Tag Archives: Validation

Environmental Control and Monitoring for Aseptic Processing

Petri dish

Hello good people of the world! Today’s post is an overview of environmental control and monitoring for aseptic processing.

Applicable references for the US are:

  • FDA Guideline for “Sterile Drug Products Produced by Aseptic Processing” September, 2004
  • FDA Guideline for the submission of “Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products”
  • 21 CFR Part 211 — Current Good Manufacturing Practices for Finished Pharmaceuticals

Purpose:

Environmental control is designed to prevent microbiological contamination of sterile products.

Environmental monitoring is designed to detect microbiological contamination in aseptic processing areas.

Scope: Environmental control and monitoring is a required part of aseptic processing, i.e. where “terminal” sterilization is not possible. Terminal sterilization means the finished drug product is sterilized at the last step of the process via heat, radiation or other. Many pharmaceuticals and most biologics do not tolerate terminal sterilization, thus the importance of aseptic processing.

Control Considerations:

  1. Air particle count: maintaining air particle counts is critical to aseptic processing, because particles themselves can be harmful, and likely carry microorganisms.
  2. Cleanroom design: for the aseptic core (where critical aseptic process steps occur, e.g. where product is open to the environment) the FDA recommends class 100. The core should surrounded by class 1,000 or class 10,000 areas.
  3. Air pressure differentials: the FDA recommends a 10-15 Pascal pressure differential between rooms of differing classification, with the higher pressure in higher-class rooms, so that air naturally flows outward to the lower class rooms.
  4. HEPA filtration: High Efficiency Particulate Air (HEPA) filters should be used in class 100 rooms to aid in particle removal
  5. Equipment: should be cleanable and non-shedding. Stainless steel is the preferred material of construction for equipment surfaces.
  6. Process design: processes should be designed with minimizing contaminate risks in mind (e.g. don’t force operators to reach over open product)
  7. Process Validation: media runs should be performed to demonstrate the process can run aseptically

Monitoring Considerations:

  1. Air quality measurements should look at viable and nonviable particulate levels
  2. Particle counting: ongoing monitoring should look at particle counts in critical areas
  3. Active sampling: devices such as impaction and membrane samplers should be used to evaluate aseptic processing areas
  4. Passive sampling: settling plates should be used to collect microbial information
  5. WFI and other excipients: should be routinely tested for microbial/particulate load
  6. Personnel: the greatest single contributor of particulates and microbes in a cleanroom. Steps (training, gowning, testing) must be taken to minimize risk

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EU Q&A on GDP Guidance

Drug Distribution

Hello, good people of the world! On March 28, 2014 the European Commission released a question and answer (Q&A) document related to their Good Distribution Practice (GDP) guidance. The original guidance is here. The Q&A document is here. Some highlights:

  1. Question: in Chapter 2 – Personnel, 2.5, does the statement “appropriate procedures relating to personnel hygiene, relevant to the activities being carried out, should be established and observed” refer to the health and/or cleanliness of the staff?Answer: It only refers to the cleanliness of the staff, so to avoid any alteration of the product.
  2. Question: in Chapter 3 – Premises and Equipment, 3.2.(3), is the intent of segregation to avoid “cross-contamination” as mentioned in chapter 5?Answer: The intent of this provision is to avoid handling errors and accidental swaps of products. This is why electronic segregation is allowed, except for falsified, expired, recalled and rejected products which always have to be segregated physically.
  3. Question: concerning Chapter 3 – Premises and Equipment, 3.2.1, how many probes are necessary to monitor the temperature?Answer: The number of probes and their placement depend on the risk analysis performed on the site and the placement should be in agreement with the mapping results.
  4. Question: Concerning Chapter 9 – Transportation, 9.2.(1), can we deviate from storage conditions if the manufacturer agrees to the transportation of the product within a certain temperature range (2°-25°c) for a limited time frame of 6 hours?Answer: No. Storage temperature limits as described by the manufacturer or on the outer packaging need to be respected for each stage of transport during the whole transport chain.

Any of these questions or answers leave you with more questions? Leave a comment below and please share this post with whomever you think would benefit.

10 Easy Steps – Deleting a Point from a Qualified Building Management System (BMS)

Siemens APOGEE

Hello, good people of the world! This post covers the procedure for deleting a point from a qualified Building Management System (BMS), specifically the Siemens APOGEE® BMS. A template for your use is here: Deleting a BMS Point TEMPLATE.

  1. Deleting a BMS Point Continue reading 10 Easy Steps – Deleting a Point from a Qualified Building Management System (BMS)

Qualifying cGMP Warehouse Space

Warehouse

Hello, good people of the world! So you have a cGMP warehouse you need to qualify? Well, this post will provide plenty of information to get you started.

First, how do you know your warehouse is a “cGMP” warehouse. Well, it is if:

  • The warehouse will house any raw material, excipient, intermediate, or finished product
  • The warehouse will house equipment or process consumables, such as filters, bags, disposable tubing, etc.
  • Any cGMP operations will occur in the warehouse, such as sampling, dispensing, kitting, track and trace, etc.

Any examples of common or even possible non-cGMP warehouse space in the Biopharma industry? Please leave a comment below.

Continue reading Qualifying cGMP Warehouse Space