilization cycle (e.g., 121°C for 15 minutes).
   • Test at the lower tolerance limit of sterilizer performance.

2. Load Configuration:

   • Simulate maximum load or densely packed loads (i.e., full chamber) with items that are challenging to sterilize (e.g., textiles, filters, large bottles).
   • Include items of varying sizes, thicknesses, or materials.

3. Worst-Case Location (Slowest-to-Heat):

   • Identify and challenge the slowest-to-heat location using temperature sensors and biological indicators.
   • Common slowest-to-heat locations include:
     • Center of the load.
     • Inside a large container or porous material.
     • Positions furthest from steam entry points.

4. Bioburden and Biological Indicators:

   • Place biological indicators (BIs) with a high D-value (e.g., spores of Geobacillus stearothermophilus) at the slowest-to-heat locations.
   • Use indicators that are more heat-resistant than the natural bioburden.

5. Challenging Porous Loads:

   • Use materials such as:
     • Wrapped instruments.
     • Long tubing.
     • Filters or complex components where steam penetration is difficult.

Revision - Manufacture of Sterile Medicinal Products

The deadline for coming into operation of Annex 1 is 25 August 2023, except for point 8.123 which is postponed until 25 August 2024.

Terminally Sterilized Products - Manufacturing Controls

Terminal Moist Heat Sterilization Process

Compliance to regulatory requirements in Pharmaceutical industries

Current regulatory inspection is come up with lots of recommendations. In this article will be discussing regarding the different regulatory requirements. This is the time to evaluate our existing procedure and mitigating the risk. Here will discuss about the recommendation which received different regulatory authority.  Keep your eyes to our blog and check whether you are complying to below mentioned recommendations,   

Global Challenges for Indian Pharmaceutical Industry

The Indian pharma industry is on a good growth path and is likely to be in the top 10 global markets by value by 2020. High burden of disease, good economic growth leading to higher disposable incomes, improvements in healthcare infrastructure and improved healthcare financing are driving growth in the domestic market.

Pharma companies are growing both organically and inorganically. Inorganic growth is happening through licensing and partnerships as high valuation of assets is making acquisitions difficult. Further, companies are organically improving their operations and productivity by increasing field force sizes, penetrating in Tier II and III cities and by expanding their product portfolios.

Recipe control in manufacturing system

Now a day’s regulators looking for control on the product /system recipe. Recipes  are very critical part of process. Because process are control through validated recipe. If firm calming that their system complying 21 CFR par 11/EU annex 11, in that case they should ensure that their system is capable for following mentioned control,

       a)      System should available with the audit trial and it should capture in case any change in individual recipe

      b)      Recipe edition, modification and deletion to be assign to only administrator, these mentioned options should not accessible to other authorization level.