PharmOut – GMP and Validation Blog

Transition from a terminal to aseptic injectable manufacturing facility: What does it take?

Businesses are always looking for opportunities to expand their portfolios to manufacture product for the commercial market. Whether you are a major or small player in the parenteral injectable market, there are increased commercial opportunities if you can have your facility regulatory approved to manufacture product aseptically.

Being able to manufacture product that is terminally sterilised, in its final container to ensure the sterility provides the foundation for the transition to an aseptic filling manufacturing facility. But there is significant cost and effort (in both documentation and activity) that an organisation will face to make that transition. Additionally, there is new expertise that must be developed and maintained within the organisation.

Taking the simplest option of non sterile components/materials being appropriately processed and sterilised and then combined aseptically, many aspects must align to ensure a sterile product in the final container. The list below provides some initial guidance on what the transition to aseptic processing will require:

1. Change in the design of the clean rooms and processes flows must be assessed, as the changes can be significant.

2. Higher level of classification of the clean room environment, with more stringent performance criteria to be met and maintained.

3. Increased number of validation studies required to assure processes and equipment are under control.

4. Increased level of ongoing testing and monitoring of the clean room facility and services.

5. Processes and procedures to perform media fills, and an understanding of the required actions based on the results obtained.

6. Greater knowledge of aseptic/microbiological aspects to the manufacture by all staff working in the manufacturing facility, this includes cleaners, maintenance crew, laboratory, validation and manufacturing personnel.

7. An increased level of oversight by knowledgeable, experienced individuals in aseptic manufacture, to develop the staff in the correct activities required to produce aseptically filled product.

Once you have convinced regulatory bodies like the TGA and FDA, through the completion of a successful audit, the company must factor the increased running costs of a facility to maintain this higher risk level of manufacturing capability.

Ongoing media fills, increased level of environmental monitoring of the facility and personnel, the need for much greater interaction between manufacturing and QA\QC (especially when manufacturing issues occur during filling), the microbiological and sterility assurance knowledge and the list goes on. With the increased activity, there is an increase in staff numbers that will be required to maintain the facility in a compliant state.

Finally, as aseptic manufacture is regarded and rated as a high risk process to manufacture sterile product, there will be an increased level of regulatory auditing.

Add comment January 8th, 2010

FDA several steps closer to becoming PICS/S members

An interesting press release was issued by PIC/S last month, commenting on the results of a PIC/S assessment team visit to the FDA: ” more progress was achieved during these
two weeks than during the previous three years of assessment. The team assessed the US GMP inspection system and also observed inspections carried out by FDA inspectors. It also met with FDA Commissioner, Dr. Margaret Hamburg, who stated that PIC/S membership was a top priority for the FDA.”!

This is exciting news for pharmaceutical and medical device manufacturers who must comply with multiple regional regulations and country-specific regulations. At long last, there may be an end in sight to the wasting of valuable time and resources in complying with multiple regulations rather than building quality and patient safety into the product. A global GMP standard may actually be achieved in my lifetime!

Whilst it’s great news that the FDA is moving closer to PIC/S membership, it would be a real shame they throw out all their regulations / guidance documents in the process. For example the draft “Process Validation Guidance” issued by the FDA last year provides a refreshing look at product development, commissioning and control. It outlines a whole life cycle development approach to product quality and risk management. So much better than the old three golden batches, how can three consecutive batch “prove” that your process is control! If the FDA does become a PIC/S member, I hope that PIC/S can pick up the best of the FDA’s work and integrate it into their own regulations and guidance documents.

It is interesting to note that there are now thirty seven PIC/S member countries. The membership applications of Indonesia / NADFC, Slovenia / JAZMP and Thailand’s FDA were recently reviewed, potentially expanding the number further. The next assessment for membership will be Latvia’s State Agency of Medicines (ZVA).

Add comment December 1st, 2009